Non-invasive assessments of adipose tissue metabolism in vitro

PubMed Central

Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.

2015-01-01

Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988

Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

PubMed

Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

2015-12-01

Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

Tissue-Informative Mechanism for Wearable Non-invasive Continuous Blood Pressure Monitoring

NASA Astrophysics Data System (ADS)

Woo, Sung Hun; Choi, Yun Young; Kim, Dae Jung; Bien, Franklin; Kim, Jae Joon

2014-10-01

Accurate continuous direct measurement of the blood pressure is currently available thru direct invasive methods via intravascular needles, and is mostly limited to use during surgical procedures or in the intensive care unit (ICU). Non-invasive methods that are mostly based on auscultation or cuff oscillometric principles do provide relatively accurate measurement of blood pressure. However, they mostly involve physical inconveniences such as pressure or stress on the human body. Here, we introduce a new non-invasive mechanism of tissue-informative measurement, where an experimental phenomenon called subcutaneous tissue pressure equilibrium is revealed and related for application in detection of absolute blood pressure. A prototype was experimentally verified to provide an absolute blood pressure measurement by wearing a watch-type measurement module that does not cause any discomfort. This work is supposed to contribute remarkably to the advancement of continuous non-invasive mobile devices for 24-7 daily-life ambulatory blood-pressure monitoring.

Tissue Damage Characterization Using Non-invasive Optical Modalities

NASA Astrophysics Data System (ADS)

Diaz, David

The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p < 0.05). Burn depth and viable vessel density were estimated via histological samples. 42% of vessels in the dermal layer were viable for superficial burns, compared to 25% for deep burns. The differences detected in optical properties and hemoglobin content by optical measurements correlated with the extent of tissue injury observed in histological stains. After proof of concept in animals, a human study was conducted and optical data was collected from 20 healthy subjects and 8 patients at risk of developing pressure ulcers. Blood flow index (BFI) values from the sacral region of patients were compared with those of healthy volunteers. Prior to loading measurements, baseline BFI values were measured in subjects in lateral position. These values were systematically higher for patients who developed open ulcers than for the other research subjects. While under the loading position, patients who developed a pressure ulcer had a decrease in BFI from baseline values an order of magnitude larger than healthy subjects (p < 0.01) and patients whose redness dissipated (p < 0.01). The hyperemic response, when pressure was released as the patient was moved back to a lateral position, showed a decreasing trend from one session to the next for patients who developed open ulcers. Overall, this work presents a novel non-invasive method of pressure ulcer assessment and provides an improvement over current assessment methods. The obtained results suggest the system may potentially predict whether non-blanchable redness will develop into an advanced pressure ulcer within four weeks from initial observation.

Differences in regulatory T-cell and dendritic cell pattern in decidual tissue of placenta accreta/increta cases.

PubMed

Schwede, S; Alfer, J; von Rango, U

2014-06-01

Primary infertility, miscarriage, and preeclampsia have been correlated with reduced numbers of regulatory T-cells (Treg) suggesting that decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT tolerance. In contrast increased numbers of Treg-cells may be responsible for over-invasion of EVT. As the maturation status of dendritic cells (DC) influences T-cell behavior (tolerance or immune activation), altered relation between immature and mature DCs may also influence EVT invasion. Paraffin-embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single-stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the leukocyte subpopulations was performed for decidua parietalis and basalis as characterized by cytokeratin-positive EVT. Statistical analysis was performed by using the Mann-Whitney test. There were significantly fewer CD4(+) cells in Pc than in IUG. Concerning the Treg-markers, FoxP3(+) cells are significantly increased. CD25(+) cells showed a small non-significant increase in Pc in comparison to IUG. Concerning dendritic cells, immature non-activated CD209(+) DCs were significantly decreased in Pc while immature activated CD205(+) DCs were slightly but non-significantly increased. Mature activated CD83(+) DC were non-significantly decreased in IUG vs Pc. The increased number of Treg-cells in Pc suggests significance for these cells in the regulation of trophoblast invasion. Their adequate interaction with other lymphocyte populations (e.g. adequately maturated dendritic cells) may be one mechanism to assure controlled EVT invasion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential Mueller matrix polarimetry technique for non-invasive measurement of glucose concentration on human fingertip.

PubMed

Phan, Quoc-Hung; Lo, Yu-Lung

2017-06-26

A differential Mueller matrix polarimetry technique is proposed for obtaining non-invasive (NI) measurements of the glucose concentration on the human fingertip. The feasibility of the proposed method is demonstrated by detecting the optical rotation angle and depolarization index of tissue phantom samples containing de-ionized water (DI), glucose solutions with concentrations ranging from 0~500 mg/dL and 2% lipofundin. The results show that the extracted optical rotation angle increases linearly with an increasing glucose concentration, while the depolarization index decreases. The practical applicability of the proposed method is demonstrated by measuring the optical rotation angle and depolarization index properties of the human fingertips of healthy volunteers.

Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis.

PubMed

Wang, Jianpeng; Wang, Dong; Wan, Dehong; Ma, Qingxia; Liu, Qian; Li, Jiye; Li, Zhaojian; Gao, Yang; Jiang, Guohui; Ma, Leina; Liu, Jia; Li, Chuzhong

2018-06-14

The invasion and recurrence of clinical nonfunctioning pituitary adenomas (NFA) often lead to surgical treatment failure. Circular RNAs (circRNAs) are a novel class of RNAs whose 3' and 5' ends are joined together and have been shown to play important roles in cancer development. Up to now, the roles of circRNAs remain unclear in invasive and recurrent NFA. We detected and summarized the circRNA expression pattern in 75 NFA tissues from 10 non-invasive cases and 65 invasive cases and 9 pairs NFA tumor tissues from 9 recurrent cases by circRNA microarrays. Accordingly, functional enrichment analysis and pathway analysis were performed and circRNA-microRNA(miRNA) network were generated by bioinformatic analysis tools. 5 new invasive NFA samples and 5 non-invasive NFA samples were collected to measure the microarray results. 570 dysregulated circRNAs (Invasive Tumor vs. Non-invasive Tumor) and 10 up-regulated circRNAs (Recurrent tumor Tissue vs. First surgery tumor Tissue) were identified based on the situation (FC>2, P<0.05). The parental genes of the dysregulated circRNAs in the comparison between invasion tumor and non-invasion tumor were found to be enriched in some cell adhesion signaling pathways such as Focal adhesion, Hippo signaling pathway, PI3K-Akt signaling pathway, and Adherens junction. The circRNA-miRNA network showed that the dysregulated circRNA may function as miRNA sponges. This is the first study to conduct and comprehensively analyze the circRNA expression profile in invasive and recurrent NFA. Our finding will provide evidence for the significance of circRNAs in NFA diagnosis, prognosis and clinical treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

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

Shan, Nianxi; Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410008; Shen, Liangfang

Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues andmore » cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.« less

Cellular phone enabled non-invasive tissue classifier.

PubMed

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro.

Cellular Phone Enabled Non-Invasive Tissue Classifier

PubMed Central

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro. PMID:19365554

Evaluation of Non-Invasive Multispectral Imaging as a Tool for Measuring the Effect of Systemic Therapy in Kaposi Sarcoma

PubMed Central

Kainerstorfer, Jana M.; Polizzotto, Mark N.; Uldrick, Thomas S.; Rahman, Rafa; Hassan, Moinuddin; Najafizadeh, Laleh; Ardeshirpour, Yasaman; Wyvill, Kathleen M.; Aleman, Karen; Smith, Paul D.; Yarchoan, Robert; Gandjbakhche, Amir H.

2013-01-01

Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA) of the data. These images were compared with clinical and pathological responses determined by conventional means. We demonstrate that cutaneous lesions have increased blood volume concentration and that changes in this parameter are a reliable indicator of treatment efficacy, differentiating responders and non-responders. Blood volume decreased by at least 20% in all lesions that responded by clinical criteria and increased in the two lesions that did not respond clinically. Responses as assessed by multi-spectral imaging also generally correlated with overall patient clinical response assessment, were often detectable earlier in the course of therapy, and are less subject to observer variability than conventional clinical assessment. Tissue oxygenation was more variable, with lesions often showing decreased oxygenation in the center surrounded by a zone of increased oxygenation. This technique could potentially be a clinically useful supplement to existing response assessment in KS, providing an early, quantitative, and non-invasive marker of treatment effect. PMID:24386302

Dynamics of cancerous tissue correlates with invasiveness

NASA Astrophysics Data System (ADS)

West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

2017-03-01

Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

PubMed Central

2011-01-01

Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi-1 in highly metastatic breast cancer cells remarkably reduces cellular motility, invasion and transformation, as well as tumorigenesis and lung metastases in nude mice. In addition, the repression of Bmi-1 reverses the expression of EMT markers and inhibits the Akt/GSK3β/Snail pathway. Conclusions This study demonstrates that Bmi-1 promotes the invasion and metastasis of human breast cancer and predicts poor survival. PMID:21276221

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

PubMed Central

Dalecki, Diane; Mercado, Karla P.; Hocking, Denise C.

2015-01-01

Non-invasive, non-destructive technologies for imaging and quantitatively monitoring the development of artificial tissues are critical for the advancement of tissue engineering. Current standard techniques for evaluating engineered tissues, including histology, biochemical assays and mechanical testing, are destructive approaches. Ultrasound is emerging as a valuable tool for imaging and quantitatively monitoring the properties of engineered tissues and biomaterials longitudinally during fabrication and post-implantation. Ultrasound techniques are rapid, non-invasive, non-destructive and can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, high-frequency quantitative ultrasound techniques can enable volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation. This review provides an overview of ultrasound imaging, quantitative ultrasound techniques, and elastography, with representative examples of applications of these ultrasound-based techniques to the field of tissue engineering. PMID:26581347

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

Expression of Caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion.

PubMed

Sun, Yanxia; Guo, Yingzhen

2018-05-01

The present study aimed to detect the expression of Caspase-1 in the tumor tissues and tumor-adjacent tissues of patients with breast cancer, and to investigate the effects of Caspase-1 on the proliferation, apoptosis and invasion of breast cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to detect Caspase-1 mRNA expression in breast cancer tissues and tumor-adjacent tissues from patients. Additionally, the human breast cancer MDA-MB-231 cell line was treated with the Caspase-1 small molecule inhibitor Ac-YVAD-CMK, following which the changes to Caspase-1 protein expression were detected via western blotting. The MTT method detected the changes to cell proliferation, flow cytometry detected the rate of apoptosis, and a Transwell assay was employed to assess invasion. Caspase-1 mRNA expression was significantly decreased in the breast cancer tissues of patients, compared with in the tumor-adjacent tissues, a difference that was statistically significant (P<0.05). Treatment with the Ac-YVAD-CMK markedly decreased the protein expression of Caspase-1 in MDA-MB-231 cells, and the difference was statistically significant (P<0.05). Following this treatment of Ac-YVAD-CMK cells, the proliferation and invasion abilities markedly increased, while the apoptotic levels significantly decreased (P<0.05). In conclusion, the expression of Caspase-1 is low in breast cancer tissues, which may promote the proliferation and invasion of breast cancer cells and could be closely associated with the occurrence and development of breast cancer.

Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water.

PubMed

Chung, S H; Cerussi, A E; Merritt, S I; Ruth, J; Tromberg, B J

2010-07-07

We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R=0.96) with a difference of 1.1+/-0.91 degrees C over a range of 28-48 degrees C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics.

Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells.

PubMed

Zhao, Hong-Bing; Zhang, Xi-Feng; Jia, Xue-Lin; Wang, Hao-Bin

2017-09-01

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression

PubMed Central

Baldwin, R. Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J.; Bell, John C.; Islam, Shahidul; Côté, Jocelyn

2015-01-01

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer. PMID:25605249

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression.

PubMed

Baldwin, R Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J; Bell, John C; Islam, Shahidul; Côté, Jocelyn

2015-02-20

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.

Do traits of invasive species influence decomposition and soil respiration of disturbed ecosystems?

NASA Astrophysics Data System (ADS)

Wells, A. J.; Balster, N. J.

2009-12-01

Large-scale landscape disturbances typically alter the terrestrial carbon cycle leading to shifts in pools of soil carbon. Restoration of disturbed landscapes with prairie vegetation has thus been practiced with the intent of increasing carbon accrual in soils. However, since disturbed soils are prone to invasion by non-native invasive species, many ecological restorations have resulted in unexpected outcomes, which may be explained by differences in plant traits such as tissue quality and biomass allocation. Typically, the tissue of invasive species has lower C:N ratios relative to native species, and consequently, faster decomposition rates, which potentially can alter the balance in soil carbon. The primary objective of this research was to compare the effects of native prairie species versus non-native invasive species on the carbon cycling within a novel environment: a recently dewatered basin in southwestern Wisconsin following dam removal. We hypothesized that a higher invasive to native species ratio would result in faster litter decomposition and a higher rate of soil respiration. To test this hypothesis, we seeded newly exposed sediments with native prairie seeds in 2005, annually collected aboveground plant biomass (by species per plot), calculated decomposition rate of native and invasive litter (underneath both canopy types), and measured soil respiration during the growing season of 2009. After four years of seeding, the aboveground biomass of the native vegetation has increased significantly (p < 0.01) from 14.4 to 351 g m-2 while invasive species biomass has decreased from 459 to 296 g m-2. Senesced tissue from mixed native species had a higher C:N ratio, 27:1 (43% C: 1.6% N), than tissue from mixed invasive species, 24:1 (35% C: 1.5% N). However, after 7 months, we found that the rate of decomposition depended on both litter type and plant canopy type (p < 0.01); invasive plant tissue had a slightly faster decomposition rate than the native litter and this rate was elevated under invasive species. Mean soil respiration rates ranged from 4.1 to 7.7 µmol C m-2 s-1. Our preliminary results suggest that respiration increases exponentially with soil temperature, as soil temperature explained 20% of the variation in soil respiration. However, the vegetation type did not have a significant effect on the respiration rate. Our results suggest that vegetation traits may be influencing the cycling of carbon at this site, but that spatial variation in abiotic conditions above and belowground appear to control decomposition and soil respiration at a local scale. Moreover, the ecophysiological interactions measured here may have practical implications on the restoration of disturbed ecosystems and the manner in which invasive species are viewed relative to the accrual soil carbon.

MALAT1 affects ovarian cancer cell behavior and patient survival

PubMed Central

Lin, Qunbo; Guan, Wencai; Ren, Weimin; Zhang, Lingyun; Zhang, Jinguo; Xu, Guoxiong

2018-01-01

Epithelial ovarian cancer (EOC) is one of the most lethal malignancies of the female reproductive organs. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) participate in tumorigenesis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is an lncRNA and plays a role in various types of tumors. However, the function of MALAT1 on cellular behavior in EOC remains unclear. The current study explored the expression of MALAT1 in ovarian cancer tissues and in EOC cell lines. Quantitative RT-PCR analysis revealed that the expression of MALAT1 was higher in human ovarian malignant tumor tissues and EOC cells than in normal ovarian tissues and non-tumorous human ovarian surface epithelial cells, respectively. By analyzing the online database Kaplan-Meier Plotter, MALAT1 was identified to be correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Furthermore, knockdown of MALAT1 by small interfering RNA (siRNA) significantly decreased EOC cell viability, migration, and invasion. Finally, dual-luciferase reporter assays demonstrated that MALAT1 interacted with miR-143-3p, a miRNA that plays a role in EOC as demonstrated in our previous study. Inhibition of MALAT1 resulted in an increase of miR-143-3p expression, leading to a decrease of CMPK protein expression. In conclusion, our results indicated that MALAT1 was overexpressed in EOC. Silencing of MALAT1 decreased EOC cell viability and inhibited EOC cell migration and invasion. These data revealed that MALAT1 may serve as a new therapeutic target of human EOC. PMID:29693187

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.

The effects of Magnetic Resonance Imaging-guided High-Intensity Focused Ultrasound ablation on human cadaver breast tissue.

PubMed

Merckel, Laura G; Deckers, Roel; Baron, Paul; Bleys, Ronald L A W; van Diest, Paul J; Moonen, Chrit T W; Mali, Willem P Th M; van den Bosch, Maurice A A J; Bartels, Lambertus W

2013-10-05

Magnetic Resonance Imaging-guided High-Intensity Focused Ultrasound (MR-HIFU) is a promising technique for non-invasive breast tumor ablation. The purpose of this study was to investigate the effects of HIFU ablation and thermal exposure on ex vivo human breast tissue. HIFU ablations were performed in three unembalmed cadaveric breast specimens using a clinical MR-HIFU system. Sonications were performed in fibroglandular and adipose tissue. During HIFU ablation, time-resolved anatomical MR images were acquired to monitor macroscopic tissue changes. Furthermore, the breast tissue temperature was measured using a thermocouple to investigate heating and cooling under HIFU exposure. After HIFU ablation, breast tissue samples were excised and prepared for histopathological analysis. In addition, thermal exposure experiments were performed to distinguish between different levels of thermal damage using immunohistochemical staining. Irreversible macroscopic deformations up to 3.7 mm were observed upon HIFU ablation both in fibroglandular and in adipose tissue. No relationship was found between the sonication power or the maximum tissue temperature and the size of the deformations. Temperature measurements after HIFU ablation showed a slow decline in breast tissue temperature. Histopathological analysis of sonicated regions demonstrated ablated tissue and morphologically complete cell death. After thermal exposure, samples exposed to three different temperatures could readily be distinguished. In conclusion, the irreversible macroscopic tissue deformations in ex vivo human breast tissue observed during HIFU ablation suggest that it might be relevant to monitor tissue deformations during MR-HIFU treatments. Furthermore, the slow decrease in breast tissue temperature after HIFU ablation increases the risk of heat accumulation between successive sonications. Since cell death was inflicted after already 5 minutes at 75°C, MR-HIFU may find a place in non-invasive treatment of breast tumors. © 2013 Elsevier B.V. All rights reserved.

Development and validation of a MRgHIFU non-invasive tissue acoustic property estimation technique.

PubMed

Johnson, Sara L; Dillon, Christopher; Odéen, Henrik; Parker, Dennis; Christensen, Douglas; Payne, Allison

2016-11-01

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment.

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

Cho, Nancy L., E-mail: nlcho@partners.org; Lin, Chi-Iou; Du, Jinyan

Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using amore » bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.« less

Photoacoustic imaging for assessing ischemic kidney damage in vivo

NASA Astrophysics Data System (ADS)

Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

2018-02-01

Ischemic reperfusion injuries (IRIs) occur after blood returns to a tissue or organ after a period without oxygen or nutrients, which causes an inflammatory response leading to heterogeneous scarring of the nearby tissue and vasculature. This is associated with long-term decreases blood flow, and necrosis. Although most commonly associated with heart attacks and strokes, IRIs are also a side effect of organ transplants, when the organ is reperfused in the recipient's body after being transported from the donor to the transplant hospital. Currently, the optimal method of monitoring for IRI is limited to biopsies, which are invasive and poorly monitor the spatial heterogeneity of the damage. To non-invasively identify changes in kidneys, the left renal artery in mice (n=3) was clamped for 45 minutes to create an IRI event. Both kidneys of each animal were monitored using photoacoustics (PA) with the VevoLAZR system (Fujifilm-VisualSonics, Toronto) three, four and eight weeks after surgery. IRI-treated kidneys show increased picosirius red staining, indicative of collagen (0.601 vs 0.042, p < 0.0001), decreased size as assessed by cross-sectional area (7.8 mm2 vs 35.9 mm2 , p < 0.0001), and decreased oxygen saturation (sO2; 62% vs 77%, p = 0.02). Analysis of the photoacoustic data shows that a two-point metric, the 715:930 nm ratio of the whole kidney (1.05 vs 0.57, p = 0.049) and the optical spectral slope (OSS) (0.8 * 10-3 vs 3.0 * 10-3, p = 0.013) are both able to differentiate between IRI-treated and healthy kidneys. These data suggest that photoacoustics can be used as a non-invasive method to observe in vivo changes in the kidney due to IRI.

Inter-electrode tissue resistance is not affected by tissue oedema when electrically stimulating the lower limb of sepsis patients.

PubMed

Durfee, William K; Young, Joseph R; Ginz, Hans F

2014-05-01

ICU patients typically are given large amounts of fluid and often develop oedema. The purpose of this study was to evaluate whether the oedema would change inter-electrode resistance and, thus, require a different approach to using non-invasive electrical stimulation of nerves to assess muscle force. Inter-electrode tissue resistance in the lower leg was measured by applying a 300 µs constant current pulse and measuring the current through and voltage across the stimulating electrodes. The protocol was administered to nine ICU patients with oedema, eight surgical patients without oedema and eight healthy controls. No significant difference in inter-electrode resistance was found between the three groups. For all groups, resistance decreased as stimulation current increased. In conclusion, inter-electrode resistance in ICU patients with severe oedema is the same as the resistance in regular surgical patients and healthy controls. This means that non-invasive nerve stimulation devices do not need to be designed to accommodate different resistances when used with oedema patients; however, surface stimulation does require higher current levels with oedema patients because of the increased distance between the skin surface and the targeted nerve or muscle.

SIRT3 functions as a tumor suppressor in hepatocellular carcinoma.

PubMed

Zeng, Xianchun; Wang, Nanzhu; Zhai, Hui; Wang, Rongpin; Wu, Jiahong; Pu, Wei

2017-03-01

Hepatocellular carcinoma is one of the leading causes for cancer-related mortality worldwide. SIRT3 may function as either oncogene or tumor suppressor in a panel of cancers; however, the role of SIRT3 in hepatocellular carcinoma remains unclear. In this study, we assayed the expression level of SIRT3 in hepatocellular carcinoma tissues by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. A loss-of-function approach was used to examine the effects of SIRT3 on biological activity, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of SIRT3 protein in hepatocellular carcinoma tissues were significantly downregulated compared with those in adjacent non-cancerous tissues. Furthermore, SIRT3 could decrease cell proliferation and inhibit cell migration/invasion in hepatocellular carcinoma cell line. Taken together, these results elucidated the function of SIRT3 in hepatocellular carcinoma development and suggested that SIRT3 might function as tumor suppressor in hepatocellular carcinoma by targeting PI3K/Akt pathway.

Pulsed-High Intensity Focused Ultrasound (HIFU) Exposures for Enhanced Delivery of Therapeutics: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Frenkel, Victor; Deng, Cheri; O'Neill, Brian E.; Quijano, Jade; Stone, Michael J.; Dromi, Sergio; Hunter, Finie; Xie, Jianwu; Quinn, Timothy P.; Wood, Bradford J.; Li, King C. P.

2006-05-01

The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed.

Towards non-invasive characterization of breast cancer and cancer metabolism with diffuse optics

PubMed Central

Busch, David R.; Choe, Regine; Durduran, Turgut; Yodh, Arjun G.

2013-01-01

We review recent developments in diffuse optical imaging and monitoring of breast cancer, i.e. optical mammography. Optical mammography permits non-invasive, safe and frequent measurement of tissue hemodynamics oxygen metabolism and components (lipids, water, etc.), the development of new compound indices indicative of the risk and malignancy, and holds potential for frequent non-invasive longitudinal monitoring of therapy progression. PMID:24244206

Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma

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

Lee, Na Keum; Lee, Jung Hwa; Park, Chan Hyuk

Highlights: • HOTAIR expression was tested in fifty patients with gastric cancer. • Cell proliferation was measured after HOTAIR silencing in gastric cancer cell line. • siRNA–HOTAIR suppresses cell invasiveness and capacity of migration. • Knock down of HOTAR leads to decreased expression of EMT markers. • Inhibition of HOTAIR induces apoptosis and cell cycle arrest. - Abstract: Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastricmore » cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.« less

New tools for non-invasive exploration of collagen network in cartilaginous tissue-engineered substitute.

PubMed

Henrionnet, Christel; Dumas, Dominique; Hupont, Sébastien; Stoltz, Jean François; Mainard, Didier; Gillet, Pierre; Pinzano, Astrid

2017-01-01

In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen. This system permitted to differentiate the quality of collagen network between ITS and TGF-β1 treatments. Multiscale large field imaging combined to multimodality approaches (SHG-TCSPC) at macroscopical scale represent an innovative and non-invasive technique to monitor the quality of collagen network in cartilage tissue-engineered substitutes before in vivo implantation.

Towards a safe non-invasive method for evaluating the carbonate substitution levels of hydroxyapatite (HAP) in micro-calcifications found in breast tissue.

PubMed

Kerssens, Marleen M; Matousek, Pavel; Rogers, Keith; Stone, Nicholas

2010-12-01

A new diagnostic concept based on deep Raman spectroscopy is proposed permitting the non-invasive determination of the level of carbonate substitution in type II calcifications (HAP). The carbonate substitution has shown to be directly associated with the pathology of the surrounding breast tissue and different pathology groups can therefore be separated using specific features in the Raman spectra of the calcifications. This study explores the principle of distinguishing between type II calcifications, found in proliferating lesions, by using the strongest Raman peak from calcium hydroxyapatites (the phosphate peak at 960 cm(-1)) to act as a surrogate marker for carbonate substitution levels. It is believed that carbonate ion substitution leads to a perturbation of the hydroxyapatite lattice which in turn affects the phosphate vibrational modes. By studying calcifications, with known carbonate content, buried in porcine tissue it has been possible to evaluate the feasibility of using the proposed approach to probe the composition of the calcifications in vivo and hence provide pathology specific information non-invasively, in real time. Using the proposed concept we were able to determine the level of carbonate substitutions through soft tissue phantom samples (total thickness of 5.6 mm). As the level of carbonate substitution has been previously correlated with mid-FTIR to the lesion type, i.e. whether benign or invasive or in situ carcinoma, the new findings provide a major step forward towards establishing a new capability for diagnosing benign and malignant lesions in breast tissue in a safe and non-invasive manner in vivo.

Non-invasive and Non-destructive Characterization of Tissue Engineered Constructs Using Ultrasound Imaging Technologies: A Review.

PubMed

Kim, Kang; Wagner, William R

2016-03-01

With the rapid expansion of biomaterial development and coupled efforts to translate such advances toward the clinic, non-invasive and non-destructive imaging tools to evaluate implants in situ in a timely manner are critically needed. The required multi-level information is comprehensive, including structural, mechanical, and biological changes such as scaffold degradation, mechanical strength, cell infiltration, extracellular matrix formation and vascularization to name a few. With its inherent advantages of non-invasiveness and non-destructiveness, ultrasound imaging can be an ideal tool for both preclinical and clinical uses. In this review, currently available ultrasound imaging technologies that have been applied in vitro and in vivo for tissue engineering and regenerative medicine are discussed and some new emerging ultrasound technologies and multi-modality approaches utilizing ultrasound are introduced.

Non-invasive and non-destructive characterization of tissue engineered constructs using ultrasound imaging technologies: a review

PubMed Central

Kim, Kang; Wagner, William R.

2015-01-01

With the rapid expansion of biomaterial development and coupled efforts to translate such advances toward the clinic, non-invasive and non-destructive imaging tools to evaluate implants in situ in a timely manner are critically needed. The required multilevel information is comprehensive, including structural, mechanical, and biological changes such as scaffold degradation, mechanical strength, cell infiltration, extracellular matrix formation and vascularization to name a few. With its inherent advantages of non-invasiveness and non-destructiveness, ultrasound imaging can be an ideal tool for both preclinical and clinical uses. In this review, currently available ultrasound imaging technologies that have been applied in vitro and in vivo for tissue engineering and regenerative medicine are discussed and some new emerging ultrasound technologies and multi-modality approaches utilizing ultrasound are introduced. PMID:26518412

Comparative study of angiostatic and anti-invasive gene expressions as prognostic factors in gastric cancer.

PubMed

Lee, J H; Koh, J T; Shin, B A; Ahn, K Y; Roh, J H; Kim, Y J; Kim, K K

2001-02-01

Genes involving angiogenesis and metastasis play an important role in the progression and infiltration of cancer. We examined the expressions of various angiostatic and potential invasion/metastasis suppressor genes through RT-PCR analyses in 32 gastric cancer specimens with or without distant metastasis. The expressions of the invasion/metastasis suppressor, nm23 and E-cadherin increased much more in the cancer tissue (CT) and metastatic lymph node (MLN) than in the extraneoplastic mucosa (EM) and non-metastatic lymph node (NLN), respectively. The expressions of the angiostatic factor, angiopoietin 2 and thrombospondin 2 increased in the CT and MLN as compared with the EM and NLN, respectively. The newly cloned angiostatic factor, brain-specific angiogenesis inhibitor 1 (BAI1) decreased much more in the CT and MLN than the EM and NLN, respectively. However, BAI1 increased in the CT compared with the EM among the patients with poor prognosis and distant metastasis, such as liver or peritoneum. The expressions of the invasive factor, matrix metalloproteinase-2 and its suppressor, tissue inhibitor metalloproteinase-2 (TIMP-2) increased in the CM as compared with the EM, but the increased expression pattern of these genes in the CT became blunted among the patients with good prognosis. Our results indicate that BAI1 and TIMP-2 expressions in the extraneoplastic mucosa and non-metastatic lymph nodes were not suppressed in the patients with good prognosis, but increased expressions of angiopoietin 2, thrombospondin 2, TIMP-2, nm23 and E-cadherin in the tumor tissue did not lead to a long survival after operation. It is suggested that the extent of BAI1 and TIMP-2 expression in the gastric mucosa may be an important prognostic factor for predicting survival in gastric cancer.

Long non-coding RNA ZNF674-1 acts as a cancer suppressor in nasopharyngeal carcinoma.

PubMed

Nie, Guo-Hui; Li, Zhao; Duan, Hong-Fang; Luo, Liang; Hu, Hong-Yi; Chen, Xiao-Fan; Zhang, Wei

2018-06-01

Nasopharyngeal carcinoma (NPC) is the most frequently occurring carcinoma of the head and neck. The complexity of NPC makes it difficult for it to be diagnosed and treated at an early stage. Certain long non-coding RNAs (lncRNAs) are closely associated with the carcinogenesis of NPC. In the present study, the expression of lncRNA ZNF674-1 in NPC tissues and an NPC cell line was analyzed and was revealed to be downregulated compared with normal tissues and cells. When the expression of lncRNA ZNF674-1 was reduced in NPC cells, the proliferation, migration and invasion of these cells was promoted, whereas the apoptosis of these cells was decreased. On the contrary, when overexpressed, the expression of lncRNA ZNF674-1 inhibited the proliferation, invasion and migration of cells, but promoted cell apoptosis. The results of the present study reveal that the lncRNA ZNF67-1 may restrain the carcinogenesis of NPC, and may also serve as a potential biomarker for the early diagnosis and treatment of NPC.

Optogenetic pacing in Drosophila melanogaster (Conference Presentation)

NASA Astrophysics Data System (ADS)

Alex, Aneesh; Li, Airong; Men, Jing; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

2016-03-01

A non-invasive, contact-less cardiac pacing technology can be a powerful tool in basic cardiac research and in clinics. Currently, electrical pacing is the gold standard for cardiac pacing. Although highly effective in controlling the cardiac function, the invasive nature, non-specificity to cardiac tissues and possible tissue damage limits its capabilities. Optical pacing of heart is a promising alternative, which is non-invasive and more specific, has high spatial and temporal precision, and avoids shortcomings in electrical stimulation. Optical coherence tomography has been proved to be an effective technique in non-invasive imaging in vivo with ultrahigh resolution and imaging speed. In the last several years, non-invasive specific optical pacing in animal hearts has been reported in quail, zebrafish, and rabbit models. However， Drosophila Melanogaster, which is a significant model with orthologs of 75% of human disease genes, has rarely been studied concerning their optical pacing in heart. Here, we combined optogenetic control of Drosophila heartbeat with optical coherence microscopy (OCM) technique for the first time. The light-gated cation channel, channelrhodopsin-2 (ChR2) was specifically expressed by transgene as a pacemaker in drosophila heart. By stimulating the pacemaker with 472 nm pulsed laser light at different frequencies, we achieved non-invasive and more specific optical control of the Drosophila heart rhythm, which demonstrates the wide potential of optical pacing for studying cardiac dynamics and development. Imaging capability of our customized OCM system was also involved to observe the pacing effect visually. No tissue damage was found after long exposure to laser pulses, which proved the safety of optogenetic control of Drosophila heart.

Non-invasive Transdermal Two-dimensional Mapping of Cutaneous Oxygenation with Rapid-drying Liquid Bandage

DTIC Science & Technology

2014-10-01

biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of...response to infections and collagen synthesis; damaged tissue deprived of adequate blood flow has a decreased ability to heal [1, 7]. The surgical...EXPRESS 3754 2.5. Monitoring wound progression of in vivo porcine full-thickness burns Animal housing and maintenance: A Yorkshire cross-bred female pig

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Smartphone spectrometer for non-invasive diffuse reflectance spectroscopy based hemoglobin sensing (Conference Presentation)

NASA Astrophysics Data System (ADS)

Edwards, Perry S.

2016-10-01

Fiber-optic based diffuse reflectance spectroscopy (DRS) is shown to be a highly specific and highly sensitive method for non-invasive detection of various cancers (e.g. cervical and oral) as well as many other diseases. Fiber-optic DRS diagnosis relies on non-invasive biomarker detection (e.g. oxy- and deoxy-hemoglobin) and can be done without the need for sophisticated laboratory analysis of samples. Thus, it is highly amenable for clinical adoption especially in resource scarce regions that have limited access to such developed laboratory infrastructure. Despite the demonstrated effectiveness of fiber-optic DRS, such systems remain cost prohibitive in many of these regions, mainly due to the use of bulky and expensive spectrometers. Here, a fiber-optic DRS system is coupled to a smartphone spectrometer and is proposed as a low-cost solution for non-invasive tissue hemoglobin sensing. The performance of the system is assessed by measuring tissue phantoms with varying hemoglobin concentrations. A DRS retrieval algorithm is used to extract hemoglobin parameters from the measurements and determine the accuracy of the system. The results are then compared with those of a previously reported fiber-optic DRS system which is based on a larger more expensive spectrometer system. The preliminary results are encouraging and indicate the potential of the smartphone spectrometer as a viable low-cost option for non-invasive tissue hemoglobin sensing.

Non-invasive Characterization of the Histopathologic Features of Pulmonary Nodules of the Lung Adenocarcinoma Spectrum using Computer Aided Nodule Assessment and Risk Yield (CANARY) – a Pilot Study

PubMed Central

Maldonado, Fabien; Boland, Jennifer M.; Raghunath, Sushravya; Aubry, Marie Christine; Bartholmai, Brian J.; deAndrade, Mariza; Hartman, Thomas E.; Karwoski, Ronald A.; Rajagopalan, Srinivasan; Sykes, Anne-Marie; Yang, Ping; Yi, Eunhee S.; Robb, Richard A.; Peikert, Tobias

2013-01-01

Introduction Pulmonary nodules of the adenocarcinoma spectrum are characterized by distinctive morphological and radiological features and variable prognosis. Non-invasive high-resolution computed-tomography (HRCT)-based risk stratification tools are needed to individualize their management. Methods Radiological measurements of histopathologic tissue invasion were developed in a training set of 54 pulmonary nodules of the adenocarcinoma spectrum and validated in 86 consecutively resected nodules. Nodules were isolated and characterized by computer-aided analysis and data were analyzed by Spearman correlation, sensitivity, specificity as well as the positive and negative predictive values. Results Computer Aided Nodule Assessment and Risk Yield (CANARY) can non-invasively characterize pulmonary nodules of the adenocarcinoma spectrum. Unsupervised clustering analysis of HRCT data identified 9 unique exemplars representing the basic radiologic building blocks of these lesions. The exemplar distribution within each nodule correlated well with the proportion of histologic tissue invasion, Spearman R=0.87,p < 0.0001 and 0.89,p < 0.0001 for the training and the validation set, respectively. Clustering of the exemplars in three-dimensional space corresponding to tissue invasion and lepidic growth was used to develop a CANARY decision algorithm, which successfully categorized these pulmonary nodules as “aggressive” (invasive adenocarcinoma) or “indolent” (adenocarcinoma in situ and minimally invasive adenocarcinoma). Sensitivity, specificity, positive predictive value and negative predictive value of this approach for the detection of “aggressive” lesions were 95.4%, 96.8%, 95.4% and 96.8%, respectively in the training set and 98.7%, 63.6%, 94.9% and 87.5%, respectively in the validation set. Conclusion CANARY represents a promising tool to non-invasively risk stratify pulmonary nodules of the adenocarcinoma spectrum. PMID:23486265

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

PubMed

Ahmed, A K; Goodwin, C R; Sarabia-Estrada, R; Lay, F; Ansari, A M; Steenbergen, C; Pang, C; Cohen, R; Born, L J; Matsangos, A E; Ng, C; Marti, G P; Abu-Bonsrah, N; Phillips, N A; Suk, I; Sciubba, D M; Harmon, J W

2016-12-01

Experimental study. The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Potential secondary poisoning risks to non-targets from a sodium nitrite toxic bait for invasive wild pigs.

PubMed

Snow, Nathan P; Foster, Justin A; VanNatta, Eric H; Horak, Katherine E; Humphrys, Simon T; Staples, Linton D; Hewitt, David G; VerCauteren, Kurt C

2018-01-01

An acute and orally delivered toxic bait containing micro-encapsulated sodium nitrite (MESN), is under development to provide a novel and humane technology to help curtail damage caused by invasive wild pigs (Sus scrofa). We evaluated potential secondary risks for non-target species by: testing whether four different types of micro-encapsulation coatings could reduce vomiting by invasive wild pigs, testing the levels of residual sodium nitrite (SN) in tissues of invasive wild pigs, testing the environmental persistence of SN in vomitus, and conducting a risk assessment for scavengers. Micro-encapsulation coatings did not affect the frequency of vomiting. We identified no risk of secondary poisoning for non-target scavengers that consume muscle, eyes, and livers of invasive wild pig carcasses because residual SN from the toxic bait was not detected in those tissues. The risk of secondary poisoning from consuming vomitus appeared low because ∼90% of the SN was metabolized or broken down prior to vomiting, and continued to degrade after being exposed to the environment. Secondary poisoning could occur for common scavengers that consume approximately ≥15% of their daily dietary requirements of digestive tract tissues or undigested bait from carcasses of invasive wild pigs in a rapid, single-feeding event. The likelihood of this occurring in a natural setting is unknown. The digestive tracts of poisoned invasive wild pigs contained an average of ∼4.35 mg/g of residual SN. Data from this study suggest no risks of secondary poisoning for non-target species (including humans) that consume muscle, liver, or eyes of invasive wild pigs poisoned with a MESN toxic bait. More species-specific testing for scavengers that consume digestive tract tissues and undigested bait is needed to reduce uncertainty about these potential risks. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Overexpression of COX-2 in Rat Oral Cancers and Prevention of Oral Carcinogenesis in Rats by Selective and Non-Selective COX Inhibitors

PubMed Central

McCormick, David L.; Phillips, Jonathan M.; Horn, Thomas L.; Johnson, William D.; Steele, Vernon E.; Lubet, Ronald A.

2009-01-01

Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO) demonstrate substantial overexpression of cyclooxygenase-2 (COX-2) when compared to adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase (5-LOX) nor 12-lipoxygenase (12-LOX) is overexpressed in rat oral cancers. Two chemoprevention studies were performed to test the resulting hypothesis that COX-2 is a useful target for oral cancer chemoprevention in the rat. In both studies, male F344 rats received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by administration of chemopreventive agents from week 10 until study termination at week 26. In the first study, groups of rats were fed basal diet (control), or basal diet supplemented with the selective COX-2 inhibitor, celecoxib (500 or 1500 mg/kg diet); the non-selective COX inhibitor, piroxicam (50 or 150 mg/kg diet); or the 5-LOX inhibitor, zileuton (2000 mg/kg diet). In the second study, rats were fed basal diet (control) or basal diet supplemented with NO-Naproxen (180 or 90 mg/kg diet), a non-selective COX inhibitor that demonstrates reduced gastrointestinal toxicity. When compared to dietary controls, celecoxib decreased oral cancer incidence, cancer invasion score, and cancer-related mortality. Piroxicam decreased cancer-related mortality and cancer invasion score, while NO-naproxen decreased oral cancer incidence and cancer invasion score. By contrast, zileuton demonstrated no chemopreventive activity by any parameter assessed. These data demonstrate that both selective and non-selective inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The chemopreventive activity of COX inhibitors may be linked to overexpression of their enzymatic target in incipient oral neoplasms. PMID:20051374

Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

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

Sun, Lin; Li, Yu; Yang, Bangxiang, E-mail: b19933009@qq.coom

Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition ofmore » proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.« less

From mini-invasive to non-invasive treatment using monopolar radiofrequency: the next orthopaedic frontier.

PubMed

Whipple, Terry L

2009-10-01

Tendinopathy arises from a failed tendon healing process. Current non-invasive therapeutic alternatives are anti-inflammatory in nature, and outcomes are unpredictable. The benefit of invasive alternatives resides in the induction of the healing response. A new technology that uses non-invasive monopolar capacitive coupled radiofrequency has demonstrated the ability to raise temperatures in tendons and ligaments above 50 degrees C, the threshold for collagen modulation, tissue shrinkage and recruitment of macrophages, fibroblasts, and heat shock protein factors, without damaging the overlying structures, resulting in activation of the wound healing response. Monopolar capacitive-coupled radiofrequency offers a new non-invasive choice for tendinopathies and sprained ligaments. It does not interfere with subsequent surgical procedures should they become necessary.

Non-invasive assessment of negative pressure wound therapy using high frequency diagnostic ultrasound: oedema reduction and new tissue accumulation.

PubMed

Young, Stephen R; Hampton, Sylvie; Martin, Robin

2013-08-01

Tissue oedema plays an important role in the pathology of chronic and traumatic wounds. Negative pressure wound therapy (NPWT) is thought to contribute to active oedema reduction, yet few studies have showed this effect. In this study, high frequency diagnostic ultrasound at 20 MHz with an axial resolution of 60 µm was used to assess the effect of NPWT at - 80 mmHg on pressure ulcers and the surrounding tissue. Wounds were monitored in four patients over a 3-month period during which changes in oedema and wound bed thickness (granulation tissue) were measured non-invasively. The results showed a rapid reduction of periwound tissue oedema in all patients with levels falling by a mean of 43% after 4 days of therapy. A 20% increase in the thickness of the wound bed was observed after 7 days due to new granulation tissue formation. Ultrasound scans through the in situ gauze NPWT filler also revealed the existence of macrodeformation in the tissue produced by the negative pressure. These preliminary studies suggest that non-invasive assessment using high frequency diagnostic ultrasound could be a valuable tool in clinical studies of NPWT. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Chick Heart Invasion Assay for Testing the Invasiveness of Cancer Cells and the Activity of Potentially Anti-invasive Compounds.

PubMed

Bracke, Marc E; Roman, Bart I; Stevens, Christian V; Mus, Liselot M; Parmar, Virinder S; De Wever, Olivier; Mareel, Marc M

2015-06-06

The goal of the chick heart assay is to offer a relevant organ culture method to study tumor invasion in three dimensions. The assay can distinguish between invasive and non-invasive cells, and enables study of the effects of test compounds on tumor invasion. Cancer cells - either as aggregates or single cells - are confronted with fragments of embryonic chick heart. After organ culture in suspension for a few days or weeks the confronting cultures are fixed and embedded in paraffin for histological analysis. The three-dimensional interaction between the cancer cells and the normal tissue is then reconstructed from serial sections stained with hematoxylin-eosin or after immunohistochemical staining for epitopes in the heart tissue or the confronting cancer cells. The assay is consistent with the recent concept that cancer invasion is the result of molecular interactions between the cancer cells and their neighbouring stromal host elements (myofibroblasts, endothelial cells, extracellular matrix components, etc.). Here, this stromal environment is offered to the cancer cells as a living tissue fragment. Supporting aspects to the relevance of the assay are multiple. Invasion in the assay is in accordance with the criteria of cancer invasion: progressive occupation and replacement in time and space of the host tissue, and invasiveness and non-invasiveness in vivo of the confronting cells generally correlates with the outcome of the assay. Furthermore, the invasion pattern of cells in vivo, as defined by pathologists, is reflected in the histological images in the assay. Quantitative structure-activity relation (QSAR) analysis of the results obtained with numerous potentially anti-invasive organic congener compounds allowed the study of structure-activity relations for flavonoids and chalcones, and known anti-metastatic drugs used in the clinic (e.g., microtubule inhibitors) inhibit invasion in the assay as well. However, the assay does not take into account immunological contributions to cancer invasion.

Long non-coding RNA linc-cdh4-2 inhibits the migration and invasion of HCC cells by targeting R-cadherin pathway

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

Gao, Yunzhen; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025; Wang, Gaoxiong

Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). Linc-cdh4-2 (TCONS-00027978) is a novel LncRNA that has been identified in HCC tissues from our previous study. Overexpression of linc-cdh4-2 in HCC cell lines (SK-Hep-1 and Huh7) significantly decreases the migration and invasion abilities of these cells, while knockdown the expression of linc-cdh4-2 significantly increases the migration and invasion abilities. Interestingly, neither the over expression nor the knock down of linc-cdh4-2 could affect the viability and proliferation of HCC cells. Mechanistically, the linc-cdh4-2 could up-regulate the protein level of R-cadherin through direct bindingmore » that might improve the protein stability. Over expression of linc-cdh4-2 could significantly increase the protein levels of R-cadherin and decrease the protein levels of small GTPase RAC1, and vice-versa. Further knockdown R-cadherin in linc-cdh4-2 stably overexpressed cells, could significantly upregulate the protein levels of RAC1 and improve the cell migration and invasion abilities. Taken together, the novel linc-cdh4-2 may negatively regulate the motility of the HCC cells through targeting R-cadherin-RAC1 signaling pathway. - Highlights: • Linc-cdh4-2 negatively related with the invasion and metastasis ability of HCC cells. • Linc-cdh4-2 could up-regulate the protein level of R-cadherin through direct binding. • Knockdown of R-cadherin increases the migration and invasion abilities of HCC cell. • Knockdown of R-cadherin could significantly upregulate the protein levels of RAC1.« less

Imaging Ultrasound Guidance and on-line Estimation of Thermal Behavior in HIFU Exposed Targets

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Haryanto, Amir

2006-05-01

Elevated temperatures have been used for many years to combat several diseases including treatment of certain types of cancers/tumors. High Intensity Focused Ultrasound (HIFU) has emerged as a potential non-invasive modality for trackless targeting of deep-seated cancers of human body. For the procedures which require thermal elevation such as hyperthermia and tissue ablation, temperature becomes a parameter of vital importance in order to monitor the treatment on-line. Also, embedding invasive temperature probes for this purpose beats the supremacy of the non-invasive ablating modality. In this paper, we describe the use of a non-invasive and inexpensive conventional imaging ultrasound modality for lesion positioning and estimation of thermal behavior of the tissue on exposure to HIFU. Representative results of our online lesion tracking algorithm for discerning lesioning behavior using image capture, processing and phase-shift measurements are presented.

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. Purpose: The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, medial gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

PubMed

Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

2011-04-01

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Monoamine oxidase A (MAO A) inhibitors decrease glioma progression.

PubMed

Kushal, Swati; Wang, Weijun; Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L; Olenyuk, Bogdan Z; Chen, Thomas C; Hofman, Florence M; Shih, Jean C

2016-03-22

Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis.

Non-invasive subcutaneous fat reduction: a review.

PubMed

Kennedy, J; Verne, S; Griffith, R; Falto-Aizpurua, L; Nouri, K

2015-09-01

The risks, financial costs and lengthy downtime associated with surgical procedures for fat reduction have led to the development of a number of non-invasive techniques. Non-invasive body contouring now represents the fastest growing area of aesthetic medicine. There are currently four leading non-invasive techniques for reducing localized subcutaneous adipose tissue: low-level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high-intensity focused ultrasound (HIFU). To review and compare leading techniques and clinical outcomes of non-invasive subcutaneous fat reduction. The terms 'non-invasive', 'low-level laser', 'cryolipolysis', 'ultrasound' and 'radio frequency' were combined with 'lipolysis', 'fat reduction' or 'body contour' during separate searches in the PubMed database. We identified 31 studies (27 prospective clinical studies and four retrospective chart reviews) with a total of 2937 patients that had been treated with LLLT (n = 1114), cryolipolysis (n = 706), HIFU (n = 843) or RF (n = 116) or other techniques (n = 158) for fat reduction or body contouring. A majority of these patients experienced significant and satisfying results without any serious adverse effects. The studies investigating these devices have all varied in treatment regimen, body locations, follow-up times or outcome operationalization. Each technique differs in offered advantages and severity of adverse effects. However, multiple non-invasive devices are safe and effective for circumferential reduction in local fat tissue by 2 cm or more across the abdomen, hips and thighs. Results are consistent and reproducible for each device and none are associated with any serious or permanent adverse effects. © 2015 European Academy of Dermatology and Venereology.

Speckle contrast optical spectroscopy, a non-invasive, diffuse optical method for measuring microvascular blood flow in tissue

PubMed Central

Valdes, Claudia P.; Varma, Hari M.; Kristoffersen, Anna K.; Dragojevic, Tanja; Culver, Joseph P.; Durduran, Turgut

2014-01-01

We introduce a new, non-invasive, diffuse optical technique, speckle contrast optical spectroscopy (SCOS), for probing deep tissue blood flow using the statistical properties of laser speckle contrast and the photon diffusion model for a point source. The feasibility of the method is tested using liquid phantoms which demonstrate that SCOS is capable of measuring the dynamic properties of turbid media non-invasively. We further present an in vivo measurement in a human forearm muscle using SCOS in two modalities: one with the dependence of the speckle contrast on the source-detector separation and another on the exposure time. In doing so, we also introduce crucial corrections to the speckle contrast that account for the variance of the shot and sensor dark noises. PMID:25136500

Non-invasive measurements of tissue hemodynamics with hybrid diffuse optical methods

NASA Astrophysics Data System (ADS)

Durduran, Turgut

Diffuse optical techniques were used to measure hemodynamics of tissues non-invasively. Spectroscopy and tomography of the brain, muscle and implanted tumors were carried out in animal models and humans. Two qualitatively different methods, diffuse optical tomography and diffuse correlation tomography, were hybridized permitting simultaneous measurement of total hemoglobin concentration, blood oxygen saturation and blood flow. This combination of information was processed further to derive estimates of oxygen metabolism (e.g. CMRO 2) in tissue. The diffuse correlation measurements of blood flow were demonstrated in human tissues, for the first time, demonstrating continous, non-invasive imaging of oxygen metabolism in large tissue volumes several centimeters below the tissue surface. The bulk of these investigations focussed on cerebral hemodynamics. Extensive validation of this methodology was carried out in in vivo rat brain models. Three dimensional images of deep tissue hemodynamics in middle cerebral artery occlusion and cortical spreading depression (CSD) were obtained. CSD hemodynamics were found to depend strongly on partial pressure of carbon dioxide. The technique was then adapted for measurement of human brain. All optical spectroscopic measurements of CMRO2 during functional activation were obtained through intact human skull non-invasively. Finally, a high spatio-temporal resolution measurement of cerebral blood flow due to somatosensory cortex activation following electrical forepaw stimulation in rats was carried out with laser speckle flowmetry. New analysis methods were introduced for laser speckle flowmetry. In other organs, deep tissue hemodynamics were measured on human calf muscle during exercise and cuff-ischemia and were shown to have some clinical utility for peripheral vascular disease. In mice tumor models, the measured hemodynamics were shown to be predictive of photodynamic therapy efficacy, again suggesting promise of clinical utility. In total, the research has pioneered the development of diffuse optical measurements of blood flow, oxygenation and oxygen metabolism in a large range of research and clinical applications.

Long non-coding RNA CASP5 promotes the malignant phenotypes of human glioblastoma multiforme.

PubMed

Zhou, Yali; Dai, Wei; Wang, Handong; Pan, Hao; Wang, Qiang

2018-06-12

Long non-coding RNAs (lncRNAs) have been demonstrated to be intensively involved in the development of various carcinomas, including glioblastoma multiforme (GBM). However, only a few of them have been well characterized. LncRNA CASP5 have been found to be up-regulated in GBM tissues compared with normal tissues in a microarray-based lncRNA profiling study. In the present study, we further explored the biological role of lncRNA CASP5 in GBM. We examined the expression level of lncRNA CASP5 in GBM tissues as well as GBM cell lines. CCK-8 assay, flow cytometric analysis, western blotting, orthotopic GBM model as well as transwell assay were performed to investigate the biological role of CASP5. We observed that lncRNA CASP5 was highly expressed in GBM tissues and cell lines. Knockdown of CASP5 greatly inhibited GBM proliferation and resulted in G1 cell cycle arrest along with higher apoptosis ratios in vitro and in vivo, while overexpression led to the opposite phenomenon. Furthermore, the migration and invasion ability of GBM cells were significantly decreased after CASP5 down-regulation, while increased migration and invasion can be observed after CASP5 up-regulation. We demonstrate for the first time the potential oncogenic role of lncRNA CASP5 which may be helpful for identifying novel therapeutic targets in GBM. Copyright © 2018 Elsevier Inc. All rights reserved.

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

NASA Astrophysics Data System (ADS)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

2015-05-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3

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

Li, Butian; Zhang, Shengping; Shen, Hao

MicroRNAs are aberrantly expressed in a wide variety of human cancers. The present study aims to elucidate the effects and molecular mechanisms of miR-144-3p that underlie gastric cancer (GC) development. It was observed that miR-144-3p expression was significantly decreased in GC tissues compared to that in paired non-tumor tissues; moreover, its expression was lower in tissues of advanced stage and larger tumor size, as well as in lymph node metastasis tissues compared to that in control groups. miR-144-3p expression was associated with depth of invasion (P = 0.030), tumor size (P = 0.047), lymph node metastasis (P = 0.047), and TNM stage (P = 0.048). Additionally, miR-144-3p significantlymore » inhibited proliferation, migration, and invasion in GC cells. It also reduced F-actin expression and suppressed epithelial-to-mesenchymal transition (EMT) in GC cells. Furthermore, pre-leukemia transcription factor 3 (PBX3) was a direct target gene of miR-144-3p. PBX3 was overexpressed in GC tissues and promoted EMT in GC cells. The effects of miR-144-3p mimics or inhibitors on cell migration, invasion, and proliferation were reversed by PBX3 overexpression or downregulation respectively. These results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3. - Highlights: • miR-144-3p is downregulated in gastric cancer tissues and associated with malignant clinical factors. • miR-144-3p inhibits proliferation, migration, and invasion in gastric cancer cells. • PBX3 is a direct target of miR-144-3p and promotes EMT in gastric cancer. • miR-144-3p suppresses EMT in gastric cancer by regulating PBX3.« less

Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

NASA Astrophysics Data System (ADS)

Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

2017-05-01

Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

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.

An integrated optical coherence microscopy imaging and optical stimulation system for optogenetic pacing in Drosophila melanogaster (Conference Presentation)

NASA Astrophysics Data System (ADS)

Alex, Aneesh; Li, Airong; Men, Jing; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

2016-03-01

Electrical stimulation is the clinical standard for cardiac pacing. Although highly effective in controlling cardiac rhythm, the invasive nature, non-specificity to cardiac tissues and possible tissue damage limits its applications. Optogenetic pacing of the heart is a promising alternative, which is non-invasive and more specific, has high spatial and temporal precision, and avoids the shortcomings in electrical stimulation. Drosophila melanogaster, which is a powerful model organism with orthologs of nearly 75% of human disease genes, has not been studied for optogenetic pacing in the heart. Here, we developed a non-invasive integrated optical pacing and optical coherence microscopy (OCM) imaging system to control the heart rhythm of Drosophila at different developmental stages using light. The OCM system is capable of providing high imaging speed (130 frames/s) and ultrahigh imaging resolutions (1.5 μm and 3.9 μm for axial and transverse resolutions, respectively). A light-sensitive pacemaker was developed in Drosophila by specifically expressing the light-gated cation channel, channelrhodopsin-2 (ChR2) in transgenic Drosophila heart. We achieved non-invasive and specific optical control of the Drosophila heart rhythm throughout the fly's life cycle (larva, pupa, and adult) by stimulating the heart with 475 nm pulsed laser light. Heart response to stimulation pulses was monitored non-invasively with OCM. This integrated non-invasive optogenetic control and in vivo imaging technique provides a novel platform for performing research studies in developmental cardiology.

Non Digestible Oligosaccharides Modulate the Gut Microbiota to Control the Development of Leukemia and Associated Cachexia in Mice.

PubMed

Bindels, Laure B; Neyrinck, Audrey M; Salazar, Nuria; Taminiau, Bernard; Druart, Céline; Muccioli, Giulio G; François, Emmanuelle; Blecker, Christophe; Richel, Aurore; Daube, Georges; Mahillon, Jacques; de los Reyes-Gavilán, Clara G; Cani, Patrice D; Delzenne, Nathalie M

2015-01-01

We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS) or inulin (INU) differently modulates the progression of leukemia and related metabolic disorders. Mice were transplanted with Bcr-Abl-transfected proB lymphocytes mimicking leukemia and received either POS or INU in their diet (5%) for 2 weeks. Combination of pyrosequencing, PCR-DGGE and qPCR analyses of the 16S rRNA gene revealed that POS decreased microbial diversity and richness of caecal microbiota whereas it increased Bifidobacterium spp., Roseburia spp. and Bacteroides spp. (affecting specifically B. dorei) to a higher extent than INU. INU supplementation increased the portal SCFA propionate and butyrate, and decreased cancer cell invasion in the liver. POS treatment did not affect hepatic cancer cell invasion, but was more efficient than INU to decrease the metabolic alterations. Indeed, POS better than INU delayed anorexia linked to cancer progression. In addition, POS treatment increased acetate in the caecal content, changed the fatty acid profile inside adipose tissue and counteracted the induction of markers controlling β-oxidation, thereby hampering fat mass loss. Non digestible carbohydrates with prebiotic properties may constitute a new nutritional strategy to modulate gut microbiota with positive consequences on cancer progression and associated cachexia.

Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.

PubMed

Wakita, Toshiaki; Hayashi, Tatsuya; Nishioka, Junji; Tamaru, Hiroshi; Akita, Nobuyuki; Asanuma, Kunihiro; Kamada, Haruhiko; Gabazza, Esteban C; Ido, Masaru; Kawamura, Juichi; Suzuki, Koji

2004-02-10

Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1 cells transfected with a PCI expression vector was significantly decreased compared to mock-transfected Caki-1 cells, and it was blocked in the presence of anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki-1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat-inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki-1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat-inactivated PCI. In addition, uPA activity was significantly decreased and uPA-PCI complex level was significantly increased in the culture medium of PCI expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells. The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion. Copyright 2003 Wiley-Liss, Inc.

Non-invasive monitoring of skin inflammation using an oxygen-sensing paint-on bandage

PubMed Central

Li, Zongxi; Navarro-Alvarez, Nalu; Keeley, Emily J.; Nowell, Nicholas H.; Goncalves, Beatriz M. M.; Huang, Christene A.; Evans, Conor L.

2017-01-01

Inflammation involves a cascade of cellular and molecular mediators that ultimately lead to the infiltration of immune cells into the affected area. This inflammatory process in skin is common to many diseases including acne, infection, and psoriasis, with the presence or absence of immune cells a potential diagnostic marker. Here we show that skin inflammation can be non-invasively measured and mapped using a paint-on oxygen sensing bandage in an in vivo porcine inflammation model. After injection of a known inflammatory agent, the bandage could track the increase, plateau, and decrease in oxygen consumption at the injury site over 7 weeks, as well as discern inflammation resultant from injection at various depths beneath the surface of the skin. Both the initial rate of pO2 change and the change in bandage pO2 at equilibration (CBP20) were found to be directly related to the metabolic oxygen consumption rate of the tissue in contact. Healthy skin demonstrated an initial pO2 decrease rate of 6.5 mmHg⋅min−1, and CBP20 of 84 mmHg. Inflamed skin had a significantly higher initial consumption rate of 55 mmHg⋅min−1, and a larger CBP20 of 140 mmHg. The change in the bandage pO2 before and after equilibration with tissue was found to correlate well with histological evidence of skin inflammation in the animals. PMID:29082091

Fluorescence spectroscopy and imaging for noninvasive diagnostics: applications to early cancer detection in the lung

NASA Astrophysics Data System (ADS)

Mycek, Mary-Ann; Urayama, Paul; Zhong, Wei; Sloboda, Roger D.; Dragnev, Konstantin H.; Dmitrovsky, Ethan

2003-10-01

Tissue fluorescence spectroscopy and imaging are being investigated as potential methods for non-invasive detection of pre-neoplastic change in the lung and other organ systems. A substantial contribution to tissue fluorescence is known to arise from endogenous cellular fluorophores. Using steady-state and time-resolved fluorescence spectroscopy and imaging, we characterized the endogenous fluorescence properties of immortalized and carcinogen-transformed human bronchial epithelial cells. Non-invasive sensing of endogenous molecular biomarkers associated with human bronchial pre-neoplasia will be discussed.

Non-invasive characterization of structure and morphology of silk fibroin biomaterials using non-linear microscopy

PubMed Central

Rice, William L.; Firdous, Shamaraz; Gupta, Sharad; Hunter, Martin; Foo, Cheryl Wong Po; Wang, Yongzhong; Kim, Hyeon Joo; Kaplan, David L.; Georgakoudi, Irene

2009-01-01

Designing biomaterial scaffolds remains a major challenge in tissue engineering. Key to this challenge is improved understanding of the relationships between the scaffold properties and its degradation kinetics, as well as the cell interactions and the promotion of new matrix deposition. Here we present the use of non-linear spectroscopic imaging as a non-invasive method to characterize not only morphological, but also structural aspects of silkworm silk fibroin-based biomaterials, relying entirely on endogenous optical contrast. We demonstrate that two photon excited fluorescence and second harmonic generation are sensitive to the hydration, overall β sheet content and molecular orientation of the sample. Thus, the functional content and high resolution afforded by these non-invasive approaches offer promise for identifying important connections between biomaterial design and functional engineered tissue development. The strategies described also have broader implications for understanding and tracking the remodeling of degradable biomaterials under dynamic conditions both in vitro and in vivo. PMID:18291520

PilY1 Promotes Legionella pneumophila Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility.

PubMed

Hoppe, Julia; Ünal, Can M; Thiem, Stefanie; Grimpe, Louisa; Goldmann, Torsten; Gaßler, Nikolaus; Richter, Matthias; Shevchuk, Olga; Steinert, Michael

2017-01-01

Legionnaires' disease is an acute fibrinopurulent pneumonia. During infection Legionella pneumophila adheres to the alveolar lining and replicates intracellularly within recruited macrophages. Here we provide a sequence and domain composition analysis of the L. pneumophila PilY1 protein, which has a high homology to PilY1 of Pseudomonas aeruginosa . PilY1 proteins of both pathogens contain a von Willebrand factor A (vWFa) and a C-terminal PilY domain. Using cellular fractionation, we assigned the L. pneumophila PilY1 as an outer membrane protein that is only expressed during the transmissive stationary growth phase. PilY1 contributes to infection of human lung tissue explants (HLTEs). A detailed analysis using THP-1 macrophages and A549 lung epithelial cells revealed that this contribution is due to multiple effects depending on host cell type. Deletion of PilY1 resulted in a lower replication rate in THP-1 macrophages but not in A549 cells. Further on, adhesion to THP-1 macrophages and A549 epithelial cells was decreased. Additionally, the invasion into non-phagocytic A549 epithelial cells was drastically reduced when PilY1 was absent. Complementation variants of a PilY1-negative mutant revealed that the C-terminal PilY domain is essential for restoring the wild type phenotype in adhesion, while the putatively mechanosensitive vWFa domain facilitates invasion into non-phagocytic cells. Since PilY1 also promotes twitching motility of L. pneumophila , we discuss the putative contribution of this newly described virulence factor for bacterial dissemination within infected lung tissue.

Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling.

PubMed

Kikuta, Kazutaka; Kubota, Daisuke; Yoshida, Akihiko; Qiao, Zhiwei; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Chuman, Hirokazu; Kawai, Akira; Kondo, Tadashi

2017-09-01

Myxofibrosarcoma (MFS) is a mesenchymal malignancy characterized by frequent recurrence even after radical wide resection. To optimize therapy for MFS patients, we aimed to identify candidate tissue biomarkers of MFS invasion potential. Invasion characteristics of MFS were evaluated by magnetic resonance imaging and protein expression profiling of primary tumor tissues performed using two-dimensional difference gel electrophoresis (2D-DIGE). Protein expression profiles were compared between invasive and non-invasive tumors surgically resected from 11 patients. Among the 3453 protein spots observed, 59 demonstrated statistically significant difference in intensity (≥2-fold) between invasive and non-invasive tumors (p<0.01 by Wilkoxon test), and were identified by mass spectrometry as 47 individual proteins. Among them, we further focused on discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2), a receptor tyrosine kinase with aberrant expression in malignant tumors. Immunohistochemistry analysis of 21 additional MFS cases revealed that higher DCBLD2 expression was significantly associated with invasive properties of tumor cells. DCBLD2 sensitivity and specificity, and positive and negative predictive values for MFS invasion were 69.2%, 87.5%, 90%, and 63.6%, respectively. The expression level of DCBLD2 was consistent in different portions of tumor tissues. Thus, DCBLD2 expression can be a useful biomarker to evaluate invasive properties of MFS. Further validation studies based on multi-institutional collaboration and comprehensive analysis of DCBLD2 biological functions in MFS are required to confirm its prognostic utility for clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-invasive mechanical ventilation and mortality in elderly immunocompromised patients hospitalized with pneumonia: a retrospective cohort study.

PubMed

Johnson, Christopher S; Frei, Christopher R; Metersky, Mark L; Anzueto, Antonio R; Mortensen, Eric M

2014-01-27

Mortality after pneumonia in immunocompromised patients is higher than for immunocompetent patients. The use of non-invasive mechanical ventilation for patients with severe pneumonia may provide beneficial outcomes while circumventing potential complications associated with invasive mechanical ventilation. The aim of our study was to determine if the use of non-invasive mechanical ventilation in elderly immunocompromised patients with pneumonia is associated with higher all-cause mortality. In this retrospective cohort study, data were obtained from the Department of Veterans Affairs administrative databases. We included veterans age ≥65 years who were immunocompromised and hospitalized due to pneumonia. Multilevel logistic regression analysis was used to determine the relationship between the use of invasive versus non-invasive mechanical ventilation and 30-day and 90-day mortality. Of 1,946 patients in our cohort, 717 received non-invasive mechanical ventilation and 1,229 received invasive mechanical ventilation. There was no significant association between all-cause 30-day mortality and non-invasive versus invasive mechanical ventilation in our adjusted model (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.66-1.10). However, those patients who received non-invasive mechanical ventilation had decreased 90-day mortality (OR 0.66, 95% CI 0.52-0.84). Additionally, receipt of guideline-concordant antibiotics in our immunocompromised cohort was significantly associated with decreased odds of 30-day mortality (OR 0.31, 95% CI 0.24-0.39) and 90-day mortality (OR 0.41, 95% CI 0.31-0.53). Our findings suggest that physicians should consider the use of non-invasive mechanical ventilation, when appropriate, for elderly immunocompromised patients hospitalized with pneumonia.

Migration-stimulating factor (MSF) is over-expressed in non-small cell lung cancer and promotes cell migration and invasion in A549 cells over-expressing MSF

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

Deng, Xuefeng, E-mail: dengxfdoctor@hotmail.com; Department of Cardio-thoracic Surgery, Affiliated Hospital of Academy of Military Medical Sciences; Ma, Qunfeng

Migration-stimulating factor (MSF), an oncofetal truncated isoform of fibronectin, is a potent stimulator of cell invasion. However, its distribution and motogenic role in non-small cell lung cancer (NSCLC) have never been identified. In this study, real-time PCR and immunohistochemical staining (IHC) were performed to detect MSF mRNA and protein levels in tumor tissues and matched adjacent tumor-free tissues. Furthermore, to examine the effect of MSF on invasiveness, MSF was upregulated in A549 cells. The invasiveness and viability of A549 cells were then determined using a transwell migration assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assays, respectively. The expression level ofmore » MSF in NSCLC tissue was markedly higher than in matched adjacent tumor-free tissue. Additionally, the level of MSF protein expression in stage III and IV NSCLC samples was higher than in stage I and II NSCLC samples. More importantly, we also demonstrated that migration and invasion of A549 cells increased substantially after upregulating MSF, although proliferation remained unchanged. Meanwhile, we found no correlation between increasing motility and invasiveness of MSF-overexpressing cells and expression levels and activities of matrix metalloprotease MMP-2 and MMP-9. Our current study shows that MSF plays a role in migration and invasion of A549 cells and suggests that MSF may be a potential biomarker of NSCLC progression. - Highlights: • MSF expression was upregulated in NSCLC and correlated with TNM stages. • MSF may be a new biomarker for NSCLC progression. • MSF promoted migration and invasion in A549 cells, independent of MMP-2/MMP-9 expression.« less

Invasive versus Non Invasive Methods Applied to Mummy Research: Will This Controversy Ever Be Solved?

PubMed Central

Day, Jasmine; Bianucci, Raffaella

2015-01-01

Advances in the application of non invasive techniques to mummified remains have shed new light on past diseases. The virtual inspection of a corpse, which has almost completely replaced classical autopsy, has proven to be important especially when dealing with valuable museum specimens. In spite of some very rewarding results, there are still many open questions. Non invasive techniques provide information on hard and soft tissue pathologies and allow information to be gleaned concerning mummification practices (e.g., ancient Egyptian artificial mummification). Nevertheless, there are other fields of mummy studies in which the results provided by non invasive techniques are not always self-explanatory. Reliance exclusively upon virtual diagnoses can sometimes lead to inconclusive and misleading interpretations. On the other hand, several types of investigation (e.g., histology, paleomicrobiology, and biochemistry), although minimally invasive, require direct contact with the bodies and, for this reason, are often avoided, particularly by museum curators. Here we present an overview of the non invasive and invasive techniques currently used in mummy studies and propose an approach that might solve these conflicts. PMID:26345295

Simulations and experiments of photon propagation in biological tissue and liquid crystal waveguides

NASA Astrophysics Data System (ADS)

Lines, Collin M.

The development of non-invasive methods to probe human tissue is an ongoing challenge in biomedical optics. In vivo measurements by conventional methods are limited by the mean free path (MFP) of a photon, which is governed by the spatial distribution of chromophores and the absorption and scattering properties of the tissue. As one of the strongest chromophores in human tissues, hemoglobin concentrations in human tissue greatly affect the MFP of photons in visible wavelengths (i.e. bruising). Changes in the concentration of hemoglobin and other chromophores within the tissue (minor trauma causing a contusion, increased bilirubin due to jaundice, etc.) will affect the MFP, leading to a visibly different appearance (color) of the tissue. As color perception is a complex physiological process, these changes are diffcult to quantify by human observation alone. The transport of hemoglobin and its breakdown products in tissue is related to a number of medical conditions that could benefit from a non-invasive method to determine the hemoglobin levels.

Time-dependent diffusion MRI in cancer: tissue modeling and applications

NASA Astrophysics Data System (ADS)

Reynaud, Olivier

2017-11-01

In diffusion weighted imaging (DWI), the apparent diffusion coefficient has been recognized as a useful and sensitive surrogate for cell density, paving the way for non-invasive tumor staging, and characterization of treatment efficacy in cancer. However, microstructural parameters, such as cell size, density and/or compartmental diffusivities affect diffusion in various fashions, making of conventional DWI a sensitive but non-specific probe into changes happening at cellular level. Alternatively, tissue complexity can be probed and quantified using the time dependence of diffusion metrics, sometimes also referred to as temporal diffusion spectroscopy when only using oscillating diffusion gradients. Time-dependent diffusion (TDD) is emerging as a strong candidate for specific and non-invasive tumor characterization. Despite the lack of a general analytical solution for all diffusion times / frequencies, TDD can be probed in various regimes where systems simplify in order to extract relevant information about tissue microstructure. The fundamentals of TDD are first reviewed (a) in the short time regime, disentangling structural and diffusive tissue properties, and (b) near the tortuosity limit, assuming weakly heterogeneous media near infinitely long diffusion times. Focusing on cell bodies (as opposed to neuronal tracts), a simple but realistic model for intracellular diffusion can offer precious insight on diffusion inside biological systems, at all times. Based on this approach, the main three geometrical models implemented so far (IMPULSED, POMACE, VERDICT) are reviewed. Their suitability to quantify cell size, intra- and extracellular spaces (ICS and ECS) and diffusivities are assessed. The proper modeling of tissue membrane permeability – hardly a newcomer in the field, but lacking applications - and its impact on microstructural estimates are also considered. After discussing general issues with tissue modeling and microstructural parameter estimation (i.e. fitting), potential solutions are detailed. The in vivo applications of this new, non-invasive, specific approach in cancer are reviewed, ranging from the characterization of gliomas in rodent brains and observation of time-dependence in breast tissue lesions and prostate cancer, to the recent preclinical evaluation of new treatments efficacy. It is expected that clinical applications of TDD will strongly benefit the community in terms of non-invasive cancer screening.

Skin carotenoids as biomarker for vegetable and fruit intake: Validation of the reflection-spectroscopy based “Veggie Meter”

USDA-ARS?s Scientific Manuscript database

Skin is a relatively stable storage medium for carotenoids; non-invasive optical measurements of carotenoids in this tissue via Resonance Raman spectroscopy (RRS) serve as a non-invasive biomarker for fruit and vegetable (F/V) intake. The RRS method has been validated with HPLC-based measurements of...

miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression

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

Yan, Chao; Yu, Jianchun, E-mail: yu_jchpumch@163.com; Kang, Weiming

Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target ofmore » miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma. - Highlights: • The expression of miR-935 is lower in GC tissue than in paired normal tissue. • The expression of miR-935 is lower in GSRCC tissue than in non-GSRCC. • Enhanced expression of miR-935 suppresses tumorigenesis of GSRCC. • Notch1 is a direct target of miR-935.« less

A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

PubMed

Sekerdag, Emine; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Öztürk, Naile; Kara, Aslı; Kaffashi, Abbas; Vural, Imran; Işıkay, Ilkay; Yavuz, Burҫin; Oguz, Kader Karlı; Söylemezoğlu, Figen; Gürsoy-Özdemir, Yasemin; Mut, Melike

2017-09-10

New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500μM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Intravital third harmonic generation microscopy of collective melanoma cell invasion

PubMed Central

Weigelin, Bettina; Bakker, Gert-Jan; Friedl, Peter

2012-01-01

Cancer cell invasion is an adaptive process based on cell-intrinsic properties to migrate individually or collectively, and their adaptation to encountered tissue structure acting as barrier or providing guidance. Whereas molecular and physical mechanisms of cancer invasion are well-studied in 3D in vitro models, their topographic relevance, classification and validation toward interstitial tissue organization in vivo remain incomplete. Using combined intravital third and second harmonic generation (THG, SHG), and three-channel fluorescence microscopy in live tumors, we here map B16F10 melanoma invasion into the dermis with up to 600 µm penetration depth and reconstruct both invasion mode and tissue tracks to establish invasion routes and outcome. B16F10 cells preferentially develop adaptive invasion patterns along preformed tracks of complex, multi-interface topography, combining single-cell and collective migration modes, without immediate anatomic tissue remodeling or destruction. The data suggest that the dimensionality (1D, 2D, 3D) of tissue interfaces determines the microanatomy exploited by invading tumor cells, emphasizing non-destructive migration along microchannels coupled to contact guidance as key invasion mechanisms. THG imaging further detected the presence and interstitial dynamics of tumor-associated microparticles with submicron resolution, revealing tumor-imposed conditioning of the microenvironment. These topographic findings establish combined THG, SHG and fluorescence microscopy in intravital tumor biology and provide a template for rational in vitro model development and context-dependent molecular classification of invasion modes and routes. PMID:29607252

A novel transcutaneous, non-focused ultrasound energy delivering device is able to induce subcutaneous adipose tissue destruction in an animal model.

PubMed

Levi, Assi; Amitai, Dan Ben; Lapidoth, Moshe

2017-01-01

The understanding that adipocytes are greatly influenced by thermal changes combined with the advancement of non-invasive ultrasound technologies have led to the application of ultrasound as an energy source to induce thermal fat destruction. While application of high intensity focused, ultrasound energy have been widely explored, there is far less information regarding the effects of non-focused ultrasound on adipose tissue. The purpose of this study was to characterize the effects of a novel transcutaneous, multi-elements, non-focused ultrasound energy regimen in an animal model, as a proof-of-concept of its potential to treat non-invasive subcutaneous benign tumors. The non-invasive transcutaneous ultrasound system prototype (LUMENIS, Ltd., Yoqneam, Israel) was applied to thermally induce adipocytes' death. During treatment, the ultrasound energy was transmitted into the subcutaneous adipose tissue (SAT) of 12 domestic adult female pigs. Two modes of operation (long and short), which differ in both the acoustic energy applied to the tissue and in their time durations (i.e., differ in their power settings), were used in this study. Efficacy and safety assessments included: Temperature measurement of skin and subcutaneous adipose tissue (SAT) visual inspection and ultrasound imaging of the thermally affected areas, histopathological assessment of tissue samples using hematoxylin & eosin, and Masson's trichrome stains and in situ cell death detection kit for apoptosis assessment. The long and short treatment modes led to a 13.2°C and 17.8°C rise from baseline, respectively, in the SAT, whereas skin surface temperature was practically unaffected. Visual, ultrasonographic, and histopathological evaluation of the treated area showed SAT ablation. No treatment-related changes were observed in the epidermis, dermis subcutaneous muscle and nerves, or in livers and kidneys of treated animals. Additionally, no significant changes from baseline in blood- and urine-borne analytes were detected post-treatment. The novel transcutaneous, multi-elements, non-focused ultrasound energy regimen used in this study, proved effective in non-invasively ablating SAT in an animal model. The usage of low energy settings such as in the current study might reduce unwanted side effects related to high energy application. Lasers Surg. Med. 49:110-121, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Enterolactone alters FAK-Src signaling and suppresses migration and invasion of lung cancer cell lines.

PubMed

Chikara, Shireen; Lindsey, Kaitlin; Borowicz, Pawel; Christofidou-Solomidou, Melpo; Reindl, Katie M

2017-01-09

Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined. We hypothesized that EL could inhibit lung cancer cell motility by affecting the FAK-Src signaling pathway. Non-toxic concentrations of EL were identified for A549 and H460 human lung cancer cells by conducting 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Dephenyltetrazolium Bromide (MTT) assays. The anti-migratory and anti-invasive potential of EL for lung cancer cell lines was determined by scratch wound healing and Matrigel® invasion assays. Changes in filamentous actin (F-actin) fiber density and length in EL-treated cells were determined using phalloidin-conjugated rhodamine dye and fluorescent microscopy. Vinculin expression in focal adhesions upon EL treatment was determined by immunocytochemistry. Gene and protein expression levels of FAK-Src signaling molecules in EL-treated lung cancer cells were determined using PCR arrays, qRT-PCR, and western blotting. Non-toxic concentrations of EL inhibited lung cancer cell migration and invasion in a concentration- and time-dependent manner. EL treatment reduced the density and number of F-actin fibers in lung cancer cell lines, and reduced the number and size of focal adhesions. EL decreased phosphorylation of FAK and its downstream targets, Src, paxillin, and decreased mRNA expression of cell motility-related genes, RhoA, Rac1, and Cdc42 in lung cancer cells. Our data suggest that EL suppresses lung cancer cell motility and invasion by altering FAK activity and subsequent activation of downstream proteins needed for focal adhesion formation and cytoskeletal rearrangement. Therefore, administration of EL may serve as a safe and complementary approach for inhibiting lung tumor cell motility, invasion, and metastasis.

Non-invasive MRI measurements of venous oxygenation, oxygen extraction fraction and oxygen consumption in neonates.

PubMed

De Vis, J B; Petersen, E T; Alderliesten, T; Groenendaal, F; de Vries, L S; van Bel, F; Benders, M J N L; Hendrikse, J

2014-07-15

Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a non-invasive MRI method to evaluate whole brain oxygen consumption in neonates. For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the 'T2 prepared tissue relaxation inversion recovery' pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements. Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12μmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic-ischemic encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01, respectively) with postnatal age. We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurement techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age. Copyright © 2014 Elsevier Inc. All rights reserved.

A review on the non-invasive evaluation of skeletal muscle oxygenation

NASA Astrophysics Data System (ADS)

Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

2016-07-01

The aim of this review is to conduct a feasibility study of non-invasive evaluation in skeletal muscle oxygenation. This non-invasive evaluation could extract many information using a safe non-invasive method regarding to the oxygenation and microcirculation status in human blood muscle. This brief review highlights the progress of the application of NIRS to evaluate skeletal muscle oxygenation in various activity of human nature from the historical point of view to the present advancement. Since the discovery of non-invasive optical method during 1992, there are many non-invasive techniques uses optical properties on human subject such as near infrared spectroscopy NIRS, optical topography, functional near infrared spectroscopy fNIRS and imaging fNIRI. Furthermore, in this paper we discuss the light absorption potential (LAP) towards chromophores content inside human muscle. Modified beer lambert law was studied in order to build a better understanding toward LAP between chromophores under tissue multilayers in human muscle. This paper will describe the NIRS principle and the basis for its proposed used in skeletal muscle oxygenation. This will cover the advantages and limitation of such application. Thus, these non-invasive techniques could open other possibilities to study muscle performance diagnosis.

Luminescent Tension-Indicating Orthopedic Strain Gauges for Non-Invasive Measurements Through Tissue

NASA Technical Reports Server (NTRS)

Anker, Jeffrey (Inventor); Anderson, Dakota (Inventor); Heath, Jonathon (Inventor); Rogalski, Melissa (Inventor)

2015-01-01

Strain gauges that can provide information with regard to the state of implantable devices are described. The strain gauges can exhibit luminescence that is detectable through living tissue, and the detectable luminescent emission can vary according to the strain applied to the gauge. A change in residual strain of the device can signify a loss of mechanical integrity and/or loosening of the implant, and this can be non-invasively detected either by simple visual detection of the luminescent emission or through examination of the emission with a detector such as a spectrometer or a camera.

Use of infrared thermography in children with shock: A case series

PubMed Central

Ortiz-Dosal, Alejandra; Rivera-Vega, Rosalina; Simón, Jorge; González, Francisco J

2014-01-01

Shock is a complex clinical syndrome caused by an acute failure of circulatory function resulting in inadequate tissue and organ perfusion. Digital infrared thermal imaging is a non-invasive technique that can detect changes in blood perfusion by detecting small changes in the temperature of the skin. In this preliminary study, eight pediatric patients (five boys, three girls), ages ranging from 6 to 14 years (average: 9.8 years), were admitted to the Intensive Care Unit at “Dr. Ignacio Morones Prieto” Central Hospital; here, the patients were examined using digital infrared thermal imaging. Patients in shock showed a significant decrease in distal temperature (at least 7°), compared to critically ill patients without shock. The latter group presented a skin temperature pattern very similar to the one previously reported for healthy children. The results show that infrared thermography can be used as a non-invasive method for monitoring the temperature in pediatric patients in intensive care units in order to detect shock in its early stages. PMID:27489669

Non-invasive Continuous Monitoring of Cerebral Edema Using Portable Microwave Based System

NASA Astrophysics Data System (ADS)

Jiang, Yuhao; Zhao, Minji; Wang, Huiqian; Li, Guoquan

2018-01-01

A portable non-invasive head detecting system based on microwave technology was developed for evaluation of cerebral edema change inside human brain. Real-time monitoring of cerebral edema in the brain helps the clinician to assess medical condition and treatment. In this work, a microwave signal was transmitted and coupled into an open-end circular waveguide sensor, incident on a 3D printed head phantom, and reflected back to receiver. Theoretically, the operation of this instrument depends on the conductivity contrast between cerebral edema and healthy brain tissues. The efficacy of the proposed detecting system is verified using 3D printed anatomically and dielectrically realistic human head phantoms with simulated cerebral edema targets with different size. Changes in the amplitude of time domain result were shown to be induced by the expansion or decrease of the edema volume. The eventual goal of this proposed head evaluating system is use in the hospital as an effective real-time monitoring tool.

Use of infrared thermography in children with shock: A case series.

PubMed

Ortiz-Dosal, Alejandra; Kolosovas-Machuca, Eleazar S; Rivera-Vega, Rosalina; Simón, Jorge; González, Francisco J

2014-01-01

Shock is a complex clinical syndrome caused by an acute failure of circulatory function resulting in inadequate tissue and organ perfusion. Digital infrared thermal imaging is a non-invasive technique that can detect changes in blood perfusion by detecting small changes in the temperature of the skin. In this preliminary study, eight pediatric patients (five boys, three girls), ages ranging from 6 to 14 years (average: 9.8 years), were admitted to the Intensive Care Unit at "Dr. Ignacio Morones Prieto" Central Hospital; here, the patients were examined using digital infrared thermal imaging. Patients in shock showed a significant decrease in distal temperature (at least 7°), compared to critically ill patients without shock. The latter group presented a skin temperature pattern very similar to the one previously reported for healthy children. The results show that infrared thermography can be used as a non-invasive method for monitoring the temperature in pediatric patients in intensive care units in order to detect shock in its early stages.

Earthworm invasion in North America: Food resource competition affects native millipede survival and invasive earthworm reproduction

Treesearch

Bruce Snyder; Mac Callaham; Christopher Lowe; Paul Hendrix

2013-01-01

The invasive non-native earthworm Amynthas agrestis (Goto and Hatai, 1899) has recently been documented invading forests of the Appalachian Mountains in the southeastern United States. This epigeic earthworm decreases the depth of organic soil horizons, and this may play a role in the decrease of millipede richness and abundance associated with A. agrestis invasion. To...

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration

PubMed Central

Trachtenberg, Jordan E.; Vo, Tiffany N.; Mikos, Antonios G.

2014-01-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth. PMID:25319726

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration.

PubMed

Trachtenberg, Jordan E; Vo, Tiffany N; Mikos, Antonios G

2015-03-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth.

The effect of pressure and shear on tissue viability of human skin in relation to the development of pressure ulcers: a systematic review.

PubMed

Hoogendoorn, Iris; Reenalda, Jasper; Koopman, Bart F J M; Rietman, Johan S

2017-08-01

Pressure ulcers are a significant problem in health care, due to high costs and large impact on patients' life. In general, pressure ulcers develop as tissue viability decreases due to prolonged mechanical loading. The relation between load and tissue viability is highly influenced by individual characteristics. It is proposed that measurements of skin blood flow regulation could provide good assessment of the risk for pressure ulcer development, as skin blood flow is essential for tissue viability. . Therefore, the aim of this systematic review is to gain insight in the relation between mechanical load and the response of the skin and underlying tissue to this loading measured in-vivo with non-invasive techniques. A systematic literature search was performed to identify articles analysing the relation between mechanical load (pressure and/or shear) and tissue viability measured in-vivo. Two independent reviewers scored the methodological quality of the 22 included studies. Methodological information as well as tissue viability parameters during load application and after load removal were extracted from the included articles and used in a meta-analysis. Pressure results in a decrease in skin blood flow parameters, compared to baseline; showing a larger decrease with higher magnitudes of load. The steepness of the decrease is mostly dependent on the anatomical location. After load removal the magnitude of the post-reactive hyperaemic peak is related to the magnitude of pressure. Lastly, shear in addition to pressure, shows an additional negative effect, but the effect is less apparent than pressure on skin viability. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Raman spectroscopy in biomedicine – non-invasive in vitro analysis of cells and extracellular matrix components in tissues

PubMed Central

Brauchle, Eva; Schenke-Layland, Katja

2013-01-01

Raman spectroscopy is an established laser-based technology for the quality assurance of pharmaceutical products. Over the past few years, Raman spectroscopy has become a powerful diagnostic tool in the life sciences. Raman spectra allow assessment of the overall molecular constitution of biological samples, based on specific signals from proteins, nucleic acids, lipids, carbohydrates, and inorganic crystals. Measurements are non-invasive and do not require sample processing, making Raman spectroscopy a reliable and robust method with numerous applications in biomedicine. Moreover, Raman spectroscopy allows the highly sensitive discrimination of bacteria. Rama spectra retain information on continuous metabolic processes and kinetics such as lipid storage and recombinant protein production. Raman spectra are specific for each cell type and provide additional information on cell viability, differentiation status, and tumorigenicity. In tissues, Raman spectroscopy can detect major extracellular matrix components and their secondary structures. Furthermore, the non-invasive characterization of healthy and pathological tissues as well as quality control and process monitoring of in vitro-engineered matrix is possible. This review provides comprehensive insight to the current progress in expanding the applicability of Raman spectroscopy for the characterization of living cells and tissues, and serves as a good reference point for those starting in the field. PMID:23161832

Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

PubMed Central

2011-01-01

Background Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer. PMID:21955589

Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination.

PubMed

Jiang, Cheng-Gang; Lv, Ling; Liu, Fu-Rong; Wang, Zhen-Ning; Liu, Fu-Nan; Li, Yan-Shu; Wang, Chun-Yu; Zhang, Hong-Yan; Sun, Zhe; Xu, Hui-Mian

2011-09-28

Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P.

PubMed

Lin, Feiyan; Zhang, Peili; Zuo, Zhigui; Wang, Fule; Bi, Ruichun; Shang, Wenjing; Wu, Aihua; Ye, Ju; Li, Shaotang; Sun, Xuecheng; Wu, Jianbo; Jiang, Lei

2017-08-10

Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival. Overexpression of Trx-1 enhanced CRC cell invasion and metastasis in vitro and in vivo. Conversely, suppression of Trx-1 expression decreased cell invasion and metastasis in vitro and in vivo. Moreover, Trx-1 activates S100P gene transcription. S100P, in turn, promotes Trx-1 expression and nuclear localization by upregulating p-ERK1/2 and downregulating TXNIP expression. Our finding provides new insight into the mechanism of Trx-1/S100P axis in the promotion of CRC metastasis, and suggests that the Trx-1/S100P axis and their related signaling pathways could be novel targets for the treatment of metastatic CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

microRNA-497 overexpression decreases proliferation, migration and invasion of human retinoblastoma cells via targeting vascular endothelial growth factor A

PubMed Central

Li, Jianjun; Zhang, Yinghui; Wang, Xiuchao; Zhao, Ruibo

2017-01-01

The expression level and roles of microRNA-497 (miR-497) have been frequently reported in previous studies on cancer. However, its expression, function and associated molecular mechanisms in retinoblastoma remain unknown. In the present study, miR-497 expression levels in human retinoblastoma tissues, normal retinal tissues and retinoblastoma cell lines were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a Cell Counting Kit-8 assay, cell migration assay, cell invasion assay, western blot analysis and Dual-Luciferase reporter assay were used to explore the expression, functions and molecular mechanisms of miR-497 in human retinoblastoma. It was demonstrated that miR-497 was significantly downregulated in retinoblastoma tissues and cell lines compared with normal retinal tissues. Ectopic expression of miR-497 decreased the proliferation, migration and invasion of retinoblastoma cells. Furthermore, VEGFA was verified as a potential direct target of miR-497 in vitro. Taken together, the results indicate that miR-497 functions as a tumor suppressor in the carcinogenesis and progression of retinoblastoma via targeting VEGFA. miR-497 should be investigated as a potential therapeutic target for the treatment of retinoblastoma. PMID:28588740

BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.

PubMed

Shi, Huiyong; Xu, Haidong; Li, Zengjun; Zhen, Yanan; Wang, Bin; Huo, Shoujun; Xiao, Ruixue; Xu, Zhongfa

2016-04-01

Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

Neural networks improve brain cancer detection with Raman spectroscopy in the presence of light artifacts

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

2016-03-01

It is often difficult to identify cancer tissue during brain cancer (glioma) surgery. Gliomas invade into areas of normal brain, and this cancer invasion is frequently not detected using standard preoperative magnetic resonance imaging (MRI). This results in enduring invasive cancer following surgery and leads to recurrence. A hand-held Raman spectroscopy is able to rapidly detect cancer invasion in patients with grade 2-4 gliomas. However, ambient light sources can produce spectral artifacts which inhibit the ability to distinguish between cancer and normal tissue using the spectral information available. To address this issue, we have demonstrated that artificial neural networks (ANN) can accurately classify invasive cancer versus normal brain tissue, even when including measurements with significant spectral artifacts from external light sources. The non-parametric and adaptive model used by ANN makes it suitable for detecting complex non-linear spectral characteristics associated with different tissues and the confounding presence of light artifacts. The use of ANN for brain cancer detection with Raman spectroscopy, in the presence of light artifacts, improves the robustness and clinical translation potential for intraoperative use. Integration with the neurosurgical workflow is facilitated by accounting for the effect of light artifacts which may occur, due to operating room lights, neuronavigation systems, windows, or other light sources. The ability to rapidly detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery, and thereby improve patient survival.

Human renal adipose tissue induces the invasion and progression of renal cell carcinoma.

PubMed

Campo-Verde-Arbocco, Fiorella; López-Laur, José D; Romeo, Leonardo R; Giorlando, Noelia; Bruna, Flavia A; Contador, David E; López-Fontana, Gastón; Santiano, Flavia E; Sasso, Corina V; Zyla, Leila E; López-Fontana, Constanza M; Calvo, Juan C; Carón, Rubén W; Creydt, Virginia Pistone

2017-11-07

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.

Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

PubMed

Ruan, Jun; Wei, Bingbing; Xu, Zhuoqun; Yang, Shudong; Zhou, You; Yu, Minhong; Liang, Jiabei; Jin, Ke; Huang, Xing; Lu, Peng; Cheng, Huan

2013-03-01

Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

Non-invasive evaluation of stable renal allograft function using point shear-wave elastography.

PubMed

Kim, Bom Jun; Kim, Chan Kyo; Park, Jung Jae

2018-01-01

To investigate the feasibility of point shear-wave elastography (SWE) in evaluating patients with stable renal allograft function who underwent protocol biopsies. 95 patients with stable renal allograft function that underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year after transplantation) were enrolled. Ultrasound and point SWE examinations were performed immediately before protocol biopsies. Patients were categorized into two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on SWE was measured in the cortex of all renal allografts. SCR was pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0 kPa) was significantly greater than that of the non-SCR group (24.5 kPa) (=0.016), while resistive index value did not show a significant difference between the two groups (p = 0.112). Tissue elasticity in renal allografts demonstrated significantly moderate negative correlation with estimated glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue elasticity was not independent factor for SCR prediction on multivariate analysis. As a non-invasive tool, point SWE appears feasible in distinguishing between patients with SCR and without SCR in stable functioning renal allografts. Moreover, it may demonstrate the functional state of renal allografts. Advances in knowledge: On point SWE, SCR has greater tissue elasticity than non-SCR.

Circular RNA 0068669 as a new biomarker for hepatocellular carcinoma metastasis.

PubMed

Yao, Ting; Chen, Qingqing; Shao, Zhouwei; Song, Zhihua; Fu, Liyun; Xiao, Bingxiu

2018-05-21

Circular RNAs (circRNAs) play important roles in disease occurrence. However, the roles of circRNAs in the diagnosis of hepatocellular carcinoma (HCC) are largely unknown. The aim of this study is to investigate the clinical diagnostic values of hsa_circ_0068669 (Alias: hsa_circ_103561), one of the representative HCC-associated circRNAs. Hsa_circ_0068669 expression levels in HCC tissues, HCC cell lines, and chronic hepatitis tissues were detected by real-time quantitative reverse transcription-polymerase chain reaction. Its expression levels between HCC tissues and adjacent non-tumorous tissues were analyzed using paired t test. Independent t test and one-way analysis of variance (ANOVA) were performed to analyze the relationships between hsa_circ_0068669 expression levels and clinicopathological factors of patients with HCC. A receiver operating characteristic (ROC) curve was established to estimate the value of hsa_circ_0068669 as a biomarker in HCC. Hsa_circ_0068669 expression was significantly downregulated in HCC tissues and HCC cell lines compared with paired non-tumorous tissues and normal hepatic cell line, respectively. Moreover, hsa_circ_0068669 expression in HCC tissues was decreased comparing with chronic hepatitis tissues. Furthermore, hsa_circ_0068669 expression was correlated with microvascular invasion and TNM stages. Our findings indicate that hsa_circ_0068669 might be served as a novel potential biomarker for HCC metastasis. © 2018 Wiley Periodicals, Inc.

Few effects of invasive plants Reynoutria japonica, Rudbeckia laciniata and Solidago gigantea on soil physical and chemical properties.

PubMed

Stefanowicz, Anna M; Stanek, Małgorzata; Nobis, Marcin; Zubek, Szymon

2017-01-01

Biological invasions are an important problem of human-induced changes at a global scale. Invasive plants can modify soil nutrient pools and element cycling, creating feedbacks that potentially stabilize current or accelerate further invasion, and prevent re-establishment of native species. The aim of this study was to compare the effects of Reynoutria japonica, Rudbeckia laciniata and Solidago gigantea, invading non-forest areas located within or outside river valleys, on soil physical and chemical parameters, including soil moisture, element concentrations, organic matter content and pH. Additionally, invasion effects on plant species number and total plant cover were assessed. The concentrations of elements in shoots and roots of invasive and native plants were also measured. Split-plot ANOVA revealed that the invasions significantly reduced plant species number, but did not affect most soil physical and chemical properties. The invasions decreased total P concentration and increased N-NO 3 concentration in soil in comparison to native vegetation, though the latter only in the case of R. japonica. The influence of invasion on soil properties did not depend on location (within- or outside valleys). The lack of invasion effects on most soil properties does not necessarily imply the lack of influence of invasive plants, but may suggest that the direction of the changes varies among replicate sites and there are no general patterns of invasion-induced alterations for these parameters. Tissue element concentrations, with the exception of Mg, did not differ between invasive and native plants, and were not related to soil element concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Invasiveness is associated with metastasis and decreased survival in hemangiopericytoma of the central nervous system.

PubMed

Kinslow, Connor J; Rajpara, Raj S; Wu, Cheng-Chia; Bruce, Samuel S; Canoll, Peter D; Wang, Shih-Hsiu; Sonabend, Adam M; Sheth, Sameer A; McKhann, Guy M; Sisti, Michael B; Bruce, Jeffrey N; Wang, Tony J C

2017-06-01

Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous system (CNS), which is distinguished clinically from meningioma by its tendency to recur and metastasize. The histological classification and grading scheme for m-HPC is still evolving and few studies have identified tumor features that are associated with metastasis. All patients at our institution with m-HPC were assessed for patient, tumor, and treatment characteristics associated with survival, recurrence, and metastasis. New findings were validated using the SEER database. Twenty-seven patients were identified in our institutional records with m-HPC with a median follow-up time of 85 months. Invasiveness was the strongest predictor of decreased overall survival (OS) and decreased metastasis-free survival (MFS) (p = 0.004 and 0.001). On subgroup analysis, bone invasion trended towards decreased OS (p = 0.056). Bone invasion and soft tissue invasion were significantly associated with decreased MFS (p = 0.001 and 0.012). An additional 315 patients with m-HPC were identified in the SEER database that had information on tumor invasion and 263 with information on distant metastasis. Invasion was significantly associated with decreased survival (HR = 5.769, p = 0.007) and metastasis (OR 134, p = 0.000) in the SEER data. In this study, the authors identified a previously unreported tumor characteristic, invasiveness, as the strongest factor associated with decreased survival and metastasis. The association of invasion with decreased survival and metastasis was confirmed in a separate, larger, publicly available database. Invasion may be a useful parameter in the histological grading and clinical management of hemangiopericytoma of the CNS.

Long non-coding RNA MIAT promotes growth and metastasis of colorectal cancer cells through regulation of miR-132/Derlin-1 pathway.

PubMed

Liu, Zhaoxia; Wang, Hai; Cai, Hongwei; Hong, Ye; Li, Yan; Su, Dongming; Fan, Zhining

2018-01-01

Recently, long non-coding RNA (lncRNA) MIAT has been demonstrated as an oncogenic gene in several types of cancer. However, the role and mechanism of MIAT in colorectal cancer (CRC) have not been investigated. Real-time PCR was used to measure MIAT expression in CRC tissues and cells. Small interfering RNA specific for MIAT (si-MIAT) was used to down-regulate MIAT expression in CRC cells. The interaction of MIAT and miR-132 was measured by RNA pull-down assay. The effect of si-MIAT on CRC cells apoptosis and metastasis were measured by flow cytometry assay, invasion and migration assay, respectively. In present study, we found that MIAT was highly expressed in CRC tissues and cells. MIAT knockdown inhibited proliferation, migration and invasion and enhanced apoptosis of CRC cells. Further, we demonstrated that MIAT acted as a competing endogenous RNA for miR-132, antagonized its functions, and resulted in the de-repression of its target gene Derlin-1, which acted as an oncogene in promoting growth and metastasis of CRC cells. In LOVO and SW480 cells with si-MIAT, miR-132 inhibitor resulted in an increase of cell proliferation, migration and invasion and a decrease of cell apoptosis, which was partially abolished by transfection of Derlin-1 shRNA. Our data indicated that highly expressed MIAT was an oncogenic lncRNA that promoted the growth and metastasis of CRC through miR-132/Derlin-1 axis.

Costs and Effectiveness of Treatment Alternatives for Proximal Caries Lesions

PubMed Central

Schwendicke, Falk; Meyer-Lueckel, Hendrik; Stolpe, Michael; Dörfer, Christof Edmund; Paris, Sebastian

2014-01-01

Objectives Invasive therapy of proximal caries lesions initiates a cascade of re-treatment cycles with increasing loss of dental hard tissue. Non- and micro-invasive treatment aim at delaying this cascade and may thus reduce both the health and economic burden of such lesions. This study compared the costs and effectiveness of alternative treatments of proximal caries lesions. Methods A Markov-process model was used to simulate the events following the treatment of a proximal posterior lesion (E2/D1) in a 20-year-old patient in Germany. We compared three interventions (non-invasive; micro-invasive using resin infiltration; invasive using composite restoration). We calculated the risk of complications of initial and possible follow-up treatments and modelled time-dependent non-linear transition probabilities. Costs were calculated based on item-fee catalogues in Germany. Monte-Carlo-microsimulations were performed to compare cost-effectiveness of non- versus micro-invasive treatment and to analyse lifetime costs of all three treatments. Results Micro-invasive treatment was both more costly and more effective than non-invasive therapy, with ceiling-value-thresholds for willingness-to-pay between 16.73 € for E2 and 1.57 € for D1 lesions. Invasive treatment was the most costly strategy. Calculated costs and effectiveness were sensitive to lesion stage, patient’s age, discounting rate and assumed initial treatment costs. Conclusions Non- and micro-invasive treatments have lower long-term costs than invasive therapy of proximal lesions. Micro-invasive therapy had the highest cost-effectiveness for treating D1 lesions in young patients. Decision makers with a willingness-to-pay over 16.73 € and 1.57 € for E2 and D1 lesions, respectively, will find micro-invasive treatment more cost-effective than non-invasive therapy. PMID:24475208

Spheroid imaging of phase-diversity homodyne OCT

NASA Astrophysics Data System (ADS)

Senda, Naoko; Osawa, Kentaro

2017-02-01

Non-invasive 3D imaging technique is essential for regenerative tissues evaluation. Optical coherence tomography (OCT) is one of 3D imaging tools with no staining and is used extensively for fundus examination. We have developed Phase-Diversity Homodyne OCT which enables cell imaging because of high resolution, whereas conventional OCT was not used for cell imaging because of low resolution. We demonstrated non-invasive imaging inside living spheroids with Phase-Diversity Homodyne OCT. Spheroids are spheroidal cell aggregates and used as regenerative tissues. Cartilage cells were cultured in low-adhesion 96-well plates and spheroids were manufactured. Cell membrane and cytoplasm of spheroid were imaged with OCT.

[Expression and clinical significance of BCL6 corepressor-like 1 in non-small cell lung cancer].

PubMed

Zhao, Xu; Tuo, Hang; Si, Meili; Wang, Lei; Liang, Ping

2015-12-01

To detect the expression of BCL6 corepressor-like 1 (BCORL1) in tumor tissues of human non-small cell lung cancer (NSCLC) and determine the effect of BCORL1 on cell migration and invasion in A549 cells by knockdown of BCORL1. Sixty-eight pairs of NSCLC and nontumor tissues were collected and the expressions of BCORL1 and E-cadherin in them were detected using immunohistochemical staining. The expression of BCORL1 was knocked down by siRNA in A549 cells. Transwell(TM) assays were performed to test NSCLC cell migration and invasion in vitro. The expression of BCORL1 in NSCLC was significantly higher than that in paired noncancerous tissues, while E-cadherin was down-regulated in NSCLC as compared with nontumor tissues. Pearson correlation coefficient analysis suggested that BCORL1 was negatively correlated with E-cadherin expression in NSCLC tissues. Clinical association analysis suggested that the elevated expression of BCORL1 was evidently associated with the higher incidence of lymph node metastasis and more advanced TNM stage. When the expression of BCORL1 was down-regulated by a specific siRNA, E-cadherin was up-regulated, and BCORL1 knockdown obviously inhibited cell migration and invasion in A549 cells. BCORL1 is overexpressed in NSCLC tissues and it is negatively correlated with E-cadherin expression. Its high expression is correlated with poor prognostic features. BCORL1 knockdown up-regulates E-cadherin expression and subsequently inhibits cell migration and invasion of lung cancer cells.

Biomimetic strategies for the glioblastoma microenvironment

NASA Astrophysics Data System (ADS)

Cha, Junghwa; Kim, Pilnam

2017-12-01

Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity, and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer.

PubMed

Altan, Bolag; Kaira, Kyoichi; Okada, Shuichi; Saito, Tsugumichi; Yamada, Eijiro; Bao, Halin; Bao, Pinjie; Takahashi, Kengo; Yokobori, Takehiko; Tetsunari, Oyama; Nishiyama, Masahiko; Yamada, Masanobu

2017-07-01

Nucleobindin 2 has been reported that its high expression is associated with poor outcome and promotes cell migration and lymph node metastasis in breast cancer, colon cancer, and prostate cancer. However, we aimed to investigate the nucleobindin 2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemical analysis. In our study, nucleobindin 2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of nucleobindin 2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and clinical stage. Furthermore, the expression level of nucleobindin 2 protein was independent predictor of progression-free survival. In summary, nucleobindin 2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

Utilization of functional near infrared spectroscopy for non-invasive evaluation

NASA Astrophysics Data System (ADS)

Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

2016-07-01

The goal of this brief review is to report the techniques of functional near infrared spectroscopy for non-invasive evaluation in human study. The development of functional near infrared spectroscopy (fNIRS) technologies has advanced quantification signal using multiple wavelength and detector to solve the propagation of light inside the tissues including the absorption, scattering coefficient and to define the light penetration into tissues multilayers. There are a lot of studies that demonstrate signal from fNIRS which can be used to evaluate the changes of oxygenation level and measure the limitation of muscle performance in human brain and muscle tissues. Comprehensive reviews of diffuse reflectance based on beer lambert law theory were presented in this paper. The principle and development of fNIRS instrumentation is reported in detail.

Long noncoding RNA MINCR regulates cellular proliferation, migration, and invasion in hepatocellular carcinoma.

PubMed

Cao, Jinyu; Zhang, Deyuan; Zeng, Liangtao; Liu, Fanrong

2018-06-01

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are aberrantly expressed in many cancer types, including hepatocellular carcinoma (HCC). lncRNA MYC-induced long non-coding RNA (MINCR) were revealed to be markedly up-regulated in gallbladder cancer and Burkitt lymphoma cells. However, the biological role and function of MINCR in HCC progression are still unknown. The expression of MINCR in HCC tissues and cell lines was determined using quantitative real-time polymerase chain reaction assays. The effects of MINCR in HCC cell proliferation, migration, and invasion were determined using cell-counting kit 8 (CCK8) assay, wound healing assay, and Transwell assays in vitro. MINCR expression was up-regulated in HCC tissues and cell lines as compared with that in the negative control. The decreased expression of MINCR in vitro markedly inhibited HCC cell proliferation, migration, and invasion. Our results showed that MINCR is important in HCC development and may act as a therapeutic target that regulates HCC cellular proliferation, migration, and invasion, which are involved in HCC tumorigenesis. To the best of our know ledge, MINCR in HCC has not been studied. Our findings showed that this study is the first to reveal that MINCR may act as a therapeutic target in HCC. The in-depth exploration of the molecular mechanism is required to illuminate the molecular mechanisms of MINCR in HCC development. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Non-Invasive Blood Perfusion Measurements Using a Combined Temperature and Heat Flux Surface Probe

PubMed Central

Ricketts, Patricia L.; Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Pullins, Clay A.; Meyers, Leah A.; Lanz, Otto I.; Scott, Elaine P.; Diller, Thomas E.

2009-01-01

Non-invasive blood perfusion measurement systems have been developed and tested in a phantom tissue and an animal model. The probes use a small sensor with a laminated flat thermocouple to measure the heat transfer and temperature response to an arbitrary thermal event (convective or conductive) imposed on the tissue surface. Blood perfusion and thermal contact resistance are estimated by comparing heat flux data with a mathematical model of the tissue. The perfusion probes were evaluated for repeatability and sensitivity using both a phantom tissue test stand and exposed rat liver tests. Perfusion in the phantom tissue tests was varied by controlling the flow of water into the phantom tissue test section, and the perfusion in the exposed liver tests was varied by temporarily occluding blood flow through the portal vein. The phantom tissue tests indicated that the probes can be used to detect small changes in perfusion (0.005 ml/ml/s). The probes qualitatively tracked the changes in the perfusion of the liver model due to occlusion of the portal vein. PMID:19885372

Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography

PubMed Central

Page, Michael J.; Lourenço, André L.; David, Tovo; LeBeau, Aaron M.; Cattaruzza, Fiore; Castro, Helena C.; VanBrocklin, Henry F.; Coughlin, Shaun R.; Craik, Charles S.

2015-01-01

Functional imaging of proteolytic activity is an emerging strategy to quantify disease and response to therapy at the molecular level. We present a new peptide-based imaging probe technology that advances these goals by exploiting enzymatic activity to deposit probes labelled with near-infrared (NIR) fluorophores or radioisotopes in cell membranes of disease-associated proteolysis. This strategy allows for non-invasive detection of protease activity in vivo and ex vivo by tracking deposited probes in tissues. We demonstrate non-invasive detection of thrombin generation in a murine model of pulmonary embolism using our protease-activated peptide probes in microscopic clots within the lungs with NIR fluorescence optical imaging and positron-emission tomography. Thrombin activity is imaged deep in tissue and tracked predominantly to platelets within the lumen of blood vessels. The modular design of our probes allows for facile investigation of other proteases, and their contributions to disease by tailoring the protease activation and cell-binding elements. PMID:26423607

Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

PubMed Central

Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

2016-01-01

Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and invasion of canine mammary cancer cells

PubMed Central

2013-01-01

Background Tumor-associated macrophages (TAMs) have high impact on the cancer development because they can facilitate matrix invasion, angiogenesis, and tumor cell motility. It gives cancer cells the capacity to invade normal tissues and metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which is an important regulator of proliferation and differentiation of monocytes and macrophages regulates most of the tissue macrophages. However, CSF-1R is expressed also in breast epithelial tissue during some physiological stages i.g.: pregnancy and lactation. Its expression has been also detected in various cancers. Our previous study has showed the expression of CSF-1R in all examined canine mammary tumors. Moreover, it strongly correlated with grade of malignancy and ability to metastasis. This study was therefore designed to characterize the role of CSF-1R in canine mammary cancer cells proliferation, apoptosis, migration, and invasion. As far as we know, the study presented hereby is a pioneering experiment in this field of veterinary medicine. Results We showed that csf-1r silencing significantly increased apoptosis (Annexin V test), decreased proliferation (measured as Ki67 expression) and decreased migration (“wound healing” assay) of canine mammary cancer cells. Treatment of these cells with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth characteristics of highly invasive cell lines on Matrigel matrix, and significantly decreased the ability of these cells to invade matrix. CSF-1 treatment increased invasion of cancer cells. Conclusion The evidence of the expression and functional role of the CSF-1R in canine mammary cancer cells indicate that CSF-1R targeting may be a good therapeutic approach. PMID:23561040

Reconstruction of input functions from a dynamic PET image with sequential administration of 15O2 and [Formula: see text] for noninvasive and ultra-rapid measurement of CBF, OEF, and CMRO2.

PubMed

Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Hiroyuki; Yamamoto, Yuka; Hatakeyama, Tetsuhiro; Nishiyama, Yoshihiro

2018-05-01

CBF, OEF, and CMRO 2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O 2 and C 15 O 2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO 2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO 2 .

Evaluating optimal superficial limb perfusion at different angles using non-invasive micro-lightguide spectrophotometry.

PubMed

Darmanin, Geraldine; Jaggard, Matthew; Hettiaratchy, Shehan; Nanchahal, Jagdeep; Jain, Abhilash

2013-06-01

It is common practice to elevate the limbs postoperatively to reduce oedema and hence optimise perfusion and facilitate rehabilitation. However, elevation may be counterproductive as it reduces the mean perfusion pressure. There are no clear data on the optimal position of the limbs even in normal subjects. The optimal position of limbs was investigated in 25 healthy subjects using a non-invasive micro-lightguide spectrophotometry system "O2C", which indirectly measures skin and superficial tissue perfusion through blood flow, oxygen saturation and relative haemoglobin concentration. We found a reduction in skin and superficial tissue blood flow of 17% (p=0.0001) on arm elevation (180° shoulder flexion) as compared to heart level and an increase in skin and superficial tissue blood flow of 25% (p=0.02) on forearm elevation of 45°. Lower limb skin and superficial tissue blood flow decreased by 15% (p=0.004) on elevation to 47 cm and by 70% on dependency (p=0.0001) compared to heart level. However, on elevation of the lower limb there was also a 28% reduction in superficial venous pooling (p=0.0001) compared to heart level. In the normal limb, the position for optimal superficial perfusion of the upper limb is with the arm placed at heart level and forearm at 45°. In the lower limb the optimal position for superficial perfusion would be at heart level. However, some degree of elevation may be useful if there is an element of venous congestion. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Effects of invasive plants on arthropods.

PubMed

Litt, Andrea R; Cord, Erin E; Fulbright, Timothy E; Schuster, Greta L

2014-12-01

Non-native plants have invaded nearly all ecosystems and represent a major component of global ecological change. Plant invasions frequently change the composition and structure of vegetation communities, which can alter animal communities and ecosystem processes. We reviewed 87 articles published in the peer-reviewed literature to evaluate responses of arthropod communities and functional groups to non-native invasive plants. Total abundance of arthropods decreased in 62% of studies and increased in 15%. Taxonomic richness decreased in 48% of studies and increased in 13%. Herbivorous arthropods decreased in response to plant invasions in 48% of studies and increased in 17%, likely due to direct effects of decreased plant diversity. Predaceous arthropods decreased in response to invasive plants in 44% of studies, which may reflect indirect effects due to reductions in prey. Twenty-two percent of studies documented increases in predators, which may reflect changes in vegetation structure that improved mobility, survival, or web-building for these species. Detritivores increased in 67% of studies, likely in response to increased litter and decaying vegetation; no studies documented decreased abundance in this functional group. Although many researchers have examined effects of plant invasions on arthropods, sizeable information gaps remain, specifically regarding how invasive plants influence habitat and dietary requirements. Beyond this, the ability to predict changes in arthropod populations and communities associated with plant invasions could be improved by adopting a more functional and mechanistic approach. Understanding responses of arthropods to invasive plants will critically inform conservation of virtually all biodiversity and ecological processes because so many organisms depend on arthropods as prey or for their functional roles, including pollination, seed dispersal, and decomposition. Given their short generation times and ability to respond rapidly to ecological change, arthropods may be ideal targets for restoration and conservation activities. © 2014 Society for Conservation Biology.

Estimation of tissue stiffness, reflex activity, optimal muscle length and slack length in stroke patients using an electromyography driven antagonistic wrist model.

PubMed

de Gooijer-van de Groep, Karin L; de Vlugt, Erwin; van der Krogt, Hanneke J; Helgadóttir, Áróra; Arendzen, J Hans; Meskers, Carel G M; de Groot, Jurriaan H

2016-06-01

About half of all chronic stroke patients experience loss of arm function coinciding with increased stiffness, reduced range of motion and a flexed wrist due to a change in neural and/or structural tissue properties. Quantitative assessment of these changes is of clinical importance, yet not trivial. The goal of this study was to quantify the neural and structural properties contributing to wrist joint stiffness and to compare these properties between healthy subjects and stroke patients. Stroke patients (n=32) and healthy volunteers (n=14) were measured using ramp-and-hold rotations applied to the wrist joint by a haptic manipulator. Neural (reflexive torque) and structural (connective tissue stiffness and slack lengths and (contractile) optimal muscle lengths) parameters were estimated using an electromyography driven antagonistic wrist model. Kruskal-Wallis analysis with multiple comparisons was used to compare results between healthy subjects, stroke patients with modified Ashworth score of zero and stroke patients with modified Ashworth score of one or more. Stroke patients with modified Ashworth score of one or more differed from healthy controls (P<0.05) by increased tissue stiffness, increased reflexive torque, decreased optimal muscle length and decreased slack length of connective tissue of the flexor muscles. Non-invasive quantitative analysis, including estimation of optimal muscle lengths, enables to identify neural and non-neural changes in chronic stroke patients. Monitoring these changes in time is important to understand the recovery process and to optimize treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long non-coding RNA AFAP1-antisense RNA 1 promotes the proliferation, migration and invasion of gastric cancer cells and is associated with poor patient survival.

PubMed

Zhao, Huazhou; Zhang, Kecheng; Wang, Ting; Cui, Jianxin; Xi, Hongqing; Wang, Yi; Song, Yanjing; Zhao, Xudong; Wei, Bo; Chen, Lin

2018-06-01

Gastric cancer (GC) is the second-leading cause of cancer-associated mortality worldwide. AFAP1-antisense RNA 1 (AFAP1-AS1), a long non-coding RNA (lncRNA), is believed to promote the aggressive progression of cancer; however, its role in GC remains largely unknown. In the present study, the expression of AFAP1-AS1 in GC tissues and cell lines was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Knockdown of AFAP1-AS1 was performed using a lentiviral vector containing a short hairpin RNA. The proliferation of GC cells was measured using Cell Counting kit-8. The migration and invasion of GC cells were analyzed using a QCM Laminin Migration Assay kit and a Cell Invasion Assay kit. The levels of epithelial-mesenchymal transition (EMT)-associated proteins were detected by western blot analysis. The cut-off value of the expression of AFAP1-AS1 was evaluated using receiver operating characteristic (ROC) curves and patient survival rate was analyzed using Kaplan-Meier. The expression of AFAP1-AS1 was significantly increased in the primary tumor tissues of GC patients with lymph node metastasis or tumor node metastasis stage (stage III or IV; P<0.01). ROC curve analysis revealed that the expression of AFAP-AS1, at a cut-off value of 0.5040, could distinguish GC tissues from the matched normal tissues, with an AUC of 0.8802, sensitivity of 81.25% and specificity of 83.75%. The overexpression of AFAP1-AS1 was positively associated with the poor survival rates of GC patients. Furthermore, the downregulation of AFAP1-AS1 significantly inhibited the proliferation, migration and invasion of GC cells in vitro (P<0.01). The decrease in AFAP1-AS1 expression significantly suppressed the expression level of N-cadherin protein in GC cells and increased that of E-cadherin. The present study demonstrated that the expression signature of AFAP1-AS1 may serve as a biomarker for the diagnosis and prognosis of GC, and its downregulation may repress the aggressive progression of GC, partially through inhibiting the EMT progress.

In vivo assessment of the structure of skin microcirculation by reflectance confocal-laser-scanning microscopy

NASA Astrophysics Data System (ADS)

Sugata, Keiichi; Osanai, Osamu; Kawada, Hiromitsu

2012-02-01

One of the major roles of the skin microcirculation is to supply oxygen and nutrition to the surrounding tissue. Regardless of the close relationship between the microcirculation and the surrounding tissue, there are few non-invasive methods that can evaluate both the microcirculation and its surrounding tissue at the same site. We visualized microcapillary plexus structures in human skin using in vivo reflectance confocal-laser-scanning microscopy (CLSM), Vivascope 3000® (Lucid Inc., USA) and Image J software (National Institutes of Health, USA) for video image processing. CLSM is a non-invasive technique that can visualize the internal structure of the skin at the cellular level. In addition to internal morphological information such as the extracellular matrix, our method reveals capillary structures up to the depth of the subpapillary plexus at the same site without the need for additional optical systems. Video images at specific depths of the inner forearm skin were recorded. By creating frame-to-frame difference images from the video images using off-line video image processing, we obtained images that emphasize the brightness depending on changes of intensity coming from the movement of blood cells. Merging images from different depths of the skin elucidates the 3-dimensional fine line-structure of the microcirculation. Overall our results show the feasibility of a non-invasive, high-resolution imaging technique to characterize the skin microcirculation and the surrounding tissue.

Cerebral oxygenation in traumatic brain injury; Can a non-invasive frequency domain near-infrared spectroscopy device detect changes in brain tissue oxygen tension as well as the established invasive monitor?

PubMed

Davies, David James; Clancy, Michael; Dehghani, Hamid; Lucas, Samuel John Edwin; Forcione, Mario; Yakoub, Kamal Makram; Belli, Antonio

2018-06-07

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma centre were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilised to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mmHg, respectively), as measured invasively. 16 individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in 9 of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576 - 0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Overexpression of secretagogin promotes cell apoptosis and inhibits migration and invasion of human SW480 human colorectal cancer cells.

PubMed

Yang, Xiang-Yi; Liu, Qiao-Rui; Wu, Li-Ming; Zheng, Xu-Lei; Ma, Cong; Na, Ri-Su

2018-05-01

In order to investigate the effect of secretagogin (SCGN) on colorectal cancer (CRC) cells apoptosis, invasion and migration in vitro. Expression of SCGN in CRC tissues and the paired adjacent non-tumorous tissues (n = 36) and four human CRC cell lines (HT29, HCT116, SW480 and SW620) were detected. SW480 cells were transfected with the SCGN overexpression plasmid (eGFP-SCGN), si-SCGN-773, and the corresponding negative controls (NCs). Then, cell-cycle distribution, cell apoptosis, migration, invasion and expression of apoptosis- and metastasis-related proteins were detected. SCGN was significantly downregulated in CRC tissues as compared with the adjacent non-tumorous tissues. The expression of SCGN in HT29 and SW480 cells were lower than those in HT116 and SW620 cells. We transfected SW480 cells with SCGN overexpression plasmid eGFP-SCGN and found the increased cell apoptosis, with cell arresting at G0/G1 phase. SW480 cells with SCGN overexpression showed wider wound width and fewer invaded cells than control and blank cells, with upregulated Bax, cleaved Caspase 3 and E-cadherin, and downregulated Bcl-2 and Vimentin. We also transfected SW480 cells with si-SCGN-773 and found si-SCGN increased cell migration and invasion, but did not affect cell apoptosis and expression of related proteins. We concluded that the overexpression of SCGN in SW480 cells promoted cell apoptosis and inhibited cell migration and invasion. Copyright © 2018. Published by Elsevier Masson SAS.

Non-invasive in vivo imaging of arthritis in a collagen-induced murine model with phosphatidylserine-binding near-infrared (NIR) dye.

PubMed

Chan, Marion M; Gray, Brian D; Pak, Koon Y; Fong, Dunne

2015-03-09

Development of non-invasive molecular imaging techniques that are based on cellular changes in inflammation has been of active interest for arthritis diagnosis. This technology will allow real-time detection of tissue damage and facilitate earlier treatment of the disease, thus representing an improvement over X-rays, which detect bone damage at the advanced stage. Tracing apoptosis, an event occurring in inflammation, has been a strategy used. PSVue 794 is a low-molecular-weight, near-infrared (NIR)-emitting complex of bis(zinc2+-dipicolylamine) (Zn-DPA) that binds to phosphatidylserine (PS), a plasma membrane anionic phospholipid that becomes flipped externally upon cell death by apoptosis. In this study, we evaluated the capacity of PSVue 794 to act as an in vivo probe for non-invasive molecular imaging assessment of rheumatoid arthritis (RA) via metabolic function in murine collagen-induced arthritis, a widely adopted animal model for RA. Male DBA/1 strain mice were treated twice with chicken collagen type II in Freund's adjuvant. Their arthritis development was determined by measuring footpad thickness and confirmed with X-ray analysis and histology. In vivo imaging was performed with the NIR dye and the LI-COR Odyssey Image System. The level of emission was compared among mice with different disease severity, non-arthritic mice and arthritic mice injected with a control dye without the Zn-DPA targeting moiety. Fluorescent emission correlated reliably with the degree of footpad swelling and the manifestation of arthritis. Ex vivo examination showed emission was from the joint. Specificity of binding was confirmed by the lack of emission when arthritic mice were given the control dye. Furthermore, the PS-binding protein annexin V displaced the NIR dye from binding, and the difference in emission was numerically measurable on a scale. This report introduces an economical alternative method for assessing arthritis non-invasively in murine models. Inflammation in feet and ankles can be measured longitudinally using the PSVue 794 probe for cell death and with a commonly available multipurpose imager. This technique provides metabolic and functional information that anatomical measurement of footpad swelling or visual determination of arthritic index cannot. It also may decrease the number of animals required per experiment because tissue damage will not necessarily require evaluation by harvesting joints for histology.

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

NASA Technical Reports Server (NTRS)

Breit, G. A.; Gross, J. H.; Watenpaugh, D. E.; Chance, B.; Hargens, A. R.

1997-01-01

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).

Non invasive blood flow assessment in diabetic foot ulcer using laser speckle contrast imaging technique

NASA Astrophysics Data System (ADS)

Jayanthy, A. K.; Sujatha, N.; Reddy, M. Ramasubba; Narayanamoorthy, V. B.

2014-03-01

Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.

miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1.

PubMed

Ye, Zaiting; Fang, Bingmu; Pan, Jiongwei; Zhang, Ning; Huang, Jinwei; Xie, Congying; Lou, Tianzheng; Cao, Zhuo

2017-06-01

The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer.

Propofol Induction's Effect on Cardiac Function

ClinicalTrials.gov

2015-03-31

This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

[Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

PubMed

Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

2016-12-01

Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.

PubMed

Babina, Irina S; McSherry, Elaine A; Donatello, Simona; Hill, Arnold D K; Hopkins, Ann M

2014-02-10

Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration. Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients. CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures. Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.

Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

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

Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.

2006-07-01

Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reductionmore » in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-{kappa}B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.« less

Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro.

PubMed

Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J

2011-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Minimally invasive soft tissue release of foot and ankle contracture secondary to stroke.

PubMed

Boffeli, Troy J; Collier, Rachel C

2014-01-01

Lower extremity contracture associated with stroke commonly results in a nonreducible, spastic equinovarus deformity of the foot and ankle. Rigid contracture deformity leads to gait instability, pain, bracing difficulties, and ulcerations. The classic surgical approach for stroke-related contracture of the foot and ankle has been combinations of tendon lengthening, tendon transfer, osteotomy, and joint fusion procedures. Recovery after traditional foot and ankle reconstructive surgery requires a period of non-weightbearing that is not typically practical for these patients. Little focus has been given in published studies on minimally invasive soft tissue release of contracture. We present the case of a 61-year-old female with an equinovarus foot contracture deformity secondary to stroke. The patient underwent Achilles tendon lengthening, posterior tibial tendon Z lengthening, and digital flexor tenotomy of each toe with immediate weightbearing in a walking boot, followed by transition to an ankle-foot orthosis. The surgical principles and technique tips are presented to demonstrate our minimally invasive approach to release of foot and ankle contracture secondary to stroke. The main goal of this approach is to improve foot and ankle alignment for ease of bracing, which, in turn, will improve gait, reduce the risk of falls, decrease pain, and avoid the development of pressure sores. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Quantitative clinical nonpulsatile and localized visible light oximeter: design of the T-Stat tissue oximeter

NASA Astrophysics Data System (ADS)

Benaron, David A.; Parachikov, Ilian H.; Cheong, Wai-Fung; Friedland, Shai; Duckworth, Joshua L.; Otten, David M.; Rubinsky, Boris E.; Horchner, Uwe B.; Kermit, Eben L.; Liu, Frank W.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W.; Talmi, Yair; Weersing, James P.

2003-07-01

We report the development of a general, quantitative, and localized visible light clinical tissue oximeter, sensitive to both hypoxemia and ischemia. Monitor design and operation were optimized over four instrument generations. A range of clinical probes were developed, including non-contact wands, invasive catheters, and penetrating needles with injection ports. Real-time data were collected (a) from probes, standards, and reference solutions to optimize each component, (b) from ex vivo hemoglobin solutions co-analyzed for StO2% and pO2 during deoxygenation, and (c) from normoxic human subject skin and mucosal tissue surfaces. Results show that (a) differential spectroscopy allows extraction of features with minimization of the effects of scattering, (b) in vitro oximetry produces a hemoglobin saturation binding curve of expected sigmoid shape and values, and (c) that monitoring human tissues allows real-time tissue spectroscopic features to be monitored. Unlike with near-infrared (NIRS) or pulse oximetry (SpO2%) methods, we found non-pulsatile, diffusion-based tissue oximetry (StO2%) to work most reliably for non-contact reflectance monitoring and for invasive catheter- or needle-based monitoring, using blue to orange light (475-600 nm). Measured values were insensitive to motion artifact. Down time was non-existent. We conclude that the T-Stat oximeter design is suitable for the collection of spectroscopic data from human subjects, and that the oximeter may have application in the monitoring of regional hemoglobin oxygen saturation in the capillary tissue spaces of human subjects.

A Microwave Ring-Resonator Sensor for Non-Invasive Assessment of Meat Aging

PubMed Central

Jilani, Muhammad Taha; Wen, Wong Peng; Cheong, Lee Yen; ur Rehman, Muhammad Zaka

2016-01-01

The assessment of moisture loss from meat during the aging period is a critical issue for the meat industry. In this article, a non-invasive microwave ring-resonator sensor is presented to evaluate the moisture content, or more precisely water holding capacity (WHC) of broiler meat over a four-week period. The developed sensor has shown significant changes in its resonance frequency and return loss due to reduction in WHC in the studied duration. The obtained results are also confirmed by physical measurements. Further, these results are evaluated using the Fricke model, which provides a good fit for electric circuit components in biological tissue. Significant changes were observed in membrane integrity, where the corresponding capacitance decreases 30% in the early aging (0D-7D) period. Similarly, the losses associated with intracellular and extracellular fluids exhibit changed up to 42% and 53%, respectively. Ultimately, empirical polynomial models are developed to predict the electrical component values for a better understanding of aging effects. The measured and calculated values are found to be in good agreement. PMID:26805828

A Microwave Ring-Resonator Sensor for Non-Invasive Assessment of Meat Aging.

PubMed

Jilnai, Muhammad Taha; Wen, Wong Peng; Cheong, Lee Yen; ur Rehman, Muhammad Zaka

2016-01-20

The assessment of moisture loss from meat during the aging period is a critical issue for the meat industry. In this article, a non-invasive microwave ring-resonator sensor is presented to evaluate the moisture content, or more precisely water holding capacity (WHC) of broiler meat over a four-week period. The developed sensor has shown significant changes in its resonance frequency and return loss due to reduction in WHC in the studied duration. The obtained results are also confirmed by physical measurements. Further, these results are evaluated using the Fricke model, which provides a good fit for electric circuit components in biological tissue. Significant changes were observed in membrane integrity, where the corresponding capacitance decreases 30% in the early aging (0D-7D) period. Similarly, the losses associated with intracellular and extracellular fluids exhibit changed up to 42% and 53%, respectively. Ultimately, empirical polynomial models are developed to predict the electrical component values for a better understanding of aging effects. The measured and calculated values are found to be in good agreement.

The Use of TissuGlu® Surgical Adhesive for Mastectomy With or Without Lymphonodectomy.

PubMed

Ohlinger, Ralf; Gieron, Leonie; Rutkowski, Rico; Kohlmann, Thomas; Zygmunt, Marek; Unger, Julia

2018-01-01

Using drains after breast surgery is a preventive, but invasive measure to reduce seroma formation. A polyurethane-based tissue adhesive (TissuGlu®) might facilitate drainage-free wound healing after mastectomy in a non-invasive manner. Retrospectively, data from 84 patients (42 receiving TissuGlu®, 42 receiving a drainage) who underwent mastectomy, were collected (90 days postoperative follow-up). Study endpoints were defined as the number of fluid-related postoperative clinical interventions, cumulative volume of postoperative wound fluid, duration of hospitalization and postoperative complications. In the entirety of postoperative interventions, no significant difference could be demonstrated (p=0.298). The drainage arm showed significantly less seroma aspirations (p=0.024) and complications (p=0.012). A significantly reduced length of hospitalization (p<0.001) and less cumulative wound secretion volume (p<0.001) appeared in the TissuGlu® group. The polyurethane-based tissue adhesive is a less invasive alternative to drain use in mastectomy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Non-invasive, multi-modal sensing of skin stretch and bioimpedance for detecting infiltration during intravenous therapy.

PubMed

Jambulingam, Jambu A; McCrory, Russell; West, Leanne; Inan, Omer T

2016-08-01

Intravenous infiltration is a condition wherein an infused solution leaks inadvertently into soft tissue surrounding a hypodermic needle site. This occurrence affects approximately 6.5% of patients in hospitals worldwide, and can lead to severe tissue damage if not treated immediately. The methods currently used by medical staff to detect an infiltration are subjective and can potentially be prone to error. Infiltration is an even larger concern in pediatric patients, who have smaller veins than adults and have more difficulty in communicating pain or other discomfort associated with the infiltration with medical staff. For these reasons, automatic IV infiltration detection could potentially reduce the risk associated with this damaging condition. This paper proposes a novel proof-of-concept system that uses non-invasive sensing in conjunction with a low-power embedded computing platform to deliver continuous infiltration monitoring around the IV catheter site. This kind of system could be able to detect an infiltration by non-invasively monitoring for known symptoms: swelling of soft tissue and increased skin firmness; these symptoms can be sensed by measuring skin stretch and local bioimpedance. Moreover, the low-power design and wireless capabilities can potentially enable continuous wear. The proposed automatic IV infiltration detection system could significantly improve the number of infiltrations identified and treated on time.

Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models.

PubMed

Brauchle, Eva; Bauer, Hannah; Fernes, Patrick; Zuk, Alexandra; Schenke-Layland, Katja; Sengle, Gerhard

2017-04-01

Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBN1) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1 GT8/GT8 fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease conditions such as aneurysms, emphysema or lax skin. Understanding how structural changes induced by fibrillin-1 mutation impact the architecture of fibrillin microfibrils, which then translates into an altered activation state of targeted growth factors, represents a huge challenge in elucidating the genotype-phenotype correlations in connective tissue disorders such as Marfan syndrome. This study shows that Raman microspectroscopy is able to reveal structural changes in fibrillin-1 microfibrils and elastic fiber networks and to discriminate between normal and diseased networks in vivo and in vitro. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

PubMed Central

Vasquez, Kristine O.; Casavant, Chelsea; Peterson, Jeffrey D.

2011-01-01

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time. PMID:21731618

TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells.

PubMed

Simeone, Ann-Marie; McMurtry, Vanity; Nieves-Alicea, René; Saavedra, Joseph E; Keefer, Larry K; Johnson, Marcella M; Tari, Ana M

2008-01-01

Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. High concentrations of nitric oxide (NO) suppress tumor invasion and metastasis in vivo. NO prodrugs generate large amounts of NO upon metabolism by appropriate intracellular enzymes, and therefore could have potential in the prevention and therapy of metastatic breast cancer. The present study was designed to determine the effects of the NO-releasing prodrug O2-(2,4-dinitrophenyl) 1- [(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) on breast cancer invasion and the mechanisms involved. MDA-MB-231, MDA-MB-231/F10, and MCF-7/COX-2 were the three breast cancer cell lines tested. NO levels were determined spectrophotometrically using a NO assay kit. Invasion and the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs were determined using Matrigel invasion assays, an MMP array kit and ELISAs. The activity and expression of extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase mitogen-activated protein kinases were determined using western blot analyses. Under conditions by which JS-K was not cytotoxic, JS-K significantly decreased (P < 0.05) the invasiveness of breast cancer cells across the Matrigel basement membrane, which was directly correlated with NO production. JS-43-126, a non-NO-releasing analog of JS-K, had no effect on NO levels or invasion. JS-K increased (P < 0.05) TIMP-2 production, and blocking TIMP-2 activity with a neutralizing antibody significantly increased (P < 0.05) the invasive activity of JS-K-treated cells across Matrigel. JS-K decreased p38 activity, whereas the activity and the expression of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase were unaffected. We report the novel findings that JS-K inhibits breast cancer invasion across the Matrigel basement membrane, and NO production is vital for this activity. Upregulation of TIMP-2 production is one mechanism by which JS-K mediates its anti-invasive effects. JS-K and other NO prodrugs may represent an innovative biological approach in the prevention and treatment of metastatic breast cancer.

Assessing the impact of thermal acclimation on physiological condition in the zebrafish model.

PubMed

Vergauwen, Lucia; Knapen, Dries; Hagenaars, An; De Boeck, Gudrun; Blust, Ronny

2013-01-01

The zebrafish has become a valuable vertebrate model organism in a wide range of scientific disciplines, but current information concerning the physiological temperature response of adult zebrafish is rather scarce. In this study, zebrafish were experimentally acclimated for 28 days to 18, 26 or 34 °C and a suite of non-invasive and invasive methods was applied to determine the thermal dependence of zebrafish physiological condition. With decreasing temperature, the metabolic rate of zebrafish decreased, as shown by the decreasing oxygen uptake and ammonia excretion rates, limiting the critical swimming speed, probably due to a decreased muscle fibre power output. In response to exercise, fuel stores were mobilized to the liver as shown by the increased hepatosomatic index, liver total absolute energetic value and liver carbohydrate concentration but due to the low metabolic rate they could not be adequately addressed to power swimming activity at 18 °C. Conversely, the increased metabolic performance at high temperature came with an increased metabolic cost resulting in decreased energy status reflected particularly well by the non-invasive condition factor and invasive measures of carcass protein concentration, carcass total absolute energetic value and liver carbohydrate concentration. We showed that the combined measurement of the relative condition factor and critical swimming speed is a powerful non-invasive tool for long-term follow-up studies. Invasive methods were redundant for measuring general energy status but they provided detailed information concerning metabolic reorganization. With this study we proved that the usefulness of the zebrafish as a model organism can easily be expanded to include physiological studies and we provided a reference dataset for the selection of measures of physiological responses for future studies using the zebrafish.

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

PubMed

Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

2016-09-01

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

Improving Diagnosis of Sepsis After Burn Injury Using a Portable Sepsis Alert System

DTIC Science & Technology

vital signs of heart rate variability, regional tissue oxygenation, and noninvasive cardiac output can diagnose burn sepsis earlier, reducing...morbidity and mortality. Rationale: Heart Rate Variability (HRV), regional Tissue Oxygenation, and non-invasive Cardiac Output (CO), have shown promise in

Rapid in vivo vertical tissue sectioning by multiphoton tomography

NASA Astrophysics Data System (ADS)

Batista, Ana; Breunig, Hans Georg; König, Karsten

2018-02-01

A conventional tool in the pathological field is histology which involves the analysis of thin sections of tissue in which specific cellular structures are stained with different dyes. The process to obtain these stained tissue sections is time consuming and invasive as it requires tissue removal, fixation, sectioning, and staining. Moreover, imaging of live tissue is not possible. We demonstrate that multiphoton tomography can provide within seconds, non-invasive, label-free, vertical images of live tissue which are in quality similar to conventional light micrographs of histologic stained specimen. In contrast to conventional setups based on laser scanning which image horizontally sections, the vertical in vivo images are directly recorded by combined line scanning and timed adjustments of the height of the focusing optics. In addition, multiphoton tomography provides autofluorescence lifetimes which can be used to determine the metabolic states of cells.

Time resolved optical biopsy spectroscopy of normal, benign and malignant tissues from NADH and FAD changes

NASA Astrophysics Data System (ADS)

Masilamani, V.; Das, B. B.; Secor, J.; AlSalhi, M.; Amer, S. B.; Farhat, K.; Rabah, D.; Alfano, R. R.

2012-01-01

Histo pathological examination is the gold standard to discriminate between benign and malignant growth of tissue. But this is invasive and stressful. Hence many non invasive imaging techniques, such as CT, MRI, PET, etc are employed, each having certain advantages and disadvantages. In this context optical biopsy is a newly emerging technique, since it employs non-ionizing radiation like light or laser, which could be shined directly or launched through optical fiber to reach any part of the body. This paper reports results of time resolved emission spectra of 24 excised tissue sample (normal control=12; benign=4; malignant=8) of breast and prostate, employing a 390nm, 100 fs, Ti-Sapphire laser pulses. The fluorescence decay times were measured using streak camera and fitted for single and bi- exponential decays with reliability of 97%. Our results show the distinct difference between normal, benign and malignant tissues attributed changes of NADH and FAD levels.

Endoscopic-assisted resection of a pedunculated uterine leiomyoma with maximal tissue preservation in a cow and a mare.

PubMed

Schneeweiss, Wilfried; Krump, Lea; Metcalfe, Lucy; Ryan, Eoin; Beltman, Marijke; Jahns, Hanne; David, Florent

2015-02-01

To report successful minimally invasive treatment of a uterine leiomyoma in a cow and a mare. Clinical report. Limousine cow (n = 1), Thoroughbred mare (n = 1). A 10-year-old cow and an 18-year-old mare were presented for difficulties in breeding and infertility, respectively. Examination of the reproductive tract revealed the presence of a large mass attached to the uterine wall via a wide and short peduncle in both cases. The mass expanded into the uterine lumen in the mare and into the abdomen in the cow. Both masses were removed using a minimally invasive endoscopic approach and a vessel-sealing and dividing device. Minimally invasive surgical resection of a subserosal and a submucosal leiomyoma with maximal sparing of uterine tissue resulted in a short convalescence period and apparent return to breeding function in a cow and a mare. Use of a vessel-sealing and dividing device provided excellent hemostasis and decreased tissue handling. Leiomyoma with short, wide, and thick peduncles were treated successfully in a cow and a mare with minimally invasive endoscopic approaches aiming at maximal uterine tissue preservation. © Copyright 2014 by The American College of Veterinary Surgeons.

Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer

PubMed Central

Lee, Myung-Shin; Lee, Jisu; Kim, Joo Heon; Kim, Won Tae; Kim, Wun-Jae; Ahn, Hanjong; Park, Jinsung

2015-01-01

The expression and function of caldesmon (CAD) in urothelial bladder carcinoma (BC) have not been reported. Here, we investigated the expression, prognostic value, and potential functional mechanism of CAD in primary non-muscle-invasive bladder cancer (NMIBC). Protein profiling of tissue samples using antibody microarrays showed significantly higher CAD expression in muscle-invasive BC tissues compared with NMIBC tissues. We then validated the CAD expression in BC cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and western blots using BC cell lines. In addition, we examined the expression of CAD variants by reverse transcription-polymerase chain reaction, and confirmed the expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI-38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an independent primary NMIBC cohort comprising 132 patients showed that positive CAD expression was significantly associated with poorer prognosis than no CAD expression with regard to recurrence- and progression-free survival (p = 0.001 and 0.014, respectively). Multivariate analyses further indicated that positive CAD expression was an independent predictor of progression-free survival (p = 0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression studies indicated that L-CAD promotes migration and invasiveness of BC cells. Immunofluorescence assays showed dramatic structural changes in the actin cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively suggest that L-CAD overexpression in primary NMIBC is significantly associated with tumor progression and that a possible mechanism for L-CAD's activity is implicated in increased cell motility and invasive characteristics through morphological changes in BC cells. PMID:26430961

A simple one-step method to prepare fluorescent carbon dots and their potential application in non-invasive glioma imaging

NASA Astrophysics Data System (ADS)

Ruan, Shaobo; Qian, Jun; Shen, Shun; Zhu, Jianhua; Jiang, Xinguo; He, Qin; Gao, Huile

2014-08-01

Fluorescent carbon dots (CD) possess impressive potential in bioimaging because of their low photobleaching, absence of optical blinking and good biocompatibility. However, their relatively short excitation/emission wavelengths restrict their application in in vivo imaging. In the present study, a kind of CD was prepared by a simple heat treatment method using glycine as the only precursor. The diameter of CD was lower than 5 nm, and the highest emission wavelength was 500 nm. However, at 600 nm, there was still a relatively strong fluorescent emission, suggesting CD could be used for in vivo imaging. Additionally, several experiments demonstrated that CD possessed good serum stability and low cytotoxicity. In vitro, CD could be taken up into C6 glioma cells in a time- and concentration-dependent manner, with both endosomes and mitochondria involved. In vivo, CD could be used for non-invasive glioma imaging because of its high accumulation in the glioma site of the brain, which was demonstrated by both in vivo imaging and ex vivo tissue imaging. Furthermore, the fluorescent distribution in tissue slices also showed CD distributed in glioma with high intensity, while with a low intensity in normal brain tissue. In conclusion, CD were prepared using a simple method with relatively long excitation and emission wavelengths and could be used for non-invasive glioma imaging.Fluorescent carbon dots (CD) possess impressive potential in bioimaging because of their low photobleaching, absence of optical blinking and good biocompatibility. However, their relatively short excitation/emission wavelengths restrict their application in in vivo imaging. In the present study, a kind of CD was prepared by a simple heat treatment method using glycine as the only precursor. The diameter of CD was lower than 5 nm, and the highest emission wavelength was 500 nm. However, at 600 nm, there was still a relatively strong fluorescent emission, suggesting CD could be used for in vivo imaging. Additionally, several experiments demonstrated that CD possessed good serum stability and low cytotoxicity. In vitro, CD could be taken up into C6 glioma cells in a time- and concentration-dependent manner, with both endosomes and mitochondria involved. In vivo, CD could be used for non-invasive glioma imaging because of its high accumulation in the glioma site of the brain, which was demonstrated by both in vivo imaging and ex vivo tissue imaging. Furthermore, the fluorescent distribution in tissue slices also showed CD distributed in glioma with high intensity, while with a low intensity in normal brain tissue. In conclusion, CD were prepared using a simple method with relatively long excitation and emission wavelengths and could be used for non-invasive glioma imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02657h

Effect of bone-soft tissue friction on ultrasound axial shear strain elastography

NASA Astrophysics Data System (ADS)

Tang, Songyuan; Chaudhry, Anuj; Kim, Namhee; Reddy, J. N.; Righetti, Raffaella

2017-08-01

Bone-soft tissue friction is an important factor affecting several musculoskeletal disorders, frictional syndromes and the ability of a bone fracture to heal. However, this parameter is difficult to determine using non-invasive imaging modalities, especially in clinical settings. Ultrasound axial shear strain elastography is a non-invasive imaging modality that has been used in the recent past to estimate the bonding between different tissue layers. As most elastography methods, axial shear strain elastography is primarily used in soft tissues. More recently, this technique has been proposed to assess the bone-soft tissue interface. In this paper, we investigate the effect of a variation in bone-soft tissue friction coefficient in the resulting axial shear strain elastograms. Finite element poroelastic models of bone specimens exhibiting different bone-soft tissue friction coefficients were created and mechanically analyzed. These models were then imported to an ultrasound elastography simulation module to assess the presence of axial shear strain patterns. In vitro experiments were performed to corroborate selected simulation results. The results of this study show that the normalized axial shear strain estimated at the bone-soft tissue interface is statistically correlated to the bone-soft tissue coefficient of friction. This information may prove useful to better interpret ultrasound elastography results obtained in bone-related applications and, possibly, monitor bone healing.

Effect of bone-soft tissue friction on ultrasound axial shear strain elastography.

PubMed

Tang, Songyuan; Chaudhry, Anuj; Kim, Namhee; Reddy, J N; Righetti, Raffaella

2017-07-12

Bone-soft tissue friction is an important factor affecting several musculoskeletal disorders, frictional syndromes and the ability of a bone fracture to heal. However, this parameter is difficult to determine using non-invasive imaging modalities, especially in clinical settings. Ultrasound axial shear strain elastography is a non-invasive imaging modality that has been used in the recent past to estimate the bonding between different tissue layers. As most elastography methods, axial shear strain elastography is primarily used in soft tissues. More recently, this technique has been proposed to assess the bone-soft tissue interface. In this paper, we investigate the effect of a variation in bone-soft tissue friction coefficient in the resulting axial shear strain elastograms. Finite element poroelastic models of bone specimens exhibiting different bone-soft tissue friction coefficients were created and mechanically analyzed. These models were then imported to an ultrasound elastography simulation module to assess the presence of axial shear strain patterns. In vitro experiments were performed to corroborate selected simulation results. The results of this study show that the normalized axial shear strain estimated at the bone-soft tissue interface is statistically correlated to the bone-soft tissue coefficient of friction. This information may prove useful to better interpret ultrasound elastography results obtained in bone-related applications and, possibly, monitor bone healing.

Photoacoustic microscopy enables multilayered histological imaging of human breast cancer without staining

NASA Astrophysics Data System (ADS)

Wong, Terence T. W.; Zhang, Ruiying; Hai, Pengfei; Aft, Rebecca L.; Novack, Deborah V.; Wang, Lihong V.

2018-02-01

In 2016, an estimated 250,000 new cases of invasive and non-invasive breast cancer were diagnosed in US women. About 60-75% of these cases were treated with breast conserving surgery (BCS) as the initial therapy. To reduce the local recurrence rate, the goal of BCS is to excise the tumor with a rim of normal surrounding tissue, so that no cancer cells remain at the cut margin, while preserving as much normal breast tissue as possible. Therefore, patients with remaining cancer cells at the cut margin commonly require a second surgical procedure to obtain clear margins. Different approaches have been used to decrease the positive margin rate to avoid re-excision. However, these techniques are variously ineffective in reducing the re-operative rate, difficult to master by surgeons, or time-consuming for large specimens. Thus, 20-60% of patients undergoing BCS still require second surgeries due to positive surgical margins. The ideal tool for margin assessment would provide the same information as histological analysis, without the need for processing specimens. To achieve this goal, we have developed and refined label-free photoacoustic microscopy (PAM) for breast specimens. Exploiting the intrinsic optical contrast of tissue, ultraviolet (UV) laser illumination can highlight cell nuclei, thus providing the same contrast as hematoxylin labeling used in conventional histology and measuring features related to the histological landscape without the need for labels. We demonstrate that our UV-PAM system can provide label-free, high-resolution, and histology-like imaging of fixed, unprocessed breast tissue.

Muscle tissue saturation in humans studied with two non-invasive optical techniques: a comparative study

NASA Astrophysics Data System (ADS)

Shaharin, Alfi; Krite Svanberg, Emilie; Ellerström, Ida; Subash, Arman Ahamed; Khoptyar, Dmitry; Andersson-Engels, Stefan; Åkeson, Jonas

2013-11-01

Muscle tissue saturation (StO2) has been measured with two non-invasive optical techniques and the results were compared. One of the techniques is widely used in the hospitals - the CW-NIRS technique. The other is the photon timeof- flight spectrometer (pTOFS) developed in the Group of Biophotonics, Lund University, Sweden. The wavelengths used in both the techniques are 730 nm and 810 nm. A campaign was arranged to perform measurements on 21 (17 were taken for comparison) healthy adult volunteers (8 women and 13 men). Oxygen saturations were measured at the right lower arm of each volunteer. To observe the effects of different provocations on the oxygen saturation a blood pressure cuff was attached in the upper right arm. For CW-NIRS, the tissue saturation values were in the range from 70-90%, while for pTOFS the values were in the range from 55-60%.

Non-invasive imaging of skin cancer with fluorescence lifetime imaging using two photon tomography

NASA Astrophysics Data System (ADS)

Patalay, Rakesh; Talbot, Clifford; Alexandrov, Yuriy; Munro, Ian; Breunig, Hans Georg; König, Karsten; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Christopher

2011-07-01

Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential.

Application of optical non-invasive methods to diagnose the state of the lower limb tissues in patients with diabetes mellitus

NASA Astrophysics Data System (ADS)

Zharkikh, E. V.; Dremin, V. V.; Filina, M. A.; Makovik, I. N.; Potapova, E. V.; Zherebtsov, E. A.; Zherebtsova, A. I.; Dunaev, A. V.

2017-11-01

The paper shows the possibility of assessing the functional state of microcirculatory-tissue systems of patients with diabetes mellitus by laser Doppler flowmetry (LDF), diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) methods. A review of the existing non-invasive optical technologies used to assess the state of microcirculation and oxygen metabolism in tissues of patients with diabetes is conducted. A series of experimental studies involving 76 patients with diabetes and 46 healthy volunteers was carried out. A wavelet analysis of LDF-grams was used to evaluate the adaptive changes of microcirculation during the temperature tests. The obtained data revealed that the proposed methodology in the form of combined use of several diagnostic technologies (LDF, FS and DRS) allows us to detect the presence or absence of trophic disorders and to evaluate adaptation processes during thermal tests.

Miniaturization of Microwave Ablation Antennas

NASA Astrophysics Data System (ADS)

Luyen, Hung

Microwave ablation (MWA) is a promising minimally invasive technique for the treatment of various types of cancers as well as non-oncological diseases. In MWA, an interstitial antenna is typically used to deliver microwave energy to the diseased tissue and heat it up to lethal temperature levels that induce cell death. The desired characteristics of the interstitial antenna include a narrow diameter to minimize invasiveness of the treatment, a low input reflection coefficient at the operating frequency, and a localized heating zone. Most interstitial MWA antennas are fed by coaxial cables and designed for operation at either 915 MHz or 2.45 GHz. Coax-fed MWA antennas are commonly equipped with coaxial baluns to achieve localized heating. However, the conventional implementation of coaxial baluns increases the overall diameters of the antennas and therefore make them more invasive. It is highly desirable to develop less invasive antennas with shorter active lengths and smaller diameters for MWA applications. In this work, we demonstrate the feasibility of using higher frequency microwaves for tissue ablation and present several techniques for decreasing diameters of MWA antennas. First, we investigated MWA at higher frequencies by conducting numerical and experimental studies to compare ablation performance at 10 GHz and 1.9 GHz. Simulation and ex vivo ablation experiment results demonstrate comparable ablation zone dimensions achieved at these two frequencies. Operating at higher frequencies enables interstitial antennas with shorter active lengths. This can be combined with smaller-diameter antenna designs to create less invasive applicators or allow integration of multiple radiating elements on a single applicator to have better control and customization of the heating patterns. Additionally, we present three different coax-fed antenna designs and a non-coaxial-based balanced antenna that have smaller-diameter configurations than conventional coax-fed balun-equipped antennas. The antennas were evaluated and optimized in electromagnetic and thermal simulations. Then prototypes of these antennas were fabricated and experimentally characterized in ex vivo ablation experiments. Simulation and experimental results are in good agreement and demonstrate that the proposed antennas provide good impedance matching and localized heating patterns at their operating frequencies while having about 30% smaller diameters compared to conventional coax-fed balun-equipped MWA antennas.

Non-invasive measurement of the temperature rise in tissue surrounding a kidney stone subjected to ultrasonic propulsion.

PubMed

Oweis, Ghanem F; Dunmire, Barbrina L; Cunitz, Bryan W; Bailey, Michael R

2015-01-01

Transcutaneous focused ultrasound (US) is used to propel kidney stones using acoustic radiation force. It is important to estimate the level of heating generated at the stone/tissue interface for safety assessment. An in-vitro experiment is conducted to measure the temperature rise in a tissue-mimicking phantom with an embedded artificial stone and subjected to a focused beam from an imaging US array. A novel optical-imaging-based thermometry method is described using an optically clear tissue phantom. Measurements are compared to the output from a fine wire thermocouple placed on the stone surface. The optical method has good sensitivity, and it does not suffer from artificial viscous heating typically observed with invasive probes and thermocouples.

Clinical Relevance of Ceramide Metabolism in the Pathogenesis of Human Head and Neck Squamous Cell Carcinoma (HNSCC): Attenuation of C18-ceramide in HNSCC Tumors Correlates with Lymphovascular Invasion and Nodal Metastasis

PubMed Central

Karahatay, Serdar; Thomas, Kesha; Koybasi, Serap; Senkal, Can E.; ElOjeimy, Saeed; Liu, Xiang; Bielawski, Jacek; Day, Terry A.; Boyd Gillespie, M; Sinha, Debajyoti; Norris, James S.; Hannun, Yusuf A.; Ogretmen, Besim

2007-01-01

It has been documented previously that defects in the generation of C18-ceramide, a product of ceramide synthase 1 (CerS1), also known as longevity assurance gene 1 (hLASS1), play important roles in the pathogenesis and/or progression of HNSCC. However, whether altered levels of ceramide generation in HNSCC tumors have any clinical relevance remains unknown. In this study, the levels of endogenous ceramides were measured in tumor tissues of 45 HNSCC patients as compared to their normal tissues using high-pressure liquid chromatography/mass spectrometry (LC/MS), and then possible link between ceramide levels and the clinical parameters of HNSCC were examined. The data showed that the levels of C16-, C24-, C24:1-ceramide were significantly elevated in the majority of tumor tissues compared to their normal tissues, while the levels of only C18-ceramide were significantly decreased in HNSCC tumors, especially in tumor tissues of male patients. Importantly, it was also shown here that decreased C18-ceramide levels in HNSCC tumor tissues were significantly associated with the higher incidences of lymphovascular invasion, and pathologic nodal metastasis. Importantly, attenuation of C18-ceramide was also positively linked to the higher overall stages of the primary HNSCC tumors. Therefore, these data suggest, for the first time, that the defects in the generation/accumulation of C18-ceramide might have important clinical roles in HNSCC, especially in lymphovascular invasion and nodal disease. PMID:17619081

Overexpression of MTA1 and loss of KAI-1 and KiSS-1 expressions are associated with invasion, metastasis, and poor-prognosis of gallbladder adenocarcinoma.

PubMed

Wang, Wenjun; Yang, Zhu-lin; Liu, Jie-qiong; Yang, Le-ping; Yang, Xiao-jing; Fu, Xi

2014-01-01

Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.

The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer

PubMed Central

Kogo, Ryunosuke; How, Christine; Chaudary, Naz; Bruce, Jeff; Shi, Wei; Hill, Richard P.; Zahedi, Payam; Yip, Kenneth W.; Liu, Fei-Fei

2015-01-01

Cervical cancer is the third most common cancer in women worldwide. In the present study, global microRNA profiling for 79 cervical cancer patient samples led to the identification of miR-218 down-regulation in cervical cancer tissues compared to normal cervical tissues. Lower miR-218 expression was associated significantly with worse overall survival (OS), disease-free survival (DFS), and pelvic/aortic lymph node recurrence. In vitro, miR-218 over-expression decreased clonogenicity, migration, and invasion. Survivin (BIRC5) was subsequently identified as an important cervical cancer target of miR-218 using in silico prediction, mRNA profiling, and quantitative real-time PCR (qRT-PCR). Concordant with miR-218 over-expression, survivin knockdown by siRNA decreased clonogenicity, migration, and invasion. YM155, a small molecule survivin inhibitor, significantly suppressed tumor growth and lymph node metastasis in vivo. Our findings demonstrate that the miR-218~survivin axis inhibits cervical cancer progression by regulating clonogenicity, migration, and invasion, and suggest that the inhibition of survivin could be a potential therapeutic strategy to improve outcome in this disease. PMID:25473903

Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts.

PubMed

Tuchscherr, Lorena; Korpos, Èva; van de Vyver, Hélène; Findeisen, Clais; Kherkheulidze, Salome; Siegmund, Anke; Deinhardt-Emmer, Stefanie; Bach, Olaf; Rindert, Martin; Mellmann, Alexander; Sunderkötter, Cord; Peters, Georg; Sorokin, Lydia; Löffler, Bettina

2018-05-22

Staphylococcus aureus is the most frequent pathogen causing diabetic foot infections. Here, we investigated the degree of bacterial virulence required to establish invasive tissue infections in diabetic organisms. Staphylococcal isolates from diabetic and non-diabetic foot ulcers were tested for their virulence in in vitro functional assays of host cell invasion and cytotoxicity. Isolates from diabetes mellitus type I/II patients exhibited less virulence than isolates from non-diabetic patients, but were nevertheless able to establish severe infections. In some cases, non-invasive isolates were detected deep within diabetic wounds, even though the strains were non-pathogenic in cell culture models. Testing of defined isolates in murine footpad injection models revealed that both low- and high-virulent bacterial strains persisted in higher numbers in diabetic compared to non-diabetic hosts, suggesting that hyperglycemia favors bacterial survival. Additionally, the bacterial load was higher in NOD mice, which have a compromised immune system, compared to C57Bl/6 mice. Our results reveal that high as well as low-virulent staphylococcal strains are able to cause soft tissue infections and to persist in diabetic humans and mice, suggesting a reason for the frequent and endangering infections in patients with diabetes. Copyright © 2018 Elsevier GmbH. All rights reserved.

Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro1

PubMed Central

Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Taylor, Hugh S.; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J.

2010-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10–12 and 18–20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10–30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis. PMID:20844278

Decreased expression of ten-eleven translocation 1 protein is associated with some clinicopathological features in gastric cancer.

PubMed

Frycz, Bartosz Adam; Murawa, Dawid; Borejsza-Wysocki, Maciej; Marciniak, Ryszard; Murawa, Paweł; Drews, Michał; Kołodziejczak, Anna; Tomela, Katarzyna; Jagodziński, Paweł Piotr

2014-03-01

A decrease in ten-eleven translocation 1 (TET1) transcript and 5-Hydroxymethylcytosine (5hmC) levels has recently been demonstrated in primary gastric cancer (GC). However, little is known about TET1 protein levels in gastric tumoral and nontumoral tissue. Therefore, using reverse transcription, real-time quantitative polymerase chain reaction and western blotting analysis, we determined the TET1 transcript and protein levels in tumoral and nontumoral tissue from 38 patients with GC. We also assessed the association between the decrease in TET1 transcript and protein levels and some clinicopathological features in primary GC. We found significantly decreased levels of TET1 transcript (P=0.0023) and protein (P=0.00024) in primary tumoral tissues as compared to nontumoral tissues in patients with GC. Moreover, we also observed significantly lower amounts of TET1 transcript (P=0.03) and protein (P=0.00018) in tumoral tissues in patients aged>60. We also found significant lowered TET1 protein levels in male patients (P=0.0014), stomach (P=0.044) and cardia (P=0.013) tumor localization, T3 depth of invasion (P=0.019), N1 (P=0.012) and N3 lymph node metastasis (P=0.013) and G3 histological grade (P=0.0012). There were also significant decreases in TET1 transcript levels in female patients (P=0.042), intestinal histological types (P=0.0079) and T4 depth of invasion (P=0.037). Our results demonstrated that a decrease in TET1 transcript and protein levels is associated with some clinicopathological features in GC. Copyright © 2014. Published by Elsevier Masson SAS.

Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human hilar cholangiocarcinoma.

PubMed

Tan, Xin-Yu; Chang, Shi; Liu, Wei; Tang, Hui-Huan

2014-03-01

To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

Burn-injured tissue detection for debridement surgery through the combination of non-invasive optical imaging techniques.

PubMed

Heredia-Juesas, Juan; Thatcher, Jeffrey E; Lu, Yang; Squiers, John J; King, Darlene; Fan, Wensheng; DiMaio, J Michael; Martinez-Lorenzo, Jose A

2018-04-01

The process of burn debridement is a challenging technique requiring significant skills to identify the regions that need excision and their appropriate excision depths. In order to assist surgeons, a machine learning tool is being developed to provide a quantitative assessment of burn-injured tissue. This paper presents three non-invasive optical imaging techniques capable of distinguishing four kinds of tissue-healthy skin, viable wound bed, shallow burn, and deep burn-during serial burn debridement in a porcine model. All combinations of these three techniques have been studied through a k-fold cross-validation method. In terms of global performance, the combination of all three techniques significantly improves the classification accuracy with respect to just one technique, from 0.42 up to more than 0.76. Furthermore, a non-linear spatial filtering based on the mode of a small neighborhood has been applied as a post-processing technique, in order to improve the performance of the classification. Using this technique, the global accuracy reaches a value close to 0.78 and, for some particular tissues and combination of techniques, the accuracy improves by 13%.

Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion

PubMed Central

Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Xuepeng; Jiang, Hao; Zhang, Zheng Gang; Chopp, Michael

2008-01-01

In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by Photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J/cm2 with 2mg/kg Photofrin). Hypoxic stress and ADAM17-EGFR-PI3K-Akt were measured using Western blot and immunostaining. Additional groups with/without pro-sublethal PDT were subsequently implanted with U87 glioma tumor cell. Tumor invasion and ADAM17-EGFR-PI3K-Akt pathway in tumor area were measured. After a sublethal dose of PDT, HIF-1α expression was increased by a factor of three in PDT-treated normal brain tissue compared to contralateral control brain tissue. PDT-treated brain tissue exhibited a significant increase in ADAM17, p-EGFR, p-Akt expression compared to non-treated tissue. ADAM17 positive area significantly increased from 1.78% to 10.89%. The percentage of p-EGFR and p-Akt positive cells significantly increased from 9.50% and 14.50% to 21.31% and 32.29%,respectively, PDT treatment significantly increased subsequent implanted U87 glioma cell invasion by 3.68-fold and increased ADAM17, EGFR, p-EGFR, Akt, p-Akt expression by 178%, 43.9%,152.7%, 89.6%,and 164.2%, respectively, compared to control group. Our data showed that a sublethal sensitization of cerebral tissue with PDT significantly increased U87 cell invasion in nude mice, and that glioma cell invasion is highly correlated with activation of the ADAM17-EGFR-PI3K-Akt pathway (r=0.928, 0.775, 0.870, 0.872, and 0.883, respectively), most likely via HIF-1α. PMID:18358600

NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

PubMed Central

Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

2008-01-01

Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

Biological significance of long non-coding RNA FTX expression in human colorectal cancer.

PubMed

Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

2015-01-01

The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer.

Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

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

Tamminen, Jenni A.; Yin, Miao; Transplantation Laboratory, Haartman Institute, University of Helsinki

Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cellsmore » in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. - Highlights: • Activin-A and activin-B are highly expressed in mesothelioma. • Mesothelioma cell migration and invasive growth can be blocked with sActR2B. • Activin induced Smad3 activity is attenuated in invasive mesothelioma cells. • Activins induce ERK activity in mesothelioma cells.« less

A Functional High-Throughput Assay of Myelination in Vitro

DTIC Science & Technology

2013-07-01

feasibility of developing microengineered human neural tissues that can be assessed non-invasively. A population of neurons has been derived from human...physiological responses in microengineered tissue constructs has been demonstrated. This works represents a unique combination of enabling...and recording from microengineered tissues. All progress and results discussed in this report are in regard to the revised Statement of Work

Isotropic non-white matter partial volume effects in constrained spherical deconvolution.

PubMed

Roine, Timo; Jeurissen, Ben; Perrone, Daniele; Aelterman, Jan; Leemans, Alexander; Philips, Wilfried; Sijbers, Jan

2014-01-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DW signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM-GM interface is especially important. We suggest acquiring data with high diffusion-weighting 2500-3000 s/mm(2), reasonable SNR (~30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.

The response of MRI contrast parameters in in vitro tissues and tissue mimicking phantoms to fractionation by histotripsy

NASA Astrophysics Data System (ADS)

Allen, Steven P.; Vlaisavljevich, Eli; Shi, Jiaqi; Hernandez-Garcia, Luis; Cain, Charles A.; Xu, Zhen; Hall, Timothy L.

2017-09-01

Histotripsy is a non-invasive, focused ultrasound lesioning technique that can ablate precise volumes of soft tissue using a novel mechanical fractionation mechanism. Previous research suggests that magnetic resonance imaging (MRI) may be a sensitive image-based feedback mechanism for histotripsy. However, there are insufficient data to form some unified understanding of the response of the MR contrast mechanisms in tissues to histotripsy. In this paper, we investigate the response of the MR contrast parameters R1, R2, and the apparent diffusion coefficient (ADC) to various treatment levels of histotripsy in in vitro porcine liver, kidney, muscle, and blood clot as well in formulations of bovine red blood cells suspended in agar gel. We also make a histological analysis of histotripsy lesions in porcine liver. We find that R2 and the ADC are both sensitive to ablation in all materials tested here, and the degree of response varies with tissue type. Correspondingly, under histologic analysis, the porcine liver exhibited various levels of mechanical disruption and necrotic debris that are characteristic of histotripsy. While the area of intact red blood cells and nuclei found within these lesions both decreased with increasing amounts of treatment, the area of red blood cells decreased much more rapidly than the area of intact nuclei. Additionally, the decrease in area of intact red blood cells saturated at the same treatment levels at which the response of the R2 saturated while the area of intact nuclei appeared to vary linearly with the response of the ADC.

HMGA2 upregulation mediates Cd-induced migration and invasion in A549 cells and in lung tissues of mice.

PubMed

Luo, Huiyuan; Li, Zhiguo; Ge, Hong; Mei, Dan; Zhao, Lian; Jiang, Liping; Geng, Chengyan; Li, Qiujuan; Yao, Xiaofeng; Cao, Jun

2017-11-01

Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities. Copyright © 2017 Elsevier B.V. All rights reserved.

Thioredoxin 1 mediates TGF-β-induced epithelial-mesenchymal transition in salivary adenoid cystic carcinoma.

PubMed

Jiang, Yang; Feng, Xin; Zheng, Lei; Li, Sheng-Lin; Ge, Xi-Yuan; Zhang, Jian-Guo

2015-09-22

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC) which is characterized by wide local infiltration, perineural spread, a propensity to local recurrence and late distant metastasis. Our recent studies have disclosed that TGF-β is a crucial factor for EMT in metastatic SACC. In this study, we further uncovered small redox protein thioredoxin 1 (TXN) as a critical mediator of TGF-β induced EMT. Immunohistochemistry analysis revealed significantly higher expressions of TXN, thioredoxin reductase 1 (TXNRD1) and N-cadherin, and lower expression of E-cadherin in human metastatic SACC compared to non-metastatic SACC tissues. Consistently, cultured SACC cells with stable TXN overexpression had decreased E-cadherin and increased N-cadherin as well as Snail and Slug expressions. The enhanced migration and invasion potential of these cells was abrogated by Akt or TXNRD1 inhibitors. Expression of N-cadherin and Akt p-Akt decreased, whereas E-cadherin expression increased in a BBSKE (TXNRD1 inhibitor)-dose-dependent manner. In a xenograft mouse model, TXN overexpression facilitated the metastatic potential of SACC-83 cells to the lung. Our results indicate that TXN plays a key role in SACC invasion and metastasis through the modulation of TGF-β-Akt/GSK-3β on EMT. TXN could be a potential therapeutic target for SACC.

Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway

PubMed Central

Xue, Xiaotong; Wang, Lihua; Meng, Xianguang; Jiao, Jing; Dang, Ningning

2017-01-01

Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target. PMID:29108247

Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

PubMed Central

Campo-Verde-Arbocco, Fiorella; López-Laur, José D.; Romeo, Leonardo R.; Giorlando, Noelia; Bruna, Flavia A.; Contador, David E.; López-Fontana, Gastón; Santiano, Flavia E.; Sasso, Corina V.; Zyla, Leila E.; López-Fontana, Constanza M.; Calvo, Juan C.; Carón, Rubén W.; Creydt, Virginia Pistone

2017-01-01

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease. PMID:29212223

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

PubMed Central

Bible, Ellen; Dell’Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter; Badylak, Stephen F.; Ahrens, Eric T.; Modo, Michel

2012-01-01

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. PMID:22244696

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung

PubMed Central

Murphy, Sean V.; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-01-01

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a ‘proof-of-concept’ experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. PMID:26546729

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.

PubMed

Murphy, Sean V; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-04-15

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. Copyright © 2015 Elsevier Inc. All rights reserved.

Suitability of [18F]altanserin and PET to determine 5-HT2A receptor availability in the rat brain: in vivo and in vitro validation of invasive and non-invasive kinetic models.

PubMed

Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas

2013-08-01

While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats. Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals. Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals. [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.

Non-invasive diagnostic methods in dentistry

NASA Astrophysics Data System (ADS)

Todea, Carmen

2016-03-01

The paper, will present the most important non-invasive methods for diagnostic, in different fields of dentistry. Moreover, the laser-based methods will be emphasis. In orthodontics, 3D laser scanners are increasingly being used to establish database for normative population and cross-sectional growth changes but also to asses clinical outcomes in orthognatic surgical and non-surgical treatments. In prevention the main methods for diagnostic of demineralization and caries detection in early stages are represented by laser fluorescence - Quantitative Light Florescence (QLF); DiagnoDent-system-655nm; FOTI-Fiberoptic transillumination; DIFOTI-Digital Imaging Fiberoptic transillumination; and Optical Coherence Tomography (OCT). In odontology, Laser Doppler Flowmetry (LDF) is a noninvasive real time method used for determining the tooth vitality by monitoring the pulp microcirculation in traumatized teeth, fractured teeth, and teeth undergoing different conservative treatments. In periodontology, recently study shows the ability of LDF to evaluate the health of gingival tissue in periodontal tissue diseases but also after different periodontal treatments.

Detection of extracellular matrix modification in cancer models with inverse spectroscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Spicer, Graham L. C.; Azarin, Samira M.; Yi, Ji; Young, Scott T.; Ellis, Ronald; Bauer, Greta M.; Shea, Lonnie D.; Backman, Vadim

2016-10-01

In cancer biology, there has been a recent effort to understand tumor formation in the context of the tissue microenvironment. In particular, recent progress has explored the mechanisms behind how changes in the cell-extracellular matrix ensemble influence progression of the disease. The extensive use of in vitro tissue culture models in simulant matrix has proven effective at studying such interactions, but modalities for non-invasively quantifying aspects of these systems are scant. We present the novel application of an imaging technique, Inverse Spectroscopic Optical Coherence Tomography, for the non-destructive measurement of in vitro biological samples during matrix remodeling. Our findings indicate that the nanoscale-sensitive mass density correlation shape factor D of cancer cells increases in response to a more crosslinked matrix. We present a facile technique for the non-invasive, quantitative study of the micro- and nano-scale structure of the extracellular matrix and its host cells.

Oxidative stress measured in vivo without an exogenous contrast agent using QUEST MRI

NASA Astrophysics Data System (ADS)

Berkowitz, Bruce A.

2018-06-01

Decades of experimental studies have implicated excessive generation of reactive oxygen species (ROS) in the decline of tissue function during normal aging, and as a pathogenic factor in a vast array of fatal or debilitating morbidities. This massive body of work has important clinical implications since many antioxidants are FDA approved, readily cross blood-tissue barriers, and are effective at improving disease outcomes. Yet, the potential benefits of antioxidants have remained largely unrealized in patients because conventional methods cannot determine the dose, timing, and drug combinations to be used in clinical trials to localize and decrease oxidative stress. To address this major problem and improve translational success, new methods are urgently needed that non-invasively measure the same ROS biomarker both in animal models and patients with high spatial resolution. Here, we summarize a transformative solution based on a novel method: QUEnch-assiSTed MRI (QUEST MRI). The QUEST MRI index is a significant antioxidant-induced improvement in pathophysiology, or a reduction in 1/T1 (i.e., R1). The latter form of QUEST MRI provides a unique measure of uncontrolled production of endogenous, paramagnetic reactive oxygen species (ROS). QUEST MRI results to-date have been validated by gold standard oxidative stress assays. QUEST MRI has high translational potential because it does not use an exogenous contrast agent and requires only standard MRI equipment. Summarizing, QUEST MRI is a powerful non-invasive approach with unprecedented potential for (i) bridging antioxidant treatment in animal models and patients, (ii) identifying tissue subregions exhibiting oxidative stress, and (iii) coupling oxidative stress localization with behavioral dysfunction, disease pathology, and genetic vulnerabilities to serve as a marker of susceptibility.

Optical spectroscopy for the detection of ischemic tissue injury

DOEpatents

Demos, Stavros [Livermore, CA; Fitzgerald, Jason [Sacramento, CA; Troppmann, Christoph [Sacramento, CA; Michalopoulou, Andromachi [Athens, GR

2009-09-08

An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient's body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

Emerging Non-Cancer Applications of Therapeutic Ultrasound

PubMed Central

O’Reilly, Meaghan A.; Hynynen, Kullervo

2015-01-01

Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer, clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programs that have great potential to impact patient care. PMID:25792225

Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression.

PubMed

Deng, Ruyuan; Wu, Huo; Ran, Hui; Kong, Xiang; Hu, Lei; Wang, Xiao; Su, Qing

2017-05-01

It is well established that the risk of colorectal cancer (CRC) is significantly increased in diabetic patients. As one of main forms of the advanced glycation end products (AGEs) that accumulate in vivo, glucose-derived AGEs play an important role in the pathogenesis of diabetic complications and may contribute to CRC progression. However, to date, both the contribution of glucose-derived AGEs to the course of CRC and the underlying mechanism are unclear. In the present study, the concentration of glucose-derived AGEs in the serum and tumor tissue of patients with CRC increased. A clinical data analysis demonstrated that the expression of the receptor for AGEs (RAGE), Specificity Protein 1 (Sp1), and matrix metallopeptidase -2 (MMP2) was significantly higher in cancerous tissues compared with non-tumor tissue in Chinese Han patients with CRC and that RAGE expression was closely associated with lymph node metastasis and TNM stage. Furthermore, in vivo and in vitro experiments showed that AGEs promoted invasion and migration of colorectal cancer, and the AGEs treatment increased the expression of RAGE, Sp1, and MMP2 in a dose-dependent manner. A RAGE blocking antibody and an Sp1-specific siRNA attenuated the AGE-induced effects. Moreover, the AGEs treatment increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. In conclusion, glucose-derived AGEs promote the invasion and metastasis of CRC partially through the RAGE/ERK/SP1/MMP2 cascade. These findings may provide an explanation for the poor prognoses of colorectal cancer in diabetic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer

PubMed Central

Dorris, Emma; O'Neill, Amanda; Hanrahan, Karen; Treacy, Ann; Watson, R. William

2017-01-01

Background Overtreatment of low-grade prostate cancer is a recognised problem for clinicians and patients. However, under-treatment runs the risk of missing the opportunity for cure in those who could benefit. Identification of new biomarkers of disease progression, including metastases, is required to better stratify and appropriately treat these patients. The ability to predict if prostate cancer will recur is an important clinical question that would impact treatment options for patients. Studies in other cancers have associated MARCKS with metastasis. Methods Tissue microarrays of local prostatectomy samples from a cohort of biochemical recurrent and non-biochemical recurrent tumours were assayed for MARCKS protein expression. Prostate cancer cell lines were transfected with siRNA targeting MARCKS or a control and functional endpoints of migration, invasion, proliferation, viability and apoptosis were measured. Actin was visualised by fluorescent microscopy and evidence of a cadherin switch and activation of the AKT pathway were assayed. Results MARCKS was upregulated in biochemical recurrent patients compared to non-biochemical recurrent. Knockdown of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9 mRNA expression, as well as decreasing cell spreading and increased cell:cell adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on proliferation, viability or apoptosis of the prostate cancer cells. Conclusions In conclusion, MARCKS promotes migration and invasion and is associated with biochemical recurrence in localised prostate cancer tumours. The mechanisms by which this occurs have yet to be fully elucidated but lack of a cadherin switch indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement indicates that MARCKS promotes invasion through regulating the architecture of the cell. PMID:29069765

The roles of HOXB7 in promoting migration, invasion, and anti-apoptosis in gastric cancer.

PubMed

Joo, Moon Kyung; Park, Jong-Jae; Yoo, Hyo Soon; Lee, Beom Jae; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

2016-10-01

The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells. Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay were performed, and Akt/PTEN activity was measured by western blotting. Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells. Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Non-invasive label-free investigation and typing of head and neck cancers by multimodal nonlinear microscopy

NASA Astrophysics Data System (ADS)

Meyer, Tobias; Vogler, Nadine; Dietzek, Benjamin; Akimov, Denis; Inhestern, Johanna; Guntinas-Lichius, Orlando; Popp, Jürgen

2012-06-01

Early detection and typing of tumors is pressing matter in clinical research with important impacts for prognosis and successful treatment. Currently, staining is the golden standard in histopathology but requires surgical removal of tissue. In order to avoid resection of non-diseased tissue a non-invasive real-time imaging method is required which can be applied ideally intrasurgically. In this proceeding a combination of second harmonic generation (SHG), two photon excited fluorescence (TPEF) and coherent anti-Stokes Raman (CARS) imaging has been employed to investigate tissue sections of head and neck carcinomas focussing on laryngeal carcinoma. Primary laryngeal and other head and neck carcinomas consist to 99% of squamous cell carcinoma. By fusing the various imaging methods it is possible to measure the thickness of the epithelial cell layer as a marker for dysplastic or cancerous tissue degradation and to differentiate keratinizing and nonkeratininzing squamous cell carcinomas (SCC). As nonkeratinizing SCCs of the oropharynx correlate with a human papillomavirus (HPV) infection as a subentity of head and neck cancer, and HPV related tumors are associated with a better clinical prognosis, the differentiation between keratinizing and non-keratinizing forms of SCCs is of high diagnostic value. TPEF is capable of displaying cell nuclei, therefore, morphologic information as cell density, cell to cytoplasm ratio, size and shape of cell nuclei can be obtained. SHG - on the other hand - selectively reveals the collagen matrix of the connective tissue, which is useful for determination of tumor-islets boundaries within epithelial tissue - a prerequisite for precise resection. Finally CARS in the CH-stretching region visualizes the lipid content of the tissue, which can be correlated with the dysplastic grade of the tissue.

Photoacoustic determination of glucose concentration in whole blood by a near-infrared laser diode

NASA Astrophysics Data System (ADS)

Zhao, Zuomin; Myllylae, Risto A.

2001-06-01

The near-infrared photoacoustic technique is recognized as a potential method for the non-invasive determination of human glucose, because near-infrared light can incident a few millimeters into human tissue, where it produces an acoustic wave capable of carrying information about the composition of the tissue. This paper demonstrates a photoacoustic glucose measurement in a blood sample as a step toward a non-invasive measurement. The experimental apparatus consists of a near-infrared laser diode operating with 4 micro joules pulse energy at 905 nm, a roller pump connected to a silicon plastic tube and a cuvette for circulating the blood sample. In addition, the apparatus comprises a PZT piezoelectric transducer integrated with a battery-powered preamplifier to receive the photoacoustic signal. During the experiment, a glucose solution is mixed into a human blood sample to change its concentration. Although the absorption coefficient of glucose is much smaller than that of blood in the near-infrared region, the osmotic and hydrophilic properties of glucose decrease the reduced scattering coefficient of blood caused by the dissolved glucose surrounding the blood cells. This changes the distribution of the absorbed optical energy in blood, which, in turn, produces a change in the photoacoustic signal. Our experiment demonstrates that signal amplitudes in fresh and stored blood samples in crease about 7% and 10%, respectively, when the glucose concentration reaches the upper limit of the physiological region (500 mg/dl).

A non-invasive diffuse reflectance calibration-free method for absolute determination of exogenous biochemicals concentration in biological tissues

NASA Astrophysics Data System (ADS)

Lappa, Alexander V.; Kulikovskiy, Artem N.; Busarov, Oleg G.

2014-03-01

The paper presents a new method for distant non-destructive determination of concentration of light absorbing admixtures in turbid media. In particular, it is intended for non-invasive in vivo control of accumulation in patient tissues of various biochemicals introduced to the patients for chemotherapy, photodynamic therapy or diagnostics. It is require that the admixture absorption spectrum should have a clearly marked peak in the wavelength region where the pure medium one varies regularly. Fluorescence of admixtures is not required. The method uses the local diffuse reflectance spectroscopy with optical fiber probe including one emitting and two reading There are several features in the method: the value to be determined is absolute concentration of admixtures; the method needs no calibration measurements on phantoms; it needs no reference measurements on sample with zero admixture concentration; it uses a two parametric kinetic light propagation model and original algorithms to resolve direct and inverse tasks of radiation transport theory. Experimental testing passed with tissue equivalent phantoms and different admixtures, including a chlorine photosensitizer, showed accuracy under 10% in all cases.

Assessment of sacrococcygeal pressure ulcers using diffuse correlation spectroscopy

NASA Astrophysics Data System (ADS)

Diaz, David; Lafontant, Alec; Neidrauer, Michael; Weingarten, Michael S.; DiMaria-Ghalili, Rose Ann; Fried, Guy W.; Rece, Julianne; Lewin, Peter A.; Zubkov, Leonid

2016-03-01

Microcirculation is essential for proper supply of oxygen and nutritive substances to the biological tissue and the removal of waste products of metabolism. The determination of microcirculatory blood flow (mBF) is therefore of substantial interest to clinicians for assessing tissue health; particularly in pressure ulceration and suspected deep tissue injury. The goal of this pilot clinical study was to assess deep-tissue pressure ulceration by non-invasively measuring mBF using Diffuse Correlation Spectroscopy (DCS). DCS provides information about the flow of red blood cells in the capillary network by measuring the temporal autocorrelation function of scattering light intensity. A novel optical probe was developed in order to obtain measurements under the load of the subject's body as pressure is applied (ischemia) and then released (reperfusion) on sacrococcygeal tissue in a hospital bed. Prior to loading measurements, baseline readings of the sacral region were obtained by measuring the subjects in a side-lying position. DCS measurements from the sacral region of twenty healthy volunteers have been compared to those of two patients who initially had similar non-blanchable redness. The temporal autocorrelation function of scattering light intensity of the patient whose redness later disappeared was similar to that of the average healthy subject. The second patient, whose redness developed into an advanced pressure ulcer two weeks later, had a substantial decrease in blood flow while under the loading position compared to healthy subjects. Preliminary results suggest the developed system may potentially predict whether non-blanchable redness will manifest itself as advanced ulceration or dissipate over time.

Non-invasive electromechanical activation imaging as a tool to study left ventricular dyssynchronous patients: Implication for CRT therapy.

PubMed

Dawoud, Fady; Spragg, David D; Berger, Ronald D; Cheng, Alan; Horáček, B Milan; Halperin, Henry R; Lardo, Albert C

2016-01-01

Electromechanical de-coupling is hypothesized to explain non-response of dyssynchrony patient to cardiac resynchronization therapy (CRT). In this pilot study, we investigated regional electromechanical uncoupling in 10 patients referred for CRT using two non-invasive electrical and mechanical imaging techniques (CMR tissue tracking and ECGI). Reconstructed regional electrical and mechanical activation captured delayed LBBB propagation direction from septal to anterior/inferior and finally to lateral walls as well as from LV apical to basal. All 5 responders demonstrated significantly delayed mechanical and electrical activation on the lateral LV wall at baseline compared to the non-responders (P<.05). On follow-up ECGI, baseline electrical activation patterns were preserved in native rhythm and global LV activation time was reduced with biventricular pacing. The combination of novel imaging techniques of ECGI and CMR tissue tracking can be used to assess spatial concordance of LV electrical and mechanical activation to gain insight into electromechanical coupling. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44

PubMed Central

2014-01-01

Introduction Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration. Methods Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients. Results CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures. Conclusion Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis. PMID:24512624

Circular RNA hsa_circ_0000673 promotes hepatocellular carcinoma malignance by decreasing miR-767-3p targeting SET.

PubMed

Jiang, Weidong; Wen, Dacheng; Gong, Lulu; Wang, Yu; Liu, Zefeng; Yin, Fangying

2018-06-02

The importance of circular RNAs (circRNAs) in human cancers has gradually been acknowledged. In hepatocellular carcinoma (HCC), several circRNAs have been reported to regulate tumor growth and metastasis. However, the role of hsa_circ_0000673 in HCC remains largely unknown. In this study, we found that hsa_circ_0000673 was significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Moreover, we found that hsa_circ_0000673 knockdown markedly inhibited the proliferation and invasion of HCC cells in vitro. Besides, hsa_circ_0000673 silence led to delayed tumor growth in vivo. In terms of mechanism, we showed that hsa_circ_0000673 directly associated with miR-767-3p in HCC cells. Via inhibiting miR-767-3p, hsa_circ_0000673 promoted HCC cell proliferation and invasion. Furthermore, we demonstrated that SET was a downstream effector of hsa_circ_0000673/miR-767-3p signaling. We showed that miR-767-3p could significantly promote SET expression by sponging miR-767-3p in HCC cells. Finally, rescue assays indicated that SET expression was essential for the effects of hsa_circ_0000673/miR-767-3p signaling on HCC cell proliferation and invasion. Taken together, our findings demonstrated that hsa_circ_0000673 promoted HCC malignant behaviors via regulating miR-767-3p/SET pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway

PubMed Central

Zhang, Chenlei; Liu, Tieqin; Wang, Gebang; Wang, Huan; Che, Xiaofang; Gao, Xinghua; Liu, Hongxu

2017-01-01

Background: The role of Rac3 in cell proliferation in lung adenocarcinoma has been tackled in our previous study. However, the role of Rac3 in cell invasion and migration of lung adenocarcinoma is still not clear. Methods: The expression of Rac3 in lung adenocarcinoma specimens and paired noncancerous normal tissues were evaluated by immunohistochemistry. Lentivirus-mediated RNA interference (RNAi) was employed to silence Rac3 in lung adenocarcinoma cell lines A549 and H1299. A p38 MAPK inhibitor (LY2228820) was employed to inhibit activity of p38 MAPK pathway. Cell invasion and migration in vitro were examined by invasion and migration assays, respectively. PathScan® intracellular signaling array kit and western blot were employed in mechanism investigation. Results: Rac3 expression was frequently higher in lung adenocarcinoma than paired noncancerous normal tissues. Rac3 expression was an independent risk factor for lymphonode metastasis, and was associated with worse survival outcome. Silencing of Rac3 inhibited cell invasion and cell migration in lung adenocarcinoma cell lines. Knockdown of Rac3 decreased activity of p38 MAPK pathway. LY2228820, which was an important p38 MAPK inhibitor, inhibited Rac3-induced cell invasion and migration of lung adenocarcinoma. E-cadherin expression was increased and vimentin expression was decreased after silencing of Rac3 or following the treatment of LY2228820. Conclusions: Our findings suggest that Rac3 regulates cell invasion, migration and EMT via p38 MAPK pathway. Rac3 may be a potential biomarker of invasion and metastasis for lung adenocarcinoma, and knockdown of Rac3 may potentially serve as a promising therapeutic target for lung adenocarcinoma. PMID:28900489

In silico simulation and in vitro evaluation of an elastomeric scaffold using ultrasonic shear wave imaging

NASA Astrophysics Data System (ADS)

Yu, Jiao; Nie, Erwei; Zhu, Yanying; Hong, Yi

2018-03-01

Biodegradable elastomeric scaffolds for soft tissue repair represent a growing area of biomaterials research. Mechanical strength is one of the key factors to consider in the evaluation of candidate materials and the designs for tissue scaffolds. It is desirable to develop non-invasive evaluation methods of the mechanical property of scaffolds which would provide options for monitoring temporal mechanical property changes in situ. In this paper, we conduct in silico simulation and in vitro evaluation of an elastomeric scaffold using a novel ultrasonic shear wave imaging (USWI). The scaffold is fabricated from a biodegradable elastomer, poly(carbonate urethane) urea using salt leaching method. A numerical simulation is performed to test the robustness of the developed inversion algorithm for the elasticity map reconstruction which will be implemented in the phantom experiment. The generation and propagation of shear waves in a homogeneous tissue-mimicking medium with a circular scaffold inclusion is simulated and the elasticity map is well reconstructed. A PVA phantom experiment is performed to test the ability of USWI combined with the inversion algorithm to non-invasively characterize the mechanical property of a porous, biodegradable elastomeric scaffold. The elastic properties of the tested scaffold can be easily differentiated from the surrounding medium in the reconstructed image. The ability of the developed method to identify the edge of the scaffold and characterize the elasticity distribution is demonstrated. Preliminary results in this pilot study support the idea of applying the USWI based method for non-invasive elasticity characterization of tissue scaffolds.

An image based vibration sensor for soft tissue modal analysis in a Digital Image Elasto Tomography (DIET) system.

PubMed

Feng, Sheng; Lotz, Thomas; Chase, J Geoffrey; Hann, Christopher E

2010-01-01

Digital Image Elasto Tomography (DIET) is a non-invasive elastographic breast cancer screening technology, based on image-based measurement of surface vibrations induced on a breast by mechanical actuation. Knowledge of frequency response characteristics of a breast prior to imaging is critical to maximize the imaging signal and diagnostic capability of the system. A feasibility analysis for a non-invasive image based modal analysis system is presented that is able to robustly and rapidly identify resonant frequencies in soft tissue. Three images per oscillation cycle are enough to capture the behavior at a given frequency. Thus, a sweep over critical frequency ranges can be performed prior to imaging to determine critical imaging settings of the DIET system to optimize its tumor detection performance.

Elevated nitrogen allows the weak invasive plant Galinsoga quadriradiata to become more vigorous with respect to inter-specific competition.

PubMed

Liu, Gang; Yang, Ying-Bo; Zhu, Zhi-Hong

2018-02-16

Elevated nitrogen associated with global change is believed to promote the invasion of many vigorous exotic plants. However, it is unclear how a weak exotic plant will respond to elevated nitrogen in the future. In this study, the competitive outcome of a weak invasive plant (Galinsoga quadriradiata) and two non-invasive plants was detected. The plants were subjected to 3 types of culture (mixed, monoculture or one-plant), 2 levels of nitrogen (ambient or elevated at a rate of 2 g m -2 yr -1 ) and 2 levels of light (65% shade or full sunlight). The results showed that elevated nitrogen significantly promoted the growth of both the weak invader and the non-invasive plants in one-plant pots; however, growth promotion was not observed for the non-invasive species in the mixed culture pots. The presence of G. quadriradiata significantly inhibited the growth of the non-invasive plants, and a decreased negative species interaction was detected as a result of elevated nitrogen. Our results suggest that competitive interactions between G. quadriradiata and the non-invasive plants were altered by elevated nitrogen. It provides exceptional evidence that an initially weak invasive plant can become an aggressive invader through elevated nitrogen deposition.

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels

PubMed Central

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L.; Bhatnagar, Deepak; Cleveland, Thomas E.

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus. PMID:24734028

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels.

PubMed

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L; Bhatnagar, Deepak; Cleveland, Thomas E

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus.

Infrared thermography, a new method for detection of brown adipose tissue activity after a meal in humans

NASA Astrophysics Data System (ADS)

Habek, Nikola; Kordić, Milan; Jurenec, Franjo; Dugandžić, Aleksandra

2018-03-01

The activation of brown adipose tissue (BAT) after cold exposure leads to heat production. However, the activation of BAT activity after a meal as part of diet induced thermogenesis is still controversial. A possible reason is that measuring BAT activity by positron emission tomography-computed tomography (PET CT) via accumulation of radiotracer fludeoxyglucose (18F-FDG), which competes with an increase in glucose concentration after a meal, fails as the method of choice. In this study, activity of BAT was determined by infrared thermography. Activation of BAT 30 min after a meal increases glucose consumption, decreases plasma glucose concentration, and leads to changes of body temperature (diet-induced thermogenesis). Detecting pathophysiological changes in BAT activity after a meal by infrared thermography, a non-invasive more sensitive method, will be of great importance for people with increased body weight and diabetes mellitus type 2.

Preliminary diffusion tensor imaging studies in limb-girdle muscular dystrophies

NASA Astrophysics Data System (ADS)

Hidalgo-Tobon, S.; Hernandez-Salazar, G.; Vargas-Cañas, S.; Marrufo-Melendez, O.; Solis-Najera, S.; Taboada-Barajas, J.; Rodriguez, A. O.; Delgado-Hernandez, R.

2012-10-01

Limb-girdle muscular dystrophies (LGMD) are a group of autosomal dominantly or recessively inherited muscular dystrophies that also present with primary proximal (limb-girdle) muscle weakness. This type of dystrophy involves the shoulder and pelvic girdles, distinct phenotypic or clinical characteristics are recognized. Imaging experiments were conducted on a 1.5T GE scanner (General Electric Medical Systems. Milwaukee. USA), using a combination of two eight-channel coil array. Diffusion Tensor Imaging (DTI) data were acquired using a SE-EPI sequence, diffusion weighted gradients were applied along 30 non-collinear directions with a b-value=550 s/mm2. The connective tissue content does not appear to have a significant effect on the directionality of the diffusion, as assessed by fractional anisotropy. The fibers of the Sartorius muscle and gracilis showed decreased number of tracts, secondary to fatty infiltration and replacement of connective tissue and muscle mass loss characteristic of the underlying pathology. Our results demonstrated the utility of non-invasive MRI techniques to characterize the muscle pathology, through quantitative and qualitative methods such as the FA values and tractrography.

Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

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

Shi, Yongguo, E-mail: 1138303166@qq.com; Lu, Jianwei, E-mail: jianwei2010077@163.com; Zhou, Jing, E-mail: 2310848@163.com

2014-04-04

Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question,more » we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.« less

Neurophotonics: non-invasive optical techniques for monitoring brain functions

PubMed Central

Torricelli, Alessandro; Contini, Davide; Mora, Alberto Dalla; Pifferi, Antonio; Re, Rebecca; Zucchelli, Lucia; Caffini, Matteo; Farina, Andrea; Spinelli, Lorenzo

2014-01-01

Summary The aim of this review is to present the state of the art of neurophotonics, a recently founded discipline lying at the interface between optics and neuroscience. While neurophotonics also includes invasive techniques for animal studies, in this review we focus only on the non-invasive methods that use near infrared light to probe functional activity in the brain, namely the fast optical signal, diffuse correlation spectroscopy, and functional near infrared spectroscopy methods. We also present an overview of the physical principles of light propagation in biological tissues, and of the main physiological sources of signal. Finally, we discuss the open issues in models, instrumentation, data analysis and clinical approaches. PMID:25764252

BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

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

Cekanova, Maria, E-mail: mcekanov@utk.edu; Fernando, Romaine I.; Siriwardhana, Nalin

We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreasedmore » the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.« less

Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

NASA Astrophysics Data System (ADS)

Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

2017-01-01

Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description

PubMed Central

Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A.

2017-01-01

A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy. PMID:28658924

Use of swabs for sampling epithelial cells for molecular genetics analyses in Enteroctopus

USGS Publications Warehouse

Hollenback, Nathan; Scheel, David; Gravley, Megan C.; Sage, George K.; Toussaint, Rebecca K.; Talbot, Sandra L.

2017-01-01

We evaluated the efficacy of using swabs to collect cells from the epidermis of octopus as a non-invasive DNA source for classical genetic studies, and demonstrated value of the technique by incorporating it into an effort to determine, within a day, the lineage of captured, live Enteroctopus (E. dofleini or a cryptic lineage). The cryptic lineage was targeted for captive behavioral and morphological studies, while once genetically identified, the non-target lineage could be more rapidly released back to the wild. We used commercially available sterile foamtipped swabs and a high-salt preservation buffer to collect and store paired swab and muscle (arm tip) tissue sampled from live Enteroctopus collected from Prince William Sound, Alaska. We performed a one-day extraction of DNA from epithelial swab samples and amplification of two diagnostic microsatellite loci to determine the lineage of each of the 21 individuals. Following this rapid lineage assessment, which allowed us to release non-target individuals within a day of laboratory work, we compared paired swab and muscle tissue samples from each individual to assess quantity of DNA yields and consistency of genotyping results, followed by assessment of locus-by-locus reliability of DNA extracts from swabs. Epithelial swabs yielded, on average, lower quantities of DNA (170.32 ± 74.72 (SD) ng/μL) relative to DNA obtained from tissues collected using invasive or destructive techniques (310.95 ± 147.37 (SD) ng/μL. We observed some decrease in yields of DNA from extractions of swab samples conducted 19 and 31 months after initial extractions when samples were stored at room temperature in lysis buffer. All extractions yielded quantities of DNA sufficient to amplify and score all loci, which included fragment data from 10 microsatellite loci (nine polymorphic loci and monomorphic locus EdoμA106), and nucleotide sequence data from a 528 base pair portion of the nuclear octopine dehydrogenase gene. All results from genotyping and sequencing using paired swab and muscle tissue extracts were concordant, and experimental reliability levels for multilocus genotypes generated from swab samples exceeded 97%. This technique is useful for studies in which invasive sampling is not optimal, and in remote field situations since samples can be stored at ambient temperatures for at least 31 months. The use of epithelial swabs is thus a noninvasive technique appropriate for sampling genetic material from live octopuses for use in classical genetic studies as well as supporting experimental and behavioral studies.

Non-invasive red light optogenetic pacing and optical coherence microscopy (OCM) imaging for drosophila melanogaster (Conference Presentation)

NASA Astrophysics Data System (ADS)

Men, Jing; Li, Airong; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

2017-02-01

Cardiac pacing could be a powerful tool for investigating mammalian cardiac electrical conduction systems as well as for treatment of certain cardiac pathologies. However, traditional electrical pacing using pacemaker requires an invasive surgical procedure. Electrical currents from the implanted electrodes can also cause damage to heart tissue, further restricting its utility. Optogenetic pacing has been developed as a promising, non-invasive alternative to electrical stimulation for controlling animal heart rhythms. It induces heart contractions by shining pulsed light on transgene-generated microbial opsins, which in turn activate the light gated ion channels in animal hearts. However, commonly used opsins in optogenetic pacing, such as channelrhodopsin-2 (ChR2), require short light wavelength stimulation (475 nm), which is strongly absorbed and scattered by tissue. Here, we performed optogenetic pacing by expression of recently engineered red-shifted microbial opsins, ReaChR and CsChrimson, in a well-established animal model, Drosophila melanogaster, using the 617 nm stimulation light pulses. The OCM technique enables non-invasive optical imaging of animal hearts with high speed and ultrahigh axial and transverse resolutions. We integrated a customized OCM system with the optical stimulation system to monitor the optogenetic pacing noninvasively. The use of red-sifted opsins enabled deeper penetration of simulating light at lower power, which is promising for applications of optogenetic pacing in mammalian cardiac pathology studies or clinical treatments in the future.

Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique.

PubMed

Rajan, Shiny Amala Priya; Towe, Bruce C

2014-01-01

A non-invasive method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm, which is a peak absorbance of hemoglobin. As the glucose concentration in blood decreases, its osmolarity also decreases and the Red Blood Cells (RBCs) swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds.

Biological significance of long non-coding RNA FTX expression in human colorectal cancer

PubMed Central

Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

2015-01-01

The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer. PMID:26629053

Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

PubMed Central

Tan, Xin-Yu; Chang, Shi; Liu, Wei

2014-01-01

Background/Aims To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. Methods An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. Results The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. Conclusions CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA. PMID:24672662

E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.

PubMed

Margulis, Alexander; Zhang, Weitian; Alt-Holland, Addy; Crawford, Howard C; Fusenig, Norbert E; Garlick, Jonathan A

2005-03-01

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in three-dimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of beta-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2Kd-Ecad). In monolayer cultures, expression of H-2Kd-Ecad resulted in decreased levels of E-cadherin, redistribution of beta-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in beta-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2Kd-Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2Kd-Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to high-grade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo.

Air-coupled acoustic radiation force for non-contact generation of broadband mechanical waves in soft media

NASA Astrophysics Data System (ADS)

Ambroziński, Łukasz; Pelivanov, Ivan; Song, Shaozhen; Yoon, Soon Joon; Li, David; Gao, Liang; Shen, Tueng T.; Wang, Ruikang K.; O'Donnell, Matthew

2016-07-01

A non-contact method for efficient, non-invasive excitation of mechanical waves in soft media is proposed, in which we focus an ultrasound (US) signal through air onto the surface of a medium under study. The US wave reflected from the air/medium interface provides radiation force to the medium surface that launches a transient mechanical wave in the transverse (lateral) direction. The type of mechanical wave is determined by boundary conditions. To prove this concept, a home-made 1 MHz piezo-ceramic transducer with a matching layer to air sends a chirped US signal centered at 1 MHz to a 1.6 mm thick gelatin phantom mimicking soft biological tissue. A phase-sensitive (PhS)-optical coherence tomography system is used to track/image the mechanical wave. The reconstructed transient displacement of the mechanical wave in space and time demonstrates highly efficient generation, thus offering great promise for non-contact, non-invasive characterization of soft media, in general, and for elasticity measurements in delicate soft tissues and organs in bio-medicine, in particular.

Air-coupled acoustic radiation force for non-contact generation of broadband mechanical waves in soft media

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

Ambroziński, Łukasz; AGH University of Science and Technology, Krakow 30059; Pelivanov, Ivan, E-mail: ivanp3@uw.edu

A non-contact method for efficient, non-invasive excitation of mechanical waves in soft media is proposed, in which we focus an ultrasound (US) signal through air onto the surface of a medium under study. The US wave reflected from the air/medium interface provides radiation force to the medium surface that launches a transient mechanical wave in the transverse (lateral) direction. The type of mechanical wave is determined by boundary conditions. To prove this concept, a home-made 1 MHz piezo-ceramic transducer with a matching layer to air sends a chirped US signal centered at 1 MHz to a 1.6 mm thick gelatin phantom mimicking softmore » biological tissue. A phase-sensitive (PhS)-optical coherence tomography system is used to track/image the mechanical wave. The reconstructed transient displacement of the mechanical wave in space and time demonstrates highly efficient generation, thus offering great promise for non-contact, non-invasive characterization of soft media, in general, and for elasticity measurements in delicate soft tissues and organs in bio-medicine, in particular.« less

Pathogenic Naegleria fowleri and non-pathogenic Naegleria lovaniensis exhibit differential adhesion to, and invasion of, extracellular matrix proteins

PubMed Central

Jamerson, Melissa; da Rocha-Azevedo, Bruno; Cabral, Guy A.

2012-01-01

Naegleria fowleri and Naegleria lovaniensis are closely related free-living amoebae found in the environment. N. fowleri causes primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system, while N. lovaniensis is non-pathogenic. N. fowleri infection occurs when the amoebae access the nasal passages, attach to the nasal mucosa and its epithelial lining, and migrate to the brain. This process involves interaction with components of the host extracellular matrix (ECM). Since the ability to invade tissues can be a characteristic that distinguishes pathogenic from non-pathogenic amoebae, the objective of this study was to assess adhesion to, and invasion of, the ECM by these two related but distinct Naegleria species. N. fowleri exhibited a higher level of adhesion to the ECM components laminin-1, fibronectin and collagen I. Scanning electron microscopy revealed that N. fowleri attached on ECM substrata exhibited a spread-out appearance that included the presence of focal adhesion-like structures. Western immunoblotting revealed two integrin-like proteins for both species, but one of these, with a molecular mass of approximately 70 kDa, was detected at a higher level in N. fowleri. Confocal microscopy indicated that the integrin-like proteins co-localized to the focal adhesion-like structures. Furthermore, anti-integrin antibody decreased adhesion of N. fowleri to ECM components. Finally, N. fowleri disrupted 3D ECM scaffolds, while N. lovaniensis had a minimal effect. Collectively, these results indicate a distinction in adhesion to, and invasion of, ECM proteins between N. fowleri and N. lovaniensis. PMID:22222499

Pathogenic Naegleria fowleri and non-pathogenic Naegleria lovaniensis exhibit differential adhesion to, and invasion of, extracellular matrix proteins.

PubMed

Jamerson, Melissa; da Rocha-Azevedo, Bruno; Cabral, Guy A; Marciano-Cabral, Francine

2012-03-01

Naegleria fowleri and Naegleria lovaniensis are closely related free-living amoebae found in the environment. N. fowleri causes primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system, while N. lovaniensis is non-pathogenic. N. fowleri infection occurs when the amoebae access the nasal passages, attach to the nasal mucosa and its epithelial lining, and migrate to the brain. This process involves interaction with components of the host extracellular matrix (ECM). Since the ability to invade tissues can be a characteristic that distinguishes pathogenic from non-pathogenic amoebae, the objective of this study was to assess adhesion to, and invasion of, the ECM by these two related but distinct Naegleria species. N. fowleri exhibited a higher level of adhesion to the ECM components laminin-1, fibronectin and collagen I. Scanning electron microscopy revealed that N. fowleri attached on ECM substrata exhibited a spread-out appearance that included the presence of focal adhesion-like structures. Western immunoblotting revealed two integrin-like proteins for both species, but one of these, with a molecular mass of approximately 70 kDa, was detected at a higher level in N. fowleri. Confocal microscopy indicated that the integrin-like proteins co-localized to the focal adhesion-like structures. Furthermore, anti-integrin antibody decreased adhesion of N. fowleri to ECM components. Finally, N. fowleri disrupted 3D ECM scaffolds, while N. lovaniensis had a minimal effect. Collectively, these results indicate a distinction in adhesion to, and invasion of, ECM proteins between N. fowleri and N. lovaniensis.

Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions

NASA Astrophysics Data System (ADS)

Davies, N.; Davies-Shaw, D.; Shaw, J. D.

2007-02-01

We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

Impact of Reclassification on Thyroid Nodules with Architectural Atypia: From Non-Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinomas to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

PubMed Central

Jeon, Min Ji; Song, Dong Eun; Jung, Chan Kwon; Kim, Won Gu; Kwon, Hyemi; Lee, Yu-Mi; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. PMID:27936121

Visualizing radiofrequency-skin interaction using multiphoton microscopy in vivo.

PubMed

Tsai, Tsung-Hua; Lin, Sung-Jan; Lee, Woan-Ruoh; Wang, Chun-Chin; Hsu, Chih-Ting; Chu, Thomas; Dong, Chen-Yuan

2012-02-01

Redundant skin laxity is a major feature of aging. Recently, radiofrequency has been introduced for nonablative tissue tightening by volumetric heating of the deep dermis. Despite the wide range of application based on this therapy, the effect of this technique on tissue and the subsequent tissue remodeling have not been investigated in detail. Our objective is to evaluate the potential of non-linear optics, including multiphoton autofluorescence and second harmonic generation (SHG) microscopy, as a non-invasive imaging modality for the real-time study of radiofrequency-tissue interaction. Electro-optical synergy device (ELOS) was used as the radiofrequency source in this study. The back skin of nude mouse was irradiated with radiofrequency at different passes. We evaluated the effect on skin immediately and 1 month after treatment with multiphoton microscopy. Corresponding histology was performed for comparison. We found that SHG is negatively correlated to radiofrequency passes, which means that collagen structural disruption happens immediately after thermal damage. After 1 month of collagen remodeling, SHG signals increased above baseline, indicating that collagen regeneration has occurred. Our findings may explain mechanism of nonablative skin tightening and were supported by histological examinations. Our work showed that monitoring the dermal heating status of RF and following up the detailed process of tissue reaction can be imaged and quantified with multiphoton microscopy non-invasively in vivo. Copyright © 2011. Published by Elsevier Ireland Ltd.

Roles of microRNA-34a in the pathogenesis of placenta accreta.

PubMed

Umemura, Kota; Ishioka, Shin-Ichi; Endo, Toshiaki; Ezaka, Yoshiaki; Takahashi, Madoka; Saito, Tsuyoshi

2013-01-01

MicroRNA-34a (miR-34a) is associated with invasion and metastasis of various cancers. The trophoblastic cells of placenta accreta invade into the myometrium in a similar way to the invasion of cancers. We studied the roles of miR-34a in the pathogenesis of placenta accreta. The human choriocarcinoma cell line JAR was used for in vitro experiments as a model of trophoblasts, and placental tissues from the operative specimen of patients with or without placenta accreta were used for experiments in vivo. Morpholino antisense oligomer against miR-34a (miR-34a Morpho/AS) was added to JAR, and the expression of miR-34a and plasminogen activator inhibitor-1 (PAI-1) was determined by real time PCR. The effects of antisense, interleukin (IL)-6 and IL-8 in the process of invasion were studied with an invasion assay. Expression of miR-34a in vivo was studied with the use of fluorescent in situ hybridization (FISH). Expression of miR-34a was inhibited by 65% with the administration of antisense, and a slight increase in miR-34a expression was observed with the addition of IL-6 and IL-8. PAI-1 expression decreased with the addition of IL-6 and IL-8, and increased with the administration of antisense. There was an increase in invasive capacity through the inhibition of miR-34a expression. Strong FISH expression of miR-34a was observed in trophoblast cells of non-placenta accreta, and a clear decrease in miR-34a expression was observed in those of placenta accreta. Expression of miR-34a was downregulated in placenta accreta. In vitro experiments also showed that the invasive potential of JAR increased by suppressing miR-34a, probably through the expression of PAI-1. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Time-domain optical mammography Softscan: initial results on detection and characterization of breast tumors

NASA Astrophysics Data System (ADS)

Intes, Xavier; Djeziri, Salim; Ichalalene, Zahia; Mincu, Niculae; Wang, Yong; St.-Jean, Philippe; Lesage, Frédéric; Hall, David; Boas, David A.; Polyzos, Margaret

2004-10-01

Near-infrared (NIR) technology appears promising as a non-invasive clinical technique for breast cancer screening and diagnosis. The technology capitalizes on the relative transparency of human tissue in this spectral range and its sensitivity to the main components of the breast:; water, lipid and hemoglobin. In this work we present initial results obtained using the SoftScan® breast-imaging system developed by ART, Advanced Research Technologies inc., Montreal. This platform consists of a 4-wavelength time-resolved scanning system used to quantify non-invasively the local functional state of breast tissue. The different aspects of the system used to retrieve 3D optical contrast will be presented. Furthermore, preliminary data obtained from a prospective study conducted at The Royal Victoria Hospital of the McGill University Health Center in Montreal will be discussed. Analysis of the data gathered by SoftScan® demonstrated the potential of the technology in discriminating between healthy and diseased tissue.

A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.

PubMed

Chen, Xin-Yu; Zhao, Si-Yu; Wang, Yan; Wang, Dong; Dong, Chang-Hu; Yang, Ying; Wang, Zhi-Hua; Wu, Yuan-Ming

2016-07-01

Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases.

PubMed

Sree Raman, Karthigesh; Nucifora, Gaetano; Selvanayagam, Joseph B

2018-05-01

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR's inherent advantages are its non-invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre-clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation-sensitive CMR (OS-CMR) is a novel non-invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS-CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases. © 2018 John Wiley & Sons Australia, Ltd.

Blockade of CXCR6 reduces invasive potential of gastric cancer cells through inhibition of AKT signaling.

PubMed

Li, Ya; Fu, Li-Xia; Zhu, Wan-Lin; Shi, Hua; Chen, Li-Jian; Ye, Bin

2015-06-01

Chemokines and their receptors have been implicated in cell migration and metastasis of multiple malignant tumors. But the function of CXCR6 signaling in gastric cancer is not comprehensively understood. In the present study, we hypothesized that CXCR6 signaling might play an essential role in the progression of gastric cancer. The expression of CXCR6 was examined by immunohistochemical assay in human gastric cancer, and lentivirus-mediated CXCR6 knockdown by shRNA (Lv-shCXCR6) was used for investigating cell migration and invasion indicated by Wound-healing and Transwell assays. Consequently, the expression level of CXCR6 was increased in gastric cancer compared with the adjacent non-tumor tissues (54.2% vs. 27.1%, P = 0.006), and was closely associated with the metastatic lymph node in gastric cancer (P = 0.021). Furthermore, blockade of the CXCR6 signaling reduced the migration and invasion of gastric cancer cells followed by decreased expression of AKT, MMP-2, and MMP-9. In conclusion, these findings demonstrate that CXCR6 may promote the development of gastric cancer cells through regulation of AKT signaling. © The Author(s) 2015.

A novel magnetic-driven tissue retraction device for minimally invasive surgery.

PubMed

Brancadoro, Margherita; Tognarelli, Selene; Ciuti, Gastone; Menciassi, Arianna

2017-02-01

The purpose of this work is to design and validate an innovative magnetic-based device for tissue retraction for minimally invasive surgery. An intra-abdominal magnetic module is coupled with an extracorporeal system for establishing a stable attraction, and consequently a reliable tissue retraction. Once the retractor has been inserted into the abdomen, tissue retraction is not constrained by a fixed access port, thus guaranteeing a more flexible, safer and less invasive operation. The intra-abdominal unit is composed of an axial permanent magnet attached to a stainless-steel non-magnetic alligator clip by a traditional suturing thread. A miniaturized mechanism to adjust the length of the suturing thread for lengthening or shortening the distance between the tissue grasper and the internal magnetic unit is included. A multiphysics approach assured a dedicated design that thoroughly fulfills anatomical, physiological and engineering constraints. System functionalities were demonstrated both in in-vitro and ex-vivo conditions, reaching good results and promising outcomes in terms of effectiveness and maneuverability. The retractor was successfully tested in an animal model, carrying out a whole retraction procedure. The proposed retraction system resulted to be intuitive, reliable, robust and easy to use, representing a suitable device for MIS procedures.

MiR-300 suppresses laryngeal squamous cell carcinoma proliferation and metastasis by targeting ROS1.

PubMed

Ge, Wensheng; Han, Chaodong; Wang, Jing; Zhang, Yunping

2016-01-01

Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck cancer with high mortality and incidence. MicroRNAs (miRNAs) are short, non-coding and endogenous RNAs that posttranscriptionally inhibit gene expression. In this study, we showed that miR-300 expression was downregulated in LSCC tissues compared with adjacent no-tumor tissues. MiR-300 overexpression inhibited Hep-2 cell proliferation, as well as the expression of ki-67 and PCNA. Moreover, overexpression of miR-300 repressed the cell invasion in Hep-2 cells. We identified c-ros oncogene 1 receptor tyrosine kinase (ROS1) as a direct target gene of miR-300 in Hep-2 cell. Furthermore, ROS1 expression was upregulated in LSCC tissues compared with adjacent no-tumor tissues. Interesting, there were an inverse correlation between ROS1 and miR-300 expression in the LSCC tissues. Overexpression of ROS1 increased the Hep-2 cells proliferation and invasion. Overexpression of ROS1 abrogated miR-300 induced cell growth and invasion inhibition. Therefore, our data suggested that miR-300 acted as a tumor suppressive gene in LSCC.

MiR-300 suppresses laryngeal squamous cell carcinoma proliferation and metastasis by targeting ROS1

PubMed Central

Ge, Wensheng; Han, Chaodong; Wang, Jing; Zhang, Yunping

2016-01-01

Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck cancer with high mortality and incidence. MicroRNAs (miRNAs) are short, non-coding and endogenous RNAs that posttranscriptionally inhibit gene expression. In this study, we showed that miR-300 expression was downregulated in LSCC tissues compared with adjacent no-tumor tissues. MiR-300 overexpression inhibited Hep-2 cell proliferation, as well as the expression of ki-67 and PCNA. Moreover, overexpression of miR-300 repressed the cell invasion in Hep-2 cells. We identified c-ros oncogene 1 receptor tyrosine kinase (ROS1) as a direct target gene of miR-300 in Hep-2 cell. Furthermore, ROS1 expression was upregulated in LSCC tissues compared with adjacent no-tumor tissues. Interesting, there were an inverse correlation between ROS1 and miR-300 expression in the LSCC tissues. Overexpression of ROS1 increased the Hep-2 cells proliferation and invasion. Overexpression of ROS1 abrogated miR-300 induced cell growth and invasion inhibition. Therefore, our data suggested that miR-300 acted as a tumor suppressive gene in LSCC. PMID:27725869

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma.

PubMed

Gardini, A; Corti, B; Fiorentino, M; Altimari, A; Ercolani, G; Grazi, G L; Pinna, A D; Grigioni, W F; D'Errico Grigioni, A

2005-04-01

Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.

European multicentre validation study of the accuracy of E/e' ratio in estimating invasive left ventricular filling pressure: EURO-FILLING study.

PubMed

Galderisi, Maurizio; Lancellotti, Patrizio; Donal, Erwan; Cardim, Nuno; Edvardsen, Thor; Habib, Gilbert; Magne, Julien; Maurer, Gerald; Popescu, Bogdan A

2014-07-01

The non-invasive estimation of left ventricular filling pressures (LVFPs) represents a main goal in the clinical setting. Current recommendations encourage the use of pulsed-wave Tissue Doppler for calculating the ratio between the preload-dependent transmitral E velocity and the average of septal and lateral early diastolic velocities (e') of the mitral annulus. Despite its wide use, real utility of the E/e' ratio has been recently challenged in patients with either very advanced heart failure or preserved left ventricular (LV) ejection fraction. However, only few studies performed the invasive and non-invasive estimation of LVFP simultaneously. The EURO-FILLING Study will validate the E/e' ratio (and additional non-invasive estimates) against simultaneously measured LVFP obtained by left heart catheterization in a multicentre study involving reference European echo laboratories collecting a wide population sample size of cardiac patients with and without heart failure. The EURO-FILLING study is a large, prospective observational study in which simultaneous assessment of invasive and non-invasive measurements of LVFP will be acquired in eight reference European centres. Centralized reading of the collected parameters will be performed in a core laboratory. Not only standardized echo Doppler measurements but also novel echo parameters such as LV global longitudinal strain and global atrial strain (obtainable by two-dimensional speckle tracking echocardiography) will be tested for predicting invasive measurements of LVFP. The EURO-FILLING study is expected to provide important information on non-invasive assessment of LVFP and to contribute to the standardization of this assessment in clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy

NASA Astrophysics Data System (ADS)

Gillies, D.; Gamal, W.; Downes, A.; Reinwald, Y.; Yang, Y.; El Haj, A.; Bagnaninchi, P. O.

2017-02-01

There is an unmet need in tissue engineering for non-invasive, label-free monitoring of cell mechanical behaviour in their physiological environment. Here, we describe a novel optical coherence phase microscopy (OCPM) set-up which can map relative cell mechanical behaviour in monolayers and 3D systems non-invasively, and in real-time. 3T3 and MCF-7 cells were investigated, with MCF-7 demonstrating an increased response to hydrostatic stimulus indicating MCF-7 being softer than 3T3. Thus, OCPM shows the ability to provide qualitative data on cell mechanical behaviour. Quantitative measurements of 6% agarose beads have been taken with commercial Cell Scale Microsquisher system demonstrating that their mechanical properties are in the same order of magnitude of cells, indicating that this is an appropriate test sample for the novel method described.

Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.

PubMed

Zhang, Shirong; Wu, Kan; Feng, Jianguo; Wu, Zhibing; Deng, Qinghua; Guo, Chao; Xia, Bing; Zhang, Jing; Huang, Haixiu; Zhu, Lucheng; Zhang, Ke; Shen, Binghui; Chen, Xufeng; Ma, Shenglin

2016-10-18

Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.

MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

PubMed

Liu, D-Z; Chang, B; Li, X-D; Zhang, Q-H; Zou, Y-H

2017-09-01

The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

Non-invasive assessment of leaf water status using a dual-mode microwave resonator.

PubMed

Dadshani, Said; Kurakin, Andriy; Amanov, Shukhrat; Hein, Benedikt; Rongen, Heinz; Cranstone, Steve; Blievernicht, Ulrich; Menzel, Elmar; Léon, Jens; Klein, Norbert; Ballvora, Agim

2015-01-01

The water status in plant leaves is a good indicator for the water status in the whole plant revealing stress if the water supply is reduced. The analysis of dynamic aspects of water availability in plant tissues provides useful information for the understanding of the mechanistic basis of drought stress tolerance, which may lead to improved plant breeding and management practices. The determination of the water content in plant tissues during plant development has been a challenge and is currently feasible based on destructive analysis only. We present here the application of a non-invasive quantitative method to determine the volumetric water content of leaves and the ionic conductivity of the leaf juice from non-invasive microwave measurements at two different frequencies by one sensor device. A semi-open microwave cavity loaded with a ceramic dielectric resonator and a metallic lumped-element capacitor- and inductor structure was employed for non-invasive microwave measurements at 150 MHz and 2.4 Gigahertz on potato, maize, canola and wheat leaves. Three leaves detached from each plant were chosen, representing three developmental stages being representative for tissue of various age. Clear correlations between the leaf- induced resonance frequency shifts and changes of the inverse resonator quality factor at 2.4 GHz to the gravimetrically determined drying status of the leaves were found. Moreover, the ionic conductivity of Maize leaves, as determined from the ratio of the inverse quality factor and frequency shift at 150 MHz by use of cavity perturbation theory, was found to be in good agreement with direct measurements on plant juice. In conjunction with a compact battery- powered circuit board- microwave electronic module and a user-friendly software interface, this method enables rapid in-vivo water amount assessment of plants by a handheld device for potential use in the field.

Research of transmissive near infrared spectroscopy for non-invasive blood glucose measurement

NASA Astrophysics Data System (ADS)

Yang, Wenming; Liao, Ningfang; Li, Yasheng; Shao, Liwei; Huang, Dehuang

2016-10-01

Near infrared (NIR) has prospectively applied in non-invasive blood glucose measurement due to glucose absorption among the 1.0-2.5m spectral bands. However, this significant technology is hard to be developed because of other blood components and low signal-to-noise ratio (SNR). In this work, we presented a non-invasive glucose measurement system using Fourier transform spectrometer which will work in fingertips or other human body tissues. A refrigerated InGaAs detector with high quantum efficiency performing well in the range of 1.0-1.7μm wavelength is used to acquire transmissive radiation. Preliminary experiment investigations were set up to test glucose levels of aqueous solutions with different concentrations. The analytical modeling of the interferogram data is based on arithmetic Fourier transform and supported by the curvilineal characterization. Experimental results show the variation of light intensity among different glucose concentrations and emphasize the obvious absorption of glucose in NIR wave-range. This study confirms the suitability that NIR can be developed in non-invasive glucose measurement.

Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

NASA Astrophysics Data System (ADS)

Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

2016-03-01

Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

Pulse oximetry in the pulmonary tissue for the non-invasive measurement of mixed venous oxygen saturation.

PubMed

Nitzan, Meir; Nitzan, Itamar

2013-08-01

The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trimodal spectra for high discrimination of benign and malignant prostate tissue

NASA Astrophysics Data System (ADS)

Al Salhi, Mohamad; Masilamani, Vadivel; Trinka, Vijmasi; Rabah, Danny; Al Turki, Mohammed R.

2011-02-01

High false positives and over diagnosis is a major problem with management of prostate cancer. A non-invasive or a minimally invasive technique to accurately distinguish malignant prostate cancers from benign tumors will be extremely helpful to overcome this problem. In this paper, we had used three different fluorescence spectroscopy techniques viz., Fluorescence Emission Spectrum (FES), Stokes' Shift Spectrum (SSS) and Reflectance Spectrum (RS) to discriminate benign prostate tumor tissues (N=12) and malignant prostate cancer tissues (N=8). These fluorescence techniques were used to determine the relative concentration of naturally occurring biomolecules such as tryptophan, elastin, NADH and flavin which are found to be out of proportion in cancer tissues. Our studies show that combining all three techniques, benign and malignant prostate tissues could be classified with accuracy greater than 90%. This preliminary report is based on in vitro spectroscopy analysis. However, by employing fluorescence endoscopy techniques, this can be extended to in vivo analysis as well. This technique has the potential to identify malignant prostate tissues without surgery.

Mapping tissue oxygen in vivo by photoacoustic lifetime imaging

NASA Astrophysics Data System (ADS)

Shao, Qi; Morgounova, Ekaterina; Choi, Jeung-Hwan; Jiang, Chunlan; Bischof, John; Ashkenazi, Shai

2013-03-01

Oxygen plays a key role in the energy metabolism of living organisms. Any imbalance in the oxygen levels will affect the metabolic homeostasis and lead to pathophysiological diseases. Hypoxia, a status of low tissue oxygen, is a key factor in tumor biology as it is highly prominent in tumor tissues. However, clinical tools for assessing tissue oxygenation are limited. The gold standard is polarographic needle electrode which is invasive and not capable of mapping (imaging) the oxygen content in tissue. We applied the method of photoacoustic lifetime imaging (PALI) of oxygen-sensitive dye to small animal tissue hypoxia research. PALI is new technology for direct, non-invasive imaging of oxygen. The technique is based on mapping the oxygen-dependent transient optical absorption of Methylene Blue (MB) by pump-probe photoacoustic imaging. Our studies show the feasibility of imaging of dissolved oxygen distribution in phantoms. In vivo experiments demonstrate that the hypoxia region is consistent with the site of subcutaneously xenografted prostate tumor in mice with adequate spatial resolution and penetration depth.

Potential application of Chinese traditional medicine (CTM) as enhancer for tissue optical clearing

NASA Astrophysics Data System (ADS)

Chen, Wei; Jiang, Jingying; Wang, Ruikang K.; Xu, Kexin

2009-02-01

Many biocompatible hyperosmotic agents such as dimethyl sulfoxide(DMSO) have been used as enhancers for tissue optical clearing technique. However, previous investigations showed that DMSO can induce bradycardia, respiratory problems, and alterations in blood pressure. Also, DMSO could potentially alter the chemical structure, and hence the functional properties, of cell membranes. In this talk, Borneol among natural and nontoxic CTMs was introduced as new enhancer for optical clearing of porcine skin tissue since it has been widely used as new penetration promoter in the field of trandermial drug delivery system(TDDS) and been proved to be effective. In the first, the spectral characteristics of borneol was obtained and analyzed by Fourier Transformation Infrared (FTIR) spectrophotometer. And further experimental studies were performed to probe if borneol is capable of optical clearing of porcine skin tissue in vitro with near infrared spectroscopy, double integrating-spheres system and Inverse Adding-Doubling(IAD) algorithm. Spectral results show that light penetration depth into skin tissue got the increase. Meanwhile, absorption coefficient and scattering coefficient of porcine skin treated by borneol got the decrease during the permeation of Borneol. Therefore, Borneol could be potentially used as enhancer for tissue optical clearing to improve non-invasive light-based diagnostic and imaging techniques while practically optical application and clinical safety are under consideration.

Non-Invasive Measurements of Carboxyhemoglobin and Methemoglobin in Children with Sickle Cell Disease

PubMed Central

Caboot, Jason B.; Jawad, Abbas F.; McDonough, Joseph M.; Bowdre, Cheryl Y.; Arens, Raanan; Marcus, Carole L.; Mason, Thornton B.A.; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L.

2012-01-01

SUMMARY Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and −0.22% for MetHb. The precision of the measured SpCO was ±2.1% within a COHb range of 0.4–6.1%, and the precision of the measured SpMet was ±0.33% within a MetHb range of 0.1–1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. PMID:22328189

Non-invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease.

PubMed

Caboot, Jason B; Jawad, Abbas F; McDonough, Joseph M; Bowdre, Cheryl Y; Arens, Raanan; Marcus, Carole L; Mason, Thornton B A; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L

2012-08-01

Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and -0.22% for MetHb. The precision of the measured SpCO was ± 2.1% within a COHb range of 0.4-6.1%, and the precision of the measured SpMet was ± 0.33% within a MetHb range of 0.1-1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. Copyright © 2012 Wiley Periodicals, Inc.

ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

PubMed

Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

2011-01-01

Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

PubMed

Nguyen, Huyen T; Shah, Zarine K; Mortazavi, Amir; Pohar, Kamal S; Wei, Lai; Jia, Guang; Zynger, Debra L; Knopp, Michael V

2017-05-01

To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

Use of minimally invasive spine surgical instruments for the treatment of bone tumors.

PubMed

Reeves, Russell A; DeWolf, Matthew C; Shaughnessy, Peter J; Ames, James B; Henderson, Eric R

2017-11-01

Orthopedic oncologists often encounter patients with minor bony lesions that are difficult to access surgically and therefore require large exposures out of proportion to the severity of disease that confer significant patient morbidity. Minimally invasive surgical techniques offer the advantage of smaller incisions, shorter operative times, decreased tissue damage, and decreased costs. A variety of surgical procedures have emerged using minimally invasive technologies, particularly in the field of spine surgery. Areas covered: In this article, we describe the Minimal Exposure Tubular Retractor (METRx TM ) System which is a minimally invasive surgical device that utilizes a series of dilators to permit access to a surgical site of interest. This system was developed for use in treatment of disc herniation, spinal stenosis, posterior lumbar interbody fusion, transforaminal lumbar interbody fusion and spinal cord stimulation implantation. We also describe novel uses of this system for minimally invasive biopsy and treatment of benign and metastatic bone lesions at our institution. Expert commentary: Minimally invasive surgical techniques will continue to expand into the field of orthopedic oncology. With a greater number of studies proving the safety and effectiveness of this technique, the demand for minimally invasive treatments will grow.

OCT-based in vivo tissue injury mapping

NASA Astrophysics Data System (ADS)

Baran, Utku; Li, Yuandong; Wang, Ruikang K.

2016-03-01

Tissue injury mapping (TIM) is developed by using a non-invasive in vivo optical coherence tomography to generate optical attenuation coefficient and microvascular map of the injured tissue. Using TIM, the infarct region development in mouse cerebral cortex during stroke is visualized. Moreover, we demonstrate the in vivo human facial skin structure and microvasculature during an acne lesion development. The results indicate that TIM may help in the study and the treatment of various diseases by providing high resolution images of tissue structural and microvascular changes.

Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer.

PubMed

Wu, Han-Qing; Wang, Bo; Zhu, Shi-Kai; Tian, Yuan; Zhang, Jing-Hui; Wu, He-Shui

2011-02-28

To determine the expression of toll-like receptor 9 (TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216 (CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance. The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues, and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1. To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells, in vitro cell adhesion, wound-healing scrape, and invasion and cell colony formation were evaluated. TLR9 was highly expressed in pancreatic cancer tissues and PANC-1 cells. The percentage of positive cells expressing TLR9 protein in human pancreatic tissues, paracancerous tissues and normal tissues were 73.3%, 33.3% and 20.0%, respectively, and the protein expression level of TLR9 was gradually descending (P < 0.05). In vitro tests in wound-healing scrape, cell adhesion, colony formation and matrigel invasion showed that the adhesion and motility of PANC-1 cells in CPG ODN 2216 treatment group were significantly lower than in the control group (P < 0.05). The cell growth assay showed that the proliferative ability of PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner (P < 0.05). The gene of TLR9 is correlated with the invasive and metastatic potential of human pancreatic carcinoma, and CPG ODN2216 induces the inhibition of migration and invasion of Panc-1 cells.

Multiphoton microscopy, fluorescence lifetime imaging and optical spectroscopy for the diagnosis of neoplasia

NASA Astrophysics Data System (ADS)

Skala, Melissa Caroline

2007-12-01

Cancer morbidity and mortality is greatly reduced when the disease is diagnosed and treated early in its development. Tissue biopsies are the gold standard for cancer diagnosis, and an accurate diagnosis requires a biopsy from the malignant portion of an organ. Light, guided through a fiber optic probe, could be used to inspect regions of interest and provide real-time feedback to determine the optimal tissue site for biopsy. This approach could increase the diagnostic accuracy of current biopsy procedures. The studies in this thesis have characterized changes in tissue optical signals with carcinogenesis, increasing our understanding of the sensitivity of optical techniques for cancer detection. All in vivo studies were conducted on the dimethylbenz[alpha]anthracene treated hamster cheek pouch model of epithelial carcinogenesis. Multiphoton microscopy studies in the near infrared wavelength region quantified changes in tissue morphology and fluorescence with carcinogenesis in vivo. Statistically significant morphological changes with precancer included increased epithelial thickness, loss of stratification in the epithelium, and increased nuclear diameter. Fluorescence changes included a statistically significant decrease in the epithelial fluorescence intensity per voxel at 780 nm excitation, a decrease in the fluorescence lifetime of protein-bound nicotinamide adenine dinucleotide (NADH, an electron donor in oxidative phosphorylation), and an increase in the fluorescence lifetime of protein-bound flavin adenine dinucleotide (FAD, an electron acceptor in oxidative phosphorylation) with precancer. The redox ratio (fluorescence intensity of FAD/NADH, a measure of the cellular oxidation-reduction state) did not significantly change with precancer. Cell culture experiments (MCF10A cells) indicated that the decrease in protein-bound NADH with precancer could be due to increased levels of glycolysis. Point measurements of diffuse reflectance and fluorescence spectra in the ultraviolet to visible wavelength range indicated that the most diagnostic optical signals originate from sub-surface tissue layers. Optical properties extracted from these spectroscopy measurements showed a significant decrease in the hemoglobin saturation, absorption coefficient, reduced scattering coefficient and fluorescence intensity (at 400 nm excitation) in neoplastic compared to normal tissues. The results from these studies indicate that multiphoton microscopy and optical spectroscopy can non-invasively provide information on tissue structure and function in vivo that is related to tissue pathology.

Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR microspectroscopy.

PubMed

Chesnick, Ingrid E; Avallone, Francis A; Leapman, Richard D; Landis, William J; Eidelman, Naomi; Potter, Kimberlee

2007-04-01

We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of 9 weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 microm resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on MTR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR microspectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro.

Evaluation of Bioreactor-Cultivated Bone by Magnetic Resonance Microscopy and FTIR Microspectroscopy

PubMed Central

Chesnick, Ingrid E.; Avallone, Frank; Leapman, Richard D.; Landis, William J.; Eidelman, Naomi; Potter, Kimberlee

2007-01-01

We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of nine weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 μm resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on MTR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR microspectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro. PMID:17174620

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

PubMed

Mohr, Annika; Lüder Ripoli, Florenza; Hammer, Susanne Conradine; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Kiełbowicz, Zdzisław; Murua Escobar, Hugo; Nolte, Ingo

2016-01-01

Immunohistochemistry (IHC) is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1), progesterone receptor (PGR), prolactin receptor (PRLR) and growth hormone receptor (GHR) gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE) was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer.

PubMed

He, Guoyang; Zou, Liyuan; Zhou, Lin; Gao, Peiqiong; Qian, Xinlai; Cui, Jing

2017-01-01

Cysteine-rich intestinal protein 1 (CRIP1), a member of the LIM/double zinc finger protein family, is abnormally expressed in several tumour types. However, few data are available on the role of CRIP1 in cancer. In the present study, we aimed to investigate the expression profile and functions of CRIP1 in colorectal cancer. To examine the protein expression level of CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer tissue samples. Western blotting was performed to investigate CRIP1 protein expression in four colon cancer cell lines. The endogenous expression of CRIP1 was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays were used to determine whether CRIP1 silencing affected cell proliferation. Flow cytometry analysis was used to detect cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion was detected using the transwell and wound-healing assays. IHC analysis showed that protein level of CRIP1 was significantly higher in tumour tissue samples than in paired non-tumour tissue samples and that the CRIP1 level was higher in metastatic tissue samples than in non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher in highly metastatic colon cancer cell lines than in colon cancer cell lines with low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and invasion obviously in SW620 and HT29 cells. The present study provides new evidence that abnormal expression of CRIP1 might be related to the degree of metastasis in colorectal cancer and that CRIP1 silencing could effectively inhibit migration and invasion during colorectal cancer development. These findings might aid the development of a biomarker for colon cancer prognosis and metastasis, and thus help to treat this common type of cancer. © 2017 The Author(s). Published by S. Karger AG, Basel.

miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer.

PubMed

Chen, Yong; Min, Lingfeng; Ren, Chuanli; Xu, Xingxiang; Yang, Jianqi; Sun, Xinchen; Wang, Tao; Wang, Fang; Sun, Changjiang; Zhang, Xizhi

2017-01-01

Lung cancer is the leading cause of cancer death in the world, and aberrant expression of miRNA is a common feature during the cancer initiation and development. Our previous study showed that levels of miRNA-148a assessed by quantitative real-time polymerase chain reaction (qRT-PCR) were a good prognosis factor for non-small cell lung cancer (NSCLC) patients. In this study, we used high-throughput formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays and in situ hybridization (ISH) to determine the clinical significances of miRNA-148a and aimed to find novel target of miRNA-148a in lung cancer. Our results showed that there were 86 of 159 patients with low miRNA-148a expression and miRNA-148a was significantly down-regulated in primary cancer tissues when compared with their adjacent normal lung tissues. Low expression of miRNA-148a was strongly associated with high tumor grade, lymph node (LN) metastasis and a higher risk of tumor-related death in NSCLC. Lentivirus mediated overexpression of miRNA-148a inhibited migration and invasion of A549 and H1299 lung cancer cells. Furthermore, we validated Wnt1 as a direct target of miRNA-148a. Our data showed that the Wnt1 expression was negatively correlated with the expression of miRNA-148a in both primary cancer tissues and their corresponding adjacent normal lung tissues. In addition, overexpression of miRNA-148a inhibited Wnt1 protein expression in cancer cells. And knocking down of Wnt-1 by siRNA had the similar effect of miRNA-148a overexpression on cell migration and invasion in lung cancer cells. In conclusion, our results suggest that miRNA-148a inhibited cell migration and invasion through targeting Wnt1 and this might provide a new insight into the molecular mechanisms of lung cancer metastasis.

[Non-invasive mechanical ventilation in the pre- and intraoperative period and difficult airway].

PubMed

Esquinas, A M; Jover, J L; Úbeda, A; Belda, F J

2015-11-01

Non-invasive mechanical ventilation is a method of ventilatory assistance aimed at increasing alveolar ventilation, thus achieving, in selected subjects, the avoidance of endotracheal intubation and invasive mechanical ventilation, with the consequent improvement in survival. There has been a systematic review and study of the technical, clinical experiences, and recommendations concerning the application of non-invasive mechanical ventilation in the pre- and intraoperative period. The use of prophylactic non-invasive mechanical ventilation before surgery that involves significant alterations in the ventilatory function may decrease the incidence of postoperative respiratory complications. Its intraoperative use will mainly depend on the type of surgery, type of anaesthetic technique, and the clinical status of the patient. Its use allows greater anaesthetic depth without deterioration of oxygenation and ventilation of patients. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Laser induced autofluorescence for diagnosis of non-melanoma skin cancer

NASA Astrophysics Data System (ADS)

Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.

2015-01-01

Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.

Mandibular Tissue Engineering: Past, Present, Future.

PubMed

Konopnicki, Sandra; Troulis, Maria J

2015-12-01

Almost 2 decades ago, the senior author's (M.T.J.) first article was with our mentor, Dr Leonard B. Kaban, a review article titled "Distraction Osteogenesis: Past, Present, Future." In 1998, many thought it would be impossible to have a remotely activated, small, curvilinear distractor that could be placed using endoscopic techniques. Currently, a U.S. patent for a curvilinear automated device and endoscopic techniques for minimally invasive access for jaw reconstruction exist. With minimally invasive access for jaw reconstruction, the burden to decrease donor site morbidity has increased. Distraction osteogenesis (DO) is an in vivo form of tissue engineering. The DO technique eliminates a donor site, is less invasive, requires a shorter operative time than usual procedures, and can be used for multiple reconstruction applications. Tissue engineering could further reduce morbidity and cost and increase treatment availability. The purpose of the present report was to review our experience with tissue engineering of bone: the past, present, and our vision for the future. The present report serves as a tribute to our mentor and acknowledges Dr Kaban for his incessant tutelage, guidance, wisdom, and boundless vision. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Dynamic tissue phantoms and their use in assessment of a noninvasive optical plethysmography imaging device

NASA Astrophysics Data System (ADS)

Thatcher, Jeffrey E.; Plant, Kevin D.; King, Darlene R.; Block, Kenneth L.; Fan, Wensheng; DiMaio, J. Michael

2014-05-01

Non-contact photoplethysmography (PPG) has been studied as a method to provide low-cost and non-invasive medical imaging for a variety of near-surface pathologies and two dimensional blood oxygenation measurements. Dynamic tissue phantoms were developed to evaluate this technology in a laboratory setting. The purpose of these phantoms was to generate a tissue model with tunable parameters including: blood vessel volume change; pulse wave frequency; and optical scattering and absorption parameters. A non-contact PPG imaging system was evaluated on this model and compared against laser Doppler imaging (LDI) and a traditional pulse oximeter. Results indicate non-contact PPG accurately identifies pulse frequency and appears to identify signals from optically dense phantoms with significantly higher detection thresholds than LDI.

Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

PubMed Central

2013-01-01

Background ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells. PMID:23289900

An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

PubMed Central

Westcott, Jill M.; Prechtl, Amanda M.; Maine, Erin A.; Dang, Tuyen T.; Esparza, Matthew A.; Sun, Han; Zhou, Yunyun; Xie, Yang; Pearson, Gray W.

2015-01-01

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these “trailblazer” cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis. PMID:25844900

In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells.

PubMed

Wang, Ming; Liu, Gang; Shan, Guo-Ping; Wang, Bing-Bing

2017-08-01

The study investigated the ability of ataxia-telangiectasia mutated (ATM)/Rad3-related (ATR) signaling pathway to influence the proliferation, apoptosis, and radiosensitivity of nasopharyngeal carcinoma (NPC) cells. NPC tissues and corresponding adjacent normal tissues were collected from 143 NPC patients. The NPC CNE2 cells were assigned into a control group, X-ray group, CGK-733 group, and X-ray+CGK-733 group. The mRNA levels of ATM and ATR were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and the protein levels of ATM and ATR using western blotting. The positive expression of ATM and ATR in tissues and nude mouse tumor tissues was determined by immunohistochemistry. Cell proliferation, migration, invasion, and apoptosis rates were analyzed by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, scratch test, transwell assay, and flow cytometry, respectively. A nude mouse model of NPC was established to observe tumor volume and growth. The mRNA levels of ATR and ATM and the expression of ATR and ATM protein in NPC tissues were significantly higher than those in adjacent normal tissues. The colony formation assay showed that the colony-forming rate decreased, showing radiation dose-dependent and CGK-733 concentration-dependent manners. Expression of ATM, ATR, Chk1, and Chk2 was evidently increased in the X-ray, CGK-733, and X-ray+CGK-733groups compared with the control group, and the aforementioned expression was highest in the X-ray+CGK-733 group among the four groups. The cell proliferation, invasion, and migration were decreased, tumor volume decreased and cell apoptosis increased in the X-ray, CGK-733, and X-ray+CGK-733 groups compared with the control group; the X-ray+CGK-733 group exhibited lowest cell proliferation, invasion and migration, smallest tumor volume, and highest cell apoptosis among the four groups. Inhibition of ATM/ATR signaling pathway reduces proliferation and enhances apoptosis and radiosensitivity of NPC cells.

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

PubMed

Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C

2015-08-01

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

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

Fukuda, Hiroki; Nakamura, Seikou; Chisaki, Yugo

2016-02-26

Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration ofmore » LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.« less

A neurotoxic pesticide changes the outcome of aggressive interactions between native and invasive ants

PubMed Central

Barbieri, Rafael F.; Lester, Philip J.; Miller, Alexander S.; Ryan, Ken G.

2013-01-01

Neurotoxic pesticides, such as neonicotinoids, negatively affect the cognitive capacity and fitness of non-target species, and could also modify interspecific interactions. We tested whether sublethal contamination with neonicotinoid could affect foraging, colony fitness and the outcome of behavioural interactions between a native (Monomorium antarcticum) and an invasive ant species (Linepithema humile). The foraging behaviour of both ants was not affected by neonicotinoid exposure. Colonies of the invasive species exposed to the neonicotinoid produced significantly fewer brood. In interspecific confrontations, individuals of the native species exposed to the neonicotinoid lowered their aggression towards the invasive species, although their survival probability was not affected. Exposed individuals of the invasive species interacting with non-exposed native ants displayed increased aggression and had their survival probability reduced. Non-exposed individuals of the invasive species were less aggressive but more likely to survive when interacting with exposed native ants. These results suggest that non-target exposure of invaders to neonicotinoids could either increase or decrease the probability of survival according to the exposure status of the native species. Given that, in any community, different species have different food preferences, and thus different exposure to pesticides, non-target exposure could potentially change the dynamics of communities and influence invasion success. PMID:24266038

Non-invasive structural and biomechanical imaging of the developing embryos (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhang, Jitao; Wu, Chen; Raghunathan, Raksha; Larin, Kirill V.; Scarcelli, Giuliano

2017-02-01

Embryos undergo dramatic changes in size, shape, and mechanical properties during development, which is regulated by both genetic and environmental factors. Quantifying mechanical properties of different embryonic tissues may represent good metrics for the embryonic health and proper development. Alternations and structure coupled with biomechanical information may provide a way for early diagnosis and drug treatment of various congenital diseases. Many methods have been developed to determine the mechanical properties of the embryo, such as atomic force microscopy (AFM), ultrasound elastography (UE), and optical coherent elastography (OCE). However, AFM is invasive and time-consuming. While UE and OCE are both non-invasive methods, the spatial resolutions are limited to mm to sub-mm, which is not enough to observe the details inside the embryo. Brillouin microscopy can potentially enable non-invasive measurement of the mechanical properties of a sample by measuring the spectra of acoustically induced light scattering therein. It has fast speed ( 0.1 second per point) and high resolution (sub-micron), and thus has been widely investigated for biomedical application, such as single cell and tissue. In this work, we utilized this technique to characterize the mechanical property of an embryo. A 2D elasticity imaging of the whole body of an E8 embryo was acquired by a Brillouin microscopy, and the stiffness changes between different organs (such as brain, heart, and spine) were shown. The elasticity maps were correlated with structural information provided by OCT.

Imaging of oral pathological tissue using optical coherence tomography

NASA Astrophysics Data System (ADS)

Canjau, Silvana; Todea, Carmen; Sinescu, Cosmin; Duma, Virgil-Florin; Topala, Florin I.; Podoleanu, Adrian G.

2014-01-01

Oral squamous cell carcinoma (OSCC) constitutes 90% of oral cancer. Early detection is a cornerstone to improve survival. Interaction of light with tissues may highlight changes in tissue structure and metabolism. We propose optical coherence tomography (OCT), as a non-invasive diagnosis method, being a new high-resolution optical technique that permits tri-dimensional (3-D), real-time imaging of near surface abnormalities in complex tissues. In this study half of the excisional biopsy was directed to the pathologist and the other half was assigned for OCT investigation. Histopathology validated the results. Areas of OSCC of the buccal mucosa were identified in the OCT images. The elements obserced included extensive epithelial down-growth, the disruption of the basement membrane, with areas of erosion, an epithelial layer that was highly variable in thickness and invasion into the sub-epithelial layers. Therefore, OCT appears to be a highly promising imaging modality.

Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics

NASA Astrophysics Data System (ADS)

Dagdeviren, Canan; Shi, Yan; Joe, Pauline; Ghaffari, Roozbeh; Balooch, Guive; Usgaonkar, Karan; Gur, Onur; Tran, Phat L.; Crosby, Jessi R.; Meyer, Marcin; Su, Yewang; Chad Webb, R.; Tedesco, Andrew S.; Slepian, Marvin J.; Huang, Yonggang; Rogers, John A.

2015-07-01

Mechanical assessment of soft biological tissues and organs has broad relevance in clinical diagnosis and treatment of disease. Existing characterization methods are invasive, lack microscale spatial resolution, and are tailored only for specific regions of the body under quasi-static conditions. Here, we develop conformal and piezoelectric devices that enable in vivo measurements of soft tissue viscoelasticity in the near-surface regions of the epidermis. These systems achieve conformal contact with the underlying complex topography and texture of the targeted skin, as well as other organ surfaces, under both quasi-static and dynamic conditions. Experimental and theoretical characterization of the responses of piezoelectric actuator-sensor pairs laminated on a variety of soft biological tissues and organ systems in animal models provide information on the operation of the devices. Studies on human subjects establish the clinical significance of these devices for rapid and non-invasive characterization of skin mechanical properties.

Non-invasive Optical Molecular Imaging for Cancer Detection

NASA Astrophysics Data System (ADS)

Luo, Zhen

Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide), which can selectively target plasma membrane of cells based on lower extracellular pH. 20 pairs of clinically normal and abnormal biopsies were obtained from consenting patients at UCDMC. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG and Alexa-647 labeled pHLIP was measured non-invasively by widefield imaging and confocal microscope. Uptake of propargyl choline was measured after topical delivery using confocal microscope. The results of all three molecular imagine probes were further correlated with pathological diagnosis. The imaging results of clinical biopsies demonstrated that 2-NBDG, propargyl choline and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. Topical application of the contrast agents generated significantly higher fluorescence signal intensity in all neoplastic tissues as compared to clinically normal biopsies irrespective of the anatomic location or patient. This unpaired comparison across all the cancer patients in this study highlights the specificity of the imaging approach. Furthermore, the results indicated that changes in intracellular glucose, choline metabolism and cancer acidosis are initiated in the early stages of cancer and these changes are correlated with the progression of the disease. In conclusion, these novel optical molecular imaging approaches to measure multiple biomarkers in cancer have significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

Validation of Non-Invasive Tracer Kinetic Analysis of 18F-Florbetaben PET Using a Dual Time-Window Acquisition Protocol.

PubMed

Bullich, Santiago; Barthel, Henryk; Koglin, Norman; Becker, Georg A; De Santi, Susan; Jovalekic, Aleksandar; Stephens, Andrew W; Sabri, Osama

2017-11-24

Accurate amyloid PET quantification is necessary for monitoring amyloid-beta accumulation and response to therapy. Currently, most of the studies are analyzed using the static standardized uptake value ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were: (1) to validate a non-invasive kinetic modeling approach for 18 F-florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and (2) to assess the impact of CBF changes and radiotracer clearance on SUVRs and non-invasive kinetic modeling data in 18 F-florbetaben PET. Methods: Data from twenty subjects (10 patients with probable Alzheimer's dementia/ 10 healthy volunteers) were used to compare the binding potential (BP ND ) obtained from the full kinetic analysis to the SUVR and to non-invasive tracer kinetic methods (simplified reference tissue model (SRTM), and multilinear reference tissue model 2 (MRTM2)). Different approaches using shortened or interrupted acquisitions were compared to the results of the full acquisition (0-140 min). Simulations were carried out to assess the effect of CBF and radiotracer clearance changes on SUVRs and non-invasive kinetic modeling outputs. Results: A 0-30 and 120-140 min dual time-window acquisition protocol using appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BP ND obtained using full and dual time-window (2TW) acquisition protocols (BP ND,2TW =0.01+ 1.00 BP ND,FULL , R2=0.97 (MRTM2); BP ND,2TW = 0.05+ 0.92·BP ND,FULL , R2=0.93 (SRTM)). Simulations showed a limited impact of CBF and radiotracer clearance changes on MRTM parameters and SUVRs. Conclusion: This study demonstrates accurate non-invasive kinetic modeling of 18 F-florbetaben PET data using a dual time-window acquisition protocol, thus providing a good compromise between quantification accuracy, scan duration and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-beta load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which a maximum quantification accuracy is desired, this non-invasive dual time-window acquisition protocol and kinetic analysis is recommended. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

PubMed

Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

2016-06-01

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

H19 promotes endometrial cancer progression by modulating epithelial-mesenchymal transition

PubMed Central

Zhao, Le; Li, Zhen; Chen, Wei; Zhai, Wen; Pan, Jingjing; Pang, Huan; Li, Xu

2017-01-01

Endometrial cancer is one of the most common types of gynecological malignancy worldwide. Novel biomarkers and therapeutic targets are imperative for improving patients' survival. Previous studies have suggested the long non-coding RNA H19 as a potential cancer biomarker. To investigate the role of H19 in endometrial cancer, the present study examined the expression pattern of H19 in endometrial cancer tissues by quantitative polymerase chain reaction, and characterized its function in the endometrial cancer cell line via knocking down its expression with small interfering RNAs. It was found that H19 level was significantly higher in tumor tissues than in paratumoral tissues. Knockdown of H19 did not affect the growth rate of HEC-1-B endometrial cancer cells, but significantly suppressed in vitro migration and invasion of HEC-1-B cells. Furthermore, H19 downregulation decreased Snail level and increased E-cadherin expression without affecting vimentin level, indicating partial reversion of epithelial-mesenchymal transition (EMT). The present findings suggested that H19 contributed to the aggressiveness of endometrial cancer by modulating EMT process. PMID:28123568

CDH4 suppresses the progression of salivary adenoid cystic carcinoma via E-cadherin co-expression.

PubMed

Xie, Jian; Feng, Yan; Lin, Ting; Huang, Xiao-Yu; Gan, Rui-Huan; Zhao, Yong; Su, Bo-Hua; Ding, Lin-Can; She, Lin; Chen, Jiang; Lin, Li-Song; Lin, Xu; Zheng, Da-Li; Lu, You-Guang

2016-12-13

The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0.001). Knockdown of CDH4 expression in vitro promoted the growth, mobility and invasion of SACC cells, and in vivo experiments showed that decreased CDH4 expression enhanced SACC tumorigenicity. Furthermore, CDH4 suppression resulted in down-regulation of E-cadherin (E-cad), which is encoded by CDH1 gene and is a well-known tumor suppressor gene by inhibition of cell proliferation and migration. These results indicate that CDH4 may play a negative role in the growth and metastasis of SACC via co-expression with E-cadherin.

MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells

PubMed Central

Ying, Xuexiang; Sun, Yunpo; He, Pingqing

2017-01-01

Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth factor β 1 (TGFβ1)-mediated fibrosis through suppressing epithelial-mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the effects of TGFβ1 in breast cancer (BC) tumorigenesis-related EMT. Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we detected significantly lower levels of BMP7 and significantly higher levels of microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor breast tissue. BMP7 and miR-137 levels were correlated inversely. Additionally, the high miR-137 levels in BC specimens were correlated with reduced patient survival. In vitro, overexpression of miR-137 significantly increased cell EMT and invasion, while depletion of miR-137 significantly decreased cell EMT and invasion in BC cells. The increases in BC cell invasiveness by miR-137 appeared to result from its suppression of BMP7, through direct binding of miR-137 to the 3'-UTR of BMP7 mRNA, thereby blocking its protein translation in BC cells. This study sheds light on miR-137 as a crucial factor that enhances BC cell EMT and invasiveness, and points to miR-137 as a promising innovative therapeutic target for BC treatment. PMID:28407692

Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

PubMed

Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

2016-02-01

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

PubMed

Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

Non-invasive imaging using reporter genes altering cellular water permeability

NASA Astrophysics Data System (ADS)

Mukherjee, Arnab; Wu, Di; Davis, Hunter C.; Shapiro, Mikhail G.

2016-12-01

Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.

PubMed

Puntmann, Valentina O; Zeiher, Andreas M; Nagel, Eike

2018-05-01

Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.

Imaging of Alkaline Phosphatase Activity in Bone Tissue

PubMed Central

Gade, Terence P.; Motley, Matthew W.; Beattie, Bradley J.; Bhakta, Roshni; Boskey, Adele L.; Koutcher, Jason A.; Mayer-Kuckuk, Philipp

2011-01-01

The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP) using a small imaging molecule in combination with 19Flourine magnetic resonance spectroscopic imaging (19FMRSI). 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP), a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using 19Fluorine magnetic resonance spectroscopy (19FMRS) and 19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. 19FMRS and 19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. 19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized 19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of 19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, 19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications. PMID:21799916

(1)H nuclear magnetic resonance (NMR) as a tool to measure dehydration in mice.

PubMed

Li, Matthew; Vassiliou, Christophoros C; Colucci, Lina A; Cima, Michael J

2015-08-01

Dehydration is a prevalent pathology, where loss of bodily water can result in variable symptoms. Symptoms can range from simple thirst to dire scenarios involving loss of consciousness. Clinical methods exist that assess dehydration from qualitative weight changes to more quantitative osmolality measurements. These methods are imprecise, invasive, and/or easily confounded, despite being practiced clinically. We investigate a non-invasive, non-imaging (1)H NMR method of assessing dehydration that attempts to address issues with existing clinical methods. Dehydration was achieved by exposing mice (n = 16) to a thermally elevated environment (37 °C) for up to 7.5 h (0.11-13% weight loss). Whole body NMR measurements were made using a Bruker LF50 BCA-Analyzer before and after dehydration. Physical lean tissue, adipose, and free water compartment approximations had NMR values extracted from relaxation data through a multi-exponential fitting method. Changes in before/after NMR values were compared with clinically practiced metrics of weight loss (percent dehydration) as well as blood and urine osmolality. A linear correlation between tissue relaxometry and both animal percent dehydration and urine osmolality was observed in lean tissue, but not adipose or free fluids. Calculated R(2) values for percent dehydration were 0.8619 (lean, P < 0.0001), 0.5609 (adipose, P = 0.0008), and 0.0644 (free fluids, P = 0.3445). R(2) values for urine osmolality were 0.7760 (lean, P < 0.0001), 0.5005 (adipose, P = 0.0022), and 0.0568 (free fluids, P = 0.3739). These results suggest that non-imaging (1)H NMR methods are capable of non-invasively assessing dehydration in live animals. Copyright © 2015 John Wiley & Sons, Ltd.

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI.

PubMed

Bible, Ellen; Dell'Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter M; Badylak, Stephen F; Ahrens, Eric T; Modo, Michel

2012-04-01

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diffuse reflectance spectroscopy of liver tissue

NASA Astrophysics Data System (ADS)

Reistad, Nina; Nilsson, Jan; Vilhelmsson Timmermand, Oskar; Sturesson, Christian; Andersson-Engels, Stefan

2015-06-01

Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

Developments in the imaging of brown adipose tissue and its associations with muscle, puberty, and health in children.

PubMed

Hu, Houchun H; Gilsanz, Vicente

2011-01-01

Fusion positron emission and computed tomography (PET/CT) remains the gold-standard imaging modality to non-invasively study metabolically active brown adipose tissue (BAT). It has been widely applied to studies in adult cohorts. In contrast, the number of BAT studies in children has been few. This is largely limited by the elevated risk of ionizing radiation and radionuclide tracer usage by PET/CT and the ethical restriction of performing such exams on healthy children. However, metabolically active BAT has a significantly higher prevalence in pediatric patients, according to recent literature. Young cohorts thus represent an ideal population to examine the potential relationships of BAT to muscle development, puberty, disease state, and the accumulation of white adipose tissue. In turn, magnetic resonance imaging (MRI) represents the most promising modality to overcome the limitations of PET/CT. The development of rapid, repeatable MRI techniques to identify and quantify both metabolically active and inactive BAT non-invasively and without the use of exogenous contrast agents or the need for sedation in pediatric patients are critically needed to advance our knowledge of this tissue's physiology.

New non-invasive safe, quick, economical method of detecting various cancers was found using QRS complex or rising part of T-wave of recorded ECGs. Cancers can be screened along with their biochemical parameters & therapeutic effects of any cancer treatments can be evaluated using recorded ECGs of the same individual.

PubMed

Omura, Yoshiaki; Lu, Dominic; O'Young, Brian; Jones, Marilyn; Nihrane, Abdallah; Duvvi, Harsha; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

There are many methods of detecting cancers including detection of cancer markers by blood test, (which is invasive, time consuming and relatively expensive), detection of cancers by non-invasive methods such as X-Ray, CT scan, and MRI & PET Scan (which are non-invasive and quick but very expensive). Our research was performed to develop new non-invasive, safe, quick economical method of detecting cancers and the 1st author already developed for clinically important non-invasive new methods including early stage of present method using his method of localizing accurate organ representation areas of face, eyebrows, upper lip, lower lip, surface and dorsal part of the tongue, surface backs, and palm side of the hands. This accurate localization of the organ representation area of the different parts of the body was performed using electromagnetic field resonance phenomenon between 2 identical molecules or tissues based on our US patented non-invasive method in 1993. Since year 2000, we developed the following non-invasive diagnostic methods that can be quickly identified by the patented simple non-invasive method without using expensive or bulky instrument at any office or field where there is no electricity or instrument available. The following are examples of non-invasive quick method of diagnosis and treatment of cancers using different approaches: 1) Soft red laser beam scanning of different parts of body; 2) By speaking voice; 3) Visible and invisible characteristic abnormalities on different organ representation areas of the different parts of the body, and 4) Mouth, Hand, and Foot Writings of both right and left side of the body. As a consequence of our latest research, we were able to develop a simple method of detecting cancer from existing recorded electrocardiograms. In this article, we are going to describe the method and result of clinical applications on many different cancers of different organs including lung, esophagus, breast, stomach, colon, uterus, ovary, prostate gland, as well as common bone marrow related malignancies such as Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Multiple Myeloma as well as Leukemia.

MicroRNA-31 inhibits RhoA-mediated tumor invasion and chemotherapy resistance in MKN-45 gastric adenocarcinoma cells.

PubMed

Korourian, Alireza; Roudi, Raheleh; Shariftabrizi, Ahmad; Madjd, Zahra

2017-12-01

microRNAs are small single-stranded non-coding RNA molecules which modify gene expression by silencing potential target genes. The aberrant expression of RhoA, a small GTPase protein of Rho family, is involved in gastric cancer tumorigenesis. Since miR-31 is a pleomorphic molecule, we evaluated the miR-31/RhoA axis in inducing the malignant phenotype of gastric cancer cells MKN-45. Also, the clinicopathological significance of RhoA was investigated in a well-defined collection of gastric carcinomas which were embedded in tissue microarray blocks. Induction of miR-31 in MKN-45 followed by suppression of RhoA expression resulted in increased sensitivity to 5-fluorouracil, inhibition of cell proliferation, and invasion compared to the control groups. Immunohistochemical analysis in gastric adenocarcinoma patients' samples showed significantly higher expression of RhoA in diffuse versus intestinal subtype tumors ( P = 0.009), poorly differentiated versus well and moderately differentiated tumors ( P = 0.03) and the presence of vascular invasion versus the absence of vascular invasion ( P = 0.04). Our findings suggest a critical role for miR-31, as a tumor suppressor gene, in gastric cancer tumorigenesis by targeting the RhoA. Impact statement Gastric cancer ranks as the third leading cause of cancer-associated deaths worldwide. The RhoA gene encodes a small GTPase protein of Rho family (RhoA) that its dysregulation is associated with cell motility and invasion. A strong line of evidence supports the regulation of RhoA by a number of miRs, including miR-31 in tumors. Our findings revealed that miR-31 is involved in gastric cancer tumorigenesis as a tumor suppressor gene. Through down-regulation of RhoA, miR-31 decreased cell proliferation, migration, and invasion in gastric cancer cells. In addition, induction of miR-31 increased sensitivity to 5-FU; thus, increasing its tissue concentrations could be a potential target for treatment of gastric cancer in the future.

MicroRNA-31 inhibits RhoA-mediated tumor invasion and chemotherapy resistance in MKN-45 gastric adenocarcinoma cells

PubMed Central

Korourian, Alireza; Roudi, Raheleh; Shariftabrizi, Ahmad

2017-01-01

microRNAs are small single-stranded non-coding RNA molecules which modify gene expression by silencing potential target genes. The aberrant expression of RhoA, a small GTPase protein of Rho family, is involved in gastric cancer tumorigenesis. Since miR-31 is a pleomorphic molecule, we evaluated the miR-31/RhoA axis in inducing the malignant phenotype of gastric cancer cells MKN-45. Also, the clinicopathological significance of RhoA was investigated in a well-defined collection of gastric carcinomas which were embedded in tissue microarray blocks. Induction of miR-31 in MKN-45 followed by suppression of RhoA expression resulted in increased sensitivity to 5-fluorouracil, inhibition of cell proliferation, and invasion compared to the control groups. Immunohistochemical analysis in gastric adenocarcinoma patients’ samples showed significantly higher expression of RhoA in diffuse versus intestinal subtype tumors (P = 0.009), poorly differentiated versus well and moderately differentiated tumors (P = 0.03) and the presence of vascular invasion versus the absence of vascular invasion (P = 0.04). Our findings suggest a critical role for miR-31, as a tumor suppressor gene, in gastric cancer tumorigenesis by targeting the RhoA. Impact statement Gastric cancer ranks as the third leading cause of cancer-associated deaths worldwide. The RhoA gene encodes a small GTPase protein of Rho family (RhoA) that its dysregulation is associated with cell motility and invasion. A strong line of evidence supports the regulation of RhoA by a number of miRs, including miR-31 in tumors. Our findings revealed that miR-31 is involved in gastric cancer tumorigenesis as a tumor suppressor gene. Through down-regulation of RhoA, miR-31 decreased cell proliferation, migration, and invasion in gastric cancer cells. In addition, induction of miR-31 increased sensitivity to 5-FU; thus, increasing its tissue concentrations could be a potential target for treatment of gastric cancer in the future. PMID:28836853

Raman Spectroscopy of Ocular Tissue

NASA Astrophysics Data System (ADS)

Ermakov, Igor V.; Sharifzadeh, Mohsen; Gellermann, Warner

The optically transparent nature of the human eye has motivated numerous Raman studies aimed at the non-invasive optical probing of ocular tissue components critical to healthy vision. Investigations include the qualitative and quantitative detection of tissue-specific molecular constituents, compositional changes occurring with development of ocular pathology, and the detection and tracking of ocular drugs and nutritional supplements. Motivated by a better understanding of the molecular mechanisms leading to cataract formation in the aging human lens, a great deal of work has centered on the Raman detection of proteins and water content in the lens. Several protein groups and the hydroxyl response are readily detectable. Changes of protein compositions can be studied in excised noncataractous tissue versus aged tissue preparations as well as in tissue samples with artificially induced cataracts. Most of these studies are carried out in vitro using suitable animal models and conventional Raman techniques. Tissue water content plays an important role in optimum light transmission of the outermost transparent ocular structure, the cornea. Using confocal Raman spectroscopy techniques, it has been possible to non-invasively measure the water to protein ratio as a measure of hydration status and to track drug-induced changes of the hydration levels in the rabbit cornea at various depths. The aqueous humor, normally supplying nutrients to cornea and lens, has an advantageous anterior location for Raman studies. Increasing efforts are pursued to non-invasively detect the presence of glucose and therapeutic concentrations of antibiotic drugs in this medium. In retinal tissue, Raman spectroscopy proves to be an important tool for research into the causes of macular degeneration, the leading cause of irreversible vision disorders and blindness in the elderly. It has been possible to detect the spectral features of advanced glycation and advanced lipooxydation end products in excised tissue samples and synthetic preparations and thus to identify potential biomarkers for the onset of this disease. Using resonance Raman detection techniques, the concentration and spatial distribution of macular pigment, a protective compound, can be detected in the living human retina Useable in clinical settings for patient screening, the technology is suitable to investigate correlations between pigment concentration levels and risk for macular degeneration and to monitor increases in pigment levels occurring as a result of dietary intervention strategies.

Quantitative spatial frequency fluorescence imaging in the sub-diffusive domain for image-guided glioma resection

PubMed Central

Sibai, Mira; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Wilson, Brian C.

2015-01-01

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue. PMID:26713206

The role of radiology in paediatric soft tissue sarcomas

PubMed Central

van Rijn, R.; McHugh, K.

2008-01-01

Abstract Paediatric soft tissue sarcomas (STS) are a group of malignant tumours that originate from primitive mesenchymal tissue and account for 7% of all childhood tumours. Rhabdomyosarcomas (RMS) and undifferentiated sarcomas account for approximately 50% of soft tissue sarcomas in children and non-rhabdomyomatous soft tissue sarcomas (NRSTS) the remainder. The prognosis and biology of STS tumours vary greatly depending on the age of the patient, the primary site, tumour size, tumour invasiveness, histologic grade, depth of invasion, and extent of disease at diagnosis. Over recent years, there has been a marked improvement in survival rates in children and adolescents with soft tissue sarcoma and ongoing international studies continue to aim to improve these survival rates whilst attempting to reduce the morbidity associated with treatment. Radiology plays a crucial role in the initial diagnosis and staging of STS, in the long term follow-up and in the assessment of many treatment related complications. We review the epidemiology, histology, clinical presentation, staging and prognosis of soft tissue sarcomas and discuss the role of radiology in their management. PMID:18442956

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

PubMed

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

PubMed

Wei, Li-Qiang; Liang, Hui-Tao; Qin, Dong-Chun; Jin, Hui-Fang; Zhao, Yong; She, Ming-Cong

2014-12-01

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

Serum protein changes in immune and nonimmune pigeons infected with various strains of Trichomonas gallinae

USGS Publications Warehouse

Kocan, R.M.; Herman, C.M.

1970-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Winter distribution and abundance of Snowy Plovers in eastern North America and the West Indies

USGS Publications Warehouse

Elliott-Smith, Elise; Haig, Susan M.; Ferland, C.L.; Gorman, Leah

2004-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Coiled-coil domain-containing protein 8 inhibits the invasiveness and migration of non-small cell lung cancer cells.

PubMed

Jiang, Gui-Yang; Zhang, Xiu-Peng; Zhang, Yong; Xu, Hong-Tao; Wang, Liang; Li, Qing-Chang; Wang, En-Hua

2016-10-01

Lung cancer has always been the leading cause of death among patients with malignant tumors, and the majority of these patients die because of cancer cell invasion and metastasis. Previous studies have implicated coiled-coil domain-containing protein 8 (CCDC8) as a tumor suppressor in several types of cancer, such as breast and prostate cancers. However, the expression levels or functions of CCDC8 in lung cancer have not been elucidated. Here, we used immunohistochemical staining to measure CCDC8 expression in 147 samples from tumors and 30 samples from the adjacent normal lung tissues of patients with non-small cell lung cancer. CCDC8 was shown to be located predominantly in the cytoplasm and partially on the cell membrane, and its expression level was significantly lower in lung cancer samples than that in the adjacent normal lung tissues (P=.001). CCDC8 expression was closely related to tumor differentiation (P=.039), tumor-node-metastasis stage (P=.009), lymph node metastasis (P=.038), and prognosis (P=.043) of lung cancer. Transfection of A549 cells with CCDC8 significantly reduced cell invasion and migration (P<.05), whereas the invasiveness and migration capacity in CCDC8-knockdown A549 cells were significantly increased in comparison with the control cells (P<.05). Furthermore, we demonstrated that CCDC8 can downregulate the expression of Snail and upregulate the expression of E-cadherin by inhibiting p-P38 and p-IκBα. Collectively, CCDC8 may suppress the invasion and metastasis of lung cancer cells, and it may represent a promising therapeutic target for non-small cell lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Minimally resective epilepsy surgery in MRI-negative children.

PubMed

Hyslop, Ann; Miller, Ian; Bhatia, Sanjiv; Resnick, Trevor; Duchowny, Michael; Jayakar, Prasanna

2015-09-01

Performing epilepsy surgery on children with non-lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom. We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5-year period. Data collected in the comprehensive non-invasive pre-surgical evaluation (including scalp video-EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra-operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients. Two years postoperatively, 15/25 (60%) children were seizure-free, three (12%) experienced >90% reduction in seizure frequency, two (8%) had a 50-90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre- and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology. In MRI-negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non-invasive and invasive testing. When such children undergo resection of a small, well-defined epileptogenic epicentre, favourable outcomes can be achieved.

Localisation of epidermal growth factor (EGF), its specific receptor (EGF-R) and aromatase at the materno-fetal interface during placentation in the pregnant mare.

PubMed

Allen, W R Twink; Gower, Susan; Wilsher, Sandra

2017-02-01

Implantation and placentation in the mare does not commence until as late as day 40 after ovulation. The reasons for this and the growth factors and/or hormones which drive placentation when it does finally occur are of considerable academic and practical interest. Placental interface tissues recovered from 11 accurately aged and perfused-fixed horse uteri between 20 and 68 days of gestation were stained immunocytochemically for Epidermal Growth Factor (EGF), its specific receptor (EGF-R) and for the steroid hormone enzyme, aromatase. EGF was present in endometrial gland and lumenal epithelia from day 20 but staining intensity increased noticeably for the protein between days 30 and 40, coincidentally with the commencing secretion of equine Chorionic Gonadotrophin (eCG) from the endometrial cups and immediately prior to attachment and commencing interdigitation between the allantochorion and endometrium. EGF-R, on the other hand, was expressed strongly on the cell surface membrane of both non-invasive and invasive trophoblast and it similarly increased in staining intensity between days 30 and 40. Aromatase, the enzyme necessary for conversion of C-19 androgens to C-18 oestrogens, was expressed strongly and constantly from as early as day 12 in the non-invasive trophoblast of the allantochorion, but not the invasive trophoblast of the chorionic girdle, the progenitor tissue of the endometrial cups. The findings support the hypothesis that, in equine pregnancy, the maternal growth factor EGF synergises with maternally and fetally secreted oestrogens to drive the rapid growth and extensive vascularisation of the non-invasive, epitheliochorial, microcotyledonary placenta which results in the birth of the precocious foal after only 11 months gestation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The management of non-invasive bladder tumours with Doxorubicin intravesical instillation after transurethral resection.

PubMed

Al-Gallab, Musa I; Naddaf, Louai A; Kanan, Mohamad R

2009-04-01

Evaluation of the intravesical instillation of doxorubicin for its effect on disease recurrence for patients with non-invasive bladder tumour. The study was performed at Al Assad University Hospital in Lattakia, Syria and included patients with non-invasive bladder tumours who were managed with transurethral resection and induction and maintenance therapy with intravesical doxorubicin. They were followed up by cystoscopy every 3 months for 2 years and every 6 months thereafter with special emphasis on recurrence rates. The study included 85 patients with non-invasive bladder tumours: 23 with non-invasive papillary carcinoma (Stage Ta), 62 with tumour invading subepithelial connective tissue (Stage T1). Twelve patients had well differentiated tumours (Grade 1), 48 had moderately differentiated (Grade 2), 25 had poorly differentiated (Grade 3) tumours. The total recurrence rate was 23%. The rates of recurrence were 56% in Grade 3 and 0% in Grade 1. The recurrence rate was 41% in patients with large tumours versus 17% in those with small tumours; 44% in those with multiple tumours compared to 18% in those with solitary tumours; 30% of Stage Ta tumours recurred and 21% of Stage T1 tumours. In short term follow-up, our rate of recurrence was 23%. Adjuvant intravesical doxorubicin was shown to reduce the recurrence of superficial bladder cancer. Tumour grade, size and number were shown to be prognostic factors for recurrence.

Blockade of the CXCR6 signaling inhibits growth and invasion of hepatocellular carcinoma cells through inhibition of the VEGF expression.

PubMed

Xu, J M; Weng, M Z; Song, F B; Chen, J Y; Zhang, J Y; Wu, J Y; Qin, J; Jin, T; Wang, X L

2014-01-01

Chemokines have been shown to play a critical role in tumor development and progression. However, little is known about the function and molecular mechanisms of CXCR6 in multiple malignancies. In the present study, we aimed to investigate the role of CXCR6 in human hepatocellular carcinoma (HCC). The expression of CXCR6 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentivirus-mediated CXCR6 shRNA (shCXCR6) on cell proliferation and invasive potential by MTT and Transwell assays in HCC cell line (SMMC-7721). It was found that the expression of CXCR6 protein was significantly increased in HCC tissues compared with that in adjacent non-cancerous tissues (ANCT) (63.04% vs 36.96%, P=0.019), and correlated with the lymph-vascular space invasion in HCC patients (P=0.038). Knockdown of CXCR6 repressed cell proliferation and invasion of HCC cells followed by the down-regulation of vascular endothelial growth factor (VEGF). Taken together, our findings show that high expression of CXCR6 is positively associated with distant invasion of HCC patients, and blockade of CXCR6 signaling suppresses the growth and invasion of HCC cells through inhibition of the VEGF expression, suggesting that CXCR6 may represent a promising therapeutic target for the treatment of HCC.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

PubMed

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2

PubMed Central

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer. PMID:26722475

Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments.

PubMed

Parekh, Dipen J; Bochner, Bernard H; Dalbagni, Guido

2006-12-10

Bladder cancer is a heterogeneous disease. Non-muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non-muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.

Bmi-1 expression modulates non-small cell lung cancer progression

PubMed Central

Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

2015-01-01

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

Infrared fiber optic evanescent wave spectroscopy: applications in biology and medicine

NASA Astrophysics Data System (ADS)

Afanasyeva, Natalia I.; Bruch, Reinhard F.; Katzir, Abraham

1999-04-01

A new powerful and highly sensitive technique for non-invasive biomedical diagnostics in vivo has been developed using Infrared Fiberoptic Evanescent Wave Fourier Transform Spectroscopy (FEW-FTIR). This compact and portable method allows to detect functional chemical groups and bonds via vibrational spectroscopy directly from surfaces including living tissue. Such differences and similarities in molecular structure of tissue and materials can be evaluated online. Operating in the attenuated total reflection (ATR) regime in the middle-infrared (MIR) range, the FEW-FTIR technique provides direct contact between the fiber probe and tissue for non-destructive, non-invasive, fast and remote (few meters) diagnostics and quality control of materials. This method utilizes highly flexible and extremely low loss unclad fibers, for example silver halide fibers. Applications of this method include investigations of normal skin, precancerous and cancerous conditions, monitoring of the process of aging, allergic reactions and radiation damage to the skin. This setup is suitable as well for the detection of the influence of environmental factors (sun, water, pollution, and weather) on skin surfaces. The FEW-FTIR technique is very promising also for fast histological examinations in vitro. In this review, we present recent investigations of skin, breast, lung, stomach, kidney tissues in vivo and ex vivo (during surgery) to define the areas of tumor localization. The main advantages of the FEW-FTIR technique for biomedical, clinical, and environmental applications are discussed.

Near-infrared optical properties of ex-vivo human skin and subcutaneous tissues using reflectance and transmittance measurements

NASA Astrophysics Data System (ADS)

Simpson, Rebecca; Laufer, Jan G.; Kohl-Bareis, Matthias; Essenpreis, Matthias; Cope, Mark

1997-08-01

The vast majority of 'non-invasive' measurements of human tissues using near infrared spectroscopy rely on passing light through the dermis and subdermis of the skin. Accurate knowledge of the optical properties of these tissues is essential to put into models of light transport and predict the effects of skin perfusion on measurements of deep tissue. Additionally, the skin could be a useful accessible organ for non-invasively determining the constituents of blood flowing through it. Samples of abdominal human skin (including subdermal tissue) were obtained from either post mortem examinations or plastic surgery. The samples were separated into a dermal layer (epidermis and dermis, 1.5 to 2 mm tick), and a sub-cutaneous layer comprised largely of fat. They were enclosed between two glass coverslips and placed in an integrating sphere to measure their reflectance and transmittance over a range of wavelengths from 600 to 1000 nm. The reflectance and transmittance values were converted into average absorption and reduced scattering coefficients by comparison with a Monte Carlo model of light transport. Improvements to the Monte Carlo model and measurement technique removed some previous uncertainties. The results show excellent separation of reduced scattering and absorption coefficient, with clear absorption peaks of hemoglobin, water and lipid. The effect of tissue storage upon measured optical properties was investigated.

Use of volume-targeted non-invasive bilevel positive airway pressure ventilation in a patient with amyotrophic lateral sclerosis*,**

PubMed Central

Diaz-Abad, Montserrat; Brown, John Edward

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which most patients die of respiratory failure. Although volume-targeted non-invasive bilevel positive airway pressure (BPAP) ventilation has been studied in patients with chronic respiratory failure of various etiologies, its use in ALS has not been reported. We present the case of a 66-year-old woman with ALS and respiratory failure treated with volume-targeted BPAP ventilation for 15 weeks. Weekly data downloads showed that disease progression was associated with increased respiratory muscle weakness, decreased spontaneous breathing, and increased use of non-invasive positive pressure ventilation, whereas tidal volume and minute ventilation remained relatively constant. PMID:25210968

Epigenetic silencing of ADAMTS5 is associated with increased invasiveness and poor survival in patients with colorectal cancer.

PubMed

Li, Jizhen; Liao, Yi; Huang, Jintuan; Sun, Yi; Chen, Hao; Chen, Chunyu; Li, Senmao; Yang, Zuli

2018-02-01

A disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p < 0.001). Negative expression of ADAMTS5 was much more common in tumor tissues than that in normal tissues (p < 0.001) and correlated with histologic types (p = 0.002), poor OS (p = 0.029) and DFS (p = 0.018). In vitro assay revealed that overexpression of ADAMTS5 inhibited the capabilities of migration and invasion of CRC cells, and no effect on cell growth, cell cycle and apoptosis. ADAMTS5 is hypermethylated and inhibits cancer cells invasion and migration in colorectal cancer, and correlates with OS and DFS, indicating that ADAMTS5 might be a useful biomarker in colorectal cancer therapy.

Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer

PubMed Central

Silva, Dilson; Cortez, Celia M.; McKenzie, Edward A.; Bitu, Carolina C.; Salo, Sirpa; Nurmenniemi, Sini; Nyberg, Pia; Risteli, Juha; deAlmeida, Carlos E. B.; Brenchley, Paul E. C.; Salo, Tuula; Missailidis, Sotiris

2014-01-01

Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use. PMID:25295847

Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells.

PubMed

Lim, S Y; Yuzhalin, A E; Gordon-Weeks, A N; Muschel, R J

2016-11-03

Myeloid cells promote the development of distant metastases, but little is known about the molecular mechanisms underlying this process. Here we have begun to uncover the effects of myeloid cells on cancer cells in a mouse model of liver metastasis. Monocytes/macrophages, but not granulocytes, isolated from experimental liver metastases stimulated migration and invasion of MC38 colon and Lewis lung carcinoma cells. In response to conditioned media from tumor-infiltrating monocytes/macrophages, cancer cells upregulated S100a8 and S100a9 messenger RNA expression through an extracellular signal-related kinase-dependent mechanism. Suppression of S100A8 and S100A9 in cancer cells using short hairpin RNA significantly diminished migration and invasion in culture. Downregulation of S100A8 and S100A9 had no effect on subcutaneous tumor growth. However, colony size was greatly reduced in liver metastases with decreased invasion into adjacent tissue. In tissue culture and in the liver colonies derived from cancer cells with knockdown of S100A8 and S100A9, MMP2 and MMP9 expression was decreased, consistent with the reduction in migration and invasion. Our findings demonstrate that monocytes/macrophages in the metastatic liver microenvironment induce S100A8 and S100A9 in cancer cells, and that these proteins are essential for tumor cell migration and invasion. S100A8 and S100A9, however, are not responsible for stimulation of proliferation. This study implicates S100A8 and S100A9 as important mediators of tumor cell aggressiveness, and highlights the therapeutic potential of S100A8 and S100A9 for interference of metastasis.

Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells

PubMed Central

Lim, S Y; Yuzhalin, A E; Gordon-Weeks, A N; Muschel, R J

2016-01-01

Myeloid cells promote the development of distant metastases, but little is known about the molecular mechanisms underlying this process. Here we have begun to uncover the effects of myeloid cells on cancer cells in a mouse model of liver metastasis. Monocytes/macrophages, but not granulocytes, isolated from experimental liver metastases stimulated migration and invasion of MC38 colon and Lewis lung carcinoma cells. In response to conditioned media from tumor-infiltrating monocytes/macrophages, cancer cells upregulated S100a8 and S100a9 messenger RNA expression through an extracellular signal-related kinase-dependent mechanism. Suppression of S100A8 and S100A9 in cancer cells using short hairpin RNA significantly diminished migration and invasion in culture. Downregulation of S100A8 and S100A9 had no effect on subcutaneous tumor growth. However, colony size was greatly reduced in liver metastases with decreased invasion into adjacent tissue. In tissue culture and in the liver colonies derived from cancer cells with knockdown of S100A8 and S100A9, MMP2 and MMP9 expression was decreased, consistent with the reduction in migration and invasion. Our findings demonstrate that monocytes/macrophages in the metastatic liver microenvironment induce S100A8 and S100A9 in cancer cells, and that these proteins are essential for tumor cell migration and invasion. S100A8 and S100A9, however, are not responsible for stimulation of proliferation. This study implicates S100A8 and S100A9 as important mediators of tumor cell aggressiveness, and highlights the therapeutic potential of S100A8 and S100A9 for interference of metastasis. PMID:27086923

BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.

PubMed

Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

2015-02-01

We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cancer cell invasion

PubMed Central

Cekanova, Maria; Fernando, Romaine I.; Siriwardhana, Nalin; Sukhthankar, Mugdha; de la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J.; Wade, Paul A.; Saxton, Arnold M.; Donnell, Robert M.; Pestell, Richard G.; Dharmawardhane, Suranganie; Wimalasena, Jay

2015-01-01

We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 were regulated by BAD with concomitant inhibition of extracellular matrix invasion. siRNA knockdown of BAD increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. PMID:25499972

Optical changes in cortical tissue during seizure activity using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ornelas, Danielle; Hasan, Md.; Gonzalez, Oscar; Krishnan, Giri; Szu, Jenny I.; Myers, Timothy; Hirota, Koji; Bazhenov, Maxim; Binder, Devin K.; Park, Boris H.

2017-02-01

Epilepsy is a chronic neurological disorder characterized by recurrent and unpredictable seizures. Electrophysiology has remained the gold standard of neural activity detection but its resolution and high susceptibility to noise and motion artifact limit its efficiency. Optical imaging techniques, including fMRI, intrinsic optical imaging, and diffuse optical imaging, have also been used to detect neural activity yet these techniques rely on the indirect measurement of changes in blood flow. A more direct optical imaging technique is optical coherence tomography (OCT), a label-free, high resolution, and minimally invasive imaging technique that can produce depth-resolved cross-sectional and 3D images. In this study, OCT was used to detect non-vascular depth-dependent optical changes in cortical tissue during 4-aminopyridine (4-AP) induced seizure onset. Calculations of localized optical attenuation coefficient (µ) allow for the assessment of depth-resolved volumetric optical changes in seizure induced cortical tissue. By utilizing the depth-dependency of the attenuation coefficient, we demonstrate the ability to locate and remove the optical effects of vasculature within the upper regions of the cortex on the attenuation calculations of cortical tissue in vivo. The results of this study reveal a significant depth-dependent decrease in attenuation coefficient of nonvascular cortical tissue both ex vivo and in vivo. Regions exhibiting decreased attenuation coefficient show significant temporal correlation to regions of increased electrical activity during seizure onset and progression. This study allows for a more thorough and biologically relevant analysis of the optical signature of seizure activity in vivo using OCT.

A Novel Combination of Thermal Ablation and Heat-Inducible Gene therapy for Breast Cancer Treatment

DTIC Science & Technology

2009-04-01

intensity focused ultrasound ( HIFU ) has been developed as an emerging non-invasive strategy for cancer treatment by thermal ablation of tumor tissue. The...Leenders, G., et al., Histopathological changes associated with high intensity focused ultrasound ( HIFU ) treatment for localised adenocarcinoma of...invasive strategy for cancer therapy [1, 2]. Through HIFU exposure, acoustic energy is focused into a deep-sited tumor volume and converted into heat

miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells

PubMed Central

Fei, Xiubin; Zhang, Jingang; Zhao, Yunwei; Sun, Meijia; Zhao, Haifeng; Li, Shuang

2018-01-01

Lung cancer is a major cause of death worldwide, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The aim of this study was to investigate whether miR-96 mediated the invasion and metastasis of NSCLC by targeting glypican-3 (GPC3). Reverse transcription-quantitative PCR (RT-qPCR) was employed to detect the level of miR-96 and GPC3 mRNA. We applied western blot analysis to measure the protein expression level of GPC3 gene. The luciferase reporter assay was employed to confirm that GPC3 was a target gene of miR-96. The Transwell assay was used to detect migration and invasion. The results revealed that miR-96 was upregulated in NSCLC tissues and lung cancer cells (A549 and H460) compared with corresponding paracancerous tissues and normal epidermic MRC-5 cells. Overexpression of miR-96 promoted invasion and migration in A549 cells. GPC3 was a direct target of miR-96 and regulated by miR-96. GPC3 could reverse partial fuction of miR-96 on proliferation. In conclusion, miR-96 was able to promote the migration and invasion of lung cancer cells by targeting GPC3 gene. The newly identified miR-96/GPC3 axis may provide a therapeutic method for the treatment of NSCLC. PMID:29805640

Microneedle-based minimally-invasive measurement of puncture resistance and fracture toughness of sclera.

PubMed

Park, Seung Hyun; Lee, Kang Ju; Lee, JiYong; Yoon, Jae Hyoung; Jo, Dong Hyun; Kim, Jeong Hun; Kang, Keonwook; Ryu, WonHyoung

2016-10-15

The sclera provides the structural support of the eye and protects the intraocular contents. Since it covers a large portion of the eye surface and has relatively high permeability for most drugs, the sclera has been used as a major pathway for drug administration. Recently, microneedle (MN) technology has shown the possibility of highly local and minimally-invasive drug delivery to the eye by MN insertion through the sclera or the suprachoroidal space. Although ocular MN needs to be inserted through the sclera, there has been no systematic study to understand the mechanical properties of the sclera, which are important to design ocular MNs. In this study, we investigated a MN-based method to measure the puncture resistance and fracture toughness of the sclera. To reflect the conditions of MN insertion into the sclera, force-displacement curves obtained from MN-insertion tests were used to estimate the puncture resistance and fracture toughness of sclera tissue. To understand the effect of the insertion conditions, dependency of the mechanical properties on insertion speeds, pre-strain of the sclera, and MN sizes were analyzed and discussed. Measurement of mechanical property of soft biological tissue is challenging due to variations between tissue samples or lack of well-defined measurement techniques. Although non-invasive measurement techniques such as nano/micro indentation were employed to locally measure the elastic modulus of soft biological materials, mechanical properties such as puncture resistance or fracture toughness, which requires "invasive" measurement and is important for the application of "microneedles or hypodermic needles", has not been well studied. In this work, we report minimally-invasive measurement of puncture resistance and fracture toughness of sclera using a double MN insertion method. Parametric studies showed that use of MN proved to be advantageous because of minimally-invasive insertion into tissue as well as higher sensitivity to sub-tissue architecture during the measurement. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Functional and morphological ultrasonic biomicroscopy for tissue engineers

NASA Astrophysics Data System (ADS)

Mallidi, S.; Aglyamov, S. R.; Karpiouk, A. B.; Park, S.; Emelianov, S. Y.

2006-03-01

Tissue engineering is an interdisciplinary field that combines various aspects of engineering and life sciences and aims to develop biological substitutes to restore, repair or maintain tissue function. Currently, the ability to have quantitative functional assays of engineered tissues is limited to existing invasive methods like biopsy. Hence, an imaging tool for non-invasive and simultaneous evaluation of the anatomical and functional properties of the engineered tissue is needed. In this paper we present an advanced in-vivo imaging technology - ultrasound biomicroscopy combined with complementary photoacoustic and elasticity imaging techniques, capable of accurate visualization of both structural and functional changes in engineered tissues, sequential monitoring of tissue adaptation and/or regeneration, and possible assistance of drug delivery and treatment planning. The combined imaging at microscopic resolution was evaluated on tissue mimicking phantoms imaged with 25 MHz single element focused transducer. The results of our study demonstrate that the ultrasonic, photoacoustic and elasticity images synergistically complement each other in detecting features otherwise imperceptible using the individual techniques. Finally, we illustrate the feasibility of the combined ultrasound, photoacoustic and elasticity imaging techniques in accurately assessing the morphological and functional changes occurring in engineered tissue.

Ultrasound Elastography: Review of Techniques and Clinical Applications

PubMed Central

Sigrist, Rosa M.S.; Liau, Joy; Kaffas, Ahmed El; Chammas, Maria Cristina; Willmann, Juergen K.

2017-01-01

Elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. These techniques take advantage of changed soft tissue elasticity in various pathologies to yield qualitative and quantitative information that can be used for diagnostic purposes. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave). Ultrasound-based methods are of particular interest due to its many inherent advantages, such as wide availability including at the bedside and relatively low cost. Several ultrasound elastography techniques using different excitation methods have been developed. In general, these can be classified into strain imaging methods that use internal or external compression stimuli, and shear wave imaging that use ultrasound-generated traveling shear wave stimuli. While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging. Here, we review the basic principles, foundation physics, and limitations of ultrasound elastography and summarize its current clinical use and ongoing developments in various clinical applications. PMID:28435467

Label-free optical imaging of lymphatic vessels within tissue beds in vivo

PubMed Central

Yousefi, Siavash; Zhi, Zhongwei; Wang, Ruikang K.

2015-01-01

Lymphatic vessels are a part of circulatory system in vertebrates that maintain tissue fluid homeostasis and drain excess fluid and large cells that cannot easily find their way back into venous system. Due to the lack of non-invasive monitoring tools, lymphatic vessels are known as forgotten circulation. However, lymphatic system plays an important role in diseases such as cancer and inflammatory conditions. In this paper, we start to briefly review the current existing methods for imaging lymphatic vessels, mostly involving dye/targeting cell injection. We then show the capability of optical coherence tomography (OCT) for label-free non-invasive in vivo imaging of lymph vessels and nodes. One of the advantages of using OCT over other imaging modalities is its ability to assess label-free blood flow perfusion that can be simultaneously observed along with lymphatic vessels for imaging the microcirculatory system within tissue beds. Imaging the microcirculatory system including blood and lymphatic vessels can be utilized for imaging and better understanding pathologic mechanisms and treatment technique development in some critical diseases such as inflammation, malignant cancer angiogenesis and metastasis. PMID:25642129

Applying Broadband Dielectric Spectroscopy (BDS) for the Biophysical Characterization of Mammalian Tissues under a Variety of Cellular Stresses

PubMed Central

Souli, Maria P.; Klonos, Panagiotis; Fragopoulou, Adamantia F.; Mavragani, Ifigeneia V.; Pateras, Ioannis S.; Kostomitsopoulos, Nikolaos; Margaritis, Lukas H.; Zoumpoulis, Pavlos; Kaklamanis, Loukas; Kletsas, Dimitris; Gorgoulis, Vassilis G.; Kyritsis, Apostolos; Pissis, Polycarpos; Georgakilas, Alexandros G.

2017-01-01

The dielectric properties of biological tissues can contribute non-invasively to a better characterization and understanding of the structural properties and physiology of living organisms. The question we asked, is whether these induced changes are effected by an endogenous or exogenous cellular stress, and can they be detected non-invasively in the form of a dielectric response, e.g., an AC conductivity switch in the broadband frequency spectrum. This study constitutes the first methodological approach for the detection of environmental stress-induced damage in mammalian tissues by the means of broadband dielectric spectroscopy (BDS) at the frequencies of 1–106 Hz. Firstly, we used non-ionizing (NIR) and ionizing radiation (IR) as a typical environmental stress. Specifically, rats were exposed to either digital enhanced cordless telecommunication (DECT) radio frequency electromagnetic radiation or to γ-radiation, respectively. The other type of stress, characterized usually by high genomic instability, was the pathophysiological state of human cancer (lung and prostate). Analyzing the results of isothermal dielectric measurements provided information on the tissues’ water fraction. In most cases, our methodology proved sufficient in detecting structural changes, especially in the case of IR and malignancy. Useful specific dielectric response patterns are detected and correlated with each type of stress. Our results point towards the development of a dielectric-based methodology for better understanding and, in a relatively invasive way, the biological and structural changes effected by radiation and developing lung or prostate cancer often associated with genomic instability. PMID:28420124

Upregulation of the long non-coding RNA SNHG1 predicts poor prognosis, promotes cell proliferation and invasion, and reduces apoptosis in glioma.

PubMed

Wang, Qiang; Li, Qing; Zhou, Peng; Deng, Danni; Xue, Lian; Shao, Naiyuan; Peng, Ya; Zhi, Feng

2017-07-01

Long non-coding RNAs (lncRNAs), which are non-coding RNAs with a length above 200 nucleotides, have emerged as novel and important gene expression modulators in carcinogenesis. Recent evidence indicates that the lncRNA small nucleolar RNA host gene 1 (SNHG1) functions as an oncogene in several types of human cancers. However, its function in the development of glioma remains unknown. The aim of this research was to investigate the clinical aspects and biological mechanisms of SNHG1 in glioma. SNHG1 expression was measured in glioma tissues and cell lines by quantitative real-time PCR (qRT-PCR). The association between SNHG1 expression in tissues and clinicopathological characteristics and prognosis in glioma patients was also explored. Gain-of-function and loss-of-function studies using SNHG1 cDNA and siRNA, respectively, were used to investigate the role of SNHG1 in cell proliferation, invasion and apoptosis in glioma. SNHG1 was highly expressed in glioma tissues, and its upregulation was closely related to old age. Kaplan-Meier analysis showed that high expression of SNHG1 was significantly associated with poor overall survival (OS). Functionally, ectopic expression of SNHG1 enhanced cell proliferation and cell invasion and reduced cell apoptosis in vitro, while SNHG1 knockdown reversed these effects. Taken together, our findings indicate that SNHG1 functions as an oncogene in glioma and may serve as a novel therapeutic target in future treatments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

NASA Astrophysics Data System (ADS)

Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

2016-08-01

Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  <8% and the calculated CBF values showed a tight correlation (r  =  0.97). The simulation showed that errors associated with the assumed parameters were  <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through {{\\text{H}}2} 15O PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

NASA Astrophysics Data System (ADS)

Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

2016-12-01

Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

Non-invasive monitoring of hemodynamic changes in orthotropic brain tumor

NASA Astrophysics Data System (ADS)

Kashyap, Dheerendra; Sharma, Vikrant; Liu, Hanli

2007-02-01

Radio surgical interventions such as Gamma Knife and Cyberknife have become attractive as therapeutic interventions. However, one of the drawbacks of cyberknife is radionecrosis, which is caused by excessive radiation to surrounding normal tissues. Radionecrosis occurs in about 10-15% of cases and could have adverse effects leading to death. Currently available imaging techniques have failed to reliably distinguish radionecrosis from tumor growth. Development of imaging techniques that could provide distinction between tumor growth and radionecrosis would give us ability to monitor effects of radiation therapy non-invasively. This paper investigates the use of near infrared spectroscopy (NIRS) as a new technique to monitor the growth of brain tumors. Brain tumors (9L glioma cell line) were implanted in right caudate nucleus of rats (250-300 gms, Male Fisher C) through a guide screw. A new algorithm was developed, which used broadband steady-state reflectance measurements made using a single source-detector pair, to quantify absolute concentrations of hemoglobin derivatives and reduced scattering coefficients. Preliminary results from the brain tumors indicated decreases in oxygen saturation, oxygenated hemoglobin concentrations and increases in deoxygenated hemoglobin concentrations with tumor growth. The study demonstrates that NIRS technology could provide an efficient, noninvasive means of monitoring vascular oxygenation dynamics of brain tumors and further facilitate investigations of efficacy of tumor treatments.

The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT

NASA Astrophysics Data System (ADS)

Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison

2009-06-01

This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P < 0.05), whilst PpIX levels in the surrounding normal tissue remained unaltered. After irradiation, the PpIX concentration was significantly decreased and returned to a level similar to the initial concentration originally observed. Lesions that received subsequent treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.

Endometriosis: Epidemiology, Diagnosis and Clinical Management

PubMed Central

Parasar, Parveen; Ozcan, Pinar; Terry, Kathryn L.

2017-01-01

Purpose of review Endometriosis is a disease of adolescents and reproductive-aged women characterized by the presence of endometrial tissue outside the uterine cavity and commonly associated with chronic pelvic pain and infertility. Here we review the epidemiology of endometriosis as well as potential biomarkers for detection and with the goal of highlighting risk factors that could be used in combination with biomarkers to identify and treat women with endometriosis earlier.. Recent findings Early age at menarche, shorter menstrual length, and taller height are associated with a higher risk of endometriosis while parity, higher body mass index (BMI) and smoking are associated with decreased risk. Endometriosis often presents as infertility or continued pelvic pain despite treatment with analgesics and cyclic oral contraceptive pills. Summary Despite a range of symptoms, diagnosis of endometriosis is often delayed due to lack of non-invasive, definitive and consistent biomarkers for diagnosis of endometriosis. Hormone therapy and analgesics are used for treatment of symptomatic endometriosis. However, the efficacy of these treatments are limited as endometriosis often recurs. In this review, we describe potential diagnostic biomarkers and risk factors that may be used as early non-invasive in vitro tools for identification of endometriosis to minimize diagnostic delay and improve reproductive health of patients. PMID:29276652

Miniature soft robots — road to the clinic

NASA Astrophysics Data System (ADS)

Sitti, Metin

2018-06-01

Soft small robots offer the opportunity to non-invasively access human tissue to perform medical operations and deliver drugs; however, challenges in materials design, biocompatibility and function control remain to be overcome for soft robots to reach the clinic.

Differential phase optical coherence probe for depth-resolved detection of photothermal response in tissue.

PubMed

Telenkov, Sergey A; Dave, Digant P; Sethuraman, Shriram; Akkin, Taner; Milner, Thomas E

2004-01-07

We describe a differential phase low-coherence interferometric probe for non-invasive, quantitative imaging of photothermal phenomena in biological materials. Our detection method utilizes principles of optical coherence tomography with differential phase measurement of interference fringe signals. A dual-channel optical low-coherence probe is used to analyse laser-induced thermoelastic and thermorefractive effects in tissue with micrometre axial resolution and nanometre sensitivity. We demonstrate an application of the technique using tissue phantoms and ex-vivo tissue specimens of rodent dorsal skin.

A new holistic 3D non-invasive analysis of cellular distribution and motility on fibroin-alginate microcarriers using light sheet fluorescent microscopy

PubMed Central

Pierini, Michela; Bevilacqua, Alessandro; Torre, Maria Luisa; Lucarelli, Enrico

2017-01-01

Cell interaction with biomaterials is one of the keystones to developing medical devices for tissue engineering applications. Biomaterials are the scaffolds that give three-dimensional support to the cells, and are vectors that deliver the cells to the injured tissue requiring repair. Features of biomaterials can influence the behaviour of the cells and consequently the efficacy of the tissue-engineered product. The adhesion, distribution and motility of the seeded cells onto the scaffold represent key aspects, and must be evaluated in vitro during the product development, especially when the efficacy of a specific tissue-engineered product depends on viable and functional cell loading. In this work, we propose a non-invasive and non-destructive imaging analysis for investigating motility, viability and distribution of Mesenchymal Stem Cells (MSCs) on silk fibroin-based alginate microcarriers, to test the adhesion capacity of the fibroin coating onto alginate which is known to be unsuitable for cell adhesion. However, in depth characterization of the biomaterial is beyond the scope of this paper. Scaffold-loaded MSCs were stained with Calcein-AM and Ethidium homodimer-1 to detect live and dead cells, respectively, and counterstained with Hoechst to label cell nuclei. Time-lapse Light Sheet Fluorescent Microscopy (LSFM) was then used to produce three-dimensional images of the entire cells-loaded fibroin/alginate microcarriers. In order to quantitatively track the cell motility over time, we also developed an open source user friendly software tool called Fluorescent Cell Tracker in Three-Dimensions (F-Tracker3D). Combining LSFM with F-Tracker3D we were able for the first time to assess the distribution and motility of stem cells in a non-invasive, non-destructive, quantitative, and three-dimensional analysis of the entire surface of the cell-loaded scaffold. We therefore propose this imaging technique as an innovative holistic tool for monitoring cell-biomaterial interactions, and as a tool for the design, fabrication and functionalization of a scaffold as a medical device. PMID:28817694

Epigenetic suppression of neprilysin regulates breast cancer invasion

PubMed Central

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-01-01

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer. PMID:26950599

Epigenetic suppression of neprilysin regulates breast cancer invasion.

PubMed

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-03-07

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.

Chromium in urothelial carcinoma of the bladder.

PubMed

Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

2017-12-23

Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

Novel Strategies to Improve Immunomodulatin and Non Invasive Clinical Monitoring in VCA

DTIC Science & Technology

2016-08-01

to patients with severe, unreconstructable vascularized composite tissue defects by safe VCA protocols with minimal side effects. Our specific aims...histology and ultrasound biomicroscopy (UBM). We are enrolling 5 subjects for VCA. ɛ months after VCA, once recipient and allograft are stable, we will...their treatment outcomes. Vascularized composite allotransplants provide a mean to functionally and cosmetically restore these tissues ; however, at

Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7

PubMed Central

Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

2015-01-01

Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression. PMID:26010572

Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7.

PubMed

Xue, Zhen; Zhao, Jindong; Niu, Liyuan; An, Gang; Guo, Yashan; Ni, Linying

2015-01-01

Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

PubMed

Gan, Yuanyuan; Han, Nana; He, Xiaoqin; Yu, Jiajun; Zhang, Meixia; Zhou, Yujie; Liang, Huiling; Deng, Junjian; Zheng, Yongfa; Ge, Wei; Long, Zhixiong; Xu, Ximing

2017-06-01

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

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

Gopalan, Vinod; Islam, Farhadul; Pillai, Suja

Purpose: This study aims to examine the expression profiles miR-1288 in oesophageal squamous cell carcinoma (ESCC). The cellular implications and target interactions of ESCC cells following miR-1288 overexpression was also examined. Methods: In total, 120 oesophageal tissues (90 primary ESCCs and 30 non-neoplastic tissues) were recruited for miR-1288 expression analysis using qRT-PCR. An exogenous miR-1288 mimic and its inhibitor were used to explore the in-vitro effects of miR-1288 on ESCC cells by performing cell proliferation, colony formation, cell invasion and migration assays. Localisation and modulatory changes of various miR-1288 regulated proteins such as FOXO1, p53, TAB3, BCL2 and kRAS wasmore » examined using immunofluorescence and western blot. Results: Overexpression of miR-1288 was more often noted in ESCC tissues when compared to non-neoplastic oesophageal tissues. High expression was often noted in high grade carcinomas and with metastases. Patients with high levels of miR-1288 expression showed a slightly better survival compared to patients with low miR-1288 levels. Furthermore, overexpression of miR-1288 showed increased cell proliferation and colony formation, improved cell migration and enhanced cell invasion properties in ESCC cells. In addition, miR-1288 overexpression in ESCC cells showed repression of cytoplasmic tumour suppressor FOXO1 protein expression. Inversely, inhibition of miR-1288 expression exhibited remarkable upregulation of FOXO1 protein, while expressions of other tested proteins remain unchanged. Conclusions: Up regulation of miR-1288 expression in ESCC tissues and miR-1288 induced oncogenic features of ESCC cells in-vitro indicates the oncogenic roles of miR-1288 in ESCCs. Overexpression of miR-1288 play a key role in the pathogenesis of ESCCs and its modulation may have potential therapeutic value in patients with ESCC. - Highlights: • miR-1288 was more often noted in neoplastic than non-neoplastic tissue. • miR-1288 overexpression increased proliferative/invasive activities of ESCC. • miR-1288 overexpression showed repression of FOXO1 protein expression. • miR-1288 functions as an oncogenic miRNA in ESCCs.« less

Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices – an experimental study in the rat

PubMed Central

2014-01-01

Introduction Within the last decades, collagen types I and III have been established as a sufficient biomaterial for GBR and GTR procedures. They might also be an adequate matrix for soft tissue augmentations. However, collagen materials differ significantly regarding resorption time, biodegradation pattern and the invasion of inflammatory cells. The aim of the present study was to compare the biodegradation and tissue integration of native, differently processed and cross-linked collagen scaffolds in rats. Methods Four experimental porcine collagen matrices of 1.0 mm thickness, developed for soft tissue augmentation procedures, were tested. Based on the same native dermal Type I and III collagen, native (ND, Mucoderm® prototype), specifically defatted (DD), ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL) dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two specimens of 1 × 1 cm were fixed around a non-absorbable spacer using non-absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each. After each period, eight rats were sacrificed and explanted specimens were prepared for histological analysis. The following parameters were evaluated: membrane thickness as a sign of biodegradation and volume stability, cell ingrowth, vascularization, tissue integration and foreign body reaction. Results Biodegradation pattern of the non cross-linked collagen scaffolds differed only slightly in terms of presence of inflammatory cells and cell invasion into the matrix. In terms of biodegradation, ECL displayed a considerable slower resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide showed a significant higher invasion of inflammatory cells. Conclusion Within the limits of the present study it was concluded that the processing techniques influenced the collagen properties in a different intensity. Dehydrothermal cross-linking and special defatting did not notably change the biodegradation pattern, whereas cross-linking using ethylene dioxide led to significant higher volume stability of the matrix. However, ECL showed an increased inflammatory response and compromised tissue integration. Therefore, ethylene dioxide seems to be not suitable for stabilization of collagen matrices for soft tissue augmentation procedures. PMID:24670219

Down-regulation of MicroRNA-133 predicts poor overall survival and regulates the growth and invasive abilities in glioma.

PubMed

Liu, Yu; Han, Lili; Bai, Yahui; Du, Wei; Yang, Bo

2018-02-01

miRNAs were reported as oncogene or tumour suppressors in various cancers and played important roles in tumour development and progression. Dysregulated miR-133 has been reported in several cancers, however, the expression and biological function of miR-133 in glioma remained unclear. In this study, we found that miR-133 expression level was significantly decreased in glioma tissues and cell lines by RT-qPCR. Then miR-133 mimics were used to evaluate the effects of miR-133 on cell proliferation and invasion in vitro. We found that overexpressed miR-133 could significantly suppress cell growth, and invasion in U87 cells. Additionally, we found that forkhead box C1 (FOXC1) was overexpressed in glioma tissue and it was directly regulated by miR-133. Overall, this study is the first proof to demonstrate that miR-133 function as tumour suppressor in glioma and inhibit cell proliferation and invasioned by directly targeting FOXC1, implying miR-133 as a potential therapeutic target for glioma.

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

Confounding factors in the use of the zero-heat-flow method for non-invasive muscle temperature measurement.

PubMed

Brajkovic, Dragan; Ducharme, Michel B

2005-07-01

This study evaluated a zero-heat-flow (ZHF), non-invasive temperature probe for in- vivo measurement of resting muscle temperature for up to 2 cm below the skin surface. The ZHF probe works by preventing heat loss from the tissue below the probe by actively heating the tissue until no temperature gradient exists across the probe. The skin temperature under the probe is then used as an indicator of the muscle temperature below. Eight subjects sat for 130 min during exposure to 28 degrees C air. Vastus lateralis (lateral thigh) muscle temperature was measured non-invasively using a ZHF probe which covered an invasive multicouple probe (which measured tissue temperature 0.5 cm, 1 cm, 1.5 cm, and 2 cm below the skin) located 15 cm superior to the patella (T (covered)). T (covered) was evaluated against an uncovered control multicouple probe located 20 cm superior to the patella (T (uncovered)). Rectal temperature and lateral thigh skin temperature were also measured. Mean T (uncovered) (based on average temperatures at the 0.5 cm, 1 cm, 1.5 cm, and 2 cm depths) and Mean T (covered) were similar from time 0 min to 60 min. However, when the ZHF was turned on at 70 min, Mean T (covered) increased by 2.11 +/- 0.20 degrees C by 130 min, while T (uncovered) remained stable. The ZHF probe temperature was similar to T (covered) at 1 cm and after time 85 min, significantly higher than T (covered) at the 0.5 cm, 1.5 cm, and 2 cm depths; however from a physiological standpoint, the temperatures between the different depths and the ZHF probe could be considered uniform (< or =0.2 degrees C separation). Rectal and thigh skin temperatures were stable at 36.99 +/- 0.08 degrees C and 32.82 +/- 0.23 degrees C, respectively. In conclusion, the non-invasive ZHF probe temperature was similar to the T (covered) temperatures directly measured up to 2 cm beneath the surface of the thigh, but all T (covered) temperatures were not representative of the true muscle temperature up to 2 cm below the skin because the ZHF probe heated the muscle by 2.11 +/- 0.20 degrees C during its operation.

Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression.

PubMed

Yoon, Sang-Oh; Shin, Sejeong; Lee, Ho-Jae; Chun, Hyo-Kon; Chung, An-Sik

2006-11-01

Matrix metalloproteinase (MMP)-9 plays a key role in tumor invasion. Inhibitors of MMP-9 were screened from Metasequoia glyptostroboides (Dawn redwood) and one potent inhibitor, isoginkgetin, a biflavonoid, was identified. Noncytotoxic levels of isoginkgetin decreased MMP-9 production profoundly, but up-regulated the level of tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of MMP-9, in HT1080 human fibrosarcoma cells. The major mechanism of Ras-dependent MMP-9 production in HT1080 cells was phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor-kappaB (NF-kappaB) activation. Expression of dominant-active H-Ras and p85 (a subunit of PI3K) increased MMP-9 activity, whereas dominant-negative forms of these molecules decreased the level of MMP-9. H-Ras did not increase MMP-9 in the presence of a PI3K inhibitor, LY294002, and a NF-kappaB inhibitor, SN50. Further studies showed that isoginkgetin regulated MMP-9 production via PI3K/Akt/NF-kappaB pathway, as evidenced by the findings that isoginkgetin inhibited activities of both Akt and NF-kappaB. PI3K/Akt is a well-known key pathway for cell invasion, and isoginkgetin inhibited HT1080 tumor cell invasion substantially. Isoginkgetin was also quite effective in inhibiting the activities of Akt and MMP-9 in MDA-MB-231 breast carcinomas and B16F10 melanoma. Moreover, isoginkgetin treatment resulted in marked decrease in invasion of these cells. In summary, PI3K/Akt is a major pathway for MMP-9 expression and isoginkgetin markedly decreased MMP-9 expression and invasion through inhibition of this pathway. This suggests that isoginkgetin could be a potential candidate as a therapeutic agent against tumor invasion.

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells

PubMed Central

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3’UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. PMID:27186275

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells.

PubMed

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3'UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5.

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1.

PubMed

Xu, Dan; Chen, Xiaofeng; He, Quanyong; Luo, Chengqun

2016-01-01

MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3' untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression decreased the tumor growth, while overexpression of NRP1 increased MM growth. In summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential target for the treatment of MM.

Liquid biopsy in non-small cell lung cancer: a key role in the future of personalized medicine?

PubMed

Pi, Can; Zhang, Ming-Feng; Peng, Xiao-Xiao; Zhang, Yi-Chen; Xu, Chong-Rui; Zhou, Qing

2017-12-01

Liquid biopsies, especially the analysis of circulating tumor DNA (ctDNA), as a novel and non-invasive method for the diagnosis and monitoring of non-small cell lung cancer (NSCLC) have already been implemented in clinical settings. The majority of ctDNA is released from apoptotic or necrotic tumor cells, thus reflecting the genetic profile of a tumor. Numerous studies have reported a high concordance in mutation profiles derived from liquid biopsy and tissue biopsy, especially in driver genes. Liquid biopsy could overcome the clonal heterogeneity of tumour biopsy, as it provides a single snapshot of a tumour tissue. Moreover, non-invasiveness is the biggest advantage for liquid biopsy, and the procedure can be repeatedly performed during the treatment for the purpose of monitoring. Therefore, ctDNA could act as a potential complementary method for tissue biopsies in diagnosis, prognostic, treatment response and resistance. Areas covered: This review summarizes the recent advancements in liquid biopsy with a focus on NSCLC, including its applications and technologies associated with assessing ctDNA. The authors conclude the review by discussing the challenges associated with liquid biopsy. Expert commentary: The analysis of ctDNA represents a promising method for liquid biopsy, which will be a novel and potentially complementary method in diagnosis, treatment and prognostic in NSCLC at all stages.

Development of a non-invasive LED based device for adipose tissue thickness measurements in vivo

NASA Astrophysics Data System (ADS)

Volceka, K.; Jakovels, D.; Arina, Z.; Zaharans, J.; Kviesis, E.; Strode, A.; Svampe, E.; Ozolina-Moll, L.; Butnere, M. M.

2012-06-01

There are a number of techniques for body composition assessment in clinics and in field-surveys, but in all cases the applied methods have advantages and disadvantages. High precision imaging methods are available, though expensive and non-portable, however, the methods devised for the mass population, often suffer from the lack of precision. Therefore, the development of a safe, mobile, non-invasive, optical method that would be easy to perform, precise and low-cost, but also would offer an accurate assessment of subcutaneous adipose tissue (SAT) both in lean and in obese persons is required. Thereof, the diffuse optical spectroscopy is advantageous over the aforementioned techniques. A prototype device using an optical method for measurement of the SAT thickness in vivo has been developed. The probe contained multiple LEDs (660nm) distributed at various distances from the photo-detector which allow different light penetration depths into the subcutaneous tissue. The differences of the reflected light intensities were used to create a non-linear model, and the computed values were compared with the corresponding thicknesses of SAT, assessed by B-mode ultrasonography. The results show that with the optical system used in this study, accurate results of different SAT thicknesses can be obtained, and imply a further potential for development of multispectral optical system to observe changes of SAT thickness as well as to determine the percentage of total body fat.

Pre-damage biomass allocation and not invasiveness predicts tolerance to damage in seedlings of woody species in Hawaii.

PubMed

Lurie, Matthew H; Barton, Kasey E; Daehler, Curtis C

2017-12-01

Plant-herbivore interactions have been predicted to play a fundamental role in plant invasions, although support for this assertion from previous research is mixed. While plants may escape from specialist herbivores in their introduced ranges, herbivory from generalists is common. Tolerance traits may allow non-native plants to mitigate the negative consequences of generalist herbivory that they cannot avoid in their introduced range. Here we address whether tolerance to herbivory, quantified as survival and compensatory growth, is associated with plant invasion success in Hawaii and investigate traits that may enhance tolerance in seedlings, the life stage most susceptible to herbivory. In a greenhouse experiment, we measured seedling tolerance to simulated herbivory through mechanical damage (50% leaf removal) of 16 non-native woody plant species differing in invasion status (invasive vs. non-invasive). Seedlings were grown for 2 weeks following damage and analyzed for biomass to determine whether damaged plants could fully compensate for the lost leaf tissue. Over 99% of all seedlings survived defoliation. Although species varied significantly in their levels of compensation, there was no consistent difference between invasive and non-invasive species. Seedlings of 11 species undercompensated and remained substantially smaller than control seedlings 2 weeks after damage; four species were close to compensating, while one species overcompensated. Across species, compensation was positively associated with an increased investment in potential storage reserves, specifically cotyledons and roots, suggesting that these organs provide resources that help seedlings re-grow following damage. Our results add to a growing consensus that pre-damage growth patterns determine tolerance to damage, even in young seedlings which have relatively low biomass. The lack of higher tolerance in highly invasive species may suggest that invaders overcome herbivory barriers to invasion in other ways, such as resistance traits, or that herbivory does not play an important role in the seedling invasion dynamics of these woody species in Hawaii. © 2017 by the Ecological Society of America.

Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

2011-03-01

Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

PubMed

Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent

2011-01-01

BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Characterization of water molecular state in in-vivo thick tissues using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Chung, So Hyun

Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water; however, detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975 nm. The precise NIR peak's shape and position are highly sensitive to water molecular disposition. A bound water index (BWI) was developed that quantifies the spectral shift and shape changes observed in tissue water absorption spectra measured by broadband diffuse optical spectroscopic imaging (DOSI). DOSI quantitatively measures light absorption and scattering spectra in cm-deep tissues and therefore reveals bound water spectral shifts. BWI as a water state index was validated by comparing broadband DOSI to MRI and a conductivity cell using bound water phantoms. Non-invasive BWI measurements of malignant and normal tissues in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p<0.0001) compared to normal tissues. BWI showed potential as a prognostic index based on high correlations with tumor grade and size. An algorithm for absolute temperature measurements in deep tissues was developed based on resolving opposing effects of water vibrational frequency shifts due to macromolecular binding. DOSI measures absolute temperature with a difference of 1.1+/-0.91°C from a thermistor. Deep tissue temperature measured in forearms during cold-stress was consistent with previously reported invasively-measured deep tissue temperature. Finally, the BWI was compared to Apparent Diffusion Coefficient (ADC) of diffusion weighted MRI in 9 breast cancer patients. The BWI and ADC correlated (R=0.8, p=<0.01) and both parameters decreased with increasing bulk water content in cancer tissues. Although BWI and ADC are positively correlated in vivo, BWI appears to be more sensitive to free water in the extracellular matrix while ADC reflects increased tumor cellularity. The relationship between ADC, BWI and bulk water concentration suggests that both parameters have potential for assessing tumor histopathological grade. My results confirm the importance of water as a critical tissue component that can potentially provide unique insight into the molecular pathophysiology of cancer.

MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro

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

Korvala, Johanna, E-mail: johanna.korvala@oulu.fi; Jee, Kowan; Department of Pathology, Haartman Institute, University of Helsinki, Helsinki

Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteinsmore » and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15.« less

High intensity focused ultrasound (HIFU) in tumor therapy.

PubMed

Sequeiros, Roberto Blanco; Joronen, Kirsi; Komar, Gaber; Koskinen, Seppo K

HIFU (high intensity focused ultrasound) is a method in which high-frequency ultrasound is focused on a tissue in order to achieve a thermal effect and the subsequent percutaneously ablation, or tissue modulation. HIFU is non-invasive and results in an immediate tissue destruction effect corresponding to surgery, either percutaneously or through body cavities. HIFU can be utilized in the treatment of both benign and malignant tumors. In neurological diseases, focused HIFU can be used in the treatment of disorders of the basal ganglia.

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

Emin, David, E-mail: emin@unm.edu; Akhtari, Massoud; Ellingson, B. M.

We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

PubMed

Latz, Stefan; Umbach, Tine; Goltz, Diane; Kristiansen, Glen; Müller, Stephan C; Ellinger, Jörg

2016-01-01

Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis. © 2015 S. Karger AG, Basel.

FABP4 suppresses proliferation and invasion of hepatocellular carcinoma cells and predicts a poor prognosis for hepatocellular carcinoma.

PubMed

Zhong, Cheng-Qian; Zhang, Xiu-Ping; Ma, Ning; Zhang, Er-Bin; Li, Jing-Jing; Jiang, Ya-Bo; Gao, Yu-Zhen; Yuan, Yan-Mei; Lan, Shi-Qian; Xie, Dong; Cheng, Shu-Qun

2018-05-07

Adipocyte fatty acid-binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non-small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence-free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p-STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Effects of bone sialoprotein on pancreatic cancer cell growth, invasion and metastasis.

PubMed

Kayed, Hany; Kleeff, Jörg; Keleg, Shereen; Felix, Klaus; Giese, Thomas; Berger, Martin R; Büchler, Markus W; Friess, Helmut

2007-01-08

Bone sialoprotein (BSP) is an acidic glycoprotein that plays an important role in cancer cell growth, migration and invasion. The expression, localization and possible function of BSP in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) were analyzed by QRT-PCR, laser capture microdissection, DNA microarray analysis, immunoblotting, radioimmunoassays and immunohistochemistry as well as cell growth, invasion, scattering, and adhesion assays. BSP mRNA was detected in 40.7% of normal, in 80% of CP and in 86.4% of PDAC samples. The median BSP mRNA levels were 6.1 and 0.9copies/microl cDNA in PDAC and CP tissues, respectively, and zero copies/microl cDNA in normal pancreatic tissues. BSP was weakly present in the cytoplasm of islet cells and ductal cells in 20% of normal pancreatic tissues. BSP was localized in the tubular complexes of both CP and PDAC, as well as in pancreatic cancer cells. Five out of 8 pancreatic cancer cell lines expressed BSP mRNA. Recombinant BSP (rBSP) inhibited Capan-1 and SU8686 pancreatic cancer cell growth, with a maximal effect of -46.4+/-12.0% in Capan-1 cells and -45.7+/-14.5% in SU8686 cells. rBSP decreased the invasion of SU8686 cells by -59.1+/-11.2% and of Capan-1 cells by -13.3+/-3.8% (P<0.05), whereas it did not affect scattering or adhesion of both cell lines. In conclusion, endogenous BSP expression levels in pancreatic cancer cells and low to absent BSP expression in the surrounding stromal tissue elements may indirectly act to enhance the proliferation and invasion of pancreatic cancer cells.

miR-128 modulates chemosensitivity and invasion of prostate cancer cells through targeting ZEB1.

PubMed

Sun, Xianglun; Li, Youkong; Yu, Jie; Pei, Hong; Luo, Pengcheng; Zhang, Jie

2015-05-01

Recent reports strongly suggest the profound role of miRNAs in cancer therapeutic response and progression, including invasion and metastasis. The sensitivity to therapy and invasion is the major obstacle for successful treatment in prostate cancer. We aimed to investigate the regulative effect of miR-128/zinc-finger E-box-binding homeobox 1 axis on prostate cancer cell chemosensitivity and invasion. The miR-128 expression pattern of prostate cancer cell lines and tissues was detected by real-time reverse transcriptase-polymerase chain reaction, while the mRNA and protein expression levels of zinc-finger E-box-binding homeobox 1 were measured by real-time reverse transcriptase-polymerase chain reaction and western blot assay, respectively. Dual-luciferase reporter gene assay was used to find the direct target of miR-128. Furthermore, prostate cancer cells were treated with miR-128 mimic or zinc-finger E-box-binding homeobox 1-siRNA, and then the cells' chemosensitivity and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and transwell assay, respectively. We found miR-128 expression obviously decreased in prostate cancer tissues compared with paired normal tissues. Restored miR-128 expression sensitized prostate cancer cells to cisplatin and inhibited the invasion. Furthermore, there was an inverse expression pattern between miR-128 and zinc-finger E-box-binding homeobox 1 in prostate cancer cells and tissues, and zinc-finger E-box-binding homeobox 1 was identified as a direct target of miR-128 in prostate cancer. Knockdown of zinc-finger E-box-binding homeobox 1 expression efficiently sensitized prostate cancer cells to cisplatin and inhibited the invasion. However, ectopic zinc-finger E-box-binding homeobox 1 expression impaired the effects of miR-128 on chemosensitivity and invasion in prostate cancer cells. miR-128 functions as a potential cancer suppressor in prostate cancer progression and rational therapeutic strategies for prostate cancer would be developed based on miR-128/zinc-finger E-box-binding homeobox 1 axis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Non-invasive quantification of lower limb mechanical alignment in flexion

PubMed Central

Deakin, Angela; Fogg, Quentin A.; Picard, Frederic

2014-01-01

Objective Non-invasive navigation techniques have recently been developed to determine mechanical femorotibial alignment (MFTA) in extension. The primary aim of this study was to evaluate the precision and accuracy of an image-free navigation system with new software designed to provide multiple kinematic measurements of the knee. The secondary aim was to test two types of strap material used to attach optical trackers to the lower limb. Methods Seventy-two registrations were carried out on 6 intact embalmed cadaveric specimens (mean age: 77.8 ± 12 years). A validated fabric strap, bone screws and novel rubber strap were used to secure the passive tracker baseplate for four full experiments with each knee. The MFTA angle was measured under the conditions of no applied stress, valgus stress, and varus stress. These measurements were carried out at full extension and at 30°, 40°, 50° and 60° of flexion. Intraclass correlation coefficients, repeatability coefficients, and limits of agreement (LOA) were used to convey precision and agreement in measuring MFTA with respect to each of the independent variables, i.e., degree of flexion, applied coronal stress, and method of tracker fixation. Based on the current literature, a repeatability coefficient and LOA of ≤3° were deemed acceptable. Results The mean fixed flexion for the 6 specimens was 12.8° (range: 6–20°). The mean repeatability coefficient measuring MFTA in extension with screws or fabric strapping of the baseplate was ≤2°, compared to 2.3° using rubber strapping. When flexing the knee, MFTA measurements taken using screws or fabric straps remained precise (repeatability coefficient ≤3°) throughout the tested range of flexion (12.8–60°); however, using rubber straps, the repeatability coefficient was >3° beyond 50° flexion. In general, applying a varus/valgus stress while measuring MFTA decreased precision beyond 40° flexion. Using fabric strapping, excellent repeatability (coefficient ≤2°) was observed until 40° flexion; however, beyond 50° flexion, the repeatability coefficient was >3°. As was the case with precision, agreement between the invasive and non-invasive systems was satisfactory in extension and worsened with flexion. Mean limits of agreement between the invasive and non-invasive system using fabric strapping to assess MFTA were 3° (range: 2.3–3.8°) with no stress applied and 3.9° (range: 2.8–5.2°) with varus and valgus stress. Using rubber strapping, the corresponding values were 4.4° (range: 2.8–8.5°) with no stress applied, 5.5° (range: 3.3–9.0°) with varus stress, and 5.6° (range: 3.3–11.9°) with valgus stress. Discussion Acceptable precision and accuracy may be possible when measuring knee kinematics in early flexion using a non-invasive system; however, we do not believe passive trackers should be mounted with rubber strapping such as was used in this study. Flexing the knee appears to decrease the precision and accuracy of the system. The functions of this new software using image-free navigation technology have many potential clinical applications, including assessment of bony and soft tissue deformity, pre-operative planning, and post-operative evaluation, as well as in further pure research comparing kinematics of the normal and pathological knee. PMID:24856249

Single shot white light interference microscopy with colour fringe analysis for quantitative phase imaging of biological cells

NASA Astrophysics Data System (ADS)

Srivastava, Vishal; Mehta, D. S.

2013-02-01

To quantitatively obtain the phase map of Onion and human red blood cell (RBC) from white light interferogram we used Hilbert transform color fringe analysis technique. The three Red, Blue and Green color components are decomposed from single white light interferogram and Refractive index profile for Red, Blue and Green colour were computed in a completely non-invasive manner for Onion and human RBC. The present technique might be useful for non-invasive determination of the refractive index variation within cells and tissues and morphological features of sample with ease of operation and low cost.

MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.

PubMed

Lee, Hae Kyung; Bier, Ariel; Cazacu, Simona; Finniss, Susan; Xiang, Cunli; Twito, Hodaya; Poisson, Laila M; Mikkelsen, Tom; Slavin, Shimon; Jacoby, Elad; Yalon, Michal; Toren, Amos; Rempel, Sandra A; Brodie, Chaya

2013-01-01

Glioblastomas (GBM), the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs) compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF) as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3'-UTR fused to luciferase. Overexpression of a CTGF plasmid lacking the 3'-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors.

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

PubMed Central

2014-01-01

Background KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. Methods We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. Results KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Conclusions Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer. PMID:24628760

Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect

PubMed Central

Solinas, Marta; Massi, Paola; Cinquina, Valentina; Valenti, Marta; Bolognini, Daniele; Gariboldi, Marzia; Monti, Elena; Rubino, Tiziana; Parolaro, Daniela

2013-01-01

In the present study, we found that CBD inhibited U87-MG and T98G cell proliferation and invasiveness in vitro and caused a decrease in the expression of a set of proteins specifically involved in growth, invasion and angiogenesis. In addition, CBD treatment caused a dose-related down-regulation of ERK and Akt prosurvival signaling pathways in U87-MG and T98G cells and decreased hypoxia inducible factor HIF-1α expression in U87-MG cells. Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways. As CBD is a non-psychoactive phytocannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anti-cancer drug in the management of gliomas. PMID:24204703

Non invasive radiofrequency diagnostics of cancer. The Bioscanner — Trimprob technology and clinical applications

NASA Astrophysics Data System (ADS)

Vedruccio, Clarbruno; Ricci Vedruccio, Carla

2011-12-01

A new paper by Pokorny, Vedruccio, Cifra, Kucera, titled Cancer physics: Diagnostics based on damped cellular elasto-electrical vibrations in microtubules, recently available on Eur. Biophys. J., discloses the mechanism of active grown cancer tissues interaction with a Non- Linear Resonance Interaction (NLRI) Bioscanner Trimprob diagnostic device that is certified and ready to be used to investigate suspected cases of disease and cancer. This technology spreads early capabilities of cancer detection by means of low level radiofrequency oscillations in UHF band. The system is based on an unique and extremely innovative non- linear radiofrequency oscillator working on 462-465 MHz plus the harmonics. The diseased tissues suspected of cancer, are irradiated by means of a handy probe near field emission, while a spectrum analyzer placed in the far field detects by means of a small antenna, the oscillator interaction within the tissues. The Bioscanner is characterized by a high dynamic range, in the order of 30 or more decibel, and is useful for detection of small cancer agglomerates, if used by a well trained operator. At the resonance, the free running oscillator locks-in on the specific interaction frequency, in a sharp frequency window centered on 462 MHz; the resulting effect is evidenced by a deep decrease of the 462 MHz spectral line propagation in the far field around the oscillator probe. The NLRI provides a selective characterization, like a sort of a electronic biopsy response of biologic tissues in support of modern imaging diagnostics. Further to existing literature describing methods for cancer detections by means of electromagnetic fields this paper shows this innovative in vivo medical diagnostic equipment and some clinical applications.

SRC family kinase (SFK) inhibition reduces rhabdomyosarcoma cell growth in vitro and in vivo and triggers p38 MAP kinase-mediated differentiation

PubMed Central

Casini, Nadia; Forte, Iris Maria; Mastrogiovanni, Gianmarco; Pentimalli, Francesca; Angelucci, Adriano; Festuccia, Claudio; Tomei, Valentina; Ceccherini, Elisa; Di Marzo, Domenico; Schenone, Silvia; Botta, Maurizio; Giordano, Antonio; Indovina, Paola

2015-01-01

Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. Overall, our findings suggest that SFK inhibition, besides reducing RMS cell growth and invasive potential, could also represent a differentiation therapeutic strategy for RMS. PMID:25762618

MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells.

PubMed

Liu, Shikai; Song, Lili; Zeng, Saitian; Zhang, Liang

2016-01-01

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1) is a large, infrequently spliced non-coding RNA aberrantly expressed in cervical cancer. But the molecular mechanisms of its oncogenic role are still not quite clear. The present study explored whether there is a competing endogenous RNAs (ceRNAs) mechanism involved in the oncogenic effect of MALAT1. MALAT1 expression was firstly verified in high-risk human papillomavirus (HR-HPV)-positive tumor tissues and cell lines. Its regulation over miR-124 and the downstream target of miR-124 in regulation of growth, invasion, and apoptosis of the cancer cells are also studied. Findings of this study confirmed higher MALAT1 expression in HR-HPV (+) cervical cancer. Knockdown of endogenous MALAT1 significantly reduced cell growth rate and invasion and increased cell apoptosis of Hela and siHa cells. Besides, knockdown of MALAT1 increased the expression of miRNA-124, while ectopic expression of miR-124 decreased MALAT1 expression. In addition, we also verified a direct interaction between miR-124 and 3'UTR of GRB2. MALAT1 can indirectly modulate GRB2 expression via competing miR-124. Knockdown of GRB2 reduced cell invasion and increased cell apoptosis. In conclusion, MALAT1 can promote HR-HPV (+) cancer cell growth and invasion at least partially through the MALAT1-miR-124-RBG2 axis. This finding might provide some useful evidence about the lncRNA interaction regulatory network in tumorigenesis cervical cancer.

Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI).

PubMed

Han, Yang; Wang, Shutao; Hibshoosh, Hanina; Taback, Bret; Konofagou, Elisa

2016-05-09

High-intensity focused ultrasound (HIFU) is a noninvasive technique used in the treatment of early-stage breast cancer and benign tumors. To facilitate its translation to the clinic, there is a need for a simple, cost-effective device that can reliably monitor HIFU treatment. We have developed harmonic motion imaging (HMI), which can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely harmonic motion imaging for focused ultrasound (HMIFU). The overall objective of this study was to develop an all ultrasound-based system for real-time imaging and ablation monitoring in the human breast in vivo. HMI was performed in 36 specimens (19 normal, 15 invasive ductal carcinomas, and 2 fibroadenomas) immediately after surgical removal. The specimens were securely embedded in a tissue-mimicking agar gel matrix and submerged in degassed phosphate-buffered saline to mimic in vivo environment. The HMI setup consisted of a HIFU transducer confocally aligned with an imaging transducer to induce an oscillatory radiation force and estimate the resulting displacement. 3D HMI displacement maps were reconstructed to represent the relative tissue stiffness in 3D. The average peak-to-peak displacement was found to be significantly different (p = 0.003) between normal breast tissue and invasive ductal carcinoma. There were also significant differences before and after HMIFU ablation in both the normal (53.84 % decrease) and invasive ductal carcinoma (44.69 % decrease) specimens. HMI can be used to map and differentiate relative stiffness in postsurgical normal and pathological breast tissues. HMIFU can also successfully monitor thermal ablations in normal and pathological human breast specimens. This HMI technique may lead to a new clinical tool for breast tumor imaging and HIFU treatment monitoring.

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6.

PubMed

Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

2016-07-15

To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

PubMed Central

Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

2016-01-01

AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection. PMID:27559432

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer

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

Jiang, Chen-Yi; Gao, Yuan; Wang, Xing-Jie

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined bymore » real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer. - Highlights: • LncRNA lnc-MX1-1 is up-regulated in prostate cancer. • Overexpression of lnc-MX1-1 is correlated with poor prostate cancer clinical features. • Knockdown of lnc-MX1-1 reduces proliferation and invasiveness of prostate cancer cells.« less

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

PubMed Central

Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

2015-01-01

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

Transcriptome Profiling of a Multiple Recurrent Muscle-Invasive Urothelial Carcinoma of the Bladder by Deep Sequencing

PubMed Central

Zhang, Shufang; Liu, Yanxuan; Liu, Zhenxiang; Zhang, Chong; Cao, Hui; Ye, Yongqing; Wang, Shunlan; Zhang, Ying'ai; Xiao, Sifang; Yang, Peng; Li, Jindong; Bai, Zhiming

2014-01-01

Urothelial carcinoma of the bladder (UCB) is one of the commonly diagnosed cancers in the world. The UCB has the highest rate of recurrence of any malignancy. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of UCB recurrence and is a key step to discovering biomarkers for diagnosis and therapeutic targets. Compared with microarray technology, which is commonly used to identify expression level changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing. In this study, we performed high-throughput transcriptome sequencing at ∼50× coverage on a recurrent muscle-invasive cisplatin-resistance UCB tissue and the adjacent non-tumor tissue. The results revealed cancer-specific differentially expressed genes between the tumor and non-tumor tissue enriched in the cell adhesion molecules, focal adhesion and ECM-receptor interaction pathway. Five dysregulated genes, including CDH1, VEGFA, PTPRF, CLDN7, and MMP2 were confirmed by Real time qPCR in the sequencing samples and the additional eleven samples. Our data revealed that more than three hundred genes showed differential splicing patterns between tumor tissue and non-tumor tissue. Among these genes, we filtered 24 cancer-associated alternative splicing genes with differential exon usage. The findings from RNA-Seq were validated by Real time qPCR for CD44, PDGFA, NUMB, and LPHN2. This study provides a comprehensive survey of the UCB transcriptome, which provides better insight into the complexity of regulatory changes during recurrence and metastasis. PMID:24622401

A non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in protected marine mammals: PBPK modeling in harbor porpoises

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

Weijs, Liesbeth, E-mail: liesbeth.weijs@ua.ac.be; Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk; Covaci, Adrian

2011-10-15

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically, these models provide a new, non-destructive tool that enables the integration of biomonitoring activities and in vitro studies. The goals of the present study were firstly to develop PBPK models for several environmental relevant PCB congeners in harbor porpoises (Phocoena phocoena), a species that is sensitive to pollution because of its limited metabolic capacity for pollutant transformation. These models were tested using tissue data of porpoises from the Black Sea. Secondly, the predictive powermore » of the models was investigated for time trends in the PCB concentrations in North Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess metabolic capacities of harbor porpoises for the investigated PCBs. In general, results show that parameter values from other species (rodents, humans) are not always suitable in marine mammal models, most probably due to differences in physiology and exposure. The PCB 149 levels decrease the fastest in male harbor porpoises from the North Sea in a time period of 18 years, whereas the PCB 101 levels decrease the slowest. According to the models, metabolic breakdown of PCB 118 is probably of lesser importance compared to other elimination pathways. For PCB 101 and 149 however, the presence of their metabolites can be attributed to bioaccumulation of metabolites from the prey and to metabolic breakdown of the parent compounds in the harbor porpoises. - Highlights: > PBPK modeling was used to study the kinetics of several PCBs in a marine mammal. > Harbor porpoises are sensitive to pollution and therefore ideal model organisms. > Black Sea data were used for parameterization. > North Sea data for assessing temporal trends (1990-2008). > PBPK modeling is a non-invasive and non-destructive tool.« less

The role of invasive and non-invasive procedures in diagnosing fever of unknown origin.

PubMed

Mete, Bilgul; Vanli, Ersin; Yemisen, Mucahit; Balkan, Ilker Inanc; Dagtekin, Hilal; Ozaras, Resat; Saltoglu, Nese; Mert, Ali; Ozturk, Recep; Tabak, Fehmi

2012-01-01

The etiology of fever of unknown origin has changed because of the recent advances in and widespread use of invasive and non-invasive diagnostic tools. However, undiagnosed patients still constitute a significant number. To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin. One hundred patients who were hospitalized between June 2001 and 2009 with a fever of unknown origin were included in this study. Clinical and laboratory data were collected from the patients' medical records retrospectively. Fifty three percent of the patients were male, with a mean age of 45 years. The etiology of fever was determined to be infectious diseases in 26, collagen vascular diseases in 38, neoplastic diseases in 14, miscellaneous in 2 and undiagnosed in 20 patients. When the etiologic distribution was analyzed over time, it was noted that the rate of infectious diseases decreased, whereas the rate of rheumatological and undiagnosed diseases relatively increased because of the advances in imaging and microbiological studies. Seventy patients had a definitive diagnosis, whereas 10 patients had a possible diagnosis. The diagnoses were established based on clinical features and non-invasive tests for 61% of the patients and diagnostic benefit was obtained for 49% of the patients undergoing invasive tests. Biopsy procedures contributed a rate of 42% to diagnoses in patients who received biopsies. Clinical features (such as detailed medical history-taking and physical examination) may contribute to diagnoses, particularly in cases of collagen vascular diseases. Imaging studies exhibit certain pathologies that guide invasive studies. Biopsy procedures contribute greatly to diagnoses, particularly for malignancies and infectious diseases that are not diagnosed by non-invasive procedures.

Advances in using MRI probes and sensors for in vivo cell tracking as applied to regenerative medicine

PubMed Central

Srivastava, Amit K.; Kadayakkara, Deepak K.; Bar-Shir, Amnon; Gilad, Assaf A.; McMahon, Michael T.; Bulte, Jeff W. M.

2015-01-01

The field of molecular and cellular imaging allows molecules and cells to be visualized in vivo non-invasively. It has uses not only as a research tool but in clinical settings as well, for example in monitoring cell-based regenerative therapies, in which cells are transplanted to replace degenerating or damaged tissues, or to restore a physiological function. The success of such cell-based therapies depends on several critical issues, including the route and accuracy of cell transplantation, the fate of cells after transplantation, and the interaction of engrafted cells with the host microenvironment. To assess these issues, it is necessary to monitor transplanted cells non-invasively in real-time. Magnetic resonance imaging (MRI) is a tool uniquely suited to this task, given its ability to image deep inside tissue with high temporal resolution and sensitivity. Extraordinary efforts have recently been made to improve cellular MRI as applied to regenerative medicine, by developing more advanced contrast agents for use as probes and sensors. These advances enable the non-invasive monitoring of cell fate and, more recently, that of the different cellular functions of living cells, such as their enzymatic activity and gene expression, as well as their time point of cell death. We present here a review of recent advancements in the development of these probes and sensors, and of their functioning, applications and limitations. PMID:26035841

Skin autofluorescence is associated with renal function and cardiovascular diseases in pre-dialysis chronic kidney disease patients.

PubMed

Tanaka, Kenichi; Tani, Yoshihiro; Asai, Jun; Nemoto, Fumihiko; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Katoh, Tetsuo; Miyata, Toshio; Watanabe, Tsuyoshi

2011-01-01

Tissue accumulation of advanced glycation end-products (AGE) is thought to be a contributing factor to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has shown associations with CVD in haemodialysis patients. The present study aimed to evaluate relationships of skin autofluorescence to renal function as well as CVD in pre-dialysis patients with chronic kidney disease (CKD). Subjects in this cross-sectional analysis comprised 304 pre-dialysis CKD patients [median age, 62.0 years; median estimated glomerular filtration rate (eGFR), 54.3 mL/min/1.73 m(2); diabetes, n = 81 (26.6%)]. AGE accumulation in skin was assessed by skin autofluorescence using an autofluorescence reader. Relationships between skin autofluorescence, eGFR, CVD history and other parameters were evaluated. Skin autofluorescence correlated negatively with eGFR (r = -0.42, P < 0.01) and increased as CKD stage advanced. Multiple regression analysis revealed significant correlations of skin autofluorescence with age, presence of diabetes, eGFR and CVD history in CKD patients (R(2) = 30%). Age, male gender, smoking history, skin autofluorescence and eGFR were significantly correlated with CVD history, and multiple logistic regression analysis identified age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.03-1.15; P < 0.01], history of smoking (OR, 6.50; 95%CI, 1.94-21.83; P < 0.01) and skin autofluorescence (OR, 3.74; 95%CI, 1.54-9.24; P < 0.01) as independent factors. Tissue AGE accumulation measured as skin autofluorescence increased as GFR decreased and was related to CVD history in CKD patients. Non-invasive autofluorescence readers may provide potential markers for clinical risk assessment in pre-dialysis CKD patients.

Non-immunologic enhancement and regression of self-healing squamous cell carcinoma (keratoacanthoma)--ground substance and inflammation.

PubMed

Stone, O J

1988-06-01

Keratoacanthomas have many characteristics of squamous cell carcinoma and in the past were interpreted as squamous cell carcinomas. It is now known that these lesions spontaneously resolve if left untreated. In man the lesions occur on sunlight damaged areas or areas exposed to tar. Many of the experimental cancers of animals produced by topical carcinogens are keratoacanthomas. Ultraviolet light and tar are known to damage fibroblast and ground substance viscosity. It has recently been proposed that anything that decreases ground substance viscosity would encourage the spread of tumors, by weakening tissue resistance. The rapidly growing keratoacanthoma produces invasive pressure and moves into deeper, less damaged dermis. An inflammatory reaction occurs in the depth of the lesion and a very characteristic granulocytic response occurs. Granulocytes release connective tissue active peptides which stimulate fibroblast and ground substance formation. The fibroblast proliferation is followed by fibrosis and the shrinking and disappearance of the tumor. The characteristic pustule that spurts granulocytes into the depth of the tumor has been experimentally blocked by hyaluronidase and other substances that damage ground substance viscosity. Edema is essential to produce this inflammatory reaction. However, this inflammatory phenomenon occurs vigorously in keratoacanthoma. It is proposed that a keratoacanthoma is a tumor that does not produce hyaluronidase or other substances that decrease ground substance viscosity. It is a deviant cell that can only move through areas of decreased ground substance viscosity. When it reaches tissues of normal viscosity edema and an inflammatory reaction occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Up-regulated EMMPRIN/CD147 protein expression might play a role in colorectal carcinogenesis and its subsequent progression without an alteration of its glycosylation and mRNA level.

PubMed

Zheng, Hua-chuan; Wang, Wei; Xu, Xiao-yan; Xia, Pu; Yu, Miao; Sugiyama, Toshiro; Takano, Yasuo

2011-04-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of colorectal carcinomas (CRC). EMMPRIN expression was examined on tissue microarray containing colorectal carcinomas, adenoma and non-neoplastic mucosa (NNM) by immunohistochemistry and in situ hybridization (ISH). Colorectal carcinoma cell lines (DLD-1, HCT-15, SW480 and WiDr) and tissues were studied for EMMPRIN expression by Western blot or RT-PCR, followed by sequencing. All carcinoma cell lines showed EMMPRIN expression at both mRNA and protein levels. Two synonymous mutations were found in carcinoma cell lines at codon109 (GCT → GCC: Ala) or 179 (GAT → GAC: Asp). Frozen CRC tissues displayed higher EMMPRIN expression than paired NNM (P < 0.05). EMMPRIN expression was immunohistochemically stronger in colorectal high-grade adenoma, adenocarcinoma and metastatic carcinoma than non-neoplastic superficial epithelium and low-grade adenoma (P < 0.05). In contrast, its mRNA level was similar from colorectal NNM, adenoma to adenocarcinoma by ISH, in line with the findings of RT-PCR (P > 0.05). Immunohistochemically, EMMPRIN expression was positively correlated with tumor size, depth of invasion, vascular or lymphatic invasion, grade of infiltration (INF), ki-67 and VEGF expression of CRCs (P < 0.05). Among them, depth of invasion was an independent associated factor for EMMPRIN expression in CRCs (P < 0.05). Up-regulated EMMPRIN protein expression might contribute to colorectal carcinogenesis without the alteration of its glycosylation and mRNA level. Aberrant EMMPRIN protein expression might promote growth or invasion of CRCs possibly through increased ki-67 expression and inducible angiogenesis via up-regulating VEGF expression.

Augmentation of the In Vivo Elastic Properties Measurement System to Include Bulk Properties

DTIC Science & Technology

2015-09-30

stranded animals. OBJECTIVES The primary objective of this project is to develop an ultrasound -based system for non-invasive determination of in...wherein ultrasound is used to both generate and observe low frequency vibration in soft tissues. While current methods have been successfully applied...pattern. A second ultrasonic transducer monitors the tissue displacement along the ultrasound beam axis, and supports an enhanced embodiment of an

In Vivo, Non-Invasive Characterization of Human Bone by Hybrid Broadband (600-1200 nm) Diffuse Optical and Correlation Spectroscopies.

PubMed

Konugolu Venkata Sekar, Sanathana; Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut

2016-01-01

Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600-1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care.

Micelles and Nanoparticles for Ultrasonic Drug and Gene Delivery

PubMed Central

Husseini, Ghaleb A.; Pitt, William G.

2008-01-01

Drug delivery research employing micelles and nanoparticles has expanded in recent years. Of particular interest is the use of these nanovehicles that deliver high concentrations of cytotoxic drugs to diseased tissues selectively, thus reducing the agent’s side effects on the rest of the body. Ultrasound, traditionally used in diagnostic medicine, is finding a place in drug delivery in connection with these nanoparticles. In addition to their non-invasive nature and the fact that they can be focused on targeted tissues, acoustic waves have been credited with releasing pharmacological agents from nanocarriers, as well as rendering cell membranes more permeable. In this article, we summarize new technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery. Ultrasonic drug delivery from micelles usually employs polyether block copolymers, and has been found effective in vivo for treating tumors. Ultrasound releases drug from micelles, most probably via shear stress and shock waves from collapse of cavitation bubbles. Liquid emulsions and solid nanoparticles are used with ultrasound to deliver genes in vitro and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nano-carriers has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive means. PMID:18486269

In Vivo, Non-Invasive Characterization of Human Bone by Hybrid Broadband (600-1200 nm) Diffuse Optical and Correlation Spectroscopies

PubMed Central

Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut

2016-01-01

Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600–1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care. PMID:27997565

The expression of MACC1 and its role in the proliferation and apoptosis of salivary adenoid cystic carcinoma.

PubMed

Li, Haifeng; Liao, Xiaoying; Liu, Yeqing; Shen, Zhuojian; Gan, Xiangfeng; Li, Haigang; Huang, Zhiquan

2015-11-01

The objective of this study was to investigate the relationship between metastasis-associated in colon cancer-1 and patient clinical characteristics. We also examined the role of metastasis-associated in colon cancer-1 in the proliferation and apoptosis in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 expression was analysed in 65 paraffin-embedded tissue specimens of salivary adenoid cystic carcinoma and 25 adjacent non-cancerous tissues by immunohistochemistry (IHC). We used RNA interference technology to silence metastasis-associated in colon cancer-1 expression in ACCM cells. Cell Counting Kit-8 tests, transwell experiments and flow cytometry were used to test the proliferation, cisplatin resistance, migration, invasion and apoptosis of ACCM cells. Metastasis-associated in colon cancer-1 nuclear and cytoplasmic expression in salivary adenoid cystic carcinoma tissue was higher than in the adjacent normal salivary tissue. The expression level was closely associated with tumour histological grading, perineural invasion and surrounding tumour invasion. The downregulation of metastasis-associated in colon cancer-1 expression inhibited proliferation and induced apoptosis in ACCM cells. The knock-down of metastasis-associated in colon cancer-1 expression had no effect on migration, invasion and chemoresistance. Metastasis-associated in colon cancer-1 may have an important role in tumour development in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 is a potential biomarker for adenoid cystic carcinoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decreased Expression of EHD2 Promotes Tumor Metastasis and Indicates Poor Prognosis in Hepatocellular Carcinoma.

PubMed

Liu, Jinxia; Ni, Wenkai; Qu, Lishuai; Cui, Xiaopeng; Lin, Zhipeng; Liu, Qingqing; Zhou, Huiling; Ni, Runzhou

2016-09-01

Metastasis remains the most common cause of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Understanding molecular mechanisms that regulate metastasis process is crucial for improving treatment of hepatocellular carcinoma. In this article, we examined whether Eps15 homology domain-containing 2 (EHD2) played a critical role in hepatocellular carcinoma metastasis and explored the possible mechanism. EHD2 and E-cadherin expression levels in hepatocellular carcinoma patients were examined using Western blotting and immunohistochemistry. The cell migration and invasion were evaluated by wound-healing assay and trans-well assay. Epithelial-mesenchymal transition was analyzed by immunofluorescence, and the vital markers were detected by Western blotting. The correlation of EHD2 and E-cadherin was confirmed by co-immunoprecipitation. EHD2 expression, along with the epithelial marker E-cadherin, was markedly reduced in tumor tissues than in adjacent noncancerous tissues. Moreover, EHD2 was positively correlated with E-cadherin, histological grade, tumor metastasis, and microvascular invasion. Kaplan-Meier survival analysis showed that hepatocellular carcinoma patients with decreased EHD2 expression had shorter overall survival times than those with higher EHD2 expression. Knockdown of EHD2 induced an increase in cell invasion and changes characteristic of epithelial-mesenchymal transition, while overexpression of EHD2 inhibited these processes. Molecular data indicated that EHD2 inhibited migration and invasion of hepatocellular carcinoma probably by interacting with E-cadherin and it might be an independent, significant risk factor for survival after curative resection.

SIRT2 Promotes the Migration and Invasion of Gastric Cancer through RAS/ERK/JNK/MMP-9 Pathway by Increasing PEPCK1-Related Metabolism.

PubMed

Li, Yang; Zhang, Mingming; Dorfman, Robert G; Pan, Yida; Tang, Dehua; Xu, Lei; Zhao, Zhenguo; Zhou, Qian; Zhou, Lixing; Wang, Yuming; Yin, Yuyao; Shen, Shanshan; Kong, Bo; Friess, Helmut; Zhao, Shimin; Wang, Lei; Zou, Xiaoping

2018-06-17

Metastasis is the most important feature of gastric cancer (GC) and the most widely recognized reason for GC-related deaths. Unfortunately, the underlying mechanism behind this metastasis remains unknown. Mounting evidence suggests the dynamic regulatory role of sirtuin2 (SIRT2), a histone deacetylase (HDAC), in cell migration and invasion. The present study aims to evaluate the biological function of SIRT2 in GC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in GC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 overexpression marginally promoted proliferation in GC cell lines, SIRT2 knockdown or treatment with SirReal2 decreased the migration and invasion of GC cells. We demonstrated both in vitro and in vivo that SirReal2 could inhibit the deacetylation activity of SIRT2 and its downstream target PEPCK1, which is related to mitochondrial metabolism and RAS/ERK/JNK/MMP-9 pathway. Taken together, these results demonstrate for the first time that SirReal2 selectively targets SIRT2 and decreases migration as well as invasion in human GC cells. SirReal2 therefore shows promise as a new drug candidate for GC therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Micro/nanostructured surface modification using femtosecond laser pulses on minimally invasive electrosurgical devices.

PubMed

Lin, Chia-Cheng; Lin, Hao-Jan; Lin, Yun-Ho; Sugiatno, Erwan; Ruslin, Muhammad; Su, Chen-Yao; Ou, Keng-Liang; Cheng, Han-Yi

2017-05-01

The purpose of the present study was to examine thermal damage and a sticking problem in the tissue after the use of a minimally invasive electrosurgical device with a nanostructured surface treatment that uses a femtosecond laser pulse (FLP) technique. To safely use an electrosurgical device in clinical surgery, it is important to decrease thermal damage to surrounding tissues. The surface characteristics and morphology of the FLP layer were evaluated using optical microscopy, scanning electron microscopy, and transmission electron microscopy; element analysis was performed using energy-dispersive X-ray spectroscopy, grazing incidence X-ray diffraction, and X-ray photoelectron spectroscopy. In the animal model, monopolar electrosurgical devices were used to create lesions in the legs of 30 adult rats. Animals were sacrificed for investigations at 0, 3, 7, 14, and 28 days postoperatively. Results indicated that the thermal damage and sticking situations were reduced significantly when a minimally invasive electrosurgical instrument with an FLP layer was used. Temperatures decreased while film thickness increased. Thermographic data revealed that surgical temperatures in an animal model were significantly lower in the FLP electrosurgical device compared with that in the untreated one. Furthermore, the FLP device created a relatively small area of thermal damage. As already mentioned, the biomedical nanostructured layer reduced thermal damage and promoted the antisticking property with the use of a minimally invasive electrosurgical device. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 865-873, 2017. © 2016 Wiley Periodicals, Inc.

[Current radionuclear methods in the diagnosis of regional myocardial circulation disorders].

PubMed

Felix, R; Winkler, C

1977-01-29

Among nuclear medical diagnostic procedures a distinction can be made between non-invasive and invasive methods. The non-invasive methods serve either to image the still viable myocardium ("cold spot" technique) or for direct visualization of recently infarcted myocardial tissue ("hot spot" technique). These methods have the advantage of simple handling and good reproducibility. Side effects and risks are thus far unknown. Improvement of local dissolution should be aimed at in the future and wound greatly increase diagnostic and topographic security. The invasive procedures always require catheterization of the coronary arteries. This is the reason why they can be performed only with coronary arteriography. The Xenon "wash out" technique permits, with some restrictions, quantitative measurement of the regional flow rate. The "inflow technique" permits determination of perfusion distribution. The possibilities of the "double-radionuclide" scintigramm are discussed. For measurement of activity distribution, sationary detectors are generally preferred. In the case of the time-activity curves with the Xenon "wash out" technique, single detectors offer certain advantages.

Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

PubMed Central

Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

2014-01-01

Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

Towards automated early cancer detection: Non-invasive, fluorescence-based approaches for quantitative assessment of cells and tissue to identify pre-cancers

NASA Astrophysics Data System (ADS)

Levitt, Jonathan Michael

Cancer is the second leading cause of death globally, second only to heart disease. As in many diseases, patient survival is directly related to how early lesions are detected. Using conventional screening methods, the early changes associated with cancer, which occur on the microscopic scale, can easily go overlooked. Due to the inherent drawbacks of conventional techniques we present non-invasive, optically based methods to acquire high resolution images from live samples and assess cellular function associated with the onset of disease. Specifically, we acquired fluorescence images from NADH and FAD to quantify morphology and metabolic activity. We first conducted studies to monitor monolayers of keratinocytes in response to apoptosis which has been shown to be disrupted during cancer progression. We found that as keratinocytes undergo apoptosis there are populations of mitochondria that exhibit a higher metabolic activity that become progressively confined to a gradually smaller perinuclear region. To further assess the changes associated with early cancer growth we developed automated methods to rapidly quantify fluorescence images and extract morphological and metabolic information from life tissue. In this study, we simultaneously quantified mitochondrial organization, metabolic activity, nuclear size distribution, and the localization of the structural protein keratin, to differentiate between normal and pre-cancerous engineered tissues. We found the degree mitochondrial organization, as determined from the fractal derived Hurst parameter, was well correlated to level of cellular differentiation. We also found that the metabolic activity in the pre-cancerous cells was greater and more consistent throughout tissue depths in comparison to normal tissue. Keratin localization, also quantified from the fluorescence images, we found it to be confined to the uppermost layers of normal tissue while it was more evenly distributed in the precancerous tissues. To allow for evaluation of the early cancerous changes in vivo, we developed video-rate confocal reflectance/multi-photon fluorescence microscope as a clinical prototype. This device was specifically designed to rapidly acquire and assess non-invasively acquire fluorescence images using the automated methods we have developed. We have demonstrated the ability of this microscope to simultaneously acquire fluorescence, confocal reflectance, and second-harmonic generation images as well as assess blood flow in vivo.

Overexpression of ZDHHC14 promotes migration and invasion of scirrhous type gastric cancer.

PubMed

Oo, Htoo Zarni; Sentani, Kazuhiro; Sakamoto, Naoya; Anami, Katsuhiro; Naito, Yutaka; Uraoka, Naohiro; Oshima, Takashi; Yanagihara, Kazuyoshi; Oue, Naohide; Yasui, Wataru

2014-07-01

Scirrhous type gastric cancer is highly aggressive and has a poorer prognosis than many other types of gastric carcinoma, due to its characteristic rapid cancer cell infiltration and proliferation, extensive stromal fibrosis, and frequent peritoneal dissemination. The aim of the present study was to identify novel prognostic markers or therapeutic targets for scirrhous type gastric cancer. We reviewed a list of genes with upregulated expression in scirrhous type gastric cancer and compared their expression with that in normal stomach from our previous Escherichia coli (E. coli) ampicillin secretion-trap (CAST) analysis. We focused on the ZDHHC14 gene, which encodes zinc finger, DHHC-type containing 14 protein. qRT-PCR analysis of ZDHHC14 in 41 gastric cancer cases revealed that compared to mRNA levels in normal non-neoplastic gastric mucosa, ZDHHC14 mRNA was overexpressed in 27% of gastric cancer tissue samples. The overexpression of ZDHHC14 was significantly associated with depth of tumor invasion, undifferentiated histology and scirrhous pattern. The invasiveness of ZDHHC14-knockdown HSC-44PE and 44As3 gastric cancer cells was decreased in comparison with that of the negative control siRNA-transfected cells, together with downregulation of MMP-17 mRNA. Integrins α5 and β1 were also downregulated in ZDHHC14-knockdown 44As3 cells. Forced expression of ZDHHC14 activated gastric cancer cell migration and invasion in vitro. These results indicate that ZDHHC14 is involved in tumor progression in patients with scirrhous type gastric cancer.

Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

PubMed Central

Valero-Cabre, Antoni; Wattiez, Nicolas; Monfort, Morgane; François, Chantal; Rivaud-Péchoux, Sophie; Gaymard, Bertrand; Pouget, Pierre

2012-01-01

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes. PMID:22701691

Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway.

PubMed

He, Yin-Yan; Cai, Bin; Yang, Yi-Xia; Liu, Xue-Lian; Wan, Xiao-Ping

2009-06-01

The regulatory mechanism of endometrial carcinoma and the signal transduction pathways involved in hormone action are poorly defined. It has become apparent that the G protein-coupled receptor (GPR) 30 mediates the non-genomic signaling of 17beta-estradiol (E2). Here we show that GPR30 is highly expressed in endometrial cancer tissues and cancer cell lines and positively regulates cell proliferation and invasion. GPR30 expression was detected in 50 human endometrial carcinomas. The transcription level of GPR30 was significantly higher in the tissue of endometrial carcinoma than in normal endometrium (P < 0.05). Immunohistochemical assays revealed that the positive expression rate of GPR30 protein in endometrial carcinoma tissue (35/50, 70%) was statistically higher than in normal endometrium tissue (8/30, 26.67%) (chi2 = 14.16, P = 0.0002). GPR30 overexpression was correlated with high-grade endometrial carcinoma. GPR30 expression was also found in two human endometrial cancer cell lines: RL95-2 (estrogen receptor positive) and KLE (estrogen receptor negative). The roles of GPR30 in proliferative and invasive responses to E2 and G1, a non-steroidal GPR30-specific agonist, in RL95-2 and KLE cell lines were then explored. We showed that E2 and G1 could initiate the MAPK/ERK mitogen-activated protein kinase pathway in both cell lines. What's more, E2 and G1 promoted KLE and RL95-2 proliferation and stimulated matrix metalloproteinase production and activity via the GPR30-mediated MEK/ERK mitogen-activated protein kinase pathway, as well as increased interleukin-6 secretion. These findings suggest that GPR30-mediated non-genomic signaling could play an important role in endometrial cancer.

New Imaging Methods for Non-invasive Assessment of Mechanical, Structural, and Biochemical Properties of Human Achilles Tendon: A Mini Review

PubMed Central

Fouré, Alexandre

2016-01-01

The mechanical properties of tendon play a fundamental role to passively transmit forces from muscle to bone, withstand sudden stretches, and act as a mechanical buffer allowing the muscle to work more efficiently. The use of non-invasive imaging methods for the assessment of human tendon's mechanical, structural, and biochemical properties in vivo is relatively young in sports medicine, clinical practice, and basic science. Non-invasive assessment of the tendon properties may enhance the diagnosis of tendon injury and the characterization of recovery treatments. While ultrasonographic imaging is the most popular tool to assess the tendon's structural and indirectly, mechanical properties, ultrasonographic elastography, and ultra-high field magnetic resonance imaging (UHF MRI) have recently emerged as potentially powerful techniques to explore tendon tissues. This paper highlights some methodological cautions associated with conventional ultrasonography and perspectives for in vivo human Achilles tendon assessment using ultrasonographic elastography and UHF MRI. PMID:27512376

Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip

PubMed Central

Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M.; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M.

2016-01-01

Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID:26883939

Snowpack, fire, and forest disturbance: interactions affect montane invasions by non-native shrubs.

PubMed

Stevens, Jens T; Latimer, Andrew M

2015-06-01

Montane regions worldwide have experienced relatively low plant invasion rates, a trend attributed to increased climatic severity, low rates of disturbance, and reduced propagule pressure relative to lowlands. Manipulative experiments at elevations above the invasive range of non-native species can clarify the relative contributions of these mechanisms to montane invasion resistance, yet such experiments are rare. Furthermore, global climate change and land use changes are expected to cause decreases in snowpack and increases in disturbance by fire and forest thinning in montane forests. We examined the importance of these factors in limiting montane invasions using a field transplant experiment above the invasive range of two non-native lowland shrubs, Scotch broom (Cytisus scoparius) and Spanish broom (Spartium junceum), in the rain-snow transition zone of the Sierra Nevada of California. We tested the effects of canopy closure, prescribed fire, and winter snow depth on demographic transitions of each species. Establishment of both species was most likely at intermediate levels of canopy disturbance, but at this intermediate canopy level, snow depth had negative effects on winter survival of seedlings. We used matrix population models to show that an 86% reduction in winter snowfall would cause a 2.8-fold increase in population growth rates in Scotch broom and a 3.5-fold increase in Spanish broom. Fall prescribed fire increased germination rates, but decreased overall population growth rates by reducing plant survival. However, at longer fire return intervals, population recovery between fires is likely to keep growth rates high, especially under low snowpack conditions. Many treatment combinations had positive growth rates despite being above the current invasive range, indicating that propagule pressure, disturbance, and climate can all strongly affect plant invasions in montane regions. We conclude that projected reductions in winter snowpack and increases in forest disturbance are likely to increase the risk of invasion from lower elevations. © 2014 John Wiley & Sons Ltd.

Effectiveness and efficacy of minimally invasive lung volume reduction surgery for emphysema

PubMed Central

Pertl, Daniela; Eisenmann, Alexander; Holzer, Ulrike; Renner, Anna-Theresa; Valipour, A.

2014-01-01

Lung emphysema is a chronic, progressive and irreversible destruction of the lung tissue. Besides non-medical therapies and the well established medical treatment there are surgical and minimally invasive methods for lung volume reduction (LVR) to treat severe emphysema. This report deals with the effectiveness and cost-effectiveness of minimally invasive methods compared to other treatments for LVR in patients with lung emphysema. Furthermore, legal and ethical aspects are discussed. No clear benefit of minimally invasive methods compared to surgical methods can be demonstrated based on the identified and included evidence. In order to assess the different methods for LVR regarding their relative effectiveness and safety in patients with lung emphysema direct comparative studies are necessary. PMID:25295123

Effectiveness and efficacy of minimally invasive lung volume reduction surgery for emphysema.

PubMed

Pertl, Daniela; Eisenmann, Alexander; Holzer, Ulrike; Renner, Anna-Theresa; Valipour, A

2014-01-01

Lung emphysema is a chronic, progressive and irreversible destruction of the lung tissue. Besides non-medical therapies and the well established medical treatment there are surgical and minimally invasive methods for lung volume reduction (LVR) to treat severe emphysema. This report deals with the effectiveness and cost-effectiveness of minimally invasive methods compared to other treatments for LVR in patients with lung emphysema. Furthermore, legal and ethical aspects are discussed. No clear benefit of minimally invasive methods compared to surgical methods can be demonstrated based on the identified and included evidence. In order to assess the different methods for LVR regarding their relative effectiveness and safety in patients with lung emphysema direct comparative studies are necessary.

In vivo determination of multiple indices of periodontal inflammation by optical spectroscopy

PubMed Central

Liu, KZ; Xiang, XM; Man, A; Sowa, MG; Cholakis, N; Ghiabi, E; Singer, DL; Scott, DA

2008-01-01

Background and Objective Visible – near infrared (optical) spectroscopy can be used to measure regional tissue hemodynamics and edema and, therefore, may represent an ideal tool with which to non-invasively study periodontal inflammation. The study objective was to evaluate the ability of optical spectroscopy to simultaneously determine multiple inflammatory indices (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin, and tissue edema) in periodontal tissues in vivo. Material and Methods Spectra were obtained, processed, and evaluated from healthy, gingivitis, and periodontitis sites (n = 133) using a portable optical – near infrared spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was used to determine the relative contribution of each inflammatory component to the overall spectrum. Results Optical spectroscopy was harnessed to successfully generate complex inflammatory profiles in periodontal tissues. Tissue oxygenation at periodontitis sites was significantly decreased (p<0.05) compared to gingivitis and healthy controls. This is largely due to an increase in deoxyhemoglobin in the periodontitis sites compared to healthy (p<0.01) and gingivitis (p=0.05) sites. Tissue water content per se showed no significant difference between the sites but a water index associated with tissue electrolyte levels and temperature differed was significantly between periodontitis sites when compared to both healthy and gingivitis sites (p<0.03). Conclusion This study establishes that optical spectroscopy can simultaneously determine multiple inflammatory indices directly in the periodontal tissues in vivo. Visible - near infrared spectroscopy has the potential to be developed into a simple, reagent-free, user friendly, chair-side, site-specific, diagnostic and prognostic test for periodontitis. PMID:18973538

Analysis of the potential for non-invasive imaging of oxygenation at heart depth, using ultrasound optical tomography (UOT) or photo-acoustic tomography (PAT).

PubMed

Walther, Andreas; Rippe, Lars; Wang, Lihong V; Andersson-Engels, Stefan; Kröll, Stefan

2017-10-01

Despite the important medical implications, it is currently an open task to find optical non-invasive techniques that can image deep organs in humans. Addressing this, photo-acoustic tomography (PAT) has received a great deal of attention in the past decade, owing to favorable properties like high contrast and high spatial resolution. However, even with optimal components PAT cannot penetrate beyond a few centimeters, which still presents an important limitation of the technique. Here, we calculate the absorption contrast levels for PAT and for ultrasound optical tomography (UOT) and compare them to their relevant noise sources as a function of imaging depth. The results indicate that a new development in optical filters, based on rare-earth-ion crystals, can push the UOT technique significantly ahead of PAT. Such filters allow the contrast-to-noise ratio for UOT to be up to three orders of magnitude better than for PAT at depths of a few cm into the tissue. It also translates into a significant increase of the image depth of UOT compared to PAT, enabling deep organs to be imaged in humans in real time. Furthermore, such spectral holeburning filters are not sensitive to speckle decorrelation from the tissue and can operate at nearly any angle of incident light, allowing good light collection. We theoretically demonstrate the improved performance in the medically important case of non-invasive optical imaging of the oxygenation level of the frontal part of the human myocardial tissue. Our results indicate that further studies on UOT are of interest and that the technique may have large impact on future directions of biomedical optics.

Nutrient Limitation of Native and Invasive N2-Fixing Plants in Northwest Prairies

PubMed Central

Thorpe, Andrea S.; Perakis, Steven; Catricala, Christina; Kaye, Thomas N.

2013-01-01

Nutrient rich conditions often promote plant invasions, yet additions of non-nitrogen (N) nutrients may provide a novel approach for conserving native symbiotic N-fixing plants in otherwise N-limited ecosystems. Lupinus oreganus is a threatened N-fixing plant endemic to prairies in western Oregon and southwest Washington (USA). We tested the effect of non-N fertilizers on the growth, reproduction, tissue N content, and stable isotope δ15N composition of Lupinus at three sites that differed in soil phosphorus (P) and N availability. We also examined changes in other Fabaceae (primarily Vicia sativa and V. hirsuta) and cover of all plant species. Variation in background soil P and N availability shaped patterns of nutrient limitation across sites. Where soil P and N were low, P additions increased Lupinus tissue N and altered foliar δ15N, suggesting P limitation of N fixation. Where soil P was low but N was high, P addition stimulated growth and reproduction in Lupinus. At a third site, with higher soil P, only micro- and macronutrient fertilization without N and P increased Lupinus growth and tissue N. Lupinus foliar δ15N averaged −0.010‰ across all treatments and varied little with tissue N, suggesting consistent use of fixed N. In contrast, foliar δ15N of Vicia spp. shifted towards 0‰ as tissue N increased, suggesting that conditions fostering N fixation may benefit these exotic species. Fertilization increased cover, N fixation, and tissue N of non-target, exotic Fabaceae, but overall plant community structure shifted at only one site, and only after the dominant Lupinus was excluded from analyses. Our finding that non-N fertilization increased the performance of Lupinus with few community effects suggests a potential strategy to aid populations of threatened legume species. The increase in exotic Fabaceae species that occurred with fertilization further suggests that monitoring and adaptive management should accompany any large scale applications. PMID:24386399

Nutrient limitation of native and invasive N2-fixing plants in northwest prairies

USGS Publications Warehouse

Thorpe, Andrea S.; Perakis, Steven S.; Catricala, Christina; Kaye, Thomas N.

2013-01-01

Nutrient rich conditions often promote plant invasions, yet additions of non-nitrogen (N) nutrients may provide a novel approach for conserving native symbiotic N-fixing plants in otherwise N-limited ecosystems. Lupinus oreganus is a threatened N-fixing plant endemic to prairies in western Oregon and southwest Washington (USA). We tested the effect of non-N fertilizers on the growth, reproduction, tissue N content, and stable isotope δ15N composition of Lupinus at three sites that differed in soil phosphorus (P) and N availability. We also examined changes in other Fabaceae (primarily Vicia sativa and V. hirsuta) and cover of all plant species. Variation in background soil P and N availability shaped patterns of nutrient limitation across sites. Where soil P and N were low, P additions increased Lupinus tissue N and altered foliar δ15N, suggesting P limitation of N fixation. Where soil P was low but N was high, P addition stimulated growth and reproduction in Lupinus. At a third site, with higher soil P, only micro- and macronutrient fertilization without N and P increased Lupinus growth and tissue N. Lupinus foliar δ15N averaged −0.010‰ across all treatments and varied little with tissue N, suggesting consistent use of fixed N. In contrast, foliar δ15N of Vicia spp. shifted towards 0‰ as tissue N increased, suggesting that conditions fostering N fixation may benefit these exotic species. Fertilization increased cover, N fixation, and tissue N of non-target, exotic Fabaceae, but overall plant community structure shifted at only one site, and only after the dominant Lupinus was excluded from analyses. Our finding that non-N fertilization increased the performance of Lupinus with few community effects suggests a potential strategy to aid populations of threatened legume species. The increase in exotic Fabaceae species that occurred with fertilization further suggests that monitoring and adaptive management should accompany any large scale applications.

Long non-coding RNA colon cancer-associated transcript 1 functions as a competing endogenous RNA to regulate cyclin-dependent kinase 1 expression by sponging miR-490-3p in hepatocellular carcinoma progression.

PubMed

Dou, Chunqing; Sun, Liyuan; Jin, Xin; Han, Mingming; Zhang, Bao; Li, Tao

2017-04-01

Hepatocellular carcinoma is an aggressive neoplasm and is one of the most common human cancers. Recently, long non-coding RNAs have been demonstrated to participate in pathogenesis of many diseases including the progression in several cancers. In this study, we found that the long non-coding RNA colon cancer-associated transcript 1 was upregulated in hepatocellular carcinoma tissues (p < 0.05), and high colon cancer-associated transcript 1 expression level was positively associated with tumor volume (p < 0.05) and American Joint Committee on Cancer stage (p < 0.05) in hepatocellular carcinoma patients. Luciferase reporter assays and RNA-pulldown assays showed that colon cancer-associated transcript 1 is a target of miR-490-3p. Real-time quantitative polymerase chain reaction and Western blot analysis indicated that colon cancer-associated transcript 1 regulated cyclin-dependent kinase 1 expression as a competing endogenous RNA by sponging miR-490-3p in hepatocellular carcinoma cells. Furthermore, colon cancer-associated transcript 1 silencing decreased hepatocellular carcinoma cells proliferation and invasion and overexpression promoted cell proliferation and invasion in vitro. These data demonstrated that the colon cancer-associated transcript 1/miR-490-3p/cyclin-dependent kinase 1 regulatory pathway promotes the progression of hepatocellular carcinoma. Inhibition of colon cancer-associated transcript 1 expression may be a novel therapeutic strategy for hepatocellular carcinoma.

DEspR roles in tumor vasculo-angiogenesis, invasiveness, CSC-survival and anoikis resistance: a 'common receptor coordinator' paradigm.

PubMed

Herrera, Victoria L; Decano, Julius L; Tan, Glaiza A; Moran, Ann M; Pasion, Khristine A; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nude(nu/nu) rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface 'common receptor coordinator', DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma.

DEspR Roles in Tumor Vasculo-Angiogenesis, Invasiveness, CSC-Survival and Anoikis Resistance: A ‘Common Receptor Coordinator’ Paradigm

PubMed Central

Herrera, Victoria L.; Decano, Julius L.; Tan, Glaiza A.; Moran, Ann M.; Pasion, Khristine A.; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nudenu/nu rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface ‘common receptor coordinator’, DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma. PMID:24465725

Thermal effects in tissues induced by interstitial irradiation of near infrared laser with a cylindrical diffuser

NASA Astrophysics Data System (ADS)

Le, Kelvin; Johsi, Chet; Figueroa, Daniel; Goddard, Jessica; Li, Xiaosong; Towner, Rheal A.; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.

2011-03-01

Laser immunotherapy (LIT), using non-invasive laser irradiation, has resulted in promising outcomes in the treatment of late-stage cancer patients. However, the tissue absorption of laser light limits the clinical applications of LIT in patients with dark skin, or with deep tumors. The present study is designed to investigate the thermal effects of interstitial irradiation using an 805-nm laser with a cylindrical diffuser, in order to overcome the limitations of the non-invasive mode of treatment. Cow liver and rat tumors were irradiated using interstitial fiber. The temperature increase was monitored by thermocouples that were inserted into the tissue at different sites around the cylinder fiber. Three-dimensional temperature distribution in target tissues during and after interstitial laser irradiation was also determined by Proton Resonance Frequency. The preliminary results showed that the output power of laser and the optical parameters of the target tissue determined the light distribution in the tissue. The temperature distributions varied in the tissue according to the locations relative to the active tip of the cylindrical diffuser. The temperature increase is strongly related to the laser power and irradiation time. Our results using thermocouples and optical sensors indicated that the PRF method is reliable and accurate for temperature determination. Although the inhomogeneous biological tissues could result in temperature fluctuation, the temperature trend still can be reliable enough for the guidance of interstitial irradiation. While this study provides temperature profiles in tumor tissue during interstitial irradiation, the biological effects of the irradiation remain unclear. Future studies will be needed, particularly in combination with the application of immunostimulant for inducing tumor-specific immune responses in the treatment of metastatic tumors.

Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma.

PubMed

Xie, Jian-Jun; Jiang, Yan-Yi; Jiang, Yuan; Li, Chun-Quan; Lim, Mei-Chee; An, Omer; Mayakonda, Anand; Ding, Ling-Wen; Long, Lin; Sun, Chun; Lin, Le-Hang; Chen, Li; Wu, Jian-Yi; Wu, Zhi-Yong; Cao, Qi; Fang, Wang-Kai; Yang, Wei; Soukiasian, Harmik; Meltzer, Stephen J; Yang, Henry; Fullwood, Melissa; Xu, Li-Yan; Li, En-Min; Lin, De-Chen; Koeffler, H Phillip

2018-06-01

Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses. We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling. We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells.

PubMed

Yang, Jing; Wang, Rong; Li, Hongjiang; Lv, Qing; Meng, Wentong; Yang, Xiaoqin

2016-07-08

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and MCF-7. In vitro, Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo, tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro, and attenuated tumor formation in vivo. High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation.

Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway

PubMed Central

Wang, Tiantian; Wang, Mei; Fang, Shuang; Wang, Qiang; Fang, Rui; Chen, Jie

2017-01-01

Fibulin-4, an extracellular glycoprotein, which plays significant roles in elastic fiber assembly, is correlated to the progression of some cancers. However, the role of fibulin-4 in endometrial cancer cell invasion and metastasis remains unexplored. In our study, fibulin-4 expression was assessed by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in normal endometrial tissues and endometrial carcinoma tissues. Using single cell cloning, strongly, and weakly, invasive subclones were derived from KLE and Ishikawa endometrial carcinoma cell lines. RT-qPCR, western blotting, and immunocytochemistry (ICC) were used to assess mRNA and protein expressions of fibulin-4 in primary cultured endometrial cells, 4 types of endometrial cancer cell lines, and the different invasive subclones. Using lentivirus transfection, fibulin-4 shRNA and pLVX-fibulin-4 were constructed and used to infect the strongly and weakly invasive subclones. The effects of fibulin-4 on the biological characteristics of endometrial carcinoma cells were detected by cell functional assays in vitro and in vivo. Using Wnt signaling pathway inhibitor XAV-939 and activator LiCl, we detected the role of fibulin-4 in the Wnt/β-catenin pathway and the relationship with epithelial to mesenchymal transition (EMT). Fibulin-4 was decreased in endometrial carcinoma tissues, and loss of fibulin-4 expression was significantly related with poor differentiation, lymph node metastasis, and poor prognosis of endometrial carcinoma. Fibulin-4 significantly inhibited endometrial carcinoma cell proliferation, invasion, metastasis, and EMT through the Wnt/β-catenin pathway. Fibulin-4 has the ability to suppress endometrial cancer progression. These results can contribute to the development of a new potential therapeutic target for patients with endometrial carcinoma. PMID:28177909

Development of luminescent pH sensor films for monitoring bacterial growth through tissue.

PubMed

Wang, Fenglin; Raval, Yash; Chen, Hongyu; Tzeng, Tzuen-Rong J; DesJardins, John D; Anker, Jeffrey N

2014-02-01

Although implanted medical devices (IMDs) offer many benefits, they are susceptible to bacterial colonization and infections. Such infections are difficult to treat because bacteria could form biofilms on the implant surface, which reduce antibiotics penetration and generate local dormant regions with low pH and low oxygen. In addition, these infections are hard to detect early because biofilms are often localized on the surface. Herein, an optical sensor film is developed to detect local acidosis on an implanted surface. The film contains both upconverting particles (UCPs) that serve as a light source and a pH indicator that alters the luminescence spectrum. When irradiated with 980 nm light, the UCPs produce deeply penetrating red light emission, while generating negligible autofluorescence in the tissue. The basic form of the pH indicator absorbs more of upconversion luminescence at 661 nm than at 671 nm and consequently the spectral ratio indicates pH. Implanting this pH sensor film beneath 6-7 mm of porcine tissue does not substantially affect the calibration curve because the peaks are closely spaced. Furthermore, growth of Staphylococcus epidermidis on the sensor surface causes a local pH decrease that can be detected non-invasively through the tissue. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensing in tissue bioreactors

NASA Astrophysics Data System (ADS)

Rolfe, P.

2006-03-01

Specialized sensing and measurement instruments are under development to aid the controlled culture of cells in bioreactors for the fabrication of biological tissues. Precisely defined physical and chemical conditions are needed for the correct culture of the many cell-tissue types now being studied, including chondrocytes (cartilage), vascular endothelial cells and smooth muscle cells (blood vessels), fibroblasts, hepatocytes (liver) and receptor neurones. Cell and tissue culture processes are dynamic and therefore, optimal control requires monitoring of the key process variables. Chemical and physical sensing is approached in this paper with the aim of enabling automatic optimal control, based on classical cell growth models, to be achieved. Non-invasive sensing is performed via the bioreactor wall, invasive sensing with probes placed inside the cell culture chamber and indirect monitoring using analysis within a shunt or a sampling chamber. Electroanalytical and photonics-based systems are described. Chemical sensing for gases, ions, metabolites, certain hormones and proteins, is under development. Spectroscopic analysis of the culture medium is used for measurement of glucose and for proteins that are markers of cell biosynthetic behaviour. Optical interrogation of cells and tissues is also investigated for structural analysis based on scatter.

[Primary non-Hodgkin's lymphoma of the breast. A case report].

PubMed

Villalón-López, José Sebastián; Souto-Del Bosque, Rosalía; Méndez-Sashida, Pedro Gonzalo

Primary breast lymphomas, a rare subtype of non-Hodgkin's lymphoma, represent 0.04 to 0.5% of all breast cancers, 0.38 to 0.7% of all lymphomas, and 1.7 to 2.2% of extranodal lymphomas. The treatment choice is based on chemotherapy containing anthracycline and rituximab. Surgery is limited to being less invasive and only for diagnostic purposes. Radiotherapy has an important role as consolidation therapy, particularly in patients with negative nodes. A 70 year old woman with a breast nodule in the left upper outer quadrant, with slow growth, expansive, painless, and accompanied by skin changes, malaise, weight loss, fatigue, chill, and sweating. There was tissue replacement by the mammary gland tumour, skin changes due to invasion, and a 5cm axillary lymphadenopathy. The mammography showed skin thickening and a dense pattern of 80% of breast tissue replacement, and the lymphadenopathy with loss of radiolucent centre and soft tissue invasion. The biopsy confirmed a diffuse high grade large cell lymphoma. She received an Rituximab (R-CHOP) chemotherapy scheme and radiotherapy with tangential and supraclavicular and axillary fields. After completing the chemotherapy, the patient is on follow-up, and at 15 months she is alive without disease activity. Primary lymphoma of the breast is a rare entity. Multimodal treatment with combined chemo-radiotherapy is the cornerstone. Surgery is reserved only for diagnostic purposes. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

NK cell recruitment and exercise: Potential immunotherapeutic role of shear stress and endothelial health.

PubMed

Evans, William

2017-11-01

Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium. Additionally, shear stress may play a role in improving NK cell function by decreasing oxidative stress. The relationship between shear stress and NK cell count and function can be tested by utilizing exercise and local heating with cuff inflation. If shear stress does play an important role, NK cell count and function will be improved in the non-cuffed exercise group, but not the cuffed limb. This paper will explore the mechanisms potentially explaining exercise-induced improvements in NK cell count and function, and propose a model for investigating these mechanisms. This mechanistic insight could aid in providing a novel, safe, relatively inexpensive, and non-invasive target for immunotherapy in cancer patients. Copyright © 2017. Published by Elsevier Ltd.

Antioxidant and molecular chaperone defences during estivation and arousal in the South American apple snail Pomacea canaliculata.

PubMed

Giraud-Billoud, Maximiliano; Vega, Israel A; Tosi, Martín E Rinaldi; Abud, María A; Calderón, María L; Castro-Vazquez, Alfredo

2013-02-15

The invasive Pomacea canaliculata estivates during periods of drought and should cope with harmful effects of reoxygenation during arousal. We studied thiobarbituric acid reactive substances (TBARS), enzymatic (superoxide dismutase, SOD and catalase, CAT) and non-enzymatic antioxidants (uric acid and reduced glutathione), and heat shock protein expression (Hsc70, Hsp70 and Hsp90) in (1) active control snails, (2) snails after 45 days of estivation, and (3) aroused snails 20 min and (4) 24 h after water exposure, in midgut gland, kidney and foot. Both kidney and foot (but not the midgut gland) showed a TBARS increase during estivation and a decrease after arousal. Tissue SOD and CAT did not change in any experimental groups. Uric acid increased during estivation in all tissues, and it decreased after arousal in the kidney. Allantoin, the oxidation product of uric acid, remained constant in the midgut gland but it decreased in the kidney until 20 min after arousal; however, allantoin levels rose in both kidney and foot 24 h after arousal. Reduced glutathione decreased during estivation and arousal, in both midgut gland and kidney, and it remained constant in the foot. Hsc70 and Hsp70 kidney levels were stable during the activity-estivation cycle and Hsp90 expression decreases during estivation and recovers in the early arousal. In foot, the expression of Hsp70 and Hsp90 was high during activity and estivation periods and disminished after arousal. Results indicate that a panoply of antioxidant and molecular chaperone defences may be involved during the activity-estivation cycle in this freshwater gastropod.

Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

NASA Astrophysics Data System (ADS)

Vigneswaran, Nadarajah

2011-03-01

Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

Circular RNA GLI2 promotes osteosarcoma cell proliferation, migration, and invasion by targeting miR-125b-5p.

PubMed

Li, Ji-Feng; Song, Yu-Ze

2017-07-01

Circular RNAs are novel identified type of endogenous non-coding RNAs, which exert vital functions in human and animals. However, the in-depth role of circular RNAs in the progression of tumorigenesis, especially osteosarcoma, is still undefined. Our preliminary study had found that cir-GLI2 was significantly upregulated in osteosarcoma tissues compared to adjacent non-tumor tissue. Moreover, cir-GLI2 silencing could effectively suppress the proliferation, migration, and invasion capacity of osteosarcoma cells, indicating the tumor-promoting role. Besides, bioinformatics analysis and luciferase reporter assay predicted the direct binding to miR-125b-5p, which has been reported to function as a tumor suppressor in osteosarcoma. Furthermore, functional experiments validated that cir-GLI2 exerted the tumor-promoting effects on osteosarcoma cells via negatively targeting miR-125b-5p. In conclusion, our study demonstrated that cir-GLI2 acts as an oncogenic circular RNA in osteosarcoma genesis, providing a novel diagnostic and therapeutic target for osteosarcoma.

Long non-coding RNA gastric carcinoma highly expressed transcript 1 promotes cell proliferation and invasion in human head and neck cancer.

PubMed

Liu, Hui; Wu, Yu

2018-05-01

Recent evidence indicates that the long non-coding RNA gastric carcinoma highly expressed transcript 1 (GHET1) is involved in the development and carcinogenesis of several tumor types; however, the exact roles of GHET1 and its underlying mechanisms in head and neck cancer (HNC) remain largely unknown. In the present study, the expression patterns of GHET1 in HNC were determined and its clinical significance was assessed. The expression level of GHET1 was significantly increased in HNC tissues, compared with paired adjacent normal tissues. High GHET1 expression was significantly associated with advanced Tumor-Node-Metastasis stages and poor prognosis. Furthermore, inhibition of GHET1 suppressed cell proliferation, induced cell apoptosis and caused cell cycle arrest in vitro . In addition, GHET1 silencing inhibited cell migration and invasion. Taken together, the results of the present study indicated that GHET1 acts as an oncogene in HNC and may represent a novel therapeutic target.

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

PubMed Central

Zhou, Ming; Hara, Hidetaka; Dai, Yifan; Mou, Lisha; Cooper, David K. C.; Wu, Changyou; Cai, Zhiming

2016-01-01

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation. PMID:27490531

Mapping oxygen concentration in the awake mouse brain

PubMed Central

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-01-01

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. DOI: http://dx.doi.org/10.7554/eLife.12024.001 PMID:26836304

The importance of optical methods for non-invasive measurements in the skin care industry

NASA Astrophysics Data System (ADS)

Stamatas, Georgios N.

2010-02-01

Pharmaceutical and cosmetic industries are concerned with treating skin disease, as well as maintaining and promoting skin health. They are dealing with a unique tissue that defines our body in space. As such, skin provides not only the natural boundary with the environment inhibiting body dehydration as well as penetration of exogenous aggressors to the body, it is also ideally situated for optical measurements. A plurality of spectroscopic and imaging methods is being used to understand skin physiology and pathology and document the effects of topically applied products on the skin. The obvious advantage of such methods over traditional biopsy techniques is the ability to measure the cutaneous tissue in vivo and non-invasively. In this work, we will review such applications of various spectroscopy and imaging methods in skin research that is of interest the cosmetic and pharmaceutical industry. Examples will be given on the importance of optical techniques in acquiring new insights about acne pathogenesis and infant skin development.

Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice.

PubMed

Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

2015-07-01

Orthotopic implantation of cancer allows metastasis to occur. The most patient-like metastatic orthotopic models are developed with surgical orthotopic implantation using intact tissue in order to preserve the natural tissue structure of the tumor which contains both cancer cells and stroma. In the present study, we performed a simple thoracotomy by making an intercostal incision between the fourth and fifth ribs on the left side of the chest of nude mice. Lung tumor fragments expressing red fluorescent protein were then implanted on the left lung. It was possible to monitor tumor formation in the lung non-invasively by spectral imaging using the Maestro system with a liquid tunable filter. The model described here has high tumorigenicity in the lung (100%) and a low mortality rate (5%). This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mapping oxygen concentration in the awake mouse brain.

PubMed

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-02-02

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

[Expression of Id1 and Id3 in endometrial carcinoma and their roles in regulating biological behaviors of endometrial carcinoma cells in vitro].

PubMed

Sun, Lili; Li, Xuenong; Liu, Guobing

2013-06-01

To investigate the expression of inhibitor of DNA differentiation/DNA binding 1 (Id1) and Id3 in endometrial carcinoma and explore their roles in regulating the proliferation, invasion, migration and adhesion of endometrial carcinoma cells in vitro. Id1 and Id3 expression in 4 fresh endometrial cancer tissue specimens and matched adjacent tissues were detected using Western blotting. Two endometrial cancer cell lines, HEC-1-B and RL-952, were both divided into 4 groups, namely the untreated group, blank virus group, promoter group and Id1/Id3 double-knockdown group, and their expressions of MMP2, CXCR4 and P21 were detected by qRT-PCR and Western blotting. The proliferation, invasion, migration and adhesion of the cells were evaluated with MTT, Transwell, wound-healing, and adhesion assays. Endometrial carcinoma tissues showed significantly higher Id1 and Id3 expression than the adjacent tissues (P<0.05). In the two endometrial carcinoma cell lines, Id1/Id3 double-knockdown significantly decreased MMP2 and CXCR4 expression and increased P21 expression at both mRNA and protein levels (P<0.05), and resulted in suppressed cell proliferation, invasion, migration and adhesion. Id1 and Id3 expressions are up-regulated in endometrial carcinoma to promote the proliferation, invasion, migration and adhesion of the tumor cells by increasing MMP2 and CXCR4 expression and reducing P21 expression. Therapies targeting Id1/Id3 can be a novel strategy for treatment of endometrial carcinoma.

Predictive analysis of optical ablation in several dermatological tumoral tissues

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

An Adhesive Patch-Based Skin Biopsy Device for Molecular Diagnostics and Skin Microbiome Studies.

PubMed

Yao, Zuxu; Moy, Ronald; Allen, Talisha; Jansen, Burkhard

2017-10-01

A number of diagnoses in clinical dermatology are currently histopathologically confirmed and this image recognition-based confirmation generally requires surgical biopsies. The increasing ability of molecular pathology to corroborate or correct a clinical diagnosis based on objective gene expression, mutation analysis, or molecular microbiome data is on the horizon and would be further supported by a tool or procedure to collect samples non-invasively. This study characterizes such a tool in form of a 'bladeless' adhesive patch-based skin biopsy device. The performance of this device was evaluated through a variety of complementary technologies including assessment of sample biomass, electron microscopy demonstrating the harvesting of layers of epidermal tissue, and isolation of RNA and DNA from epidermal skin samples. Samples were obtained by application of adhesive patches to the anatomical area of interest. Biomass assessment demonstrated collection of approximately 0.3mg of skin tissue per adhesive patch and electron microscopy confirmed the nature of the harvested epidermal skin tissue. The obtained tissue samples are stored in a stable fashion on adhesive patches over a wide range of temperatures (-80oC to +60oC) and for extended periods of time (7 days or more). Total human RNA, human genomic DNA and microbiome DNA yields were 23.35 + 15.75ng, 27.72 + 20.71ng and 576.2 + 376.8pg, respectively, in skin samples obtained from combining 4 full patches collected non-invasively from the forehead of healthy volunteers. The adhesive patch skin sampling procedure is well tolerated and provides robust means to obtain skin tissue, RNA, DNA, and microbiome samples without involving surgical biopsies. The non-invasively obtained skin samples can be shipped cost effectively at ambient temperature by mail or standard courier service, and are suitable for a variety of molecular analyses of the skin microbiome as well as of keratinocytes, T cells, dendritic cells, melanocytes, and other skin cells involved in the pathology of various skin conditions and conditions where the skin can serve as a surrogate target organ.

J Drugs Dermatol. 2017;16(10):979-986.

Downregulation of long non-coding RNA LET predicts poor prognosis and increases Notch signaling in non-small cell lung cancer

PubMed Central

Li, Shengwen; Zhao, Hui; Li, Jianqiang; Zhang, Aizheng; Wang, Haibin

2018-01-01

Long non-coding RNAs (lncRNAs) have been found to be dysregulated in a variety of tumors. The lncRNA-Low Expression in Tumor (LET) is a recently identified lncRNA, but its expression pattern and biological significance in human non-small cell lung cancer (NSCLC) are still largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in human NSCLC lung tissues and cell lines. Decreased lncRNA-LET expression was strongly associated with advanced tumor stages and poorer overall survival of NSCLC patients. Functionally, overexpression of lncRNA-LET in NSCLC H292 cells significantly suppressed cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis, while knockdown of lncRNA-LET in NSCLC H1975 cells showed an opposite effect, pointing to a tumor-suppressive role for lncRNA-LET in NSCLC. Mechanistically, we demonstrated that lncRNA-LET overexpression significantly reduced the expression of Notch1 intracellular Domain (NICD1) in H292 cells while knockdown of lncRNA-LET increased NICD1 expression in H1975 cells. Similarly, NSCLC lung tissues with high levels of lncRNA-LET had lower NICD1 expression. Thus, our results provide a strong rationale for lncRNA-LET to be used as a prognostic indicator and a potent therapeutic target for NSCLC patients, and highlight a novel lncRNA-LET/Notch axis in regulating NSCLC cell fate and tumor progression. PMID:29416684

1300 nm and 890 nm OCT images of oral cancer tissue engineered models and biopsy samples offer complimentary performance (Conference Presentation)

NASA Astrophysics Data System (ADS)

Boadi, Joseph; Byers, Robert A.; Fernandes, Jon; Mittar, Shweta; Hearnden, Vanessa; Lu, Zenghai; MacNeil, Sheila; Thornhill, Martin; Murdoch, Craig; Hunter, Keith D.; McKechnie, Alasdair; Matcher, Stephen J.

2016-02-01

OCT has demonstrated great potential to non-invasively detect oral epithelial cancers, potentially guiding biopsy and surgical resection. On non-ophthalmic tissues the preferred illumination wavelength is 1300 nm. Previous studies on skin have shown that useful image data can also be obtained at shorter wavelengths, with systems at 1060 nm and 820 nm offering reduced depth penetration but higher contrast. Here we apply a similar comparison to tissue engineered models of oral cancer and also to human biopsy samples, generally finding a similar trend. 1300 nm multi-beam OCT (Michelson Diagnostics EX1301) visualises stromal structures and surface keratin more clearly, providing useful image contrast down to around 1 mm. This system was compared with an ultra-high resolution home-built system operating at 890 nm (2.5 micron resolution vs 7.5 micron axial resolution for the EX1301). The UHR system reveals epithelial features more clearly, especially in the DOK pre-invasive cell line model and the biopsy samples. The relative effects of center wavelength vs axial resolution in generating the differential, wavelength-dependent contrast are assessed and the OCT biopsy images are compared with contemporary histology.

Diffusing wave spectroscopy and its application for monitoring of skin blood microcirculation

NASA Astrophysics Data System (ADS)

Meglinski, Igor V.

2003-10-01

Diffusing Wave Spectroscopy (DWS) is a novel modern technique uniquely suited for the non-invasive measurements of the particles size and their motion within the randomly inhomogeneous highly scattering and absorbing media, including biological tissues as a human skin. The technique is based on the illuminating the media (tissues) with a coherent laser light, and analyzing the loss of coherence of the scattered field arises from motion of the scattering particles with respect to each other. Both theoretical and experimental results has shown the potentialities and viability of DWS application for the express non-invasive quantitative monitoring and functional diagnostics of skin blood microcirculation, with down to 1 μm/sec resolution. This is likely lead to quantitative monitoring in general diagnostics, diabetes studies, pharmacological intervention for the failing surgical skin flaps or replants, blood microcirculation monitoring during sepsis, assess burn depth, diagnose atherosclerotic disease, and investigate mechanisms of photodynamic therapy for cancer treatment. In frame of current report we describe the recent developments of DWS further to the point that skin blood micro-flow can be routinely and accurately obtained in a separate skin vascular bed on normal skin tissues.

Non-invasive endotracheal delivery of paclitaxel-loaded alginate microparticles.

PubMed

Alipour, Shohreh; Montaseri, Hashem; Khalili, Azadeh; Tafaghodi, Mohsen

2016-10-01

Aerosolized chemotherapeutics leads to higher, localized and continuous concentrations of active agents in lung tissue with lower side effects for other organs. The present study was performed on jugular vein cannulated rats which endothracheally received 4 mg/kg of free paclitaxel powder (Free-PTX), paclitaxel-loaded alginate microparticles (PTX-ALG-MPs) and i.v. paclitaxel (Anzatax(®)). Pharmacokinetic parameters for Free-PTX and PTX-ALG-MPs contain higher AUC, mean residence time (MRT),half-life and bioavailability, with lower elimination constant (ke). Statistical analysis showed that the amount of paclitaxel per gram of lung tissue after 0.5, 6 and 24 h after administration of Free-PTX was lower than PTX-ALG-MPs. Lung tissue AUC for Free-PTX was lower than PTX-ALG-MPs. According to the obvious advantages obtained, such as dose lowering and increasing paclitaxel residence time and half-life. It should be noted that cell cytotoxicity test on normal airway cell lines was not examined in this study but due to previous reports on safety of inhaled paclitaxel, it can be suggested that pulmonary delivery of paclitaxel can be a useful non-invasive route of administration compared with i.v administration.

Transcriptional profiling: a potential anti-doping strategy.

PubMed

Rupert, J L

2009-12-01

Evolving challenges require evolving responses. The use of illicit performance enhancing drugs by athletes permeates the reality and the perception of elite sports. New drugs with ergogenic or masking potential are quickly adopted, driven by a desire to win and the necessity of avoiding detection. To counter this trend, anti-doping authorities are continually refining existing assays and developing new testing strategies. In the post-genome era, genetic- and molecular-based tests are being evaluated as potential approaches to detect new and sophisticated forms of doping. Transcriptome analysis, in which a tissue's complement of mRNA transcripts is characterized, is one such method. The quantity and composition of a tissue's transcriptome is highly reflective of milieu and metabolic activity. There is much interest in transcriptional profiling in medical diagnostics and, as transcriptional information can be obtained from a variety of easily accessed tissues, similar approaches could be used in doping control. This article briefly reviews current understanding of the transcriptome, common methods of global analysis of gene expression and non-invasive sample sources. While the focus of this article is on anti-doping, the principles and methodology described could be applied to any research in which non-invasive, yet biologically informative sampling is desired.

Towards novel compact laser sources for non-invasive diagnostics and treatment

NASA Astrophysics Data System (ADS)

Rafailov, Edik U.; Litvinova, Karina S.; Sokolovski, Sergei G.

2015-08-01

An important field of application of lasers is biomedical optics. Here, they offer great utility for diagnosis, therapy and surgery. For the development of novel methods of laser-based biomedical diagnostics careful study of light propagation in biological tissues is necessary to enhance our understanding of the optical measurements undertaken, increase research and development capacity and the diagnostic reliability of optical technologies. Ultimately, fulfilling these requirements will increase uptake in clinical applications of laser based diagnostics and therapeutics. To address these challenges informative biomarkers relevant to the biological and physiological function or disease state of the organism must be selected. These indicators are the results of the analysis of tissues and cells, such as blood. For non-invasive diagnostics peripheral blood, cells and tissue can potentially provide comprehensive information on the condition of the human organism. A detailed study of the light scattering and absorption characteristics can quickly detect physiological and morphological changes in the cells due to thermal, chemical, antibiotic treatments, etc [1-5]. The selection of a laser source to study the structure of biological particles also benefits from the fact that gross pathological changes are not induced and diagnostics make effective use of the monochromatic directional coherence properties of laser radiation.

[Non-invasive, spatially resolved determination of tissue properties of the crystalline lens with regard to rheology, refractive index, density and protein concentration by using Brillouin spectroscopy].

PubMed

Reiss, S; Stachs, O; Guthoff, R; Stolz, H

2011-12-01

The confocal Brillouin spectroscopy is an innovative measurement method that allows the non-invasive determination of the rheological properties of materials. Its application in ophthalmology can offer the possibility to determine in-vivo the deformation properties of sections of transparent biological tissue such as the cornea or eye lens with spatial resolution. This seems to be a promising approach concerning current presbyopia research. Due to the spatially resolved detection of the viscoelastic lens properties, a better understanding of the natural aging process of the lens and the influences of different lens opacities on the stiffness is expected. From the obtained spectral data the relative protein levels, the relative refractive index profile and the relative density profile within the lens tissue can be derived in addition. A measurement set-up for confocal Brillouin microscopy based on spectral analysis of spontaneous Brillouin scattering signals by using a high-resolution dispersive device is presented. First in-vitro test results on animal and human lenses are presented and evaluated concerning their rheological significance. These data are compared with known research results. © Georg Thieme Verlag KG Stuttgart · New York.

Vinculin contributes to Cell Invasion by Regulating Contractile Activation

NASA Astrophysics Data System (ADS)

Mierke, Claudia Tanja

2008-07-01

Vinculin is a component of the focal adhesion complex and is described as a mechano-coupling protein connecting the integrin receptor and the actin cytoskeleton. Vinculin knock-out (k.o.) cells (vin-/-) displayed increased migration on a 2-D collagen- or fibronectin-coated substrate compared to wildtype cells, but the role of vinculin in cell migration through a 3-D connective tissue is unknown. We determined the invasiveness of established tumor cell lines using a 3-D collagen invasion assay. Gene expression analysis of 4 invasive and 4 non-invasive tumor cell lines revealed that vinculin expression was significantly increased in invasive tumor cell lines. To analyze the mechanisms by which vinculin increased cell invasion in a 3-D gel, we studied mouse embryonic fibroblasts wildtype and vin-/- cells. Wildtype cells were 3-fold more invasive compared vin-/- cells. We hypothesized that the ability to generate sufficient traction forces is a prerequisite for tumor cell migration in a 3-D connective tissue matrix. Using traction microscopy, we found that wildtype exerted 3-fold higher tractions on fibronectin-coated polyacrylamide gels compared to vin-/- cells. These results show that vinculin controls two fundamental functions that lead to opposite effects on cell migration in a 2-D vs. a 3-D environment: On the one hand, vinculin stabilizes the focal adhesions (mechano-coupling function) and thereby reduces motility in 2-D. On the other hand, vinculin is also a potent activator of traction generation (mechano-regulating function) that is important for cell invasion in a 3-D environment.

Imitation-tumor targeting based on continuous-wave near-infrared tomography.

PubMed

Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

2017-12-01

Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

Association between human papilloma virus/Epstein-Barr virus coinfection and oral carcinogenesis.

PubMed

Jiang, Ru; Ekshyyan, Oleksandr; Moore-Medlin, Tara; Rong, Xiaohua; Nathan, Sean; Gu, Xin; Abreo, Fleurette; Rosenthal, Eben L; Shi, Mingxia; Guidry, Joseph T; Scott, Rona S; Hutt-Fletcher, Lindsey M; Nathan, Cherie-Ann O

2015-01-01

The recent epidemic of head and neck squamous cell carcinomas associated with human papilloma virus (HPV) has not addressed its association with lymphoid tissue in the oropharynx or the potential role of Epstein-Barr virus (EBV)/HPV coinfection. The prevalence of HPV and EBV infection/coinfection and CD21 mRNA expression were determined in normal and cancerous tissues from the oropharynx using in situ hybridization (ISH), p16, and quantitative reverse transcriptase PCR (qRT-PCR). The effects of coinfection on tumorigenicity were evaluated using proliferation and invasion assays. Normal oropharynx, tonsil, non-cancer base of tongue (BOT), and BOT from sleep apnea patients demonstrated EBV positivity ranging from 7% to 36% depending on the site and methods of detection used (qRT-PCR or ISH). Among non-malignant BOT samples, HPV positivity was noted only in 20%. The percent of tonsil and BOT cancers positive for HPV (up to 63% and 80%, respectively) or coinfected with HPV/EBV (up to 25% and 70%, respectively) were both significantly associated with cancer status. Notably, HPV/EBV coinfection was observed only in malignant tissue originating in lymphoid-rich oropharynx sites (tonsil, BOT). CD21 mRNA (the major EBV attachment receptor) was detected in tonsil and BOT epithelium, but not in soft-palate epithelium. Coinfected cell lines showed a significant increase in invasiveness (P < 0.01). There is a high prevalence of HPV/EBV infection and coinfection in BOT and tonsil cancers, possibly reflecting their origins in lymphoid-rich tissue. In vitro, cells modeling coinfection have an increased invasive potential. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

PubMed Central

Bronowicka-Kłys, Dorota Ewa; Roszak, Andrzej; Pawlik, Piotr; Sajdak, Stefan; Sowińska, Anna; Jagodziński, Paweł Piotr

2017-01-01

Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients. Significantly decreased TET1 transcript levels, as compared to non-cancerous cervical tissues, were also observed in tissue samples with the following characteristics: Stage I (P=0.016), II (P<0.0001), III (P=0.00007) and grade of differentiation G1 (P=0.026), G2 (P=0.00006), G3 (P=0.0007) and Gx (P=0.0004) and squamous histological type (P<0.00001). TET1 transcript levels were significantly lower in patients aged 45–60 years (P=0.0002) and patients age >60 years (P=0.003), as compared with non-cancerous cervical tissues. TET2 transcript levels were lower in cervical cancer tissues classified as stage II (P=0.043) and TET3 transcript levels were lower in stage III samples (P=0.010), tissue samples with a grade of differentiation of G3 (P=0.025) and tissue with squamous type histology (P=0.047), all compared with non-cancerous cervical tissues. The present study demonstrated a significantly reduced level of TET1 transcripts in cancerous cervical tissues, as compared with non-cancerous tissues. Furthermore, decreased TET1-3 transcript levels were identified when patients with CC were stratified by clinicopathological variables, as compared with non-cancerous cervical tissues. PMID:28521490

Clinical implications of the HPV-16 infection & 7 beneficial effects of optimal dose of Vitamin D3 in safe, effective cancer treatment: Non-invasive rapid cancer screening using "Mouth, Hand & Foot Writing Form" of 40 participants during 150- minute workshop on the Bi-Digital 0-ring Test, in the 1st day of European Congress for Integrative Medicine, September 9-11, 2016 in Budapest.

PubMed

Omura, Yoshiaki

During the 1st day of European Congress for Integrative Medicine held September 9-11, 2016, almost the entire 1st day was scheduled for the Bi-Digital O-Ring Test, which was originally developed by this author, & consists of 2 main parts for which a U.S. patent was issued in 1993. One is a non-invasive, detection of various molecules using very strong Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with identical weight. Using this strong EMF Resonance Phenomenon, most molecules & microorganisms can be detected rapidly and non-invasively without directly contacting patients. We measured the HPV-16 infection of 70 participants non-invasively in the first 30 minutes, then screened cancers for 40 volunteers who completed one page "Mouth, Hand & Foot Writing Form," which took an average of 5∼10 minutes for each person to complete. Screening of 75 common cancers was made in 2-5 minutes for each patient. Analysis of 40 volunteers revealed 32 persons had some malignancies including 5 Anaplastic Astrocytomas of the L-brain, 3 Multiple Myelomas, 7 Hodgkin's Lymphomas, 8 Non-Hodgkin's Lymphomas, 2 rectum cancers (with chief complaints of worsening Irritable Bowel Syndrome). Although everyone had HPV-16 infections between about 6,000ng & 250ng, malignancy could not be found among those who had less than 1,200ng. Our individualized safe, effective and economical treatment of various cancers consists of optimal doses of Vitamin D3 with or without Taurine and/or PQQ depending on the positive synergetic compatibility among these 3 substances as normal parts of human tissue. The most serious 2 cases of rectum cancer with multiple metastasis, we confirmed very significant anti-cancer effects of their optimal doses of vitamin D3, which is increased to 800~1,000 I.U. (due to advanced cancer with multiple metastasis instead of the usual 400 I.U. for average adults). The unique 7 beneficial effects of optimal dose of Vitamin D3 (also Taurine or PQQ) include: 1) significant Anti-cancer effects without side effects; 2) marked decrease in DNA mutation as decreases in 8-OH-dG; 3) marked urinary excretion of Viruses, Bacteria, Fungi, & Toxic substances, including Asbestos & metals; 4) marked increase in Acetylcholine in the brain & the rest of the body; 5) marked increase in DHEA; 6) marked decrease in β-Amyloid (I-42); 7) marked decrease in Cardiac Troponin I. Optimal dose of Vitamin D3 is clinically most important for cancer, ischemic heart, and memory problems. Optimal dose of Taurine is 150∼175mg and PQQ is 5-7.5mg and should be taken 3-4 times a day, depending on the patient. Medications and supplements including excessive Vitamin C (as well as multivitamins) but also inhibited optimal doses of Vitamin D3, Taurine & PQQ. Often coffee, drinks containing high Vitamin C content (e.g., some green tea & orange juice), & multivitamins as well as pain medicine (e.g., Oxycodone), strong EMF from cellular phones, and strong negative BDORT underwear often completely eliminate the above beneficial effects of Vitamin D3 and promote growth of cancer.

Spectral grading and Gleason grading of malignant prostate tissue using Stokes shift spectra

NASA Astrophysics Data System (ADS)

Al Salhi, M.; Masilamani, V.; Rabah, D.; Farhat, K.; Liu, C. H.; Pu, Y.; Alfano, R. R.

2012-01-01

Gleason score is the most common method of grading the virulence of prostate malignancy and is based on the pathological assessment of morphology of cellular matrix. Since this involves the excision of the tissue, we are working on a new, minimally invasive, non contact, procedure of spectral diagnosis of prostate malignancy. In this preliminary in vitro study reported here, we have analyzed 27 tissue samples (normal control =7: benign=8: malignant =12) by Stokes' shift spectra (SSS) to establish a one- to- one correlation between spectral grading and Gleason grading.

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer.

PubMed

Wojtczyk-Miaskowska, Anita; Presler, Malgorzata; Michajlowski, Jerzy; Matuszewski, Marcin; Schlichtholz, Beata

2017-01-01

This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology. © 2017 The Author(s). Published by S. Karger AG, Basel.

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

PubMed

Nevins, Marc L; Said, Sherif

2017-12-28

Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

Fast diffuse correlation spectroscopy (DCS) for non-invasive measurement of intracranial pressure (ICP) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Farzam, Parisa; Sutin, Jason; Wu, Kuan-Cheng; Zimmermann, Bernhard B.; Tamborini, Davide; Dubb, Jay; Boas, David A.; Franceschini, Maria Angela

2017-02-01

Intracranial pressure (ICP) monitoring has a key role in the management of neurosurgical and neurological injuries. Currently, the standard clinical monitoring of ICP requires an invasive transducer into the parenchymal tissue or the brain ventricle, with possibility of complications such as hemorrhage and infection. A non-invasive method for measuring ICP, would be highly preferable, as it would allow clinicians to promptly monitor ICP during transport and allow for monitoring in a larger number of patients. We have introduced diffuse correlation spectroscopy (DCS) as a non-invasive ICP monitor by fast measurement of pulsatile cerebral blood flow (CBF). The method is similar to Transcranial Doppler ultrasound (TCD), which derives ICP from the amplitude of the pulsatile cerebral blood flow velocity, with respect to the amplitude of the pulsatile arterial blood pressure. We believe DCS measurement is superior indicator of ICP than TCD estimation because DCS directly measures blood flow, not blood flow velocity, and the small cortical vessels measured by DCS are more susceptible to transmural pressure changes than the large vessels. For fast DCS measurements to recover pulsatile CBF we have developed a custom high-power long-coherent laser and a strategy for delivering it to the tissue within ANSI standards. We have also developed a custom FPGA-based correlator board, which facilitates DCS data acquisitions at 50-100 Hz. We have tested the feasibility of measuring pulsatile CBF and deriving ICP in two challenging scenarios: humans and rats. SNR is low in human adults due to large optode distances. It is similarly low in rats because the fast heart rate in this setting requires a high repetition rate.

Optical monitoring of spinal cord hemodynamics, a feasibility study

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Kwon, Brian K.; Streijger, Femke; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Cripton, Peter A.; Macnab, Andrew

2017-02-01

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

Non-native seagrass Halophila stipulacea forms dense mats under eutrophic conditions in the Caribbean

NASA Astrophysics Data System (ADS)

van Tussenbroek, B. I.; van Katwijk, M. M.; Bouma, T. J.; van der Heide, T.; Govers, L. L.; Leuven, R. S. E. W.

2016-09-01

Seagrasses comprise 78 species and are rarely invasive. But the seagrass Halophila stipulacea, firstly recorded in the Caribbean in the year 2002, has spread quickly throughout the region. Previous works have described this species as invasive in the Caribbean, forming dense mats that exclude native seagrass species. During a reconnaissance field survey of Caribbean seagrass meadows at the islands of Bonaire and Sint Maarten in 2013, we observed that this species was only extremely dense at 5 out of 10 studied meadows. Compared to areas with sparse growth of H. stipulacea, these dense meadows showed consistently higher nutrient concentrations, as indicated by higher leaf tissue N contents of the seagrass Thalassia testudinum (dense when C:N < 22.5) and sediments (dense when %N > 11.3). Thus, the potential invasiveness of this non-native seagrass most likely depends on the environmental conditions, especially the nutrient concentrations.

Thermo-chemotherapy Induced miR-218 upregulation inhibits the invasion of gastric cancer via targeting Gli2 and E-cadherin.

PubMed

Ruan, Qiang; Fang, Zhi-Yuan; Cui, Shu-Zhong; Zhang, Xiang-Liang; Wu, Yin-Bing; Tang, Hong-Sheng; Tu, Yi-Nuo; Ding, Yan

2015-08-01

Thermo-chemotherapy has been proven to reduce the invasion capability of cancer cells. However, the molecular mechanism underlying this anti-invasion effect is still unclear. In this study, the role of thermo-chemotherapy in the inhibition of tumor invasion was studied. The results demonstrated that expression of miR-218 was downregulated in gastric cancer tissues, which had a positive correlation with tumor invasion and metastasis. In vitro thermo-chemotherapy increased miR-218 expression in SGC7901 cells and inhibited both proliferation and invasion of cancer cells. Gli2 was identified as a downstream target of miR-218, and its expression was negatively regulated by miR-218. The thermo-chemotherapy induced miR-218 upregulation was also accompanied by increasing of E-cadherin expression. In conclusion, the present study indicates that thermo-chemotherapy can effectively decrease the invasion capability of cancer cells and increase cell-cell adhesion. miR-218 and its downstream target Gli2, as well as E-cadherin, participate in the anti-invasion process.

Belowground competition drives invasive plant impact on native species regardless of nitrogen availability.

PubMed

Broadbent, Arthur; Stevens, Carly J; Peltzer, Duane A; Ostle, Nicholas J; Orwin, Kate H

2018-02-01

Plant invasions and eutrophication are pervasive drivers of global change that cause biodiversity loss. Yet, how invasive plant impacts on native species, and the mechanisms underpinning these impacts, vary in relation to increasing nitrogen (N) availability remains unclear. Competition is often invoked as a likely mechanism, but the relative importance of the above and belowground components of this is poorly understood, particularly under differing levels of N availability. To help resolve these issues, we quantified the impact of a globally invasive grass species, Agrostis capillaris, on two co-occurring native New Zealand grasses, and vice versa. We explicitly separated above- and belowground interactions amongst these species experimentally and incorporated an N addition treatment. We found that competition with the invader had large negative impacts on native species growth (biomass decreased by half), resource capture (total N content decreased by up to 75%) and even nutrient stoichiometry (native species tissue C:N ratios increased). Surprisingly, these impacts were driven directly and indirectly by belowground competition, regardless of N availability. Higher root biomass likely enhanced the invasive grass's competitive superiority belowground, indicating that root traits may be useful tools for understanding invasive plant impacts. Our study shows that belowground competition can be more important in driving invasive plant impacts than aboveground competition in both low and high fertility ecosystems, including those experiencing N enrichment due to global change. This can help to improve predictions of how two key drivers of global change, plant species invasions and eutrophication, impact native species diversity.

3-D in vitro estimation of temperature using the change in backscattered ultrasonic energy.

PubMed

Arthur, R Martin; Basu, Debomita; Guo, Yuzheng; Trobaugh, Jason W; Moros, Eduardo G

2010-08-01

Temperature imaging with a non-invasive modality to monitor the heating of tumors during hyperthermia treatment is an attractive alternative to sparse invasive measurement. Previously, we predicted monotonic changes in backscattered energy (CBE) of ultrasound with temperature for certain sub-wavelength scatterers. We also measured CBE values similar to our predictions in bovine liver, turkey breast muscle, and pork rib muscle in 2-D in vitro studies and in nude mice during 2-D in vivo studies. To extend these studies to three dimensions, we compensated for motion and measured CBE in turkey breast muscle. 3-D data sets were assembled from images formed by a phased-array imager with a 7.5-MHz linear probe moved in 0.6-mm steps in elevation during uniform heating from 37 to 45 degrees C in 0.5 degrees C increments. We used cross-correlation as a similarity measure in RF signals to automatically track feature displacement as a function of temperature. Feature displacement was non-rigid. Envelopes of image regions, compensated for non-rigid motion, were found with the Hilbert transform then smoothed with a 3 x 3 running average filter before forming the backscattered energy at each pixel. CBE in 3-D motion-compensated images was nearly linear with an average sensitivity of 0.30 dB/ degrees C. 3-D estimation of temperature in separate tissue regions had errors with a maximum standard deviation of about 0.5 degrees C over 1-cm(3) volumes. Success of CBE temperature estimation based on 3-D non-rigid tracking and compensation for real and apparent motion of image features could serve as the foundation for the eventual generation of 3-D temperature maps in soft tissue in a non-invasive, convenient, and low-cost way in clinical hyperthermia.

SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.

PubMed

Meng, Qingbing; Zheng, Minqian; Liu, Hongbing; Song, Changzhi; Zhang, Wensheng; Yan, Juan; Qin, Ling; Liu, Xiaolan

2013-01-01

SASH1, a member of the SLY-family of signal adapter proteins, is a candidate tumor suppressor in breast and colon cancer. The SASH1 protein possesses both the SH3 and SAM domains, indicating that it may play an important role in intracellular signal transduction. Reduced expression of SASH1 is closely related to tumor growth, invasion, metastasis, and poor prognosis. However, the biological role of SASH1 remains unknown in osteosarcoma. To unravel the function of SASH1, we explored the expression of SASH1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and analyzed the relationship between SASH1 expression and cell cycle, apoptosis and invasion of osteosarcoma MG-63 cells, using the flow cytometry analysis and transwell invasion chamber experiments. Furthermore, the effect of SASH1 on the expression of cyclin D1, caspase-3, matrix metalloproteinase (MMP)-9 were observed by western blot. Our results showed that the expression rate of SASH1 mRNA in osteosarcoma tissues was significantly lower than that in normal bone tissue (p = 0.000), that the expression rate of SASH1 mRNA in the carcinoma tissues from patients with lung metastasis was significantly lower than that from patients without lung metastasis (p = 0.041), and that the expression rate of SASH1 mRNA also decreased with increasing Enneking stage (p = 0.032). However, the mRNA expression of SASH1 in osteosarcoma was independent of the patient's gender, age, and tumor size (p = 0.983, 0.343, 0.517, respectively). The SASH1 protein displayed a down-regulation in osteosarcoma tissues compared to normal bone tissue (p = 0.000), displayed a down-regulation in osteosarcoma tissues from patients with lung metastasis compared to from patients without lung metastasis (p = 0.000), and displayed a gradual decrease with increasing Enneking stage (p = 0.000). In addition, the MG-63 cells from pcDNA3.1-SASH1 group exhibited significantly reduced cell viability, proliferation, and invasive ability compared to the empty vector group and blank control group (p = 0.023, 0.001, respectively), and there was no difference between the empty vector group and blank control group. The pcDNA3.1-SASH1 group displayed significantly more apoptotic cells than the empty vector group and blank control group (p = 0.004). The expression of cyclin D1, MMP-9 displayed a down-regulation in MG-63 cells from pcDNA3.1-SASH1 group compared to the empty vector group and blank control group (p = 0.000, 0.001, respectively) and the expression levels of caspase-3 displayed an up-regulation in MG-63 cells from pcDNA3.1-SASH1 group compared to the empty vector group and blank control group (p = 0.000). Taken together, these data indicated that the overexpression of SASH1 might be associated with the inhibition of growth, proliferation, and invasion of MG-63 cells and the promotion of apoptosis of MG-63 cells.

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Invasive hybridization in a threatened species is accelerated by climate change

NASA Astrophysics Data System (ADS)

Muhlfeld, Clint C.; Kovach, Ryan P.; Jones, Leslie A.; Al-Chokhachy, Robert; Boyer, Matthew C.; Leary, Robb F.; Lowe, Winsor H.; Luikart, Gordon; Allendorf, Fred W.

2014-07-01

Climate change will decrease worldwide biodiversity through a number of potential pathways, including invasive hybridization (cross-breeding between invasive and native species). How climate warming influences the spread of hybridization and loss of native genomes poses difficult ecological and evolutionary questions with little empirical information to guide conservation management decisions. Here we combine long-term genetic monitoring data with high-resolution climate and stream temperature predictions to evaluate how recent climate warming has influenced the spatio-temporal spread of human-mediated hybridization between threatened native westslope cutthroat trout (Oncorhynchus clarkii lewisi) and non-native rainbow trout (Oncorhynchus mykiss), the world's most widely introduced invasive fish. Despite widespread release of millions of rainbow trout over the past century within the Flathead River system, a large relatively pristine watershed in western North America, historical samples revealed that hybridization was prevalent only in one (source) population. During a subsequent 30-year period of accelerated warming, hybridization spread rapidly and was strongly linked to interactions between climatic drivers--precipitation and temperature--and distance to the source population. Specifically, decreases in spring precipitation and increases in summer stream temperature probably promoted upstream expansion of hybridization throughout the system. This study shows that rapid climate warming can exacerbate interactions between native and non-native species through invasive hybridization, which could spell genomic extinction for many species.

Improvement in abdominal and flank contouring by a novel adipocyte-selective non-contact radiofrequency device.

PubMed

Choi, Sun Young; Kim, Young Jae; Kim, So Yeon; Lee, Woo Jin; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Won, Chonghyun

2018-05-07

The demand for undergoing subcutaneous fat reduction has been gradually increasing, and there are many methods and devices for performing non-surgical and non-invasive fat reduction, such as high-intensity focused ultrasound, cryolipolysis, radiofrequency (RF) devices, and lasers. This study evaluated the efficacy and safety of a novel adipocyte-selective non-contact RF device for improving abdominal contouring in Asian subjects. Twenty-four Asian subjects with abundant subcutaneous abdominal and love handle fat tissues were enrolled in this prospective clinical study. They received six 45-min weekly treatments with an RF field device over the abdominal and love handle regions. The body mass index and abdominal circumference were measured at baseline and at 4 and 8 weeks post the last treatment. The thickness of the abdomen and depth of subcutaneous abdominal fat tissue were respectively assessed using calipers and abdominal ultrasonography. A subset of 15 subjects was selected by randomization for fat volume measurement via abdominal CT. For safety evaluation, serum lipid, and liver-related blood tests were performed at baseline and at the sixth treatment session. Subjects rated their heat perception level using a four point scale and their pain score using an 11-point visual analog scale during RF treatment. Twenty-four subjects (21 females and 3 males) completed this study with an 8-week follow-up. The average decreases in abdominal circumference at 4 and 8 weeks post treatment were 3.48 ± 2.11 cm (P < 0.001) and 5.12 ± 0.47 cm (P < 0.001), respectively. The average decreases in abdominal fat thickness at 4 and 8 weeks treatment were 0.27 ± 0.61 cm (P = 0.041) and 0.47 ± 0.60 cm (P = 0.001), respectively. The average decreases in subcutaneous fat tissue depth at 4 and 8 weeks post treatment were 0.16 ± 0.43 cm (P = 0.091) and 0.34 ± 0.39 cm (P < 0.001), respectively. However, there was no significant change in the subcutaneous fat tissue volume. The mean heat perception level was 2.24, and the mean pain score was 0.74. No serious adverse effects were observed during treatment and the follow-up periods, and there were no clinically significant changes in lipid or liver-related levels. The adipocyte-selective non-contact RF field device appears to be effective and safe for improving abdominal contouring. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Complications of Minimally Invasive Cosmetic Procedures: Prevention and Management

PubMed Central

Levy, Lauren L; Emer, Jason J

2012-01-01

Over the past decade, facial rejuvenation procedures to circumvent traditional surgery have become increasingly popular. Office-based, minimally invasive procedures can promote a youthful appearance with minimal downtime and low risk of complications. Injectable botulinum toxin (BoNT), soft-tissue fillers, and chemical peels are among the most popular non-invasive rejuvenation procedures, and each has unique applications for improving facial aesthetics. Despite the simplicity and reliability of office-based procedures, complications can occur even with an astute and experienced injector. The goal of any procedure is to perform it properly and safely; thus, early recognition of complications when they do occur is paramount in dictating prevention of long-term sequelae. The most common complications from BoNT and soft-tissue filler injection are bruising, erythema and pain. With chemical peels, it is not uncommon to have erythema, irritation and burning. Fortunately, these side effects are normally transient and have simple remedies. More serious complications include muscle paralysis from BoNT, granuloma formation from soft-tissue filler placement and scarring from chemical peels. Thankfully, these complications are rare and can be avoided with excellent procedure technique, knowledge of facial anatomy, proper patient selection, and appropriate pre- and post-skin care. This article reviews complications of office-based, minimally invasive procedures, with emphasis on prevention and management. Practitioners providing these treatments should be well versed in this subject matter in order to deliver the highest quality care. PMID:23060707

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

EPA Science Inventory

Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying de...

Differential population responses of native and alien rodents to an invasive predator, habitat alteration and plant masting.

PubMed

Fukasawa, Keita; Miyashita, Tadashi; Hashimoto, Takuma; Tatara, Masaya; Abe, Shintaro

2013-12-22

Invasive species and anthropogenic habitat alteration are major drivers of biodiversity loss. When multiple invasive species occupy different trophic levels, removing an invasive predator might cause unexpected outcomes owing to complex interactions among native and non-native prey. Moreover, external factors such as habitat alteration and resource availability can affect such dynamics. We hypothesized that native and non-native prey respond differently to an invasive predator, habitat alteration and bottom-up effects. To test the hypothesis, we used Bayesian state-space modelling to analyse 8-year data on the spatio-temporal patterns of two endemic rat species and the non-native black rat in response to the continual removal of the invasive small Indian mongoose on Amami Island, Japan. Despite low reproductive potentials, the endemic rats recovered better after mongoose removal than did the black rat. The endemic species appeared to be vulnerable to predation by mongooses, whose eradication increased the abundances of the endemic rats, but not of the black rat. Habitat alteration increased the black rat's carrying capacity, but decreased those of the endemic species. We propose that spatio-temporal monitoring data from eradication programmes will clarify the underlying ecological impacts of land-use change and invasive species, and will be useful for future habitat management.

Multimodal noninvasive monitoring of soft tissue wound healing.

PubMed

Bodo, Michael; Settle, Timothy; Royal, Joseph; Lombardini, Eric; Sawyer, Evelyn; Rothwell, Stephen W

2013-12-01

Here we report results of non-invasive measurements of indirect markers of soft tissue healing of traumatic wounds in an observational swine study and describe the quantification of analog physiological signals. The primary purpose of the study was to measure bone healing of fractures with four different wound treatments. A second purpose was to quantify soft tissue wound healing by measuring the following indirect markers: (1) tissue oxygenation, (2) fluid content, and (3) blood flow, which were all measured by non-invasive modalities, measured with available devices. Tissue oxygenation was measured by near infrared spectroscopy; fluid content was measured by bipolar bio-impedance; and blood flow was measured by Doppler ultrasound. Immediately after comminuted femur fractures were produced in the right hind legs of thirty anesthetized female Yorkshire swine, one of four wound treatments was instilled into each wound. The four wound treatments were as follows: salmon fibrinogen/thrombin-n = 8; commercial bone filler matrix-n = 7; bovine collagen-n = 8; porcine fibrinogen/thrombin-n = 7. Fractures were stabilized with an external fixation device. Immediately following wound treatments, measurements were made of tissue oxygenation, fluid content and blood flow; these measurements were repeated weekly for 3 weeks after surgery. Analog signals of each modality were recorded on both the wounded (right) hind leg and the healthy (left) hind leg, for comparison purposes. Data were processed off-line. The mean values of 10-s periods were calculated for right-left leg comparison. ANOVA was applied for statistical analysis. Results of the bone healing studies are published separately (Rothwell et al. in J Spec Oper Med 13:7-18, 2013). For soft tissue wounds, healing did not differ significantly among the four wound treatments; however, regional oxygenation of wounds treated with salmon fibrinogen/thrombin showed slightly different time trends. Further studies are needed to establish standards for healthy wound healing and for detection of pathological alterations such as infection. Non-invasive measurement and quantification of indirect markers of soft tissue wound healing support the goals and principles of evidence-based medicine and show potential as easy to administer tools for clinicians and battlefield medical personnel to apply when procedures such as the PET scan are not available or affordable. The method we developed for storing analog physiological signals could be used for maintaining electronic health records, by incorporating vital signs such as ECG and EEG, etc.

Monitoring for neuroprotection. New technologies for the new millennium

NASA Technical Reports Server (NTRS)

Andrews, R. J.

2001-01-01

Monitoring for neuroprotection, like surgery, has placed on emphasis on minimal or non-invasiveness. Monitoring of parameters that truly reflect the degree of injury to the nervous system is another goal. Thus, two themes for the coming decade in neuromonitoring will be: (1) less-invasive monitoring; and (2) parameters that more closely reflect the etiological factors in ischemic or other neuroinjury. In this paper, we review neuromonitoring techniques and devices that can be used readily in the operating room or intensive care unit setting. Those that require transport of the patient to a special facility (e.g., for computed tomography or magnetic resonance imaging/spectroscopy) and those that have been in standard practice for neuromonitoring (e.g., electrophysiological monitoring--EEG, evoked potentials) are not considered. The two techniques considered in detail are (1) continuous multiparameter local brain tissue monitoring with microprobes, and (2) non-invasive continuous local brain tissue oxygenation monitoring by near infrared spectroscopy. Both techniques have been cleared by the Food and Drug Administration (FDA) for clinical use. The rationale for their use, the nature of the devices, and clinical results to date are reviewed. It is expected that both techniques will gain wide acceptance during the coming decade; further advances in neuromonitoring that can be expected further into the twenty-first century are also discussed.

LncRNA CCAT2 promotes tumorigenesis by over-expressed Pokemon in non-small cell lung cancer.

PubMed

Zhao, Zhihong; Wang, Ju; Wang, Shengfa; Chang, Hao; Zhang, Tiewa; Qu, Junfeng

2017-03-01

Non-small cell lung cancer (NSCLC) remains one of the most important death-related diseases, with poor effective diagnosis and less therapeutic biomarkers. LncRNA colon cancer-associated transcript 2 (CCAT2) was identified as an oncogenic lncRNA and over-expressed in many tumor cells. The aims of this study were to detect the correlation between CCAT2 and its regulatory genes and then explore the potential mechanism between them in NSCLC. In this study, qRT-PCR was used to detect CCAT2, Pokemon and p21 expression. Western-blot was used to detect protein levels of Pokemon and p21. CCK-8 assay and Transwell chambers were used to assess cell viability and invasion. CCAT2 and Pokemon were over-expressed in NSCLC tissue and cells. In NSCLC cells, CCAT2 knockdown significantly decreased cell viability and invasion as well as Pokemon expression, but increased the expression of p21; then CCAT2 overexpression revealed an opposite result. In addition, over-expressed Pokemon reversed the results that induced by si-CCAT2, while down-regulation of Pokemon significantly reversed the results that induced by CCAT2 overexpression. The results indicated that CCAT2 promotes tumorigenesis by over-expression of Pokemon, and the potential mechanism might relate to the Pokemon related gene p21. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Long non-coding RNA H19 regulates viability and metastasis, and is upregulated in retinoblastoma.

PubMed

Li, Li; Chen, Wei; Wang, Yuchuan; Tang, Luosheng; Han, Mei

2018-06-01

Retinoblastoma is the most common type of intraocular pediatric malignant tumor, which typically affects children <6 years of age. However, the underlying molecular mechanisms of retinoblastoma progression remain unclear. The aim of the present study was to investigate the function of long non-coding RNA (lncRNA) H19 in retinoblastoma clinical samples and cell lines, using reverse transcription-quantitative polymerase chain reaction, western blotting, colony formation, MTT, fluorescence activated cell sorting, cell invasion and migration, and in vivo growth assays. The results demonstrated that H19 may serve a critical oncogenic function in the progression of retinoblastoma, as lncRNA H19 levels were markedly increased in retinoblastoma cells and tissues compared with corresponding controls. In addition, patients with retinoblastoma with increased lncRNA H19 expression experienced poorer survival time compared with those with decreased lncRNA H19 levels. Knockdown of lncRNA H19 significantly suppressed retinoblastoma cell proliferation, migration and invasion in vitro and in vivo . Furthermore, lncRNA H19 expression was also associated with multiple proteins, including cyclin-dependent kinase 1, B-cell lymphoma-associated X protein, apoptosis regulator, tumor protein p53, vimentin, cadherin 13 and matrix metallopeptidase 9. In conclusion, lncRNA H19 may serve an important function in tumorigenesis and may be a potential target for therapy and prognosis in retinoblastoma.

Non-contact, Ultrasound-based Indentation Method for Measuring Elastic Properties of Biological Tissues Using Harmonic Motion Imaging (HMI)

PubMed Central

Vappou, Jonathan; Hou, Gary Y.; Marquet, Fabrice; Shahmirzadi, Danial; Grondin, Julien; Konofagou, Elisa E.

2015-01-01

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by Harmonic Motion Imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking RF signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the actual Young’s modulus and the HMI modulus in the numerical study (r2>0.99, relative error <10%) and on polyacrylamide gels (r2=0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI=2.62±0.41 kPa, compared to EMechTesting=4.2±2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens. PMID:25776065

Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI).

PubMed

Vappou, Jonathan; Hou, Gary Y; Marquet, Fabrice; Shahmirzadi, Danial; Grondin, Julien; Konofagou, Elisa E

2015-04-07

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by harmonic motion imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking radiofrequency signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the measured Young's modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI = 2.62  ±  0.41 kPa, compared to EMechTesting = 4.2  ±  2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens.

Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy

NASA Astrophysics Data System (ADS)

Blockhuys, Stéphanie; Agarwal, Nisha Rani; Hildesjö, Camilla; Jarlsfelt, Ingvar; Wittung-Stafshede, Pernilla; Sun, Xiao-Feng

2017-10-01

Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer.

miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.

PubMed

Götte, M; Mohr, C; Koo, C-Y; Stock, C; Vaske, A-K; Viola, M; Ibrahim, S A; Peddibhotla, S; Teng, Y H-F; Low, J-Y; Ebnet, K; Kiesel, L; Yip, G W

2010-12-16

Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.

Quantitative Evaluation of Atherosclerotic Plaque Using Ultrasound Tissue Characterization.

NASA Astrophysics Data System (ADS)

Yigiter, Ersin

Evaluation of therapeutic methods directed toward interrupting and/or delaying atherogenesis is impeded by the lack of a reliable, non-invasive means for monitoring progression or regression of disease. The ability to characterize the predominant component of plaque may be very valuable in the study of this disease's natural history. The earlier the lesion, the more likely is lipid to be the predominant component. Progression of plaque is usually by way of overgrowth of fibrous tissues around the fatty pool. Calcification is usually a feature of the older or complicated lesion. To explore the feasibility of using ultrasound to characterize plaque we have conducted measurements of the acoustical properties of various atherosclerotic lesions found in freshly excised samples of human abdominal aorta. Our objective has been to determine whether or not the acoustical properties of plaque correlate with the type and/or chemical composition of plaque and, if so, to define a measurement scheme which could be done in-vivo and non-invasively. Our current data base consists of individual tissue samples from some 200 different aortas. Since each aorta yields between 10 to 30 tissue samples for study, we have data on some 4,468 different lesions or samples. Measurements of the acoustical properties of plaque were found to correlate well with the chemical composition of plaque. In short, measurements of impedance and attenuation seem sufficient to classify plaque as to type and to composition. Based on the in-vitro studies, the parameter of attenuation was selected as a means of classifying the plaque. For these measurements, an intravascular ultrasound scanner was modified according to our specifications. Signal processing algorithms were developed which would analyze the complex ultrasound waveforms and estimate tissue properties such as attenuation. Various methods were tried to estimate the attenuation from the pulse-echo backscattered signal. Best results were obtained by comparing averaged power spectra in small time windows at different depths for a series of A-lines. Comparisons between consequent averaged spectra at different depths provided the magnitude and frequency dependence of attenuation. Non-invasive characterization of the physical state of the tissue with quantitative ultrasound holds great promise for the extension of the diagnostic power of conventional B-mode imaging.

miR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151

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

Wang, Xun; Yu, Honggang, E-mail: honggang_yuwh@163.com; Lu, Xinyao

2014-02-28

Highlights: • miR-22 was decreased in GC tissue samples and cell lines. • miR-22 suppressed GC cell growth and motility in vitro. • CD151 was a direct target of miR-22. • miR-22 suppressed GC cell growth and motility by inhibiting CD151. - Abstract: Gastric cancer (GC) is the second common cause of cancer-related death worldwide. microRNAs (miRNAs) play important roles in the carcinogenesis of GC. Here, we found that miR-22 was significantly decreased in GC tissue samples and cell lines. Ectopic overexpression of miR-22 remarkably suppressed cell proliferation and colony formation of GC cells. Moreover, overexpression of miR-22 significantly suppressedmore » migration and invasion of GC cells. CD151 was found to be a target of miR-22. Furthermore, overexpression of CD151 significantly attenuated the tumor suppressive effect of miR-22. Taken together, miR-22 might suppress GC cells growth and motility partially by inhibiting CD151.« less

Visualizing the effects of metformin on tumor growth, vascularity, and metabolism in head and neck cancer.

PubMed

Verma, Aparajita; Rich, Laurie J; Vincent-Chong, Vui King; Seshadri, Mukund

2018-05-01

The antidiabetic drug metformin (Met) is believed to inhibit tumor proliferation by altering the metabolism of cancer cells. In this study, we examined the effects of Met on tumor oxygenation, metabolism, and growth in head and neck squamous cell carcinoma (HNSCC) using non-invasive multimodal imaging. Severe combined immunodeficient (SCID) mice bearing orthotopic FaDu HNSCC xenografts were treated with Met (200 mg/kg, ip) once daily for 5 days. Tumor oxygen saturation (%sO 2 ) and hemoglobin concentration (HbT) were measured using photoacoustic imaging (PAI). Fluorescence imaging was employed to measure intratumoral uptake of 2-deoxyglucosone (2-DG) following Met treatment while magnetic resonance imaging (MRI) was utilized to measure tumor volume. Correlative immunostaining of tumor sections for markers of proliferation (Ki67) and vascularity (CD31) was also performed. At 5 days post-Met treatment, PAI revealed a significant increase (P < .05) in %sO 2 and HbT levels in treated tumors compared to untreated controls. Fluorescence imaging at this time point revealed a 46% decrease in mean 2-DG uptake compared to controls. No changes in hemodynamic parameters were observed in mouse salivary gland tissue. A significant decrease in Ki-67 staining (P < .001) and MR-based tumor volume was also observed in Met-treated tumors compared to controls with no change in CD31 + vessel count following Met therapy. Our results provide, for the first time, direct in vivo evidence of Met-induced changes in tumor microenvironmental parameters in HNSCC xenografts. Our findings highlight the utility of multimodal functional imaging for non-invasive mapping of the effects of Met in HNSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of oral squamous-cell cancer and precancerous lesions by fluorescence imaging in a hamster cheek-pouch model

NASA Astrophysics Data System (ADS)

Lam, Stephen; Kluftinger, A. M.; Hung, J.; Davis, N. L.; Quenville, N. F.; Palcic, Branko

1993-03-01

The role of non-skin phototoxic dose of Photofrin in the detection of dysplasia and carcinoma in situ was assessed in a small animal model of oral squamous cell cancer (SCC). Nine,10-dimethyl 1,2-benzanthracene (DMBA) impregnated cotton sutures, covered with a silicone sheath, were sewn into the hamster cheek pouch to produce dysplasia, carcinoma in situ, and invasive cancer. The yield of SCC was 83% by 20 weeks. Fluorescence imaging was performed using a specially designed device that exploits differences of fluorescence properties of normal, precancerous, and cancerous tissues with and without Photofrin. The fluorescence was induced by a helium-cadmium laser (442 nm) and then measured at two different wavelengths by an image intensified camera. Computed images using a mathematical transformation of fluorescence data were then displayed on a video monitor. Areas with dysplasia and both in situ and invasive cancers could be clearly delineated from the adjacent normal tissues. Lesions as small as 2 mm in diameter could be identified. Because of the presence of endogenous porphyrins, the addition of a non-skin phototoxic dose of Photofrin (0.25 mg/kg iv) did not enhance the signal to noise ratio. Our results suggest that fluorescence imaging can accurately detect both precancerous and cancerous lesions in the oral mucosa without exogenous porphyrins. It may have an important role as a non-invasive, clinical diagnostic tool in oropharyngeal cancer.

Trends in the epidemiology of invasive Haemophilus influenzae disease in Queensland, Australia from 2000 to 2013: what is the impact of an increase in invasive non-typable H. influenzae (NTHi)?

PubMed

Wan Sai Cheong, J; Smith, H; Heney, C; Robson, J; Schlebusch, S; Fu, J; Nourse, C

2015-10-01

Following the introduction of vaccination against Haemophilus influenzae type b (Hib), cases of invasive encapsulated Hib disease have decreased markedly. This study aimed to examine subsequent epidemiological trends in invasive H. influenzae disease in Queensland, Australia and in particular, assess the clinical impact and public health implications of invasive non-typable H. influenzae (NTHi) strains. A multicentre retrospective study was conducted from July 2000 to June 2013. Databases of major laboratories in Queensland including Queensland Forensic and Scientific Services (jurisdictional referral laboratory for isolate typing) were examined to identify cases. Demographic, infection site, Indigenous status, serotype, and mortality data were collected. In total, 737 invasive isolates were identified, of which 586 (79·5%) were serotyped. Hib, NTHi and encapsulated non-b strains, respectively, constituted 12·1%, 69·1% and 18·8% of isolates. The predominant encapsulated non-b strains were f (45·5%) and a (27·3%) serotypes. Of isolates causing meningitis, 48·9% were NTHi, 14·9% Hib, 14·9% Hie, 10·6% Hif, 6·4% Hia and 4·3% were untyped. During the study period, there was an increase in the incidence of invasive NTHi disease (P = 0·007) with seasonal peaks in winter and spring (P 0·001) and Hib (P = 0·039) than non-Indigenous patients. In Queensland, invasive H. influenzae disease is now predominantly encountered in adults and most commonly caused by NTHi strains with demonstrated pathogenicity extending to otherwise young or immunocompetent individuals. Routine public health notification of these strains is recommended and recent available immunization options should be considered.

Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness

PubMed Central

Xu, Zheli; Wang, Wan; Deng, Chu-Xia; Man, Yan-gao

2009-01-01

Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC) has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1) in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU), acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be significantly associated with tumor aggressiveness and invasiveness. PMID:19173015

Multimodal nonlinear microscopy of biopsy specimen: towards intraoperative diagnostics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Schmitt, Michael; Heuke, Sandro; Meyer, Tobias; Chernavskaia, Olga; Bocklitz, Thomas W.; Popp, Juergen

2016-03-01

The realization of label-free molecule specific imaging of morphology and chemical composition of tissue at subcellular spatial resolution in real time is crucial for many envisioned applications in medicine, e.g., precise surgical guidance and non-invasive histopathologic examination of tissue. Thus, new approaches for a fast and reliable in vivo and near in vivo (ex corpore in vivo) tissue characterization to supplement routine pathological diagnostics is needed. Spectroscopic imaging approaches are particularly important since they have the potential to provide a pathologist with adequate support in the form of clinically-relevant information under both ex vivo and in vivo conditions. In this contribution it is demonstrated, that multimodal nonlinear microscopy combining coherent anti-Stokes Raman scattering (CARS), two photon excited fluorescence (TPEF) and second harmonic generation (SHG) enables the detection of characteristic structures and the accompanying molecular changes of widespread diseases, particularly of cancer and atherosclerosis. The detailed images enable an objective evaluation of the tissue samples for an early diagnosis of the disease status. Increasing the spectral resolution and analyzing CARS images at multiple Raman resonances improves the chemical specificity. To facilitate handling and interpretation of the image data characteristic properties can be automatically extracted by advanced image processing algorithms, e.g., for tissue classification. Overall, the presented examples show the great potential of multimodal imaging to augment standard intraoperative clinical assessment with functional multimodal CARS/SHG/TPEF images to highlight functional activity and tumor boundaries. It ensures fast, label-free and non-invasive intraoperative tissue classification paving the way towards in vivo optical pathology.

Imaging of the interaction of low frequency electric fields with biological tissues by optical coherence tomography

NASA Astrophysics Data System (ADS)

Peña, Adrian F.; Devine, Jack; Doronin, Alexander; Meglinski, Igor

2014-03-01

We report the use of conventional Optical Coherence Tomography (OCT) for visualization of propagation of low frequency electric field in soft biological tissues ex vivo. To increase the overall quality of the experimental images an adaptive Wiener filtering technique has been employed. Fourier domain correlation has been subsequently applied to enhance spatial resolution of images of biological tissues influenced by low frequency electric field. Image processing has been performed on Graphics Processing Units (GPUs) utilizing Compute Unified Device Architecture (CUDA) framework in the frequencydomain. The results show that variation in voltage and frequency of the applied electric field relates exponentially to the magnitude of its influence on biological tissue. The magnitude of influence is about twice more for fresh tissue samples in comparison to non-fresh ones. The obtained results suggest that OCT can be used for observation and quantitative evaluation of the electro-kinetic changes in biological tissues under different physiological conditions, functional electrical stimulation, and potentially can be used non-invasively for food quality control.

The Assembly of Cell-Encapsulating Microscale Hydrogels Using Acoustic Waves

PubMed Central

Xu, Feng; Finley, Thomas Dylan; Turkaydin, Muge; Sung, Yuree; Gurkan, Umut Atakan; Yavuz, Ahmet Sinan; Guldiken, Rasim; Demirci, Utkan

2011-01-01

Microscale hydrogels find widespread applications in medicine and biology, e.g., as building blocks for tissue engineering and regenerative medicine. In these applications, these microgels are assembled to fabricate large complex 3D constructs. The success of this approach requires non-destructive and high throughput assembly of the microgels. Although various assembly methods have been developed based on modifying interfaces, and using microfluidics, so far, none of the available assembly technologies have shown the ability to assembly microgels using non-invasive fields rapidly within seconds in an efficient way. Acoustics has been widely used in biomedical area to manipulatedroplets, cells and biomolecules. In this study, we developed a simple, non-invasiveacoustic assembler for cell-encapsulating microgels with maintained cell viability (>93%). We assessed the assembler for both microbeads (with diameter of 50 µm and 100 µm) and microgels of different sizes and shapes (e.g., cubes, lock-and-key shapes, tetris, saw) in microdroplets (with volume of 10 µL, 20 µL, 40 µL, 80 µL). The microgels were assembled in second sin a non-invasive manner. These results indicate that the developed acoustic approach could become an enabling biotechnology tool for tissue engineering, regenerative medicine, pharmacology studies and high throughput screening applications. PMID:21820734

Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies

PubMed Central

2012-01-01

Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review. PMID:22857649

Near-infrared muscle functional monitoring

NASA Astrophysics Data System (ADS)

Ferrari, Marco; De Blasi, Roberto A.; Ferrari, Adriano; Pizzi, Assunta; Quaresima, Valentina

1994-01-01

The oxygenation of human muscle tissue can be investigated using near IR spectroscopy (NIRS). Oxy and deoxy hemoglobin changes can be quantified combining attenuation measurements with pathlength data obtained by time resolved spectroscopy. This study reports the application of NIRS to non- invasive measurements of quadriceps oxygenation on muscular dystrophy patients during treadmill exercise.

FGFR4 Role in Epithelial-Mesenchymal Transition and Its Therapeutic Value in Colorectal Cancer

PubMed Central

Torres, Sofía; Hernández-Varas, Pablo; Teixidó, Joaquín; Bonilla, Félix; de Herreros, Antonio Garcia; Casal, J. Ignacio

2013-01-01

Fibroblast growth factor receptor 4 (FGFR4) is vital in early development and tissue repair. FGFR4 expression levels are very restricted in adult tissues, except in several solid tumors including colorectal cancer, which showed overexpression of FGFR4. Here, FGFR4 mutation analysis discarded the presence of activating mutations, other than Arg388, in different colorectal cancer cell lines and tumoral samples. Stable shRNA FGFR4-silencing in SW480 and SW48 cell lines resulted in a significant decrease in cell proliferation, adhesion, cell migration and invasion. This decrease in the tumorigenic and invasive capabilities of colorectal cancer cells was accompanied by a decrease of Snail, Twist and TGFβ gene expression levels and an increase of E-cadherin, causing a reversion to a more epithelial phenotype, in three different cell lines. In addition, FGFR4-signaling activated the oncogenic SRC, ERK1/2 and AKT pathways in colon cancer cells and promoted an increase in cell survival. The relevance of FGFR4 in tumor growth was supported by two different strategies. Kinase inhibitors abrogated FGFR4-related cell growth and signaling pathways at the same extent than FGFR4-silenced cells. Specific FGFR4-targeting using antibodies provoked a similar reduction in cell growth. Moreover, FGFR4 knock-down cells displayed a reduced capacity for in vivo tumor formation and angiogenesis in nude mice. Collectively, our data support a crucial role for FGFR4 in tumorigenesis, invasion and survival in colorectal cancer. In addition, FGFR4 targeting demonstrated its applicability for colorectal cancer therapy. PMID:23696849

[Epidemiology of invasive group A streptococcal infections in developed countries : the Canadian experience with necrotizing fasciitis].

PubMed

Ovetchkine, Ph; Bidet, Ph; Minodier, Ph; Frère, J; Bingen, E

2014-11-01

In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

PubMed Central

Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-01-01

Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell-cell interaction with integrins-based cell-matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells' interaction with extracellular matrix component fibronectin. Silibinin (50-200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these results showed that silibinin targets PCA cells' interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression. PMID:25285031

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling.

PubMed

Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-10-01

Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell-cell interaction with integrins-based cell-matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells' interaction with extracellular matrix component fibronectin. Silibinin (50-200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these results showed that silibinin targets PCA cells' interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

PubMed

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Mechanisms of Normal and Abnormal Endometrial Bleeding

PubMed Central

Lockwood, Charles J.

2011-01-01

Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

A Low Frequency Electromagnetic Sensor for Indirect Measurement of Glucose Concentration: In Vitro Experiments in Different Conductive Solutions

PubMed Central

Tura, Andrea; Sbrignadello, Stefano; Cianciavicchia, Domenico; Pacini, Giovanni; Ravazzani, Paolo

2010-01-01

In recent years there has been considerable interest in the study of glucose-induced dielectric property variations of human tissues as a possible approach for non-invasive glycaemia monitoring. We have developed an electromagnetic sensor, and we tested in vitro its ability to estimate variations in glucose concentration of different solutions with similarities to blood (sodium chloride and Ringer-lactate solutions), differing though in the lack of any cellular components. The sensor was able to detect the effect of glucose variations over a wide range of concentrations (∼78–5,000 mg/dL), with a sensitivity of ∼0.22 mV/(mg/dL). Our proposed system may thus be useful in a new approach for non-invasive and non-contact glucose monitoring. PMID:22219665

Neural and Decision Theoretic Approaches for the Automated Segmentation of Radiodense Tissue in Digitized Mammograms

NASA Astrophysics Data System (ADS)

Eckert, R.; Neyhart, J. T.; Burd, L.; Polikar, R.; Mandayam, S. A.; Tseng, M.

2003-03-01

Mammography is the best method available as a non-invasive technique for the early detection of breast cancer. The radiographic appearance of the female breast consists of radiolucent (dark) regions due to fat and radiodense (light) regions due to connective and epithelial tissue. The amount of radiodense tissue can be used as a marker for predicting breast cancer risk. Previously, we have shown that the use of statistical models is a reliable technique for segmenting radiodense tissue. This paper presents improvements in the model that allow for further development of an automated system for segmentation of radiodense tissue. The segmentation algorithm employs a two-step process. In the first step, segmentation of tissue and non-tissue regions of a digitized X-ray mammogram image are identified using a radial basis function neural network. The second step uses a constrained Neyman-Pearson algorithm, developed especially for this research work, to determine the amount of radiodense tissue. Results obtained using the algorithm have been validated by comparing with estimates provided by a radiologist employing previously established methods.

RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK

PubMed Central

Ziv-Av, Amotz; Giladi, Nissim David; Lee, Hae Kyung; Cazacu, Simona; Finniss, Susan; Xiang, Cunli; Pauker, Maor H.; Barda-Saad, Mira; Poisson, Laila; Brodie, Chaya

2015-01-01

Glioblastoma (GBM) are characterized by increased invasion into the surrounding normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the migration and invasion of glioma cells. To further study RTVP-1 effects we performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry and found that RTVP-1 was associated with the actin polymerization regulator, N-WASP. This association was further validated by co-immunoprecipitation and FRET analysis. We found that RTVP-1 increased cell spreading, migration and invasion and these effects were at least partly mediated by N-WASP. Another protein which was found by the pull-down assay to interact with RTVP-1 is hnRNPK. This protein has been recently reported to associate with and to inhibit the effect of N-WASP on cell spreading. hnRNPK decreased cell migration, spreading and invasion in glioma cells. Using co-immunoprecipitation we validated the interactions of hnRNPK with N-WASP and RTVP-1 in glioma cells. In addition, we found that overexpression of RTVP-1 decreased the association of N-WASP and hnRNPK. In summary, we report that RTVP-1 regulates glioma cell spreading, migration and invasion and that these effects are mediated via interaction with N-WASP and by interfering with the inhibitory effect of hnRNPK on the function of this protein. PMID:26305187