Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

PubMed Central

Doherty, Alison H.; Florant, Gregory L.; Donahue, Seth W.

2014-01-01

Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. PMID:24556365

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

PubMed

Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

2017-01-01

Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

PubMed Central

Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

2015-01-01

Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice. PMID:25789143

Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging

PubMed Central

Kyung, Eun Jung; Kim, Hyun Bum; Hwang, Eun Sang; Lee, Seok; Choi, Bup Kyung; Lim, Sang Moo; Kwon, Oh In

2018-01-01

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction. PMID:29887757

Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats.

PubMed

Coban, Funda Karabag; Ince, Sinan; Kucukkurt, Ismail; Demirel, Hasan Huseyin; Hazman, Omer

2015-10-01

Organophosphorus compounds cause oxidative stress and lead to alterations in antioxidant status in organisms. In this study, the effects of subchronic exposure to malathion and the protective effects of boron (B) were evaluated in 48 Wistar rats, which were divided equally into six groups. For 28 d, the control group received a normal diet and tap water, the corn oil group received a normal diet and 0.5 mL of corn oil by gastric gavage and the malathion group received a normal diet and malathion (100 mg/kg/d) by gastric gavage. During the same period, each of the three other groups received a different dosage of B (5, 10 and 20 mg/kg/d, respectively) and malathion (100 mg/kg/d) by gastric gavage. Malathion administration during the period increased malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as markers of liver function, yet decreased acetylcholinesterase, reduced glutathione, superoxide dismutase, and catalase activities in blood, liver, kidney and brain tissues. Administration of B in a dose-dependent manner also reversed malathion-induced oxidative stress, lipid peroxidation (LPO) and antioxidant enzyme activity. Moreover, B exhibited protective action against malathion-induced histopathological changes in liver, kidney and brain tissues. These results demonstrate that, if used in a dose-dependent manner, B decreases malathion-induced oxidative stress, enhances the antioxidant defense mechanism and regenerates tissues in rats.

CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation*

PubMed Central

Miller, Thomas W.; Soto-Pantoja, David R.; Schwartz, Anthony L.; Sipes, John M.; DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.; Roberts, David D.

2015-01-01

Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury. PMID:26311851

Confocal laser endomicroscopy for brain tumor surgery: a milestone journey from microscopy to cellular surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Charalampaki, Cleopatra

2017-02-01

The aim in brain tumor surgery is maximal tumor resection with minimal damage of normal neuronal tissue. Today diagnosis of tumor and definition of tumor borders intraoperatively is based on various visualization methods as well as on the histopathologic examination of a limited number of biopsy specimens via frozen sections. Unfortunately, intraoperative histopathology bears several shortcomings, and many biopsies are inconclusive. Therefore, the desirable treatment could be to have the ability to identify intraoperative cellular structures, and differentiate tumor from normal functional brain tissue on a cellular level. To achieve this goal new technological equipment integrated with new surgical concepts is needed.Confocal Laser Endomicroscopy (CLE) is an imaging technique which provides microscopic information of tissue in real-time. We are able to use these technique to perform intraoperative "optical biopsies" in bringing the microscope inside to the patients brain through miniaturized fiber-optic probes, and allow real-time histopathology. In our knowledge we are worldwide the only one neurosurgical group using CLE intraoperative for brain tumor surgery. We can detect and characterize intraoperative tumor cells, providing immediate online diagnosis without the need for frozen sections. It also provides delineation of borders between tumor and normal tissue on a cellular level, making surgical margins more accurate than ever before. The applications of CLE-assisted neurosurgery help to accurate the therapy by extending the resection borders and protecting the functionality of normal brain tissue in critical eloquent areas.

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

PubMed

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

PubMed Central

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

WORKSHOP REPORT: MOLECULAR & CELLULAR BIOLOGY OF MODERATE DOSE (1-10 GY) RADIATION & POTENTIAL MECHANISMS OF RADIATION PROTECTION

EPA Science Inventory

EXECUTIVE SUMMARY

Normal tissue response and injury after exposure to ionizing radiation are of great importance to patients with cancer, populations potentially subjected to military, accidental or intentional exposure including bioterrorism, and workers in the nuclear po...

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities.

PubMed

Coleman, Thomas R; Westenfelder, Christof; Tögel, Florian E; Yang, Ying; Hu, Zhuma; Swenson, Leanne; Leuvenink, Henri G D; Ploeg, Rutger J; d'Uscio, Livius V; Katusic, Zvonimir S; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E; Cerami, Anthony; Brines, Michael

2006-04-11

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia-hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities

PubMed Central

Coleman, Thomas R.; Westenfelder, Christof; Tögel, Florian E.; Yang, Ying; Hu, Zhuma; Swenson, LeAnne; Leuvenink, Henri G. D.; Ploeg, Rutger J.; d’Uscio, Livius V.; Katusic, Zvonimir S.; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E.; Cerami, Anthony; Brines, Michael

2006-01-01

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia–hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection. PMID:16585502

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

NASA Technical Reports Server (NTRS)

Smith, B. J.; Lucas, E. A.; Turner, R. T.; Evans, G. L.; Lerner, M. R.; Brackett, D. J.; Stoecker, B. J.; Arjmandi, B. H.

2005-01-01

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

Effect of Shock Wave Lithotripsy on Renal Hemodynamics

NASA Astrophysics Data System (ADS)

Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.

2008-09-01

Extracorporeal shock wave lithotripsy (SWL) can injure tissue and decrease blood flow in the SWL-treated kidney, both tissue and functional effects being largely localized to the region targeted with shock waves (SWs). A novel method of limiting SWL-induced tissue injury is to employ the "protection" protocol, where the kidney is pretreated with low-energy SWs prior to the application of a standard clinical dose of high-energy SWs. Resistive index measurements of renal vascular resistance/impedance to blood flow during SWL treatment protocols revealed that a standard clinical dose of high-energy SWs did not alter RI during SW application. However, there was an interaction between low- and high-energy SWL treatment phases of the "protection" protocol such that an increase in RI (vasoconstriction) was observed during the later half of SW application, a time when tissue damage is occurring during the standard high-energy SWL protocol. We suggest that renal vasoconstriction may be responsible for reducing the degree of tissue damage that normally results from a standard clinical dose of high-energy SWs.

Hypothermia postpones DNA damage repair in irradiated cells and protects against cell killing.

PubMed

Baird, Brandon J; Dickey, Jennifer S; Nakamura, Asako J; Redon, Christophe E; Parekh, Palak; Griko, Yuri V; Aziz, Khaled; Georgakilas, Alexandros G; Bonner, William M; Martin, Olga A

2011-06-03

Hibernation is an established strategy used by some homeothermic organisms to survive cold environments. In true hibernation, the core body temperature of an animal may drop to below 0°C and metabolic activity almost cease. The phenomenon of hibernation in humans is receiving renewed interest since several cases of victims exhibiting core body temperatures as low as 13.7°C have been revived with minimal lasting deficits. In addition, local cooling during radiotherapy has resulted in normal tissue protection. The experiments described in this paper were prompted by the results of a very limited pilot study, which showed a suppressed DNA repair response of mouse lymphocytes collected from animals subjected to 7-Gy total body irradiation under hypothermic (13°C) conditions, compared to normothermic controls. Here we report that human BJ-hTERT cells exhibited a pronounced radioprotective effect on clonogenic survival when cooled to 13°C during and 12h after irradiation. Mild hypothermia at 20 and 30°C also resulted in some radioprotection. The neutral comet assay revealed an apparent lack on double strand break (DSB) rejoining at 13°C. Extension of the mouse lymphocyte study to ex vivo-irradiated human lymphocytes confirmed lower levels of induced phosphorylated H2AX (γ-H2AX) and persistence of the lesions at hypothermia compared to the normal temperature. Parallel studies of radiation-induced oxidatively clustered DNA lesions (OCDLs) revealed partial repair at 13°C compared to the rapid repair at 37°C. For both γ-H2AX foci and OCDLs, the return of lymphocytes to 37°C resulted in the resumption of normal repair kinetics. These results, as well as observations made by others and reviewed in this study, have implications for understanding the radiobiology and protective mechanisms underlying hypothermia and potential opportunities for exploitation in terms of protecting normal tissues against radiation. 2011. Published by Elsevier B.V.

Graphdiyne Nanoparticles with High Free Radical Scavenging Activity for Radiation Protection.

PubMed

Xie, Jiani; Wang, Ning; Dong, Xinghua; Wang, Chengyan; Du, Zhen; Mei, Linqiang; Yong, Yuan; Huang, Changshui; Li, Yuliang; Gu, Zhanjun; Zhao, Yuliang

2018-03-06

Numerous carbon networks materials comprised of benzene moieties, such as graphene and fullerene, have held great fascination for radioprotection because of their acknowledged good biocompatibility and strong free radical scavenging activity derived from their delocalized π-conjugated structure. Recently, graphdiyne, a new emerging carbon network material consisting of a unique chemical structure of benzene and acetylenic moieties, has gradually attracted attention in many research fields. Encouraged by its unique structure with strong conjugated π-system and highly reactive diacetylenic linkages, graphdiyne might have free radical activity and can thus be used as a radioprotector, which has not been investigated so far. Herein, for the first time, we synthesized bovine serum albumin (BSA)-modified graphdiyne nanoparticles (graphdiyne-BSA NPs) to evaluate their free radical scavenging ability and investigate their application for radioprotection both in cell and animal models. In vitro studies indicated that the graphdiyne-BSA NPs could effectively eliminate the free-radicals, decrease radiation-induced DNA damage in cells, and improve the viability of cells under ionizing radiation. In vivo experiments showed that the graphdiyne-BSA NPs could protect the bone marrow DNA of mice from radiation-induced damage and make the superoxide dismutase (SOD) and malondialdehyde (MDA) (two kinds of vital indicators of radiation-induced injury) recover back to normal levels. Furthermore, the good biocompatibility and negligible systemically toxicity responses of the graphdiyne-BSA NPs to mice were verified. All these results manifest the good biosafety and radioprotection activity of graphdiyne-BSA NPs to normal tissues. Therefore, our studies not only provide a new radiation protection platform based on graphdiyne for protecting normal tissues from radiation-caused injury but also provide a promising direction for the application of graphdiyne in the biomedicine field.

Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain

NASA Astrophysics Data System (ADS)

Wu, Z. H.; Zhang, H.; Wang, X. Y.; Yang, R.; Liu, B.; Liu, Y.; Zhao, W. P.; Feng, H. Y.; Xue, L. G.; Hao, J. F.; Niu, B. T.; Wang, Z. H.

2012-01-01

The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.

Lycopene as A Carotenoid Provides Radioprotectant and Antioxidant Effects by Quenching Radiation-Induced Free Radical Singlet Oxygen: An Overview

PubMed Central

Pirayesh Islamian, Jalil; Mehrali, Habib

2015-01-01

Radio-protectors are agents that protect human cells and tissues from undesirable effects of ionizing radiation by mainly scavenging radiation-induced free radicals. Although chemical radio-protectors diminish these deleterious side effects they induce a number of unwanted effects on humans such as blood pressure modifications, vomiting, nausea, and both local and generalized cutaneous reactions. These disadvantages have led to emphasis on the use of some botanical radio-protectants as alternatives. This review has collected and organized studies on a plant-derived radio-protector, lycopene. Lycopene protects normal tissues and cells by scavenging free radicals. Therefore, treatment of cells with lycopene prior to exposure to an oxidative stress, oxidative molecules or ionizing radiation may be an effective approach in diminishing undesirable effects of radiation byproducts. Studies have designated lycopene to be an effective radio-protector with negligible side effects. PMID:25685729

A Therapeutic Role for Survivin in Mitigating the Harmful Effects of Ionizing Radiation

PubMed Central

Carruthers, Katherine H.; Metzger, Gregory; Choi, Eugene; During, Matthew J.; Kocak, Ergun

2016-01-01

Background. Radiation therapy is a form of adjuvant care used in many oncological treatment protocols. However, nonmalignant neighboring tissues are harmed as a result of this treatment. Therefore, the goal of this study was to induce the production of survivin, an antiapoptotic protein, to determine if this protein could provide protection to noncancerous cells during radiation exposure. Methods. Using a murine model, a recombinant adenoassociated virus (rAAV) was used to deliver survivin to the treatment group and yellow fluorescence protein (YFP) to the control group. Both groups received targeted radiation. Visual inspection, gait analysis, and tissue histology were used to determine the extent of damage caused by the radiation. Results. The YFP group demonstrated ulceration of the irradiated area while the survivin treated mice exhibited only hair loss. Histology showed that the YFP treated mice experienced dermal thickening, as well as an increase in collagen that was not present in the survivin treated mice. Gait analysis demonstrated a difference between the two groups, with the YFP mice averaging a lower speed. Conclusions. The use of gene-modification to induce survivin expression in normal tissues allows for the protection of nontarget areas from the negative side effects normally associated with ionizing radiation. PMID:27190495

[The influence of alcohol on the oral cavity, salivary glands and saliva].

PubMed

Waszkiewicz, Napoleon; Zalewska, Anna; Szulc, Agata; Kepka, Alina; Konarzewska, Beata; Zalewska-Szajda, Beata; Chojnowska, Sylwia; Waszkiel, Danuta; Zwierz, Krzysztof

2011-01-01

Ethanol diffuses rapidly into saliva during the drinking, and immediately after its salivary concentration is temporarily much higher than in plasma. Within 30 minutes, salivary ethanol concentration equilibrates with the plasma level, thus suggesting that ethanol easily penetrates the whole body, including oral cavity tissues and salivary glands. After alcohol intake, the level of acetaldehyde in saliva strikingly exceeds the level in systemic blood. From saliva, acetaldehyde and ethanol easily reach all local tissues. Damage to the oral tissues seems to be ascribed mostly to the action of acetaldehyde, although some acute effects depend on a direct action of ethanol and formation of reactive oxygen species (ROS) and fatty acid ethyl esters (FAEEs). It is known that the oral mucosal surface is the home of numerous normal flora microorganisms and is the portal of entry for the majority of pathogens. The oral cavity and salivary antimicrobial immune defense systems eliminate pathogens and prevent massive overgrowth of microorganisms. An oral defense system participate in the protection of not only oral tissues, but also in the protection of upper digestive and respiratory tracts, against a number of microbial pathogens. Saliva plays the role in the oral cavity lubrication, maintenance of mucosal and tooth integrity, esophageal physiology, digestion and gastric cytoprotection. As alcohol abuse affects the structure and function of oral cavity mucosa, salivary glands and saliva, the maintenance of oral and general health under normal conditions is seriously impaired during the drinking. The severe tissue damage occurs in particular when alcohol abuse coincides with smoking.

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

PubMed Central

Kim, Hyun Mi; Kim, Suk Hee

2018-01-01

BACKGROUND/OBJECTIVES Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy. PMID:29399295

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

PubMed

Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

2013-07-01

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (P<0.05). Despite reduced regional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier Ltd.

Normal and cancer mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR Axis

PubMed Central

Celià-Terrassa, Toni; Liu, Daniel; Choudhury, Abrar; Hang, Xiang; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi-Zhou; Koh, Bong Ihn; Smith, Heath; DeCoste, Christina; Li, Jun-Jing; Shao, Zhi-Ming; Kang, Yibin

2017-01-01

Tumor-initiating cells (TICs), or cancer stem cells (CSC), possess stem cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER− breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. Our study therefore reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signaling. PMID:28530657

Telomere 1 (POT1) gene expression and its association with telomerase activity in colorectal tumor samples with different pathological features.

PubMed

Izgi, Ahu; Gunal, Armagan; Yalcin, Serap; Gunduz, Ufuk

2014-09-01

The ends of chromosoms, telomeres are bound with a number of proteins which protect and stabilize telomeres against degredation, end to end fusion and aberrant recombinations. Telomeric DNA is bound of two groups of proteins, which are double-stranded telomeric DNA bindings proteins, and single stranded telomeric binding proteins. Among telomere binding proteins, protections of telomere 1 protein is a single stranded telomere binding proteins and suggested to be a significant player for telomere elongation and has an association with an enzyme called as telomerase which is an intrinsic reverse transcriptase. Telomerase synthesizes hexameric telomeric repeats onto the chromosomes thereby compansating telomere loss in immortal cells, such as tumor cells, whereas telomeres are shorthened with each division in normal cells. PCR-based TRAP (telomeric repeat amplification protocol) assay is a very sensitive assay for the detection of enzymatic activity of telomerase even if a few numbers of cancerous cells are available. The association between telomerase activity and hPOT1 expression in colorectal cancer is still unclear. Protein extraction was performed from specimens of matched normal and colorectal cancer specimens. Protein concentrations were determined by Bradford assay. Optimized protein concentrations were used for TRAP Assay. TRAP products were seperated by vertical gel electrophoresis on 12.5% polyacrylamide gels and visualized by silver staining. Gene expression of hPOT1 was determined by qPCR analysis. The results demonstrated that all tumor tissues were telomerase positive whereas all corresponding normal tissue was telomerase negative. Among clinicopathological findings, telomerase activity was found to be associated with stage, histology, localization, distant metastasis and lymph node metastasis of tumor in the current study. Although all of the clinicopathological findings differed in the expression of hPOT1 compared to normal tissues, they did not differ from each other significantly, except side of tumor and lymph node metastasis. Telomerase activity and hPOT1 gene expression may serve as a promising tumor marker for colorectal cancer and there is a close association between the enzymatic activty of telomerase and the expression of human protection of telomere 1 gene. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

Pre-Conditioning with Low-Level Laser (Light) Therapy: Light Before the Storm

PubMed Central

Agrawal, Tanupriya; Gupta, Gaurav K.; Rai, Vikrant; Carroll, James D.; Hamblin, Michael R.

2014-01-01

Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. PMID:25552961

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PROTECTION OF THE EMBRYO AGAINST THE CONGENITAL AND LETHAL EFFECTS OF X- IRRADIATION. PART I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rugh, R.; Grupp, E.

1960-04-01

The effects of 15 agents, some given before and some after x irradiation to 200 r, have been studied for their effectiveness in protecting the 8.5-day mouse embryo against embryonic or fetal death and the development of the severe cephalic congenital anomaly known as exencephalia (or brain hernia). Some 4979 fetuses were examined. Of the agents studied, only cysteinamine, cystamine, and anoxia proved to be statistically "protective" at all. Cysteinamine and cystamine (both -SH compounds) given I.P. before x irradiation to 200 r allowed 73 to 80% of the 8.5-day embryos to survive to term while the untreated but irradiatedmore » control litters had a survival of only 41%. Funther, there was considerable reduction in bcth uterine death and the congenital anomaly of exencephalia. Anoxia (6% O/sub 2/ + 94% N/sub 2/) aIlowed 71% to come through as ""apparently normal," an increase of 30% over the unprotected irradiated controls. Whether there is long-term damage to the 8.5day embryo from the temporary anoxia alone has not been determined, although the anoxic controls showed 96% " apparently nornnal." Distilled water given I.P. before irradiation, making the milieu of the embryos hypotonic, appeared to be deleterious, causing 2% exencephalia even without x irradiation. When combined with x rays, distilled water reduced the "apparentiy normals" to 31%, or 10% lower than with irradiation alone. Saline in various concentrations was not protective. None of the tissue homogenates (spleen, marrow, liver, or brain of a homologous newborn source) proved to be of any protective value. It is suggested that the protective element in such tissue homogenates may be cellular since the placenta acts as the most efficient filter to allow only the dialyzable substances through to the embryo. However, the fact that the 8.5-day mouse embryo has not yet developed its hematopoietic syatem may explain the failure of homogenates which seem to protect through hematopoietic regeneration. Hypoxia from hypoglycemia following insulin injection was not protective. Insulin or dextrose or the two in combination were -not panticularly harraful to the 8.5-day mouse embryo but when combined with x irradiation were very damaging. "Protection" as used in this study is statistical and relates to the percentage changes in ""apparently normal" fetuses, resorptions, deaths, and congenital anomalies. It does not imply that the surviving mice are without irradiation sequelae. In fact many of the "apparently normals" have eye defects and this might well reveal other and more subtle C. N. 8. damage. On the basis of survival, however, cysteinamine, cystamine, and anoxia did afford some protection. (auth)« less

Selection of internal reference genes for normalization of reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis in the rumen epithelium

USDA-ARS?s Scientific Manuscript database

The rumen is lined on the luminal side by a stratified squamous epithelium that is responsible for not only absorption, but also transport, extensive short-chain fatty acid (SCFA) metabolism and protection. Butyrate has been demonstrated to initiate the differentiation of the tissue following intro...

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

PubMed Central

Tuohy, Vincent K.; Jaini, Ritika; Johnson, Justin M.; Loya, Matthew G.; Wilk, Dennis; Downs-Kelly, Erinn; Mazumder, Suparna

2016-01-01

We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC)—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC. PMID:27322324

Coniferyl Aldehyde Reduces Radiation Damage Through Increased Protein Stability of Heat Shock Transcriptional Factor 1 by Phosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Seo-Young; Lee, Hae-June; Nam, Joo-Won

Purpose: We previously screened natural compounds and found that coniferyl aldehyde (CA) was identified as an inducer of HSF1. In this study, we further examined the protective effects of CA against ionizing radiation (IR) in normal cell system. Methods and Materials: Western blotting and reverse transcription-polymerase chain reaction tests were performed to evaluate expression of HSF1, HSP27, and HSP70 in response to CA. Cell death and cleavage of PARP and caspase-3 were analyzed to determine the protective effects of CA in the presence of IR or taxol. The protective effects of CA were also evaluated using animal models. Results: CAmore » increased stability of the HSF1 protein by phosphorylation at Ser326, which was accompanied by increased expression of HSP27 and HSP70. HSF1 phosphorylation at Ser326 by CA was mediated by EKR1/2 activation. Cotreatment of CA with IR or taxol in normal cells induced protective effects with phosphorylation- dependent patterns at Ser326 of HSF1. The decrease in bone marrow (BM) cellularity and increase of terminal deoxynucleotidyl transferase dUTP nick end labeling–positive BM cells by IR were also significantly inhibited by CA in mice (30.6% and 56.0%, respectively). A549 lung orthotopic lung tumor model indicated that CA did not affect the IR-mediated reduction of lung tumor nodules, whereas CA protected normal lung tissues from the therapeutic irradiation. Conclusions: These results suggest that CA may be useful for inducing HSF1 to protect against normal cell damage after IR or chemotherapeutic agents.« less

Effects of Spirulina on Cyclophosphamide-Induced Ovarian Toxicity in Rats: Biochemical and Histomorphometric Evaluation of the Ovary

PubMed Central

Yener, Nese Arzu; Sinanoglu, Orhun; Ilter, Erdin; Celik, Aygen; Sezgin, Gulbuz; Midi, Ahmet; Aksungar, Fehime

2013-01-01

Cyclophosphamide (Cyc) is known to cause ovotoxicity and infertility in women. Our aim is to investigate the possible ovotoxic effects of Cyc and possible antioxidant and protective effects of blue-green algae, Spirulina (Sp), in rat ovaries. Eighteen rats were given: group I (n = 6, control); group II (n = 6, CP), a single dose Cyc; group III (n = 6, Sp+Cyc), 7 days Sp+single dose Cyc. Tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities are assessed biochemically. Normal and atretic primordial and primary follicle counts for all sections obtained for each ovary are calculated. Mean number of follicle counts for each group are compared. In Sp+Cyc group, tissue MDA levels were significantly lower than those in the CP and higher than those in the C group (CP > Sp+Cyc > C). Tissue SOD activity was significantly higher in Sp+Cyc group than that in the CP group and lower than that in the C group (C > Sp+Cyc > C). No statistically significant difference was found between the ovarian CAT activities in any group. Histomorphometrically, there was also no significant difference between the mean numbers of normal and atretic small follicle counts. Our results suggest that single dose Cyc has adverse effects on oxidant status of the ovaries and Sp has protective effects in Cyc-induced ovotoxicity. PMID:23762559

Mangiferin protects rat myocardial tissue against cyclophosphamide induced cardiotoxicity.

PubMed

Bhatt, Laxit; Sebastian, Binu; Joshi, Viraj

Mangiferin is a highly potent antioxidant present in mango leaves which is utilized for therapeutic purposes. The present study was undertaken to evaluate the cardioprotective effect of mangiferin against cyclophosphamide induced cardiotoxicity. Rats were treated with 100 mg/kg of mangiferin in alone and interactive groups for 10 days. Apart from normal and mangiferin control groups, all the groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on Day 1 and effects of different treatments were analyzed by changes in serum biomarkers, tissue antioxidant levels, electrocardiographic parameters, lipid profile and histopathological evaluation. Mangiferin treated group showed decrease in serum biomarker enzyme levels and increase in tissue antioxidant levels. Compared to cyclophosphamide control group, mangiferin treated animals showed improvement in lipid profile, electrocardiographic parameters, histological score and mortality. The present findings clearly suggest the protective role of mangiferin as a powerful antioxidant preventing cardiotoxicity caused by cyclophosphamide. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Thermal therapy techniques for skin and superficial tissue disease

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.

2000-01-01

There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.

A Novel Microbicide/Contraceptive Intravaginal Ring Protects Macaque Genital Mucosa against SHIV-RT Infection Ex Vivo.

PubMed

Villegas, Guillermo; Calenda, Giulia; Ugaonkar, Shweta; Zhang, Shimin; Kizima, Larisa; Mizenina, Olga; Gettie, Agegnehu; Blanchard, James; Cooney, Michael L; Robbiani, Melissa; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2016-01-01

Women need multipurpose prevention products (MPTs) that protect against sexually transmitted infections (STIs) and provide contraception. The Population Council has developed a prototype intravaginal ring (IVR) releasing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (M), zinc acetate (ZA), carrageenan (CG) and levonorgestrel (LNG) (MZCL IVR) to protect against HIV, HSV-2, HPV and unintended pregnancy. Our objective was to evaluate the anti-SHIV-RT activity of MZCL IVR in genital mucosa. First, macaque vaginal tissues were challenged with SHIV-RT in the presence of (i) MIV-150 ± LNG or (ii) vaginal fluids (VF); available from studies completed earlier) collected at various time points post insertion of MZCL and MZC IVRs. Then, (iii) MZCL IVRs (vs. LNG IVRs) were inserted in non-Depo Provera-treated macaques for 24h and VF, genital biopsies, and blood were collected and tissues were challenged with SHIV-RT. Infection was monitored with one step SIV gag qRT-PCR or p27 ELISA. MIV-150 (LCMS/MS, RIA), LNG (RIA) and CG (ELISA) were measured in different compartments. Log-normal generalized mixed linear models were used for analysis. LNG did not affect the anti-SHIV-RT activity of MIV-150 in vitro. MIV-150 in VF from MZC/MZCL IVR-treated macaques inhibited SHIV-RT in vaginal mucosa in a dose-dependent manner (p<0.05). MIV-150 in vaginal tissue from MZCL IVR-treated animals inhibited ex vivo infection relative to baseline (96%; p<0.0001) and post LNG IVR group (90%, p<0.001). No MIV-150 dose-dependent protection was observed, likely because of high MIV-150 concentrations in all vaginal tissue samples. In cervical tissue, MIV-150 inhibited infection vs. baseline (99%; p<0.05). No cervical tissue was available for MIV-150 measurement. Exposure to LNG IVR did not change tissue infection level. These observations support further development of MZCL IVR as a multipurpose prevention technology to improve women's sexual and reproductive health.

The Meninges: New Therapeutic Targets For Multiple Sclerosis

PubMed Central

Russi, Abigail E.; Brown, Melissa A.

2014-01-01

The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats.

PubMed

Ghoneim, Mona A M; Hassan, Amal I; Mahmoud, Manal G; Asker, Mohsen S

2016-01-01

The baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interleukin-1 β (IL-1 β), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GPX) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GPX and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200 µg/rats/day) showed predominantly normal myocardial structure and no inflammatory cell infiltration. It has been concluded that Baobab fruit pulp has cardio protective effect against ISP-induced oxidative stress in rats.

New Approaches to Radiation Protection

PubMed Central

Rosen, Eliot M.; Day, Regina; Singh, Vijay K.

2015-01-01

Radioprotectors are compounds that protect against radiation injury when given prior to radiation exposure. Mitigators can protect against radiation injury when given after exposure but before symptoms appear. Radioprotectors and mitigators can potentially improve the outcomes of radiotherapy for cancer treatment by allowing higher doses of radiation and/or reduced damage to normal tissues. Such compounds can also potentially counteract the effects of accidental exposure to radiation or deliberate exposure (e.g., nuclear reactor meltdown, dirty bomb, or nuclear bomb explosion); hence they are called radiation countermeasures. Here, we will review the general principles of radiation injury and protection and describe selected examples of radioprotectors/mitigators ranging from small-molecules to proteins to cell-based treatments. We will emphasize agents that are in more advanced stages of development. PMID:25653923

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats.

PubMed

Kucukkurt, Ismail; Ince, Sinan; Demirel, Hasan Huseyin; Turkmen, Ruhi; Akbel, Erten; Celik, Yasemin

2015-12-01

The aim of the present study was to investigate the possible protective effects of boron, an antioxidant agent, against arsenic-induced oxidative stress in male and female rats. In total, 42 Wistar albino male and female rats were divided into three equal groups: The animals in the control group were given normal drinking water, the second group was given drinking water with 100 mg/L arsenic, and the third group was orally administered drinking water with 100 mg/kg boron together with arsenic. At the end of the 28-day experiment, arsenic increased lipid peroxidation and damage in the tissues of rats. However, boron treatment reversed this arsenic-induced lipid peroxidation and activities of antioxidant enzymes in rats. Moreover, boron exhibited a protective action against arsenic-induced histopathological changes in the tissues of rats. In conclusion, boron was found to be effective in protecting rats against arsenic-induced lipid peroxidation by enhancing antioxidant defense mechanisms. © 2015 Wiley Periodicals, Inc.

Metabolically normal obese people are protected from adverse effects following weight gain

PubMed Central

Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L.; Patterson, Bruce W.; Klein, Samuel

2015-01-01

BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as “metabolically normal obese” (MNO), but not those defined as “metabolically abnormal obese” (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain–induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation. PMID:25555214

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.

PubMed

Ghosh, Amiya K; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-09-07

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation.

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging

PubMed Central

Ghosh, Amiya K.; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-01-01

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation. PMID:28898202

Reducing radiation-induced gastrointestinal toxicity — the role of the PHD/HIF axis

PubMed Central

Olcina, Monica M.; Giaccia, Amato J.

2016-01-01

Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at reducing or preventing normal tissue toxicity induced by radiotherapy is a long-held goal. Hypoxia-inducible factors (HIFs) regulate the production of factors that may protect several cellular compartments affected by radiation-induced toxicity. Pharmacological inhibitors of prolyl hydroxylase domain–containing enzymes (PHDs), which result in stabilization of HIFs, have recently been proposed as a new class of radioprotectors. In this review, radiation-induced toxicity in the gastrointestinal (GI) tract and the main cellular compartments studied in this context will be discussed. The effects of PHD inhibition on GI radioprotection will be described in detail. PMID:27548524

Bombesin-like peptide receptors in human bronchial epithelial cells.

PubMed

Kane, M A; Toi-Scott, M; Johnson, G L; Kelley, K K; Boose, D; Escobedo-Morse, A

1996-01-01

Northern blot and RNAse protection assays previously failed to detect bombesin-like peptide (BLP) receptors in normal human lung tissue, but by RT/PCR cultured human bronchial epithelial (HBE) cells expressed all three BLP receptor subtypes, predominantly neuromedin B (NMB) receptor. By RT/PCR, we found expression of all three BLP receptor subtypes by human lung tissue and confirmed NMB receptor expression in six out of six HBE samples. However, transformed HBE BEAS B2B cells expressed only gastrin-releasing peptide (GRP) receptors; saturable, high-affinity (Kd = 3.5 nM) specific [125I]GRP binding confirmed functional GRP receptor, with M(r) = 75 kDa and immunologic cross-reactivity with GRP receptor from human small-cell lung carcinoma (SCLC) NCI-H345 cells. Altered regulation of BLP receptors may accompany transformation of normal lung cells to cancer.

Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury

PubMed Central

Najafi, Houshang; Mohamadi Yarijani, Zeynab; Changizi-Ashtiyani, Saeed; Mansouri, Kamran; Modarresi, Masoud; Madani, Seyed Hamid

2017-01-01

Mallow (Malva sylvestris L.) has had medicinal and therapeutic uses in addition to its oral consumption. The present study was conducted to examine the protective effect of Malva sylvestris L. extract on ischemia-reperfusion-induced kidney injury and remote organ injuries in the liver. Before ischemia-reperfusion, rats in the different groups received intraperitoneal normal saline or mallow extract at the doses of 200, 400 or 600 mg/kg of body weight. After 30-minutes of bilateral renal ischemia followed by 24-hours of reperfusion, tissue damage in the kidney and liver samples were determined through studying H&E-stained slides under a light microscope. The degree of leukocyte infiltration and tissue mRNA expressions of TNF- and ICAM-1 were then measured to examine the degree of renal inflammation. The renal tissue MDA and FRAP levels were measured for determining the amount of oxidative stress. Plasma concentrations of creatinine, urea, ALT and ALP were also measured. Ischemia-reperfusion led to a significant increase in plasma concentrations of creatinine, urea, ALT and ALP, and renal tissue MDA, and a significant decrease in renal tissue FRAP. The expression of pro-inflammatory factors in the kidney tissue, the level of leukocyte infiltration and the amount of tissue damage in the kidney and liver also increased. Pretreatment by mallow extract led to a significant improvement in all the variables measured. The 200- and 400-mg doses yielded better results in most parameters compared to the 600-mg dose. The findings showed that mallow extract protects the kidney against ischemia-reperfusion and reduces remote organ injury in the liver. PMID:29155898

Role of Hsp-70 responses in cold acclimation of HUVEC-12 cells.

PubMed

Guan, Hao; Hu, Dahai; Zhao, Zhijing; Cai, Weixia; Zhou, Qin; Yang, Ximing; Yan, Ying; Zhu, Xiongxiang

2015-01-01

Endothelial recovery is a central feature of tissues after frostbite injuries. Thermo tolerance plays an important role in protecting cells against injury after frozen and thawing. The present study aimed to quantitatively assess the injury of human umbilical vein endothelial cells HUVEC-12 after repeated low temperature. Pretreatments (HUVEC-12) cells were repeatedly exposed to cold (1°C/min decrement to -20°C). Their proliferation, death, apoptosis, and protein and mRNA expressions of HSP70 were determined. Endothelial cells after repeated cold exposures were more resistant to apoptosis and necrosis than normal cells. The expressions of HSP70 in cells after repeated cold exposures were significantly higher than in normal HUVEC-12 cells (P < 0.05). Cold acclimation may induce the expression of HSP-70 which plays a protective role in the temperature tolerance.

Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaghloul, M.S.; Dorie, M.J.; Kallman, R.F.

1993-06-15

This study was conducted to examine the radioprotective and radiochemoprotective capabilities of interleukin 1[beta] (IL-1) on two acute-reacting normal tissues of the C3H mouse, the mucosa of the lip and the duodenum. Also assessed was the modulating effect of IL-1 on tumor growth in the same strain of mice. IL-1 was administered to C3H-Km mice in combination with fractionated irradiation, or with cyclophosphamide, cisplatin, or 5-fluorouracil (5FU) followed by irradiation. Normal tissue damage was evaluated in the mouse lip, using a subjective scoring system for tissue reaction, and in the duodenum, using the crypt cell survival assay. RIF-1 fibrosarcoma tumormore » response was assayed with the regrowth delay method. IL-1 protected against the acute reaction produced by fractionated irradiation in the lip mucosa, shifting the dose-response curve by 3.8 Gy. IL-1 was protective when injected intraperitoneally 24 hr before CY or c-DDP, which were given immediately before the first of five daily radiation dose fractions. The dose-response curves for cyclophosphamide and cisplatin were shifted 4.0 Gy and 1.6 Gy, respectively. IL-1 did not protect against 5FU toxicity when treatments were administered in that same sequence; however, when 5FU was given 4 or 8 hr before IL-1 and the first radiation dose fraction followed 20 or 16 hr later, there was significant protection and the curves were separated by 1.5 Gy or 3.5 Gy. IL-1 also protected duodenal crypt cells against the cytocidal effect of fractionated irradiation, with a dose difference of 1.5 Gy and an improvement of crypt survival of 11.7%. It was even more immediately before the first of five daily radiation doses, with the dose differences of 4.4 and 5.3 Gy, respectively, and improvements of crypt survival of 33.8 and 29.9%, respectively. There was no modification by IL-1 of the effect of irradiation alone on the RIF-1 tumor. 45 refs., 8 figs., 1 tab.« less

Mathematical study of probe arrangement and nanoparticle injection effects on heat transfer during cryosurgery.

PubMed

Mirkhalili, Seyyed Mostafa; Ramazani S A, Ahmad; Nazemidashtarjandi, Saeed

2015-11-01

Blood vessels, especially large vessels have a greater thermal effect on freezing tissue during cryosurgery. Vascular networks act as heat sources in tissue, and cause failure in cryosurgery and reappearance of cancer. The aim of this study is to numerically simulate the effect of probe location and multiprobe on heat transfer distribution. Furthermore, the effect of nanoparticles injection is studied. It is shown that the small probes location near large blood vessels could help to reduce the necessary time for tissue freezing. Nanoparticles injection shows that the thermal effect of blood vessel in tissue is improved. Using Au, Ag and diamond nanoparticles have the most growth of ice ball during cryosurgery. However, polytetrafluoroethylene (PTFE) nanoparticle can be used to protect normal tissue around tumor cell due to its influence on reducing heat transfer in tissue. Introduction of Au, Ag and diamond nanoparticles combined with multicryoprobe in this model causes reduction of tissue average temperature about 50% compared to the one probe. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Receptor That Tames the Innate Immune Response

PubMed Central

Brines, Michael; Cerami, Anthony

2012-01-01

Tissue injury, hypoxia and significant metabolic stress activate innate immune responses driven by tumor necrosis factor (TNF)-α and other proinflammatory cytokines that typically increase damage surrounding a lesion. In a compensatory protective response, erythropoietin (EPO) is synthesized in surrounding tissues, which subsequently triggers antiinflammatory and antiapoptotic processes that delimit injury and promote repair. What we refer to as the sequelae of injury or disease are often the consequences of this intentionally discoordinated, primitive system that uses a “scorched earth” strategy to rid the invader at the expense of a serious lesion. The EPO-mediated tissue-protective system depends on receptor expression that is upregulated by inflammation and hypoxia in a distinctive temporal and spatial pattern. The tissue-protective receptor (TPR) is generally not expressed by normal tissues but becomes functional immediately after injury. In contrast to robust and early receptor expression within the immediate injury site, EPO production is delayed, transient and relatively weak. The functional EPO receptor that attenuates tissue injury is distinct from the hematopoietic receptor responsible for erythropoiesis. On the basis of current evidence, the TPR is composed of the β common receptor subunit (CD131) in combination with the same EPO receptor subunit that is involved in erythropoiesis. Additional receptors, including that for the vascular endothelial growth factor, also appear to be a component of the TPR in some tissues, for example, the endothelium. The discoordination of the EPO response system and its relative weakness provide a window of opportunity to intervene with the exogenous ligand. Recently, molecules were designed that preferentially activate only the TPR and thus avoid the potential adverse consequences of activating the hematopoietic receptor. On administration, these agents successfully substitute for a relative deficiency of EPO production in damaged tissues in multiple animal models of disease and may pave the way to effective treatment of a wide variety of insults that cause tissue injury, leading to profoundly expanded lesions and attendant, irreversible sequelae. PMID:22183892

The receptor that tames the innate immune response.

PubMed

Brines, Michael; Cerami, Anthony

2012-05-09

Tissue injury, hypoxia and significant metabolic stress activate innate immune responses driven by tumor necrosis factor (TNF)-α and other proinflammatory cytokines that typically increase damage surrounding a lesion. In a compensatory protective response, erythropoietin (EPO) is synthesized in surrounding tissues, which subsequently triggers antiinflammatory and antiapoptotic processes that delimit injury and promote repair. What we refer to as the sequelae of injury or disease are often the consequences of this intentionally discoordinated, primitive system that uses a "scorched earth" strategy to rid the invader at the expense of a serious lesion. The EPO-mediated tissue-protective system depends on receptor expression that is upregulated by inflammation and hypoxia in a distinctive temporal and spatial pattern. The tissue-protective receptor (TPR) is generally not expressed by normal tissues but becomes functional immediately after injury. In contrast to robust and early receptor expression within the immediate injury site, EPO production is delayed, transient and relatively weak. The functional EPO receptor that attenuates tissue injury is distinct from the hematopoietic receptor responsible for erythropoiesis. On the basis of current evidence, the TPR is composed of the β common receptor subunit (CD131) in combination with the same EPO receptor subunit that is involved in erythropoiesis. Additional receptors, including that for the vascular endothelial growth factor, also appear to be a component of the TPR in some tissues, for example, the endothelium. The discoordination of the EPO response system and its relative weakness provide a window of opportunity to intervene with the exogenous ligand. Recently, molecules were designed that preferentially activate only the TPR and thus avoid the potential adverse consequences of activating the hematopoietic receptor. On administration, these agents successfully substitute for a relative deficiency of EPO production in damaged tissues in multiple animal models of disease and may pave the way to effective treatment of a wide variety of insults that cause tissue injury, leading to profoundly expanded lesions and attendant, irreversible sequelae.

Development of siRNA Technology to Prevent Scar Formation in Tendon Repair

DTIC Science & Technology

2013-12-01

Anti-sense RNA technologies: Under normal conditions cells produce small interfering (si) RNAs that inhibit protein synthesis and stimulate...stimulation of fibroblast proliferation and migration, collagen and fibronectin synthesis , and altered tissue remodeling through regulation of MMPs...expression by an antisense oligonucleotide protects mice from fulminant hepatitis. Nat Biotechnol 2000;18:862-7. 7. Guha M, Xu ZG, Tung D, Lanting L

Snipper, an Eri1 homologue, affects histone mRNA abundance and is crucial for normal Drosophila melanogaster development.

PubMed

Alexiadis, Anastasios; Delidakis, Christos; Kalantidis, Kriton

2017-07-01

The conserved 3'-5' RNA exonuclease ERI1 is implicated in RNA interference inhibition, 5.8S rRNA maturation and histone mRNA maturation and turnover. The single ERI1 homologue in Drosophila melanogaster Snipper (Snp) is a 3'-5' exonuclease, but its in vivo function remains elusive. Here, we report Snp requirement for normal Drosophila development, since its perturbation leads to larval arrest and tissue-specific downregulation results in abnormal tissue development. Additionally, Snp directly interacts with histone mRNA, and its depletion results in drastic reduction in histone transcript levels. We propose that Snp protects the 3'-ends of histone mRNAs and upon its absence, histone transcripts are readily degraded. This in turn may lead to cell cycle delay or arrest, causing growth arrest and developmental perturbations. © 2017 Federation of European Biochemical Societies.

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

PubMed Central

Corre, Isabelle; Guillonneau, Maëva; Paris, François

2013-01-01

Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation. PMID:24252908

Acid sphingomyelinase deficiency in Western diet-fed mice protects against adipocyte hypertrophy and diet-induced liver steatosis.

PubMed

Sydor, Svenja; Sowa, Jan-Peter; Megger, Dominik A; Schlattjan, Martin; Jafoui, Sami; Wingerter, Lena; Carpinteiro, Alexander; Baba, Hideo A; Bechmann, Lars P; Sitek, Barbara; Gerken, Guido; Gulbins, Erich; Canbay, Ali

2017-05-01

Alterations in sphingolipid and ceramide metabolism have been associated with various diseases, including nonalcoholic fatty liver disease (NAFLD). Acid sphingomyelinase (ASM) converts the membrane lipid sphingomyelin to ceramide, thereby affecting membrane composition and domain formation. We investigated the ways in which the Asm knockout (Smpd1 -/- ) genotype affects diet-induced NAFLD. Smpd1 -/- mice and wild type controls were fed either a standard or Western diet (WD) for 6 weeks. Liver and adipose tissue morphology and mRNA expression were assessed. Quantitative proteome analysis of liver tissue was performed. Expression of selected genes was quantified in adipose and liver tissue of obese NAFLD patients. Although Smpd1 -/- mice exhibited basal steatosis with normal chow, no aggravation of NAFLD-type injury was observed with a Western diet. This protective effect was associated with the absence of adipocyte hypertrophy and the increased expression of genes associated with brown adipocyte differentiation. In white adipose tissue from obese patients with NAFLD, no expression of these genes was detectable. To further elucidate which pathways in liver tissue may be affected by Smpd1 -/- , we performed an unbiased proteome analysis. Protein expression in WD-fed Smpd1 -/- mice indicated a reduction in Rictor (mTORC2) activity; this reduction was confirmed by diminished Akt phosphorylation and altered mRNA expression of Rictor target genes. These findings indicate that the protective effect of Asm deficiency on diet-induced steatosis is conferred by alterations in adipocyte morphology and lipid metabolism and by reductions in Rictor activation.

The meninges: new therapeutic targets for multiple sclerosis.

PubMed

Russi, Abigail E; Brown, Melissa A

2015-02-01

The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Compton scattering by internal shields based on melanin-containing mushrooms provides protection of gastrointestinal tract from ionizing radiation.

PubMed

Revskaya, Ekaterina; Chu, Peter; Howell, Robertha C; Schweitzer, Andrew D; Bryan, Ruth A; Harris, Matthew; Gerfen, Gary; Jiang, Zewei; Jandl, Thomas; Kim, Kami; Ting, Li-Min; Sellers, Rani S; Dadachova, Ekaterina; Casadevall, Arturo

2012-11-01

There is a need for radioprotectors that protect normal tissues from ionizing radiation in patients receiving high doses of radiation and during nuclear emergencies. We investigated the possibility of creating an efficient oral radioprotector based on the natural pigment melanin that would act as an internal shield and protect the tissues via Compton scattering followed by free radical scavenging. CD-1 mice were fed melanin-containing black edible mushrooms Auricularia auricila-judae before 9 Gy total body irradiation. The location of the mushrooms in the body before irradiation was determined by in vivo fluorescent imaging. Black mushrooms protected 80% of mice from the lethal dose, while control mice or those given melanin-devoid mushrooms died from gastrointestinal syndrome. The crypts of mice given black mushrooms showed less apoptosis and more cell division than those in control mice, and their white blood cell and platelet counts were restored at 45 days to preradiation levels. The role of melanin in radioprotection was proven by the fact that mice given white mushrooms supplemented with melanin survived at the same rate as mice given black mushrooms. The ability of melanin-containing mushrooms to provide remarkable protection against radiation suggests that they could be developed into oral radioprotectors.

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

PubMed

Uçar, Semra; Pandir, Dilek

2017-11-01

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene.

PubMed

Melo, Luis G; Agrawal, Reitu; Zhang, Lunan; Rezvani, Mojgan; Mangi, Abeel A; Ehsan, Afshin; Griese, Daniel P; Dell'Acqua, Giorgio; Mann, Michael J; Oyama, Junichi; Yet, Shaw-Fang; Layne, Matthew D; Perrella, Mark A; Dzau, Victor J

2002-02-05

Ischemia and oxidative stress are the leading mechanisms for tissue injury. An ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protection from repeated ischemia/reperfusion injury with a single administration of a therapeutic gene. In the present study, we used recombinant adeno-associated virus (rAAV) as a vector for direct delivery of the cytoprotective gene heme oxygenase-1 (HO-1) into the rat myocardium, with the purpose of evaluating this strategy as a therapeutic approach for long-term protection from ischemia-induced myocardial injury. Human HO-1 gene (hHO-1) was delivered to normal rat hearts by intramyocardial injection. AAV-mediated transfer of the hHO-1 gene 8 weeks before acute coronary artery ligation and release led to a dramatic reduction (>75%) in left ventricular myocardial infarction. The reduction in infarct size was accompanied by decreases in myocardial lipid peroxidation and in proapoptotic Bax and proinflammatory interleukin-1beta protein abundance, concomitant with an increase in antiapoptotic Bcl-2 protein level. This suggested that the transgene exerts its cardioprotective effects in part by reducing oxidative stress and associated inflammation and apoptotic cell death. This study documents the beneficial therapeutic effect of rAAV-mediated transfer, before myocardial injury, of a cytoprotective gene that confers long-term myocardial protection from ischemia/reperfusion injury. Our data suggest that this novel "pre-event" gene transfer approach may provide sustained tissue protection from future repeated episodes of injury and may be beneficial as preventive therapy for patients with or at risk of developing coronary ischemic events.

TU-H-CAMPUS-TeP2-05: Selective Protection of Normal Tissue by Cerium Oxide Nanoparticles During Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Z; Ngwa, W; Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA

2016-06-15

Purpose: Cerium oxide nanoparticles (CONPs) have unique pH dependent properties such that they act as a radical modulator. These properties may be used in radiation therapy (RT) to protect normal tissue. This work investigates the selective radioprotection of CONPs in-vitro and potential for in-situ delivery of CONPs in prostate cancer RT. Methods: i) Normal human umbilical vein endothelial cells (HUVEC) and human prostate cancer cells (PC-3) were treated with 0 or 2 ng/mL CONPs (NP size: 5 nm). 2 Gy of 100 kVp radiation was delivered to the cells 4 hours after the CONP treatment. Cell viability was checked 48more » hours later using MTS assays. ii) A prostate tumor was modeled as a 2-cm diameter sphere. CONPs were proposed to be loaded in a hollow radiotherapy fiducial marker. The concentration profile for the CONPs within the tumor was modeled with a previously validated diffusion equation employed in other studies for nanoparticles 10 nm or less. Results: i) Without radiation, cell viability was above 90% when treated with 2 ng/mL CONPs for both HUVEC and PC-3. After irradiation, a slightly higher viability was observed in HUVEC with CONPs than the ones without CONPs, and this effect was not observed in PC-3. ii) Based on the calculations, 2 ng/mL of CONPs could be delivered to normal cells by diffusion with a 1 µg/mL initial concentration within two weeks. Conclusion: We conclude that CONPs can provide selective radioprotection. The delivery of needed concentrations of CONPs is feasible via in-situ release from radiotherapy biomaterials (e.g. fiducials) loaded with the CONPs.« less

Evaluation of adenoassociated virus 2 and human papilloma virus 16 and 18 infection in cervical cancer biopsies.

PubMed

Ahn, Woong Shick; Bae, Su Mi; Chung, Jae Eun; Lee, Hyun Kyung; Kim, Byung Kee; Lee, Joon Mo; Namkoong, Sung Eun; Kim, Chong Kook; Sin, Jeong- Im

2003-04-01

Protective roles of adenoassociated virus (AAV) 2 in cervical tumorigenesis are controversial. In an effort to clarify this issue, we tested prevalence of AAV 2 and human papillomavirus (HPV) infection in cervical lesions and adjacent normal tissues. Tissues of cervical intraepithelial neoplasm (CIN) I (20 patients), CIN II (24 patients), CIN III (25 patients), and invasive cancer (23 patients) were investigated by microdissection and PCR using HPV-16-, HVP-18-, and AAV-2-specific primers. AAV 2 was detected in 11 out of 20 CIN I (55%), 21 out of 24 CIN II (84.5%), 13 out of 25 CIN III (52%), and 12 out of 23 invasive cancer cases (52.2%). However, HPV 16 was detected in none out of 20 CIN I, 2 out of 24 CIN II (8.3%), 6 out of 25 CIN III (24%), and 6 out of 23 invasive cancer cases (26.1%). HPV 18 was detected in 1 case in CIN II (4.2%) and 2 cases in CIN III (8%). In 92 perilesional normal tissues, AAV 2 was detected in 53 cases (57.6%), displaying 25% of CIN I, 83.3% of CIN II, 52% of CIN III, and 65.2% of invasive cancer. The differences in AAV 2 prevalence are not significant between CIN and normal tissues. However, differences in HPV 16 are significant in CIN III and invasive cancer, as compared to CIN I, CIN II, and normal, suggesting no significant correlation between AAV 2 and cervical cancer. Thus, these results support the notion that AAV 2 is not associated with cervical tumorigenesis.

Toll-like Receptor 5 Agonist Protects Mice From Dermatitis and Oral Mucositis Caused by Local Radiation: Implications for Head-and-Neck Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burdelya, Lyudmila G.; Gleiberman, Anatoli S.; Toshkov, Ilia

2012-05-01

Purpose: Development of mucositis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. We have recently reported that bacterial flagellin, an agonist of Toll-like receptor 5 (TLR5), can protect rodents and primates from acute radiation syndrome caused by total body irradiation. Here we analyzed the radioprotective efficacy of TLR5 agonist under conditions of local, single dose or fractionated radiation treatment. Methods and Materials: Mice received either single-dose (10, 15, 20, or 25 Gy) or fractioned irradiation (cumulative dose up to 30 Gy) of the head-and-neck area with or without subcutaneous injection of pharmacologically optimized flagellin, CBLB502, 30more » min before irradiation. Results: CBLB502 significantly reduced the severity of dermatitis and mucositis, accelerated tissue recovery, and reduced the extent of radiation induced weight loss in mice after a single dose of 15 or 20 Gy but not 25 Gy of radiation. CBLB502 was also protective from cumulative doses of 25 and 30 Gy delivered in two (10 + 15 Gy) or three (3 Multiplication-Sign 10 Gy) fractions, respectively. While providing protection to normal epithelia, CBLB502 did not affect the radiosensitivity of syngeneic squamous carcinoma SCCVII grown orthotopically in mice. Use of CBLB502 also elicited a radiation independent growth inhibitory effect upon TLR5-expressing tumors demonstrated in the mouse xenograft model of human lung adenocarcinoma A549. Conclusion: CBLB502 combines properties of supportive care (radiotherapy adjuvant) and anticancer agent, both mediated via activation of TLR5 signaling in the normal tissues or the tumor, respectively.« less

Nigella sativa oil protects against tartrazine toxicity in male rats.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Hamed, Amani Mohammed; Zamazami, Mazin A

2018-01-01

This study aimed to evaluate the protective role of Nigella sativa oil against the adverse effects of tartrazine on male rats. 18 albino rats were divided randomly into four groups (n = 6). The first (G1) is the negative control, the second group (G2) is the positive control received 10 mg/kg b.w. tartrazine in the diet and the third (G3) received the same dose of tartrazine as in G2 and co-treated with Nigella sativa oil for 8 weeks. Tartrazine decreased total protein, antioxidants and high density lipoproteins, whereas increased liver enzyme, kidney function parameters, total cholesterol, triglycerides, low density lipoproteins and lipid peroxidation in the positive control group. In addition, it caused pathological changes in the tissues of liver, kidney, testes and stomach. Treating tartrazine supplemented rats of G3 with Nigella sativa oil for 8 weeks significantly improved all biochemical parameters and restored the tissues of kidney, stomach, testes and liver to normal. It could be concluded that N. sativa oil succeeded in protecting male rats against the adverse conditions resulted from tartrazine administration.

Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

PubMed

Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

2017-03-01

- Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

PAF levels and PAF-AH activities in placentas from normal and preeclamptic pregnancies.

PubMed

Gu, Y; Burlison, S A; Wang, Y

2006-01-01

The aim of this study was to determine: (1) platelet-activating factor (PAF) levels and PAF-acetylhydrolase (PAF-AH) activities in normal and preeclamptic placentas; (2) lipid peroxide production by placental tissues stimulated with PAF. Placentas were obtained immediately after delivery from normal and preeclamptic pregnancies. Tissue pieces were snap frozen in liquid nitrogen and stored at -70 degrees C. One gram of tissue from each placenta was used for PAF extraction and for total RNA isolation. PAF was measured by PAF [3H] scintillation proximity assay (SPA) system. Trophoblast PAF-AH activity was determined by enzyme-linked immunosorbent assay (ELISA). mRNA expression for PAF receptor was assessed by RNase protection assay (RPA). Normal placental explants were incubated with PAF at concentrations of 1 and 10 microg/ml for 48 h. Lipid peroxide productions of 8-isoprostane and malondialdehyde (MDA) were measured by ELISA and thiobarbituric acid reaction, respectively. Data were presented as mean+/-SE and analyzed by nonparametric Mann-Whitney U test and ANOVA. A p level less than 0.05 was considered statistically significant. (1) The mean tissue level for PAF was elevated, but not statistically different, in preeclamptic (n=7) than in normal (n=8) placentas, 6.45+/-1.05 versus 4.47+/-0.60 ng/g, p=0.42. (2) PAF-AH activity was higher in trophoblasts from preeclamptic (n=7) placentas than that in trophoblasts from normal (n=8) placentas, 0.69+/-0.16 versus 0.38+/-0.03 micromol/min/microg protein, p<0.05. (3) The relative mRNA expression for PAF receptor was not different between normal (0.70+/-0.08) and preeclamptic (0.76+/-0.13) placental tissues, p=0.60. (4) Productions of 8-isoprostane and MDA were not increased in tissues with PAF in culture, 8-isoprostane: 0.37+/-0.09 ng/mg (control) versus 0.32+/-0.09 ng/mg (1 microg/ml) and 0.37+/-0.07 ng/mg (10 microg/ml), p>0.5; MDA: 0.62+/-0.05 nmol/mg (control) versus 0.68+/-0.04 nmol/mg (1 microg/ml) and 0.69+/-0.03 nmol/mg (10 microg/ml), p>0.5. Increased PAF-AH activity in trophoblasts may be a compensatory effect to control PAF level in the preeclamptic placenta. The co-existence of PAF-AH and PAF receptor in trophoblasts suggests an autocrine regulation of PAF in these cells to limit PAF and its metabolites within the placenta.

RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

PubMed

Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

2017-01-01

According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Amelioration of ethanol induced apoptotic DNA damage and ulcerative injuries in the mice gastric tissues by starch oral administration.

PubMed

Hamad, Sherin Ramadan; Hamad Mohamed, Hanan Ramadan

2018-02-01

Nowadays, gastric ulcers have become very common gastrointestinal disorders and numerous natural plant extracts exert promising anti-ulcerative effects. Therefore, this study was designed to evaluate the possible protective effect of dietary starch against ethanol induced gastric ulcers in mice. Post-administration of dietary starch for three consecutive days caused remarkable ameliorations in hemorrhagic lesions in gastric mucus and significant suppression in % incidence of ulceration, ulcer index and ulcer score induced by ethanol single administration. Indeed, deep ulceration, necrosis, disruption and degeneration in large areas of mucosa layer together with dense inflammatory cells infiltration and edema in sub-mucosal layer induced by ethanol administration were attenuated by starch post-administration and normalized the tissue architecture of the stomach. This potential protective effect could be attributed to the potent anti-oxidative capacity of starch that causes scavenger of the reactive oxygen species and thereby decreasing single and double DNA stranded break inductions and apoptotic DNA damage revealed by returning the p53 and caspase-3 expression levels to the normal level compared to the ethanol treated group. In conclusion, dietary starch has a potent therapeutic effect against ethanol induced gastric ulcer in mice via its free radical scavengers ability. Thus, we recommended further studies on its possible use as antiulcer drugs.

Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

NASA Astrophysics Data System (ADS)

Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

2011-01-01

We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

Cellular Mechanisms of Somatic Stem Cell Aging

PubMed Central

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

Acoustic microscopy analyses to determine good vs. failed tissue engineered oral mucosa under normal or thermally stressed culture conditions.

PubMed

Winterroth, Frank; Lee, Junho; Kuo, Shiuhyang; Fowlkes, J Brian; Feinberg, Stephen E; Hollister, Scott J; Hollman, Kyle W

2011-01-01

This study uses scanning acoustic microscopy (SAM) ultrasonic profilometry to determine acceptable vs. failed tissue engineered oral mucosa. Specifically, ex vivo-produced oral mucosal equivalents (EVPOMEs) under normal or thermally stressed culture conditions were scanned with the SAM operator blinded to the culture conditions. As seeded cells proliferate, they fill in and smooth out the surface irregularities; they then stratify and produce a keratinized protective upper layer. Some of these transformations could alter backscatter of ultrasonic signals and in the case of the thermally stressed cells, produce backscatter similar to an unseeded device. If non-invasive ultrasonic monitoring could be developed, then tissue cultivation could be adjusted to measure biological variations in the stratified surface. To create an EVPOME device, oral mucosa keratinocytes were seeded onto acellular cadaveric dermis. Two sets of EVPOMEs were cultured: one at physiological temperature 37 °C and the other at 43 °C. The specimens were imaged with SAM consisting of a single-element transducer: 61 MHz center frequency, 32 MHz bandwidth, 1.52 f#. Profilometry for the stressed and unseeded specimens showed higher surface irregularities compared to unstressed specimens. Elevated thermal stress retards cellular differentiation, increasing root mean square values; these results show that SAM can potentially monitor cell/tissue development.

Iodide Protects Heart Tissue from Reperfusion Injury

PubMed Central

Iwata, Akiko; Morrison, Michael L.; Roth, Mark B.

2014-01-01

Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury. PMID:25379708

Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase.

PubMed Central

Baker, G L; Corry, R J; Autor, A P

1985-01-01

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3840348

Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system

PubMed Central

Imanaka-Yoshida, Kyoko; Aoki, Hiroki

2014-01-01

Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID:25120494

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action

PubMed Central

Bhattacharya, S; Banerjee, D; Bauri, AK; Chattopadhyay, S; Bandyopadhyay, SK

2007-01-01

AIM: To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties. METHODS: Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 μg/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. RESULTS: Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 μg/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better. CONCLUSION: APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties. PMID:17659730

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action.

PubMed

Bhattacharya, S; Banerjee, D; Bauri, A-K; Chattopadhyay, S; Bandyopadhyay, S-K

2007-07-21

To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties. Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 mug/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 mug/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better. APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

PubMed Central

Han, Mingda

2016-01-01

Background Embryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation. Methods On the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein. Results EtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta. Conclusion EtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27296863

Monitoring Sunitinib-Induced Vascular Effects to Optimize Radiotherapy Combined with Soy Isoflavones in Murine Xenograft Tumor1

PubMed Central

Hillman, Gilda Gali; Singh-Gupta, Vinita; Al-Bashir, Areen K; Yunker, Christopher K; Joiner, Michael C; Sarkar, Fazlul H; Abrams, Judith; Haacke, E Mark

2011-01-01

Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor vascular changes induced by sunitinib within a murine xenograft kidney tumor, we previously determined a dose that caused only partial destruction of blood vessels leading to “normalization” of tumor vasculature and improved blood flow. In the current study, kidney tumors were treated with this dose of sunitinib to modify the tumor microenvironment and enhance the effect of kidney tumor irradiation. The addition of soy isoflavones to this combined antiangiogenic and radiotherapy approach was investigated based on our studies demonstrating that soy isoflavones can potentiate the radiation effect on the tumors and act as antioxidants to protect normal tissues from treatment-induced toxicity. DCE-MRI was used to monitor vascular changes induced by sunitinib and schedule radiation when the uptake and washout of the contrast agent indicated regularization of blood flow. The combination of sunitinib with tumor irradiation and soy isoflavones significantly inhibited the growth and invasion of established kidney tumors and caused marked aberrations in the morphology of residual tumor cells. DCE-MRI studies demonstrated that the three modalities, sunitinib, radiation, and soy isoflavones, also exerted antiangiogenic effects resulting in increased uptake and clearance of the contrast agent. Interestingly, DCE-MRI and histologic observations of the normal contralateral kidneys suggest that soy could protect the vasculature of normal tissue from the adverse effects of sunitinib. An antiangiogenic approach that only partially destroys inefficient vessels could potentially increase the efficacy and delivery of cytotoxic therapies and radiotherapy for unresectable primary renal cell carcinoma tumors and metastatic disease. PMID:21461174

Epilobium angustifolium extract demonstrates multiple effects on dermal fibroblasts in vitro and skin photo-protection in vivo.

PubMed

Ruszová, Ema; Cheel, José; Pávek, Stanislav; Moravcová, Martina; Hermannová, Martina; Matějková, Ilona; Spilková, Jiřina; Velebný, Vladimír; Kubala, Lukáš

2013-09-01

Stress-induced fibroblast senescence is thought to contribute to skin aging. Ultraviolet light (UV) radiation is the most potent environmental risk factor in these processes. An Epilobium angustifolium (EA) extract was evaluated for its capacity to reverse the senescent response of normal human dermal fibroblasts (NHDF) in vitro and to exhibit skin photo-protection in vivo. The HPLC-UV-MS analysis of the EA preparation identified three major polyphenol groups: tannins (oenothein B), phenolic acids (gallic and chlorogenic acids) and flavonoids. EA extract increased the cell viability of senescent NHDF induced by serum deprivation. It diminished connective tissue growth factor and fibronectin gene expressions in senescent NHDF. Down-regulation of the UV-induced release of both matrix metalloproteinase-1 and -3 and the tissue inhibitor of matrix metalloproteinases-1 and -2, and also down-regulation of the gene expression of hyaluronidase 2 were observed in repeatedly UV-irradiated NHDF after EA extract treatment. Interestingly, EA extract diminished the down-regulation of sirtuin 1 dampened by UV-irradiation. The application of EA extract using a sub-irritating dose protected skin against UV-induced erythema formation in vivo. In summary, EA extract diminished stress-induced effects on NHDF, particularly on connective tissue growth factor, fibronectin and matrix metalloproteinases. These results collectively suggest that EA extract may possess anti-aging properties and that the EA polyphenols might account for these benefits.

Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

PubMed Central

Marinković, Aleksandar; Mih, Justin D.; Park, Jin-Ah; Liu, Fei

2012-01-01

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation. PMID:22659883

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

PubMed Central

Kosmacek, Elizabeth A.; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley, Rebecca E.

2016-01-01

Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers. PMID:27119354

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells.

PubMed

Kosmacek, Elizabeth A; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley-Deegan, Rebecca E

2016-06-07

Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers.

Protection and Sensitization of Human Cells to Proton Radiation by Cerium Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Carlson, Nathan B.

In radiation therapy for the treatment of cancer, there is demand for novel approaches that will improve tumor cell killing while protecting healthy tissue. One such approach that has shown considerable promise is the application of nanoparticles as radiation sensitizers for tumor cells and as radiation protectants for healthy tissue. In this investigation, cerium oxide nanoparticles (CNPs) obtained from the University of Central Florida's NanoScience Technology Center were studied for their protective effect to charged particle radiation in non-malignant breast cells, and for their sensitizing effect in breast and prostate cancer cell lines. These experiments were conducted at East Carolina University, where human cells were grown in the cell culture facility in the Department of Biology and then irradiated with energetic protons in the Accelerator Laboratory in the Department of Physics. Prior to irradiation, the cells were treated with distinct CNP preparations ranging in concentrations from 10 nanomolar to 10 micromolar, and cell viability was assessed using multiple assays post-irradiation. Radioprotection and radiosensitization were observed for several of the CNP treatments tested. Ultimately, the goal is to find a specific nanoparticle treatment that holds the synergistic effect of enhancing the rate of killing in tumor cells while simultaneously improving the survival of normal cells.

Release of overexpressed CypB activates ERK signaling through CD147 binding for hepatoma cell resistance to oxidative stress.

PubMed

Kim, Kiyoon; Kim, Hunsung; Jeong, Kwon; Jung, Min Hyung; Hahn, Bum-Soo; Yoon, Kyung-Sik; Jin, Byung Kwan; Jahng, Geon-Ho; Kang, Insug; Ha, Joohun; Choe, Wonchae

2012-08-01

Cyclophilin, a cytosolic receptor for the immunosuppressive drug cyclosporin A, plays a role in diverse pathophysiologies along with its receptor, CD147. Although the interaction between cyclophilin A and CD147 is well established in inflammatory disease, that of cyclophilin B (CypB) with CD147 has not been fully explored, especially in cancer cell biology, and the exact molecular mechanism underlying such an association is poorly understood. In this study, we first identified high expression levels of CypB in 54 % of hepatocellular carcinoma patient tissues but in only 12.5 % of normal liver tissues. Then, we demonstrated that CypB overexpression protects human hepatoma cells against oxidative stress through its binding to CD147; this protective effect depends on the peptidyl prolyl isomerase activity of CypB. siRNA-mediated knockdown of CypB expression rendered hepatoma cells more vulnerable to ROS-mediated apoptosis. Furthermore, we also determined that a direct interaction between secreted CypB and CD147 regulates the extracellular signal-regulated kinase intracellular signaling pathway and is indispensible for the protective functions of CypB. For the first time, we demonstrated that CypB has an essential function in protecting hepatoma cells against oxidative stress through binding to CD147 and regulating the ERK pathway.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

PubMed

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

NASA Astrophysics Data System (ADS)

Rendon, Cesar A.; Lilge, Lothar

2004-10-01

In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

Predicting Sensitivity of Breast Tumors to Src-targeted Therapies Through Assessment of Cas/Src/BCAR3 Activity

DTIC Science & Technology

2017-10-01

expression is elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and DCIS... compared to IDC. (2) BCAR3 is significantly upregulated in triple negative breast cancer and normal tissue; (3) BCAR3 expression shows a modest...expression was seen to be elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and

Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

PubMed

Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

2009-06-01

In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy.

Protectin D1n-3 DPA and resolvin D5n-3 DPA are effectors of intestinal protection

PubMed Central

Gobbetti, Thomas; Dalli, Jesmond; Colas, Romain A.; Federici Canova, Donata; Aursnes, Marius; Bonnet, Delphine; Alric, Laurent; Vergnolle, Nathalie; Deraison, Celine; Hansen, Trond V.; Serhan, Charles N.

2017-01-01

The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within the affected tissue; failure of effective resolution may lead to tissue injury. Because persistence of inflammatory signals is a main feature of chronic inflammatory conditions, including inflammatory bowel diseases (IBDs), herein we investigate expression and functions of SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human IBD colon biopsies, quantifying a significant up-regulation of the resolvin and protectin pathway compared with normal gut tissue. Systemic treatment with protectin (PD)1n-3 DPA or resolvin (Rv)D5n-3 DPA protected against colitis and intestinal ischemia/reperfusion-induced inflammation in mice. Inhibition of 15-lipoxygenase activity reduced PD1n-3 DPA and augmented intestinal inflammation in experimental colitis. Intravital microscopy of mouse mesenteric venules demonstrated that PD1n-3 DPA and RvD5n-3 DPA decreased the extent of leukocyte adhesion and emigration following ischemia-reperfusion. These data were translated by assessing human neutrophil–endothelial interactions under flow: PD1n-3 DPA and RvD5n-3 DPA reduced cell adhesion onto TNF-α–activated human endothelial monolayers. In conclusion, we propose that innovative therapies based on n-3 DPA-derived mediators could be developed to enable antiinflammatory and tissue protective effects in inflammatory pathologies of the gut. PMID:28356517

BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

PubMed Central

Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi, Marco Martins; Caetano, Edie Benedito

2015-01-01

Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers. PMID:27022549

Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

NASA Astrophysics Data System (ADS)

Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

2011-08-01

Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

Transvaginal photoacoustic imaging probe and system based on a multiport fiber-optic beamsplitter and a real time imager for ovarian cancer detection

NASA Astrophysics Data System (ADS)

Kumavor, Patrick D.; Alqasemi, Umar; Tavakoli, Behnoosh; Li, Hai; Yang, Yi; Zhu, Quing

2013-03-01

This paper presents a real-time transvaginal photoacoustic imaging probe for imaging human ovaries in vivo. The probe consists of a high-throughput (up to 80%) fiber-optic 1 x 19 beamsplitters, a commercial array ultrasound transducer, and a fiber protective sheath. The beamsplitter has a 940-micron core diameter input fiber and 240-micron core diameter output fibers numbering 36. The 36 small-core output fibers surround the ultrasound transducer and delivers light to the tissue during imaging. A protective sheath, modeled in the form of the transducer using a 3-D printer, encloses the transducer with array of fibers. A real-time image acquisition system collects and processes the photoacoustic RF signals from the transducer, and displays the images formed on a monitor in real time. Additionally, the system is capable of coregistered pulse-echo ultrasound imaging. In this way, we obtain both morphological and functional information from the ovarian tissue. Photoacousitc images of malignant human ovaries taken ex vivo with the probe revealed blood vascular and networks that was distinguishable from normal ovaries, making the probe potential useful for characterizing ovarian tissue.

Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue

PubMed Central

Into, T; Inomata, M; Kanno, Y; Matsuyama, T; Machigashira, M; Izumi, Y; Imamura, T; Nakashima, M; Noguchi, T; Matsushita, K

2006-01-01

Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In this study, we found that the expression of secretory leucocyte protease inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was reduced in gingival tissues with chronic periodontitis associated with P. gingivalis infection. The addition of vesicles of P. gingivalis decreased the amount of SLPI in the media of primary human gingival keratinocytes compared to untreated cultures. We therefore investigated how arginine-specific gingipains (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors in the vesicles and cleave a wide range of in-host proteins. We found that Rgps digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI disrupted SLPI functions, which normally suppresses neutrophil elastase and neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured human gingival fibroblasts. The protease inhibitory action of SLPI was not exerted towards Rgps. These results suggest that Rgps reduce the protective effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds, by which disease in gingival tissue may be accelerated at the sites with P. gingivalis infection. PMID:16907925

The significance of saliva during sleep and the relevance of oromotor movements.

PubMed

Thie, Norman M R; Kato, Takafumi; Bader, Gaby; Montplaisir, Jacques Y; Lavigne, Gilles J

2002-06-01

Saliva is an essential component of the oroesophageal milieu and allows for normal speech, taste, mastication, food bolus formation and swallowing. Saliva has important functions in protecting the hard and soft tissues of the oral cavity from acids and pathogenic microbes. A large number of people suffer either subjective or objective alterations in quantity and/or quality of their saliva that may be secondary to disease, medications, medical treatments or emotional events. Sleep-related xerostomia is a sensation of dry mouth associated with a report of either mouth and/or throat discomfort that induces awakenings for water intake. The prevalence of self-reported dry mouth complaint during sleep (associated with awakening and water intake) in a Canadian survey was estimated at 23%. The biological significance of decreased saliva during sleep is unknown and it is unclear how the oral cavity compensates for this period of relative dryness. The amount of saliva produced is greatest during the waking hours of the day and diminishes dramatically during sleep and may represent another process in the human body that displays a circadian rhythmicity. Salivary secretion during wakefulness is, in part, associated with oromotor activity involving the masticatory muscles. Rhythmic masticatory muscle activity and swallowing are non-disruptive events that occur during normal sleep. We hypothesize herein that lubrication from saliva is necessary during sleep to protect tissue integrity and health of oroesophageal structures.

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage.

PubMed

Velalopoulou, Anastasia; Chatterjee, Shampa; Pietrofesa, Ralph A; Koziol-White, Cynthia; Panettieri, Reynold A; Lin, Liyong; Tuttle, Stephen; Berman, Abigail; Koumenis, Constantinos; Christofidou-Solomidou, Melpo

2017-11-25

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

PubMed Central

Velalopoulou, Anastasia; Chatterjee, Shampa; Pietrofesa, Ralph A.; Koziol-White, Cynthia; Panettieri, Reynold A.; Lin, Liyong; Tuttle, Stephen; Berman, Abigail; Koumenis, Constantinos; Christofidou-Solomidou, Melpo

2017-01-01

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung. PMID:29186841

Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

PubMed Central

Kim, J. Julie; Kurita, Takeshi

2013-01-01

Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.

PubMed

Elloumi, Fathi; Hu, Zhiyuan; Li, Yan; Parker, Joel S; Gulley, Margaret L; Amos, Keith D; Troester, Melissa A

2011-06-30

Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.

Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity.

PubMed

Eisinger, Kristina; Rein-Fischboeck, Lisa; Neumeier, Markus; Schmidhofer, Sandra; Pohl, Rebekka; Haberl, Elisabeth M; Liebisch, Gerhard; Kopp, Andrea; Schmid, Andreas; Krautbauer, Sabrina; Buechler, Christa

2018-06-01

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA-/- animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans. Copyright © 2018 Elsevier Inc. All rights reserved.

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orton, C; Borras, C; Carlson, D

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protectionmore » will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how they might be used to address clinically relevant problems. Underlying assumptions and limitations of existing models and their proper application will be discussed. This multidisciplinary educational session combines the fundamentals of radiobiology for radiation therapy and radiation protection with the practical application of biophysical models for treatment planning and evaluation. Learning Objectives: To understand fractionation in teletherapy and dose rate techniques in brachytherapy. To understand how the linear-quadratic models the effect of radiobiological parameters for radiotherapy. To understand the radiobiological basis of radiation protection standards applied to radiotherapy. To distinguish between stochastic effects and tissue reactions. To learn how to apply concepts of biological effective dose and RBE-weighted dose and to incorporate biological factors that alter radiation response. To discuss clinical strategies to increase therapeutic ratio, i.e., maximize local control while minimizing the risk of acute and late normal tissue effects.« less

Application of hyperosmotic agent to determine gastric cancer with optical coherence tomography ex vivo in mice

NASA Astrophysics Data System (ADS)

Xiong, Honglian; Guo, Zhouyi; Zeng, Changchun; Wang, Like; He, Yonghong; Liu, Songhao

2009-03-01

Noninvasive tumor imaging could lead to the early detection and timely treatment of cancer. Optical coherence tomography (OCT) has been reported as an ideal diagnostic tool for distinguishing tumor tissues from normal tissues based on structural imaging. In this study, the capability of OCT for functional imaging of normal and tumor tissues based on time- and depth-resolved quantification of the permeability of biomolecules through these tissues is investigated. The orthotopic graft model of gastric cancer in nude mice is used, normal and tumor tissues from the gastric wall are imaged, and a diffusion of 20% aqueous solution of glucose in normal stomach tissues and gastric tumor tissues is monitored and quantified as a function of time and tissue depth by an OCT system. Our results show that the permeability coefficient is (0.94+/-0.04)×10-5 cm/s in stomach tissues and (5.32+/-0.17)×10-5 cm/s in tumor tissues, respectively, and that tumor tissues have a higher permeability coefficient compared to normal tissues in optical coherence tomographic images. From the results, it is found that the accurate and sensitive assessment of the permeability coefficients of normal and tumor tissues offers an effective OCT image method for detection of tumor tissues and clinical diagnosis.

Mesenchymal stem cells for cartilage repair in osteoarthritis

PubMed Central

2012-01-01

Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA. PMID:22776206

Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility

PubMed Central

Fang, Xue; Li, Xuelian; Yin, Zhihua; Xia, Lingzi; Quan, Xiaowei; Zhao, Yuxia; Zhou, Baosen

2017-01-01

Single nucleotide polymorphism (SNP) may influence the genesis and development of cancer in a variety of ways depending on their location. Here we conducted a study in Chinese female non-smokers to investigate the relationship between rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. Finally, we evaluated the relationship between expression level of CAV1 and prognosis of lung cancer. The results showed that the rs1049337-C allele and rs926198-C allele were the protective alleles of lung cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The result of luciferase reporter assay showed that rs1049337 can affect the binding affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and H1299 cell line. Compared with C allele, T allele had a relatively decreased luciferase activity. Compared with paired normal adjacent tissue or normal lung tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those patients at early stage of lung cancer, the expression level of CAV1 in patients at late stage of lung cancer was relatively low. In conclusion, the results indicated that rs1049337, it's a SNP located at 3′UTR region of CAV1 may affect lung cancer risk by altering the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. PMID:29190968

Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

PubMed

Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

2017-04-01

Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

SR-BI as target in atherosclerosis and cardiovascular disease - A comprehensive appraisal of the cellular functions of SR-BI in physiology and disease.

PubMed

Hoekstra, Menno

2017-03-01

High-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein species due to its role in reverse cholesterol transport. HDL delivers cholesterol esters to the liver through selective uptake by scavenger receptor class B type I (SR-BI). In line with the protective role for HDL in the context of cardiovascular disease, studies in mice and recently also in humans have shown that a disruption of normal SR-BI function predisposes subjects to the development of atherosclerotic lesions and cardiovascular disease. Although SR-BI function has been studied primarily in the liver, it should be acknowledged that the SR-BI protein is expressed in multiple tissues and cell types across the body, albeit at varying levels between the different tissues. Given that SR-BI is widely expressed throughout the body, multiple cell types and tissues can theoretically contribute to the atheroprotective effect of SR-BI. In this review the different functions of SR-BI in normal physiology are highlighted and the (potential) consequences of cell type-specific disruption of SR-BI function for atherosclerosis and cardiovascular disease susceptibility discussed. It appears that hepatocyte and platelet SR-BI inhibit respectively the development of atherosclerotic lesions and thrombosis, suggesting that SR-BI located on these cell compartments should be regarded as being a protective factor in the context of cardiovascular disease. The relative contribution of SR-BI present on endothelial cells, steroidogenic cells, adipocytes and macrophages to the pathogenesis of atherosclerosis and cardiovascular disease remains less clear, although proper SR-BI function in these cells does appear to influence multiple processes that impact on cardiovascular disease susceptibility. Copyright © 2017 The Author. Published by Elsevier B.V. All rights reserved.

Modulation of Genetic and Epigenetic Biomarkers of Colorectal Cancer in Humans by Black Raspberries: A Phase I Pilot Study

PubMed Central

Wang, Li-Shu; Arnold, Mark; Huang, Yi-Wen; Sardo, Christine; Seguin, Claire; Martin, Edward; Huang, Tim H.-M.; Riedl, Ken; Schwartz, Steven; Frankel, Wendy; Pearl, Dennis; Xu, Yiqing; Winston, John; Yang, Guang-Yu; Stoner, Gary

2010-01-01

Purpose This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis and expression of Wnt pathway genes. Experimental Design Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60g/day) for 1-to-9 wks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured. Results The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received an average of 4 wks of BRB treatment, but not in all 20 patients with 1-to-9 wks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis and angiogenesis in a protective direction. Conclusions These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted. PMID:21123457

THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE

PubMed Central

Fell, Honor B.; Weiss, L.

1965-01-01

1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes. PMID:14276776

ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

PubMed

Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response?

PubMed

Razmkhah, Mahboobeh; Jaberipour, Mansooreh; Erfani, Nasrollah; Habibagahi, Mojtaba; Talei, Abdol-rasoul; Ghaderi, Abbas

2011-01-01

Immunomodulatory function of bone marrow derived mesenchymal stem cells in cancer has recently been investigated. But the resident mesenchymal stem cells as whole in cancer and in the breast cancer tissue have not been studied well. In the present work we isolated adipose derived stem cells (ASCs) from breast cancer and normal breast tissues to investigate the expressions of IL-4, IL-10 and transforming growth factor (TGF)-β1 in ASCs and to see if ASCs isolated from patients can modulate the regulatory molecules on peripheral blood lymphocytes. Our results showed that IL-10 and TGF-β1 have significantly higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals (P value <0.05). The culture supernatant of ASCs isolated from breast cancer patients with pathological stage III induced upregulation of the mRNA expression levels of IL-4, TGF-β1, IL-10, CCR4 and CD25 in PBLs. In addition, the percentage of CD4+CD25(high)Foxp3(+) T regulatory cells was increased in vitro. When the same culture supernatant was added to ASCs isolated from normal subjects augmentation of the mRNA expressions of IL-4, IL-10, IL-8, MMP2, VEGF and SDF-1 in normal ASCs was also observed. These data collectively conclude that resident ASCs in breast cancer tissue may have crucial roles in breast tumor growth and progression by inducing regulatory molecules and promoting anti-inflammatory reaction within the tumor microenvironment. Further investigation is required to see if the immune suppression induced by ASCs is an independent property from tumor cells or ASCs gain their immunosuppressive potential from malignant cells. Copyright © 2010 Elsevier Inc. All rights reserved.

JV Task 96 - Phase 2 - Investigating the Importance of the Mercury-Selenium Interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas Ralston; Laura Raymond

2008-03-01

In order to improve the understanding of the mercury issue, it is vital to study mercury's effects on selenium physiology. While mercury present in the environment or food sources may pose health risks, the protective effects of selenium have not been adequately considered in establishing regulatory policy. Numerous studies report that vulnerability to mercury toxicity is inversely proportional to selenium status or level. However, selenium status has not been considered in the development of the reference dosage levels for mercury exposure. Experimental animals fed low-selenium diets are far more vulnerable to mercury toxicity than animals fed normal selenium, and animalsmore » fed selenium-rich diets are even more resistant. Selenium-dependent enzymes in brain and endocrine tissues can be impaired by excessive mercury exposure, apparently because mercury has an extremely high binding affinity for selenium. When selenium becomes bound to mercury, it is unable to participate in the metabolic cycling of selenoprotein synthesis. Because of mercury-dependent impairments of selenoprotein synthesis, various antioxidant and regulatory functions in brain biochemistry are compromised. This report details a 2-year multiclient-funded research program designed to examine the interactions between mercury and selenium in animal models. The studies explored the effects of dietary intakes of toxic amounts of methylmercury and the protective effects of the normal dietary range of selenium in counteracting mercury toxicity. This study finds that the amounts of selenium present in ocean fish are sufficient to protect against far larger quantities of methylmercury than those present in typical seafoods. Toxic effects of methylmercury exposure were not directly proportional to mercury concentrations in blood, brain, or any other tissues. Instead, mercury toxicity was proportional to molar ratios of mercury relative to selenium. In order to accurately assess risk associated with methylmercury or mercury exposures, mercury-selenium ratios appear to be far more accurate and effective in identifying risk and protecting human and environmental health. This study also finds that methylmercury toxicity can be effectively treated by dietary selenium, preventing the death and progressive disabilities that otherwise occur in methylmercury-treated subjects. Remarkably, the positive response to selenium therapy was essentially equivalent regardless of whether or not toxic amounts of methylmercury were still administered. The findings of the Physiologically Oriented Integration of Nutrients and Toxins (POINT) models of the effects of mercury and selenium developed in this project are consistent with the hypothesis that mercury toxicity arises because of mercury-dependent inhibition of selenium availability in brain and endocrine tissues. This appears to occur through synergistic effects of mercury-dependent inhibition of selenium transport to these tissues and selective sequestration of the selenium present in the tissues. Compromised transport of selenium to the brain and endocrine tissues would be particularly hazardous to the developing fetus because the rapidly growing tissues of the child have no selenium reserves. Therefore, maternal consumption of foods with high mercury-selenium ratios is hazardous. In summation, methylmercury exposure is unlikely to cause harm in populations that eat selenium-rich diets but may cause harm among populations that consume certain foods that have methylmercury present in excess of selenium.« less

How to use PRICE treatment for soft tissue injuries.

PubMed

Norton, Cormac

2016-08-24

Rationale and key points This article assists nurses to use the acronym PRICE (protection, rest, ice, compression and elevation) to guide the treatment of patients with uncomplicated soft tissue injuries to their upper or lower limbs. » Treatment of soft tissue injuries to limbs is important to reduce complications following injury, alleviate pain and ensure normal limb function is restored promptly. » Nurses should have an understanding of the rationale and evidence base supporting PRICE treatment of soft tissue injuries. » Providing accurate information to patients and carers about the management of soft tissue injuries and anticipated recovery time is an important aspect of treatment. » Further research is required to develop best practice in the treatment of soft tissue injuries. Reflective activity 'How to' articles can help you update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How this article might change your practice when managing patients with soft tissue injuries to upper or lower limbs. 2. Positive elements of your current practice and those that could be enhanced. Subscribers can upload their reflective accounts at: rcni.com/portfolio.

Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine against Trypanosoma cruzi infection.

PubMed

Cerny, Natacha; Sánchez Alberti, Andrés; Bivona, Augusto E; De Marzi, Mauricio C; Frank, Fernanda M; Cazorla, Silvia I; Malchiodi, Emilio L

2016-01-01

Therapeutic vaccine research and development are especially important in Chagas disease considering the characteristics of the chronic infection and the number of people in the Americas living with a parasite infection for decades. We have previously reported the efficacy of attenuated Salmonella enterica (S) carrying plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection. In the present work we investigated whether Cz DNA vaccine immunotherapy could be effective in controlling an ongoing T. cruzi infection in mice. We here report the intramuscular administration of naked Cz DNA or the oral administration of Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute or chronic infection. The coadministration of a plasmid encoding GM-CSF improved vaccine performance, indicating that the stimulation of innate immune cells is needed in the event of an ongoing infection. These therapeutic vaccines were able to address the response to a protective and sustained Th1 biased profile not only against Cz but also against a variety of parasite antigens. The combined therapeutic vaccine during the chronic phase of infection prevents tissue pathology as shown by a reduced level of enzyme activity characteristic of tissue damage and a tissue status compatible with normal tissue. The obtained results suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in combination with other drug treatments, may represent a promising alternative for Chagas disease therapy.

Tumor-infiltrating lymphocyte composition, organization and PD-1/ PD-L1 expression are linked in breast cancer

PubMed Central

Garaud, Soizic; de Wind, Alexandre; Van den Eynden, Gert; Boisson, Anais; Gu-Trantien, Chunyan; Naveaux, Céline; Lodewyckx, Jean-Nicolas; Duvillier, Hugues; Craciun, Ligia; Veys, Isabelle; Larsimont, Denis; Piccart-Gebhart, Martine; Stagg, John; Sotiriou, Christos

2017-01-01

ABSTRACT The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC. Tumor and normal breast tissues were analyzed using both flow cytometry and immunohistochemistry. TIL density distribution is a continuum with 25% of tumors identified as TIL-negative at a TIL density equivalent to normal breast tissues. TIL-positive tumors (75%) were equally divided into TIL-intermediate and TIL-high. Tumors had higher mean frequencies of CD4+ T cells and CD19+ B cells and a lower mean frequency of CD8+ T cells compare with normal tissues, increasing the CD4+/CD8+ T-cell ratio. Tertiary lymphoid structures (TLS), principally located in the peri-tumoral stroma, were detected in 60% of tumors and correlated with higher TIL infiltration. PD-1 and PD-L1 expression were also associated with higher TIL densities and TLS. TIL density, TLS and PD-L1 expression were correlated with more aggressive tumor characteristics, including higher proliferation and hormone receptor negativity. Our findings reveal an important relationship between PD-1/PD-L1 expression, increased CD4+ T and B-cell infiltration, TIL density and TLS, suggesting that evaluating not only the extent but also the nature and location of the immune infiltrate should be considered when evaluating antitumor immunity and the potential for benefit from immunotherapies. PMID:28197375

Combined hyperthermia and radiotherapy for the treatment of cancer.

PubMed

Kaur, Punit; Hurwitz, Mark D; Krishnan, Sunil; Asea, Alexzander

2011-09-30

Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in-tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, car-diac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threat-ening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy.

Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

PubMed Central

Kaur, Punit; Hurwitz, Mark D.; Krishnan, Sunil; Asea, Alexzander

2011-01-01

Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy. PMID:24213112

Detection and Persistence of Vi Antigen in Tissues of Actively Immunized Mice1

PubMed Central

Gaines, Sidney; Currie, Julius A.; Tully, Joseph G.

1965-01-01

Gaines, Sidney (Walter Reed Army Institute of Research, Washington, D.C.), Julius A. Currie, and Joseph G. Tully. Detection and persistence of Vi antigen in tissues of actively immunized mice. J. Bacteriol. 89:776–781. 1965.—The presence, distribution, and persistence of Vi antigen in mouse tissue was determined by means of active immunization tests with tissue extracts. Mice were injected intraperitoneally with purified Vi antigen or Vi-containing bacilli. At appropriate intervals, animals were killed, and saline extracts of their tissues were prepared. Mice were immunized with these extracts and challenged 6 days later with 10 ld50 of Salmonella typhosa Ty2. Protection was afforded by tissue extracts from Vi-injected mice, but not by normal tissue extracts. That the immunizing capacity of tissue extracts from Vi-injected mice was attributable to Vi antigen was affirmed by the demonstration that these extracts stimulated the production of Vi antibody in mice, coated erythrocytes for agglutination by Vi antiserum, and inhibited agglutination of Vi-sensitized red blood cells by known Vi antisera. Vi antigen could be detected in the liver and spleen of mice injected with as little as 1 μg. In mice given 150 μg, the antigen was still present in liver tissue 231 days later. PMID:14273660

Multidrug Resistance Protein 1 Deficiency Promotes Doxorubicin-Induced Ovarian Toxicity in Female Mice.

PubMed

Wang, Yingzheng; Liu, Mingjun; Zhang, Jiyang; Liu, Yuwen; Kopp, Megan; Zheng, Weiwei; Xiao, Shuo

2018-05-01

Multidrug resistance protein 1 (MDR1), a phase III drug transporter that exports substrates out of cells, has been discovered in both cancerous and normal tissues. The over expression of MDR1 in cancer cells contributes to multiple drug resistance, whereas the MDR1 in normal tissues protects them from chemical-induced toxicity. Currently, the role of MDR1 in the ovary has not been entirely understood. Our objective is to determine the function of MDR1 in protecting against chemotherapy-induced ovarian toxicity. Using both the in vivo transgenic mouse model and in vitro follicle culture model, we investigated the expression of MDR1 in the ovary, the effect of MDR1 deficiency on doxorubicin (DOX)-induced ovarian toxicity, and the ovarian steroid hormonal regulation of MDR1. Results showed that the MDR1 was expressed in the ovarian epithelial cells, stroma cells, theca cell layers, endothelial cells, and luteal cells. The lack of MDR1 did not affect female ovarian function and fertility; however, its deficiency significantly exacerbated the DOX-induced ovarian toxicity in both in vivo and in vitro models. The MDR1 showed significantly higher expression levels in the ovaries at estrus and metestrus stages than those at proestrus and diestrus stages. However, this dynamic expression pattern was not regulated by the ovarian steroid hormones of estrogen (E2) and progesterone (P4) but correlated to the number and status of corpus luteum. In conclusion, our study demonstrates that the lack of MDR1 promotes DOX-induced ovarian toxicity, suggesting the critical role of MDR1 in protecting female ovarian functions during chemotherapy.

[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

PubMed

Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

2002-12-01

To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

PubMed Central

Pan, Youdong; Tian, Tian; Park, Chang Ook; Lofftus, Serena Y.; Mei, Shenglin; Liu, Xing; Luo, Chi; O’Malley, John T.; Gehad, Ahmed; Teague, Jessica E.; Divito, Sherrie J.; Fuhlbrigge, Robert; Puigserver, Pere; Krueger, James G.; Hotamisligil, Gökhan S.; Clark, Rachael A.; Kupper, Thomas S.

2017-01-01

Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens1–4. However, the biological pathways that enable the long-term survival of TRM cells are obscure4,5. Here we show that mouse CD8+ TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8+ TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes. In vitro, CD8+ TRM cells, but not CD8+ TCM, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8+ TRM cells. The persistence of CD8+ TRM cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8+ TRM cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8+ TRM cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity. PMID:28219080

[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].

PubMed

Liu, Jun-Feng; Ke, Chang-Shu; Chen, Xi; Xu, Yu; Zhang, Hua-Qiu; Chen, Juan; Gan, Chao; Li, Chao-Xi; Lei, Ting

2013-05-01

To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.

[Protective effects of polysaccharides from Dendrobium huoshanense on CCl4-induced acute liver injury in mice].

PubMed

Huang, Jing; Li, Sheng-Li; Zhao, Hong-Wei; Pan, Li-Hua; Sun, Hao-Qiao; Luo, Jian-Ping

2013-02-01

To study the protective effects of polysaccharides from Dendrobium huoshanense (DHP) against CCl4-induced liver injury in mice. Eighty male Kunming mice were randomly divided into normal control group, model control group, dextran control group, starch control group, hydrolyzate control group, three different dose of DPH groups consisting of high-dosage group, middle-dosage group and low-dosage group (200, 100, 50 mg x kg(-1)). Each group contained ten mice. The mice were treated with DHP via intragastric administration for 15 days before treatment of 50% CCl4 in olive oil for consecutive two days. Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in liver tissues were determined in all groups. Immunohistochemistry was used to detect the expression of TNF-alpha in hepatic tissue. Hepatic histopathological examination was observed. DHP effectively decreased the activities of ALT and AST in serum and the contents of hepatic MDA, and restored hepatic SOD activities in acute liver injury mice. Liver tissue damage induced by CCl4 was ameliorated in mice with DHP administration through histopathology examination. Furthermore, the expression of TNF-alpha was greatly decreased in groups treated with polysaccharides. DHP has a significantly hepatoprotective effect on CCl4-induced acute liver injury in mice. Protective effect of DHP on the liver may be related to its function of scavenging free radicals and inhibiting lipid peroxidation and TNF-alpha expression.

Anatomy and imaging of the normal meninges.

PubMed

Patel, Neel; Kirmi, Olga

2009-12-01

The meninges are an important connective tissue envelope investing the brain. Their function is to provide a protective coating to the brain and also participate in the formation of blood-brain barrier. Understanding their anatomy is fundamental to understanding the location and spread of pathologies in relation to the layers. It also provides an insight into the characteristics of such pathologies when imaging them. This review aims to describe the anatomy of the meninges, and to demonstrate the imaging findings of specific features.

Fluorescence spectroscopy using excitation and emission matrix for quantification of tissue native fluorophores and cancer diagnosis

NASA Astrophysics Data System (ADS)

Wu, Binlin; Gayen, S. K.; Xu, M.

2014-03-01

Native fluorescence spectrum of normal and cancerous human prostate tissues is studied to distinguish between normal and cancerous tissues, and cancerous tissues at different cancer grade. The tissue samples were obtained from Cooperative Human Tissue Network (CHTN) and National Disease Research Interchange(NDRI). An excitation and emission matrix (EEM) was generated for each tissue sample by acquiring native fluorescence spectrum of the sample using multiple excitation wavelengths. The non-negative matrix factorization algorithm was used to generate fluorescence EEMs that correspond to the fluorophores in biological tissues, including tryptophan, collagen, elastin, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and the background paraffin. We hypothesize that, as a consequence of metabolic changes associated with the development of cancer, the concentrations of NADH and FAD are different in normal and cancerous tissues, and also different for different cancer grades. We used the ratio of the abundances of FAD and NADH to distinguish between normal and cancerous tissues, and the tissue cancer grade. The FAD-to-NADH ratio was found to be the highest for normal tissue and decreased as the cancer grade increased.

Caffeic acid phenethyl ester protects kidneys against acetylsalicylic acid toxicity in rats.

PubMed

Bozkurt, Yasar; Bozkurt, Mehtap; Turkçu, Gul; Sancaktutar, Ahmet Ali; Soylemez, Haluk; Penbegul, Necmettin; Atar, Murat; Bodakcı, Mehmet Nuri; Hatipoglu, Namık Kemal; Yuksel, Hatice; Kıbrıslı, Erkan; Yavuz, Celal

2012-01-01

The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in rats. A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) + CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity of the blood samples and kidney tissues were determined. Histopathological examinations of the kidneys were performed using light microscopic methods. The TOS level in the serum of rats and kidney tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC and PON-1 in these tissues significantly decreased in group 4 when compared with the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues increased and the levels of TOS decreased in the CAPE treatment groups (groups 3 and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and 4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when compared to group 4 (p < 0.05). These results were supported by histopathological observation. Oxidative stress plays an important role in ASA-induced nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

A western type of bacterial gill disease

USGS Publications Warehouse

Fish, F.F.

1935-01-01

The first reference to a pathological condition of the gill tissues of salmonid fishes was made by Osburn in 1910. This author in describing a progressive infolding of the opercula of trout, commonly known to hatcherymen as "short gill covers," mentioned a marked proliferation on the gill epithelium as accompanying this condition. Osburn assumed that the club-like appearance of the gill filaments due to the proliferated epithelium was the result of continual irritation of the delicate gill tissue in the absence of the usual protection offered by the normal opercula. Although such a conclusion seems quite logical, it is also possible that Osburn was dealing with "short gill covers" complicated by the unknown bacterial gill disease which was subsequently described by Davis.

Heat shock-initiated apoptosis is accelerated and removal of damaged cells is delayed in the testis of clusterin/ApoJ knock-out mice.

PubMed

Bailey, Robert W; Aronow, Bruce; Harmony, Judith A K; Griswold, Michael D

2002-04-01

The secretion and localization of clusterin in the testis has led to the hypothesis that clusterin plays a role in spermatogenesis. Furthermore, the association of clusterin with apoptosis, cellular injury, disease, and regression of nongonadal tissues has led to the hypothesis that clusterin acts to protect cells from apoptosis or may be involved in tissue remodeling. To investigate the role of clusterin in the testis, we analyzed clusterin knock-out (cluKO) mice to determine the impact of the absence of clusterin on spermatogenesis. Furthermore, we investigated the cellular response to injury caused by methoxyacetic acid (MAA) toxicity and mild heat exposure in the cluKO mice to determine the extent to which clusterin protects against apoptosis or participates in tissue remodeling. We found that cluKO mice were fertile and had essentially normal spermatogenesis with the exception of some incomplete spermiation after stage VIII. No differences in testicular morphology or the incidence of apoptosis in the testis were seen between the cluKO and clusterin wild-type (cluWT) mice after MAA treatment. In contrast, apoptosis was delayed in the cluWT mice compared with the cluKO mice after heat exposure, suggesting that clusterin does have a slight protective effect against apoptosis under some conditions. Also, a dramatic loss of germ cells after heat stress occurred earlier in the cluWT testes than in the cluKO testes. Clusterin is clearly acting in a dual role in that cells can be protected from damage and dead cells can be more easily removed after some types of cellular damage but not after others.

Putting tumours in context

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bissell, Mina J.; Radisky, Derek

2001-10-01

The interactions between cancer cells and their micro- and macroenvironment create a context that promotes tumor growth and protects it from immune attack. The functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses. Investigation of this process might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets. Under normal conditions, ORGANS are made up of TISSUES that exchange information with other cell types via cell-cell contact, cytokines and the EXTRACELLULAR MATRIX (ECM). The ECM, which is produced by collaboration between STROMAL fibroblasts and EPITHELIALmore » cells, provides structural scaffolding for cells, as well as contextual information. The endothelial vasculature provides nutrients and oxygen, and cells of the immune system combat pathogens and remove apoptotic cells. Epithelial cells associate into intact, polarized sheets. These tissues communicate through a complex network of interactions: physically, through direct contact or through the intervening ECM, and biochemically, through both soluble and insoluble signalling molecules. In combination, these interactions provide the information that is necessary to maintain cellular differentiation and to create complex tissue structures. Occasionally, the intercellular signals that define the normal context become disrupted. Alterations in epithelial tissues can lead to movement of epithelial sheets and proliferation - for example, after activation of mesenchymal fibroblasts due to wounding.Normally, these conditions are temporary and reversible, but when inflammation is sustained, an escalating feedback loop ensues.Under persistent inflammatory conditions, continual upregulation of enzymes such as matrix metalloproteinases (MMPs) by stromal fibroblasts can disrupt the ECM, and invading immune cells can overproduce factors that promote abnormal proliferation. As this process progresses, the normal organization of the organ is replaced by a functional disorder. If there are pre-existing epithelial cells within this changing context that possess tumorigenic potential, they can start to proliferate. Alternatively, the abnormal interactions might lead to genomic instability within the epithelial cells and the acquisition of tumorigenic potential. The proliferating cancer cells can then interact with their microenvironment and enhance the abnormal interactions. At this point, the tumor has become its own organ, with a distinct context that now defines all its cellular responses. Here, we will examine how the mechanisms that contribute to the normal context also act to suppress developing tumors, how disruption of this context initiates and supports the process of tumorigenicity, and how some cells with a tumorigenic genotype can become phenotypically normal if the context is appropriately manipulated.« less

Elastic light single-scattering spectroscopy for detection of dysplastic tissues

NASA Astrophysics Data System (ADS)

Canpolat, Murat; Denkçeken, Tuba; Akman, Ayşe.; Alpsoy, Erkan; Tuncer, Recai; Akyüz, Mahmut; Baykara, Mehmet; Yücel, Selçuk; Başsorgun, Ibrahim; ćiftçioǧlu, M. Akif; Gökhan, Güzide Ayşe.; Gürer, ElifInanç; Peştereli, Elif; Karaveli, Šeyda

2013-11-01

Elastic light single-scattering spectroscopy (ELSSS) system has been developed and tested in diagnosis of cancerous tissues of different organs. ELSSS system consists of a miniature visible light spectrometer, a single fiber optical probe, a halogen tungsten light source and a laptop. Measurements were performed on excised brain, skin, cervix and prostate tumor specimens and surrounding normal tissues. Single fiber optical probe with a core diameter of 100 μm was used to deliver white light to and from tissue. Single optical fiber probe mostly detects singly scattered light from tissue rather than diffused light. Therefore, measured spectra are sensitive to size of scatters in tissue such as cells, nuclei, mitochondria and other organelles of cells. Usually, nuclei of tumor cells are larger than nuclei of normal cells. Therefore, spectrum of singly scattered light of tumor tissue is different than normal tissue. The spectral slopes were shown to be positive for normal brain, skin and prostate and cervix tissues and negative for the tumors of the same tissues. Signs of the spectral slopes were used as a discrimination parameter to differentiate tumor from normal tissues for the three organ tissues. Sensitivity and specificity of the system in differentiation between tumors from normal tissues were 93% and %100 for brain, 87% and 85% for skin, 93.7% and 46.1% for cervix and 98% and 100% for prostate.

Tissue-specific targeting of Hsp26 has no effect on heat resistance of neural function in larval Drosophila.

PubMed

Mileva-Seitz, Viara; Xiao, Chengfeng; Seroude, Laurent; Robertson, R Meldrum

2008-01-01

Hsp26 belongs to the small heat-shock protein family and is normally expressed in all cells during heat stress. We aimed to determine if overexpression of this protein protects behavior and neural function in Drosophila melanogaster during heat stress, as has previously been shown for Hsp70. We used the UAS-GAL4 expression system to drive expression of Hsp26 in the whole animal (ubiquitously), in the motoneurons, and in the muscles of wandering third-instar larvae. There were slight increases in time to crawling failure and normalized excitatory junction potential (EJP) area for some of the transgenic lines, but these were not consistent. In addition, Hsp26 had no effect on the temperature at failure of EJPs, normalized EJP peak amplitude, and normalized EJP half-width. Overexpression larvae had a similar number of motoneuronal boutons and length of nerve terminals as controls, indicating that the occasional protective effects on locomotion were not due to changes at the synapse. We conclude that overexpression had a small thermoprotective effect on locomotion and no effect on neural function. As it has been shown that Hsp26 requires action of other Hsps to reactivate the denatured proteins to which it binds, we propose that at least in larvae, the function of Hsp26 was masked in the relative absence of other Hsps.

Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer

PubMed Central

Danforth, David N.

2016-01-01

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID:27559297

Release of the antioxidants ascorbate and urate from a nitrergically-innervated smooth muscle.

PubMed

Lilley, E; Gibson, A

1997-12-01

1. The main object of the present study was to determine whether ascorbate, an antioxidant which has been shown to protect nitric oxide (NO) from attack by scavenger molecules, might be released from nitrergically-innervated smooth muscle; ascorbate release from the rat anococcygeus was measured by use of h.p.l.c. with electrochemical detection. 2. Incubation of rat anococcygeus muscles in normal physiological salt solution (PSS; 30 min) resulted in release of ascorbate into the bathing medium (7.7 +/- 0.9 nmol g-1 tissue). This release was increased by 96% when muscles were incubated in high K+ (70 mM) PSS. The resting release of ascorbate was unaffected by tetrodotoxin (TTX; 1 microM), omega-conotoxin GVIA (10 nM) or omission of calcium ions from the PSS (with addition of 0.2 mM EGTA), but all three procedures attenuated the increased release observed under depolarizing conditions. Resting release of ascorbate was unaffected by glutamate (100 microM), aspartate (100 microM), gamma-aminobutyric acid (100 microM) or carbachol (50 microM). 3. A second h.p.l.c. peak, which always preceded the ascorbate peak, was identified as urate. Urate release from the anococcygeus, following 30 min incubation in normal PSS, was 64.6 +/- 12.7 nmol g-1 tissue but, unlike ascorbate, urate release was unchanged in high K+ PSS. In functional experiments, urate (100-400 microM) partially protected NO (15 microM)-induced relaxations of the rat anococcygeus from inhibition by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO; 50 microM), but not from inhibition by hydroquinone or duroquinone (both 100 microM). 4. Muscles chemically sympathectomized with 6-hydroxydopamine (6-OHDA, 500 microM; 2 h) still exhibited release of ascorbate (2.5 +/- 0.4 nmol g-1 tissue) and urate (22.2 +/- 2.9 nmol g-1 tissue); in both cases the release was similar to that observed in time-matched control tissues not exposed to 6-OHDA. High K+ PSS produced a TTX-sensitive increase in release of ascorbate, but not urate, from 6-OHDA-treated muscles. 5. The results demonstrate that significant amounts of ascorbate and urate are released from the rat anococcygeus muscle. Ascorbate, but not urate, release appears to be enhanced by activation of nerves which are resistant to 6-OHDA pretreatment. Since both antioxidants can protect NO from attack by scavenger molecules, their release in nitrergically-innervated tissues may be important for the provision of the correct redox environment to allow NO to fulfill its proposed neurotransmitter role.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

PubMed

Yu, Zhengze; Ge, Yegang; Sun, Qiaoqiao; Pan, Wei; Wan, Xiuyan; Li, Na; Tang, Bo

2018-04-14

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen ( 1 O 2 ) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

Protective role of Parkin in skeletal muscle contractile and mitochondrial function.

PubMed

Gouspillou, Gilles; Godin, Richard; Piquereau, Jérome; Picard, Martin; Mofarrahi, Mahroo; Mathew, Jasmin; Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T; Burelle, Yan; Hussain, Sabah N A

2018-04-22

Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are degraded. The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored. Using Park2 -/- mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore. These results demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in skeletal muscles. Parkin is an E3 ubiquitin ligase encoded by the Park2 gene. Parkin has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Although Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson disease, its role in other tissues remains largely unknown. In the present study, we investigated the skeletal muscles of Park2 knockout (Park2 -/- ) mice to test the hypothesis that Parkin plays a physiological role in mitochondrial quality control in normal skeletal muscle, a tissue highly reliant on mitochondrial content and function. We first show that the tibialis anterior (TA) of Park2 -/- mice display a slight but significant decrease in its specific force. Park2 -/ - muscles also show a trend for type IIB fibre hypertrophy without alteration in muscle fibre type proportion. Compared to Park2 +/+ muscles, the mitochondrial function of Park2 -/- skeletal muscles was significantly impaired, as indicated by the significant decrease in ADP-stimulated mitochondrial respiratory rates, uncoupling, reduced activities of respiratory chain complexes containing mitochondrial DNA (mtDNA)-encoded subunits and increased susceptibility to opening of the permeability transition pore. Muscles of Park2 -/- mice also displayed a decrease in the content of the mitochondrial pro-fusion protein Mfn2 and an increase in the pro-fission protein Drp1 suggesting an increase in mitochondrial fragmentation. Finally, Park2 ablation resulted in an increase in basal autophagic flux in skeletal muscles. Overall, the results of the present study demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in normal skeletal muscles. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Vascular protective actions of a nitric oxide aspirin analog in both in vitro and in vivo models of diabetes mellitus.

PubMed

Pieper, Galen M; Siebeneich, Wolfgang; Olds, Cara L; Felix, Christopher C; Del Soldato, Piero

2002-06-01

Defective endothelium-dependent relaxation is observed in experimental and human diabetes mellitus. The nature of this defect is not fully understood but may involve decreased nitric oxide (NO) bioactivity due to enhanced production of reactive oxygen species (ROS). In this paper, we examine the benefits and actions of a novel NO-donating, antioxidant called 2-acetoxybenzoic acid 2-(2-nitrooxymethyl) phenyl ester, and denoted as NCX4016, on NO-mediated endothelium-dependent relaxation in normal arteries exposed to acute elevations in glucose or in arteries derived from chronic diabetic animals. Intrinsic free radical scavenging by NO-NSAIDs in solution were evaluated using electron paramagnetic resonance (EPR) spectroscopy and spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In acute studies, normal rat aortas were exposed in tissue culture for 18 h to 5.5 mM or 40 mM in the presence or absence of NCX4016, a NO-donating NSAID unrelated to aspirin (NCX2216) or aspirin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined. For chronic hyperglycemia, diabetes was induced in rats by intravenous injection with streptozotocin. Vascular reactivity of thoracic aortic rings to endothelium-dependent relaxation to acetylcholine in vitro was determined after 8 wks in untreated animals or animals chronically-treated with NCX4016. Antioxidant efficacy in vivo was determined by measurement of plasma isoprostanes and by nuclear binding activity of NF-kappaB in nuclear fractions of aortae. Incubation with NCX4016 and NCX2216 produced a concentration-dependent inhibition of DMPO-OH formation indicating scavenging of hydroxyl radicals (HO(*)). In contrast, little efficacy to scavenge superoxide anion radicals was noted. Acute incubation of normal arteries with elevated glucose concentration caused inhibition of normal relaxation to acetylcholine. This impairment was prevented by co-incubation with NCX4106 but not by mannitol, the parent compound (aspirin) or by NCX2216. In addition, chronic treatment with NCX4016 prevented the development of defective endothelium-dependent relaxation to acetylcholine. This protection did not occur as a result to any changes in blood glucose concentration or hemoglobin glycation. Treatment with NCX4016 did decrease the elevation in plasma isoprostanes and normalized the diabetes-induced increase in NF-kappaB binding activity in nuclear fractions derived from aortic tissue. Collectively, these studies suggest that antioxidant interventions using NO-donating NSAIDs may provide an important novel therapeutic strategy to protect the diabetic endothelium.

Effects of an Agaricus blazei aqueous extract pretreatment on paracetamol-induced brain and liver injury in rats.

PubMed

Soares, Andréia A; de Oliveira, Andrea L; Sá-Nakanishi, Anacharis B; Comar, Jurandir F; Rampazzo, Ana P S; Vicentini, Fernando A; Natali, Maria R M; Gomes da Costa, Sandra M; Bracht, Adelar; Peralta, Rosane M

2013-01-01

The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma) but also in terms of functional and metabolic parameters (e.g., gluconeogenesis). Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP) and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products.

Effects of an Agaricus blazei Aqueous Extract Pretreatment on Paracetamol-Induced Brain and Liver Injury in Rats

PubMed Central

Soares, Andréia A.; de Oliveira, Andrea L.; Sá-Nakanishi, Anacharis B.; Comar, Jurandir F.; Rampazzo, Ana P. S.; Vicentini, Fernando A.; Natali, Maria R. M.; Gomes da Costa, Sandra M.; Peralta, Rosane M.

2013-01-01

The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma) but also in terms of functional and metabolic parameters (e.g., gluconeogenesis). Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP) and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products. PMID:23984368

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

PubMed

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

Transmembrane mucins as novel therapeutic targets.

PubMed

Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja; Carson, Daniel D

2011-11-01

Membrane-tethered mucin glycoproteins are abundantly expressed at the apical surfaces of simple epithelia, where they play important roles in lubricating and protecting tissues from pathogens and enzymatic attack. Notable examples of these mucins are MUC1, MUC4 and MUC16 (also known as cancer antigen 125). In adenocarcinomas, apical mucin restriction is lost and overall expression is often highly increased. High-level mucin expression protects tumors from killing by the host immune system, as well as by chemotherapeutic agents, and affords protection from apoptosis. Mucin expression can increase as the result of gene duplication and/or in response to hormones, cytokines and growth factors prevalent in the tumor milieu. Rises in the normally low levels of mucin fragments in serum have been used as markers of disease, such as tumor burden, for many years. Currently, several approaches are being examined that target mucins for immunization or nanomedicine using mucin-specific antibodies.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.

1996-01-01

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, T.; Panjehpour, M.; Overholt, B.F.

1996-12-03

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample. 5 figs.

Measurement of glutathione S-transferase and its class-pi in plasma and tissue biopsies obtained after laparoscopy and endoscopy from subjects with esophagus and gastric cancer.

PubMed

Mohammadzadeh, G S; Nasseri Moghadam, S; Rasaee, M J; Zaree, A B; Mahmoodzadeh, H; Allameh, A

2003-06-01

To develop an indirect enzyme-linked immunosorbent assay (ELISA) for measuring class-pi glutathione S-transferase (GST) in plasma, and tissue biopsies obtained from upper gastrointestinal cancer (UGI Ca) patients. GST activity and GST-pi concentration were detected in normal human squamous esophageal epithelium, normal gastric cardia and their corresponding malignant tumor biopsies. Plasma GST was significantly higher (p < 0.05) in UGI Ca patients as compared to those obtained from normal individuals. Plasma GST-pi concentration in normal subjects was 6.6 +/- 1.9 ng/mg protein, whereas it was higher in UGI Ca patients (esophageal, 10.0 +/- 1.8; gastric, 10.7 +/- 1.7 ng/mL, p

Low level light in combination with metabolic modulators for effective therapy

NASA Astrophysics Data System (ADS)

Dong, Tingting; Zhang, Qi; Hamblin, Michael R.; Wu, Mei X.

2015-03-01

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced ATP generation, and increased formation of reactive oxygen species (ROS) and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). LLL illumination sustained the mitochondrial membrane potential, constrained cytochrome C leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas those treated with LLL or pyruvate alone, or sham light displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by a combination of LLL and pyruvate, in marked contrast to the severe loss of hippocampal tissue due to secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissues like injured brain. Keywords:

Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.

PubMed

Liao, Q; Kleeff, J; Xiao, Y; Guweidhi, A; Schambony, A; Töpfer-Petersen, E; Zimmermann, A; Büchler, M W; Friess, H

2003-04-01

Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

NASA Astrophysics Data System (ADS)

Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

2007-10-01

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

PubMed

Basarslan, Fatmagul; Yilmaz, Nigar; Davarci, Isil; Akin, Mustafa; Ozgur, Mustafa; Yilmaz, Cahide; Ulutas, Kemal Turker

2013-09-01

Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

Toxic effects of lead exposure in Wistar rats: involvement of oxidative stress and the beneficial role of edible jute (Corchorus olitorius) leaves.

PubMed

Dewanjee, Saikat; Sahu, Ranabir; Karmakar, Sarmila; Gangopadhyay, Moumita

2013-05-01

Lead (Pb) is considered to be a multi-target toxicant. The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves against Pb-acetate induced toxic manifestation in blood, liver, kidney, brain and heart of Wistar rats. The Pb-acetate (5mg/kg body weight) treated rats exhibited a significant inhibition of co-enzymes Q, antioxidant enzymes and reduced glutathione levels in the tissues. In addition, the extent of lipid peroxidation, DNA fragmentation and haematological parameters were significantly altered in the Pb-acetate treated rats as compared to control. Simultaneous administration of test extract (25, 50 and 100mg/kg body weight), could significantly restore the biochemical and haematological parameters near to the normal status through antioxidant activity and/or by preventing bioaccumulation of Pb within the tissues of experimental rats. Presence of substantial quantity of phenolics and flavonoids in the extract may be responsible for the observed protective role against Pb-intoxication. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protective Effect of High Molecular Weight Protein Sub-fraction of Calotropis procera Latex in Monoarthritic Rats.

PubMed

Chaudhary, Priyanka; Ramos, Marcio V; Vasconcelos, Mirele da Silveira; Kumar, Vijay L

2016-05-01

Proteins present in the latex of Calotropis procera have been shown to produce anti-inflammatory effect and to afford protection in various disease models. To determine the efficacy of high molecular weight protein sub-fraction (LPPI) of latex of C. procera in ameliorating joint inflammation and hyperalgesia in a preclinical model of arthritis. Monoarthritis was induced in rats by intra-articular injection of Freund's complete adjuvant (FCA) and the effect of two doses of LPPI (5 and 25 mg/kg) and diclofenac (5 mg/kg) was evaluated on joint swelling, stair climbing ability, motility, and dorsal flexion pain on day 3. The rats were sacrificed on day 3 to measure tissue levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Evaluation of joint histology was also made. Intra-articular injection of FCA produced joint swelling and difficulty in stair climbing ability, motility, and pain on flexion of the joint as revealed by scores obtained for these functional parameters. LPPI produced a dose-dependent decrease in joint swelling and improved joint functions. Arthritic rats also revealed altered oxidative homeostasis where joint tissue GSH levels were decreased and TBARS levels were increased as compared to normal rats. The levels of these oxidative stress markers were near normal in arthritic rats treated with LPPI. Moreover, treatment with LPPI also maintained the structural integrity of the joint. The protective effect of LPPI was comparable to the standard anti-inflammatory drug, diclofenac. The findings of the present study show that LPPI fraction comprising high molecular weight proteins could be used for the alleviation of arthritic symptoms. High molecular weight protein sub-fraction of latex of Calotropis procera (LPPI) reduced joint swelling and hyperalgesia in arthritic ratsLPPI produced a significant improvement in stair climbing ability and motility in arthritic ratsLPPI normalized the levels of oxidative stress markers in the arthritic jointsTreatment with LPPI reduced neutrophil influx and edema in the arthritic joints Abbreviations used: FCA: Freund's complete adjuvant, GSH: Glutathione, TBARS: Thiobarbituric acid reactive substances, TBA: Thiobarbituric acid, MDA: Malondialdehyde, LPPI: Latex protein fraction PI.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe.

PubMed

O'Rourke, Ann P; Lazebnik, Mariya; Bertram, John M; Converse, Mark C; Hagness, Susan C; Webster, John G; Mahvi, David M

2007-08-07

Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

Adenosine A2A Receptor Blockade or Deletion Diminishes Fibrocyte Accumulation in the Skin in a Murine Model of Scleroderma, Bleomycin-induced Fibrosis

PubMed Central

Katebi, Majid; Fernandez, Patricia; Chan, Edwin S. L.; Cronstein, Bruce N.

2015-01-01

Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. Previous studies in our lab demonstrated that A2A receptor-deficient and A2A antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis, thus the aim of this study was to determine whether the adenosine A2A receptor regulates recruitment of fibrocytes to the dermis in this bleomycin-induced model of dermal fibrosis. Sections of skin from normal mice and bleomycin-treated wild type, A2A knockout and A2A antagonist-treated mice were stained for Procollagen α2 Type I and CD34 and the double stained cells, fibrocytes, were counted in the tissue sections. There were more fibrocytes in the dermis of bleomycin-treated mice than normal mice and the increase was abrogated by deletion or blockade of adenosine A2A receptors. Because fibrocytes play a central role in tissue fibrosis these results suggest that diminished adenosine A2A receptor-mediated recruitment of fibrocytes into tissue may play a role in the pathogenesis of fibrosing diseases of the skin. Moreover, these results provide further evidence that adenosine A2A receptors may represent a new target for the treatment of such fibrosing diseases as scleroderma or nephrogenic fibrosing dermopathy. PMID:18709547

Time-Resolved Spectroscopy and Near Infrared Imaging for Prostate Cancer Detection: Receptor-targeted and Native Biomarker

NASA Astrophysics Data System (ADS)

Pu, Yang

Optical spectroscopy and imaging using near-infrared (NIR) light provides powerful tools for non-invasive detection of cancer in tissue. Optical techniques are capable of quantitative reconstructions maps of tissue absorption and scattering properties, thus can map in vivo the differences in the content of certain marker chromophores and/or fluorophores in normal and cancerous tissues (for example: water, tryptophan, collagen and NADH contents). Potential clinical applications of optical spectroscopy and imaging include functional tumor detection and photothermal therapeutics. Optical spectroscopy and imaging apply contrasts from intrinsic tissue chromophores such as water, collagen and NADH, and extrinsic optical contrast agents such as Indocyanine Green (ICG) to distinguish disease tissue from the normal one. Fluorescence spectroscopy and imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as small receptor-targeted dye-peptide conjugate contrast agent offer high contrast between normal and cancerous tissues hence provide promising future for early tumour detection. This thesis focus on a study to distinguish the cancerous prostate tissue from the normal prostate tissues with enhancement of specific receptor-targeted prostate cancer contrast agents using optical spectroscopy and imaging techniques. The scattering and absorption coefficients, and anisotropy factor of cancerous and normal prostate tissues were investigated first as the basis for the biomedical diagnostic and optical imaging. Understanding the receptors over-expressed prostate cancer cells and molecular target mechanism of ligand, two small ICG-derivative dye-peptides, namely Cypate-Bombesin Peptide Analogue Conjugate (Cybesin) and Cypate-Octreotate Peptide Conjugate (Cytate), were applied to study their clinical potential for human prostate cancer detection. In this work, the steady-state and time-resolved fluorescence spectroscopy of Cybesin (Cytate) in solution, and in cancerous and normal prostate tissues were studied. It was found that more Cybesin (Cytate) was uptaken in the cancerous prostate tissue than those in the normal tissue. The preferential uptake of Cybesin (Cytate) in cancerous tissue was used to image and distinguish cancerous areas from the normal tissue. To investigate rotational dynamics and fluorescence polarization anisotropy of the contrast agents in prostate tissues, an analytical model was used to extract the rotational times and polarization anisotropies, which were observed for higher values of Cybesin (Cytate)-stained cancerous prostate tissue in comparison with the normal tissue. These reflect changes of microstructures of cancerous and normal tissues and their different binding affinity with contrast agents. The results indicate that the use of optical spectroscopy and imaging combined with receptor-targeted contrast agents is a valuable tool to study microenvironmental changes of tissue, and detect prostate cancer in early stage.

In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

PubMed

Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo

2017-09-01

The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6C high ) to a repair (Ly6C low ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway.

PubMed

Aslan, Abdullah; Can, Muhammed İsmail

2014-11-04

The objective of this study was to examine whether MT plays a protective role against the damage in the liver by administering carbontetrachloride (CCl4) to rats. 28 male Wistar albino (n=28, 8weeks old) rats have been used in the study. The rats were distributed into 4 groups according to their live weights. The groups were: (i) negative control (NC): normal water consuming group to which no CCl4 and milk thistle (MT) is administered; (ii) positive control (PC): normal water consuming group to which no CCl4 is administered but MT is administered; (iii) CCl4 group: normal water consuming and group to which CCl4 is administered (2ml/kg live weight, ip); and (iv) CCl4+MT group: CCl4 and MT administered group (2ml/kg live weight, ip). Caspase-3, caspase-9, bax, and bcl-2 protein syntheses were examined via western blotting. MDA determination in liver tissue was made using spectrophotometer. MDA amount has decreased in the CCl4+MT group in comparison to CCl4 group whereas caspase-3 and caspase-9 has increased and bax and bcl-2 has decreased. These results show that MT protects the liver against oxidative damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.

PubMed

Hay, William W; Brown, Laura D; Denne, Scott C

2014-01-01

Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis. © 2014 S. Karger AG, Basel.

Characterizing T-cell response in low-grade and high-grade vulval intraepithelial neoplasia, study of CD3, CD4 and CD8 expressions.

PubMed

Gul, Nahid; Ganesan, Raji; Luesley, David M

2004-07-01

The objective of our study was to compare immunocyte infiltrates in vulval epithelium from low-grade and high-grade vulval intraepithelial neoplasia (VIN) lesions to determine if difference in T-cell presence reflected the grade of VIN. Thirty-six vulval specimens were obtained from 24 patients who had previously undergone vulval biopsies for VIN, 14 high-grade diseases (VIN 3 with or without HPV) and 14 low-grade diseases (VIN 1 and VIN 2 with or without HPV). Eight samples of normal vulval tissue were selected from the excision margins of resected vulval biopsies. The lymphocyte surface markers included CD3 (Pan T-cell marker), CD4 (T helper cells), and CD8 (T cytotoxic cells). Each tissue section was visualized under high power magnification and cells were counted in 10 random areas at the dermo-epidermal junction. A significantly higher number of total mean T lymphocytes were detected in VIN specimens compared to normal vulval tissue (P = 0.002). In low-grade VIN, there were significantly more CD8 cells than CD4 when compared to high-grade VIN. This difference in CD4/CD8 ratio was significant (P = 0.001). This study suggests that increased CD8 response in VIN is a feature of low-grade disease and we speculate that this may be a protective mechanism. In high-grade disease, both CD4 cells and CD8 cells are equally present with preservation of normal CD4/CD8 ratio.

The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

PubMed

Ma, Long; Liu, Jiangguang

2014-12-02

Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this activity displayed a concentration-dependent manner. The efficacy of 10 and 20mg/mL CBS was comparable with colloidal bismuth subcitrate (P<0.05). All three level of CBS tested were able to significantly reduce UI, MDA and enhance SOD level (P<0.05). It was deduced that the mechanism for such activity would be anti-lipid peroxidation, facilitating free radicals clearance. In addition , histopathology examination of the gastric mucous membrane supported the same conclusion, that CBS can efficiently suppress the inflammatory reactions, bleeding and protect the gastric mucosa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine against Trypanosoma cruzi infection

PubMed Central

Cerny, Natacha; Sánchez Alberti, Andrés; Bivona, Augusto E; De Marzi, Mauricio C; Frank, Fernanda M; Cazorla, Silvia I; Malchiodi, Emilio L

2016-01-01

Therapeutic vaccine research and development are especially important in Chagas disease considering the characteristics of the chronic infection and the number of people in the Americas living with a parasite infection for decades. We have previously reported the efficacy of attenuated Salmonella enterica (S) carrying plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection. In the present work we investigated whether Cz DNA vaccine immunotherapy could be effective in controlling an ongoing T. cruzi infection in mice. We here report the intramuscular administration of naked Cz DNA or the oral administration of Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute or chronic infection. The coadministration of a plasmid encoding GM-CSF improved vaccine performance, indicating that the stimulation of innate immune cells is needed in the event of an ongoing infection. These therapeutic vaccines were able to address the response to a protective and sustained Th1 biased profile not only against Cz but also against a variety of parasite antigens. The combined therapeutic vaccine during the chronic phase of infection prevents tissue pathology as shown by a reduced level of enzyme activity characteristic of tissue damage and a tissue status compatible with normal tissue. The obtained results suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in combination with other drug treatments, may represent a promising alternative for Chagas disease therapy. PMID:26312947

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy.

PubMed

de Bever, Joshua; Todd, Nick; Payne, Allison; Christensen, Douglas A; Roemer, Robert B

2014-11-01

Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up. The controller realises time savings by modelling the heated treatment cell's future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell. Selected tissues are safeguarded by a configurable temperature constraint. Simulations quantified the time savings realised by each controller feature as well as the trade-offs between competing safety and treatment time parameters. In vivo experiments in rabbit thighs established the controller's effectiveness and reliability. In all in vivo experiments the target thermal dose of at least 240 CEM43 was delivered everywhere in the treatment volume. The controller's temperature safety limit reliably activated and constrained all protected tissues to <9 CEM43. Simulations demonstrated the path independence of the controller, and that a path which successively proceeds to the hottest untreated neighbouring cell leads to significant time savings, e.g. when compared to a concentric spiral path. Use of the AMPC produced a compounding time-saving effect; reducing the treatment cells' heating times concurrently reduced heating of normal tissues, which eliminated cooling periods. Adaptive model-predictive control can automatically deliver safe, effective MRgFUS treatments while significantly reducing treatment times.

Microgravity Stress: Bone and Connective Tissue.

PubMed

Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

2016-03-15

The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

Glioprotective effects of Ashwagandha leaf extract against lead induced toxicity.

PubMed

Kumar, Praveen; Singh, Raghavendra; Nazmi, Arshed; Lakhanpal, Dinesh; Kataria, Hardeep; Kaur, Gurcharan

2014-01-01

Withania somnifera (Ashwagandha), also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25  μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200  μM) resulted in normalization of glial fibrillary acidic protein (GFAP) expression as well as heat shock protein (HSP70), mortalin, and neural cell adhesion molecule (NCAM) expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx) levels, catalase, and superoxide dismutase (SOD) but not reduced glutathione (GSH) contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma.

PubMed

Meier, Jeremy D; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D Gregory

2010-06-01

The objectives of this study were to 1) determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract, and 2) evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). Cross-sectional study. University-based medical center. Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700-picosecond pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared with the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than that of normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360 to approximately 660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7 +/- 0.06 ns [not significant] for normal and 1.3 +/- 0.06 ns for tumor, P = 0.0025) and the second-order Laguerre expansion coefficient (LEC-2) (i.e., at 460 nm: 0.135 +/- 0.001 for normal and 0.155 +/- 0.007 for tumor, P < 0.05). These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a noninvasive diagnostic technique for HNSCC. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma

PubMed Central

Meier, Jeremy D.; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D. Gregory

2011-01-01

OBJECTIVE 1) Determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract. 2) Evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN Cross-sectional study. SETTING University-based medical center. SUBJECTS AND METHODS Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700 ps pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared to the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. RESULTS Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than the normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360~660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7±0.06 ns for normal and 1.3±0.06 ns for tumor, P=0.0025), and the Laguerre coefficients, LEC-2 (i.e., at 460 nm: 0.135±0.001 for normal and 0.155±0.007 for tumor, P<0.05). CONCLUSION These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a non-invasive diagnostic technique for HNSCC. PMID:20493355

Electrical conductivity measurement of excised human metastatic liver tumours before and after thermal ablation.

PubMed

Haemmerich, Dieter; Schutt, David J; Wright, Andrew W; Webster, John G; Mahvi, David M

2009-05-01

We measured the ex vivo electrical conductivity of eight human metastatic liver tumours and six normal liver tissue samples from six patients using the four electrode method over the frequency range 10 Hz to 1 MHz. In addition, in a single patient we measured the electrical conductivity before and after the thermal ablation of normal and tumour tissue. The average conductivity of tumour tissue was significantly higher than normal tissue over the entire frequency range (from 4.11 versus 0.75 mS cm(-1) at 10 Hz, to 5.33 versus 2.88 mS cm(-1) at 1 MHz). We found no significant correlation between tumour size and measured electrical conductivity. While before ablation tumour tissue had considerably higher conductivity than normal tissue, the two had similar conductivity throughout the frequency range after ablation. Tumour tissue conductivity changed by +25% and -7% at 10 Hz and 1 MHz after ablation (0.23-0.29 at 10 Hz, and 0.43-0.40 at 1 MHz), while normal tissue conductivity increased by +270% and +10% at 10 Hz and 1 MHz (0.09-0.32 at 10 Hz and 0.37-0.41 at 1 MHz). These data can potentially be used to differentiate tumour from normal tissue diagnostically.

JV Task 77 - Health Implications of Mercury - Selenium Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas Ralstion; Laura Raymond

2007-12-15

Exposure to mercury (Hg) commonly results from eating fish containing bioaccumulated methylmercury (MeHg). However, conflicting observations and conclusions have arisen from the ongoing human studies of MeHg exposure from fish consumption. Resolving these uncertainties has important implications for human health since significant nutritional benefits will be lost if fish consumption is needlessly avoided. Selenium (Se), an important nutrient that is abundant in ocean fish, has a potent protective effect against Hg toxicity. This protective effect was thought to be due to the high binding affinities between Hg and Se resulting in Se sequestration of Hg to prevent its harmful effects.more » However, it is imperative to consider the opposing effect of Hg on Se physiology. Crucial proteins that require Se normally protect the brain and hormone-producing glands from oxidative damage. MeHg is able to cross all biological barriers and enter cells in these tissues, where its high Se affinity results in Se sequestration. Sequestration in association with Hg prevents Se from participating in proteins that perform essential antioxidant activities. Supplemental dietary Se is able to replace Se sequestered by Hg and maintain normal antioxidant protection of brain and glands. The goal of this research project was to assess the potency of normal dietary levels of Se in protection against MeHg toxicity. Results from this project indicate that MeHg toxicity is only evident in situations resulting in Hg occurring in high molar excess of Se. Additionally, the common method of MeHg risk assessments using measurements of toenail and blood levels of Hg was shown to provide an accurate reflection of Hg exposure but did not accurately indicate risk of toxicity resulting from that exposure. Instead, Hg:Se molar ratios are proposed as a superior means of assessing risks associated with MeHg exposure.« less

Microarray expression profiling in adhesion and normal peritoneal tissues.

PubMed

Ambler, Dana R; Golden, Alicia M; Gell, Jennifer S; Saed, Ghassan M; Carey, David J; Diamond, Michael P

2012-05-01

To identify molecular markers associated with adhesion and normal peritoneal tissue using microarray expression profiling. Comparative study. University hospital. Five premenopausal women. Adhesion and normal peritoneal tissue samples were obtained from premenopausal women. Ribonucleic acid was extracted using standard protocols and processed for hybridization to Affymetrix Whole Transcript Human Gene Expression Chips. Microarray data were obtained from five different patients, each with adhesion tissue and normal peritoneal samples. Real-time polymerase chain reaction was performed for confirmation using standard protocols. Gene expression in postoperative adhesion and normal peritoneal tissues. A total of 1,263 genes were differentially expressed between adhesion and normal tissues. One hundred seventy-three genes were found to be up-regulated and 56 genes were down-regulated in the adhesion tissues compared with normal peritoneal tissues. The genes were sorted into functional categories according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down-regulated genes were identified with functions potentially relevant to the pathophysiology of postoperative adhesions. We evaluated and confirmed expression of 12 of these specific genes via polymerase chain reaction. The pathogenesis, natural history, and optimal treatment of postoperative adhesive disease remains unanswered. Microarray analysis of adhesions identified specific genes with increased and decreased expression when compared with normal peritoneum. Knowledge of these genes and ontologic pathways with altered expression provide targets for new therapies to treat patients who have or are at risk for postoperative adhesions. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

PubMed Central

2010-01-01

Background Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women. Methods A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry. Results Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer. Conclusion Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy. PMID:21162745

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

NASA Astrophysics Data System (ADS)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

PubMed Central

2010-01-01

Introduction Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues. PMID:20964822

Development of the technique of terahertz pulse spectroscopy for diagnostic malignant tumors during gastrointestinal surgeries

NASA Astrophysics Data System (ADS)

Goryachuk, A. A.; Khodzitsky, M. K.; Borovkova, M. A.; Khamid, A. K.; Dutkinskii, P. S.; Shishlo, D. A.

2016-08-01

Samples of fresh excised tissues obtained from patients who had undergone gastric cancer have been investigated. Samples were consisted of cancer zone, normal zone and zone mixed of normal and cancer tissues. Their optical properties and spectral features were investigated by terahertz time-domain spectroscopy (TDS) in reflection mode. It was found that waveforms of reflected signals from normal and cancer tissues were well distinguished so it can be concluded that it is easy to discriminate gastric cancer tissue from normal by using THz TDS.

A computational framework to detect normal and tuberculosis infected lung from H and E-stained whole slide images

NASA Astrophysics Data System (ADS)

Niazi, M. Khalid Khan; Beamer, Gillian; Gurcan, Metin N.

2017-03-01

Accurate detection and quantification of normal lung tissue in the context of Mycobacterium tuberculosis infection is of interest from a biological perspective. The automatic detection and quantification of normal lung will allow the biologists to focus more intensely on regions of interest within normal and infected tissues. We present a computational framework to extract individual tissue sections from whole slide images having multiple tissue sections. It automatically detects the background, red blood cells and handwritten digits to bring efficiency as well as accuracy in quantification of tissue sections. For efficiency, we model our framework with logical and morphological operations as they can be performed in linear time. We further divide these individual tissue sections into normal and infected areas using deep neural network. The computational framework was trained on 60 whole slide images. The proposed computational framework resulted in an overall accuracy of 99.2% when extracting individual tissue sections from 120 whole slide images in the test dataset. The framework resulted in a relatively higher accuracy (99.7%) while classifying individual lung sections into normal and infected areas. Our preliminary findings suggest that the proposed framework has good agreement with biologists on how define normal and infected lung areas.

Heat treatment of human esophageal tissues: Effect on esophageal cancer detection using oxygenated hemoglobin diffuse reflectance ratio

NASA Astrophysics Data System (ADS)

Zhao, Q. L.; Guo, Z. Y.; Si, J. L.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Guo, X.; Zhong, H. Q.; Li, L. Q.; Li, X. Y.

2011-03-01

The main objective of the present work is to study the influence of heat treatment on the esophageal cancer detection using the diffuse reflectance (DR) spectral intensity ratio R540/R575 of oxygenated hemoglobin (HbO2) absorption bands to distinguish the epithelial tissues of normal human esophagus and moderately differentiated esophageal squamous cell carcinoma (ESCC) at different heat treatment temperature of 20, 37, 42, 50, and 60°C, respectively. The DR spectra for the epithelial tissues of the normal esophagus and ESCC in vitro at different heat-treatment temperature in the wavelength range 400-650 nm were measured with a commercial optical fiber spectrometer. The results indicate that the average DR spectral intensity overall enhancement with concomitant increase of heat-treatment temperature for the epithelial tissues of normal esophagus and ESCC, but the average DR spectral intensity for the normal esophageal epithelial tissues is relatively higher than that for ESCC epithelial tissues at the same heat-treatment temperature. The mean R540/R575 ratios of ESCC epithelial tissues were always lower than that of normal esophageal epithelial tissues at the same temperature, and the mean R540/R575 ratios of the epithelial tissues of the normal esophagus and ESCC were decreasing with the increase of different heat-treatment temperatures. The differences in the mean R540/R575 ratios between the epithelial tissues of normal esophagus and ESCC were 13.33, 13.59, 11.76, and 11.11% at different heat-treatment temperature of 20, 37, 42, and 50°C, respectively. These results also indicate that the DR intensity ratio R540/R575 of the hemoglobin bands is a useful tool for discrimination between the epithelial tissues of normal esophagus and ESCC in the temperature range from room temperature to 50°C, but it was non-effective at 60°C or over 60°C.

The Genome Austria Tissue Bank (GATiB).

PubMed

Asslaber, M; Abuja, P M; Stark, K; Eder, J; Gottweis, H; Trauner, M; Samonigg, H; Mischinger, H J; Schippinger, W; Berghold, A; Denk, H; Zatloukal, K

2007-01-01

In the context of the Austrian Genome Program, a tissue bank is being established (Genome Austria Tissue Bank, GATiB) which is based on a collection of diseased and corresponding normal tissues representing a great variety of diseases at their natural frequency of occurrence from a non-selected Central European population of more than 700,000 patients. Major emphasis is put on annotation of archival tissue with comprehensive clinical data, including follow-up data. A specific IT infrastructure supports sample annotation, tracking of sample usage as well as sample and data storage. Innovative data protection tools were developed which prevent sample donor re-identification, particularly if detailed medical and genetic data are combined. For quality control of old archival tissues, new techniques were established to check RNA quality and antigen stability. Since 2003, GATiB has changed from a population-based tissue bank to a disease-focused biobank comprising major cancers such as colon, breast, liver, as well as metabolic liver diseases and organs affected by the metabolic syndrome. Prospectively collected tissues are associated with blood samples and detailed data on the sample donor's disease, lifestyle and environmental exposure, following standard operating procedures. Major emphasis is also placed on ethical, legal and social issues (ELSI) related to biobanks. A specific research project and an international advisory board ensure the proper embedding of GATiB in society and facilitate international networking. (c) 2007 S. Karger AG, Basel.

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

2009-01-01

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Automated classification of tissue by type using real-time spectroscopy

NASA Astrophysics Data System (ADS)

Benaron, David A.; Cheong, Wai-Fung; Duckworth, Joshua L.; Noles, Kenneth; Nezhat, Camran; Seidman, Daniel; Hintz, Susan R.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W., Jr.; Liu, Frank W.; Stevenson, David K.; Kermit, Eben L.

1997-12-01

Each tissue type has a unique spectral signature (e.g. liver looks distinct from bowel due to differences in both absorbance and in the way the tissue scatters light). While differentiation between normal tissues and tumors is not trivial, automated discrimination among normal tissue types (e.g. nerve, artery, vein, muscle) is feasible and clinically important, as many medical errors in medicine involve the misidentification of normal tissues. In this study, we have found that spectroscopic differentiation of tissues can be successfully applied to tissue samples (kidney and uterus) and model systems (fruit). Such optical techniques may usher in use of optical tissue diagnosis, leading to automated and portable diagnostic devices which can identify tissues, and guide use of medical instruments, such as during ablation or biopsy.

Quantitative ultrasound backscatter for pulsed cavitational ultrasound therapy- histotripsy.

PubMed

Wang, Tzu-yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L; Fowlkes, J Brian; Rothman, Edward D; Roberts, William W; Cain, Charles A

2009-05-01

Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs.This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology.Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated.

Evaluation of a mixed beam therapy for post-mastectomy breast cancer patients: bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy.

PubMed

Zhang, Rui; Heins, David; Sanders, Mary; Guo, Beibei; Hogstrom, Kenneth

2018-05-10

The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided post-mastectomy breast cancer patients. Mixed beam treatment plans were produced for nine post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT+IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs. 0.53, p < 0.001) and DHI (0.12 vs. 0.20, p < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs. 0.80%, p = 0.01) and SCCP for contralateral breast (1.7% vs. 3.1% based on linear model, and 1.2% vs. 1.9% based on linear-exponential model, p < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs. 49.3 Gy, p < 0.001) and maximum skin doses (59.7 Gy vs. 53.3 Gy, p < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm 3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. This work has demonstrated that mixed beam therapy (BECT+IMRT : VMAT = 4 : 1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating post-mastectomy patients, possibly leading to reduced normal tissue complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Diagnosis of breast cancer by tissue analysis

PubMed Central

Bhattacharyya, Debnath; Bandyopadhyay, Samir Kumar

2013-01-01

In this paper, we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test, when require. We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps. Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper. In fact, features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue. We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent. PMID:23372340

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

PubMed

Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-05-21

The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

[The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory].

PubMed

Pang, Jing-yao; Bai, Zhao-fang; Niu, Ming; Tu, Can; Ma, Zhi-jie; Zhao, Yan-ling; Zhao, Kui-jun; You, Yun; Wang, Jia-bo; Xiao, Xiao-he

2015-08-01

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

Distribution of Flunixin Residues in Muscles of Dairy Cattle Dosed with Lipopolysaccharide or Saline and Treated with Flunixin by Intravenous or Intramuscular Injection.

PubMed

Shelver, Weilin L; Schneider, Marilyn J; Smith, David J

2016-12-28

Twenty dairy cows received flunixin meglumine at 2.2 mg/kg bw, administered once daily by either the intravenous (IV) or intramuscular (IM) route for three consecutive days with either intravenous normal saline (NS) or lipopolysaccharide (LPS) providing a balanced design with five animals per group. Cows were sacrificed after a 4 day withdrawal period, and 13 muscle types were collected and assayed for flunixin by LC-MS/MS. After elimination of sample outliers, the main effects of route of administration (IV or IM), treatment (NS or LPS), and tissue type significantly (P < 0.05) affected flunixin residues, with no interaction (P > 0.05). Intramuscular (nonlabel) flunixin administration produced greater (P < 0.05) flunixin residues in muscle than the IV (label) administration, whereas LPS resulted in lower flunixin levels. Differences among the tissue levels indicate it is necessary to specify the tissue to be used for any monitoring of drug levels for consumer protection.

Detection of survivin 2α gene expression in thyroid nodules.

PubMed

Kyani, Keyhaneh; Babaei, Esmaeil; Feizi, Mohammad Ali Hosseinpour; Vandghanooni, Somayeh; Montazeri, Vahid; Halimi, Monireh

2014-01-01

Functional studies of the survivin splice variants have been performed almost exclusively in various types of cancer and produced remarkable advances in our understanding of cancer biology and cancer genetics. To observation the expression of survivin 2α in thyroid nodules and estimate its potential as a new molecular marker in thyroid nodules screening and malignant thyroid, as well. We detected the expression of a splice variant of survivin, survivin 2α, in thyroid nodules. Expression of survivin 2α mRNA was evaluated with specific primers by Hemi-Nested RT-PCR in 77 thyroid nodules including malignant and benign tumors, non-tumoral (goiter and thyroiditis) as well as surgical margin, non-neoplastic normal tissues adjacent to the malignant lesions. Our data revealed for the first time the expression of survivin 2α in thyroid nodules. It was detected in 85.7% of non-neoplastic surgical margin tissues, 71.4% of non tumoral, 63.2% of tumoral samples. Also, the expression of survivin 2α in benign tumor samples (64.2%) is more than malignant groups (62.8%). Survivin 2α expression is the highest in non-neoplastic surgical margin rather than other samples and the lowest expression was that of malignancy. According to the results, it can be concluded that survivin 2α protein may be has a vital protective effect throw survivin quenching due to the high expression in normal tissue compared with lesions.

Glutamine prevents gastric oxidative stress in an animal model of portal hypertension gastropathy.

PubMed

Marques, Camila; Mauriz, José L; Simonetto, Douglas; Marroni, Claudio A; Tuñon, María J; González-Gallego, Javier; Marrón, Norma P

2011-01-01

Portal hypertension (PHI) is a clinical syndrome characterized by increases of the blood flow and/or of the vascular resistance in the portal system. A direct consequence of PHI can appearance different lesions on the gastric mucosa and submucosa, cumulatively termed portal hypertensive gastropathy (PHG). To investigate the effects of glutamine on oxidative stress in an experimental model of PHG induced by partial portal vein ligation (PPVL). Portal pressure, transaminase and alkaline phosphatase activity were quantified. Gastric tissue damage was assessed by histological analysis. Oxidative stress was measured by quantification of cytosolic concentration of thiobarbituric acid reactive substances (TBARS), hydroperoxide-initiated chemiluminescence (QL), and nitric oxide (NO) production. Moreover, activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were analyzed. Transaminase and alkaline phosphatase activities were not significantly modified by PPVL, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. TBARS, QL, and NO production were significantly increased in PPVL animals. A reduction of SOD activity was found. Glutamine administration markedly alleviated histological abnormalities and oxidative stress, normalized SOD activity, and blocked NO overproduction. Our results confirm that the use of molecules with antioxidant capacity can provide protection of the gastric tissue in portal hypertension. Glutamine treatment can be useful to reduce the oxidative damage induced by PHI on gastric tissue.

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

PubMed

Abend, M; Pfeiffer, R M; Ruf, C; Hatch, M; Bogdanova, T I; Tronko, M D; Hartmann, J; Meineke, V; Mabuchi, K; Brenner, A V

2013-10-15

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

[Emodin alleviates pulmonary fibrosis through inactivation of TGF-β1/ADAMTS-1 signaling pathway in rats].

PubMed

Liu, Lijing; Qian, Hong; Xiao, Hua; He, Jianbin; Xie, Maofeng; Wang, Zaiyan; Long, Xingyun

2016-10-01

Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group. From the second day, rats in the low- and high-dose emodin intervention groups were intragastrically treated with 2 mL of 20 and 80 mg/kg emodin, respectively. Rats in the prednisone group were intragastrically administrated with 2 mL of 5 mg/kg prednisone acetate. However, rats in the normal control and sham-operated and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28 after modeling. Subsequently, blood and pulmonary tissue specimen were taken. The pathological changes of pulmonary tissues were observed using routine HE and Masson staining. The expressions of TGF-β1, ADAMTS-1, collagen type 1 (Col1) and Col3 in pulmonary tissues were measured by quantitative real-time PCR and Western blotting. Serum levels of procollagen type 1 carboxy terminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) were detected by ELISA. Results Compare with the model group, the alveolitis and pulmonary fibrosis extent in each drug-treated group were significantly alleviated. In comparison with normal control group or sham-operated group, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP increased, but the mRNA and protein levels of ADAMTS-1 decreased in model group. After treatment with low- and high-dose emodin or prednisone, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP were significantly downregulated, while the mRNA and protein levels of ADAMTS-1 in pulmonary tissues were significantly upregulated as compared with the model group. Moreover, In comparison with the low-dose emodin intervention group, the above indicators were significantly improved in the high-dose emodin intervention or prednisone group. However, the above indicators were not significantly different between the high-dose emodin intervention group and the prednisone group. Conclusion Increased degradation of Col1 and Col3 in pulmonary tissues due to the inactivation of TGF-β1/ADAMTS-1 signaling pathway may be a significant mechanism by which emodin protects rats against pulmonary fibrosis.

PIXE analysis of tumors and localization behavior of a lanthanide in nude mice

NASA Astrophysics Data System (ADS)

Chang, Pei-Jiun; Yang, Czau-Siung; Chou, Ming-Ji; Wei, Chau-Chin; Hsu, Chu-Chung; Wang, Chia-Yu

1984-04-01

We have used particle induced X-ray emission (PIXE) to analyze the elemental compositions and uptakes of a lanthanide, yttrium in this report, in tumors and normal tissues of nude mice. A small amount of yttrium nitrate was injected into nude mice with tumors. Samples of normal and malignant tissues taken from these mice were bombarded by the 2 MeV proton beam from a 3 MeV Van de Graaff accelerator with a Ge detector system to determine the relative elemental compositions of tissues and the relative concentrations of yttrium taken up by these tissues. We found that the uptakes of yttrium by tumors were at least five times more than those by normal tissues. Substantial differences were often observed between the trace element weight (or concentration) pattern of the cancerous and normal tissues. The present result is compared with human tissues.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

PubMed

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E

PubMed Central

Al-Damegh, Mona Abdullah

2012-01-01

OBJECTIVE: The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. MATERIALS AND METHODS: The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. RESULTS: There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. CONCLUSION: Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes. PMID:22892924

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E.

PubMed

Al-Damegh, Mona Abdullah

2012-07-01

The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo

PubMed Central

Tao, Rong-Hua; Berkova, Zuzana; Wise, Jillian F.; Rezaeian, Abdol-Hossein; Daniluk, Urszula; Ao, Xue; Hawke, David H.; Karp, Judith E.; Lin, Hui-Kuan; Molldrem, Jeffrey J.

2011-01-01

Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML–retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)–derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIPL/S and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas. PMID:21803845

Biochemistry of epidermal stem cells.

PubMed

Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

2013-02-01

The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Biochemistry of epidermal stem cells☆

PubMed Central

Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

2014-01-01

Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. PMID:22820019

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

PubMed

Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

2013-10-04

Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.

Resonance Raman of BCC and normal skin

NASA Astrophysics Data System (ADS)

Liu, Cheng-hui; Sriramoju, Vidyasagar; Boydston-White, Susie; Wu, Binlin; Zhang, Chunyuan; Pei, Zhe; Sordillo, Laura; Beckman, Hugh; Alfano, Robert R.

2017-02-01

The Resonance Raman (RR) spectra of basal cell carcinoma (BCC) and normal human skin tissues were analyzed using 532nm laser excitation. RR spectral differences in vibrational fingerprints revealed skin normal and cancerous states tissues. The standard diagnosis criterion for BCC tissues are created by native RR biomarkers and its changes at peak intensity. The diagnostic algorithms for the classification of BCC and normal were generated based on SVM classifier and PCA statistical method. These statistical methods were used to analyze the RR spectral data collected from skin tissues, yielding a diagnostic sensitivity of 98.7% and specificity of 79% compared with pathological reports.

Preventive activity of banana peel polyphenols on CCl4-induced experimental hepatic injury in Kunming mice.

PubMed

Wang, Rui; Feng, Xia; Zhu, Kai; Zhao, Xin; Suo, Huayi

2016-05-01

The aim of the present study was to evaluate the preventive effects of banana peel polyphenols (BPPs) against hepatic injury. Mice were divide into normal, control, 100 mg/kg and 200 mg/kg banana peel polyphenol and silymarin groups. All the mice except normal mice were induced with hepatic damage using CCl 4 . The serum and tissue levels of mice were determined by a kit and the tissues were further examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. BPPs reduced the serum levels of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase in a CCl 4 -induced mouse model of hepatic injury. Furthermore, BPPs reduced the levels of malondialdehyde and triglyceride, while increasing glutathione levels in the serum and liver tissues of mice. In addition, the effects of 200 mg/kg treatment were more evident, and these effects were comparable to those of the drug silymarin. Serum levels of the cytokines, interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon-γ, were reduced in the mice treated with BPPs compared with injury control group mice, and these levels were comparable to those of the normal and silymarin-treated groups. Histopathological examination indicated that BPPs were able to reduce the extent of CCl 4 -induced liver tissue injury and protect the liver cells. Furthermore, the mRNA and protein expression levels of the inflammation-associated factors cyclooxygenase-2, nitric oxide synthase, TNF-α and IL-1β were reduced in mice treated with BPPs compared with the control group mice. Mice that received 200 mg/kg BPP exhibited reduced expression levels of these factors compared with mice that received 100 mg/kg BPP. In conclusion, the results of the present study suggested that BPPs exert a good preventive effect against hepatic injury.

Protective effect of Pterocarpus marsupium bark extracts against cataract through the inhibition of aldose reductase activity in streptozotocin-induced diabetic male albino rats.

PubMed

Xu, YanLi; Zhao, Yongxia; Sui, YaNan; Lei, XiaoJun

2018-04-01

The present study was aimed to investigate the protective effect of Pterocarpus marsupium bark extracts against cataract in streptozotocin-induced diabetic male albino rats. Aldose reductase is a key enzyme in the intracellular polyol pathway, which plays a major role in the development of diabetic cataract. Rats were divided into five groups as normal control, diabetic control, and diabetic control treated with different concentrations of Pterocarpus marsupium bark extracts. Presence of major constituents in Pterocarpus marsupium bark extract was performed by qualitative analysis. Body weight changes, blood glucose, blood insulin, and reduced glutathione (GSH) and aldose reductase mRNA and protein expression were determined. Rat body weight gain was noted following treatment with bark extracts. The blood glucose was reduced up to 36% following treatment with bark extracts. The blood insulin and tissue GSH contents were substantially increased more than 100% in diabetic rats following treatment with extracts. Aldose reductase activity was reduced up to 79.3% in diabetic rats following treatment with extracts. V max , K m , and K i of aldose reductase were reduced in the lens tissue homogenate compared to the diabetic control. Aldose reductase mRNA and protein expression were reduced more than 50% following treatment with extracts. Treatment with Pterocarpus marsupium bark was able to normalize these levels. Taking all these data together, it is concluded that the use of Pterocarpus marsupium bark extracts could be the potential therapeutic approach for the reduction of aldose reductase against diabetic cataract.

Comparison of stretched-Exponential and monoexponential model diffusion-Weighted imaging in prostate cancer and normal tissues.

PubMed

Liu, Xiaohang; Zhou, Liangping; Peng, Weijun; Wang, He; Zhang, Yong

2015-10-01

To compare stretched-exponential and monoexponential model diffusion-weighted imaging (DWI) in prostate cancer and normal tissues. Twenty-seven patients with prostate cancer underwent DWI exam using b-values of 0, 500, 1000, and 2000 s/mm(2) . The distributed diffusion coefficients (DDC) and α values of prostate cancer and normal tissues were obtained with stretched-exponential model and apparent diffusion coefficient (ADC) values using monoexponential model. The ADC, DDC (both in 10(-3) mm(2)/s), and α values (range, 0-1) were compared among different prostate tissues. The ADC and DDC were also compared and correlated in each tissue, and the standardized differences between DDC and ADC were compared among different tissues. Data were obtained for 31 cancers, 36 normal peripheral zone (PZ) and 26 normal central gland (CG) tissues. The ADC (0.71 ± 0.12), DDC (0.60 ± 0.18), and α value (0.64 ± 0.05) of tumor were all significantly lower than those of the normal PZ (1.41 ± 0.22, 1.47 ± 0.20, and 0.85 ± 0.09) and CG (1.25 ± 0.14, 1.32 ± 0.13, and 0.82 ± 0.06) (all P < 0.05). ADC was significantly higher than DDC in cancer, but lower than DDC in the PZ and CG (all P < 0.05). The ADC and DDC were strongly correlated (R(2)  = 0.99, 0.98, 0.99, respectively, all P < 0.05) in all the tissue, and standardized difference between ADC and DDC of cancer was slight but significantly higher than that in normal tissue. The stretched-exponential model DWI provides more parameters for distinguishing prostate cancer and normal tissue and reveals slight differences between DDC and ADC values. © 2015 Wiley Periodicals, Inc.

The Resistance of Certain Tissues to Invasion

PubMed Central

Eisenstein, Reuben; Sorgente, Nino; Soble, Lawrence W.; Miller, Alexander; Kuettner, Klaus E.

1973-01-01

If puppy tissues are explanted onto the chick chorioallantoic membrane, those tissues which normally have a blood supply are rapidly invaded by vascularized mesenchyme of host origin. Hyaline cartilage, a tissue virtually devoid of blood vessels, is impenetrable by proliferating mesenchyme of the host, while calcified cartilage, which normally is vascularized, is penetrable. The stroma of the cornea, another normally avascular tissue, is readily penetrable, but Descemet's membrane forms a barrier to invasion by host tissues. The experimental system used permits the design of experiments in which the study of factors responsible for the resistance of tissues such as cartilage to invasion can be undertaken. ImagesFig 1Fig 2Fig 3Fig 4 PMID:4129060

Trace elemental analysis in cancer-afflicted tissues of penis and testis by PIXE technique

NASA Astrophysics Data System (ADS)

Naga Raju, G. J.; John Charles, M.; Bhuloka Reddy, S.; Sarita, P.; Seetharami Reddy, B.; Rama Lakshmi, P. V. B.; Vijayan, V.

2005-04-01

PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher. The concentrations of K, Ca, Ti, Cr, Mn, Br, Sr and Pb are in agreement within standard deviations in both cancerous and normal tissues. In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy. The Cu/Zn ratios of both penis and testis were higher in cancer tissues compared to that of normal.

Optical characterization of pancreatic normal and tumor tissues with double integrating sphere system

NASA Astrophysics Data System (ADS)

Kiris, Tugba; Akbulut, Saadet; Kiris, Aysenur; Gucin, Zuhal; Karatepe, Oguzhan; Bölükbasi Ates, Gamze; Tabakoǧlu, Haşim Özgür

2015-03-01

In order to develop minimally invasive, fast and precise diagnostic and therapeutic methods in medicine by using optical methods, first step is to examine how the light propagates, scatters and transmitted through medium. So as to find out appropriate wavelengths, it is required to correctly determine the optical properties of tissues. The aim of this study is to measure the optical properties of both cancerous and normal ex-vivo pancreatic tissues. Results will be compared to detect how cancerous and normal tissues respond to different wavelengths. Double-integrating-sphere system and computational technique inverse adding doubling method (IAD) were used in the study. Absorption and reduced scattering coefficients of normal and cancerous pancreatic tissues have been measured within the range of 500-650 nm. Statistical significant differences between cancerous and normal tissues have been obtained at 550 nm and 630 nm for absorption coefficients. On the other hand; there were no statistical difference found for scattering coefficients at any wavelength.

Tryptophan as key biomarker to detect gastrointestinal tract cancer using non-negative biochemical analysis of native fluorescence and Stokes Shift spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Leana; Zhou, Yan; Liu, Cheng-hui; Zhou, Lixin; He, Yong; Pu, Yang; Nguyen, Thien An; Alfano, Robert R.

2015-03-01

The objective of this study was to find out the emission spectral fingerprints for discrimination of human colorectal and gastric cancer from normal tissue in vitro by applying native fluorescence. The native fluorescence (NFL) and Stokes shift spectra of seventy-two human cancerous and normal colorectal (colon, rectum) and gastric tissues were analyzed using three selected excitation wavelengths (e.g. 300 nm, 320 nm and 340 nm). Three distinct biomarkers, tryptophan, collagen and reduced nicotinamide adenine dinucleotide hydrate (NADH), were found in the samples of cancerous and normal tissues from eighteen subjects. The spectral profiles of tryptophan exhibited a sharp peak in cancerous colon tissues under a 300 nm excitation when compared with normal tissues. The changes in compositions of tryptophan, collagen, and NADH were found between colon cancer and normal tissues under an excitation of 300 nm by the non-negative basic biochemical component analysis (BBCA) model.

Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

PubMed

Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

2012-01-01

Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and represent important end-points for analysis in studies of therapeutic strategies to protect patients from neural dysfunction.

Anti-inflammatory and cytoprotective properties of hydrogen sulfide.

PubMed

Gemici, Burcu; Wallace, John L

2015-01-01

Hydrogen sulfide is an endogenous gaseous mediator that plays important roles in many physiological processes in microbes, plants, and animals. This chapter focuses on the important roles of hydrogen sulfide in protecting tissues against injury, promoting the repair of damage, and downregulating the inflammatory responses. The chapter focuses largely, but not exclusively, on these roles of hydrogen sulfide in the gastrointestinal tract. Hydrogen sulfide is produced throughout the gastrointestinal tract, and it contributes to maintenance of mucosal integrity. Suppression of hydrogen sulfide synthesis renders the tissue more susceptible to injury and it impairs repair. In contrast, administration of hydrogen sulfide donors can increase resistance to injury and accelerate repair. Hydrogen sulfide synthesis is rapidly and dramatically enhanced in the gastrointestinal tract after injury is induced. These increases occur specifically at the site of tissue injury. Hydrogen sulfide also plays an important role in promoting resolution of inflammation, and restoration of normal tissue function. In recent years, these beneficial actions of hydrogen sulfide have provided the basis for development of novel hydrogen sulfide-releasing drugs. Nonsteroidal anti-inflammatory drugs that release small amounts of hydrogen sulfide are among the most advanced of the hydrogen sulfide-based drugs. Unlike the parent drugs, these modified drugs do not cause injury in the gastrointestinal tract, and do not interfere with healing of preexisting damage. Because of the increased safety profile of these drugs, they can be used in circumstances in which the toxicity of the parent drug would normally limit their use, such as in chemoprevention of cancer. © 2015 Elsevier Inc. All rights reserved.

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Cultured normal mammalian tissue and process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor)

1993-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cell aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

CCl4 induced genotoxicity and DNA oxidative damages in rats: hepatoprotective effect of Sonchus arvensis.

PubMed

Alkreathy, Huda Mohammad; Khan, Rahmat Ali; Khan, Muhammad Rashid; Sahreen, Sumaira

2014-11-21

Sonchus arvesis is traditionally reported in various human ailments including hepatotoxicity in Pakistan. Presently we designed to assess the protective effects of methanolic extract of Sonchus arvesis against carbon tetrachloride induced genotoxicity and DNA oxidative damages in hepatic tissues of experimental rats. 36 male Sprague-Dawley rats were randomly divided into 6 groups to evaluate the hepatoprotective effects of Sonchus arvensis against CCl4 induced genotoxicity, DNA damages and antioxidant depletion. Rats of normal control group were given free access of food and water add labitum. Group II rats received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for four weeks. Group III and IV received 1 ml of 100 mg/kg b.w. and 200 mg/kg b.w. SME via gavage after 48 h of CCl4 treatment whereas group V was given 1 ml of silymarin (100 mg/kg b.w.) after 48 h of CCl4 treatment. Group VI only received 200 mg/kg b.w. SME. Protective effects of SME were checked by measuring serum markers, activities of antioxidant enzymes, genotoxicity and DNA dmages. Results of the present study showed that treatment of SME reversed the activities of serum marker enzymes and cholesterol profile as depleted with CCl4 treatment. Activities of endogenous antioxidant enzymes of liver tissue homogenate; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) were reduced with administration of CCl4, which were returned to the control level with SME treatment. CCl4-induced hepatic cirrhosis decreased hepatic glutathione (GSH) and increased lipid peroxidative products (TBARS), were normalized by treatment with SME. Moreover, administration of CCl4 caused genotoxicity and DNA fragmentation which were significantly restored towards the normal level with SME. These results reveal that treatment of SME may be useful in the prevention of hepatic stress.

Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage.

PubMed

Deng, Guoying; Chen, Changzhe; Zhang, Junjie; Zhai, Yue; Zhao, Jingpeng; Ji, Anqi; Kang, Yingjie; Liu, Xijian; Dou, Kefei; Wang, Qiugen

2018-03-23

Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO 2 nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO 2 nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO 2 nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO 2 . And Se@SiO 2 has few interference to the therapeutic effect of DOX. Particularly, Se@SiO 2 significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO 2 in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO 2 nanocomposite in the clinical use of DOX.

Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

PubMed Central

Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

2017-01-01

Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. PMID:27672101

Screening prostate cancer using a portable near infrared scanning imaging unit with an optical fiber-based rectal probe

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, Wubao; Tang, Guichen; Budansky, Yury; Sharonov, Mikhail; Xu, Min; Achilefu, Samuel; Eastham, James A.; Alfano, Robert R.

2012-01-01

A portable near infrared scanning polarization imaging unit with an optical fiber-based rectal probe, namely Photonic Finger, was designed and developed o locate the 3D position of abnormal prostate site inside normal prostate tissue. An inverse algorithm, Optical Tomography using Independent Component Analysis (OPTICA) was improved particularly to unmix the signal from targets (cancerous tissue) embedded in a turbid medium (normal tissue) in the backscattering imaging geometry. Photonic Finger combined with OPTICA was tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded by large piece of normal tissue.

Raman spectroscopy of oral tissues: correlation of spectral and biochemical markers

NASA Astrophysics Data System (ADS)

Singh, S. P.; Krishna, C. Murali

2014-03-01

Introduction Optical spectroscopic methods are being explored as novel tools for early and non-invasive cancer diagnosis. Both ex vivo and in vivo Raman spectroscopic studies carried out in oral cancer over the past decade have demonstrated that spectra of normal tissues are rich in lipids while tumor spectra show predominance of proteins. An accurate understanding of spectral features with respect to the biochemical composition is a pre-requisite before transferring these technologies for routine clinical usage. Therefore, in the present study, we have carried out Raman and biochemical studies on same tissues to correlate spectral markers and biochemical composition of normal and tumor oral tissues. Materials and Methods Spectra of 20 pairs of normal and tumor oral tissues were acquired using fiber-optic probe coupled HE-785 Raman spectrometer. Intensity associated with lipid (1440 cm-1) and protein (1450 and 1660 cm-1) bands were computed using curve-deconvolution method. Same tissues were then subjected to biochemical estimations of major biomolecules i.e., protein, lipid and phospholipids. Results and Discussion The intensity of the lipid band was found to be higher in normal tissues with respect to tumors, and the protein band was higher in tumors compared to normal tissues. Biochemical estimation yielded similar results i.e. high protein to lipid or phospholipid ratio in tumors with-respect to normal tissues. These differences were found to be statistically significant. Conclusion Findings of curve-deconvolution and biochemical estimation correlate very well and corroborate the spectral profile noted in earlier studies.

The classification of secondary colorectal liver cancer in human biopsy samples using angular dispersive x-ray diffraction and multivariate analysis

NASA Astrophysics Data System (ADS)

Theodorakou, Chrysoula; Farquharson, Michael J.

2009-08-01

The motivation behind this study is to assess whether angular dispersive x-ray diffraction (ADXRD) data, processed using multivariate analysis techniques, can be used for classifying secondary colorectal liver cancer tissue and normal surrounding liver tissue in human liver biopsy samples. The ADXRD profiles from a total of 60 samples of normal liver tissue and colorectal liver metastases were measured using a synchrotron radiation source. The data were analysed for 56 samples using nonlinear peak-fitting software. Four peaks were fitted to all of the ADXRD profiles, and the amplitude, area, amplitude and area ratios for three of the four peaks were calculated and used for the statistical and multivariate analysis. The statistical analysis showed that there are significant differences between all the peak-fitting parameters and ratios between the normal and the diseased tissue groups. The technique of soft independent modelling of class analogy (SIMCA) was used to classify normal liver tissue and colorectal liver metastases resulting in 67% of the normal tissue samples and 60% of the secondary colorectal liver tissue samples being classified correctly. This study has shown that the ADXRD data of normal and secondary colorectal liver cancer are statistically different and x-ray diffraction data analysed using multivariate analysis have the potential to be used as a method of tissue classification.

Glutathione-related enzymes and the eye.

PubMed

Ganea, Elena; Harding, John J

2006-01-01

Glutathione and the related enzymes belong to the defence system protecting the eye against chemical and oxidative stress. This review focuses on GSH and two key enzymes, glutathione reductase and glucose-6-phosphate dehydrogenase in lens, cornea, and retina. Lens contains a high concentration of reduced glutathione, which maintains the thiol groups in the reduced form. These contribute to lens complete transparency as well as to the transparent and refractive properties of the mammalian cornea, which are essential for proper image formation on the retina. In cornea, gluthatione also plays an important role in maintaining normal hydration level, and in protecting cellular membrane integrity. In retina, glutathione is distributed in the different types of retinal cells. Intracellular enzyme, glutathione reductase, involved in reducing the oxidized glutathione has been found at highest activity in human and primate lenses, as compared to other species. Besides the enzymes directly involved in maintaining the normal redox status of the cell, glucose-6-phosphate dehydrogenase which catalyzes the first reaction of the pentose phosphate pathway, plays a key role in protection of the eye against reactive oxygen species. Cornea has a high activity of the pentose phosphate pathway and glucose-6-phosphate dehydrogenase activity. Glycation, the non-enzymic reaction between a free amino group in proteins and a reducing sugar, slowly inactivates gluthathione-related and other enzymes. In addition, glutathione can be also glycated. The presence of glutathione, and of the related enzymes has been also reported in other parts of the eye, such as ciliary body and trabecular meshwork, suggesting that the same enzyme systems are present in all tissues of the eye to generate NADPH and to maintain gluthatione in the reduced form. Changes of glutathione and related enzymes activity in lens, cornea, retina and other eye tissues, occur with ageing, cataract, diabetes, irradiation and administration of some drugs.

Effects of Pistacia Atlantica Extract on Erythrocyte Membrane Rigidity, Oxidative Stress, and Hepatotoxicity Induced by CCl4 in Rats.

PubMed

Tolooei, Mohsen; Mirzaei, Ali

2015-03-26

Previous findings have suggested that antioxidants may reduce the levels of free radicals, which induce oxidative damage and play a key role in various diseases. Thus, we evaluated the protective activity of a Pistacia atlantica extract on erythrocyte membrane rigidity, oxidative stress, and hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. Fresh leaves of P.atlantica were collected from the mountains in Yasuj, Iran. Acute oral toxicity (LD50) was evaluated in Wistar rats (200-230 g). Animals were randomly divided into 4 groups, out of which the negative and plant control groups received distilled water and P. atlantica extracts (500 mg/kg), respectively. The toxic rat group received CCl4, while the treatment group received CCl4+P. atlantica extract. Blood plasma was utilized for the estimation of enzyme markers and lipid peroxidation, whereas hemolysate was applied for the determination of superoxide dismutase (SOD) and catalase activities. The levels of cholesterol and phospholipids in erythrocyte membranes were also determined. Rats were killed under anesthesia by cervical dislocation; liver was isolated from each rat and tissues homogenization was prepared for biochemical parameters such as malondialdehyde (MDA) and reduced glutathione (GSH) levels. LD50 values were determined for doses>3000 mg/kg (p.o.). The activities of glutamic pyruvate transaminase (GPT), glutamic oxaloacetate transaminase (GOT), alkaline phosphatase (ALP) and GSH in the protected group were significantly (p<0.001) reduced compared with those of toxic rats. In addition, we observed a decrease in the cholesterol level and an increase in red blood cell membrane phospholipids, SOD, and catalase activities (p<0.001) in the protected group, as compared with toxic rats. Administration of Pistacia atlantica extract normalized liver tissue MDA level (p<0.01) when compared to CCl4 treated group. The P. atlantica extract was able to normalize the levels of biochemical markers, including liver enzyme markers, first-line defense enzymes, and lipid peroxidation markers.

[Protective effect of Angelica sinensis polysaccharides on subacute renal damages induced by D-galactose in mice and its mechanism].

PubMed

Fan, Yan-ling; Xia, Jie-yu; Jia, Dao-yong; Zhang, Meng-si; Zhang, Yan-yan; Wang, Lu; Huang, Guo-ning; Wang, Ya-ping

2015-11-01

To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury.

Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

PubMed

Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

2018-06-15

Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

[Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

PubMed

Knop, E; Knop, N

2003-11-01

Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer.

PubMed

Son, Yeonghoon; Lee, Hae June; Rho, Jin Kyung; Chung, Soo Young; Lee, Chang Geun; Yang, Kwangmo; Kim, Sung Ho; Lee, Minyoung; Shin, In Sik; Kim, Joong Sun

2015-07-05

Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone. Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation.

Meninges: from protective membrane to stem cell niche.

PubMed

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction.

A large-scale measurement of dielectric properties of normal and malignant colorectal tissues obtained from cancer surgeries at Larmor frequencies.

PubMed

Li, Zhou; Deng, Guanhua; Li, Zhe; Xin, Sherman Xuegang; Duan, Song; Lan, Maoying; Zhang, Sa; Gao, Yixin; He, Jun; Zhang, Songtao; Tang, Hongming; Wang, Weiwei; Han, Shuai; Yang, Qing X; Zhuang, Ling; Hu, Jiani; Liu, Feng

2016-11-01

Knowledge of dielectric properties of malignant human tissues is necessary for the recently developed magnetic resonance (MR) technique called MR electrical property tomography. This technique may be used in early tumor detection based on the obvious differentiation of the dielectric properties between normal and malignant tissues. However, the dielectric properties of malignant human tissues in the scale of the Larmor frequencies are not completely available in the literature. In this study, the authors focused only on the dielectric properties of colorectal tumor tissue. The dielectric properties of 504 colorectal malignant samples excised from 85 patients in the scale of the Larmor frequencies were measured using the precision open-ended coaxial probe method. The obtained complex-permittivity data were fitted to the single-pole Cole-Cole model. The median permittivity and conductivity for the malignant tissue sample were 79.3 and 0.881 S/m at 128 MHz, which were 14.6% and 17.0% higher, respectively, than those of normal tissue samples. Significant differences between normal and malignant tissues were found for the dielectric properties (p < 0.05). Experimental results indicated that the dielectric properties were significantly different between normal and malignant tissues for colorectal tissue. This large-scale clinical measurement provides more subtle base data to validate the technique of MR electrical property tomography.

Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.

PubMed

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2008-10-01

Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.

Quantitative Ultrasound Backscatter for Pulsed Cavitational Ultrasound Therapy—Histotripsy

PubMed Central

Wang, Tzu-Yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L.; Fowlkes, J. Brian; Rothman, Edward D.; Roberts, William W.; Cain, Charles A.

2011-01-01

Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs. This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology. Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated. PMID:19750596

Evaluation of immunoreactivity of normal tissues from dogs, using monoclonal antibody B72.3.

PubMed

Clemo, F A; DeNicola, D B; Zimmermann, J L

1994-08-01

Monoclonal antibody (MAB) B72.3, which recognizes human tumor-associated glycoprotein-72, has immunoreactivity for malignant epithelial neoplasms in human beings and dogs. To further characterize the range of immunoreactivity of MAB B72.3 in canine tissues, MAB B72.3 and 2 other tumor-associated glycoprotein-72 antibodies (MAB CC49 and CC83) were tested against a wide spectrum of normal tissues from dogs. Immunoreactivity was detected, using an avidin-biotin-complex immunoperoxidase method. Monoclonal antibody B72.3 did not stain most types of normal canine tissues, but various types of epithelial cells within the gastrointestinal and respiratory tract mucosae, salivary gland, esophagus, epididymis, uterus, thymus, hair follicle, and apocrine glands of the anal sac had variable staining with MAB B72.3. A similar range of immunoreactivity in comparable types of normal tissues was seen for MAB CC49 and CC83; however, MAB CC49, but not MAB B72.3 and CC83, stained the endothelium of capillaries and small vessels in most normal tissues. Staining of frozen and paraffin-embedded tissues was similar. In conclusion, we found that MAB B72.3, CC49, and CC83 had selected immunoreactivity for specific types of normal canine epithelial cells, especially those involved with mucin production.

Depth-resolved monitoring of diffusion of hyperosmotic agents in normal and malignant human esophagus tissues using optical coherence tomography in-vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Qingliang; Guo Zhouyi; Wei Huajiang

2011-10-31

Depth-resolved monitoring with differentiation and quantification of glucose diffusion in healthy and abnormal esophagus tissues has been studied in vitro. Experiments have been performed using human normal esophagus and esophageal squamous cell carcinoma (ESCC) tissues by the optical coherence tomography (OCT). The images have been continuously acquired for 120 min in the experiments, and the depth-resolved and average permeability coefficients of the 40 % glucose solution have been calculated by the OCT amplitude (OCTA) method. We demonstrate the capability of the OCT technique for depth-resolved monitoring, differentiation, and quantifying of glucose diffusion in normal esophagus and ESCC tissues. It ismore » found that the permeability coefficients of the 40 % glucose solution are not uniform throughout the normal esophagus and ESCC tissues and increase from (3.30 {+-} 0.09) Multiplication-Sign 10{sup -6} and (1.57 {+-} 0.05) Multiplication-Sign 10{sup -5} cm s{sup -1} at the mucous membrane of normal esophagus and ESCC tissues to (1.82 {+-} 0.04) Multiplication-Sign 10{sup -5} and (3.53 {+-} 0.09) Multiplication-Sign 10{sup -5} cm s{sup -1} at the submucous layer approximately 742 {mu}m away from the epithelial surface of normal esophagus and ESCC tissues, respectively. (optical coherence tomography)« less

Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats.

PubMed

Martínez-Moya, P; Ortega-González, M; González, R; Anzola, A; Ocón, B; Hernández-Chirlaque, C; López-Posadas, R; Suárez, M D; Zarzuelo, A; Martínez-Augustin, O; Sánchez de Medina, F

2012-08-01

Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1β (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.

PubMed

Xiong, Hui; Zhang, Jiangnan

2017-12-01

The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (P<0.05). The results showed that ATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

Human brain cancer studied by resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.

2012-11-01

The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

Role of Oxidative Damage in Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

2014-01-01

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats.

PubMed

Gelen, Volkan; Şengül, Emin; Yıldırım, Serkan; Atila, Gözde

2018-04-01

5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage.

The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats

PubMed Central

Gelen, Volkan; Şengül, Emin; Yıldırım, Serkan; Atila, Gözde

2018-01-01

Objective(s): 5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. Materials and Methods: Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. Results: It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. Conclusion: Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage. PMID:29796225

Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway

PubMed Central

Jun, Hyoung-Oh; Kim, Dong-hun; Lee, Sae-Won; Lee, Hye Shin; Seo, Ji Hae; Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Min, Bon Hong

2011-01-01

Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induced activation of Akt and GSK-3β. In addition, the protective effect of clusterin is independednt on its receptor megalin, because inhibition of megalin has no effect on clusturin-mediated Akt/GSK-3β phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3β signaling mediates anti-apoptotic effect of clusterin. PMID:21270507

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

PubMed

Bektur, Nuriye Ezgi; Sahin, Erhan; Baycu, Cengiz; Unver, Gonul

2016-04-01

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects. © The Author(s) 2013.

Liposomal Antioxidants for Protection against Oxidant-Induced Damage

PubMed Central

Suntres, Zacharias E.

2011-01-01

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. PMID:21876690

The Prospective Role of Plant Products in Radiotherapy of Cancer: A Current Overview

PubMed Central

Hazra, Banasri; Ghosh, Subhalakshmi; Kumar, Amit; Pandey, B. N.

2012-01-01

Treatment of cancer often requires exposure to radiation, which has several limitations involving non-specific toxicity toward normal cells, reducing the efficacy of treatment. Efforts are going on to find chemical compounds which would effectively offer protection to the normal tissues after radiation exposure during radiotherapy of cancer. In this regard, plant-derived compounds might serve as “leads” to design ideal radioprotectors/radiosensitizers. This article reviews some of the recent findings on prospective medicinal plants, phytochemicals, and their analogs, based on both in vitro and in vivo tumor models especially focused with relevance to cancer radiotherapy. Also, pertinent discussion has been presented on the molecular mechanism of apoptotic death in relation to the oxidative stress in cancer cells induced by some of these plant samples and their active constituents. PMID:22291649

On the possibility of spectroscopic cancer diagnostics

NASA Astrophysics Data System (ADS)

Khairullina, Alphiya Y.; Oleinik, Tatiana V.; Korolevich, Alexander N.; Sevkovsky, Yacob I.

1993-07-01

The diffuse reflection and transmission coefficients, other optical parameters of normal and cancer tissues have been investigated in visible and infrared spectra. The optimal spectral range for distinguishing the cancer is found. The spectral absorption coefficients and size of cells parameter determined using our approach are analyzed to be different for normal and pathological tissues. The method is proposed for calculating the diffuse reflectance and transmittance of multiple tissue layers. The investigations have shown that cancer may be distinguished under the layers of skin and normal tissue.

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Photomedicine and Stem Cells; The Janus face of photodynamic therapy (PDT) to kill cancer stem cells, and photobiomodulation (PBM) to stimulate normal stem cells

NASA Astrophysics Data System (ADS)

Abrahamse, Heidi; Hamblin, Michael R.

2017-12-01

Janus, the ancient Roman god depicted with two faces is an appropriate metaphor for light therapy. In the right photodynamic therapy conditions, light is able to kill nearly anything that is living such as cancers, microorganisms, parasites, and more. On the opposite face, light of the correct wavelength and proper dose (photobiomodulation) can heal, regenerate, protect, revitalize and restore any kind of dead, damaged, stressed, dying, degenerating cells, tissue, or organ system. This book discusses both sides of Janus' face in regards to light therapy.

Utilization of robotic-arm assisted total knee arthroplasty for soft tissue protection.

PubMed

Sultan, Assem A; Piuzzi, Nicolas; Khlopas, Anton; Chughtai, Morad; Sodhi, Nipun; Mont, Michael A

2017-12-01

Despite the well-established success of total knee arthroplasty (TKA), iatrogenic ligamentous and soft tissue injuries are infrequent, but potential complications that can have devastating impact on clinical outcomes. These injuries are often related to technical errors and excessive soft tissue manipulation, particularly during bony resections. Recently, robotic-arm assisted TKA was introduced and demonstrated promising results with potential technical advantages over manual surgery in implant positioning and mechanical accuracy. Furthermore, soft tissue protection is an additional potential advantage offered by these systems that can reduce inadvertent human technical errors encountered during standard manual resections. Therefore, due to the relative paucity of literature, we attempted to answer the following questions: 1) does robotic-arm assisted TKA offer a technical advantage that allows enhanced soft tissue protection? 2) What is the available evidence about soft tissue protection? Recently introduced models of robotic-arm assisted TKA systems with advanced technology showed promising clinical outcomes and soft tissue protection in the short- and mid-term follow-up with results comparable or superior to manual TKA. In this review, we attempted to explore this dimension of robotics in TKA and investigate the soft tissue related complications currently reported in the literature.

A Compendium of Canine Normal Tissue Gene Expression

PubMed Central

Chen, Qing-Rong; Wen, Xinyu; Khan, Javed; Khanna, Chand

2011-01-01

Background Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. Methodology/Principal Findings The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. Conclusions/Significance These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large. PMID:21655323

The Brassicaceae species Heliophila coronopifolia produces root border-like cells that protect the root tip and secrete defensin peptides.

PubMed

Weiller, Florent; Moore, John P; Young, Philip; Driouich, Azeddine; Vivier, Melané A

2017-03-01

Root border cells and border-like cells (BLCs), the latter originally described in Arabidopsis thaliana , have been described as cells released at the root tips of the species in which they occur. BLCs are thought to provide protection to root meristems similar to classical root border cells. In addition, four defensin peptides (Hc-AFP1-4) have previously been characterized from Heliophila coronopifolia , a South African semi-desert flower, and found to be strongly antifungal. This provided an opportunity to evaluate if the BLCs of H. coronopifolia indeed produce these defensins, which would provide evidence towards a defence role for BLCs. Fluorescence microscopy, using live-cell-imaging technology, was used to characterize the BLCs of H. coronopifolia . Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence microscopy was used to characterize these defensin peptides. BLCs originated at the root apical meristem and formed a protective sheath at the tip and along the sides as the root elongated in solid medium. BLCs have a cellulose-enriched cell wall, intact nuclei and are embedded in a layer of pectin-rich mucilage. Pectinase treatments led to the dissolution of the sheath and dissociation of the root BLCs. Hc-AFP1-4 genes were all expressed in root tissues, but Hc-AFP3 transcripts were the most abundant in these tissues as measured by qRT-PCR. A polyclonal antibody that was cross-reactive with all four defensins, and probably recognizing a general plant defensin epitope, was used in fluorescence microscopy analysis to examine the presence of the peptides in the root tip and BLCs. Data confirmed the peptides present in the root tip tissues, the mucilage sheath and the BLCs. This study provides a link between defensin peptides and BLCs, both embedded in a protective pectin mucilage sheath, during normal plant growth and development. The presence of the Hc-AFP3 defensin peptides in the BLCs suggests a role for these cells in root protection. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Brassicaceae species Heliophila coronopifolia produces root border-like cells that protect the root tip and secrete defensin peptides

PubMed Central

Weiller, Florent; Young, Philip; Driouich, Azeddine; Vivier, Melané A.

2017-01-01

Background and Aims Root border cells and border-like cells (BLCs), the latter originally described in Arabidopsis thaliana, have been described as cells released at the root tips of the species in which they occur. BLCs are thought to provide protection to root meristems similar to classical root border cells. In addition, four defensin peptides (Hc-AFP1–4) have previously been characterized from Heliophila coronopifolia, a South African semi-desert flower, and found to be strongly antifungal. This provided an opportunity to evaluate if the BLCs of H. coronopifolia indeed produce these defensins, which would provide evidence towards a defence role for BLCs. Methods Fluorescence microscopy, using live-cell-imaging technology, was used to characterize the BLCs of H. coronopifolia. Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence microscopy was used to characterize these defensin peptides. Key Results BLCs originated at the root apical meristem and formed a protective sheath at the tip and along the sides as the root elongated in solid medium. BLCs have a cellulose-enriched cell wall, intact nuclei and are embedded in a layer of pectin-rich mucilage. Pectinase treatments led to the dissolution of the sheath and dissociation of the root BLCs. Hc-AFP1–4 genes were all expressed in root tissues, but Hc-AFP3 transcripts were the most abundant in these tissues as measured by qRT-PCR. A polyclonal antibody that was cross-reactive with all four defensins, and probably recognizing a general plant defensin epitope, was used in fluorescence microscopy analysis to examine the presence of the peptides in the root tip and BLCs. Data confirmed the peptides present in the root tip tissues, the mucilage sheath and the BLCs. Conclusions This study provides a link between defensin peptides and BLCs, both embedded in a protective pectin mucilage sheath, during normal plant growth and development. The presence of the Hc-AFP3 defensin peptides in the BLCs suggests a role for these cells in root protection. PMID:27481828

Comparative study of Hsp27, GSK3β, Wnt1 and PRDX3 in Hirschsprung's disease.

PubMed

Gao, Hong; Liu, Xiaomei; Chen, Dong; Lv, Liangying; Wu, Mei; Mi, Jie; Wang, Weilin

2014-06-01

Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system characterized by aganglionosis in distal gut. In this study, we used two-dimensional gel electrophoresis (2-DE) technology coupled with matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis to identify differentially expressed proteins in the aganglionic (stenotic) and ganglionic (normal) colon segment tissues from patients with HSCR. We identified 15 proteins with different expression levels between the stenotic and the normal colon segment tissues from patients with HSCR. Nine proteins were upregulated and six proteins downregulated in the stenotic colon segment tissues compared to the normal colon segment tissues. Based on the biological functions, we selected the Hsp27 upregulated proteins and the PRDX3 downregulated proteins to confirm their expression in 20 patients. The protein and mRNA expressions of Hsp27 were statistically higher in the stenotic colon segment tissues than in the normal colon segment tissues, whereas the protein and mRNA expressions of PRDX3 were statistically lower in the stenotic colon segment tissues than in the normal colon segment tissues. These findings of changes in mRNA and protein in tissues from patients with HSCR provide information which may be helpful in understanding the pathomechanism that is implicated in the disease. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

RBFOX2 Is an Important Regulator of Mesenchymal Tissue-Specific Splicing in both Normal and Cancer Tissues

PubMed Central

Venables, Julian P.; Brosseau, Jean-Philippe; Gadea, Gilles; Klinck, Roscoe; Prinos, Panagiotis; Beaulieu, Jean-François; Lapointe, Elvy; Durand, Mathieu; Thibault, Philippe; Tremblay, Karine; Rousset, François; Tazi, Jamal; Abou Elela, Sherif

2013-01-01

Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype. To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues, we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR (RT-PCR) platform. Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues, with many changes from mostly one splice variant to predominantly the other. Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer. Furthermore, because splicing profiling could classify cancer cell lines according to their epithelial/mesenchymal characteristics, we used these cancer cell lines to identify regulators for these specific splicing signatures. By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue-specific splicing. PMID:23149937

Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

2013-06-01

The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

funtooNorm: an R package for normalization of DNA methylation data when there are multiple cell or tissue types.

PubMed

Oros Klein, Kathleen; Grinek, Stepan; Bernatsky, Sasha; Bouchard, Luigi; Ciampi, Antonio; Colmegna, Ines; Fortin, Jean-Philippe; Gao, Long; Hivert, Marie-France; Hudson, Marie; Kobor, Michael S; Labbe, Aurelie; MacIsaac, Julia L; Meaney, Michael J; Morin, Alexander M; O'Donnell, Kieran J; Pastinen, Tomi; Van Ijzendoorn, Marinus H; Voisin, Gregory; Greenwood, Celia M T

2016-02-15

DNA methylation patterns are well known to vary substantially across cell types or tissues. Hence, existing normalization methods may not be optimal if they do not take this into account. We therefore present a new R package for normalization of data from the Illumina Infinium Human Methylation450 BeadChip (Illumina 450 K) built on the concepts in the recently published funNorm method, and introducing cell-type or tissue-type flexibility. funtooNorm is relevant for data sets containing samples from two or more cell or tissue types. A visual display of cross-validated errors informs the choice of the optimal number of components in the normalization. Benefits of cell (tissue)-specific normalization are demonstrated in three data sets. Improvement can be substantial; it is strikingly better on chromosome X, where methylation patterns have unique inter-tissue variability. An R package is available at https://github.com/GreenwoodLab/funtooNorm, and has been submitted to Bioconductor at http://bioconductor.org. © The Author 2015. Published by Oxford University Press.

Optical diagnostic of breast cancer using Raman, polarimetric and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Anwar, Shahzad; Firdous, Shamaraz; Rehman, Aziz-ul; Nawaz, Muhammed

2015-04-01

We presented the optical diagnostic of normal and cancerous human breast tissues using Raman, polarimetric and fluorescence spectroscopic techniques. Breast cancer is the second leading cause of cancer death among women worldwide. Optical diagnostics of cancer offered early intervention and the greatest chance of cure. Spectroscopic data were collected from freshly excised surgical specimens of normal tissues with Raman bands at 800, 1171 and 1530 cm-1 arising mainly by lipids, nucleic acids, proteins, carbohydrates and amino acids. For breast cancer, Raman bands are observed at 1070, 1211, 1495, 1583 and 1650 cm-1. Results demonstrate that the spectra of normal tissue are dominated by lipids and amino acids. Polarization decomposition of the Mueller matrix and confocal microscopic fluorescence provides detailed description of cancerous tissue and distinguishes between the normal and malignant one. Based on these findings, we successfully differentiate normal and malignant breast tissues at an early stage of disease. There is a need to develop a new tool for noninvasive, real-time diagnosis of tissue abnormalities and a test procedure for detecting breast cancer at an early stage.

Concentration of cadmium, nickel and aluminium in female breast cancer.

PubMed

Romanowicz-Makowska, Hanna; Forma, Ewa; Bryś, Magdalena; Krajewska, Wanda M; Smolarz, Beata

2011-12-01

The aim of this study was to investigate the cadmium (Cd), nickel (Ni) and aluminium (Al) concentrations in female breast cancer and normal tissue. The concentration of metals in 16 non-cancerous breast tissues and 67 breast cancer samples was measured by flame atomic absorption spectrometry. In the case of normal breast tissue the concentrations were 0.61 ± 0.24 μg Cd/g dry tissue, 1.84 ± 0.67 μg Ni/g dry tissue, and 3.63 ± 1.00 μg Al/g dry tissue, whereas in breast cancer concentrations of metals were 0.76 ± 0.38 μg/g dry tissue, 2.26 ± 0.79 μg/g dry tissue, and 4.40 ± 1.82 μg/g dry tissue, respectively. The concentration of Cd and Al in normal breast tissue was significantly lower than in breast cancer. In the case of Ni concentration, we did not observe statistically significant differences between normal and cancerous tissue. There were no significant differences in concentration of studied metals, in breast cancer, in the context of age, menopausal status, and cancer histological grading. The data obtained show higher concentration of cadmium and aluminium and support a possible relationship between those metals and breast cancer.

Silver nanoparticle based surface enhanced Raman scattering spectroscopy of diabetic and normal rat pancreatic tissue under near-infrared laser excitation

NASA Astrophysics Data System (ADS)

Huang, H.; Shi, H.; Feng, S.; Lin, J.; Chen, W.; Huang, Z.; Li, Y.; Yu, Y.; Lin, D.; Xu, Q.; Chen, R.

2013-04-01

This paper presents the use of high spatial resolution silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) from rat pancreatic tissue to obtain biochrmical information about the tissue. A high quality SERS signal from a mixture of pancreatic tissues and silver nanoparticles can be obtained within 10 s using a Renishaw micro-Raman system. Prominent SERS bands of pancreatic tissue were assigned to known molecular vibrations, such as the vibrations of DNA bases, RNA bases, proteins and lipids. Different tissue structures of diabetic and normal rat pancreatic tissues have characteristic features in SERS spectra. This exploratory study demonstrated great potential for using SERS imaging to distinguish diabetic and normal pancreatic tissues on frozen sections without using dye labeling of functionalized binding sites.

Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Zhifang; Li, Hui

2012-12-01

In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response.

PubMed

Brines, M; Cerami, A

2008-11-01

In its classic hormonal role, erythropoietin (EPO) is produced by the kidney and regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation. EPO also mediates other effects directed towards optimizing oxygen delivery to tissues, e.g. modulating regional blood flow and reducing blood loss by promoting thrombosis within damaged vessels. Over the past 15 years, many unexpected nonhaematopoietic functions of EPO have been identified. In these more recently appreciated nonhormonal roles, locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response, in which it counteracts the effects of pro-inflammatory cytokines. Acutely, EPO prevents programmed cell death and reduces the development of secondary, pro-inflammatory cytokine-induced injury. Within a longer time frame, EPO provides trophic support to enable regeneration and healing. As the region immediately surrounding damage is typically relatively deficient in endogenous EPO, administration of recombinant EPO can provide increased tissue protection. However, effective use of EPO as therapy for tissue injury requires higher doses than for haematopoiesis, potentially triggering serious adverse effects. The identification of a tissue-protective receptor isoform has facilitated the engineering of nonhaematopoietic, tissue-protective EPO derivatives, e.g. carbamyl EPO, that avoid these complications. Recently, regions within the EPO molecule mediating tissue protection have been identified and this has enabled the development of potent tissue-protective peptides, including some mimicking EPO's tertiary structure but unrelated in primary sequence.

Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

PubMed Central

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2013-01-01

Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats

PubMed Central

Al-Dbass, Abeer M.; Al- Daihan, Sooad K.; Bhat, Ramesa Shafi

2012-01-01

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury. PMID:23961190

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats.

PubMed

Al-Dbass, Abeer M; Al-Daihan, Sooad K; Bhat, Ramesa Shafi

2012-07-01

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

PubMed Central

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

PubMed Central

Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A; Baez, Axel; Arroyo, Axel; González-Marqués, William A; González-Keelan, Carmen; Torres, Esther A; Appleyard, Caroline B

2015-01-01

AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to normal tissue (0.07 ± 0.25, P < 0.05, P < 0.001, respectively). Cox-2 was significantly increased in sporadic colorectal cancer (2.20 ± 0.23 vs 0.80 ± 0.37 for normal tissues, P < 0.05). In comparison to normal (2.80 ± 0.13) and CAC (2.50 ± 0.33) tissues, VDR was significantly decreased in sporadic dysplasia (0.00 ± 0.00, P < 0.001 vs normal, P < 0.001 vs CAC) and sporadic CRC (0.47 ± 0.23, P < 0.001 vs normal, P < 0.001 vs CAC). VDR levels negatively correlated with NK-1R (r = -0.48) and pEGFR (r = -0.56) in normal, IBD, sporadic dysplasia and sporadic CRC tissue, but not in CAC. CONCLUSION: Immunohistochemical NK-1R and pEGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia. VDR immunoreactivity can distinguish CAC from sporadic cancer. PMID:25684939

Near-infrared confocal micro-Raman spectroscopy combined with PCA-LDA multivariate analysis for detection of esophageal cancer

NASA Astrophysics Data System (ADS)

Chen, Long; Wang, Yue; Liu, Nenrong; Lin, Duo; Weng, Cuncheng; Zhang, Jixue; Zhu, Lihuan; Chen, Weisheng; Chen, Rong; Feng, Shangyuan

2013-06-01

The diagnostic capability of using tissue intrinsic micro-Raman signals to obtain biochemical information from human esophageal tissue is presented in this paper. Near-infrared micro-Raman spectroscopy combined with multivariate analysis was applied for discrimination of esophageal cancer tissue from normal tissue samples. Micro-Raman spectroscopy measurements were performed on 54 esophageal cancer tissues and 55 normal tissues in the 400-1750 cm-1 range. The mean Raman spectra showed significant differences between the two groups. Tentative assignments of the Raman bands in the measured tissue spectra suggested some changes in protein structure, a decrease in the relative amount of lactose, and increases in the percentages of tryptophan, collagen and phenylalanine content in esophageal cancer tissue as compared to those of a normal subject. The diagnostic algorithms based on principal component analysis (PCA) and linear discriminate analysis (LDA) achieved a diagnostic sensitivity of 87.0% and specificity of 70.9% for separating cancer from normal esophageal tissue samples. The result demonstrated that near-infrared micro-Raman spectroscopy combined with PCA-LDA analysis could be an effective and sensitive tool for identification of esophageal cancer.

Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment.

PubMed

Gonçalves, Bianca F; de Campos, Silvana G P; Góes, Rejane M; Scarano, Wellerson R; Taboga, Sebastião R; Vilamaior, Patricia S L

2017-06-01

Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. © 2017 Wiley Periodicals, Inc.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

PubMed

Kim, Jin You; Suh, Hie Bum; Kang, Hyun Jung; Shin, Jong Ki; Choo, Ki Seok; Nam, Kyung Jin; Lee, Seok Won; Jung, Young Lae; Bae, Young Tae

2016-05-01

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

PubMed Central

Bardin, Allison; Boulle, Nathalie; Lazennec, Gwendal; Vignon, Françoise; Pujol, Pascal

2004-01-01

The characterization of estrogen receptor beta (ERβ) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues and the mitogenic effects of estrogen in these tissues (e.g. breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERβ expression in cancer as compared to benign tumors or normal tissues, whereas ERα expression persists. The loss of ERβ expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERα target genes by ERβ, or ERβ specific gene induction could indicate that ERβ has a differential effect on proliferation as compared to ERα. ERβ may exert a protective effect and thus constitute a new target for hormone therapy, e.g. via ligand specific activation. The potential distinct roles of ERα and ERβ expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review. PMID:15369453

Immunohistochemical analysis of S6K1 and S6K2 localization in human breast tumors.

PubMed

Filonenko, Valeriy V; Tytarenko, Ruslana; Azatjan, Sergey K; Savinska, Lilya O; Gaydar, Yuriy A; Gout, Ivan T; Usenko, Vasiliy S; Lyzogubov, Valeriy V

2004-12-01

To perform an immunohistochemical analysis of human breast adenomas and adenocarcinomas as well as normal breast tissues in respect of S6 ribosomal protein kinase (S6K) expression and localization in normal and transformed cells. The expression level and localization of S6K have been detected in formalin fixed, paraffin embedded sections of normal human breast tissues, adenomas and adenocarcinomas with different grade of differentiation. Immunohistochemical detection of S6K1 and S6K2 in normal human breast tissues and breast tumors were performed using specific monoclonal and polyclonal antibodies against S6K1 and S6K2 with following semiquantitative analysis. The increase of S6K content in the cytoplasm of epithelial cells in benign and malignant tumors has been detected. Nuclear accumulation of S6K1 and to a greater extend S6K2 have been found in breast adenocarcinomas. About 80% of breast adenocarcinomas cases revealed S6K2 nuclear staining comparing to normal tissues. In 31% of cases more then 50% of cancer cells had strong nuclear staining. Accumulation of S6K1 in the nucleus of neoplastic cells has been demonstrated in 25% of cases. Nuclear localization of S6K in the epithelial cells in normal breast tissues has not been detected. Immunohistochemical analysis of S6K1 and S6K2 expression in normal human breast tissues, benign and malignant breast tumors clearly indicates that both kinases are overexpressed in breast tumors. Semiquantitative analysis of peculiarities of S6K localization in normal tissues and tumors revealed that nucleoplasmic accumulation of S6K (especially S6K2) is a distinguishing feature of cancer cells.

Relationship Between Speed of Sound in and Density of Normal and Diseased Rat Livers

NASA Astrophysics Data System (ADS)

Hachiya, Hiroyuki; Ohtsuki, Shigeo; Tanaka, Motonao

1994-05-01

Speed of sound is an important acoustic parameter for quantitative characterization of living tissues. In this paper, the relationship between speed of sound in and density of rat liver tissues are investigated. The speed of sound was measured by the nondeformable technique based on frequency-time analysis of a 3.5 MHz pulse response. The speed of sound in normal livers varied minimally between individuals and was not related to body weight or age. In liver tissues which were administered CCl4, the speed of sound was lower than the speed of sound in normal tissues. The relationship between speed of sound and density in normal, fatty and cirrhotic livers can be fitted well on the line which is estimated using the immiscible liquid model assuming a mixture of normal liver and fat tissues. For 3.5 MHz ultrasound, it is considered that the speed of sound in fresh liver with fatty degeneration is responsible for the fat content and is not strongly dependent on the degree of fibrosis.

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

PubMed

Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

2015-04-01

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology

NASA Astrophysics Data System (ADS)

Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

2014-03-01

It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bingsong Lei; Xiaoyuan Deng; Huajiang Wei

2014-12-31

We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{supmore » -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)« less

A Comparison of Raman Spectral Features of Frozen and Deparaffinized Tissues in Neuroblastoma and Ganglioneuroma

NASA Astrophysics Data System (ADS)

Devpura, Suneetha; Thakur, Jagdish S.; Poulik, Janet M.; Rabah, Raja; Naik, Vaman M.; Naik, Ratna

2012-02-01

We have investigated the cellular regions in neuroblastoma and ganglioneuroma using Raman spectroscopy and compared their spectral characteristics with those of normal adrenal gland. Thin sections from both frozen and deparaffinized tissues, obtained from the same tissue specimen, were studied in conjunction with the pathological examination of the tissues. We found a significant difference in the spectral features of frozen sections of normal adrenal gland, neuroblastoma, and ganglioneuroma when compared to deparaffinized tissues. The quantitative analysis of the Raman data using chemometric methods of principal component analysis and discriminant function analysis obtained from the frozen tissues show a sensitivity and specificity of 100% each. The biochemical identification based on the spectral differences shows that the normal adrenal gland tissues have higher levels of carotenoids, lipids, and cholesterol compared to the neuroblastoma and ganglioneuroma frozen tissues. However, deparaffinized tissues show complete removal of these biochemicals in adrenal tissues. This study demonstrates that Raman spectroscopy combined with chemometric methods can successfully distinguish neuroblastoma and ganglioneuroma at cellular level.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

LINE1 and Alu repetitive element DNA methylation in tumors and white blood cells from epithelial ovarian cancer patients.

PubMed

Akers, Stacey N; Moysich, Kirsten; Zhang, Wa; Collamat Lai, Golda; Miller, Austin; Lele, Shashikant; Odunsi, Kunle; Karpf, Adam R

2014-02-01

We determined whether DNA methylation of repetitive elements (RE) is altered in epithelial ovarian cancer (EOC) patient tumors and white blood cells (WBC), compared to normal tissue controls. Two different quantitative measures of RE methylation (LINE1 and Alu bisulfite pyrosequencing) were used in normal and tumor tissues from EOC cases and controls. Tissues analyzed included: i) EOC, ii) normal ovarian surface epithelia (OSE), iii) normal fallopian tube surface epithelia (FTE), iv) WBC from EOC patients, obtained before and after treatment, and v) WBC from demographically-matched controls. REs were significantly hypomethylated in EOC compared to OSE and FTE, and LINE1 and Alu methylation showed a significant direct association in these tissues. In contrast, WBC RE methylation was significantly higher in EOC cases compared to controls. RE methylation in patient-matched EOC tumors and pre-treatment WBC did not correlate. EOC shows robust RE hypomethylation compared to normal tissues from which the disease arises. In contrast, RE are generally hypermethylated in EOC patient WBC compared to controls. EOC tumor and WBC methylation did not correlate in matched patients, suggesting that RE methylation is independently controlled in tumor and normal tissues. Despite the significant differences observed over the population, the range of RE methylation in patient and control WBC overlapped, limiting their specific utility as an EOC biomarker. However, our data demonstrate that DNA methylation is deranged in normal tissues from EOC patients, supporting further investigation of WBC DNA methylation biomarkers suitable for EOC risk assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress

PubMed Central

Bhatt, Laxit; Joshi, Viraj

2017-01-01

Aim: The study was undertaken to evaluate the cardioprotective effect of the alcoholic leaf extract of Mangifera indica L. against cardiac stress caused by doxorubicin (DOX). Materials and Methods: Rats were treated with 100 mg/kg of M. indica leaf extract (MILE) in alone and interactive groups for 21 days. Apart from the normal and MILE control groups, all the groups were subjected to DOX (15 mg/kg, i.p.) toxicity for 21 days and effects of different treatments were analyzed by changes in serum biomarkers, tissue antioxidant levels, electrocardiographic parameters, lipid profile, and histopathological evaluation. Results: The MILE treated group showed decrease in serum biomarker enzyme levels and increase in tissue antioxidants levels. Compared to DOX control group, MILE treated animals showed improvement in lipid profile, electrocardiographic parameters, histological score, and mortality. Conclusion: These findings clearly suggest the protective role of alcoholic leaf extract of M. indica against oxidative stress induced by DOX. PMID:28894627

Pathogenesis of Pain.

PubMed

Dinakar, Pradeep; Stillman, Alexandra Marion

2016-08-01

The pathogenesis of pain sensation includes mechanisms that result in acute or chronic pain. Pain itself is described as an unpleasant sensory and emotional experience beginning with a peripheral stimulus that undergoes a physiological process ultimately resulting in the sensation of pain. Biologists recognize pain to be a common sign of potential tissue damage. Hence, pain sensation is protective in function. However, pathologic states of pain exist secondary to disruption of the nociceptive process both peripherally and centrally or secondary to psychological conditions. It is essential to identify these aberrant states of pain and distinguish them from situations of potential tissue damage. Chronic pain is defined as pain that exceeds 3 or 6 months duration. This article is an overview of the essential neuroanatomy and neurophysiology of normal pain nociception, its clinical implications, and the development of persistent and pathological pain conditions following improperly or poorly treated pain. Copyright © 2016. Published by Elsevier Inc.

40 CFR 190.10 - Standards for normal operations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Standards for normal operations. 190.10 Section 190.10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR NUCLEAR POWER OPERATIONS Environmental...

40 CFR 190.10 - Standards for normal operations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Standards for normal operations. 190.10 Section 190.10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR NUCLEAR POWER OPERATIONS Environmental Standards...

Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in normal tissues and in the breast tumoral processes.

PubMed

Bruzzoni-Giovanelli, Heriberto; Fernandez, Plinio; Veiga, Lucía; Podgorniak, Marie-Pierre; Powell, Darren J; Candeias, Marco M; Mourah, Samia; Calvo, Fabien; Marín, Mónica

2010-02-09

SIAH proteins are the human members of an highly conserved family of E3 ubiquitin ligases. Several data suggest that SIAH proteins may have a role in tumor suppression and apoptosis. Previously, we reported that SIAH-1 induces the degradation of Kid (KIF22), a chromokinesin protein implicated in the normal progression of mitosis and meiosis, by the ubiquitin proteasome pathway. In human breast cancer cells stably transfected with SIAH-1, Kid/KIF22 protein level was markedly reduced whereas, the Kid/KIF22 mRNA level was increased. This interaction has been further elucidated through analyzing SIAH and Kid/KIF22 expression in both paired normal and tumor tissues and cell lines. It was observed that SIAH-1 protein is widely expressed in different normal tissues, and in cells lines but showing some differences in western blotting profiles. Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1 and Kid/KIF22 appears to be modified in human tumor tissues compared to normal controls. When mRNA expression of SIAH-1 and Kid/KIF22 was analyzed by real-time PCR in normal and cancer breast tissues from the same patient, a large variation in the number of mRNA copies was detected between the different samples. In most cases, SIAH-1 mRNA is decreased in tumor tissues compared to their normal counterparts. Interestingly, in all breast tumor tissues analyzed, variations in the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. This concerted variation of SIAH-1 and Kid/KIF22 messengers suggests the existence of an additional level of control than the previously described protein-protein interaction and protein stability regulation. Our observations also underline the need to re-evaluate the results of gene expression obtained by qRT-PCR and relate it to the protein expression and cellular localization when matched normal and tumoral tissues are analyzed.

Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint Disorders.

PubMed

Aryaei, Ashkan; Vapniarsky, Natalia; Hu, Jerry C; Athanasiou, Kyriacos A

2016-12-01

Temporomandibular disorders (TMDs) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function, is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ.

Recent tissue engineering advances for the treatment of temporomandibular joint disorders

PubMed Central

Aryaei, Ashkan; Vapniarsky, Natalia; Hu, Jerry C; Athanasiou, Kyriacos A

2016-01-01

Temporomandibular disorders (TMD) are among the most common maxillofacial complaints and a major cause of orofacial pain. Although, current treatments provide short- and long-term relief, alternative tissue engineering solutions are in great demand. Particularly, the development of strategies, providing long-term resolution of TMD to help patients regain normal function is a high priority. An absolute prerequisite of tissue engineering is to understand normal structure and function. The current knowledge of anatomical, mechanical, and biochemical characteristics of the temporomandibular joint (TMJ) and associated tissues will be discussed, followed by a brief description of current TMD treatments. The main focus is on recent tissue engineering developments for regenerating TMJ tissue components, with or without a scaffold. The expectation for effectively managing TMD is that tissue engineering will produce biomimetic TMJ tissues that recapitulate the normal structure and function of the TMJ. PMID:27704395

Transcriptional expression analysis of survivin splice variants reveals differential expression of survivin-3α in breast cancer.

PubMed

Moniri Javadhesari, Solmaz; Gharechahi, Javad; Hosseinpour Feizi, Mohammad Ali; Montazeri, Vahid; Halimi, Monireh

2013-04-01

Survivin, which is a novel member of the inhibitor of apoptosis family proteins, is known to play an important role in the regulation of cell cycle and apoptosis. Differential expression of survivin in tumor tissues introduces it as a new candidate molecular marker for cancer. Here we investigated the expression of survivin and its splice variants in breast tumors, as well as normal adjacent tissues obtained from the same patients. Thirty five tumors and 17 normal adjacent tissues from women diagnosed with breast cancer were explored in this study. Differential expression of different survivin splice variants was detected and semiquantitatively analyzed using reverse transcription-polymerase chain reaction. Results showed that survivin and its splice variants were differentially expressed in tumor specimens compared with normal adjacent tissues. The expression of survivin-3B and survivin-3α was specifically detected in tumor tissues compared with normal adjacent ones (53% in tumor tissues compared to 5% in normal adjacent for survivin-3B and 65% in tumor tissues and 0.0% in normal adjacent tissues for survivin-3α). Statistical analysis showed that survivin and survivin-ΔEx3 were upregulated in benign (90%, p<0.034) and malignant (76%, p<0.042) tumors, respectively. On the other hand, our results showed that survivin-2α (100% of the cases) was the dominant expressed variant of survivin in breast cancer. The data presented here showed that survivin splice variants were differentially expressed in benign and malignant breast cancer tissues, suggesting their potential role in breast cancer development. Differential expression of survivin-2α and survivin-3α splice variants highlights their usefulness as new candidate markers for breast cancer diagnosis and prognosis.

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin

PubMed Central

Brines, Michael; Patel, Nimesh S. A.; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C.; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

2008-01-01

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the β common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58–82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia–reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure. PMID:18676614

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.

PubMed

Brines, Michael; Patel, Nimesh S A; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

2008-08-05

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

PubMed Central

Xiong, Yuxia; Chen, Li; Fan, Ling; Wang, Lulu; Zhou, Yejiang; Qin, Dalian; Sun, Qin; Wu, Jianming; Cao, Shousong

2018-01-01

Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically. PMID:29487524

Heat transfer within hydrodissection fluids: An analysis of thermal conduction and convection using liquid and gel materials.

PubMed

Johnson, Alexander; Brace, Christopher

2015-01-01

Interventional oncology procedures such as thermal ablation are becoming widely used for many tumours in the liver, kidney and lung. Thermal ablation refers to the focal destruction of tissue by generating cytotoxic temperatures in the treatment zone. Hydrodissection - separating tissues with fluids - protects healthy tissues adjacent to the ablation treatment zone to improve procedural safety, and facilitate more aggressive power application or applicator placement. However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate into the peritoneum, reducing their protective efficacy. As an alternative, a thermo-gelable poloxamer 407 (P407) solution has been recently developed to facilitate hydrodissection procedures. We hypothesise that the P407 gel material does not provide convective heat dissipation from the ablation site, and therefore may alter the heat transfer dynamics compared to liquid materials during hydrodissection-assisted thermal ablation. The purpose of this study was to investigate the heat dissipation mechanics within D5W, liquid P407 and gel P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated heat primarily through conduction, whereas the liquid P407 and D5W dissipated heat through convection. Furthermore, the rate of temperature change within the gel P407 was greater than liquid P407 and D5W. Testing to evaluate the in vivo efficacy of the fluids with different modes of heat dissipation seems warranted for further study.

Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

PubMed

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

2017-03-01

Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Systemic immunity influences hearing preservation in cochlear implantation.

PubMed

Souter, Melanie; Eastwood, Hayden; Marovic, Paul; Kel, Gordana; Wongprasartsuk, Sarin; Ryan, Allen F; O'Leary, Stephen John

2012-06-01

To determine whether a systemic immune response influences hearing thresholds and tissue response after cochlear implantation of hearing guinea pigs. Guinea pigs were inoculated with sterile antigen (Keyhole limpet hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem response thresholds were performed before implantation and 1 and 4 weeks later. Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid carboxymethylcellulose sponge and was applied to the round window for 30 minutes before electrode insertion. Normal saline was used for controls. Cochlear histology was performed at 4 weeks after implantation to assess the tissue response to implantation. To control for the effect of keyhole limpet hemocyanin priming, a group of unprimed animals underwent cochlear implantation with a saline-soaked pledget applied to the round window. Keyhole limpet hemocyanin priming had no significant detrimental effect on thresholds without implantation. Thresholds were elevated after implantation across all frequencies tested (2-32 kHz) in primed animals but only at higher frequencies (4-32 kHz) in unprimed controls. In primed animals, dexamethasone treatment significantly reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the more frequent observation of lymphocytes in the tissue response to the implant. Systemic immune activation at the time of cochlear implantation broadened the range of frequencies experiencing elevated thresholds after implantation. Local dexamethasone provides partial protection against this hearing loss, but the degree and extent of protection are less compared to previous studies with unprimed animals.

Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

PubMed

Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie

2009-06-12

Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet,) 21.9+/-1.4 g (EPO, normal diet), 35.3+/-3.3 g (control, high-fat diet) and 28.8+/-2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

PubMed Central

Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie

2009-01-01

Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo. At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass. The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles. In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles. PMID:19521513

A PPAR-gamma agonist protects from radiation-induced intestinal toxicity

PubMed Central

Sottili, Mariangela; Gerini, Chiara; Desideri, Isacco; Bastida, Cinzia; Pallotta, Stefania; Castiglione, Francesca; Bonomo, Pierluigi; Meattini, Icro; Greto, Daniela; Cappelli, Sabrina; Di Brina, Lucia; Loi, Mauro; Biti, Giampaolo; Livi, Lorenzo

2016-01-01

Objective Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells. Methods Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day). After 24 and 72 hours, mice were sacrificed and the jejunum was collected. HT-29 human colon cancer cells were irradiated with a single dose of 2 (1000 cells), 4 (1500 cells) or 6 (2000 cells) Gy, with or without adding rosiglitazone (20 µM) 1 hour before irradiation. HT-29-xenografted CD1 mice were irradiated (16 Gy) with or without rosiglitazone; tumour volumes were measured for 33 days. Results Rosiglitazone markedly reduced histological signs of altered bowel structures, that is, villi shortening, submucosal thickening, necrotic changes in crypts, oedema, apoptosis, and inflammatory infiltrate induced by irradiation. Rosiglitazone significantly decreased p-NF-kB p65 phosphorylation and TGFβ protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression of Collagen1, Mmp13, Tnfα and Bax at 24 hours and p53 at 72 hours post-irradiation. Rosiglitazone reduced HT-29 clonogenic survival, but only produced a slight reduction of xenograft tumour growth. Conclusion Rosiglitazone exerts a protective effect on normal tissues and reduces alterations in bowel structures and inflammation in a radiation-induced bowel toxicity model, without interfering with the radiation effect on HT-29 cancer cells. PPAR-γ agonists should be further investigated for their application in abdominal and pelvic irradiation. PMID:28344789

The effect of folic acid on porphyrin synthesis in tumors and normal skin of mice treated with 5-aminolevulinic acid or methyl 5-aminolevulinate.

PubMed

Ma, LiWei; Steindal, Arnfinn E; Juzeniene, Asta; Iani, Vladimir; Moan, Johan

2006-08-01

5-Aminolevulinic acid (ALA) or its derivative methyl 5-aminolevulinate (MAL) combined with folic acid was applied in nude mice bearing human colon adenocarcinoma. The aim of the study is to see whether folic acid may increase biosynthesis of porphyrins in tumor tissue after systemic or topical administration of ALA or MAL. The production of porphyrins was determined by spectrofluorometric measurements with an optical fibre probe. It was found that the porphyrin production after i.p injection of 200 mg kg(-1) ALA or MAL was significantly increased by i.p injection of 100 mg kg(-1) folic acid. However, in the case of topically applied 20% ALA, folic acid had no effect. In the case of topically applied 20% MAL, folic acid (i.p or topically applied) reduced the porphyrin synthesis. This might be used for the protection of normal skin against photosensitization. The effects of folic acid were similar in tumors and normal skin. Two mechanisms may explain the results: enhancement of the efficiency of the rate-limiting enzyme porphobilinogen deaminase by folic acid or interference of folic acid with the transport of ALA and MAL to and into the cells synthesizing porphyrins in the tissues. The present data seem to favour the latter mechanism. Folic acid may have a role as an adjuvant in photodynamic therapy with systemically administered ALA and its derivatives.

Long-term treatment with a Yang-invigorating Chinese herbal formula produces generalized tissue protection against oxidative damage in rats.

PubMed

Chiu, Po Yee; Leung, Hoi Yan; Siu, Ada Hoi Ling; Chen, Na; Poon, Michel K T; Ko, Kam Ming

2008-02-01

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process.

Pancreatic tissue assessment using fluorescence and reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Chandra, Malavika; Heidt, David; Simeone, Diane; McKenna, Barbara; Scheiman, James; Mycek, Mary-Ann

2007-07-01

The ability of multi-modal optical spectroscopy to detect signals from pancreatic tissue was demonstrated by studying human pancreatic cancer xenografts in mice and freshly excised human pancreatic tumor tissue. Measured optical spectra and fluorescence decays were correlated with tissue morphological and biochemical properties. The measured spectral features and decay times correlated well with expected pathological differences in normal, pancreatitis and adenocarcinoma tissue states. The observed differences between the fluorescence and reflectance properties of normal, pancreatitis and adenocarcinoma tissue indicate a possible application of multi-modal optical spectroscopy to differentiating between the three tissue classifications.

Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2016-10-01

Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ai, H; Zhang, H

Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant thatmore » represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.« less

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Characterization of cancer and normal tissue fluorescence through wavelet transform and singular value decomposition

NASA Astrophysics Data System (ADS)

Gharekhan, Anita H.; Biswal, Nrusingh C.; Gupta, Sharad; Pradhan, Asima; Sureshkumar, M. B.; Panigrahi, Prasanta K.

2008-02-01

The statistical and characteristic features of the polarized fluorescence spectra from cancer, normal and benign human breast tissues are studied through wavelet transform and singular value decomposition. The discrete wavelets enabled one to isolate high and low frequency spectral fluctuations, which revealed substantial randomization in the cancerous tissues, not present in the normal cases. In particular, the fluctuations fitted well with a Gaussian distribution for the cancerous tissues in the perpendicular component. One finds non-Gaussian behavior for normal and benign tissues' spectral variations. The study of the difference of intensities in parallel and perpendicular channels, which is free from the diffusive component, revealed weak fluorescence activity in the 630nm domain, for the cancerous tissues. This may be ascribable to porphyrin emission. The role of both scatterers and fluorophores in the observed minor intensity peak for the cancer case is experimentally confirmed through tissue-phantom experiments. Continuous Morlet wavelet also highlighted this domain for the cancerous tissue fluorescence spectra. Correlation in the spectral fluctuation is further studied in different tissue types through singular value decomposition. Apart from identifying different domains of spectral activity for diseased and non-diseased tissues, we found random matrix support for the spectral fluctuations. The small eigenvalues of the perpendicular polarized fluorescence spectra of cancerous tissues fitted remarkably well with random matrix prediction for Gaussian random variables, confirming our observations about spectral fluctuations in the wavelet domain.

Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic Shock

DTIC Science & Technology

2012-11-01

Award Number: W81XWH-11-2-0019 TITLE: Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic...REPORT TYPE Final 3. DATES COVERED 4 October 2010- 3 October 2012 4. TITLE AND SUBTITLE Intraosseous Erythropoietin for Acute Tissue Protection in...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT- The project investigated whether intraosseous administration of erythropoietin (EPO) during

Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection.

PubMed

Alimova, Alexandra; Katz, A; Sriramoju, Vidyasagar; Budansky, Yuri; Bykov, Alexei A; Zeylikovich, Roman; Alfano, R R

2007-01-01

Fluorescence and phosphorescence measurements are performed on normal and malignant ex vivo human breast tissues using UV LED and xenon lamp excitation. Tryptophan (trp) phosphorescence intensity is higher in both normal glandular and adipose tissue when compared to malignant tissue. An algorithm based on the ratio of trp fluorescence intensity at 345 nm to phosphorescence intensity at 500 nm is successfully used to separate normal from malignant tissue types. Normal specimens consistently exhibited a low I(345)I(500) ratio (<10), while for malignant specimens, the I(345)I(500) ratio is consistently high (>15). The ratio analysis correlates well with histopathology. Intensity ratio maps with a spatial resolution of 0.5 mm are generated in which local regions of malignancy could be identified.

Expression and Significance of Cyclophilin J in Primary Gastric Adenocarcinoma.

PubMed

Gong, Zhaohua; Mu, Yuling; Chen, Jian; Chu, Hongjin; Lian, Peiwen; Wang, Congcong; Wang, Jiahui; Jiang, Lixin

2017-08-01

Biomarkers are essential in early diagnosis and understanding of the molecular mechanism of human cancer. The expression of cyclophilin J, a novel member of the cyclophilin family, was investigated in primary gastric adenocarcinoma. Western blot analysis was carried out on 36 paired tumor and normal tissue samples; immunohistochemical analysis was carried out on 120 gastric carcinoma tissues and normal adjacent tissue. Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues compared to adjacent normal tissues. Immunohistochemical analysis revealed that cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric carcinoma tissues and adjacent tissues, respectively (p<0.05). Expression of cyclophilin J was associated with the degree of differentiation, but not with lymph node metastasis, gender or depth of tumor infiltration. The overall survival of patients showed no association with the overexpression of cyclophilin J protein. Cyclophilin J expression was up-regulated in gastric carcinoma compared to normal gastric tissues. However, in order to confirm its association with the survival of patients with gastric cancer, more cases need to be studied. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

40 CFR 406.50 - Applicability; description of the normal rice milling subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the normal rice milling subcategory. 406.50 Section 406.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Normal Rice...

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats.

PubMed

Peng, Qiuxian; Zhang, Qin; Xiao, Wei; Shao, Meng; Fan, Qin; Zhang, Hongwei; Zou, Yukai; Li, Xin; Xu, Wenxue; Mo, Zhixian; Cai, Hongbing

2014-07-18

Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver. Copyright © 2014. Published by Elsevier Inc.

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats.

PubMed

Taslidere, Elif; Esrefoglu, Mukaddes; Elbe, Hulya; Cetin, Asli; Ates, Burhan

2014-03-01

Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Meninges: from protective membrane to stem cell niche

PubMed Central

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction. PMID:23671802

Rho inhibition by lovastatin affects apoptosis and DSB repair of primary human lung cells in vitro and lung tissue in vivo following fractionated irradiation

PubMed Central

Ziegler, Verena; Henninger, Christian; Simiantonakis, Ioannis; Buchholzer, Marcel; Ahmadian, Mohammad Reza; Budach, Wilfried; Fritz, Gerhard

2017-01-01

Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy). The statin improved the repair of radiation-induced DNA double-strand breaks (DSBs) in all cell types and, moreover, protected lung endothelial cells from IR-induced caspase-dependent apoptosis, likely involving p53-regulated mechanisms. Under the in vivo situation, treatment with lovastatin or the Rac1-specific small molecule inhibitor EHT1864 attenuated the IR-induced increase in breathing frequency and reduced the percentage of γH2AX and 53BP1-positive cells. This indicates that inhibition of Rac1 signaling lowers IR-induced residual DNA damage by promoting DNA repair. Moreover, lovastatin and EHT1864 protected lung tissue from IR-triggered apoptosis and mitigated the IR-stimulated increase in regenerative proliferation. Our data document beneficial anti-apoptotic and genoprotective effects of pharmacological targeting of Rho signaling following hypo-fractionated irradiation of lung cells in vitro and in vivo. Rac1-targeting drugs might be particular useful for supportive care in radiation oncology and, moreover, applicable to improve the anticancer efficacy of radiotherapy by widening the therapeutic window of thoracic radiation exposure. PMID:28796249

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

PubMed Central

Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

2013-01-01

Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

Telomeres and telomere dynamics: relevance to cancers of the gastrointestinal tract

PubMed Central

Basu, Nivedita; Skinner, Halcyon G.; Litzelman, Kristin; Vanderboom, Russell; Baichoo, Esha; Boardman, Lisa A.

2013-01-01

Summary Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to GI tract cancer. Peripheral blood telomeres are shorter in patients with many types of GI tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres (ALT) is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and ALT activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere related phenotypes, and its relationship to carcinogenesis increases. PMID:24161135

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

NASA Astrophysics Data System (ADS)

Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

2002-10-01

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

PubMed

Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

1985-08-01

Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

NASA Astrophysics Data System (ADS)

Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

2015-07-01

Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

NASA Astrophysics Data System (ADS)

Pu, Yang; Chen, Jun; Wang, Wubao

2014-02-01

The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

PubMed

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi

2008-10-20

In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissuesmore » in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.« less

Flexible cystoscopic bladder biopsies: a technique for outpatient evaluation of the lower urinary tract urothelium.

PubMed

Beaghler, M; Grasso, M

1994-11-01

Routine urothelial biopsies of the lower urinary tract are obtained using the cold cup biopsy technique. This procedure is most often performed in the surgical suite and requires rigid endoscopic access and the use of biopsy forceps and Bugbee electrodes to obtain tissue for histologic examination. A new single-step biopsy forceps has been used through the flexible cystoscope. Using a 16 F actively deflectable, flexible cystoscope and the 5.4 F Therma Jaw Hot Urologic Forceps, bladder biopsies were obtained in 27 patients for a variety of indications. This biopsy forceps allows simultaneous tissue sampling and electrocoagulation of the biopsy site, thus eliminating the need for exchange of instruments through the flexible cystoscope. Tissue samples are somewhat protected from thermal changes during coagulation through the use of a Faraday cage. Biopsies were frequently obtained in an outpatient setting, requiring only local topical anesthesia (2% lidocaine jelly). Carcinoma in situ, transitional cell carcinoma, acute and chronic inflammation, and normal bladder mucosa were differentiated histologically. Using this technique, lower urinary tract urothelial mapping can be performed safely in the office with minimal patient discomfort.

Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals

PubMed Central

Wang, Shu; Su, Rui; Nie, Shufang; Sun, Ming; Zhang, Jia; Wu, Dayong; Moustaid-Moussa, Naima

2013-01-01

Nanotechnology is an innovative approach that has potential applications in nutraceutical research. Phytochemicals have promising potential for maintaining and promoting health, as well as preventing and potentially treating some diseases. However, the generally low solubility, stability, bioavailability and target specificity, together with the side-effects seen when used at high levels, have limited their application. Indeed, nanoparticles can increase solubility and stability of phytochemicals, enhance their absorption, protect them from premature degradation in the body, and prolong their circulation time. Moreover, these nanoparticles exhibit high differential uptake efficiency in the target cells (or tissue) over normal cells (or tissue)through preventing them from prematurely interacting with the biological environment, enhanced permeation and retention effect in disease tissues, and improving their cellular uptake, resulting in decreased toxicity, In this review we outline the commonly used biocompatible and biodegradable nanoparticles including liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly (lactic-co-glycolic acid) (PLGA) nanoparticles. We then summarize studies that have used these nanoparticles as carriers for EGCG, quercetin, resveratrol and curcuminadministration to enhance their aqueous solubility, stability, bioavailability, target specificity, and bioactivities. PMID:24406273

Telomere length in normal and neoplastic canine tissues.

PubMed

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Evaluation of Extended-wear Hearing Aid Technology for Operational Military Use

DTIC Science & Technology

2017-07-01

for a transparent hearing protection device that could protect the hearing of normal-hearing listeners without degrading auditory situational...method, suggest that continuous noise protection is also comparable to conventional earplug devices. Behavioral testing on listeners with normal...associated with the extended-wear hearing aid could be adapted to provide long-term hearing protection for listeners with normal hearing with minimal

In-vitro micro-Raman study of tissue samples for detecting cervical and ovarian cancer with 785-nm laser excitation

NASA Astrophysics Data System (ADS)

Sharma, S. K.; Kamemoto, L. E.; Misra, A. K.; Goodman, M. T.; Luk, H. W.; Killeen, J. L.

2010-04-01

We present results of in vitro micro-Raman spectroscopy of normal and cancerous cervical and ovarian tissues excited with 785 nm near-infrared (NIR) laser. Micro- Raman spectra of squamous cervical cells of both cervix and ovarian tissues show significant differences in the spectra of normal and cancerous cells. In particular, several well-defined Raman peaks in the 775-975 cm-1 region are observed in the spectra of normal cervix squamous cells but are completely missing in the spectra of invasive cervical cancer cells. In the high-frequency 2800-3100 cm-1 region it is shown that the peak area under CH stretching band is much lower than the corresponding area in the spectra of normal cells. In the case of ovarian tissues, the micro-Raman spectra show noticeable spectral differences between normal cells and ovarian serous cancer cells. In particular, we observed the accumulation of β-carotene in ovarian serous cancer cells compared to normal ovarian cells from women with no ovarian cancer. The NIR micro-Raman spectroscopy offers a potential molecular technique for detecting cervical and ovarian cancer from the respective tissues.

HPLC assisted Raman spectroscopic studies on bladder cancer

NASA Astrophysics Data System (ADS)

Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

2015-04-01

We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

Terahertz spectroscopy for the study of paraffin-embedded gastric cancer samples

NASA Astrophysics Data System (ADS)

Wahaia, Faustino; Kasalynas, Irmantas; Seliuta, Dalius; Molis, Gediminas; Urbanowicz, Andrzej; Carvalho Silva, Catia D.; Carneiro, Fatima; Valusis, Gintaras; Granja, Pedro L.

2015-01-01

Terahertz (THz) spectroscopy constitute promising technique for biomedical applications as a complementary and powerful tool for diseases screening specially for early cancer diagnostic. The THz radiation is not harmful to biological tissues. As increased blood supply in cancer-affected tissues and consequent local increase in tissue water content makes THz technology a potentially attractive. In the present work, samples of healthy and adenocarcinoma-affected gastric tissue were analyzed using transmission time-domain THz spectroscopy (THz-TDS). The work shows the capability of the technique to distinguish between normal and cancerous regions in dried and paraffin-embedded samples. Plots of absorption coefficient α and refractive index n of normal and cancer affected tissues, are presented and the conditions for discrimination between normal and affected tissues are discussed.

Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide

PubMed Central

Vaghasiya, Jitendra D.; Sheth, Navin R.; Bhalodia, Yagnik S.; Jivani, Nurudin P.

2010-01-01

Background/Aim: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. Materials and Methods: In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Results: Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Conclusion: Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes. PMID:20616412

Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling

PubMed Central

Li, Wei; Zhao, Yuguang; Wen, Xue; Liang, Xinyue; Zhang, Xiaoying; Zhou, Lei; Hu, Jifan; Niu, Chao; Tian, Huimin; Han, Fujun; Chen, Xiao; Dong, Lihua; Cai, Lu; Cui, Jiuwei

2016-01-01

Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells but not in cancer cells, suggesting its potential protection of normal tissue against damage induced by conventional radiotherapy. However, the underlying mechanisms are not well established. We addressed this in the present study by examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7 (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the initiating event in hormesis and adaptive response to LDR in HBE cells. ATM activation increased the expression of CDK4/CDK6/cyclin D1 by activating the AKT/glycogen synthase kinase (GSK)-3β signaling pathway, which stimulated HBE cell proliferation. Activation of ATM/AKT/GSK-3β signaling also increased nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to increased expression of antioxidants, which mitigated cellular damage from excessive reactive oxygen species production induced by high-dose radiation. However, these effects were not observed in A549 cells. Thus, the failure to activate these pathways in A549 cells likely explains the difference between normal and cancer cells in terms of hormesis and adaptive response to LDR. PMID:27708248

The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center: a unique resource for defining the "molecular histology" of the breast.

PubMed

Sherman, Mark E; Figueroa, Jonine D; Henry, Jill E; Clare, Susan E; Rufenbarger, Connie; Storniolo, Anna Maria

2012-04-01

"Molecular histology" of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website. 2012 AACR

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

PubMed Central

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

[Chosen non-enzymatic substances that participate in a protection against overproduction of free radicals].

PubMed

Gałecka, Elzbieta; Mrowicka, Małgorzata; Malinowska, Katarzyna; Gałecki, Piotr

2008-09-01

Free radicals are substantial elements that take part in proper function of metabolic pathways of human cells and tissues in hydrophobic as well as in hydrophilic environment. Nevertheless overproduction of above molecules causes oxidative stress, a process which is very harmful for lipids, proteins, and others molecules what reduces their normal function. To protect against adverse effects of free radicals and theirs derivatives to human body there is a group of antioxidants divided into enzymatic and non-enzymatic substances. Enzymatic antioxidants are represented mainly by enzymes such as: copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Glutathione (GSH), thioredoxin (Trx), vitamins, melatonin, polyphenols, trace elements, albumin, and others function as non-enzymatic free radicals scavengers. This work in a brief way describes properties of chosen representants of non-enzymatic antioxidant system.

Effects of Cell-Free Spleen Extract Treatment on the Hematopoietic Tissues of Irradiated Guinea-Pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellinger, Friedrigh; Strike, Thomas A.

2004-07-01

Guinea pigs were given whole-body Co 60 irradiation (650 r) and injected daily thereafter with cell-free extracts of homologous and heterologous spleen. Spleen of irradiated control guinea pigs showed a progressive reduction of alkaline phosphatase staining commencing after the 3rd postirradiation day and reaching a maximum on or about the 9th day. Treatment of the animals with spleen extracts modified the radioinduced changes in alkaline phosphatase staining, so that an almost normal appearance was noted over the entire 14-day observation period. Most of the alkaiine phosphatase-staining spleen elements were mature neutrophils. It was concluded that spleen extract treatment affects apparentlymore » various celluiar elements of spleen in a different way. The results support the hypothesis that protection of phosphorylization processes against effects of irradiation represent one of the mechanisms by which the radiation protective effect of spleen extracts is effected.« less

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

40 CFR 406.30 - Applicability; description of the normal wheat flour milling subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the normal wheat flour milling subcategory. 406.30 Section 406.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Normal...

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

PubMed

Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

2016-11-08

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [ 18 F]-L-FBPA, an 18 F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [ 18 F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [ 19 F]-L-FBPA as alternatives to [ 18 F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [ 19 F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [ 19 F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [ 19 F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [ 19 F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation.

Raman spectroscopy differentiates squamous cell carcinoma (SCC) from normal skin following treatment with a high-powered CO2 laser.

PubMed

Fox, Sara A; Shanblatt, Ashley A; Beckman, Hugh; Strasswimmer, John; Terentis, Andrew C

2014-12-01

The number of cases of non-melanoma skin cancer (NMSC), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), continues to rise as the aging population grows. Mohs micrographic surgery has become the treatment of choice in many cases but is not always necessary or feasible. Ablation with a high-powered CO2 laser offers the advantage of highly precise, hemostatic tissue removal. However, confirmation of complete cancer removal following ablation is difficult. In this study we tested for the first time the feasibility of using Raman spectroscopy as an in situ diagnostic method to differentiate NMSC from normal tissue following partial ablation with a high-powered CO2 laser. Twenty-five tissue samples were obtained from eleven patients undergoing Mohs micrographic surgery to remove NMSC tumors. Laser treatment was performed with a SmartXide DOT Fractional CO2 Laser (DEKA Laser Technologies, Inc.) emitting a wavelength of 10.6 μm. Treatment levels ranged from 20 mJ to 1200 mJ total energy delivered per laser treatment spot (350 μm spot size). Raman spectra were collected from both untreated and CO2 laser-treated samples using a 785 nm diode laser. Principal Component Analysis (PCA) and Binary Logistic Regression (LR) were used to classify spectra as originating from either normal or NMSC tissue, and from treated or untreated tissue. Partial laser ablation did not adversely affect the ability of Raman spectroscopy to differentiate normal from cancerous residual tissue, with the spectral classification model correctly identifying SCC tissue with 95% sensitivity and 100% specificity following partial laser ablation, compared with 92% sensitivity and 60% selectivity for untreated NMSC tissue. The main biochemical difference identified between normal and NMSC tissue was high levels of collagen in the normal tissue, which was lacking in the NMSC tissue. The feasibility of a combined high-powered CO2 laser ablation, Raman diagnostic procedure for the treatment of NMSC is demonstrated since CO2 laser treatment does not hinder the ability of Raman spectroscopy to differentiate normal from diseased tissue. This combined approach could be employed clinically to greatly enhance the speed and effectiveness of NMSC treatment in many cases. © 2014 Wiley Periodicals, Inc.

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Q; Lei, Y; Zheng, D

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness weremore » created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.« less

Dynamic Contrast-enhanced Magnetic Resonance Imaging for Differentiating Between Primary Tumor, Metastatic Node and Normal Tissue in Head and Neck Cancer.

PubMed

Chen, Liangliang; Ye, Yufeng; Chen, Hanwei; Chen, Shihui; Jiang, Jinzhao; Dan, Guo; Huang, Bingsheng

2018-06-01

To study the difference of the Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) parameters among the primary tumor, metastatic node and peripheral normal tissue of head and neck cancer. Consecutive newly-diagnosed head and neck cancer patients with nodal metastasis between December 2010 and July 2013 were recruited, and 25 patients (8 females; 24~63,mean 43±11 years old) were enrolled. DCE-MRI was performed in the primary tumor region including the regional lymph nodes on a 3.0-T MRI system. Three quantitative parameters: Ktrans (volume transfer constant), ve (volume fraction of extravascular extracellular space) and kep (the rate constant of contrast transfer) were calculated for the largest node. A repeated-measure ANOVA with a Greenhouse-Geisser correction and post hoc tests using the Bonferroni correction were used to evaluate the differences in Ktrans, ve and kep among primary tumors, metastatic nodes and normal tissue. The values of both Ktrans and ve of normal tissue differed significantly from those of nodes (both P < 0.001) and primary tumors (both P < 0.001) respectively, while no significant differences of Ktrans and ve were observed between nodes and primary tumors (P = 0.075 and 0.365 respectively). The kep values of primary tumors were significantly different from those of nodes (P = 0.001) and normal tissue (P = 0.002), while no significant differences between nodes and normal tissue (P > 0.999). The DCE-MRI parameters were different in the tumors, metastatic nodes and normal tissue in head and neck cancer. These findings may be useful in the characterization of head and neck cancer.

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.

PubMed

Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius; Collins, Nicholas; Dzutsev, Amiran; Shaik, Jahangheer; Morais da Fonseca, Denise; Harrison, Oliver J; Tamoutounour, Samira; Byrd, Allyson L; Smelkinson, Margery; Bouladoux, Nicolas; Bliska, James B; Brenchley, Jason M; Brodsky, Igor E; Belkaid, Yasmine

2017-12-19

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory. Published by Elsevier Inc.

A Modified Protocol for the Isolation of Primary Human Hepatocytes with Improved Viability and Function from Normal and Diseased Human Liver.

PubMed

Bartlett, David C; Newsome, Philip N

2017-01-01

Successful hepatocyte isolation is critical for continued development of cellular transplantation. However, most tissue available for research is from diseased liver and the results of hepatocyte isolation from such tissue are inferior compared to normal tissue. Here we describe a modified method, combining the use of Liberase and N-acetylcysteine (NAC), for the isolation of primary human hepatocytes with high viability from normal and diseased liver.

Downregulation of external death receptor genes FAS and DR5 in colorectal cancer samples positive for human papillomavirus infection.

PubMed

Karbasi, Ashraf; Borhani, Nasim; Daliri, Karim; Kazemi, Bahram; Manoochehri, Mehdi

2015-06-01

Human papillomaviruses (HPV) have frequently been detected in colorectal cancer tumor samples, and may play a role in the pathogenesis of colorectal cancer. This study was designed to investigate the presence of DNA and RNA for the high-risk HPV genotypes 16 and 18 in samples of colorectal cancer tumors and adjacent normal tissues. We also investigated the expression of proapoptotic genes in HPV-positive colorectal tumors compared to normal tissue samples. Samples of tumoral and adjacent normal tissues were fresh-frozen, and HPV DNA was identified by nested and semiquantitative PCR. Real time PCR was used to quantitatively compare the expression of HPV-18 E6 and nine proapoptotic genes in HPV-positive tumors and samples of adjacent normal tissue. HPV-16 DNA was found in 10.5% of the tumor samples, and HPV-18 DNA was found in 23.6% of the samples. Real time PCR results showed lower expression of the E6 gene in HPV-positive tumors than in adjacent normal tissue. The expression of two proapoptotic genes, FAS and DR5, was significantly lower in tumor samples than in adjacent normal tissues. HPV infection, especially HPV-18, may play a role in colorectal cancer tumorigenesis by downregulating death receptor genes and interfering with the extrinsic pathway of apoptosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Simulation study of pO2 distribution in induced tumour masses and normal tissues within a microcirculation environment.

PubMed

Li, Mao; Li, Yan; Wen, Peng Paul

2014-01-01

The biological microenvironment is interrupted when tumour masses are introduced because of the strong competition for oxygen. During the period of avascular growth of tumours, capillaries that existed play a crucial role in supplying oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply from capillaries, healthy cells have to compete for oxygen with tumourous cells. In this study, an improved Krogh's cylinder model which is more realistic than the previously reported assumption that oxygen is homogeneously distributed in a microenvironment, is proposed to describe the process of the oxygen diffusion from a capillary to its surrounding environment. The capillary wall permeability is also taken into account. The simulation study is conducted and the results show that when tumour masses are implanted at the upstream part of a capillary and followed by normal tissues, the whole normal tissues suffer from hypoxia. In contrast, when normal tissues are ahead of tumour masses, their pO2 is sufficient. In both situations, the pO2 in the whole normal tissues drops significantly due to the axial diffusion at the interface of normal tissues and tumourous cells. As the existence of the axial oxygen diffusion cannot supply the whole tumour masses, only these tumourous cells that are near the interface can be partially supplied, and have a small chance to survive.

THE PROS AND CONS OF APOPTOSIS ASSAYS FOR USE IN THE STUDY OF CELLS, TISSUES AND ORGANS

EPA Science Inventory

Abstract
Programmed cell death or apoptosis occurs in many tissues during normal development and in the normal homeostasis of adult tissues. Apoptosis also plays a significant role in abnormal development and disease. Increased interest in apoptosis and cell death in general...

Protection and sensitization of normal and malignant cells by a naturally occurring compound in a model of photochemical damage

NASA Astrophysics Data System (ADS)

Lee, Yuan-Hao; Kumar, Neeru; Glickman, Randolph D.

2012-03-01

Certain phytonutrients are known to confer protection and immunosuppression against radiation insults. Radiation-induced reactive oxygen species (ROS) can either lead to the destruction of normal tissue cells, or induce tumor radioresistance by activating ROS scavenging proteins. To identify whether the triterpene phytonutrient, ursolic acid, reduces radiation-induced damage in normal cells and promotes the apoptosis of malignant cells, we investigated the biologic mechanisms and effect of radiation-cell interaction with or without treatment with ursolic acid in human skin melanoma cells (ATCC CRL-11147TM) and transformed human retinal pigment epithelial (hTERT-RPE) cells. UV-VIS light was employed to investigate the efficacy of ursolic acid in altering cellular viability by modulations of p53 and NF-κB p65 signaling. Cell response was investigated by changes in proliferative activity and free radical generation assessed by 2',7'-dichlorofluorescin liquid chromatography. Ursolic acid pretreatment strongly increased the level of p53 and decreased the level of phosphorylated p65 leading to enhanced cell death of skin melanoma cells in response to UV-VIS exposure. In contrast, ursolic acid appeared to downregulate p53 levels without disturbing NF-κB activation along with an increase of oxidative stress in hTERT-RPE cells. These findings indicate that ursolic acid may beneficially increase the radiosensitivity of tumor cells while potentiating a photoprotective effect on benign cells through differential effects on the NF-κB and p53 signaling pathways.

Prostate Cancer Detection Using Near Infrared Spectral Polarization Imaging

DTIC Science & Technology

2005-07-01

position. This indicates the polarization preservation nature of Cybesin. Time Resolved Fluorescence Intensity of Cybesin 60000 Perpendicular 3000 0...absorption than that of normal tissue at water absorption peaks indicating cancer tissue has less water content than that of normal tissue; (5) preliminary...rectum-and-membrane tissues.’ This indicates that our proposed approach of imaging a prostate gland through rectum using spectral polarization imaging

Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using (1)H and (31)P magic angle spinning MRS of intact tissue.

PubMed

De Silva, Sonali S; Payne, Geoffrey S; Thomas, Valerie; Carter, Paul G; Ind, Thomas E J; deSouza, Nandita M

2009-02-01

The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). (1)H HR-MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell-Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). (31)P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a (1)H-decoupled pulse-acquire sequence (TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P = 0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright (c) 2008 John Wiley & Sons, Ltd.

Ultra-Wideband Millimeter-Wave Dielectric Characteristics of Freshly Excised Normal and Malignant Human Skin Tissues.

PubMed

Mirbeik-Sabzevari, Amir; Ashinoff, Robin; Tavassolian, Negar

2018-06-01

Millimeter waves have recently gained attention for the evaluation of skin lesions and the detection of skin tumors. Such evaluations heavily rely on the dielectric contrasts existing between normal and malignant skin tissues at millimeter-wave frequencies. However, current studies on the dielectric properties of normal and diseased skin tissues at these frequencies are limited and inconsistent. In this study, a comprehensive dielectric spectroscopy study is conducted for the first time to characterize the ultra-wideband dielectric properties of freshly excised normal and malignant skin tissues obtained from skin cancer patients having undergone Mohs micrographic surgeries at Hackensack University Medical Center. Measurements are conducted using a precision slim-form open-ended coaxial probe in conjunction with a millimeter-wave vector network analyzer over the frequency range of 0.5-50 GHz. A one-pole Cole-Cole model is fitted to the complex permittivity dataset of each sample. Statistically considerable contrasts are observed between the dielectric properties of malignant and normal skin tissues over the ultra-wideband millimeter-wave frequency range considered.

Altered expression of Matrix Remodeling Associated 7 (MXRA7) in psoriatic epidermis: evidence for a protective role in the psoriasis imiquimod mouse model.

PubMed

Ning, Jinling; Shen, Ying; Wang, Ting; Wang, Mengru; Liu, Wei; Sun, Yonghu; Zhang, Furen; Chen, Lingling; Wang, Yiqiang

2018-05-21

Preliminary datamining performed with Gene Expression Omnibus datasets implied that psoriasis may involve the matrix remodeling associated 7 (MXRA7), a gene with little function information yet. To test that hypothesis, studies were performed in human samples and murine models. Immunohistochemistry in normal human skin showed that MXRA7 proteins were present across the full epidermal layer, with highest expression level detected in the basal layer. In psoriatic samples, MXRA7 proteins were absent in the basal stem cells layer while suprabasal keratinocytes stained at a higher level than in normal tissues. In an imiquimod-induced psoriasis-like disease model in mice, diseased skins manifested similar MXRA7 expression pattern and change as in human samples, and MXRA7-deficient mice developed severer psoriasis-like diseases than wild-type mice did. While levels of pro-psoriatic genes (e.g. IL17, IL22, IL23, etc) in imiquimod-stimulated MXRA7-deficient mice were higher than in wild-type mice, keratinocytes isolated from MXRA7-deficient mice showed increased proliferation upon differentiation induction in culture. These data demonstrated that MXRA7 gene might function as a negative modulator in psoriasis development when pro-psoriatic factors attack, presumably via expression alteration or redistribution of MXRA7 proteins in keratinocytes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats.

PubMed

Mostafa, Rasha E; Salama, Abeer A A; Abdel-Rahman, Rehab F; Ogaly, Hanan A

2017-05-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.

[Tissue collagenase MMP-14 and endogenous regulators of its activity in the corpus uteri in squamous cell carcinoma of the cervix].

PubMed

Timoshenko, O S; Gureeva, T A; Kugaevskaya, E V; Zavalishina, L E; Andreeva, Yu Yu; Solovyeva, N I

to investigate the expression of the membrane-bound matrix metalloproteinase MT1-MMP (MMP-14), its tissue inhibitor TIMP-2, and the proMMP-14 activator furin in the corpus uteri from the vaginal wall to the bottom of the uterine cavity in squamous cell carcinoma of the cervix (SCCC). Hysterectomy material was examined in patients with SCCC. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and enzyme assays were used. In SCCC, higher levels of MMP-14 expression were established in tumor cells, as evidenced by IHC (+3) and RT-PCR. IHC showed that the expression of MMP-14 was absent or insignificant in the normal uterine endometrial and myometrial tissues. However, that of MMP-14 mRNA was also found in the normal tissues to the bottom of the uterine cavity. Furin activity in the tumor was much higher than that in normal tissues. IHC indicated that TIMP-2 expression was low or absent in both the tumor and normal tissues. The expression of TIMP-2 mRNA was sufficiently obvious in both the tumor and normal tissues to the bottom of the uterine cavity. In SCCC, MMP-14 expression was substantially increased in tumors. The expression of MMP-14 and regulators of its activity is aimed at enhancing the tumor destructive (invasive) potential in the pericellular space and can occur (be induced) in the morphologically normal uterine tissue apparently with involvement of signaling through the epithelial-mesenchymal interaction. Data are important for understanding the role of MMP-14 in the development of a multistage process of carcinogenesis and may have prognostic value and an impact on therapeutic strategy for the patient.

In vitro simulation of pathological bone conditions to predict clinical outcome of bone tissue engineered materials

NASA Astrophysics Data System (ADS)

Nguyen, Duong Thuy Thi

According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and non-unions. Compromised innate bone healing reactions of patients with bone diseases are exacerbated with protective bone therapy. Once these patients sustain a fracture, bone healing is a challenge, especially when fracture stabilization is unsuccessful. Traditional stabilizing screw and plate systems were designed with emphasis on bone mechanics rather than biology. Bone grafts are often used with fixation devices to provide skeletal continuity at the fracture gap. Current bone grafts include autologous bone tissue and donor bone tissue; however, the quality and quantity demanded by fragility fractures sustained by high-risk geriatric patients and patients with bone diseases are not met. Consequently, bone tissue engineering strategies are advancing towards functionalized bone substitutes to provide fracture reconstruction while effectively mediating bone healing in normal and diseased fracture environments. In order to target fragility fractures, fracture management strategies should be tailored to allow bone regeneration and fracture stabilization with bioactive bone substitutes designed for the pathological environment. The clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted treatment strategy should focus on simulating, in vitro, a physiological bone environment to predict clinical effectiveness of engineered bone and understand cellular responses due to the proposed agents and bioactive scaffolds. An in vitro test system can be the necessary catalyst to reduce implant failures and non-unions in fragility fractures.

Effects of histone deacetylase inhibitory prodrugs on epigenetic changes and DNA damage response in tumor and heart of glioblastoma xenograft.

PubMed

Tarasenko, Nataly; Nudelman, Abraham; Rozic, Gabriela; Cutts, Suzanne M; Rephaeli, Ada

2017-08-01

The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity. In order to determine the processes underlying these opposing effects, the changes induced by these treatments on the epigenetic landscape, the DDR, and fibrosis were compared in tumors and hearts of glioblastoma xenografts. The potency of AN7 and AN446 as HDAC inhibitors was correlated with their effects on the viability of the cancer and non-cancer cells. The prodrugs affected the epigenetic landscape and the DDR in a tissue-specific and context-dependent manner. Findings suggest that the selectivity of the prodrugs could be attributed to their different effects on histone modification patterns in normal vs. transformed tissues. Further studies are warranted to substantiate the potential of AN446 as a new anticancer drug for glioblastoma patients.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature).

PubMed

Abbaszadeh, A; Haddadi, G H; Haddadi, Z

2017-06-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature)

PubMed Central

Abbaszadeh, A.; Haddadi, G.H.; Haddadi, Z.

2017-01-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses. PMID:28580334

Differentiation of Normal and Malignant Breast Tissues using Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Mehrotra, Ranjana; Jangir, Deepak Kumar; Gupta, Alka; Kandpal, H. C.

2008-11-01

Infrared spectra of carcinomatous and their normal fore bearing tissues were collected in the 600 cm-1 to 4000 cm-1 region. Fourier Transform Infrared (FTIR) data of infiltrating ductal carcinoma of breast with different grades of malignancy from patients of different age groups were analyzed. Infrared spectra demonstrate significant spectral differences between the tumor sections of normal and the malignant breast tissues. In particular, changes in frequency and intensity in the spectra of protein, nucleic acid and glycogen were observed. This allows to make a qualitative and semi quantitative evaluation of the changes in proliferation activities from normal to diseased tissue. The findings establish a framework for additional studies, which may enable us to establish a relation of the diseased state with its infrared spectra.

Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

2016-07-01

Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population.

PubMed

Yamaoka, Yuko; Suehiro, Yutaka; Hashimoto, Shinichi; Hoshida, Tomomi; Fujimoto, Michiyo; Watanabe, Michiya; Imanaga, Daiki; Sakai, Kouhei; Matsumoto, Toshihiko; Nishioka, Mitsuaki; Takami, Taro; Suzuki, Nobuaki; Hazama, Shoichi; Nagano, Hiroaki; Sakaida, Isao; Yamasaki, Takahiro

2018-04-01

Accumulating evidence shows an overabundance of Fusobacterium nucleatum in colorectal tumor tissues. However, the correlation between the absolute copy number of F. nucleatum in colorectal cancer tissues and colorectal cancer progression is unclear from previous reports. Therefore, we performed a study to compare the abundance of F. nucleatum in colorectal tissues with clinicopathologic and molecular features of colorectal cancer. We collected 100 colorectal cancer tissues and 72 matched normal-appearing mucosal tissues. Absolute copy numbers of F. nucleatum were measured by droplet digital PCR. The detection rates of F. nucleatum were 63.9% (46/72) in normal-appearing mucosal tissues and 75.0% (75/100) in CRC tissue samples. The median copy number of F. nucleatum was 0.4/ng DNA in the normal-appearing colorectal mucosa in patients with colorectal cancer and 1.9/ng DNA in the colorectal cancer tissues (P = 0.0031). F. nucleatum copy numbers in stage IV colorectal cancer tissues were significantly higher than those in the normal-appearing mucosa in patients with colorectal cancer (P = 0.0016). The abundance of F. nucleatum in colorectal cancer tissues correlated with tumor size and KRAS mutation and was significantly associated with shorter overall survival times; this trend was notable in the patients with stage IV colorectal cancer. Focusing on normal-appearing mucosa in the patients with colorectal cancer, the F. nucleatum copy number was significantly higher in the patients with stage IV rather than stages I-III. These results suggest that determining F. nucleatum levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

PubMed Central

Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

Prevention of recrudescent malaria in nude mice by thymic grafting or by treatment with hyperimmune serum.

PubMed Central

Roberts, D W; Rank, R G; Weidanz, W P; Finerty, J F

1977-01-01

Nude mice died when infected with the normally avirulent malarial parasite Plasmodium berghei yoelii. Furthermore, malaria recrudesced in Nu/Nu mice after the termination of acute disease by treatment with clindamycin. Recrudescence was not observed in Nu/Nu mice that had been grafted with thymic tissue or treated with hyperimmune serum. Mice mad B cell deficient by treatment with anti-mu-chain serum also died when infected with P. berghei yoelii. The data suggest that a crucial role of the thymus in preventing recrudescent malaria in this model system is to provide a helper function in the production of protective antibody. PMID:330396

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

PubMed Central

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

Correlation of tissue-plasma partition coefficients between normal tissues and subcutaneous xenografts of human tumor cell lines in mouse as a prediction tool of drug penetration in tumors.

PubMed

Poulin, Patrick; Hop, Cornelis Eca; Salphati, Laurent; Liederer, Bianca M

2013-04-01

Understanding drug distribution and accumulation in tumors would be informative in the assessment of efficacy in targeted therapy; however, existing methods for predicting tissue drug distribution focus on normal tissues and do not incorporate tumors. The main objective of this study was to describe the relationships between tissue-plasma concentration ratios (Kp ) of normal tissues and those of subcutaneous xenograft tumors under nonsteady-state conditions, and establish regression equations that could potentially be used for the prediction of drug levels in several human tumor xenografts in mouse, based solely on a Kp value determined in a normal tissue (e.g., muscle). A dataset of 17 compounds was collected from the literature and from Genentech. Tissue and plasma concentration data in mouse were obtained following oral gavage or intraperitoneal administration. Linear regression analyses were performed between Kp values in several normal tissues (muscle, lung, liver, or brain) and those in human tumor xenografts (CL6, EBC-1, HT-29, PC3, U-87, MCF-7-neo-Her2, or BT474M1.1). The tissue-plasma ratios in normal tissues reasonably correlated with the tumor-plasma ratios in CL6, EBC-1, HT-29, U-87, BT474M1.1, and MCF-7-neo-Her2 xenografts (r(2) in the range 0.62-1) but not with the PC3 xenograft. In general, muscle and lung exhibited the strongest correlation with tumor xenografts, followed by liver. Regression coefficients from brain were low, except between brain and the glioblastoma U-87 xenograft (r(2) in the range 0.62-0.94). Furthermore, reasonably strong correlations were observed between muscle and lung and between muscle and liver (r(2) in the range 0.67-0.96). The slopes of the regressions differed depending on the class of drug (strong vs. weak base) and type of tissue (brain vs. other tissues and tumors). Overall, this study will contribute to our understanding of tissue-plasma partition coefficients for tumors and facilitate the use of physiologically based pharmacokinetics (PBPK) modeling for chemotherapy in oncology studies. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1355-1369, 2013. Copyright © 2013 Wiley Periodicals, Inc.

Epithelium percentage estimation facilitates epithelial quantitative protein measurement in tissue specimens.

PubMed

Chen, Jing; Toghi Eshghi, Shadi; Bova, George Steven; Li, Qing Kay; Li, Xingde; Zhang, Hui

2013-12-01

The rapid advancement of high-throughput tools for quantitative measurement of proteins has demonstrated the potential for the identification of proteins associated with cancer. However, the quantitative results on cancer tissue specimens are usually confounded by tissue heterogeneity, e.g. regions with cancer usually have significantly higher epithelium content yet lower stromal content. It is therefore necessary to develop a tool to facilitate the interpretation of the results of protein measurements in tissue specimens. Epithelial cell adhesion molecule (EpCAM) and cathepsin L (CTSL) are two epithelial proteins whose expressions in normal and tumorous prostate tissues were confirmed by measuring staining intensity with immunohistochemical staining (IHC). The expressions of these proteins were measured by ELISA in protein extracts from OCT embedded frozen prostate tissues. To eliminate the influence of tissue heterogeneity on epithelial protein quantification measured by ELISA, a color-based segmentation method was developed in-house for estimation of epithelium content using H&E histology slides from the same prostate tissues and the estimated epithelium percentage was used to normalize the ELISA results. The epithelium contents of the same slides were also estimated by a pathologist and used to normalize the ELISA results. The computer based results were compared with the pathologist's reading. We found that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly affected by epithelium content in the tissue specimens. Without adjusting for epithelium percentage, both EpCAM and CTSL levels appeared significantly higher in tumor tissues than normal tissues with a p value less than 0.001. However, after normalization by the epithelium percentage, ELISA measurements of both EpCAM and CTSL were in agreement with IHC staining results, showing a significant increase only in EpCAM with no difference in CTSL expression in cancer tissues. These results were obtained with normalization by both the computer estimated and pathologist estimated epithelium percentage. Our results show that estimation of tissue epithelium percentage using our color-based segmentation method correlates well with pathologists' estimation of tissue epithelium percentages. The epithelium contents estimated by color-based segmentation may be useful in immuno-based analysis or clinical proteomic analysis of tumor proteins. The codes used for epithelium estimation as well as the micrographs with estimated epithelium content are available online.

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

NASA Astrophysics Data System (ADS)

Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

2015-03-01

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

NASA Astrophysics Data System (ADS)

Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

2010-07-01

Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach.

PubMed

Busk, Morten; Munk, Ole L; Jakobsen, Steen; Frøkiær, Jørgen; Overgaard, Jens; Horsman, Michael R

2017-05-01

Current [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) procedures in tumor-bearing mice typically includes fasting, anesthesia, and standardized uptake value (SUV)-based quantification. Such procedures may be inappropriate for prolonged multiscan experiments. We hypothesize that normalization of tumor FDG retention relative to a suitable reference tissue may improve accuracy as this method may be less susceptible to uncontrollable day-to-day changes in blood glucose levels, physical activity, or unnoticed imperfect tail vein injections. Fed non-anesthetized tumor-bearing mice were administered FDG intravenously (i.v.) or intraperitoneally (i.p.) and PET scanned on consecutive days using a Mediso nanoScan PET/magnetic resonance imaging (MRI). Reproducibility of various PET-deduced measures of tumor FDG retention, including normalization to FDG signal in reference organs and a conventional SUV approach, was evaluated. Day-to-day variability in i.v. injected mice was lower when tumor FDG retention was normalized to brain signal (T/B), compared to normalization to other tissues or when using SUV-based normalization. Assessment of tissue radioactivity in dissected tissues confirmed the validity of PET-derived T/B ratios. Mean T/B and SUV values were similar in i.v. and i.p. administered animals, but SUV normalization was more robust in the i.p. group than in the i.v. group. Multimodality scanners allow tissue delineation and normalization of tumor FDG uptake relative to reference tissues. Normalization to brain, but not liver or kidney, improved scan reproducibility considerably and was superior to traditional SUV quantification in i.v. tracer-injected animals. Day-to-day variability in SUV's was lower in i.p. than in i.v. injected animals, and i.p. injections may therefore be a valuable alternative in prolonged rodent studies, where repeated vein injections are undesirable.

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies.

PubMed

Mohamed, H R H; Hamad, S R

2017-08-30

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.

Autofluorescence spectroscopy of oral mucosa

NASA Astrophysics Data System (ADS)

Majumdar, S. K.; Uppal, A.; Gupta, P. K.

1998-06-01

We report the results of an in-vitro study on autofluorescence from pathologically characterized normal and malignant squamous tissues from the oral cavity. The study involved biopsy samples from 47 patients with oral cancer of which 11 patients had cancer of tongue, 17 of buccal mucosa and 19 of alveolus. The results of excitation and emission spectroscopy at several wavelengths (280 nm less than or equal to (lambda) exless than or equal to 460 nm; 340 nm less than or equal to (lambda) em less than or equal to 520 nm) showed that at (lambda) ex equals 337 nm and 400 nm the mean value for the spectrally integrated fluorescence intensity [(Sigma) (lambda ) IF((lambda) )] from the normal tissue sites was about a factor of 2 larger than that from the malignant tissue sites. At other excitation wavelengths the difference in (Sigma) (lambda ) IF((lambda) ) was not statistically significant. Similarly, for (lambda) em equals 390 nm and 460 nm, the intensity of the 340 nm band of the excitation spectra from normal tissues was observed to be a factor of 2 larger than that from malignant tissues. Analysis of these results suggests that NADH concentration is higher in normal oral tissues compared to the malignant. This contrasts with our earlier observation of an reduced NADH concentration in normal sites of breast tissues vis a vis malignant sites. For the 337 nm excited emission spectra a 10-variable MVLR score (using (Sigma) (lambda ) IF((lambda) ) and normalized intensities at nine wavelengths as input parameters) provided a sensitivity and specificity of 95.7% and 93.1% over the sample size investigated.

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

PubMed Central

Gay, Hiram A.; Barthold, H. Joseph; O’Meara, Elizabeth; Bosch, Walter R.; El Naqa, Issam; Al-Lozi, Rawan; Rosenthal, Seth A.; Lawton, Colleen; Lee, W. Robert; Sandler, Howard; Zietman, Anthony; Myerson, Robert; Dawson, Laura A.; Willett, Christopher; Kachnic, Lisa A.; Jhingran, Anuja; Portelance, Lorraine; Ryu, Janice; Small, William; Gaffney, David; Viswanathan, Akila N.; Michalski, Jeff M.

2012-01-01

Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. PMID:22483697

Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

DTIC Science & Technology

2016-10-01

Report We will continue to recruit African American patients and bank their prostate tissue . We will continue dissecting tumor samples into tumor...in prostate tumors and adjacent normal tissue derived from both AA and EA individuals. We will determine if DNA methylation patterns in prostate... tissue (both cancerous and normal tissue ) differ between AA and EA individuals. We will also identify methylation features that differ between tumor

Optical scattering coefficient estimated by optical coherence tomography correlates with collagen content in ovarian tissue

NASA Astrophysics Data System (ADS)

Yang, Yi; Wang, Tianheng; Biswal, Nrusingh C.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2011-09-01

Optical scattering coefficient from ex vivo unfixed normal and malignant ovarian tissue was quantitatively extracted by fitting optical coherence tomography (OCT) A-line signals to a single scattering model. 1097 average A-line measurements at a wavelength of 1310 nm were performed at 108 sites obtained from 18 ovaries. The average scattering coefficient obtained from the normal tissue group consisted of 833 measurements from 88 sites was 2.41 mm-1 (+/-0.59), while the average coefficient obtained from the malignant tissue group consisted of 264 measurements from 20 sites was 1.55 mm-1 (+/-0.46). The malignant ovarian tissue showed significant lower scattering than the normal group (p < 0.001). The amount of collagen within OCT imaging depth was analyzed from the tissue histological section stained with Sirius Red. The average collagen area fraction (CAF) obtained from the normal tissue group was 48.4% (+/-12.3%), while the average CAF obtained from the malignant tissue group was 11.4% (+/-4.7%). A statistical significance of the collagen content was found between the two groups (p < 0.001). These results demonstrated that quantitative measurements of optical scattering coefficient from OCT images could be a potential powerful method for ovarian cancer detection.

It takes a tissue to make a tumor: epigenetics, cancer and the microenvironment

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

2001-01-01

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.

Tissue Physiology and Pathology of Aromatase

PubMed Central

Stocco, Carlos

2011-01-01

Summary Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies. PMID:22108547

Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in normal tissues and in the breast tumoral processes

PubMed Central

2010-01-01

SIAH proteins are the human members of an highly conserved family of E3 ubiquitin ligases. Several data suggest that SIAH proteins may have a role in tumor suppression and apoptosis. Previously, we reported that SIAH-1 induces the degradation of Kid (KIF22), a chromokinesin protein implicated in the normal progression of mitosis and meiosis, by the ubiquitin proteasome pathway. In human breast cancer cells stably transfected with SIAH-1, Kid/KIF22 protein level was markedly reduced whereas, the Kid/KIF22 mRNA level was increased. This interaction has been further elucidated through analyzing SIAH and Kid/KIF22 expression in both paired normal and tumor tissues and cell lines. It was observed that SIAH-1 protein is widely expressed in different normal tissues, and in cells lines but showing some differences in western blotting profiles. Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1 and Kid/KIF22 appears to be modified in human tumor tissues compared to normal controls. When mRNA expression of SIAH-1 and Kid/KIF22 was analyzed by real-time PCR in normal and cancer breast tissues from the same patient, a large variation in the number of mRNA copies was detected between the different samples. In most cases, SIAH-1 mRNA is decreased in tumor tissues compared to their normal counterparts. Interestingly, in all breast tumor tissues analyzed, variations in the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. This concerted variation of SIAH-1 and Kid/KIF22 messengers suggests the existence of an additional level of control than the previously described protein-protein interaction and protein stability regulation. Our observations also underline the need to re-evaluate the results of gene expression obtained by qRT-PCR and relate it to the protein expression and cellular localization when matched normal and tumoral tissues are analyzed. PMID:20144232

SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Hossain, S; Hildebrand, K

Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

NASA Astrophysics Data System (ADS)

Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

2008-02-01

Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

Terahertz spectroscopic investigation of human gastric normal and tumor tissues

NASA Astrophysics Data System (ADS)

Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

2014-09-01

Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2~0.5 THz and 1~1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications.

Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

PubMed

An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

2016-09-01

1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

2016-03-01

In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery.

PubMed

Warram, Jason M; de Boer, Esther; Moore, Lindsay S; Schmalbach, Cecelia E; Withrow, Kirk P; Carroll, William R; Richman, Joshua S; Morlandt, Anthony B; Brandwein-Gensler, Margaret; Rosenthal, Eben L

2015-07-01

Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n = 11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%). Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer. © 2015 Wiley Periodicals, Inc.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

PubMed

Liu, Yan; Miao, Yuhua; Li, Xiaoming

2015-06-01

To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.

Characterization of DNA isolated from normal and cancerous ovarian tissues by ultraviolet resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zhao, Xiaojie; Vinson, Michael A.; Malins, Donald C.; Spiro, Thomas G.

2000-05-01

We report significant differences in UV resonance Raman (UVRR) spectra of DNA samples from normal and cancerous tissues. The four bases of DNA, adenosine, thymine, guanosine and cytidine, can be enhanced in UVRR spectra, and their intensities are very sensitive to base stacking and DNA H-bonding. 14 DNA samples from patients at different stages of ovarian cancer, 5 from normal, 2 from primary, 3 from metastasis primary and 4 from distant metastasis tumor tissues, were characterized by 257, 238, 229, 220 and 210 nm-excited UVRR spectra. Raman spectral difference between normal and tumor DNA could be readily detected.

Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues.

PubMed

Bachmayr-Heyda, Anna; Reiner, Agnes T; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W; Zeillinger, Robert; Pils, Dietmar

2015-01-27

Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells.

Correlation of circular RNA abundance with proliferation – exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues

PubMed Central

Bachmayr-Heyda, Anna; Reiner, Agnes T.; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W.; Zeillinger, Robert; Pils, Dietmar

2015-01-01

Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells. PMID:25624062

The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center: A Unique Resource for Defining the “Molecular Histology” of the Breast

PubMed Central

Sherman, Mark E.; Figueroa, Jonine D.; Henry, Jill E.; Clare, Susan E.; Rufenbarger, Connie; Storniolo, Anna Maria

2014-01-01

“Molecular histology” of the breast may be conceptualized as encompassing the normative ranges of histological structure and marker expression in normal breast tissues in relation to a woman’s age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin fixed paraffin embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank’s website. PMID:22345117

Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

2016-03-01

Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

Ginger Treatment Ameliorates Alcohol-induced Myocardial Damage by Suppression of Hyperlipidemia and Cardiac Biomarkers in Rats.

PubMed

Subbaiah, Ganjikunta Venkata; Mallikarjuna, Korivi; Shanmugam, Bhasha; Ravi, Sahukari; Taj, Patan Usnan; Reddy, Kesireddy Sathyavelu

2017-01-01

Alcohol-induced hyperlipidemia is positively correlated with cardiovascular diseases. Several herbal extracts have been reported to protect the cardiac injury and suppress the hyperlipidemia. However, the effect of ginger extracts on alcohol-induced hyperlipidemia and associated myocardial damage remains unclear. This study investigated the cardio-protective properties of ginger ethanolic extract (Gt) against alcohol-induced myocardial damage, and further distinguished the association between hyperlipidemia and occurrence of myocardial damage in rats. Twenty four Wistar male albino rats (250 ± 20 g) were divided into four groups including, Normal control (NC) (0.9% NaCl), Ginger treated (Gt) (200 mg/Kg b.w.), Alcohol treated (At) (20% of 6g/kg b.w. alcohol), and Alcohol along with Ginger treatment (At+Gt). In this study, lipid profiles such as fatty acids, triglycerides, total cholesterol, phospholipids, low density lipoprotein and high density lipoproteins, and cardiac biomarkers, including LDH, AST, CK-MB, cTn-T and cTn-I were examined in rats. Furthermore, histopathological studies were also conducted. We found that alcohol-induced myocardial damage was associated with increased lipid profile except high density lipoprotein in alcohol treated (20%, 6g/kg b.w.) rats compared with control. Ginger treatment significantly reduced the alcohol-induced lipid profiles except high density lipoproteins. Furthermore, elevated cardiac biomarkers activity with alcohol intoxication was substantially suppressed by ginger treatment. In addition, ginger treatment for 7-weeks significantly minimized the alcohol-induced myocardial damage. Our results concluded that ginger could protect alcohol-induced myocardial damage by suppression of hyperlipidemia and cardiac biomarkers. Ginger extract could alleviate the myocardial injury partially due to the suppression of circulating FFAs and TG levels.Increased circulating cholesterol, LDL and phospholipids with alcohol intake were substantially suppressed by ginger treatmentAlcohol, induced an increase in cardiac damage biomarkers, CK-MB, cTn-T and cTn-I were remarkably suppressed by ginger treatmentPerformed histopathological studies by transmission electron microscopy and light microscopy shows additional convincing evidence on ginger cardio-protective effects. The drastic changes were rehabilitated in cardiac tissue by ginger treatment may be it acts as a good antioxidant and possessing hypolipidemic activity.Collectively, our findings confirm hypothesis that ginger has cardio protective potential through suppression of hyperlipidemia, preserving the tissue damage bio markers, cardiac biomarkers in plasma and preservation of histoarchitecture of myocytes. Abbreviations used: Gt: Ginger Ethanolic Extract; NC: Normal Control; At: Alcohol treated; MI: Myocardial Infarction.

40 CFR 406.50 - Applicability; description of the normal rice milling subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... normal rice milling subcategory. 406.50 Section 406.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Normal Rice Milling Subcategory § 406.50 Applicability; description of the normal rice milling subcategory. The...

Estrogen receptor β expression and colorectal cancer: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2015-12-01

Estrogen receptor β (ERβ) is a potential tumor-suppressor gene in colorectal cancer (CRC). This hypothesis is supported by clinical and laboratory observations. In this meta-analysis, we looked at studies that investigated the relationship between ERβ protein expression and CRC, comparing the lesion with normal adjacent mucosa. English medical literature searches were performed for ERβ expression in patients with CRC, tumor tissue versus normal mucosa. Searches were performed up to 31 May 2015, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Meta-analysis was carried out using Comprehensive Meta-analysis Software. Pooled odds ratios and 95% confidence intervals were calculated and ERβ expression was compared in individual studies using the fixed-effects model. The odds ratio of ERβ expression was 0.216 (95% confidence interval 0.152-0.307, P<0.0001), lower in cancer tissue than normal mucosa. Funnel plot did not indicate a significant publication bias. There was no significant heterogeneity in the studies included: Q=5.897, d.f.(Q)=9, I=0.000, P=0.750. In this meta-analysis, we confirm the observation of decreased ERβ expression in CRC. Our results support the hypothesis of ERβ being a tumor-suppressor gene in the large bowel, and the ERβ protein protects against carcinogenesis and development of CRC when activated by estrogen. Further studies are needed to examine the potential of selective/specific ligands to activate ERβ without the side effects found with estrogen and without activating ERα. In this meta-analysis, we looked at studies that investigated the relationship between CRC and ERβ expression in the tumor and normal mucosa of CRC patients. English medical literature searches were performed for studies comparing ERβ expression in the cancer and normal colonic mucosa in patients with CRC. Meta-analysis was carried out, pooled odds ratios were calculated, and ERβ expression was compared in individual studies.

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Qiuxian; Department of Biology, Hong Kong Baptist University, Kowloon Tong; Zhang, Qin

Highlights: • AESM is able to prevent the elevation of ALT and AST, and to decreased LDL-C level. • AESM demonstrates the effects of down-regulating blood fat level and protecting liver. • AESM consistent with the efficacy of simvastatin in NAFLD. - Abstract: Objectives: Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Methods: Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertnmore » group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. Results: High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Conclusions: Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver.« less

Fish tissue lipid-C:N relationships for correcting δ(13) C values and estimating lipid content in aquatic food-web studies.

PubMed

Hoffman, Joel C; Sierszen, Michael E; Cotter, Anne M

2015-11-15

Normalizing δ(13) C values of animal tissue for lipid content is necessary to accurately interpret food-web relationships from stable isotope analysis. To reduce the effort and expense associated with chemical extraction of lipids, various studies have tested arithmetic mass balance to mathematically normalize δ(13) C values for lipid content; however, the approach assumes that lipid content is related to the tissue C:N ratio. We evaluated two commonly used models for estimating tissue lipid content based on C:N ratio (a mass balance model and a stoichiometric model) by comparing model predictions to measure the lipid content of white muscle tissue. We then determined the effect of lipid model choice on δ(13) C values normalized using arithmetic mass balance. To do so, we used a collection of fish from Lake Superior spanning a wide range in lipid content (5% to 73% lipid). We found that the lipid content was positively related to the bulk muscle tissue C:N ratio. The two different lipid models produced similar estimates of lipid content based on tissue C:N, within 6% for tissue C:N values <7. Normalizing δ(13) C values using an arithmetic mass-balance equation based on either model yielded similar results, with a small bias (<1‰) compared with results based on chemical extraction. Among-species consistency in the relationship between fish muscle tissue C:N ratio and lipid content supports the application of arithmetic mass balance to normalize δ(13) C values for lipid content. The uncertainty associated with both lipid extraction quality and choice of model parameters constrains the achievable precision of normalized δ(13) C values to about ±1.0‰. Published in 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.

Reconstitution of full-thickness skin by microcolumn grafting.

PubMed

Tam, Joshua; Wang, Ying; Vuong, Linh N; Fisher, Jeremy M; Farinelli, William A; Anderson, R Rox

2017-10-01

In addition to providing a physical barrier, skin also serves a diverse range of physiological functions through different specialized resident cell types/structures, including melanocytes (pigmentation and protection against ultraviolet radiation), Langerhans cells (adaptive immunity), fibroblasts (maintaining extracellular matrix, paracrine regulation of keratinocytes), sweat glands (thermoregulation) and hair follicles (hair growth, sensation and a stem cell reservoir). Restoration of these functional elements has been a long-standing challenge in efforts to engineer skin tissue, while autologous skin grafting is limited by the scarcity of donor site skin and morbidity caused by skin harvesting. We demonstrate an alternative approach of harvesting and then implanting μm-scale, full-thickness columns of human skin tissue, which can be removed from a donor site with minimal morbidity and no scarring. Fresh human skin microcolumns were used to reconstitute skin in wounds on immunodeficient mice. The restored skin recapitulated many key features of normal human skin tissue, including epidermal architecture, diverse skin cell populations, adnexal structures and sweat production in response to cholinergic stimulation. These promising preclinical results suggest that harvesting and grafting of microcolumns may be useful for reconstituting fully functional skin in human wounds, without donor site morbidity. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio.

PubMed

Özkan-Yilmaz, Ferbal; Özlüer-Hunt, Arzu; Gündüz, Suna Gül; Berköz, Mehmet; Yalin, Serap

2014-04-01

In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)2) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex(®)) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.

Vinpocetine modulates metabolic activity and function during retinal ischemia.

PubMed

Nivison-Smith, Lisa; O'Brien, Brendan J; Truong, Mai; Guo, Cindy X; Kalloniatis, Michael; Acosta, Monica L

2015-05-01

Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues. Copyright © 2015 the American Physiological Society.

The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression.

PubMed

Koontz, Laura M; Liu-Chittenden, Yi; Yin, Feng; Zheng, Yonggang; Yu, Jianzhong; Huang, Bo; Chen, Qian; Wu, Shian; Pan, Duojia

2013-05-28

The Hippo tumor suppressor pathway restricts tissue growth by inactivating the transcriptional coactivator Yki. Although Sd has been implicated as a DNA-binding transcription factor partner for Yki and can genetically account for gain-of-function Yki phenotypes, how Yki regulates normal tissue growth remains a long-standing puzzle because Sd, unlike Yki, is dispensable for normal growth in most Drosophila tissues. Here we show that the yki mutant phenotypes in multiple developmental contexts are rescued by inactivation of Sd, suggesting that Sd functions as a default repressor and that Yki promotes normal tissue growth by relieving Sd-mediated default repression. We further identify Tgi as a cofactor involved in Sd's default repressor function and demonstrate that the mammalian ortholog of Tgi potently suppresses the YAP oncoprotein in transgenic mice. These findings fill a major gap in Hippo-mediated transcriptional regulation and open up possibilities for modulating the YAP oncoprotein in cancer and regenerative medicine. Copyright © 2013 Elsevier Inc. All rights reserved.

FT-IR Spectroscopic Analysis of Normal and Malignant Human Oral Tissues

NASA Astrophysics Data System (ADS)

Krishnakumar, N.; Madhavan, R. Nirmal; Sumesh, P.; Palaniappan, Pl. Rm.; Venkatachalam, P.; Ramachandran, C. R.

2008-11-01

FT-IR spectroscopy has been used to explore the changes in the vibrational bands of normal and oral squamous cell carcinoma (OSCC) tissues in the region 4000-400 cm-1. Significant changes in the spectral features were observed. The spectral changes were the results of characteristics structural alterations at the molecular level in the malignant tissues. These alterations include structural changes of proteins and possible increase of its content, an increase in the nucleic-to-cytoplasm ratio, an increase in the relative amount of DNA, an increase in the rate of phosphorylation process induced by carcinogenesis, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins, a decrease in the relative amount of lipids compared to normal epithelial oral tissues. The results of the present study demonstrate that the FT-IR technique has the feasibility of discriminating malignant from normal tissues and other pathological states in a short period of time and may detect malignant transformation earlier than the standard histological examination stage.

Brain cancer probed by native fluorescence and stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2012-12-01

Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

PubMed

Acharjee, B K; Mahanta, R

2009-04-01

Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

Lactational ectopic breast tissue of the vulva: case report and brief historical review.

PubMed

Pieh-Holder, Kelly L

2013-04-01

Ectopic breast tissue is defined as glands of breast tissue located outside of the normal anatomic breasts. Historically, ectopic breast tissue has been thought to arise from a remnant of the embryonic mammary ridge along the "milk line" or the midaxillary line from the axilla to the groin, including the vulvar region. Extramammary tissue displays the same pathologic and physiologic changes as normal breast tissue and is often discovered in multiparous women as the result of swelling from lactational activity. We present a case report of a gravid patient with lactating vulvar mass and a brief historical perspective of vulvar ectopic breast tissue.

Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

PubMed Central

Ling, C. R.; Foster, M. A.; Mallard, J. R.

1979-01-01

In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered. PMID:526431

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

NASA Astrophysics Data System (ADS)

Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-06-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

PubMed

Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

2013-11-01

CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

Expression of Folliculogenesis-Related Genes in Vitrified Human Ovarian Tissue after Two Weeks In Vitro Culture.

PubMed

Shams Mofarahe, Zahra; Salehnia, Mojdeh; Ghaffari Novin, Marefat; Ghorbanmehr, Nassim; Fesharaki, Mohammad Gholami

2017-01-01

This study was designed to evaluate the effects of vitrification and in vitro culture of human ovarian tissue on the expression of oocytic and follicular cell-related genes. In this experimental study, ovarian tissue samples were obtained from eight transsexual women. Samples were cut into small fragments and were then assigned to vitrified and non-vitrified groups. In each group, some tissue fragments were divided into un-cultured and cultured (in α-MEM medium for 2 weeks) subgroups. The normality of follicles was assessed by morphological observation under a light microscope using hematoxylin and eosin (H&E) staining. Expression levels of factor in the germ line alpha ( FIGLA ), KIT ligand ( KL ), growth differentiation factor 9 ( GDF-9 ) and follicle stimulating hormone receptor ( FSHR ) genes were quantified in both groups by real-time reverse transcriptase polymerase chain reaction (RT-PCR) at the beginning and the end of culture. The percentage of normal follicles was similar between non-cultured vitrified and non-vitrified groups (P>0.05), however, cultured tissues had significantly fewer normal follicles than non-cultured tissues in both vitrified and non-vitrified groups (P<0.05). In both cultured groups the rate of primary and secondary follicles was significantly higher than non-cultured tissues (P<0.05). The expression of all examined genes was not significantly altered in both non-cultured groups. Whiles, in comparison with cultured tissues non-cultured tissues, the expression of FIGLA gene was significantly decreased, KL gene was not changed, GDF-9 and FSHR genes was significantly increased (P<0.05). Human ovarian vitrification following in vitro culture has no impairing effects on follicle normality and development and expression of related-genes. However, in vitro culture condition has deleterious effects on normality of follicles.

Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

PubMed Central

Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

2011-01-01

Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

NASA Astrophysics Data System (ADS)

Giese, A.; Böhringer, H. J.; Leppert, J.; Kantelhardt, S. R.; Lankenau, E.; Koch, P.; Birngruber, R.; Hüttmann, G.

2006-02-01

Optical coherence tomography (OCT) is a non-invasive imaging technique with a micrometer resolution. It allows non-contact / non-invasive analysis of central nervous system tissues with a penetration depth of 1-3,5 mm reaching a spatial resolution of approximately 4-15 μm. We have adapted spectral-domain OCT (SD-OCT) and time-domain OCT (TD-OCT) for intraoperative detection of residual tumor during brain tumor surgery. Human brain tumor tissue and areas of the resection cavity were analyzed during the resection of gliomas using this new technology. The site of analysis was registered using a neuronavigation system and biopsies were taken and submitted to routine histology. We have used post image acquisition processing to compensate for movements of the brain and to realign A-scan images for calculation of a light attenuation factor. OCT imaging of normal cortex and white matter showed a typical light attenuation profile. Tumor tissue depending on the cellularity of the specimen showed a loss of the normal light attenuation profile resulting in altered light attenuation coefficients compared to normal brain. Based on this parameter and the microstructure of the tumor tissue, which was entirely absent in normal tissue, OCT analysis allowed the discrimination of normal brain tissue, invaded brain, solid tumor tissue, and necrosis. Following macroscopically complete resections OCT analysis of the resection cavity displayed the typical microstructure and light attenuation profile of tumor tissue in some specimens, which in routine histology contained microscopic residual tumor tissue. We have demonstrated that this technology may be applied to the intraoperative detection of residual tumor during resection of human gliomas.

Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna

The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

Autofluorescence of normal and neoplastic human brain tissue: an aid for intraoperative delineation of tumor resection margins

NASA Astrophysics Data System (ADS)

Bottiroli, Giovanni F.; Croce, Anna C.; Locatelli, Donata; Nano, Rosanna; Giombelli, Ermanno; Messina, Alberto; Benericetti, Eugenio

1998-01-01

Light-induced autofluorescence measurements were made on normal and tumor brain tissues to assess their spectroscopic properties and to verify the potential of this parameter for an intraoperative delineation of tumor resection margins. Spectrofluorometric analysis was performed both at the microscope on tissue sections from surgical resection, and on patients affected by glioblastoma, during surgical operation. Significant differences in autofluorescence emission properties were found between normal and tumor tissues in both ex vivo and in vivo measurements, indicating that the lesion can be distinguished from the informal surrounding tissues by the signal amplitude and the spectral shape. The non-invasiveness of the technique opens interesting prospects for improving the efficacy of neurosurgical operation, by allowing an intraoperative delimitation of tumor resection margins.

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

PubMed Central

Khalifa, Hesham A.; Al-Quraishy, Saleh A.

2017-01-01

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

Reconstitution of full‐thickness skin by microcolumn grafting

PubMed Central

Wang, Ying; Vuong, Linh N.; Fisher, Jeremy M.; Farinelli, William A.; Anderson, R. Rox

2016-01-01

Abstract In addition to providing a physical barrier, skin also serves a diverse range of physiological functions through different specialized resident cell types/structures, including melanocytes (pigmentation and protection against ultraviolet radiation), Langerhans cells (adaptive immunity), fibroblasts (maintaining extracellular matrix, paracrine regulation of keratinocytes), sweat glands (thermoregulation) and hair follicles (hair growth, sensation and a stem cell reservoir). Restoration of these functional elements has been a long‐standing challenge in efforts to engineer skin tissue, while autologous skin grafting is limited by the scarcity of donor site skin and morbidity caused by skin harvesting. We demonstrate an alternative approach of harvesting and then implanting μm‐scale, full‐thickness columns of human skin tissue, which can be removed from a donor site with minimal morbidity and no scarring. Fresh human skin microcolumns were used to reconstitute skin in wounds on immunodeficient mice. The restored skin recapitulated many key features of normal human skin tissue, including epidermal architecture, diverse skin cell populations, adnexal structures and sweat production in response to cholinergic stimulation. These promising preclinical results suggest that harvesting and grafting of microcolumns may be useful for reconstituting fully functional skin in human wounds, without donor site morbidity. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. PMID:27296503

Cell wars: regulation of cell survival and proliferation by cell competition

PubMed Central

Vivarelli, Silvia; Wagstaff, Laura; Piddini, Eugenia

2012-01-01

During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels. Many of the pathways implicated in cell competition have been previously linked with cancer, and this has led to the hypothesis that cell competition could play a role in tumour formation. Cell competition could be co-opted by cancer cells to kill surrounding normal cells and boost their own tissue colonization. However, in some cases, cell competition could have a tumour suppressor role, as cells harbouring mutations in a subset of tumour suppressor genes are killed by wild-type cells. Originally described in developing epithelia, competitive interactions have also been observed in some stem cell niches, where they play a role in regulating stem cell selection, maintenance and tissue repopulation. Thus competitive interactions could be relevant to the maintenance of tissue fitness and have a protective role against aging. PMID:22928509

Effects of Pistacia Atlantica Extract on Erythrocyte Membrane Rigidity, Oxidative Stress, and Hepatotoxicity Induced by CCl4 in Rats

PubMed Central

Tolooei, Mohsen; Mirzaei, Ali

2015-01-01

Background: Previous findings have suggested that antioxidants may reduce the levels of free radicals, which induce oxidative damage and play a key role in various diseases. Thus, we evaluated the protective activity of a Pistacia atlantica extract on erythrocyte membrane rigidity, oxidative stress, and hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. Materials and Methods: Fresh leaves of P. atlantica were collected from the mountains in Yasuj, Iran. Acute oral toxicity (LD50) was evaluated in Wistar rats (200–230 g). Animals were randomly divided into 4 groups, out of which the negative and plant control groups received distilled water and P. atlantica extracts (500 mg/kg), respectively. The toxic rat group received CCl4, while the treatment group received CCl4 + P. atlantica extract. Blood plasma was utilized for the estimation of enzyme markers and lipid peroxidation, whereas hemolysate was applied for the determination of superoxide dismutase (SOD) and catalase activities. The levels of cholesterol and phospholipids in erythrocyte membranes were also determined. Rats were killed under anesthesia by cervical dislocation; liver was isolated from each rat and tissues homogenization was prepared for biochemical parameters such as malondialdehyde (MDA) and reduced glutathione (GSH) levels. Results: LD50 values were determined for doses >3000 mg/kg (p.o.). The activities of glutamic pyruvate transaminase (GPT), glutamic oxaloacetate transaminase (GOT), alkaline phosphatase (ALP) and GSH in the protected group were significantly (p < 0.001) reduced compared with those of toxic rats. In addition, we observed a decrease in the cholesterol level and an increase in red blood cell membrane phospholipids, SOD, and catalase activities (p < 0.001) in the protected group, as compared with toxic rats. Administration of Pistacia atlantica extract normalized liver tissue MDA level (p < 0. 01) when compared to CCl4 treated group. Conclusion: The P. atlantica extract was able to normalize the levels of biochemical markers, including liver enzyme markers, first-line defense enzymes, and lipid peroxidation markers. PMID:26153201

Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

2013-01-01

The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

SWIR dispersive Raman spectroscopy for discrimination of normal and malignant kidney tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Haifler, Miki; Pence, Isaac J.; Zisman, Amnon; Uzzo, Robert G.; Greenberg, Richard; Kutikov, Alexander; Smaldone, Marc; Chen, David; Viterbo, Rosalia; Ristau, Benjamin; Mahadevan-Jansen, Anita; Dumont, Alexander; Patil, Chetan A.

2017-02-01

Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

Anti-Fas Antibody Conjugated Nanoparticles Enhancing the Antitumor Effect of Camptothecin by Activating the Fas-FasL Apoptotic Pathway.

PubMed

Yu, Hongliang; He, Jian; Lu, Qian; Huo, Da; Yuan, Shanmei; Zhou, Zhengyang; Xu, Peipei; Hu, Yong

2016-11-09

Emerging evidence suggest that the introduction of Fas ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL-based therapeutic strategies. Herein, smart nanoparticles (NPs) with a sandwich structure were fabricated. These NPs consist of a matrix metalloproteinase (MMP) cleavable PEG outer layer, an anti-Fas antibody middle layer, and a camptothecin (CPT)-loaded inner core. They could accumulate at a tumor site by the enhanced permeability and retention (EPR) effect. The removable PEG layer protects the cytotoxic anti-Fas antibody from premature contact with normal tissues, thus avoiding the unexpected lethal side effect before they reach the tumor site. Due to the high level of MMP expressed by tumor cells inside the tumor tissue, these NPs would shed their PEG layers, resulting in the exposure of anti-Fas antibody to bind the Fas receptor and triggering the apoptosis of tumor cells. Results of Western blot confirmed that these NPs could mimic the function of activated cytotoxic lymphocyte (CTL) to activate the Fas-FasL apoptosis pathway of tumor cells. With the aid of CPT payload, these anti-Fas antibody conjugated NPs achieved a high tumor inhibition in the B16 allograft tumor animal model. The design of these NPs provides a method for delivering cytotoxic ligand to targeting tissue, which may be valuable in cancer therapy.

Calcineurin Regulates Myocardial Function during Acute Endotoxemia

PubMed Central

Joshi, Mandar S.; Julian, Mark W.; Huff, Jennifer E.; Bauer, John A.; Xia, Yong; Crouser, Elliott D.

2006-01-01

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia. PMID:16424445

[Normal and pathological elastic tissue under the electron microscope on thin and ultrathin sections (author's transl)].

PubMed

Adnet, J J; Pinteaux, A; Pousse, G; Caulet, T

1976-04-01

Three simple methods (adapted from optical techniques) for normal and pathological elastic tissue caracterisation in electron microscopy on thin and ultrathin sections are proposed. Two of these methods (orcein and fuchsin resorcin) seem to have a specificity for arterial and breast cancer elastic tissue. Weigert's method gives the best contrast.

Radioprotective Role in Lung of the Flaxseed Lignan Complex Enriched in the Phenolic Secoisolariciresinol Diglucoside (SDG)

PubMed Central

Christofidou-Solomidou, Melpo; Tyagi, Sonia; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Turowski, Jason; Grieshaber, Philip A.; Solomides, Charalambos C.; Cengel, Keith A.

2012-01-01

While dietary wholegrain Flaxseed (FS) has potent anti-inflammatory, anti-fibrotic and antioxidant properties in murine models of acute and chronic lung injury, the main bioactive ingredient that contributes to these protective effects remains unknown. This study evaluated the lignan complex of FS (FLC) enriched in secoisolariciresinol diglucoside with respect to lung radioprotective and tumor radiosensitizing efficacy using a mouse model of thoracic radiation-induced pneumonopathy. C57/Bl6 mice were fed 0% FS, 10% FS, 10% FLC or 20% FLC for 3 weeks, then irradiated with a single fraction (13.5 Gy) of X-ray radiation treatment (XRT). Mouse survival was monitored for 4 months after irradiation and inflammatory lung parameters were evaluated in bronchoalveolar lavage (BAL) fluid. Gene and protein levels of protective antioxidant and phase II enzymes were evaluated in lung tissue using qPCR and protein levels were verified by immunoblotting. Prolonged administration of the FLC diet was well tolerated and was not associated with any toxicity. Importantly, comparable to the whole grain 10% FS diet, irradiated mice fed 10% and 20% FLC diets displayed improved survival. Improved hemodynamic measurements were also recorded in irradiated mice fed 10% FS or 10% FLC diet compared to irradiated 0% FS fed mice. Flaxseed lignan complex diet also attenuated polymorphonuclear infiltration and overall lung inflammation to levels comparable to those in nonirradiated mice. Flaxseed lignan complex, similarly to FS, up-regulated gene expression as well as protein levels of protective antioxidant enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Dietary FLC induced radiosensitizing effects in our murine model of metastatic lung cancer. Importantly, protection of normal tissue does not thwart tumor cell death by radiation treatment. The dietary lignan complex of FS, mainly consisting of the phenolic secoisolariciresinol, is protective against radiation pneumonopathy in vivo while not hindering the tumoricidal effects of radiotherapy. PMID:23106213

Radioprotective role in lung of the flaxseed lignan complex enriched in the phenolic secoisolariciresinol diglucoside (SDG).

PubMed

Christofidou-Solomidou, Melpo; Tyagi, Sonia; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Turowski, Jason; Grieshaber, Philip A; Solomides, Charalambos C; Cengel, Keith A

2012-12-01

While dietary wholegrain Flaxseed (FS) has potent anti-inflammatory, anti-fibrotic and antioxidant properties in murine models of acute and chronic lung injury, the main bioactive ingredient that contributes to these protective effects remains unknown. This study evaluated the lignan complex of FS (FLC) enriched in secoisolariciresinol diglucoside with respect to lung radioprotective and tumor radiosensitizing efficacy using a mouse model of thoracic radiation-induced pneumonopathy. C57/Bl6 mice were fed 0% FS, 10% FS, 10% FLC or 20% FLC for 3 weeks, then irradiated with a single fraction (13.5 Gy) of X-ray radiation treatment (XRT). Mouse survival was monitored for 4 months after irradiation and inflammatory lung parameters were evaluated in bronchoalveolar lavage (BAL) fluid. Gene and protein levels of protective antioxidant and phase II enzymes were evaluated in lung tissue using qPCR and protein levels were verified by immunoblotting. Prolonged administration of the FLC diet was well tolerated and was not associated with any toxicity. Importantly, comparable to the whole grain 10% FS diet, irradiated mice fed 10% and 20% FLC diets displayed improved survival. Improved hemodynamic measurements were also recorded in irradiated mice fed 10% FS or 10% FLC diet compared to irradiated 0% FS fed mice. Flaxseed lignan complex diet also attenuated polymorphonuclear infiltration and overall lung inflammation to levels comparable to those in nonirradiated mice. Flaxseed lignan complex, similarly to FS, up-regulated gene expression as well as protein levels of protective antioxidant enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Dietary FLC induced radiosensitizing effects in our murine model of metastatic lung cancer. Importantly, protection of normal tissue does not thwart tumor cell death by radiation treatment. The dietary lignan complex of FS, mainly consisting of the phenolic secoisolariciresinol, is protective against radiation pneumonopathy in vivo while not hindering the tumoricidal effects of radiotherapy.

Protection of chickens against infectious bronchitis by a recombinant fowlpox virus co-expressing IBV-S1 and chicken IFNgamma.

PubMed

Wang, Yun-Feng; Sun, Yong-Ke; Tian, Zhan-Cheng; Shi, Xing-Ming; Tong, Guang-Zhi; Liu, Sheng-Wang; Zhi, Hai-Dong; Kong, Xian-Gang; Wang, Mei

2009-11-23

A fowlpox virus expressing the chicken infectious bronchitis virus (IBV) S1 gene of the LX4 strain (rFPV-IBVS1) and a fowlpox virus co-expressing the S1 gene and the chicken type II interferon gene (rFPV-IBVS1-ChIFNgamma) were constructed. These viruses were assessed for their immunological efficacy on specific-pathogen-free (SPF) chickens challenged with a virulent IBV. Although the antibody levels in the rFPV-IBVS1-ChIFNgamma-vaccinated group were lower than those in the attenuated live IB vaccine H120 group and the rFPV-IBVS1 group, the rFPV-IBVS1-ChIFNgamma provided the strongest protection against an IBV LX4 virus challenge (15 out of 16 chickens immunized with rFPV-IBVS1-ChIFNgamma were protected), followed by the attenuated live IB vaccine (13/16 protected) and the rFPV-IBVS1 (12/16 protected). Compared to those of the rFPV-IBVS1 and the attenuated live IB vaccine groups, chickens in the rFPV-IBVS1-ChIFNgamma group eliminated virus more quickly and decreased the presence of viral antigen more significantly in renal tissue. Examination of affected tissues revealed abnormalities in the liver, spleen, kidney, lung and trachea of chickens vaccinated with the attenuated live IB vaccine and the rFPV-IBVS1 vaccine. In rFPV-IBVS1-ChIFNgamma-vaccinated chickens, pathological changes were also observed in those organs, but were milder and lasted shorter. The lesions in the mock control group were the most severe and lasted for at least 20 days. This study demonstrated that chicken type II interferon increased the immunoprotective efficacy of rFPV-IBVS1-ChIFNgamma and normal weight gain in vaccinated chickens although it inhibited serum antibody production.

Biophysical interpretation and ex-vivo characterization of scattered light from tumor-associated breast stroma

NASA Astrophysics Data System (ADS)

Laughney, Ashley; Krishnaswamy, Venkat; Schwab, Mary; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.

2009-02-01

The purpose of this study was to extract scatter parameters related to tissue ultra-structures from freshly excised breast tissue and to assess whether evident changes in scatter across diagnostic categories is primarily influenced by variation in the composition of each tissues subtypes or by physical remodeling of the extra-cellular environment. Pathologists easily distinguish between epithelium, stroma and adipose tissues, so this classification was adopted for macroscopic subtype classification. Micro-sampling reflectance spectroscopy was used to characterize single-backscattered photons from fresh, excised tumors and normal reduction specimens with sub-millimeter resolution. Phase contrast microscopy (sub-micron resolution) was used to characterize forward-scattered light through frozen tissue from the DHMC Tissue Bank, representing normal, benign and malignant breast tissue, sectioned at 10 microns. The packing density and orientation of collagen fibers in the extracellular matrix (ECM) associated with invasive, normal and benign epithelium was evaluated using transmission electron microscopy (TEM). Regions of interest (ROIs) in the H&E stained tissues were identified for analysis, as outlined by a pathologist as the gold standard. We conclude that the scatter parameters associated with tumor specimens (Npatients=6, Nspecimens=13) significantly differs from that of normal reductions (Npatients=6, Nspecimens=10). Further, tissue subtypes may be identified by their scatter spectra at sub-micron resolution. Stromal tissue scatters significantly more than the epithelial cells embedded in its ECM and adipose tissue scatters much less. However, the scatter signature of the stroma at the sub-micron level is not particularly differentiating in terms of a diagnosis.

Signs of antimetastatic activity of palladium complexes of methylenediphosphonic acid in IR spectra

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Pekhnio, V. I.; Kozachkova, A. N.; Sharykina, N. I.

2012-07-01

We have used Fourier transform IR spectroscopy methods to study normal mouse lung tissue and also after subcutaneous transplantation of a B-16 melanoma tumor in the tissue. We also studied tissues with B-16 melanoma after they were treated with coordination compounds based on palladium complexes of methylenediphosphonic acid. The IR spectra of the lung tissues with metastases in the region of the C = O stretching vibrations are different from the IR spectra of normal tissue. We identified spectroscopic signs of the presence of metastases in the lung. We show that when a cancerous tumor is treated with a preparation of palladium complexes of methylenediphosphonic acid, the spectroscopic signs of the presence of metastases in the lung are missing. After treatment with the optimal dose of this drug, the IR spectrum of the lung tissue in which multiple metastases were present before treatment corresponds to the spectrum of normal tissue. We have determined the efficacy of the antitumor activity of coordination compounds based on palladium complexes of methylenediphosphonic acid.

The diagnostic capability of laser induced fluorescence in the characterization of excised breast tissues

NASA Astrophysics Data System (ADS)

Galmed, A. H.; Elshemey, Wael M.

2017-08-01

Differentiating between normal, benign and malignant excised breast tissues is one of the major worldwide challenges that need a quantitative, fast and reliable technique in order to avoid personal errors in diagnosis. Laser induced fluorescence (LIF) is a promising technique that has been applied for the characterization of biological tissues including breast tissue. Unfortunately, only few studies have adopted a quantitative approach that can be directly applied for breast tissue characterization. This work provides a quantitative means for such characterization via introduction of several LIF characterization parameters and determining the diagnostic accuracy of each parameter in the differentiation between normal, benign and malignant excised breast tissues. Extensive analysis on 41 lyophilized breast samples using scatter diagrams, cut-off values, diagnostic indices and receiver operating characteristic (ROC) curves, shows that some spectral parameters (peak height and area under the peak) are superior for characterization of normal, benign and malignant breast tissues with high sensitivity (up to 0.91), specificity (up to 0.91) and accuracy ranking (highly accurate).

Epoxyeicosanoids promote organ and tissue regeneration.

PubMed

Panigrahy, Dipak; Kalish, Brian T; Huang, Sui; Bielenberg, Diane R; Le, Hau D; Yang, Jun; Edin, Matthew L; Lee, Craig R; Benny, Ofra; Mudge, Dayna K; Butterfield, Catherine E; Mammoto, Akiko; Mammoto, Tadanori; Inceoglu, Bora; Jenkins, Roger L; Simpson, Mary A; Akino, Tomoshige; Lih, Fred B; Tomer, Kenneth B; Ingber, Donald E; Hammock, Bruce D; Falck, John R; Manthati, Vijaya L; Kaipainen, Arja; D'Amore, Patricia A; Puder, Mark; Zeldin, Darryl C; Kieran, Mark W

2013-08-13

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

Expression of the cytoskeleton regulatory protein Mena in human gastric carcinoma and its prognostic significance

PubMed Central

Xu, Lihua; Tan, Huo; Liu, Ruiming; Huang, Qungai; Zhang, Nana; Li, Xi; Wang, Jiani

2017-01-01

The cytoskeleton regulatory protein Mena is reportedly overexpressed in breast cancer; however, data regarding its expression level and clinical significance in gastric carcinoma (GC) is limited. The aim of the present study was to investigate Mena expression levels and prognostic significance in GC. Mena mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction in 10 paired GC and adjacent normal tissues. The Mena protein expression level was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. Statistical analyses were also performed to evaluate the clinicopathological significance of Mena. The results revealed that the mRNA expression level of Mena was significantly higher in G Ct issues compared with in adjacent normal tissues from10 paired samples. In the paraffin-embedded tissue samples, the protein expression level of Mena was higher in G Ct issues compared with in adjacent normal tissues. Compared with adjacent normal tissues, Mena overexpression was observed in 52.83% (56/106) of patients. The overexpression of Mena was significantly associated with the T stage (P=0.033), tumor-node-metastasis (TNM) stage (P<0.001) and decreased overall survival (P<0.001). Based on a multivariate analysis, Mena expression level was an independent prognostic factor for overall survival time. In conclusion, Mena wasoverexpressed in G C tissues and significantly associated with the T stage, TNM stage and overall survival time. Mena may therefore be suitable as a prognostic indicator for patients with GC. PMID:29113241

Expression of the cytoskeleton regulatory protein Mena in human gastric carcinoma and its prognostic significance.

PubMed

Xu, Lihua; Tan, Huo; Liu, Ruiming; Huang, Qungai; Zhang, Nana; Li, Xi; Wang, Jiani

2017-11-01

The cytoskeleton regulatory protein Mena is reportedly overexpressed in breast cancer; however, data regarding its expression level and clinical significance in gastric carcinoma (GC) is limited. The aim of the present study was to investigate Mena expression levels and prognostic significance in GC. Mena mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction in 10 paired GC and adjacent normal tissues. The Mena protein expression level was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. Statistical analyses were also performed to evaluate the clinicopathological significance of Mena. The results revealed that the mRNA expression level of Mena was significantly higher in G Ct issues compared with in adjacent normal tissues from10 paired samples. In the paraffin-embedded tissue samples, the protein expression level of Mena was higher in G Ct issues compared with in adjacent normal tissues. Compared with adjacent normal tissues, Mena overexpression was observed in 52.83% (56/106) of patients. The overexpression of Mena was significantly associated with the T stage (P=0.033), tumor-node-metastasis (TNM) stage (P<0.001) and decreased overall survival (P<0.001). Based on a multivariate analysis, Mena expression level was an independent prognostic factor for overall survival time. In conclusion, Mena wasoverexpressed in G C tissues and significantly associated with the T stage, TNM stage and overall survival time. Mena may therefore be suitable as a prognostic indicator for patients with GC.

Ameliorating effects of dexpanthenol in cerebral ischaemia reperfusion induced injury in rat brain.

PubMed

Zakaria, Mohammad Mehdi Hosseinian; Hajipour, Babak; Khodadadi, Ali; Afshari, Fatemeh

2011-09-01

To study the attenuating effect of Dexpanthenol (Dxp) provitamin B5 on neuronal damage after cerebral ischaemia/reperfusion. This was a randomized, controlled experimental study conducted at the Islamic Azad University, Tabriz, Iran, from April to September 2008. Male wistar rats were divided into 4 groups randomly (n=13): 1- sham group, Group 2 :two hours occlusion of middle cerebral artery (MCA) and 24 hours reperfusion. Group 3: two hours occlusion of MCA and 24 hours reperfusion + Dxp (250mg/kg) since 3 days before ischaemia. Group 4: two hours occlusion of MCA and 24 hours reperfusion which had received Dxp (500mg/kg) since 3 days before ischaemia. Glutathione (GSH) and malondialdehyde (MDA) levels were studied in brain tissue and numbers of cornu ammonis (CA1 and CA3) pyramidal neurons were studied with light microscopy. The GSH levels were significantly higher in groups 3 and 4 as compared with group 2. In group 3 and group 4 animals, the MDA levels were significantly lower than in group 2 (P < 0.05). Numbers of CA1 and CA3 neurons were completely normal in appearance in the group 1. The surviving neurons in the CA1 and CA3 subfield were markedly decreased in number, in group 2 (P < 0.05). Our pathologic and biochemical study has proven positive effect of Dxp on protection of cerebral tissue after I/R. The present findings correlate with previous studies on the protective effects of Dxp against cell and tissue injury by I/R.

Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced neuronal apoptosis

PubMed Central

CANTRES-ROSARIO, Yisel M.; HERNANDEZ, Natalia; NEGRON, Karla; PEREZ-LASPIUR, Juliana; LESZYK, John; SHAFFER, Scott A.; MELENDEZ, Loyda M.

2015-01-01

Objective HIV-1 infection of macrophages increases cathepsin B secretion and induces neuronal apoptosis, but the molecular mechanism remains unclear. Design We identified macrophage secreted cathepsin B protein interactions extracellularly and their contribution to neuronal death in vitro. Methods Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernatants after 12 days post-infection. The cathepsin B interactome was quantified by label-free tandem mass spectrometry and compared to uninfected supernatants. Proteins identified were validated by western blot. Neurons were exposed to macrophage-conditioned media in presence or absence of antibodies against cathepsin B and interacting proteins. Apoptosis was measured using TUNEL labeling. Immunohistochemistry of post-mortem brain tissue samples from healthy, HIV-infected, and Alzheimer’s disease patients was performed to observe the ex vivo expression of the proteins identified. Results Nine proteins co-immunoprecipitated differentially with cathepsin B between uninfected and HIV-infected macrophages. Serum amyloid p component (SAPC) -cathepsin B interaction increased in HIV-infected macrophage supernatants, while matrix metalloprotease 9 (MMP-9) -cathepsin B interaction decreased. Pre-treatment of HIV-infected macrophage-conditioned media with antibodies against cathepsin B and SAPC decreased neuronal apoptosis. The addition of MMP-9 antibodies was not protective. SAPC was over-expressed in post-mortem brain tissue from HIV-positive neurocognitive impaired patients compared to HIV positive with normal cognition and healthy controls, while MMP-9 expression was similar in all tissues. Conclusions Inhibiting SAPC-cathepsin B interaction protects against HIV–induced neuronal death and may help to find alternative treatments for HIV-associated neurocognitive disorders. PMID:26208400

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Neural stem cells rescue nervous purkinje neurons by restoring molecular homeostasis of tissue plasminogen activator and downstream targets.

PubMed

Li, Jianxue; Imitola, Jaime; Snyder, Evan Y; Sidman, Richard L

2006-07-26

Neural stem cells (NSCs) offer special therapeutic prospects because they can be isolated from the CNS, expanded ex vivo, and re-implanted into diseased CNS where they not only migrate and differentiate according to cues from host tissue but also appear to be capable of affecting host cells. In nervous (nr) mutant mice Purkinje neuron (PN) mitochondria become abnormal by the second postnatal week, and a majority of PNs die in the fourth to fifth weeks. We previously identified in nr cerebellum a 10-fold increase in tissue plasminogen activator (tPA) as a key component of the mechanism causing nr PN death. Here we report that undifferentiated wild-type murine NSCs, when transplanted into the newborn nr cerebellar cortex, do not replace host PNs but contact imperiled PNs and support their mitochondrial function, dendritic growth, and synaptogenesis, subsequently leading to the rescue of host PNs and restoration of motor coordination. This protection of nr PNs also is verified by an in vitro organotypic slice model in which nr cerebellar slices are cocultured with NSCs. Most importantly, the integrated NSCs in young nr cerebellum rectify excessive tPA mRNA and protein to close to normal levels and protect the mitochondrial voltage-dependent anion channel and neurotrophins, downstream targets of the tPA/plasmin proteolytic system. This report demonstrates for the first time that NSCs can rescue imperiled host neurons by rectifying their gene expression, elevating somatic stem cell therapeutic potential beyond solely cell replacement strategy.

Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

PubMed

Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

2017-07-10

The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value <0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

Evaluation of normal lung tissue complication probability in gated and conventional radiotherapy using the 4D XCAT digital phantom.

PubMed

Shahzadeh, Sara; Gholami, Somayeh; Aghamiri, Seyed Mahmood Reza; Mahani, Hojjat; Nabavi, Mansoure; Kalantari, Faraz

2018-06-01

The present study was conducted to investigate normal lung tissue complication probability in gated and conventional radiotherapy (RT) as a function of diaphragm motion, lesion size, and its location using 4D-XCAT digital phantom in a simulation study. Different time series of 3D-CT images were generated using the 4D-XCAT digital phantom. The binary data obtained from this phantom were then converted to the digital imaging and communication in medicine (DICOM) format using an in-house MATLAB-based program to be compatible with our treatment planning system (TPS). The 3D-TPS with superposition computational algorithm was used to generate conventional and gated plans. Treatment plans were generated for 36 different XCAT phantom configurations. These included four diaphragm motions of 20, 25, 30 and 35 mm, three lesion sizes of 3, 4, and 5 cm in diameter and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe and left upper lobe). The complication of normal lung tissue was assessed in terms of mean lung dose (MLD), the lung volume receiving ≥20 Gy (V20), and normal tissue complication probability (NTCP). The results showed that the gated RT yields superior outcomes in terms of normal tissue complication compared to the conventional RT. For all cases, the gated radiation therapy technique reduced the mean dose, V20, and NTCP of lung tissue by up to 5.53 Gy, 13.38%, and 23.89%, respectively. The results of this study showed that the gated RT provides significant advantages in terms of the normal lung tissue complication, compared to the conventional RT, especially for the lesions near the diaphragm. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

PubMed Central

Radovich, Milan; Clare, Susan E.; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A.; Solzak, Jeffrey P.; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V.; Rufenbarger, Connie; Lillemoe, Heather A.; Blosser, Rachel J.; Choi, Mi Ran; Sauder, Candice A.; Doxey, Diane; Henry, Jill E.; Hilligoss, Eric E.; Sakarya, Onur; Hyland, Fiona C.; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W.; Schneider, Bryan P.

2014-01-01

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER−,PR−,HER2−). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90% of TNBCs revealing an over-expressed central network. In conclusion, Use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos. PMID:24292813

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

PubMed

Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

2014-01-01

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

MR elastographic methods for the evaluation of plantar fat pads: preliminary comparison of the shear modulus for shearing deformation and compressive deformation in normal subjects

NASA Astrophysics Data System (ADS)

Weaver, John B.; Miller, Timothy B.; Perrinez, Philip R.; Doyley, Marvin M.; Wang, Huifang; Cheung, Yvonne Y.; Wrobel, James S.; Comi, Richard J.; Kennedy, Francis E.; Paulsen, Keith D.

2006-03-01

MR elastography (MRE) images the intrinsic mechanical properties of soft tissues; e.g., the shear modulus, μ. The μ of the plantar soft tissues is important in understanding the mechanisms whereby the forces induced during normal motion produce ulcers that lead to amputation in diabetic feet. We compared the compliance of the heel fat pad to compressive forces and to shearing forces. The design of prosthetics to protect the foot depends on the proper understanding of the mechanisms inducing damage. In the heel fat pads of six normal subjects, between 25 and 65 years of age, the μ for deformation perpendicular to the direction of weight bearing is similar but not identical to that determined for deformation along the weight bearing axis. The average difference between μ along the weight bearing axis and μ perpendicular to the weight bearing axis, is well correlated with age (Correlation Coefficient = 0.789). The p-value for the data being random was 0.0347 indicating that the observed difference is not likely to be random. The p-value for control points is 0.8989, indicating a random process. The results are suggestive that the high compressive forces imposed during walking damage the heel fat pads over time resulting in softening to compression preferentially over shearing. It is important to validate the observed effect with larger numbers of subjects, and better controls including measures of activity, and to understand if diseases like diabetes increase the observed damage.

The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

NASA Astrophysics Data System (ADS)

Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

2015-04-01

Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

Malignant Transformation and Stromal Invasion from Normal or Hyperplastic Tissues: True or False?

PubMed Central

Man, Yan-gao; Grinkemeyer, Michael; Izadjoo, Mina; Stojadinovic, Alexander

2011-01-01

Carcinogenesis is believed to be a multi-step process, progressing sequentially from normal to hyperplastic, to in situ, and to invasive stages. A number of studies, however, have detected malignancy-associated alterations in normal or hyperplastic tissues. As the molecular profile and clinical features of these tissues have not been defined, the authors invited several well-recognized pathologist, oncologists, biologist, surgeons, and molecular biologist to offer their opinion on: (1) whether these tissues belong to a previously unrevealed malignant entity or focal alterations with no significant consequence? (2) whether these alterations are linked to early onset of cancer or cancer of unknown primary site, and (3) how to further define these lesions? PMID:21811519

It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barcellos-Hoff, Mary Helen

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises itsmore » ability to suppress carcinogenesis.« less

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu; Barthold, H. Joseph; Beth Israel Deaconess Medical Center, Boston, MA

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The followingmore » were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.« less

Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma.

PubMed

Morales, Angélica; Vilchis, Felipe; Chávez, Bertha; Chan, Carlos; Robles-Díaz, Guillermo; Díaz-Sánchez, Vicente

2007-10-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) was recently identified as the first tissue-specific angiogenic molecule. EG-VEGF (the gene product of PROK-1) appears to be expressed exclusively in steroid-producing organs such as the ovary, testis, adrenals and placenta. Since the human pancreatic cells retain steroidogenic activity, in the present study we ascertained whether this angiogenic factor is expressed in normal pancreas and pancreatic adenocarcinoma. Tissue samples from normal males (n=5), normal females (n=5) and from surgically resected adenocarcinomas (n=2) were processed for RT-PCR and immunohistochemical studies. Results from semi-quantitative analysis by RT-PCR suggest a distinct expression level for EG-VEGF in the different tissue samples. The relative amount of EG-VEGF mRNA in pancreas was more abundant in female adenocarcinoma (0.89) followed by male adenocarcinoma (0.71), than normal female (0.64) and normal male (0.38). The expression of mRNA for EG-VEGF in normal tissue was significantly higher in females than in males. All samples examined showed specific immunostaining for EG-VEGF. In male preparations, the positive labeling was localized predominantly within the pancreatic islets while in female preparations the main staining was detected towards the exocrine portion. Specific immunolabeling was also observed in endothelial cells of pancreatic blood vessels. Our data provide evidence that the human pancreas expresses the EG-VEGF, a highly specific mitogen which regulates proliferation and differentiation of the vascular endothelium. The significance of this finding could be interpreted as either, EG-VEGF is not exclusive of endocrine organs, or the pancreas should be considered as a functional steroidogenic tissue. The extent of the expression of EG-VEGF appears to have a dimorphic pattern in normal and tumoral pancreatic tissue.

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats.

PubMed

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats

PubMed Central

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Background and purpose Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier. PMID:28144140

Study of gastric cancer samples using terahertz techniques

NASA Astrophysics Data System (ADS)

Wahaia, Faustino; Kasalynas, Irmantas; Seliuta, Dalius; Molis, Gediminas; Urbanowicz, Andrzej; Carvalho Silva, Catia D.; Carneiro, Fatima; Valusis, Gintaras; Granja, Pedro L.

2014-08-01

In the present work, samples of healthy and adenocarcinoma-affected human gastric tissue were analyzed using transmission time-domain THz spectroscopy (THz-TDS) and spectroscopic THz imaging at 201 and 590 GHz. The work shows that it is possible to distinguish between normal and cancerous regions in dried and paraffin-embedded samples. Plots of absorption coefficient α and refractive index n of normal and cancer affected tissues, as well as 2-D transmission THz images are presented and the conditions for discrimination between normal and affected tissues are discussed.

[Expression and significance of tumor necrosis factor alpha, matrix metalloproteinase 2 and collagen in skin tissue of pressure ulcer of rats].

PubMed

Wang, X H; Mao, T T; Pan, Y Y; Xie, H H; Zhang, H Y; Xiao, J; Jiang, L P

2016-03-01

To observe the expressions of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2) and collagen in local skin tissue of pressure ulcer of rats, and to explore the possible mechanism of the pathogenesis of pressure ulcer. Forty male SD rats were divided into normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group according to the random number table, with 8 rats in each group. The rats in normal control group did not receive any treatment, whereas the rats in the latter 4 groups were established the deep tissue injury model (3 d compression group) and pressure ulcer model (the other 3 groups) on the gracilis muscle on both hind limbs using a way of cycle compression of ischemia-reperfusion magnet. The rats in 3 d compression group received only three cycles of compression, while the compressed skin of the rats in 5 d compression group, 7 d compression group, and 9 d compression group were cut through and received pressure to 5, 7 and 9 cycles after three cycles of compression, respectively. The rats in 3 d compression group were sacrificed immediately after receiving compression for 3 d (the rats in normal control group were sacrificed at the same time), and the rats in the other 3 groups were respectively sacrificed after receiving compression for 5, 7, and 9 d, and the skin tissue on the central part of gracilis muscle on both hind limbs were harvested. The morphology of the skin tissue was observed with HE staining. The expression of collagen fiber was observed with Masson staining. The expressions of collagen type Ⅳ and MMP-2 were detected by immunohistochemical method. The expressions of TNF-α and phosphorylated NF kappa B (NF-κB) were determined by Western blotting. Data were processed with one-way analysis of variance and LSD test. (1) In normal control group, the skin tissue of rats was stratified squamous epithelium, with the clear skin structure, and there was no obvious infiltration of inflammatory cells. In 3 d compression group, the skin layers of rats were clear, with quite a few fibroblasts, and the inflammatory cells began to infiltrate. In 5 d compression group, 7 d compression group, and 9 d compression group, the epidermis of rats thickened, with the number of fibroblasts reduced, and the infiltration of inflammatory cells enhanced with the compressed time prolonging. (2) In normal control group, the collagen fibers in skin tissue of rats were arranged in order, with rich content. In 3 d compression group, the collagen fibers in skin tissue of rats were arranged orderly, with high expression level, which was similar to that in normal control group (P>0.05). In 5 d compression group and 7 d compression group, the collagen fibers in skin tissue of rats were arranged in disorder, with the expression level gradually reduced, which were significantly lower than that in normal control group (with P values below 0.01). In 9 d compression group, the expression of collagen fiber in skin tissue of rats was a little higher than that in 7 d compression group, but it was still significantly lower than that in normal control group (P<0.01). (3) The expressions of collagen type Ⅳ in skin tissue of rats in normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 11.0±2.8, 9.0±1.7, 8.3±2.8, 5.1±1.8, and 5.4±1.2. The expression of collagen type Ⅳ in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of collagen type Ⅳ in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly lower than that in normal control group (P<0.05 or P<0.01). The expression of MMP-2 in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of MMP-2 in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01). (4) The expression of TNF-α in skin tissue of rats in normal control group was 0.48±0.11, and the expressions of TNF-α in skin tissue of rats in 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 0.84±0.08, 1.13±0.19, 1.34±0.16, and 1.52±0.23, which were all significantly higher than that in normal control group (with P values below 0.01). The expressions of phosphorylated NF-κB in skin tissue of rats in 3 d compression group and 9 d compression group were similar to that in normal control group (with P values above 0.05), and the expressions of phosphorylated NF-κB in skin tissue of rats in 5 d compression group and 7 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01). The high expression of MMP-2 and reduction of collagen induced by inflammatory reaction mediated by the high expression of TNF-α in local skin tissue of pressure ulcer of rats may be one of the important reasons for the formation of pressure ulcer.

Fluorescence Spectroscopic Properties of Normal and Abnormal Biomedical Materials

NASA Astrophysics Data System (ADS)

Pradhan, Asima

Steady state and time-resolved optical spectroscopy and native fluorescence is used to study the physical and optical properties occurring in diseased and non-diseased biological human tissue, in particular, cancer of the human breast, artery and the dynamics of a photosensitizer useful in photodynamic therapy. The main focus of the research is on the optical properties of cancer and atherosclerotic tissues as compared to their normal counterparts using the different luminescence based spectroscopic techniques such as steady state fluorescence, time-resolved fluorescence, excitation spectroscopy and phosphorescence. The excitation and steady-state spectroscopic fluorescence using visible excitation wavelength displays a difference between normal and malignant tissues. This difference is attributed to absorption of the emission by hemoglobin in normal tissues. This method using 488nm fails to distinguish neoplastic tissue such as benign tissues and tumors from malignant tumors. The time-resolved fluorescence at visible, near -uv and uv excitation wavelengths display non-exponential profiles which are significantly different for malignant tumors as compared to non-malignant tissues only with uv excitation. The differences observed with visible and near-uv excitation wavelengths are not as significant. The non-exponential profiles are interpreted as due to a combination of fluorophores along with the action of non-radiative processes. Low temperature luminescence studies confirm the occurrence of non-radiative decay processes while temporal studies of various relevant biomolecules indicate the probable fluorophores responsible for the observed signal in tissues. Phosphorescence from human tissues have been observed for the first time and lifetimes of a few hundred nanoseconds are measured for malignant and benign tissues. Time-resolved fluorescence studies of normal artery and atherosclerotic plaque have shown that a combination of two excitation wavelengths can distinguish fibrous and calcified atherosclerotic plaque from normal artery. A minor effort of the study involves the high intensity effects on the optical properties of the dye, doxycycline (a particular photosensitizer of the tetracycline group) occurring during relaxation when excited at different laser intensities. This study has been performed by observing the fluorescence lifetimes and quantum yields of DOTC at different excitation intensities. The results obtained support the sequential excited state absorption model.

Fiber-probe optical spectroscopy discriminates normal brain from focal cortical dysplasia in pediatric subjects

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Conti, Valerio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

2017-02-01

Focal cortical dysplasia (FCD) is an abnormality in the cerebral cortex that is caused by malformations during cortical development. Currently, magnetic resonance imaging (MRI) and electro-corticography (ECoG) are used for detecting FCD. On the downside, MRI is very much insensitive to small malformations in the brain, while ECoG is an invasive and time consuming procedure. Recently, optical techniques were widely exploited as a minimally invasive and quantitative approaches for disease diagnosis. These techniques include fluorescence and Raman spectroscopy. The aim of this investigation is to study the diagnostic performances of optical spectroscopy incorporating fluorescence (at 378 nm and 445 nm excitation wavelengths) and Raman spectroscopy (at 785 nm excitation) for the discrimination of FCD from normal brain in pediatric subjects. The study included 10 normal and 17 FCD tissue sites from 3 normal and 7 FCD samples. The emission spectra of FCD at 378 nm excitation wavelength presented a blue-shifted peak with respect to normal tissue. Prominent spectral differences between normal and FCD tissue were observed at 1298 cm-1, 1302 cm-1, 1445 cm-1 and 1660 cm-1 using Raman spectroscopy. Tissue classification models were developed using a multivariate statistical method, principal component analysis. This study demonstrates that a combined spectroscopic approach can provide a better diagnostic capability for classifying normal and FCD tissues. Further, the implementation of the technology within a fiber probe could open the way for in vivo diagnostics and intra-operative surgical guidance.

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage.

PubMed

Caprodossi, Sara; Lucciarini, Roberta; Amantini, Consuelo; Nabissi, Massimo; Canesin, Giacomo; Ballarini, Patrizia; Di Spilimbergo, Adriana; Cardarelli, Marco Andrea; Servi, Lucilla; Mammana, Gabriele; Santoni, Giorgio

2008-09-01

To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.

Promoter methylation, mRNA expression of goat tumor‑associated genes and mRNA expression of DNA methyltransferase in enzootic nasal tumors.

PubMed

Quan, Zifang; Ye, Ni; Hao, Zhongxiang; Wen, Caifang; Liao, Hong; Zhang, Manli; Luo, Lu; Cao, Sanjie; Wen, Xintian; Wu, Rui; Yan, Qigui

2015-10-01

The aim of the present study was to investigate the promoter methylation status and mRNA expression of goat tumor‑associated genes, in addition to the mRNA expression of DNA methyltransferase genes in enzootic nasal tumors (ENT). Methylation‑specific polymerase chain reaction and SYBR Green reverse transcription‑quantitative polymerase chain reaction were used to detect the methylation status and the mRNA expression levels of DNA methyltransferases (DNMTs), O6‑methylguanine‑DNA methyltransferase (MGMT), the tumor suppressor genes P73, P53, GADD45G, CHFR and THBS1, the transcription factor CEBPA, the proto‑oncogenes KRAS, NRAS and C‑myc and EGFR in 24 nasal tumor tissue samples and 20 normal nasal epithelia tissue samples. The associations between promoter methylation and DNMT, and promoter methylation and mRNA expression of the genes were analyzed. The results indicated that the expression levels of DNMT1 increased by 56% compared with those in normal nasal epithelial tissues, while MGMT, DNMT3a and DNMT3b had similar expression levels in the two tissue types. The expression levels of P53 decreased by 36.8% and those of THBS1 by 43%, while C‑myc increased by 2.9‑fold and CEBPA by 2‑fold compared with that in normal nasal epithelial tissues. GADD45G, P73, CHFR and NRAS were observed to have similar expression levels in the two tissue types. However, no expression was observed for EGFR and KRAS. CHFR, GADD45G and THBS1 were identified to be methylated in tumor suppressor genes. The methylation expression rate of the CHFR gene was ~60% in the two tissue types and for THBS1 it was 100% in the nasal tumor tissues as opposed to 20% in the normal nasal epithelial tissues. The exhaustive methylation expression rate of GADD45G was 62.5% and the partial methylation expression rate was 37.5% in nasal tumor tissue, while no methylation was observed in normal nasal epithelial tissues. C‑myc was the only gene identified to be methylated amongst proto‑oncogenes. The methylation expression rate of C‑myc was 87.5% in nasal tumor tissues and 15% in normal nasal epithelial tissues. The methylation expression rate of CEBPA was 100% in nasal tumor tissues and 40% in normal nasal epithelial tissues. The methylation expression rate of the EGFR gene was ~80% in the two tissues. In summary, the present study identified abnormal methylation of the C‑myc, CEBPA, GADD45G and THBS1 genes in nasal tumor tissues. The expression levels of DNMT1, C‑myc and CEBPA were upregulated and the expression of P53 and THBSI were downregulated in nasal tumor tissues, with a significant difference between the two groups (P<0.05). Therefore, it is suggested that these six genes may be used as diagnostic marker candidates for ENT. The results may serve as a foundation for screening of tumor‑specific markers for early diagnosis of ENT and further investigate the epigenetic mechanisms of enzootic nasal tumor virus (ENTV)‑induced nasal epithelium cell carcinoma.

Spectroscopic analysis of normal and neoplastic (WI-FTC) thyroid tissue.

PubMed

Depciuch, Joanna; Stanek-Widera, Agata; Lange, Dariusz; Biskup-Frużyńska, Magdalena; Stanek-Tarkowska, Jadwiga; Czarny, Wojciech; Cebulski, Jozef

2018-06-07

Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is β-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate. Copyright © 2018. Published by Elsevier B.V.

Lipoprotein lipase activity in surgical patients: influence of trauma and infection.

PubMed

Robin, A P; Askanazi, J; Greenwood, M R; Carpentier, Y A; Gump, F E; Kinney, J M

1981-08-01

Hypertriglyceridemia commonly accompanies clinical sepsis and may be caused by increased hepatic production or decreased clearance of triglyceride from the bloodstream. In contrast, enhanced lipid clearing capacity is usually seen after uncomplicated trauma. The purpose of the study was to determine the role of lipoprotein lipase (LPL) in effecting the above changes. Enzyme activity was assayed in skeletal muscle and adipose tissue biopsy samples from 11 normal subjects and from 17 injured and 11 infected surgical patients. Normal subjects after 4 days of 5% dextrose infusion (D5) showed a significant decrease in adipose tissue LPL activity but no change in skeletal muscle activity. Trauma patients after several days of D5 had higher activity in adipose tissue and higher plasma insulin levels than diet-matched control subjects but showed no change in skeletal muscle activity. Infected patients with high plasma triglyceride levels had significantly decreased LPL activity in both tissues. A linear relationship was found between insulin concentration and adipose tissue LPL activity in normal subjects. We conclude that: (1) low tissue LPL activity in sepsis may result in diminished lipid clearance and contribute to hypertriglyceridemia, (2) after trauma, changes in tissue LPL activity as well as other factors such as altered hemodynamics play a role in determining in vivo lipid clearance, and (3) adipose tissue LPL activity is related to the plasma insulin concentration in normal subjects.

Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder.

PubMed

Legan, Mateja; Tevžič, Spela; Tolar, Ana; Luzar, Boštjan; Marolt, Vera Ferlan

2011-03-01

GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.

Electrical impedance characterization of normal and cancerous human hepatic tissue.

PubMed

Laufer, Shlomi; Ivorra, Antoni; Reuter, Victor E; Rubinsky, Boris; Solomon, Stephen B

2010-07-01

The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m(-1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation.

Value of in vitro acoustic radiation force impulse application on uterine adenomyosis.

PubMed

Bildaci, Tevfik Berk; Cevik, Halime; Yilmaz, Birnur; Desteli, Guldeniz Aksan

2017-11-24

Adenomyosis is the presence of endometrial glandular and stromal tissue in the myometrium. This phenomenon can be the cause of excessive bleeding and menstrual pain in premenopausal women. Diagnosis of adenomyosis may present difficulty with conventional methods such as ultrasound and magnetic resonance imaging. Frequently, diagnosis is accomplished retrospectively based on the hysterectomy specimen. This is a prospective case control study done in vitro on 90 patients' hysterectomy specimens. Acoustic radiation force impulse (ARFI) and color elastography were used to determine the elasticity of hysterectomy specimens of patients undergoing indicated surgeries. Based on histopathological examinations, two groups were formed: a study group (n = 28-with adenomyosis) and a control group (n = 62-without adenomyosis). Elasticity measurements of tissue with adenomyosis were observed to be significantly higher than measurements of normal myometrial tissue (p < 0.01). Uterine fibroids were found to have higher values on ARFI study compared to normal myometrial tissues (p < 0.01). The findings lead to the conclusion that adenomyosis tissue is significantly softer than the normal myometrium. ARFI was found to be beneficial in differentiating myometrial tissue with adenomyosis from normal myometrial tissue. It was found to be feasible and beneficial to implement ARFI in daily gynecology practice for diagnosis of adenomyosis.

Protection of Hardware: Powering Systems (Power Converter, Normal Conducting, and Superconducting Magnets)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeffer, H.; Flora, B.; Wolff, D.

2016-01-01

Along with the protection of magnets and power converters, we have added a section on personnel protection because this is our highest priority in the design and operation of power systems. Thus, our topics are the protection of people, power converters, and magnet loads (protected from the powering equipment), including normal conducting magnets and superconducting magnets.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

A Ratiometric Threshold for Determining Presence of Cancer During Fluorescence-guided Surgery

PubMed Central

Warram, Jason M; de Boer, Esther; Moore, Lindsay S.; Schmalbach, Cecelia E; Withrow, Kirk P; Carroll, William R; Richman, Joshua S; Morlandt, Anthony B; Brandwein-Gensler, Margaret; Rosenthal, Eben L

2015-01-01

Background&Objective Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. Methods Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n=11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. Results During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%). Conclusion Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer. PMID:26074273

Estimation of stress relaxation time for normal and abnormal breast phantoms using optical technique

NASA Astrophysics Data System (ADS)

Udayakumar, K.; Sujatha, N.

2015-03-01

Many of the early occurring micro-anomalies in breast may transform into a deadliest cancer tumor in future. Probability of curing early occurring abnormalities in breast is more if rightly identified. Even in mammogram, considered as a golden standard technique for breast imaging, it is hard to pick up early occurring changes in the breast tissue due to the difference in mechanical behavior of the normal and abnormal tissue when subjected to compression prior to x-ray or laser exposure. In this paper, an attempt has been made to estimate the stress relaxation time of normal and abnormal breast mimicking phantom using laser speckle image correlation. Phantoms mimicking normal breast is prepared and subjected to precise mechanical compression. The phantom is illuminated by a Helium Neon laser and by using a CCD camera, a sequence of strained phantom speckle images are captured and correlated by the image mean intensity value at specific time intervals. From the relation between mean intensity versus time, tissue stress relaxation time is quantified. Experiments were repeated for phantoms with increased stiffness mimicking abnormal tissue for similar ranges of applied loading. Results shows that phantom with more stiffness representing abnormal tissue shows uniform relaxation for varying load of the selected range, whereas phantom with less stiffness representing normal tissue shows irregular behavior for varying loadings in the given range.

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

PubMed Central

Zhang, Jun; Zhang, Zhiwei; Ding, Yulei; Xu, Peng; Wang, Tingting; Xu, Wenjing; Lu, Huan; Li, Jun; Wang, Yan; Li, Siyuan; Liu, Zongzhi; An, Na; Yang, Li; Xie, Jianxin

2015-01-01

Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P < 0.01). The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P < 0.01). In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue. PMID:26273678

Glycyrrhetinic acid alleviates radiation-induced lung injury in mice.

PubMed

Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

2017-01-01

Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Proanthocyanidin-rich date seed extract protects against chemically induced hepatorenal toxicity.

PubMed

Ahmed, Atallah F; Al-Qahtani, Jawaher H; Al-Yousef, Hanan M; Al-Said, Mansour S; Ashour, AbdelKader E; Al-Sohaibani, Mohammed; Rafatullah, Syed

2015-03-01

A hydroacetone extract was prepared from seeds of Phoenix dactylifera L. var. Khalas, which is an industrial by-product of date processing. The proanthocyanidin nature of the extract (coded as DTX) was characterized by phytochemical and nuclear magnetic resonance (NMR) analyses. The total phenol/proanthocyanidin content and antioxidant activity of DTX were estimated by Folin-Ciocalteu, vanillin-sulfuric acid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, respectively. The hepatorenal protective activity of DTX was evaluated using CCl4-induced toxicity model in rats, in comparison with silymarin (SYL). Results of the histopathological examination and measurements of various hepatorenal serum indices and tissue biochemical markers demonstrated that DTX displayed marked protective potential against CCl4-induced liver and kidney injury at 100 mg/kg/rat. Relative to the control CCl4-intoxicated group, pretreatment with DTX significantly (P<.001) suppressed the elevated serum levels of alanine aminotransferase and aspartate aminotransferase (ALT and AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), bilirubin, creatinine, and calcium, whereas it significantly (P<.001) increased the diminished serum levels of high-density lipoprotein cholesterol (HDL-C) and total protein (TP). Moreover, DTX significantly decreased malondialdehyde (MDA) formation and increased TP synthesis in hepatorenal tissues compared with the intoxicated control. The improvement in biochemical parameters by DTX was observed in a dose-dependent manner and confirmed by restoration of normal histological features. The acute toxicity test of DTX in rats revealed safety of the extract. This study reveals that DTX enhances the recovery from xenobiotics-induced toxicity initiated by free radicals.

Media Compositions for Three Dimensional Mammalian Tissue Growth Under Microgravity Culture Conditions

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

1998-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Media Compositions for Three-Dimensional Mammalian Tissue Growth under Microgravity Culture Conditions

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

1998-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue.The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

The effect of uterine motion and uterine margins on target and normal tissue doses in intensity modulated radiation therapy of cervical cancer

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Weiss, E.; Abayomi, O. K.; Siebers, J. V.; Dogan, N.

2011-05-01

In intensity modulated radiation therapy (IMRT) of cervical cancer, uterine motion can be larger than cervix motion, requiring a larger clinical target volume to planning target volume (CTV-to-PTV) margin around the uterine fundus. This work simulates different motion models and margins to estimate the dosimetric consequences. A virtual study used image sets from ten patients. Plans were created with uniform margins of 1 cm (PTVA) and 2.4 cm (PTVC), and a margin tapering from 2.4 cm at the fundus to 1 cm at the cervix (PTVB). Three inter-fraction motion models (MM) were simulated. In MM1, all structures moved with normally distributed rigid body translations. In MM2, CTV motion was progressively magnified as one moved superiorly from the cervix to the fundus. In MM3, both CTV and normal tissue motion were magnified as in MM2, modeling the scenario where normal tissues move into the void left by the mobile uterus. Plans were evaluated using static and percentile DVHs. For a conventional margin (PTVA), quasi-realistic uterine motion (MM3) reduces fundus dose by about 5 Gy and increases normal tissue volumes receiving 30-50 Gy by ~5%. A tapered CTV-to-PTV margin can restore fundus and CTV doses, but will increase normal tissue volumes receiving 30-50 Gy by a further ~5%.

Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.

PubMed

Shalaby, Nourhan; Al-Ebraheem, Alia; Le, Du; Cornacchi, Sylvie; Fang, Qiyin; Farrell, Thomas; Lovrics, Peter; Gohla, Gabriela; Reid, Susan; Hodgson, Nicole; Farquharson, Michael

2018-03-01

One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure. A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery. Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue. The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

PubMed

Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

2015-01-01

Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

Role of adipose tissue-derived stem cells in the progression of renal disease.

PubMed

Donizetti-Oliveira, Cassiano; Semedo, Patricia; Burgos-Silva, Marina; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antônia Dos; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2011-03-01

To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Differential Expression of c-fos Proto-Oncogene in Normal Oral Mucosa versus Squamous Cell Carcinoma

PubMed Central

Krishna, Akhilesh; Bhatt, Madan Lal Brahma; Singh, Vineeta; Singh, Shraddha; Gangwar, Pravin Kumar; Singh, Uma Shankar; Kumar, Vijay; Mehrotra, Divya

2018-01-01

Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form the transcription factor AP-1 complex which participates in signal transduction and regulation of normal cellular processes. In tumorigenesis, c-Fos promotes invasive growth through down-regulation of tumor suppressor genes but its role in oral carcinogenesis is not clear. Objectives: This study concerned c-fos gene expression in normal and malignant tissues of the oral cavity, with attention to associations between expression status and clinico-pathological profiles of OSCC patients. Method: A total of 65 histopathologically confirmed OSCC tissue samples were included in case group along with an equal number of age and sex-matched normal tissue samples of oral cavity for the control group. c-Fos protein and m-RNA expressions were analyzed using immunohistochemistry and qRT-PCR, respectively. Results: A significant low expression of c-Fos protein was observed in OSCC cases than normal control subjects (p= <0.001). The mean percent positivity of c-Fos protein in cases vs. controls was 24.91± 2.7 vs. 49.68± 2.2 (p= <0.001). Most OSCC tissue samples showed weak or moderate c-Fos expression whereas 53.8% of normal tissue sections presented with strong immunostaining. Moreover, the relative m-RNA expression for the c-fos gene was significantly decreased in case group (0.93± 0.48) as compared to the control group (1.22± 0.87). Majority of c-Fos positive cases were diagnosed with well developed tumor. The mean percent positivity of c-Fos protein was significantly lower in higher grade tumor as compared with normal oral mucosa (p= < 0.001). Conclusion: The present study suggested that the c-fos gene is downregulated in oral carcinomas. The disparity of c-Fos protein levels in different pathological grades of tumor and normal oral tissue samples may indicate that loss of c-Fos expression is related with the progression of OSCC. PMID:29582647

Analysis of the association of the expression of KiSS-1 in colorectal cancer tissues with the pathology and prognosis.

PubMed

Huo, Xinkai; Zhang, Lei; Li, Tao

2018-03-01

Colorectal cancer is a common malignant tumor of the digestive tract with high morbidity and mortality rates. The aim of the present study was to examine the expression level of KiSS-1 in tumor tissues of patients with colorectal cancer, and to explore the relationship with the clinicopathology and prognosis of patients with colorectal cancer. Frozen tumor tissue and corresponding cancer-adjacent normal tissue specimens were selected from 56 patients with colorectal cancer who were treated in the Department of Surgery of our hospital from May 2009 to December 2011. The expression levels of KiSS-1 messenger ribonucleic acid (mRNA) in tumor tissues and cancer-adjacent normal tissues were detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The expression levels of KiSS-1 proteins in colorectal cancer tissues and cancer-adjacent normal tissues were further detected by immunohistochemistry. In addition, the association of the expression level of KiSS-1 proteins in tissues of colorectal cancer patients with pathological parameters and the prognosis of patients with colorectal cancer was analyzed combined with clinical data. The RT-qPCR results showed that the expression of KiSS-1 mRNA in colorectal cancer tissues was significantly lower than that in cancer-adjacent normal tissues (P<0.05). Immunohistochemistry results indicated that the positive expression rate of KiSS-1 proteins in colorectal cancer tissues (26.79%) was significantly lower than that in cancer-adjacent normal tissues (80.36%). The low expression of KiSS-1 in colorectal cancer tissues was associated with the degree of differentiation, invasion and metastasis, as well as clinical staging. The 5-year overall survival rate of patients with colorectal cancer was 55.36% (31/56). The univariate survival analysis showed that patients with lowly expressed KiSS-1 had worse prognosis. The low expression of KiSS-1 is closely associated with the occurrence and development of colorectal cancer, especially to the degree of differentiation, invasion and metastasis, as well as clinical staging. Thus, the expression of KiSS-1 in colorectal cancer tissues can be used as a reference for the prognosis of colorectal cancer, and KiSS-1 is a potential new target for the treatment of colorectal cancer.

Common strategic research agenda for radiation protection in medicine.

PubMed

2017-04-01

Reflecting the change in funding strategies for European research projects, and the goal to jointly improve medical radiation protection through sustainable research efforts, five medical societies involved in the application of ionising radiation (European Association of Nuclear Medicine, EANM; European Federation of Organizations for Medical Physics. EFOMP; European Federation of Radiographer Societies, EFRS; European Society of Radiology, ESR; European Society for Radiotherapy and Oncology, ESTRO) have identified research areas of common interest and developed this first edition of the Common Strategic Research Agenda (SRA) for medical radiation protection. The research topics considered necessary and most urgent for effective medical care and efficient in terms of radiation protection are summarised in five main themes: 1. Measurement and quantification in the field of medical applications of ionising radiation 2. Normal tissue reactions, radiation-induced morbidity and long-term health problems 3. Optimisation of radiation exposure and harmonisation of practices 4. Justification of the use of ionising radiation in medical practice 5. Infrastructures for quality assurance The SRA is a living document; thus comments and suggestions by all stakeholders in medical radiation protection are welcome and will be dealt with by the European Alliance for Medical Radiation Protection Research (EURAMED) established by the above-mentioned societies. • Overcome the fragmentation of medical radiation protection research in Europe • Identify research areas of joint interest in the field of medical radiation protection • Improve the use of ionising radiation in medicine • Collect stakeholder feedback and seek consensus • Emphasise importance of clinical translation and evaluation of research results.

Study of arsenic accumulation in rice and evaluation of protective effects of Chorchorus olitorius leaves against arsenic contaminated rice induced toxicities in Wistar albino rats.

PubMed

Hosen, Saeed Mohammed Imran; Das, Dipesh; Kobi, Rupkanowar; Chowdhury, Dil Umme Salma; Alam, Md Jibran; Rudra, Bashudev; Bakar, Muhammad Abu; Islam, Saiful; Rahman, Zillur; Al-Forkan, Mohammad

2016-10-14

In the present study, we investigated the arsenic accumulation in different parts of rice irrigated with arsenic contaminated water. Besides, we also evaluated the protective effects of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities in animal model. A pot experiment was conducted with arsenic amended irrigation water (0.0, 25.0, 50.0 and 75.0 mg/L As) to investigate the arsenic accumulation in different parts of rice. In order to evaluate the protective effects of Corchorus olitorius leaves, twenty Wistar albino rats were divided into four different groups. The control group (Group-I) was supplied with normal laboratory pellets while groups II, III, and IV received normal laboratory pellets supplemented with arsenic contaminated rice, C. olitorius leaf powder (4 %), arsenic contaminated rice plus C. olitorius leaf powder (4 %) respectively. Different haematological parameters and serum indices were analyzed to evaluate the protective effects of Corchorus olitorius leaves against arsenic intoxication. To gather more supportive evidences of Corchorus olitorius potentiality against arsenic intoxication, histopathological analysis of liver, kidney, spleen and heart tissues was also performed. From the pot experiment, we have found a significant (p ≤ 0.05) increase of arsenic accumulation in different parts of rice with the increase of arsenic concentrations in irrigation water and the trend of accumulation was found as root > straw > husk > grain. Another part of the experiment revealed that supplementation of C. olitorius leaves with arsenic contaminated rice significantly (p < 0.05) restored the altered haematological parameters and other serum indices towards the normal values. Arsenic deposition pattern on different organs and histological studies on the ultrastructural changes of liver, kidneys, spleen and heart also supported the protective roles of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities. Arsenic accumulation in different parts of rice increased dose-dependently. Hence, for irrigation purpose arsenic contaminated water cannot be used. Furthermore, arsenic contaminated rice induced several toxicities in animal model, most of which could be minimized with the food supplementation of Corchorus olitorius leaves. Therefore, Corchorus olitorius can be used as a potential food supplement to the affected people of arsenic prone zone to ensure the food security.

Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers.

PubMed Central

van Leengoed, H. L.; Schuitmaker, J. J.; van der Veen, N.; Dubbelman, T. M.; Star, W. M.

1993-01-01

Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA-PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm and occlusion probably due to thrombi formation. Oedema was notable, especially following PDT with 600 J cm-2 at 24 h p.i. Images Figure 1 PMID:8494722

Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

PubMed

Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

2018-01-01

This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.

Various clinical application of phase contrast X-ray

NASA Astrophysics Data System (ADS)

Oh, Chilhwan; Park, Sangyong; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Je, Jungho

2008-02-01

In biomedical application study using phase contrast X-ray, both sample thickness or density and absorption difference are very important factors in aspects of contrast enhancement. We present experimental evidence that synchrotron hard X-ray are suitable for radiological imaging of biological samples down to the cellular level. We investigated the potential of refractive index radiology using un-monochromatized synchrotron hard X-rays for the imaging of cell and tissue in various diseases. Material had been adopted various medical field, such as apoE knockout mouse in cardiologic field, specimen from renal and prostatic carcinoma patient in urology, basal cell epithelioma in dermatology, brain tissue from autosy sample of pakinson's disease, artificially induced artilrtis tissue from rabbits and extracted tooth from patients of crack tooth syndrome. Formalin and paraffin fixed tissue blocks were cut in 3 mm thickness for the X-ray radiographic imaging. From adjacent areas, 4 μm thickness sections were also prepared for hematoxylin-eosin staining. Radiographic images of dissected tissues were obtained using the hard X-rays from the 7B2 beamline of the Pohang Light Source (PLS). The technique used for the study was the phase contrast images were compared with the optical microscopic images of corresponding histological slides. Radiographic images of various diseased tissues showed clear histological details of organelles in normal tissues. Most of cancerous lesions were well differentiated from adjacent normal tissues and detailed histological features of each tumor were clearly identified. Also normal microstructures were identifiable by the phase contrast imaging. Tissue in cancer or other disease showed clearly different findings from those of surrounding normal tissue. For the first time we successfully demonstrated that synchrotron hard X-rays can be used for radiological imaging of relatively thick tissue samples with great histological details.

Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.

PubMed

Ayyildiz, Simel; Sahin, Cem; Akgün, Ozlem Marti; Basak, Feridun

2013-01-01

Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

PubMed Central

Sahin, Cem; Akgün, Özlem Marti; Basak, Feridun

2013-01-01

Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics. PMID:23533828

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

PubMed Central

Lough, Kendall J.; Patel, Jeet H.; Descovich, Carlos Patiño; Curtis, T. Anthony

2016-01-01

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. PMID:27317810

Reductions in muscle quality and quantity in CIDP patients assessed by magnetic resonance imaging.

PubMed

Gilmore, Kevin J; Doherty, Timothy J; Kimpinski, Kurt; Rice, Charles L

2018-05-09

Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but these have not been explored. Twelve patients with CIDP (mean 61 years) and ten age- matched (mean 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. Isometric strength was lower in CIDP patients by 36% compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ∼17% than controls, and non-contractile tissue volume was ∼58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ∼ 29% and ∼18% lower, respectively in CIDP patients DISCUSSION: These results provide insight into structural integrity of muscle contractile proteins and pathological changes to whole-muscle tissue composition that contribute to impaired muscle function in CIDP. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Highly restricted diversity of TCR delta chains of the amphibian Mexican axolotl (Ambystoma mexicanum) in peripheral tissues.

PubMed

André, Sébastien; Kerfourn, Fabienne; Affaticati, Pierre; Guerci, Aline; Ravassard, Philippe; Fellah, Julien S

2007-06-01

Gammadelta T cells localize at mammalian epithelial surfaces to exert both protective and regulatory roles in response to infections. We have previously characterized the Mexican axolotl (Ambystoma mexicanum) T cell receptor delta (TRD) chain. In this study, TRD repertoires in spleen, liver, intestine and skin from larvae, pre-adult and adult axolotls were examined and compared to the thymic TRD repertoire. A TRDV transcript without N/D diversity, TRDV1S1-TRDJ1, dominates the TRD repertoires until sexual maturation. In adult tissues, this canonical transcript is replaced by another dominant TRDV1S1-TRDJ1 transcript. In the thymus, these two transcripts are detected early in development. Our results suggest that gammadelta T cells that express the canonical TRDV1S1-TRDJ1 transcript emerge from the thymus and colonize the peripheral tissues, where they are selectively expanded by recurrent ligands. This particular situation is probably related to the neotenic state and the slow development of the axolotl. In thymectomized axolotls, TRD repertoires appear different from those of normal axolotls, suggesting that extrathymic gammadelta T cell differentiation could occur. Gene expression analysis showed the importance of the gut in T cell development.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

PubMed

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-08-15

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

PubMed Central

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-01-01

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. PMID:25206528

Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy.

PubMed

Kim, Hyun Ah; Rhim, Taiyoun; Lee, Minhyung

2011-07-18

Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: is this a possible reason for unexplained spontaneous abortion?

PubMed

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies.

Association Study of Estrogen Receptor Alpha Gene Polymorphisms with Spontaneous Abortion: Is This a Possible Reason for Unexplained Spontaneous Abortion?

PubMed Central

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies. PMID:24228243

Dental Pulp Defence and Repair Mechanisms in Dental Caries

PubMed Central

Farges, Jean-Christophe; Alliot-Licht, Brigitte; Renard, Emmanuelle; Ducret, Maxime; Gaudin, Alexis; Smith, Anthony J.; Cooper, Paul R.

2015-01-01

Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo. PMID:26538821