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Sample records for cancer kidney tissues

  1. Kidney Cancer

    MedlinePlus

    ... common cancers in the United States. Cancer Home Kidney Cancer Language: English Español (Spanish) Recommend on Facebook ... work with the chemical trichloroethylene. What Are the Kidneys? The body has two kidneys, one on each ...

  2. The AKT-mTOR signalling pathway in kidney cancer tissues

    NASA Astrophysics Data System (ADS)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Kolegova, E. S.

    2015-11-01

    An increased expression of phospho-AKT, m-TOR, glycogen regulator GSK-3-beta and transcription inhibitor 4E-BP1 was observed in kidney cancer tissues. Tumor size growth was associated with a high level of c-Raf and low content of phospho-m-TOR. Cancer metastasis development led to a decreased PTEN and phospho-AKT expression.

  3. Targeted Therapies for Kidney Cancer

    MedlinePlus

    ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  4. Investigation of trace elements in cancer kidney tissues by SRIXE and PIXE

    NASA Astrophysics Data System (ADS)

    Kwiatek, W. M.; Drewniak, T.; Lekka, M.; Wajdowicz, A.

    1996-04-01

    In November 1994 we performed some preliminary studies on cancer kidney tissues. The objective of the measurements was to find a difference in trace element concentrations between normal and cancerous kidney tissue. All targets were prepared as pellets of more or less the same weight and thickness. Kidney samples were obtained during surgical operations done in the Clinic of Urology in Cracow. All kidneys were subject to removal due to cancer disease. Samples for analysis were taken from the cancerous part of the kidney and the non-cancerous one. All samples were analyzed by means of SRIXE (Synchrotron Radiation Induced X-ray Emission) at the NSLS (National Synchrotron Light Source) in BNL (Brookhaven National Laboratory) and by means of PIXE at INP (Institute of Nuclear Physics) in Cracow. According to the physician's investigations, cadmium plays a role in oxidation process during tumor growth. Also the other elements i.e. selenium plays here a significant role. The results obtained so far seem to be interesting and may confirm our hypothesis about the cancer process in the kidney, the hypothesis will be a subject of further study. The applied analytical technique enables us to analyze with high precision even a small region of samples.

  5. Kidney Cancer

    MedlinePlus

    You have two kidneys. They are fist-sized organs on either side of your backbone above your waist. The tubes inside filter and ... blood, taking out waste products and making urine. Kidney cancer forms in the lining of tiny tubes ...

  6. Kidney cancer.

    PubMed

    Linehan, W Marston; Rathmell, W Kimryn

    2012-01-01

    Over 65,000 Americans are diagnosed with kidney cancer each year and nearly 13,000 die of this disease. Kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Study of the 13 genes that are known to cause kidney cancer has led to the understanding that kidney cancer is a metabolic disease. Recent discoveries of chromatin remodeling/histone modifying genes, such as PBRM1 and SETD2, have opened up new areas of intense interest in the study of the fundamental genetic basis of kidney cancer. New approaches to immunotherapy with agents such as the CTLA4 inhibitor, ipilumumab, have opened up promising new directions for clinical trials. A number of new agents targeting of VEGF receptor signaling and the mTOR pathways as well as novel approaches targeting HIF2 will hopefully provide the foundation for the development of effective forms of therapy for this disease.

  7. Biologic Therapy (Immunotherapy) for Kidney Cancer

    MedlinePlus

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  8. Kidney Cancer in Children

    MedlinePlus

    What is Kidney Cancer in Children? Kidney (renal) tumors are very rare in children. Still, the three most common renal tumors ... treatable and curable. What are the Types of Kidney Cancer in Children? Male urinary tract Medical Illustration ...

  9. Living with Kidney Cancer

    MedlinePlus

    ... Award Living With Kidney Cancer Living With Cancer Day to Day The impact of kidney cancer on your life ... least one half hour of exercise every other day. Vigorous walking, jogging, swimming, or other aerobic exercise ...

  10. Detection of cancerous kidney tissue areas by means of infrared spectroscopy of intercellular fluid

    NASA Astrophysics Data System (ADS)

    Urboniene, V.; Jankevicius, F.; Zelvys, A.; Steiner, G.; Sablinskas, V.

    2014-03-01

    In this work the infrared absorption spectra of intercellular fluid of normal and tumor kidney tissue were recorded and analyzed. The samples were prepared by stamping freshly resected tissue onto a CaF2 substrate. FT-IR spectra obtained from intracellular fluid of tumor tissue exhibit stronger absorption bands in the spectral region from 1000-1200 cm-1 and around 1750 cm-1 than those obtained from normal tissue. It is likely the spectra of extracellular matrix of kidney tumor tissue with large increases in the intensities of these bands represent a higher concentration of fatty acids and glycerol. Amide I and amide II bands are stronger in spectra of normal tissue indicating a higher level of proteins. The results demonstrate that FT-IR spectroscopy of intercellular fluids is a novel approach for a quick diagnosis during surgical resection, which can improve the therapy of kidney tumors.

  11. What Is Kidney Cancer (Renal Cell Carcinoma)?

    MedlinePlus

    ... Treatment? Kidney Cancer About Kidney Cancer What Is Kidney Cancer? Kidney cancer is a cancer that starts ... and spread, see What Is Cancer? About the kidneys To understand more about kidney cancer, it helps ...

  12. Intra-operative on-line discrimination of kidney cancer from normal tissue by IR ATR spectroscopy of extracellular fluid

    NASA Astrophysics Data System (ADS)

    Urboniene, V.; Velicka, M.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.; Steiner, G.

    2016-03-01

    Determination of cancerous and normal kidney tissues during partial, simple or radical nephrectomy surgery was performed by using differences in the IR absorption spectra of extracellular fluid taken from the corresponding tissue areas. The samples were prepared by stamping of the kidney tissue on ATR diamond crystal. The spectral measurements were performed directly in the OR during surgery for 58 patients. It was found that intensities of characteristic spectral bands of glycogen (880-1200 cm-1) in extracellular fluid are sensitive to the type of the tissue and can be used as spectral markers of tumours. Characteristic spectral band of lactic acid (1730 cm-1) - product of the anaerobic glycolysis, taking place in the cancer cells is not suitable for use as a spectral marker of cancerous tissue, since it overlaps with the band of carbonyl stretch in phospholipids and fatty acids. Results of hierarchical cluster analysis of the spectra show that the spectra of healthy and tumour tissue films can be reliably separated into two groups. On the other hand, possibility to differentiate between tumours of different types and grades remains in question. While the fluid from highly malignant G3 tumour tissue contains highly pronounced glycogen spectral bands and can be well separated from benign and G1 tumours by principal component analysis, the variations between spectra from sample to sample prevent from obtaining conclusive results about the grouping between different tumour types and grades. The proposed method is instant and can be used in situ and even in vivo.

  13. Kidney Cancer

    MedlinePlus

    ... are synthetic versions of chemicals made in your body. Side effects of these drugs include chills, fever, nausea, vomiting and loss of ... cancer cells to grow and survive. Targeted therapy drugs can cause side ... areas of the body, such as the bones. No complementary and alternative ...

  14. What Happens After Treatment for Kidney Cancer?

    MedlinePlus

    ... Cancer After Treatment What Happens After Treatment for Kidney Cancer? For some people with kidney cancer, treatment can ... Treatment for Kidney Cancer Stops Working More In Kidney Cancer About Kidney Cancer Causes, Risk Factors, and Prevention ...

  15. Ablation and Other Local Therapy for Kidney Cancer

    MedlinePlus

    ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  16. Hereditary kidney cancer syndromes.

    PubMed

    Haas, Naomi B; Nathanson, Katherine L

    2014-01-01

    Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of kidney cancer, which are reviewed herein. Clear cell kidney cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome, and mutations in the BAP1 gene as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary kidney cancers arise in conjunction with germline mutations in MET and type 2 as part of hereditary leiomyomatosis and kidney cell cancer (fumarate hydratase [FH] mutations). Chromophone and oncocytic kidney cancers are predominantly associated with Birt-Hogg-Dubé syndrome. Patients with Tuberous Sclerosis Complex (TSC) commonly have angiomyolipomas and rarely their malignant counterpart epithelioid angiomyolipomas. The targeted therapeutic options for the kidney cancer associated with these diseases are just starting to expand and are an area of active clinical research.

  17. Kidney diseases and tissue engineering.

    PubMed

    Moon, Kyung Hyun; Ko, In Kap; Yoo, James J; Atala, Anthony

    2016-04-15

    Kidney disease is a worldwide public health problem. Renal failure follows several disease stages including acute and chronic kidney symptoms. Acute kidney injury (AKI) may lead to chronic kidney disease (CKD), which can progress to end-stage renal disease (ESRD) with a mortality rate. Current treatment options are limited to dialysis and kidney transplantation; however, problems such as donor organ shortage, graft failure and numerous complications remain a concern. To address this issue, cell-based approaches using tissue engineering (TE) and regenerative medicine (RM) may provide attractive approaches to replace the damaged kidney cells with functional renal specific cells, leading to restoration of normal kidney functions. While development of renal tissue engineering is in a steady state due to the complex composition and highly regulated functionality of the kidney, cell therapy using stem cells and primary kidney cells has demonstrated promising therapeutic outcomes in terms of restoration of renal functions in AKI and CKD. In this review, basic components needed for successful renal kidney engineering are discussed, and recent TE and RM approaches to treatment of specific kidney diseases will be presented.

  18. Distribution study of cisplatin in rat kidney and liver cancer tissues by using liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-06-01

    A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and

  19. Epidemiology of Kidney Cancer

    PubMed Central

    Pascual, D.; Borque, A.

    2008-01-01

    Some tumors are known to have a definite cause-effect etiology, but renal cell carcinoma (RCC) is not one of them precisely. With regard to RCC we can only try to identify some clinical and occupational factors as well as substances related to tumorigenesis. Smoking, chemical carcinogens like asbestos or organic solvents are some of these factors that increase the risk of the RCC. Viral infections and radiation therapy have also been described as risk factors. Some drugs can increase the incidence of RCC as well as other neoplasms. Of course, genetics plays an outstanding role in the development of some cases of kidney cancer. Chronic renal failure, hypertension, and dialysis need to be considered as special situations. Diet, obesity, lifestyle, and habits can also increase the risk of RCC. The aim of this review is to summarize the well-defined causes of renal cell carcinoma. PMID:19009036

  20. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  1. Spectroscopic monitoring of kidney tissue ischemic injury

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Jason T.; Michalopoulou, Andromachi P.; Troppmann, Christoph; Demos, Stavros G.

    2004-07-01

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  2. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  3. Simultaneously targeting tissue transglutaminase and kidney type glutaminase sensitizes cancer cells to acid toxicity and offers new opportunities for therapeutic intervention.

    PubMed

    Katt, William P; Antonyak, Marc A; Cerione, Richard A

    2015-01-05

    Most cancer cells undergo characteristic metabolic changes that are commonly referred to as the Warburg effect, with one of the hallmarks being a dramatic increase in the rate of lactic acid fermentation. This leads to the production of protons, which in turn acidifies the microenvironment surrounding tumors. Cancer cells have acquired resistance to acid toxicity, allowing them to survive and grow under these detrimental conditions. Kidney type glutaminase (GLS1), which is responsible for the conversion of glutamine to glutamate, produces ammonia as part of its catalytic activities and has been shown to modulate cellular acidity. In this study, we show that tissue, or type 2, transglutaminase (TG2), a γ-glutamyl transferase that is highly expressed in metastatic cancers and produces ammonia as a byproduct of its catalytic activity, is up-regulated by decreases in cellular pH and helps protect cells from acid-induced cell death. Since both TG2 and GLS1 can similarly function to protect cancer cells, we then proceeded to demonstrate that treatment of a variety of cancer cell types with inhibitors of each of these proteins results in synthetic lethality. The combination doses of the inhibitors induce cell death, while individual treatment with each compound shows little or no ability to kill cells. These results suggest that combination drug treatments that simultaneously target TG2 and GLS1 might provide an effective strategy for killing cancer cells.

  4. Living with Kidney Cancer

    MedlinePlus

    ... Institute for Cancer Research website ( www.aicr.org ). Self-medication Many cancer patients medicate themselves with food and ... cancer. There is little research evidence that such self-medication can directly influence recurrence or cure. Patients should ...

  5. What Should You Ask Your Doctor about Kidney Cancer?

    MedlinePlus

    ... Staging What Should You Ask Your Doctor About Kidney Cancer? It’s important to have frank, open discussions ... Ask Your Doctor About Kidney Cancer? More In Kidney Cancer About Kidney Cancer Causes, Risk Factors, and ...

  6. New application of a subcellular fractionation method to kidney and testis for the determination of conjugated linoleic acid in selected cell organelles of healthy and cancerous human tissues.

    PubMed

    Hoffmann, Kristina; Blaudszun, Jörg; Brunken, Claus; Höpker, Wilhelm-Wolfgang; Tauber, Roland; Steinhart, Hans

    2005-03-01

    To clarify the mechanism of the anticarcinogenic effect of conjugated linoleic acid (CLA), its intracellular distribution needs to be determined. Subcellular fractionation using centrifugation techniques is a method that is frequently used for isolation of cell organelles from different tissues. But as the size and density of the organelles differ, the method needs to be optimised for every type of tissue. The novelty of this study is the application of a subcellular fractionation method to human healthy and cancerous renal and testicular tissue. Separation of total tissue homogenate into nuclei, cytosol, and a mixture of mitochondria and plasma membranes was achieved by differential centrifugation. As mitochondria and plasma membranes seemed to be too similar in size and weight to be separated by differential centrifugation, discontinuous density-gradient centrifugation was carried out successfully. The purity of the subcellular fractions was checked by measuring the activity of marker enzymes. All fractions were highly enriched in their corresponding marker enzyme. However, the nuclear fractions of kidney and renal cell carcinoma were slightly contaminated with mitochondria and plasma membrane fractions of all tissues with lysosomes. The fraction designated the cytosolic fraction contained not only cytosol, but also microsomes and lysosomes. The CLA contents of the subcellular fractions were in the range 0.13-0.37% of total fatty acids and were lowest in the plasma membrane fractions of all types of tissue studied. C16:0, C18:0, C18:1 c9, C18:2 n-6, and C20:4 n-6 were found to be the major fatty acids in all the subcellular fractions studied. However, marked variations in fatty acid content between subcellular fractions and between types of tissue were detectable. Because of these differences between tissues, no general statement on characteristic fatty acid profiles of single subcellular fractions is possible.

  7. Soft Tissue Sarcomas of the Kidney

    PubMed Central

    Köhle, Olivia; Abt, Dominik; Rothermundt, Christian; Öhlschlegel, Christian; Brugnolaro, Christiane; Schmid, Hans-Peter

    2015-01-01

    Soft tissue sarcomas are rare mesenchymal tumors. Amongst others, primitive neuroectodermal tumors (PNET) of the kidney and synovial sarcoma of the kidney belong to the group of soft tissue sarcomas. Synovial sarcomas can occur almost anywhere in the body, most frequently, however, in the lower (62%) or upper extremities (21%). Metastases occur in 50-70% of cases, and thus the prognosis is poor. PNETs are rare, highly aggressive neoplastic lesions which mainly occur in the torso or axial skeleton in young adults. The prognosis is poor with a 5-year disease-free survival rate of 45-55%. The primary therapeutic approach is surgical resection. Most randomized studies assessing adjuvant chemotherapy for all types of localized soft tissue sarcomas did not show statistically significantly better overall survival times after chemotherapy, although they did show longer progression-free survival. We report on two cases of primary renal synovial sarcoma and one case of PNET of the kidney. PMID:25918607

  8. [Kidney function and renal cancer surgery].

    PubMed

    Izzedine, Hassan; Méjean, Arnaud; Escudier, Bernard

    2014-02-01

    Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.

  9. What You Need to Know about Kidney Cancer

    MedlinePlus

    ... Publications Reports What You Need To Know About™ Kidney Cancer This booklet is about cancer that starts in ... choices about your care. This booklet covers: How kidney cancer is diagnosed Common symptoms for kidney cancer Treatments ...

  10. Tumour suppressor gene (CDKNA2) status on chromosome 9p in resected renal tissue improves prognosis of localised kidney cancer

    PubMed Central

    El-Mokadem, Ismail; Kidd, Thomas; Pratt, Norman; Fleming, Stewart; Nabi, Ghulam

    2016-01-01

    Background Genetic alterations on chromosome 9p, including inactivation of the tumour suppressor gene, CDKN2A, result in cellular proliferation and growth of tumours. Our aim was to use microsatellite analysis and fluorescence in situ hybridization (FISH) to characterise the architecture of this region. Results Seventy-five out of 77 clear cell renal cell cancers (tumour/normal pairs) were interpretable for LOH analysis on chromosome 9p (two tumours were excluded, as all five primers were uninformative). Twenty out of 75 (26.6%) tumours showed LOH in at least one of the five primers employed. Most allelic deletions were detected, telomeric to the CDKN2A region at D9S916, with 11 out of 52 informative tumours (21%) displaying LOH. The LOH in the coding region of CDKN2A, at D9S974 and D9S942, was associated with a higher pT-stage (p = 0.004) and metastasis (p = 0.006, both markers). The rate of chromosome 9p deletion in ccRCC was 44% (35/80 cases) according to FISH. Somatic copy number loss of chromosome 9p was associated with a larger tumour size (p = 0.002), higher pathological tumour stage (p = 0.021), presence of tumour necrosis (p = 0.019) and microvascular invasion (p = 0.032). The cases with copy number loss, loss of heterozygosity and copy number neutral (n = 42) were at a higher risk of cancer-specific death when compared to tumours in category D (n = 32) (Log-rank: p = 0.001). Seventeen patients with localised ccRCC developed recurrence, and fourteen of those showed either LOH or somatic copy number loss at CDKN2A (Log-rank: p = 0.005). Multivariate analysis showed that LOH or copy number loss at CDKN2A retained its independent prognostic effect, improving the predictive accuracy of stage and SSIGN score by concordance Index C from 0.823 to 0.878 (p = 0.001). Materials and Methods Cytogenetics data, microsatellite analysis and FISH were acquired for a cohort of patients undergoing resection for clinically localised renal cancer between January 2001 and

  11. What Are the Key Statistics about Kidney Cancer?

    MedlinePlus

    ... Cancer About Kidney Cancer What Are the Key Statistics About Kidney Cancer? The American Cancer Society’s most ... by stage .” Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

  12. Studying the Genetic Basis of Kidney Cancer - TCGA

    Cancer.gov

    Dr. Marston Linehan, NCI's Chief of Urologic Surgery, has spent the last several decades studying kidney cancer genes and treating kidney cancer patients. Learn more about his experience as a kidney cancer physician scientist and TCGA contributor in this

  13. What's New in Kidney Cancer Research and Treatment?

    MedlinePlus

    ... and Treatment? Kidney Cancer About Kidney Cancer What’s New in Kidney Cancer Research and Treatment? Research on ... can also be used to develop new treatments. New approaches to local treatment High-intensity focused ultrasound ( ...

  14. Role of Grainyhead in Kidney Cancer

    DTIC Science & Technology

    2014-12-01

    AD______________ Award Number: W81XWH-12-1-0428 TITLE: Role of Grainyhead in Kidney Cancer PRINCIPAL INVESTIGATOR: Steven Frisch CONTRACTING...SUBTITLE Role of Grainyhead in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0428 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Steven...metastatic gene expression in RCC. 15. SUBJECT TERMS Grainyhead-like-2/ kidney /collecting ducts/proximal tubules/distal tubules/clear cell renal

  15. RLIP76 Targeted Therapy for Kidney Cancer.

    PubMed

    Singhal, Sharad S; Singhal, Jyotsana; Figarola, James; Horne, David; Awasthi, Sanjay

    2015-10-01

    Despite recent improvements in chemotherapeutic approaches to treating kidney cancer, this malignancy remains deadly if not found and removed at an early stage of the disease. Kidney cancer is highly drug-resistant, which may at least partially result from high expression of transporter proteins in the cell membranes of kidney cells. Although these transporter proteins can contribute to drug-resistance, targeting proteins from the ATP-binding cassette transporter family has not been effective in reversing drug-resistance in kidney cancer. Recent studies have identified RLIP76 as a key stress-defense protein that protects normal cells from damage caused by stress conditions, including heat, ultra-violet light, X-irradiation, and oxidant/electrophilic toxic chemicals, and is crucial for protecting cancer cells from apoptosis. RLIP76 is the predominant glutathione-electrophile-conjugate (GS-E) transporter in cells, and inhibiting it with antibodies or through siRNA or antisense causes apoptosis in many cancer cell types. To date, blocking of RLIP76, either alone or in combination with chemotherapeutic drugs, as a therapeutic strategy for kidney cancer has not yet been evaluated in human clinical trials, although there is considerable potential for RLIP76 to be developed as a therapeutic agent for kidney cancer. In the present review, we discuss the mechanisms underlying apoptosis caused by RLIP76 depletion, the role of RLIP76 in clathrin-dependent endocytosis deficiency, and the feasibility of RLIP76-targeted therapy for kidney cancer.

  16. Kidney stem cells in development, regeneration and cancer.

    PubMed

    Dziedzic, Klaudyna; Pleniceanu, Oren; Dekel, Benjamin

    2014-12-01

    The generation of nephrons during development depends on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. These cells may transform to generate oncogenic stem cells and drive pediatric renal cancer. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex vivo preserve and expand the observed in vivo kidney-forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephron stem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells toward expandable renal progenitors.

  17. What Are the Risk Factors for Kidney Cancer?

    MedlinePlus

    ... and Prevention What Are the Risk Factors for Kidney Cancer? A risk factor is anything that affects ... not cancer). Other risk factors Family history of kidney cancer People with a strong family history of ...

  18. Cabozantinib and lenvatinib for kidney cancer

    Cancer.gov

    An NCI’s Cancer Currents blog on the FDA’s recent approval of cabozantinib (Cometriq®) and lenvatinib (Lenvima®) for the treatment of patients whose advanced kidney cancers have progressed after prior treatment with antiangiogenic therapies.

  19. Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling of Multiple Spatially Separated Samples within Tumors.

    PubMed

    Okegawa, Takatsugu; Morimoto, Megumi; Nishizawa, Satoru; Kitazawa, Satoshi; Honda, Kohei; Araki, Hideo; Tamura, Toshiya; Ando, Ayumi; Satomi, Yoshinori; Nutahara, Kikuo; Hara, Takahito

    2017-04-06

    Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here, we used global metabolomics analysis and tissue slice tracer studies to demonstrate that different portions of a human primary kidney tumor possess different metabolic characteristics and drug sensitivity. Pyruvate levels were elevated and pyruvate metabolism was altered in some tumor sections. These observations indicated that pyruvate metabolism may constitute a possible vulnerability of kidney cancer; indeed, pyruvate stimulated the growth of primary kidney cancer cells and pharmacological inhibition of pyruvate transporters slowed the growth of patient-derived kidney tumors in mice. These findings deepen our understanding of the intratumor metabolic heterogeneity of kidney cancer and may inform novel therapeutic approaches in human kidney cancer.

  20. How Is Kidney Cancer Diagnosed?

    MedlinePlus

    ... a person is healthy enough for surgery . Blood chemistry tests Blood chemistry tests are usually done in people who might ... a doctor to order a bone scan. Blood chemistry tests also look at kidney function, which is ...

  1. Acute kidney injury in the cancer patient.

    PubMed

    Campbell, G Adam; Hu, Daniel; Okusa, Mark D

    2014-01-01

    Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.

  2. Epidemiology and risk factors for kidney cancer

    PubMed Central

    Chow, Wong-Ho; Dong, Linda M.; Devesa, Susan S.

    2010-01-01

    After over two decades of increasing rates, kidney cancer incidence trends worldwide show signs of plateauing or decreases in recent years. In the United States, rates for renal cell cancer, the predominant form of kidney cancer in adults, continue to rise but mainly for early stage tumors. Incidence rates for renal pelvis cancer have declined, while kidney cancer mortality rates overall have leveled. These patterns are consistent with reports of incidental diagnosis and downward shift of tumor stage and size in clinical series. The changing prevalence of known risk factors for renal cell cancer, including cigarette smoking, obesity, and hypertension, may also be influencing the incidence trends, although their relative impact may differ in various populations,. Evidence is accumulating to suggest an etiologic role for physical activity, alcohol consumption, occupational exposure to trichloroethylene, and high parity among women, but causal conclusions are not yet supported. Genetic susceptibility and its interaction with environmental exposures are believed to influence renal cell cancer risk, but limited studies based on candidate gene approaches have not produced conclusive results. Large consortium efforts employing genome-wide scanning technology are underway, which hold promise for novel discoveries in renal carcinogenesis. PMID:20448658

  3. Researching the experience of kidney cancer patients.

    PubMed

    Taylor, K

    2002-09-01

    The author's personal experience as a kidney cancer patient, researcher and founder of a kidney cancer support group forms the basis for consideration of the challenges involved in researching patients' experiences. The researcher needs to understand the variability of those experiences in both clinical and psychological-emotional terms, and in relation to the personal, familial and social contexts of the patient. It is also essential to define the purpose of the research and to show how an understanding of personal experiences of cancer can be used to enhance the quality of care for cancer patients. The research encounter with a patient is also in some respects a therapeutic encounter requiring a considerable degree of sensitivity on the part of the researcher. The person-centred approach of Carl Rogers is of value in supporting such an encounter.

  4. Renal cancer in kidney transplanted patients.

    PubMed

    Frascà, Giovanni M; Sandrini, Silvio; Cosmai, Laura; Porta, Camillo; Asch, William; Santoni, Matteo; Salviani, Chiara; D'Errico, Antonia; Malvi, Deborah; Balestra, Emilio; Gallieni, Maurizio

    2015-12-01

    Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90% of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.

  5. Kidney Cancer Treatment | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  6. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen/Deuterium (H/D) Exchange Study.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-01-01

    In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II]) (CP) which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group). The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents.

  7. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of kidney cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for kidney cancer and research aimed at prevention of this disease.

  8. Tissue Specificity of Decellularized Rhesus Monkey Kidney and Lung Scaffolds

    PubMed Central

    Nakayama, Karina H.; Lee, C. Chang I.; Batchelder, Cynthia A.; Tarantal, Alice F.

    2013-01-01

    Initial steps in establishing an optimal strategy for functional bioengineered tissues is generation of three-dimensional constructs containing cells with the appropriate organization and phenotype. To effectively utilize rhesus monkey decellularized kidney scaffolds, these studies evaluated two key parameters: (1) residual scaffold components after decellularization including proteomics analysis, and (2) the use of undifferentiated human embryonic stem cells (hESCs) for recellularization in order to explore cellular differentiation in a tissue-specific manner. Sections of kidney and lung were selected for a comparative evaluation because of their similar pattern of organogenesis. Proteomics analysis revealed the presence of growth factors and antimicrobial proteins as well as stress proteins and complement components. Immunohistochemistry of recellularized kidney scaffolds showed the generation of Cytokeratin+ epithelial tubule phenotypes throughout the scaffold that demonstrated a statistically significant increase in expression of kidney-associated genes compared to baseline hESC gene expression. Recellularization of lung scaffolds showed that cells lined the alveolar spaces and demonstrated statistically significant upregulation of key lung-associated genes. However, overall expression of kidney and lung-associated markers was not statistically different when the kidney and lung recellularized scaffolds were compared. These results suggest that decellularized scaffolds have an intrinsic spatial ability to influence hESC differentiation by physically shaping cells into tissue-appropriate structures and phenotypes, and that additional approaches may be needed to ensure consistent recellularization throughout the matrix. PMID:23717553

  9. Grade-dependent Proteomics Characterization of Kidney Cancer*S⃞

    PubMed Central

    Perroud, Bertrand; Ishimaru, Tatz; Borowsky, Alexander D.; Weiss, Robert H.

    2009-01-01

    Kidney cancer is frequently metastatic on presentation at which point the disease is associated with a 95% mortality. Assessment of tumor grade on pathological examination is the most powerful means for prognostication as well as for stratification of patients into those who might respond to conventional or targeted therapy. Although there exist several grading systems in common use, all suffer from significant disparity among observers. In an attempt to objectify this process as well as to acquire grade-specific mechanistic information, we performed LC-MS/MS-based proteomics analysis on 50 clear cell kidney cancers equally distributed among normal tissues and Fuhrman grades 1–4. Initial experiments confirmed the utility of using archived formalin-fixed paraffin-embedded samples for LC-MS/MS-based proteomics analysis, and the LC-MS/MS findings were validated by extensive immunoblotting. We now show that changes among many biochemical processes and pathways are strongly grade-dependent with the glycolytic and amino acid synthetic pathways highly represented. In addition, proteins relating to acute phase and xenobiotic metabolism signaling are highly represented. Self-organized mapping of proteins with similar patterns of expression led to the creation of a heat map that will be useful in grade characterization as well as in future research relating to oncogenic mechanisms and targeted therapies for kidney cancer. PMID:19164279

  10. Comprehensive Metabolomic and Lipidomic Profiling of Human Kidney Tissue: A Platform Comparison.

    PubMed

    Leuthold, Patrick; Schaeffeler, Elke; Winter, Stefan; Büttner, Florian; Hofmann, Ute; Mürdter, Thomas E; Rausch, Steffen; Sonntag, Denise; Wahrheit, Judith; Fend, Falko; Hennenlotter, Jörg; Bedke, Jens; Schwab, Matthias; Haag, Mathias

    2017-02-03

    Metabolite profiling of tissue samples is a promising approach for the characterization of cancer pathways and tumor classification based on metabolic features. Here, we present an analytical method for nontargeted metabolomics of kidney tissue. Capitalizing on different chemical properties of metabolites allowed us to extract a broad range of molecules covering small polar molecules and less polar lipid classes that were analyzed by LC-QTOF-MS after HILIC and RP chromatographic separation, respectively. More than 1000 features could be reproducibly extracted and analyzed (CV < 30%) in porcine and human kidney tissue, which were used as surrogate matrices for method development. To further assess assay performance, cross-validation of the nontargeted metabolomics platform to a targeted metabolomics approach was carried out. Strikingly, from 102 metabolites that could be detected on both platforms, the majority (>90%) revealed Spearman's correlation coefficients ≥0.3, indicating that quantitative results from the nontargeted assay are largely comparable to data derived from classical targeted assays. Finally, as proof of concept, the method was applied to human kidney tissue where a clear differentiation between kidney cancer and nontumorous material could be demonstrated on the basis of unsupervised statistical analysis.

  11. Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune Cells.

    PubMed

    Winfree, Seth; Khan, Shehnaz; Micanovic, Radmila; Eadon, Michael T; Kelly, Katherine J; Sutton, Timothy A; Phillips, Carrie L; Dunn, Kenneth W; El-Achkar, Tarek M

    2017-02-02

    Analysis of the immune system in the kidney relies predominantly on flow cytometry. Although powerful, the process of tissue homogenization necessary for flow cytometry analysis introduces bias and results in the loss of morphologic landmarks needed to determine the spatial distribution of immune cells. An ideal approach would support three-dimensional (3D) tissue cytometry: an automated quantitation of immune cells and associated spatial parameters in 3D image volumes collected from intact kidney tissue. However, widespread application of this approach is limited by the lack of accessible software tools for digital analysis of large 3D microscopy data. Here, we describe Volumetric Tissue Exploration and Analysis (VTEA) image analysis software designed for efficient exploration and quantitative analysis of large, complex 3D microscopy datasets. In analyses of images collected from fixed kidney tissue, VTEA replicated the results of flow cytometry while providing detailed analysis of the spatial distribution of immune cells in different regions of the kidney and in relation to specific renal structures. Unbiased exploration with VTEA enabled us to discover a population of tubular epithelial cells that expresses CD11C, a marker typically expressed on dendritic cells. Finally, we show the use of VTEA for large-scale quantitation of immune cells in entire human kidney biopsies. In summary, we show that VTEA is a simple and effective tool that supports unique digital interrogation and analysis of kidney tissue from animal models or biobanked human kidney biopsies. We have made VTEA freely available to interested investigators via electronic download.

  12. Urinary acylcarnitines are altered in human kidney cancer.

    PubMed

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer.

  13. Human Kidney-Derived Cells Ameliorate Acute Kidney Injury Without Engrafting into Renal Tissue.

    PubMed

    Santeramo, Ilaria; Herrera Perez, Zeneida; Illera, Ana; Taylor, Arthur; Kenny, Simon; Murray, Patricia; Wilm, Bettina; Gretz, Norbert

    2017-04-04

    Previous studies have suggested that CD133(+) cells isolated from human kidney biopsies have the potential to ameliorate injury following intravenous (IV) administration in rodent models of kidney disease by integrating into damaged renal tissue and generating specialized renal cells. However, whether renal engraftment of CD133(+) cells is a prerequisite for ameliorating injury has not yet been unequivocally resolved. Here, we have established a cisplatin-induced nephropathy model in immunodeficient rats to assess the efficacy of CD133(+) human kidney cells in restoring renal health, and to determine the fate of these cells after systemic administration. Specifically, following IV administration, we evaluated the impact of the CD133(+) cells on renal function by undertaking longitudinal measurements of the glomerular filtration rate using a novel transcutaneous device. Using histological assays, we assessed whether the human kidney cells could promote renal regeneration, and if this was related to their ability to integrate into the damaged kidneys. Our results show that both CD133(+) and CD133(-) cells improve renal function and promote renal regeneration to a similar degree. However, this was not associated with engraftment of the cells into the kidneys. Instead, after IV administration, both cell types were exclusively located in the lungs, and had disappeared by 24 hours. Our data therefore indicate that renal repair is not mediated by CD133(+) cells homing to the kidneys and generating specialized renal cells. Instead, renal repair is likely to be mediated by paracrine or endocrine factors. © Stem Cells Translational Medicine 2017.

  14. Kidney cancer progression linked to shifts in tumor metabolism

    Cancer.gov

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  15. Change in expression of cyclin G2 in kidney cancer cell and its significance.

    PubMed

    Cui, D W; Sun, G G; Cheng, Y J

    2014-04-01

    This study aims to analyze the expression and clinical significance of cyclin G2 (CCNG2) in kidney carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 63 cases of kidney cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into kidney ACHN cell line. During immunohistochemistry, the level of CCNG2 protein expression was found to be significantly lower in kidney cancer tissue than normal tissues (P < 0.05). After Western blot, the relative amount of CCNG2 protein in kidney cancer tissue was respectively found to be significantly lower than in normal tissues (P < 0.05). The level of CCNG2 protein expression was not correlated with gender, age, tumor size, and pathological types (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function show that ACHN cell-transfected CCNG2 had a lower survival fraction, higher percentage of the G0/G1 phases, and lower CDK2 protein expression compared with ACHN cell-untransfected CCNG2 (P < 0.05). CCNG2 expression decreased in kidney cancer and correlated significantly with lymph node metastasis, clinical stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to kidney cancer ACHN cell by promoting degradation of CDK2.

  16. Urology and nephrology update: bladder and kidney cancer.

    PubMed

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care.

  17. Understanding kidney morphogenesis to guide renal tissue regeneration.

    PubMed

    Little, Melissa H; Combes, Alexander N; Takasato, Minoru

    2016-10-01

    The treatment of renal failure has seen little change in the past 70 years. Patients with end-stage renal disease (ESRD) are treated with renal replacement therapy, including dialysis or organ transplantation. The growing imbalance between the availability of donor organs and prevalence of ESRD is pushing an increasing number of patients to undergo dialysis. Although the prospect of new treatment options for patients through regenerative medicine has long been suggested, advances in the generation of human kidney cell types through the directed differentiation of human pluripotent stem cells over the past 2 years have brought this prospect closer to delivery. These advances are the result of careful research into mammalian embryogenesis. By understanding the decision points made within the embryo to pattern the kidney, it is now possible to recreate self-organizing kidney tissues in vitro. In this Review, we describe the key decision points in kidney development and how these decisions have been mimicked experimentally. Recreation of human nephrons from human pluripotent stem cells opens the door to patient-derived disease models and personalized drug and toxicity screening. In the long term, we hope that these efforts will also result in the generation of bioengineered organs for the treatment of kidney disease.

  18. Classification of kidney and liver tissue using ultrasound backscatter data

    NASA Astrophysics Data System (ADS)

    Aalamifar, Fereshteh; Rivaz, Hassan; Cerrolaza, Juan J.; Jago, James; Safdar, Nabile; Boctor, Emad M.; Linguraru, Marius G.

    2015-03-01

    Ultrasound (US) tissue characterization provides valuable information for the initialization of automatic segmentation algorithms, and can further provide complementary information for diagnosis of pathologies. US tissue characterization is challenging due to the presence of various types of image artifacts and dependence on the sonographer's skills. One way of overcoming this challenge is by characterizing images based on the distribution of the backscatter data derived from the interaction between US waves and tissue. The goal of this work is to classify liver versus kidney tissue in 3D volumetric US data using the distribution of backscatter US data recovered from end-user displayed Bmode image available in clinical systems. To this end, we first propose the computation of a large set of features based on the homodyned-K distribution of the speckle as well as the correlation coefficients between small patches in 3D images. We then utilize the random forests framework to select the most important features for classification. Experiments on in-vivo 3D US data from nine pediatric patients with hydronephrosis showed an average accuracy of 94% for the classification of liver and kidney tissues showing a good potential of this work to assist in the classification and segmentation of abdominal soft tissue.

  19. [Immune Checkpoint for a Kidney Cancer and Other Cancers].

    PubMed

    Kageyama, Shunichiro; Yamaguchi, Shigeo; Miura, Kayo; Kato, Shunsuke

    2016-06-01

    Immune checkpoint inhibitors have been getting increasing attention in the field of cancer treatment, resulting in the investigation of numerous drugs and target cancers. Clinical trials of immune checkpoint inhibitors have focused on malignant melanomas and non-small cell lung cancer;however, recently, clinical trials have been carried out for other cancers. To date, 31 phase III clinical trials have been conducted for 13 types of cancer. Recently, the results of the CheckMate025 kidney cancer and CheckMate141 head and neck cancer trials have been reported. These reports showed that nivolumab significantly enhanced overall survival in comparison to that associated with an existing second-line treatment drug. Based on these results, the approval of nivolumab for use in renal cell cancer and head and neck cancer is expected in the near future. Furthermore, the results of 20 phase III clinical trials will be submitted from 2017 to 2019, expanding the approval of immune checkpoint inhibitors. However, many issues such as biomarker searches, the evaluation of antitumor effects, and the impact on medical economy remain to be resolved. In this report, we outline clinical trial trends and the future prospects for immune checkpoint inhibitors.

  20. Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage: effects of triiodothyronine and dinitrophenol in normoglycemic rats.

    PubMed

    Friederich-Persson, Malou; Persson, Patrik; Fasching, Angelica; Hansell, Peter; Nordquist, Lina; Palm, Fredrik

    2013-01-01

    Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.

  1. Sirolimus use and cancer incidence among US kidney transplant recipients.

    PubMed

    Yanik, E L; Gustafson, S K; Kasiske, B L; Israni, A K; Snyder, J J; Hess, G P; Engels, E A; Segev, D L

    2015-01-01

    Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.

  2. Kidney Tumors | Office of Cancer Genomics

    Cancer.gov

    Pediatric kidney tumors fall into four primary categories: Wilms tumors (~85% of all cases), clear cell sarcomas of the kidney (~5%), congenital mesoblastic nephromas (~4%), and rhabdoid tumors of the kidney (~3%). The TARGET initiative is investigating three of these tumor types.

  3. 3rd Pavia international symposium on advanced kidney cancer.

    PubMed

    Porta, Camillo; Bracarda, Sergio

    2012-02-01

    Kidney cancers' natural history has radically changed in the past few years, due to the development of novel targeted agents. Despite these improvements, several unanswered questions still remain on the table, regarding the best first-line treatment, the ideal sequence of treatments, the management of specific subgroups of patients (e.g., elderly patients or those with comorbidities) and the relevance of prognostic factors, among many others. To foster discussions among clinicians and investigators working in this field, and to exchange different viewpoints concerning the newest advances in kidney cancer pathogenesis and treatment, the 3rd Pavia International Symposium on Advanced Kidney cancer was held in Pavia (Italy) between 30 June and 1 July 2011. The aim of this report is to summarize the most significant advances in the different disciplines applied to advanced kidney cancer, which were presented and discussed during the meeting, and how these advances will be changing the perspective of patients with this disease.

  4. Breast cancer metastatic to the kidney with renal vein involvement.

    PubMed

    Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

    2015-02-01

    The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

  5. Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway

    PubMed Central

    Zhang, Hao-jie; Tao, Jing; Sheng, Lu; Hu, Xin; Rong, Rui-ming; Xu, Ming; Zhu, Tong-yu

    2016-01-01

    Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human kidney-cancer-derived cells in vitro. Twist2 also promoted tumor growth in vivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in kidney cancer progression. The identification of the role of Twist2 in the migration and invasion of kidney cancer provides a potential appropriate treatment for human kidney cancer. PMID:27099513

  6. The role of inflammation in kidney cancer.

    PubMed

    de Vivar Chevez, Antonio Roma; Finke, James; Bukowski, Ronald

    2014-01-01

    Renal cell carcinoma (RCC) constitutes more than 90 % of primary kidney tumors with the development of metastatic disease in the lung, bone, liver, and brain. Clear-cell RCC (CCRCC) is the most common histologic form of sporadic kidney cancer where the majority of tumors have inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene resulting in the accumulation of hypoxia-inducible factor (HIF) leading to dysregulation of cell growth and angiogenesis. Understanding of the genetic changes in RCC and the downstream events have led to the development of tyrosine kinase inhibitors (TKI) that target HIF-regulated proteins which currently represents front-line therapy for metastatic disease although resistance develops in most patients overtime. Despite the fact that RCC is an immunogenic tumor, there is mounting evidence that immune cells and inflammatory pathways can enhance tumor growth and immune escape. However, recent studies are beginning to uncover the mechanisms of immune escape in RCC, and the role inflammatory immune cells and cytokines play is this process. These new findings have led to renewed interest in the use of immunotherapy for the treatment of this disease that includes strategies to regulate inflammatory responses. Here, we will discuss the different inflammatory signaling pathways (e.g., VHL, hypoxia, TNF-α, STAT, and TGF-β) and the downstream transcription factors, cytokines, and chemokines involved in tumor development, and disease progression. This will include assessment of the role inflammatory molecules (e.g., pVHL, TGFb, IL6, select chemokines/chemokine receptors) play in promoting cell transformation, survival, proliferation of tumor cells, and metastasis derived from in vitro and in vivo studies. Included is a section on how select inflammatory cells (TAM, MDSC, and neutrophils) promote tumor evasion of immune cells. We also provide examples of molecules/cells that correlate negatively (CXCL12, CXCR4, and MMP, neutrophils, and

  7. Donor cancer transmission in kidney transplantation: a systematic review.

    PubMed

    Xiao, D; Craig, J C; Chapman, J R; Dominguez-Gil, B; Tong, A; Wong, G

    2013-10-01

    Transplantation of any biological material from a donor to a host will carry some inherent risk of disease transmission. Our aims were to summarize the totality of the published evidence about donor cancer transmission among kidney transplant recipients and to determine the cancer-specific survival of these patients. We systematically reviewed all case reports, case series and registry studies that described the outcomes of kidney transplant recipients with donor cancer transmission published to December 2012. A total of 69 studies with 104 donor-transmitted cancer cases were identified. The most common transmitted cancer types were renal cancer (n = 20, 19%), followed by melanoma (n = 18, 17%), lymphoma (n = 15, 14%) and lung cancer (n = 9, 9%). Patients with melanoma and lung cancers had the worst prognosis, with less than 50% of recipients surviving after 24 months from transplantation. Recipients with transmitted renal cancers had the best outcomes, with over 70% of recipients surviving for at least 24 months after transplantation. Overall, the risk of donor transmission of cancer appears low, but there is a high likelihood of reporting bias. Our findings support the current recommendations for rejecting organs from donors with a history of melanoma and lung cancer, but suggest that the use of donor kidneys with a history of small, incidental renal cell cancer may be reasonable.

  8. Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles

    PubMed Central

    Bock Axelsen, Jacob; Lotem, Joseph; Sachs, Leo; Domany, Eytan

    2007-01-01

    We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis. PMID:17664417

  9. Electrolyte disturbances and acute kidney injury in patients with cancer.

    PubMed

    Lameire, Norbert; Van Biesen, Wim; Vanholder, Raymond

    2010-11-01

    The interrelation between kidney disease and cancer is complex and reciprocal. Among the most frequent cancer-associated kidney diseases are the electrolyte and acid-base disturbances, which occur frequently and often are associated with an ominous prognosis, and acute kidney injury. Tumor lysis syndrome is a potentially life-threatening condition that frequently occurs in patients with a high tumor burden and high cellular turnover after cytotoxic therapy (including steroids in steroid-sensitive hematologic malignancies). Electrolyte and acid-base disturbances are the consequence of neoplastic spread, anticancer treatment, or, more rarely, paraneoplastic phenomena of all types of tumors. This article reviews hyponatremia and hypernatremia, hypokalemia and hyperkalemia, hypomagnesemia, hypercalcemia and hypocalcemia, hypophosphatemia, and the most important disturbances in acid-base balance in cancer patients. Acute kidney injury (AKI) is a frequent occurrence in cancer patients and has the potential to substantially alter the outcome of patients with cancer and jeopardize their chances of receiving optimal cancer treatment and a potential cure. As in many other circumstances, the etiology of AKI in cancer patients is multifactorial. Initiation and/or continuation of dialysis in the AKI cancer patient should be based on the general clinical condition and overall life expectancy and the personal patient expectations on quality of life after eventual recovery.

  10. Racial/ethnic differences in cancer risk after kidney transplantation.

    PubMed

    Hall, E C; Segev, D L; Engels, E A

    2013-03-01

    Transplant recipients have elevated cancer risk, but it is unknown if cancer risk differs across race and ethnicity as in the general population. US kidney recipients (N = 87,895) in the Transplant Cancer Match Study between 1992 and 2008 were evaluated for racial/ethnic differences in risk for six common cancers after transplantation. Compared to white recipients, black recipients had lower incidence of non-Hodgkin lymphoma (NHL) (adjusted incidence rate ratio [aIRR] 0.60, p<0.001) and higher incidence of kidney (aIRR 2.09, p<0.001) and prostate cancer (aIRR 2.14, p<0.001); Hispanic recipients had lower incidence of NHL (aIRR 0.64, p = 0.001), lung (aIRR 0.41, p < 0.001), breast (aIRR 0.53, p = 0.003) and prostate cancer (aIRR 0.72, p = 0.05). Colorectal cancer incidence was similar across groups. Standardized incidence ratios (SIRs) measured the effect of transplantation on cancer risk and were similar for most cancers (p≥0.1). However, black and Hispanic recipients had larger increases in kidney cancer risk with transplantation (SIRs: 8.96 in blacks, 5.95 in Hispanics vs. 4.44 in whites), and only blacks had elevated prostate cancer risk following transplantation (SIR: 1.21). Racial/ethnic differences in cancer risk after transplantation mirror general population patterns, except for kidney and prostate cancers where differences reflect the effects of end-stage renal disease or transplantation.

  11. The immune phenotype may relate to cancer development in kidney transplant recipients.

    PubMed

    Hope, Christopher M; Grace, Blair S; Pilkington, Katherine R; Coates, Patrick T; Bergmann, Ivo P; Carroll, Robert P

    2014-07-01

    High regulatory T-cell (Treg) numbers predict recurrent cutaneous squamous cell carcinoma in kidney transplant recipients, and the Treg immune phenotype may identify kidney transplant recipients at risk of developing squamous cell carcinoma and/or solid-organ cancer. To investigate this, a total of 116 kidney transplant recipients, of whom 65 had current or past cancer, were immune-phenotyped and followed up prospectively for a median of 15 months. Higher Treg (CD3+CD4+FOXP3+CD25(Hi)CD127(Lo)) proportion and numbers significantly increased the odds of developing cancer (odds ratios (95% CI) 1.61 (1.17-2.20) and 1.03 (1.00-1.06), respectively) after adjusting for age, gender, and duration of immunosuppression. Class-switched memory B cells (CD19+CD27+IgD-) had a significant association to cancer, 1.04 (1.00-1.07). Receiver operator characteristic (ROC) curves for squamous cell carcinoma development within 100 days of immune phenotyping were significant for Tregs, memory B cells, and γδ T cells (AUC of 0.78, 0.68, and 0.65, respectively). After cancer resection, Treg, NK cell, and γδ T-cell numbers fell significantly. Immune-phenotype profiles associated with both squamous cell carcinoma and solid-organ cancer in kidney transplant recipients and depended on the presence of cancer tissue. Thus, immune profiling could be used to stratify kidney transplant recipients at risk of developing cancers to identify those who could qualify for prevention therapy.

  12. Ionizing radiation and kidney cancer among Japanese atomic bomb survivors.

    PubMed

    Richardson, David B; Hamra, Ghassan

    2010-06-01

    Understanding of the role of radiation as a cause of kidney cancer remains limited. The most common types of kidney cancer are renal cell carcinoma and renal pelvis carcinoma. It has been posited that these entities differ in their degree of radiogenicity. Recent analyses of cancer incidence and mortality in the Life Span Study (LSS) of Japanese atomic bomb survivors have examined associations between ionizing radiation and renal cell carcinoma, but these analyses have not reported results for cancer of the renal pelvis and ureters. This paper reports the results of analyses of kidney cancer incidence during the period 1958-1998 among 105,427 atomic bomb survivors. Poisson regression methods were used to derive estimates of associations between radiation dose (in sievert, Sv) and cancer of the renal parenchyma (n = 167), and cancer of the renal pelvis and ureter (n = 80). Heterogeneity by cancer site was tested by joint modeling of cancer risks. Radiation dose was positively associated with cancers of the renal pelvis and ureter [excess relative rate (ERR)/Sv = 1.65; 90% confidence interval (CI): 0.37, 3.78]. The magnitude of this association was larger than the estimated association between radiation dose and cancer of the renal parenchyma (ERR/Sv = 0.27; 90% CI = -0.19, 0.98). While the association between radiation and cancer of the renal parenchyma was of greater magnitude at ages <55 years (ERR/Sv = 2.82; 90% CI = 0.45, 8.89) than at older attained ages (ERR/Sv = -0.11; 90% CI = nd, 0.53), the association between radiation and cancers of the renal pelvis and ureter varied minimally across these categories of attained age. A test of heterogeneity of type-specific risks provides modest support for the conclusion that risks vary by kidney cancer site (LRT = 2.34, 1 d.f., P = 0.13). Since some studies of radiation-exposed populations examine these sites in aggregate, results were also derived for the combined category of cancer of the renal parenchyma, renal

  13. Carbonic anhydrase expression in kidney and renal cancer: implications for diagnosis and treatment.

    PubMed

    Oosterwijk, Egbert

    2014-01-01

    Four different carbonic anhydrases are expressed in the human nephron, the functional unit of the kidney. These are specifically expressed in different nephron segments, emphasizing the critical role carbonic anhydrases play in maintaining the homeostasis of this crucial organ.Whereas the localization of carbonic anhydrases in the kidney has been long established, interest in carbonic anhydrases has increased dramatically for renal cancer, in particular for the clear cell variant of renal cell carcinoma (ccRCC) because carbonic anhydrase IX is specifically expressed in ccRCC. Therefore carbonic anhydrase IX is being studied as potential diagnostic and therapeutic target, despite carbonic anhydrase IX expression in non-renal tissues.

  14. Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer.

    PubMed

    Chen, Ke; Zhang, Jing; Guo, Zhongqiang; Ma, Qin; Xu, Zhengzheng; Zhou, Yuanyuan; Xu, Ziying; Li, Zhongwu; Liu, Yiqiang; Ye, Xiongjun; Li, Xuesong; Yuan, Bifeng; Ke, Yuwen; He, Chuan; Zhou, Liqun; Liu, Jiang; Ci, Weimin

    2016-01-01

    Both 5-methylcytosine (5mC) and its oxidized form 5-hydroxymethylcytosine (5hmC) have been proposed to be involved in tumorigenesis. Because the readout of the broadly used 5mC mapping method, bisulfite sequencing (BS-seq), is the sum of 5mC and 5hmC levels, the 5mC/5hmC patterns and relationship of these two modifications remain poorly understood. By profiling real 5mC (BS-seq corrected by Tet-assisted BS-seq, TAB-seq) and 5hmC (TAB-seq) levels simultaneously at single-nucleotide resolution, we here demonstrate that there is no global loss of 5mC in kidney tumors compared with matched normal tissues. Conversely, 5hmC was globally lost in virtually all kidney tumor tissues. The 5hmC level in tumor tissues is an independent prognostic marker for kidney cancer, with lower levels of 5hmC associated with shorter overall survival. Furthermore, we demonstrated that loss of 5hmC is linked to hypermethylation in tumors compared with matched normal tissues, particularly in gene body regions. Strikingly, gene body hypermethylation was significantly associated with silencing of the tumor-related genes. Downregulation of IDH1 was identified as a mechanism underlying 5hmC loss in kidney cancer. Restoring 5hmC levels attenuated the invasion capacity of tumor cells and suppressed tumor growth in a xenograft model. Collectively, our results demonstrate that loss of 5hmC is both a prognostic marker and an oncogenic event in kidney cancer by remodeling the DNA methylation pattern.

  15. Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.

    PubMed

    Linehan, W Marston

    2012-11-01

    Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.

  16. Tissue lipid composition in fatty liver and kidney syndrome in chicks.

    PubMed

    Whitehead, C C

    1975-01-01

    The lipid composition of the liver, kidneys, heart and adipose tissue of chicks affected by the fatty liver and kidney syndrome were analysed. Livers and kidneys showed 400 to 500 per cent increases in heart lipid levels. Liver and kidney triglycerides contained increased proportions of mono-unsaturated fatty acids, mainly palmitoleic acid, at the expense of the saturated fatty acids, mainly stearic acid. Phospholipid and adipose tissue fatty acid composition were not markedly altered. The abnormalities were regressing in birds recovering from the syndrome.

  17. Hysterectomy and kidney cancer risk: a meta-analysis.

    PubMed

    Karami, Sara; Daugherty, Sarah E; Purdue, Mark P

    2014-01-15

    Recent cohort findings suggest that women who underwent a hysterectomy have an elevated relative risk of kidney cancer, although evidence from past studies has been inconsistent. We conducted a systematic review and meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence investigating hysterectomy and kidney cancer. Studies published from 1950 through 2012 were identified through a search of PubMed and of references from relevant publications. Meta-analyses were conducted using random-effects models to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for hysterectomy, age at hysterectomy (<45, 45+ years) and time since hysterectomy (<10, 10+ years). The SRR for hysterectomy and kidney cancer for all published studies (seven cohort, six case-control) was 1.29 (95% CI, 1.16-1.43), with no evidence of between-study heterogeneity or publication bias. The summary effect was slightly weaker, although still significant, for cohorts (SRR, 1.26; 95% CI, 1.11-1.42) compared with case-control findings (1.37; 95% CI, 1.09-1.73) and was observed irrespective of age at hysterectomy, time since the procedure and model adjustment for body mass index, smoking status and hypertension. Women undergoing a hysterectomy have an approximate 30% increased relative risk of subsequent kidney cancer. Additional research is needed to elucidate the biological mechanisms underlying this association.

  18. Adipose tissue immunity and cancer.

    PubMed

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2013-10-02

    Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs.

  19. Accuracy and Readability of Websites on Kidney and Bladder Cancers.

    PubMed

    Azer, Samy A; Alghofaili, Maha M; Alsultan, Rana M; Alrumaih, Najla S

    2017-03-09

    The aim of this study was to assess the scientific accuracy and the readability level of websites on kidney and bladder cancers. The search engines Google™, Yahoo™ and Bing™ were searched independently by assessors in November 2014 using the following keywords: "bladder cancer", "kidney cancer", "patient bladder cancer", "patient kidney cancer" and "bladder and kidney cancer". Only English-language websites were selected on the bases of predetermined inclusion and exclusion criteria. Assessors independently reviewed the findings and evaluated the accuracy and quality of each website by using the DISCERN and the LIDA instruments. The readability of the websites was calculated using the Flesch-Kincaid Grade Level Index and the Coleman-Liau Readability Index. Sixty-two websites were finally included in the study. The overall accuracy scores varied; for the DISCERN, the range was 28 to 76; out of 80 (mean ± SD, 47.1 ± 12.1; median = 46.0, interquartile range (IQR) = 19.2), and for the LIDA, the range was 52 to 125; out of 144 (mean ± SD, 101.9 ± 15.2; median, 103; IQR, 16.5). The creators of these websites were universities and research centres (n = 25, 40%), foundations and associations (n = 10, 16%), commercial and pharmaceutical companies (n = 13, 21%), charities and volunteer work (n = 4, 6%) and non-university educational bodies (n = 10, 16%). The readability scores (mean ± SD) were 11.2 ± 2.2 for the Flesch-Kincaid Grade Level Index and 11.2 ± 1.6 for the Coleman-Liau Readability Index. The accuracy and the quality of the websites on kidney and bladder cancers varied. In most websites, there were deficiencies in clarity of aims, presenting symptoms, investigations and treatment options. The readability matched grades 10-11 literacy levels-a level above the public readability level. The study highlights the needs for further improvement of the online information created for public and patients with kidney and bladder

  20. Polycystic kidney disease and cancer after renal transplantation.

    PubMed

    Wetmore, James B; Calvet, James P; Yu, Alan S L; Lynch, Charles F; Wang, Connie J; Kasiske, Bertram L; Engels, Eric A

    2014-10-01

    Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia. However, it is not known whether renal transplant recipients with PKD have an increased risk of cancer. Data from the Scientific Registry of Transplant Recipients, which contains information on all solid organ transplant recipients in the United States, were linked to 15 population-based cancer registries in the United States. For PKD recipients, we compared overall cancer risk with that in the general population. We also compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poisson regression, and we determined incidence rate ratios (IRRs) adjusted for age, sex, race/ethnicity, dialysis duration, and time since transplantation. The study included 10,166 kidney recipients with PKD and 107,339 without PKD. Cancer incidence in PKD recipients was 1233.6 per 100,000 person-years, 48% higher than expected in the general population (standardized incidence ratio, 1.48; 95% confidence interval [95% CI], 1.37 to 1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000 person-years. The unadjusted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01 to 1.20). However, PKD recipients were older (median age at transplantation, 51 years versus 45 years for non-PKD recipients), and after multivariable adjustment, cancer incidence was lower in PKD recipients than in others (IRR, 0.84; 95% CI, 0.77 to 0.91). The reason for the lower cancer risk in PKD recipients is not known but may relate to biologic characteristics of ADPKD or to cancer risk behaviors associated with ADPKD.

  1. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  2. Assessment of photoacoustic computed tomography to classify tissue in a polycystic-kidney disease mouse model

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Gattone, Vincent H., II; Kruger, Robert A.; Stantz, Keith M.

    2006-02-01

    Purpose: The purpose of this study is to evaluate PCT Imaging technique to classify tissue and extract kidney cysts in pcy mice model of human adolescent nephronophthisis. Method: Four mice with late stages of nephronophthisis with polycystic kidney disease-PKD and one normal mouse were scanned in the PCT Small Animal Scanner. Both vivo and ex-vivo images of mice kidney were taken at wavelength from 680 nm to 940 nm. The ex-vivo PCT images were compared with histology photographs to check the sensitivity of detecting cysts. Histograms of kidney images were generated over slices and fitted to Gaussian-curve model for volumetric analysis. The portions of cysts in kidneys were estimated and kidney images were segmented by three different colors to present the distribution of different tissues. Result: A good correspondence between PCT imaging findings and PKD histology result was observed. Histogram curves from images of pcy kidneys and normal kidneys were fitted to Gaussian-curve model. Portions of cysts, parenchyma and area of high level hemoglobin were estimated according to the curve fit result. A growth of cysts associated with relatively volume decrease of parenchyma and tissues with high perfusion of hemoglobin was observed. Conclusion: The PCT enabled visualization of renal cysts for mouse model and had the potential for volumetric measurements of kidney.

  3. Kidney cancer mortality in Spain: geographic patterns and possible hypotheses

    PubMed Central

    López-Abente, Gonzalo; Aragonés, Nuria; Pérez-Gómez, Beatriz; Ramis, Rebeca; Vidal, Enrique; García-Pérez, Javier; Fernández-Navarro, Pablo; Pollán, Marina

    2008-01-01

    Background Since the second half of the 1990s, kidney cancer mortality has tended to stabilize and decline in many European countries, due to the decrease in the prevalence of smokers. Nevertheless, incidence of kidney cancer is rising across the sexes in some of these countries, a trend which may possibly reflect the fact that improvements in diagnostic techniques are being outweighed by the increased prevalence of some of this tumor's risk factors. This study sought to: examine the geographic pattern of kidney cancer mortality in Spain; suggest possible hypotheses that would help explain these patterns; and enhance existing knowledge about the large proportion of kidney tumors whose cause remains unknown. Methods Smoothed municipal relative risks (RRs) for kidney cancer mortality were calculated in men and women, using the conditional autoregressive model proposed by Besag, York and Molliè. Maps were plotted depicting smoothed relative risk estimates, and the distribution of the posterior probability of RR>1 by sex. Results Municipal maps displayed a marked geographic pattern, with excess mortality in both sexes, mainly in towns along the Bay of Biscay, including areas of Asturias, the Basque Country and, to a lesser extent, Cantabria. Among women, the geographic pattern was strikingly singular, not in evidence for any other tumors, and marked by excess risk in towns situated in the Salamanca area and Extremaduran Autonomous Region. This difference would lead one to postulate the existence of different exposures of environmental origin in the various regions. Conclusion The reasons for this pattern of distribution are not clear, and it would thus be of interest if the effect of industrial emissions on this disease could be studied. The excess mortality observed among women in towns situated in areas with a high degree of natural radiation could reflect the influence of exposures which derive from the geologic composition of the terrain and then become manifest

  4. Do We Know What Causes Kidney Cancer?

    MedlinePlus

    ... some of the body’s hormones. Researchers are now learning how certain hormones help control the growth ... up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, ...

  5. Adjuvant Everolimus for Resected Kidney Cancer

    Cancer.gov

    In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

  6. Cancer incidence in kidney transplant recipients: a study protocol

    PubMed Central

    2009-01-01

    Background Different publications show an increased incidence of neoplasms in renal transplant patients. The objective of this study is to determine the incidence of cancer in the recipients of renal transplants performed in the A Coruña Hospital (Spain) during the period 1981–2007. Methods/Design During the study period 1967 kidney transplants were performed, corresponding to 1710 patients. Patients with neoplasms prior to the transplant will be excluded (n = 38). A follow-up study was carried out in order to estimate cancer incidence after transplantation. For each patient, information included donor and recipient characteristics, patients and graft survival and cancer incidence after transplantation. Incident cancer is considered as new cases of cancer after the transplant with anatomopathological confirmation. Their location will be classified according to the ICD-9. The analysis will be calculated using the indirect standardisation method. Age-adjusted cancer incidence rates in the Spanish general population will be obtained from the Carlos III Health Institute, the National Epidemiology Centre of the Ministry of Science and Technology. Crude first, second and third-year post-transplantation cancer incidence rates will be calculated for male and female recipients. The number of cases of cancer at each site will be calculated from data in the clinical records. The expected number of cancers will be calculated from data supplied by the Carlos III Health Institute. For each tumour location we will estimate the standardized incidence ratios (SIRs), using sex-specific cancer incidence rates, by dividing the incidence rate for the transplant patients by the rate of the general population. The 95% confidence intervals of the SIRs and their associated p-values will be calculated by assuming that the observed cancers follow a Poisson distribution. Stratified analysis will be performed to examine the variation in the SIRs with sex and length of follow-up. Competing

  7. Childhood Soft Tissue Sarcoma: Treatment Information

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  8. [Metastatic kidney cancer: new therapeutic approaches].

    PubMed

    Negrier, Sylvie; Mejean, Arnaud; Oudard, Stéphane; Escudier, Bernard

    2002-09-01

    Several promising approaches to the treatment of renal cancer have been developed over recent years. Two independent North American and European studies have demonstrated the value of nephrectomy in patients with metastatic disease: the overall survival of patients treated with interferon was improved by nephrectomy, essentially in patients with a good general status. Several publications have also emphasized the value of surgery for metastases. New experimental approaches have also been developed. Dendritic cells fused with tumour cells induced 4 complete remissions and 2 partial remissions in a series of 17 patients. Allogeneic haematopoietic stem cell transplantation induced lasting remissions in 10 out of 17 patients. The National Cancer Institute team, in the United States, has developed this approach for patients with an HLA-compatible relative. Finally, various molecules with promising antiangiogenic properties are currently under development in renal cancer.

  9. Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

    PubMed

    Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

    2010-08-01

    The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue

  10. Kidney cancer and hydrocarbon exposures among petroleum refinery workers

    SciTech Connect

    Poole, C.; Dreyer, N.A.; Satterfield, M.H.; Levin, L.

    1993-12-01

    To evaluate the hypothesis of increased kidney cancer risk after exposure to hydrocarbons, especially those present in gasoline, we conducted a case-control study in a cohort of approximately 100,000 male refinery workers from five petroleum companies. A review of 18,323 death certificates identified 102 kidney cancer cases, to each of whom four controls were matched by refinery location and decade of birth. Work histories, containing an average of 15.7 job assignments per subject, were found for 98% of the cases and 94% of the controls. Tb each job, industrial hygienists assigned semiquantitative ratings for the intensity and frequency of exposures to three hydrocarbon categories: nonaromatic liquid gasoline distillates, aromatic hydrocarbons, and the more volatile hydrocarbons. Ratings of {open_quotes}present{close_quotes} or {open_quotes}absent{close_quotes} were assigned for seven additional exposures: higher boiling hydrocarbons, polynuclear aromatic hydrocarbons, asbestos, chlorinated solvents, ionizing radiation, and lead. Each exposure had either no association or a weak association with kidney cancer. For the hydrocarbon category of principal a priori interest, the nonaromatic liquid gasoline distillates, the estimated relative risk (RR) for any exposure above refinery background was 1.0 (95% confidence interval [CI] 0.5-1.9). Analyses of cumulative exposures and of exposures in varying time periods before kidney cancer occurrence also produced null or near-null results. In an analysis of the longest job held by each subject (average duration 9.2 years or 40% of the refiner&y work history), three groups appeared to be at increased risk: laborers (RR = 1.9,95% CI 1.0-3.9); workers in receipt, storage, and movements (RR = 2.5,95% CI 0.9-6.6); and unit cleaners (RR = 2.3, 95% CI 0.5-9.9). 53 refs., 7 tabs.

  11. Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer.

    PubMed

    Linehan, W Marston; Rouault, Tracey A

    2013-07-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid (TCA) cycle enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer, levels of AMP-activated protein kinase (AMPK), a cellular energy sensor, are decreased resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate-limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of hypoxia-inducible factor (HIF)-1α and increased expression of genes such as VEGF and glucose transporter 1 (GLUT1) to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, lactate dehydrogenase A (LDHA), the antioxidant response pathway, the heme oxygenase pathway, and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the

  12. Disparate companions: tissue engineering meets cancer research.

    PubMed

    Tilkorn, Daniel J; Lokmic, Zerina; Chaffer, Christine L; Mitchell, Geraldine M; Morrison, Wayne A; Thompson, Erik W

    2010-01-01

    Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue-specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit.

  13. Human cancers overexpress genes that are specific to a variety of normal human tissues

    PubMed Central

    Lotem, Joseph; Netanely, Dvir; Domany, Eytan; Sachs, Leo

    2005-01-01

    We have analyzed gene expression data from three different kinds of samples: normal human tissues, human cancer cell lines, and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are overexpressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues, we identified 4,346 genes with a high variability of expression and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and one to two other tissues; 28 clusters included genes preferentially expressed in various nonhematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas, and placenta. Analysis of the expression levels of these two groups of genes in the human cancer cell lines and leukemias identified genes that were highly expressed in cancer cells but not in their normal counterparts and, thus, were overexpressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these overexpressed genes. The results indicate that many genes that are overexpressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential. PMID:16339305

  14. Onco-nephrology: an appraisal of the cancer and chronic kidney disease links.

    PubMed

    Izzedine, Hassan; Perazella, Mark A

    2015-12-01

    A bidirectional relationship has been observed for kidney disease and cancer. On the one hand, cancer is an important complication noted in kidney disease as well as a major cause of morbidity and mortality in this group. On the other hand, improved cancer treatment has prolonged survival, but also increased the development of acute and chronic kidney disease. The combination of cancer and kidney disease makes it challenging for clinicians to provide comprehensive and safe therapies for this group of patients. As such, clinicians caring for this group must develop expertise and become competent in the practice of a newly evolving subspecialty of nephrology known as 'onco-nephrology'. This brief narrative review will focus on the cancer risk in patients with underlying kidney disease, the therapies such as erythropoiesis-stimulating agents on cancer progression and other outcomes, and the appropriate dosing of anti-cancer agents in patients with underlying kidney disease.

  15. Tertiary Lymphoid Organs in Cancer Tissues

    PubMed Central

    Hiraoka, Nobuyoshi; Ino, Yoshinori; Yamazaki-Itoh, Rie

    2016-01-01

    Tertiary lymphoid organs (TLOs) are induced postnatally in non-lymphoid tissues such as those affected by chronic infections, autoimmune diseases, and chronic allograft rejection, and also in cancer tissues. TLOs are thought to provide important lymphocytic functional environments for both cellular and humoral immunity, similar to lymph nodes or Peyer’s patches. TLOs have a structure similar to that of lymph nodes or Peyer’s patches, including T cell zones, B cell follicles, and high endothelial venules (HEV) without encapsulation. Here, we review recent advances in our knowledge of TLOs in human solid cancers, including their location, structure, methods of evaluation, and clinicopathological impact. We also discuss the formation and/or maintenance of TLOs in cancer tissues in association with the tumor immune microenvironment, cancer invasion, and the tissue structure of the cancer stroma. PMID:27446075

  16. What Is Cancer?

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  17. Childhood Cancer Statistics

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  18. 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.

  19. Dynamics of cancerous tissue correlates with invasiveness.

    PubMed

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

    2017-03-06

    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.

  20. Dynamics of cancerous tissue correlates with invasiveness

    PubMed Central

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

    2017-01-01

    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. PMID:28262796

  1. LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer

    PubMed Central

    Zhao, Zuohui; Azadzoi, Kazem M.; Choi, Han-Pil; Jing, Ruirui; Lu, Xin; Li, Cuiling; Wang, Fengqin; Lu, Jiaju; Yang, Jing-Hua

    2017-01-01

    Manganese superoxide dismutase (MNSOD) is one of the major scavengers of reactive oxygen species (ROS) in mitochondria with pivotal regulatory role in ischemic disorders, inflammation and cancer. Here we report oxidative modification of MNSOD in human renal cell carcinoma (RCC) by the shotgun method using data-dependent liquid chromatography tandem mass spectrometry (LC-MS/MS). While 5816 and 5571 proteins were identified in cancer and adjacent tissues, respectively, 208 proteins were found to be up- or down-regulated (p < 0.05). Ontological category, interaction network and Western blotting suggested a close correlation between RCC-mediated proteins and oxidoreductases such as MNSOD. Markedly, oxidative modifications of MNSOD were identified at histidine (H54 and H55), tyrosine (Y58), tryptophan (W147, W149, W205 and W210) and asparagine (N206 and N209) residues additional to methionine. These oxidative insults were located at three hotspots near the hydrophobic pocket of the manganese binding site, of which the oxidation of Y58, W147 and W149 was up-regulated around three folds and the oxidation of H54 and H55 was detected in the cancer tissues only (p < 0.05). When normalized to MNSOD expression levels, relative MNSOD enzymatic activity was decreased in cancer tissues, suggesting impairment of MNSOD enzymatic activity in kidney cancer due to modifications. Thus, LC-MS/MS analysis revealed multiple oxidative modifications of MNSOD at different amino acid residues that might mediate the regulation of the superoxide radicals, mitochondrial ROS scavenging and MNSOD activity in kidney cancer. PMID:28165386

  2. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    PubMed Central

    Perroud, Bertrand; Lee, Jinoo; Valkova, Nelly; Dhirapong, Amy; Lin, Pei-Yin; Fiehn, Oliver; Kültz, Dietmar; Weiss, Robert H

    2006-01-01

    Background Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids

  3. Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes.

    PubMed

    Habib, Samy L; Liang, Sitai

    2014-05-15

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have explored one of the mechanisms by which diabetes accelerates tumorigenesis in the kidney. Kidney cancer tissue from patients with diabetes showed a higher activity of Akt and decreased in total protein of tuberin compared to kidney cancer patient without diabetes or diabetes alone. In addition, a significant increase in phospho-Akt/tuberin expression was associated with an increase in Ki67 expression and activation of mTOR in kidney tumor with or without diabetes compared to diabetes alone. In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes. Importantly, these data showed that the majority of the staining of Akt/tuberin/p70S6K phosphorylation was more prominently in the tubular cells. In addition, accumulation of oxidative DNA damage is localized only in the nucleus of tubular cells within the cortex region. These data suggest that Akt/tuberin/mTOR pathway plays an important role in the regulation DNA damage and repair pathways that may predispose diabetic kidneys to pathogenesis of renal cell carcinoma.

  4. Histopathologic changes in liver and kidney tissues induced by carbaryl in Bufotes variabilis (Anura: Bufonidae).

    PubMed

    Çakıcı, Özlem

    2015-03-01

    The purpose of this work was to investigate for the first time histopathologic effects of carbaryl in liver and kidney tissues of Bufotes variabilis. After 96h following exposure to carbaryl (low dose: 0.05, medium dose: 0.1 and high dose: 0.2mg/g), the toads were euthanized and dissected. In liver tissue, vacuolization in hepatocytes, necrosis, mononuclear cell infiltration, an increase in melanomacrophage number, enlargement of sinusoids, hemorrhage and congestion were determined in exposed toads. In kidney tissue, mononuclear cell infiltration, hypertrophied Bowman's capsule cells, deformation, vacuolization, karyolysis and necrosis of renal tubule epithelium, brush border destruction, glomerular shrinkage, hemorrhage and fibrosis were observed in carbaryl-treated groups. According to this investigation, carbaryl caused histopathologic damages in liver and kidney tissues of B. variabilis.

  5. [Local immune tolerance mechanisms in kidney cancer].

    PubMed

    Patard, Jean-Jacques; Bouet, Françoise; Rioux-Leclercq, Nathalie; Lobel, Bernard; Catros-Quemener, Véronique; Guillé, François

    2002-04-01

    Many arguments suggest that renal tumours are immunogenic. However, the immune cells present around or within the tumour are unable to induce tumour rejection and the results of immunotherapy in metastatic renal cancer remain disappointing regardless of the protocols used. The objective of this study was to review the main mechanisms by which a renal tumour can escape immune destruction. These mechanisms can concern: tumour antigens, antigen-presenting molecules on the cell surface or defects of the cell machinery leading to the preparation of these molecules. Defects may also concern intercellular communications, especially adhesion and co-stimulation molecules. The immune cells present may also be defective, presenting qualitative or quantitative deficits, abnormalities of the T receptor, defect of cytokine production and these defects may concern both effector cells and antigen-presenting cells. The capacity of tumour cells to release anergic substances, i.e. substances which paralyze the immune system, also constitutes another very powerful immunosuppressive mechanism. These substances are cytokines, especially TGF-b. This anergy can also be mediated by intercellular contacts between tumour cells and lymphocytes, especially via the Fas system. It is important to study these mechanisms for several reasons: 1/Understanding of anergy mechanisms in order to discover new therapeutic targets or to short-circuit these mechanisms in vitro; 2/Definition of an "immune phenotype" of the tumour which should be evaluated as a prognostic marker both for survival after radical surgery of localized tumours as a prognostic factor for response to immunotherapy in metastatic forms.

  6. Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

    PubMed Central

    Li, Zhenyu; Li, Aiping; Gao, Jining; Li, Hong; Qin, Xuemei

    2016-01-01

    Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF. PMID:27695416

  7. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

    PubMed Central

    Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

    2016-01-01

    On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression. PMID:27695507

  8. Oestrone sulphate, adipose tissue, and breast cancer.

    PubMed

    Hawkins, R A; Thomson, M L; Killen, E

    1985-01-01

    Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91-4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23-4.63 nmol/l) or without (0.18-1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49-0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways: In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37 degrees C, cancers (131-412 fmol/g tissue/hr) and adipose tissues (23-132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1-36 fmol/g tissue/hr). In tissue homogenates incubated with 5-25 microM [3H] oestrone sulphate at 37 degrees much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2-16.5 microM: cancers (34-394) and benign tissues (9-485) had significantly higher sulphatase activities than adipose tissues (9-39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and that in vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findings in vivo remains to be established.

  9. Elemental composition of liver and kidney tissues of rough-toothed dolphins (Steno bredanensis).

    PubMed

    Mackey, E A; Oflaz, R D; Epstein, M S; Buehler, B; Porter, B J; Rowles, T; Wise, S A; Becker, P R

    2003-05-01

    On December 14, 1997, 62 rough-toothed dolphins (Steno bredanensis) stranded on Cape San Blas, on the Florida coast of the Gulf of Mexico. Approximately 30 animals died either on the beach or in rehabilitation facilities. Two were successfully rehabilitated and released. Liver, kidney, blubber, and muscle tissues were collected from 15 animals that died on the beach. Portions of the liver and kidney from each dolphin were analyzed using instrumental neutron activation analysis and inductively coupled plasma mass spectrometry to determine mass fractions of 37 elements. Levels of several electrolytes (Na, Cl, K, Br, Rb, I, Cs) and of the essential trace elements Fe, Cu, and Zn in both tissues were similar to those found in other Odontoceti. Mass fractions of Ca ranged from 60 mg/kg to 1,200 mg/kg (wet mass basis), indicating significant inhomogeneity in the kidney tissues of several animals. Necropsy reports noted that the kidneys of many of these animals contained fibrous nodules. The measured Ca inhomogeneity may be due to mineralization of the fibrous kidney tissue. Hepatic levels of Hg and Se were at the high end of the ranges generally found in livers of other Odontoceti and were slightly higher in animals with fibrous kidneys than in the others. Mass fractions of Se, Ag, and Hg in liver tissues increased with the size and age of the animals indicating accumulation of these elements in the liver with age. Results also indicate that Se and Hg accumulate in rough-toothed dolphin kidney. Accumulation of these elements with age has been reported commonly for marine mammals and other species.

  10. The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease.

    PubMed

    Seeger-Nukpezah, Tamina; Geynisman, Daniel M; Nikonova, Anna S; Benzing, Thomas; Golemis, Erica A

    2015-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited disorder in which renal tissue is gradually replaced with fluid-filled cysts, giving rise to chronic kidney disease (CKD) and progressive loss of renal function. ADPKD is also associated with liver ductal cysts, hypertension, chronic pain and extra-renal problems such as cerebral aneurysms. Intriguingly, improved understanding of the signalling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of solid tumours, even though the gross presentation of tumours and the greater morbidity and mortality associated with tumour invasion and metastasis would initially suggest entirely different disease processes. The commonalities between ADPKD and cancer are provocative, particularly in the context of recent preclinical and clinical studies of ADPKD that have shown promise with drugs that were originally developed for cancer. The potential therapeutic benefit of such repurposing has led us to review in detail the pathological features of ADPKD through the lens of the defined, classic hallmarks of cancer. In addition, we have evaluated features typical of ADPKD, and determined whether evidence supports the presence of such features in cancer cells. This analysis, which places pathological processes in the context of defined signalling pathways and approved signalling inhibitors, highlights potential avenues for further research and therapeutic exploitation in both diseases.

  11. Limb Salvage After Bone Cancer

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  12. Rapid evaluation of fresh ex vivo kidney tissue with full-field optical coherence tomography

    PubMed Central

    Jain, Manu; Robinson, Brian D.; Salamoon, Bekheit; Thouvenin, Olivier; Boccara, Claude; Mukherjee, Sushmita

    2015-01-01

    Background: Full-field optical coherence tomography (FFOCT) is a real-time imaging technique that rapidly generates images reminiscent of histology without any tissue processing, warranting its exploration for evaluation of ex vivo kidney tissue. Methods: Fresh tissue sections from tumor and adjacent nonneoplastic kidney (n = 25 nephrectomy specimens; clear cell renal cell carcinoma (CCRCC) = 12, papillary RCC (PRCC) = 4, chromophobe RCC (ChRCC) = 4, papillary urothelial carcinoma (PUC) = 1, angiomyolipoma (AML) = 2 and cystic nephroma = 2) were imaged with a commercial FFOCT device. Sections were submitted for routine histopathological diagnosis. Results: Glomeruli, tubules, interstitium, and blood vessels were identified in nonneoplastic tissue. In tumor sections, the normal architecture was completely replaced by either sheets of cells/trabeculae or papillary structures. The former pattern was seen predominantly in CCRCC/ChRCC and the latter in PRCC/PUC (as confirmed on H&E). Although the cellular details were not very prominent at this resolution, we could identify unique cytoplasmic signatures in some kidney tumors. For example, the hyper-intense punctate signal in the cytoplasm of CRCC represents glycogen/lipid, large cells with abundant hyper-intense cytoplasm representing histiocytes in PRCC, and signal-void large polygonal cell representing adipocytes in AML. According to a blinded analysis was performed by an uropathologist, all nonneoplastic tissues were differentiated from neoplastic tissues. Further, all benign tumors were called benign and malignant were called malignant. A diagnostic accuracy of 80% was obtained in subtyping the tumors. Conclusion: The ability of FFOCT to reliably differentiate nonneoplastic from neoplastic tissue and identify some tumor types makes it a valuable tool for rapid evaluation of ex vivo kidney tissue e.g. for intraoperative margin assessment and kidney biopsy adequacy. Recently, higher resolution images were achieved

  13. Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals.

    PubMed

    Yanik, Elizabeth L; Clarke, Christina A; Snyder, Jon J; Pfeiffer, Ruth M; Engels, Eric A

    2016-05-01

    Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.

  14. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    PubMed

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.

  15. Expression of lumbosacral HOX genes, crucial in kidney organogenesis, is systematically deregulated in clear cell kidney cancers.

    PubMed

    Cantile, Monica; Schiavo, Giulia; Franco, Renato; Cindolo, Luca; Procino, Alfredo; D'Armiento, Maria; Facchini, Gaetano; Terracciano, Luigi; Botti, Gerardo; Cillo, Clemente

    2011-06-01

    Homeobox-containing genes are involved in different stages of kidney organogenesis, from the early events in intermediate mesoderm to terminal differentiation of glomerular and tubular epithelia. The HOX genes show a unique genomic network organization and regulate normal development. The targeted disruption of paralogous group 11 HOX genes (HOX A11, HOX C11 and HOX D11) results in a complete loss of metanephric kidney induction. Despite a large amount of data are related to the early events in the kidney development, not much is known about HOX genes in advanced kidney organogenesis and carcinogenesis. Here, we compare the expression of the whole HOX gene network in late-stage human foetal kidney development with the same patterns detected in 25 pairs of normal clear cell renal carcinomas (RCCs) and 15 isolated RCC biopsy samples. In the majority of RCCs tested, HOX C11 is upregulated, whereas HOX D11, after an early involvement becomes active again at the 23rd week of the foetal kidney development, is always expressed in normal adult kidneys and is deregulated, together with HOX A11 and lumbosacral locus D HOX genes. Thus, through its function of regulating phenotype cell identity, the HOX network plays an important role in kidney carcinogenesis. Lumbosacral HOX genes are involved in the molecular alterations associated with clear cell kidney cancers and represent, through their deregulation, a molecular mark of tubular epithelial dedifferentiation occurring along tumour evolution, with the restoration of genetic programs associated with kidney organogenesis. The deregulation of lumbosacral HOX genes in RCCs supports (i) the consideration of the HOX gene transcriptome as the potential prognostic tool in kidney carcinogenesis and (ii) the possibility to foresee clinical trials with the purpose of targeting these genes to achieve a therapeutic effect in RCC patients.

  16. Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120

    PubMed Central

    Velenosi, Thomas J.; Hennop, Anzel; Feere, David A.; Tieu, Alvin; Kucey, Andrew S.; Kyriacou, Polydoros; McCuaig, Laura E.; Nevison, Stephanie E.; Kerr, Michael A.; Urquhart, Bradley L.

    2016-01-01

    Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD. PMID:26932318

  17. Amyloidosis: A cancer-derived paraproteinemia and kidney involvement.

    PubMed

    Małyszko, Jolanta; Kozłowska, Klaudia; Małyszko, Jacek Stanisław

    2017-01-30

    Amyloidosis is the general term describing the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins. There are multiple different human protein precursors of amyloid fibrils. Amyloid deposits are stained using Congo Red and show typical apple-green birefringence in polarized microscopy. Nowadays, a novel technique LMD/MS technique or laser microdissection combined with mass spectrometry help to diagnose amyloidosis. Amyloidosis of the kidney is typically classified as being either one of two types: AL or AA. Less common is the hereditary amyloidosis. Clinical manifestations are usually determined by the type of precursor protein, the tissue distribution, and the amount of amyloid deposition. Renal manifestation is usually present as asymptomatic proteinuria or clinically apparent nephrotic syndrome. In some patients clinical presentation include impaired kidney function with no or mild proteinuria. Patients with renal amyloidosis who progress to end-stage renal disease (ESRD) can be treated with either dialysis or renal transplantation. Diagnosis of amyloidosis is prerequisite to consider treatment options to avoid unnecessary chemotherapy. Treatment of amyloidosis is aimed at decreasing the precursors of fibrillary proteins and/or decrease in synthesis/deposition of amyloid fibrils. It depends upon the type of amyloidosis and cause of excess fibril production.

  18. Direct fluorescent antibody technique for the detection of bacterial kidney disease in paraffin-embedded tissues

    USGS Publications Warehouse

    Ochiai, T.; Yasutake, W.T.; Gould, R.W.

    1985-01-01

    The direct fluorescent antibody technique (FAT) was successfully used to detect the causative agent of bacterial kidney disease (BKD), Renibacterium salmoninarum, in Bouin's solution flexed and paraffinembedded egg and tissue sections. This method is superior to gram stain and may be particularly useful in detecting the BKD organism in fish with low-grade infection.

  19. Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering.

    PubMed

    Batchelder, Cynthia A; Martinez, Michele L; Tarantal, Alice F

    2015-01-01

    Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise

  20. Tissue damage in kidney, adrenal glands and diaphragm following extracorporeal shock wave lithotripsy.

    PubMed

    Gecit, Ilhan; Kavak, Servet; Oguz, Elif Kaval; Pirincci, Necip; Günes, Mustafa; Kara, Mikail; Ceylan, Kadir; Kaba, Mehmet; Tanık, Serhat

    2014-10-01

    This study was designed to investigate whether exposure to short-term extracorporeal shock wave lithotripsy (ESWL) produces histologic changes or induces apoptosis in the kidney, adrenal glands or diaphragm muscle in rats. The effect of shock waves on the kidney of male Wistar rats (n = 12) was investigated in an experimental setting using a special ESWL device. Animals were killed at 72 h after the last ESWL, and the tissues were stained with an in situ Cell Death Detection Kit, Fluorescein. Microscopic examination was performed by fluorescent microscopy. Apoptotic cell deaths in the renal tissue were not observed in the control group under fluorescent microscopy. In the ESWL group, local apoptotic changes were observed in the kidney in the area where the shock wave was focused. The apoptotic cell deaths observed in the adrenal gland of the control group were similar to those observed in the ESWL groups, and apoptosis was occasionally observed around the capsular structure. Apoptotic cell deaths in the diaphragm muscle were infrequently observed in the control group. Apoptosis in the ESWL group was limited to the mesothelial cells. This study demonstrated that serious kidney, adrenal gland and diaphragm muscles damage occurred following ESWL, which necessitated the removal of the organ in the rat model. It is recognized that the ESWL complications related to the kidney, adrenal gland and diaphragm muscles are rare and may be managed conservatively.

  1. Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues.

    PubMed

    Nath, K A

    2006-08-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, converting heme to biliverdin, during which iron is released and carbon monoxide (CO) is emitted; biliverdin is subsequently converted to bilirubin by biliverdin reductase. At least two isozymes possess HO activity: HO-1 represents the isozyme induced by diverse stressors, including ischemia, nephrotoxins, cytokines, endotoxin, oxidants, and vasoactive substances; HO-2 is the constitutive, glucocorticoid-inducible isozyme. HO-1 is upregulated in the kidney in assorted conditions and diseases. Interest in HO is driven by the capacity of this system to protect the kidney against injury, a capacity likely reflecting, at least in part, the cytoprotective properties of its products: in relatively low concentrations, CO exerts vasorelaxant, antiapoptotic, and anti-inflammatory effects while bile pigments are antioxidant and anti-inflammatory metabolites. This article reviews the HO system and the extent to which it influences the function of the healthy kidney; it summarizes conditions and stimuli that elicit HO-1 in the kidney; and it explores the significance of renal expression of HO-1 as induced by ischemia, nephrotoxins, nephritides, transplantation, angiotensin II, and experimental diabetes. This review also points out the tissue specificity of the HO system, and the capacity of HO-1 to induce renal injury in certain settings. Studies of HO in other tissues are discussed insofar as they aid in elucidating the physiologic and pathophysiologic significance of the HO system in the kidney.

  2. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan

    PubMed Central

    Lee, Kwai-Fong; Tsai, Yi-Ting; Lin, Chih-Yuan; Hsieh, Chung-Bao; Wu, Sheng-Tang; Ke, Hung-Yen; Lin, Yi-Chang; Lin, Feng-Yen; Lee, Wei-Hwa; Tsai, Chien-Sung

    2016-01-01

    Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex. PMID:27196400

  3. Identification of the genes for kidney cancer: opportunity for disease-specific targeted therapeutics.

    PubMed

    Linehan, W Marston; Pinto, Peter A; Srinivasan, Ramaprasad; Merino, Maria; Choyke, Peter; Choyke, Lynda; Coleman, Jonathan; Toro, Jorge; Glenn, Gladys; Vocke, Cathy; Zbar, Bert; Schmidt, Laura S; Bottaro, Donald; Neckers, Len

    2007-01-15

    Recent advances in understanding the kidney cancer gene pathways has provided the foundation for the development of targeted therapeutic approaches for patients with this disease. Kidney cancer is not a single disease; it includes a number of different types of renal cancers, each with different histologic features, a different clinical course, a different response to therapy, and different genes causing the defects. Most of what is known about the genetic basis of kidney cancer has been learned from study of the inherited forms of kidney cancer: von Hippel Lindau (VHL gene), hereditary papillary renal carcinoma (c-Met gene), Birt Hogg Dubé (BHD gene), and hereditary leiomyomatosis renal cell cancer (fumarate hydratase gene). These Mendelian single-gene syndromes provide a unique opportunity to evaluate the effectiveness of agents that target the VHL, c-Met, BHD, and fumarate hydratase pathways.

  4. 2'-Hydroxyflavanone: A promising molecule for kidney cancer prevention.

    PubMed

    Singhal, Sharad S; Singhal, Jyotsana; Figarola, James L; Riggs, Arthur; Horne, David; Awasthi, Sanjay

    2015-08-01

    Kidney cancer, also known as renal cell carcinoma (RCC), is one of the top 10 diagnosed cancers in the USA, and the incidence is rising. Despite major improvements in drug therapy strategies, RCC remains a deadly malignancy if not found and removed in its early stages. RCC is so highly drug-resistant that no effective life-prolonging regimen of cytotoxic chemotherapy has been demonstrated for RCC, despite several decades of effort. It is also highly radiation-resistant, thus circumventing therapies to prevent local recurrence or to control metastatic disease. In the last few years, extensive research has been conducted to elucidate the functional significance of the plant-derived compounds, and their derivatives, as anticancer agents. This review is focussed on a chemo-dietary prevention strategy against RCC using a citrus-derived compound called 2'-hydroxyflavanone. RCC is frequently caused by VHL gene mutations, which contribute to 75% of all RCCs. These mutations are positively linked to cigarette smoking, and exposure to the tobacco carcinogen, N-nitrosodimethylamine and benzopyrene, can disrupt VHL. According to in vitro and preclinical mouse studies, 2'-hydroxyflavanone can both protect the VHL locus and prevent the progression of VHL-mutant cancer. Human clinical trials examining the effect of supplementation of 2'-hydroxyflavanone, either alone or in combination with chemotherapeutic drugs, on RCC prevention have not been conducted, although there is considerable potential for 2'-hydroxyflavanone and its derivatives to be developed as RCC chemoprevention agents. Therefore, the discovery of plant-derived cancer therapies, such as 2'-hydroxyflavanone, offers a new strategy for combating this highly resistant cancer.

  5. Environmental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain

    PubMed Central

    2012-01-01

    The role of steroids in carcinogenesis has become a major concern in environmental protection, biomonitoring, and clinical research. Although historically oestrogen has been related to development of reproductive system, research over the last decade has confirmed its crucial role in the development and homeostasis of other organ systems. As a number of anthropogenic agents are xenoestrogens, environmental health research has focused on oestrogen receptor level disturbances and of aromatase polymorphisms. Oestrogen and xenoestrogens mediate critical points in carcinogenesis by binding to oestrogen receptors, whose distribution is age-, gender-, and tissue-specific. This review brings data about cancer types whose eatiology may be found in environmental exposure to xenoestrogens. Cancer types that have been well documented in literature to be related with environmental exposure include the reproductive system, breast, lung, kidney, pancreas, and brain. The results of our data mining show (a) a significant correlation between exposure to xenoestrogens and increased, gender-related, cancer risk and (b) a need to re-evaluate agents so far defined as endocrine disruptors, as they are also key molecules in carcinogenesis. This revision may be used to further research of cancer aetiology and to improvement of related legislation. Investigation of cancers caused by xenoestrogens may elucidate yet unknown mechanisms also valuable for oncology and the development of new therapies. PMID:22759508

  6. Laser Capture Microdissection of Archival Kidney Tissue for qRT-PCR.

    PubMed

    Hewitson, Tim D; Christie, Michael; Smith, Edward R

    2016-01-01

    Whole-organ molecular analysis of the kidney potentially misses important factors involved in the pathogenesis of disease in glomeruli and tubules. Organ wide analysis can however be augmented by using laser capture microdissection (LCM) to isolate morphologically similar cells and nephron structures from a heterogeneous tissue section via direct visualization of the cells. The protocol here provides a practical approach utilizing LCM in combination with RNA isolation techniques for downstream analysis. This technique is readily applicable to study mRNA expression in isolated glomeruli and tubules in both experimental animal models and human kidney biopsy material.

  7. Tivozanib: a novel VGFR inhibitor for kidney cancer.

    PubMed

    Boyle, Helen

    2013-06-01

    Treatment of kidney cancer has changed over the past 10 years with the approval of several targeted agents. These drugs are given on a long term base and toxicity is an issue for most patients. Despite improvement compared to immunotherapy, most patients will progress on these drugs. There is a need for more portent and better tolerated drugs. Tivozanib is a potent pan VEGR specific inhibitor. In this phase II trial it gave interesting results with an overall median PFS throughout the study of 11.7 months (95% CI: 8.3-14.3 months) and an overall objective response rate of 24% (95% CI: 19-30%). "Off"-target toxicity was mild.

  8. Kidney cancer mortality and ionizing radiation among French and German uranium miners.

    PubMed

    Drubay, Damien; Ancelet, Sophie; Acker, Alain; Kreuzer, Michaela; Laurier, Dominique; Rage, Estelle

    2014-08-01

    The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.

  9. Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis.

    PubMed

    Yanik, Elizabeth L; Siddiqui, Kulsoom; Engels, Eric A

    2015-09-01

    Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20-0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.

  10. Temporal Trends in the Histology of the Rabbit Kidney after Cavitational Tissue Ablation

    NASA Astrophysics Data System (ADS)

    Hall, Timothy L.; Kieran, Kathleen; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2007-05-01

    Tissue can be mechanically ablated through inertial cavitation generated by high intensity pulsed ultrasound. The ablation appears acutely as a fine slurry with absent cellular structure. Long-term effects and the evolution of histologic changes in disrupted tissue remain poorly understood. This study aimed to characterize the 0-60 day histology of cavitational ablation in a rabbit model. 29 New Zealand White rabbits were anesthetized and exposed to high intensity pulses of ultrasound (60000 pulses, 20 usec duration, 750 kHz, 1 kHz PRF, 18 MPa peak rarefactional pressure, lower pole, left kidney). Kidneys were harvested immediately from five rabbits. The others were recovered and the kidneys were harvested 1, 2, 7, 20, or 60 days after treatment. Grossly, kidneys from 0-2 days displayed subcapsular bruising near the exposure site and some hemorrhage in the adjacent perirenal fat; microscopically, a disrupted, acellular zone measuring 3-5 mm by 5-10 mm accompanied by local infiltration of neutrophils (acute inflammation) was seen. Kidneys harvested after 7 days displayed tubular dilatation adjacent to the targeted area and collagen deposition consistent with scar formation. Decreased collagen deposition, decreased size of the disrupted zone, and regeneration of the tubular basal cell layer of dilated tubules was evident by day 20. Kidneys harvested at 20 and 60 days had contour defects near the exposure site with an apparent volume loss. Cavitation causes orderly and predictable histologic changes. Local renal damage induced during histotripsy may be partially reversible. Further research is needed to identify the clinical correlates of the observed histologic findings.

  11. Risk of Cancer in Retransplants Compared to Primary Kidney Transplants in the United States

    PubMed Central

    Kalil, Roberto S.; Lynch, Charles F.; Engels, Eric A.

    2015-01-01

    Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109,224 primary recipients and 6,621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 years), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5,757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [IRR] 1.06, 95%CI 0.93-1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma (RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95%CI 1.45-2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation. PMID:26255999

  12. Risk of cancer in retransplants compared to primary kidney transplants in the United States.

    PubMed

    Kalil, Roberto S; Lynch, Charles F; Engels, Eric A

    2015-10-01

    Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109 224 primary recipients and 6621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 yr), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [IRR] 1.06, 95% CI 0.93-1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma (RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95% CI 1.45-2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation.

  13. Structural transition of kidney cystatin in dimethylnitrosamine-induced renal cancer in rats: identification as a novel biomarker for kidney cancer and prognosis.

    PubMed

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

    2017-04-01

    In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.

  14. Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

    PubMed Central

    Sato, Yuki; Mii, Akiko; Hamazaki, Yoko; Fujita, Harumi; Nakata, Hirosuke; Masuda, Kyoko; Nishiyama, Shingo; Shibuya, Shinsuke; Haga, Hironori; Ogawa, Osamu; Shimizu, Akira; Narumiya, Shuh; Kaisho, Tsuneyasu; Arita, Makoto; Yanagisawa, Masashi; Sharma, Kumar; Minato, Nagahiro; Kawamoto, Hiroshi

    2016-01-01

    Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor+ (p75NTR+) fibroblasts and homeostatic chemokine–producing fibroblasts inside TLTs, and retinoic acid–producing fibroblasts around TLTs. Deletion of CD4+ cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly. PMID:27699223

  15. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury

    PubMed Central

    Hoyt, Kenneth; Warram, Jason M.; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Purpose The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. Procedures A population of rats underwent 30 min of renal ischemia (acute kidney injury, N=6) or sham injury (N=4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Results Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Conclusions Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted. PMID:25905474

  16. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    PubMed

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  17. Trace elements determinations in cancerous and non-cancerous human tissues using instrumental neutron activation analysis

    SciTech Connect

    Choi, Insup.

    1989-01-01

    Recent improvements in analyzing techniques when coupled to the growing knowledge of trace element biochemistry provide a powerful tool to investigate the relationship between trace elements and cancer. It is hoped that selective delivery or restriction of specific minerals may aid in cancer prevention or treatment. Tissues were collected at the time of surgery of various cancer patients including colon cancer and breast cancer. Three kinds of tissues were taken from a patient; cancerous, noncancerous, and transitional tissue obtained from a region located between the cancer and healthy tissues. A total of 57 tissues were obtained from 19 cancer patients. Seven of them were colon cancer patients, and 5 of them were breast cancer patients. Nine elements were determined using instrumental activation analysis. Cancerous colon tissue had significantly higher concentrations of selenium and iron than healthy tissues. Cancerous breast tissue had significantly higher concentrations of selenium, iron, manganese, and rubidium than healthy tissues. Iron can be enriched in cancer tissue because cancer tissue retains more blood vessels. Selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumors. The manganese enrichment can be explained in the same manner as selenium considering its suspected anticarcinogenicity. It is not certain why rubidium was enriched in cancer tissue. It could be that this is the result of alteration of cell membrane permeability, change in extracellular matrix, or increased metabolism in cancer tissue.

  18. Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

    Cancer.gov

    Results from a recent clinical trial show that post-surgical therapy with two anti-angiogenesis drugs does not improve progression-free survival for patients with kidney cancer and may cause serious side effects.

  19. Inside the 2016 American Society of Clinical Oncology Genitourinary Cancers Symposium: part 1 - kidney cancer.

    PubMed

    Buti, Sebastiano; Ciccarese, Chiara; Iacovelli, Roberto; Bersanelli, Melissa; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The American Society of Clinical Oncology Genitourinary Cancers Symposium, Moscone West Building, San Francisco, CA, USA, 7-9 January 2016 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco (CA, USA), from 7 to 9 January 2016, focused on 'patient-centric care: translating research to results'. Every year, this meeting is a must for anyone studying genitourinary tumors to keep abreast of the most recent innovations in this field, exchange views on behaviors customarily adopted in daily clinical practice, and discuss future topics of scientific research. This two-part report highlights the key themes presented at the 2016 ASCO Genitourinary Cancers Symposium, with part 1 reporting the main novelties of kidney cancer and part 2 discussing the most relevant issues which have emerged for bladder and prostate tumors.

  20. Palpation Device for the Identification of Kidney and Bladder Cancer: A Pilot Study

    PubMed Central

    Lee, Jae Won; Lorenzo, Enrique Ian S.; Ahn, Bummo; Oh, Cheol Kyu; Kim, Hyung-Joo; Han, Woong Kyu; Kim, Jung

    2011-01-01

    Purpose To determine the ability of a novel palpation device to differentiate between benign and malignant tissues of the kidney and bladder by measuring tissue elasticity. Materials and Methods A novel palpation device was developed, mainly composed of a micromotor, a linear position sensor, a force transducer, and a hemisphere tip and cylindrical body probe. Motion calibration as well as performance validation was done. The tissue elasticity of both benign and malignant tissues of the kidney and bladder was measured using this device. A single investigator performed the ex-vivo palpation experiment in twelve kidneys and four bladder specimens. Malignant tissues were made available from partial nephrectomy specimens and radical cystectomy specimens. Palpations for benign renal parenchyma tissue were carried out on nephroureterectomy specimens while non-involved areas in the radical cystectomy specimens were used for benign bladder samples. Elastic modulus (Young's modulus) of tissues was estimated using the Hertz-Sneddon equation from the experimental results. These were then compared using a t-test for independent samples. Results Renal cell carcinoma tissues appear to be softer than normal kidney tissues, whereas tissues from urothelial carcinoma of the bladder appear to be harder than normal bladder tissues. The results from renal cell carcinoma differed significantly from those of normal kidney tissues (p=0.002), as did urothelial carcinoma of the bladder from normal bladder tissues (p=0.003). Conclusion Our novel palpation device can potentially differentiate between malignant and benign kidney and bladder tissues. Further studies are necessary to verify our results and define its true clinical utility. PMID:21786441

  1. Zinc prevention of electromagnetically induced damage to rat testicle and kidney tissues.

    PubMed

    Ozturk, Ahmet; Baltaci, Abdülkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2003-01-01

    The aim of this study was to investigate the extent of lipid peroxidation when zinc is administered to rats periodically exposed to a 50-Hz electromagnetic field for 5 min at a time over a period of 6 mo. Twenty-four Sprague-Dawley adult male rats were subdivided in groups of eight animals each. Group 1 served as untreated controls, group 2 was exposed to an electromagnetic field but received no additional treatment, and group 3 was exposed to electromagnetic radiation and treated with 3-mg/kg daily intraperitoneal injections of zinc sulfate. The erythrocyte glutathione activity (GSH) and the plasma, testicle, and kidney tissue levels of zinc (Zn) and of malondialdehyde (MDA) were measured in all of the animals. The plasma and testicle MDA levels in group 2 were higher than those in groups 1 and 3, with group 3 values significantly higher than those in group 1 (p<0.001). The kidney MDA levels in group 2 were higher than in groups 1 and 3 (p<0.001). The erythrocyte GSH level was lower in group 2 than in groups 1 and 3, with group 1 significantly lower than group 3 (p<0.001). In testicle and kidney tissues, the GSH levels in group 1 were lower than for groups 2 and 3, with group 2 significantly lower than group 3 (p<0.001) The plasma zinc levels were highest in group 3, followed by group 1 and group 2, which showed the lowest value (p<0.001). These results indicate that testicle and kidney tissue damage caused by periodic exposure to an electromagnetic field are ameliorated or prevented by zinc supplementation.

  2. Medication use and survival in diabetic patients with kidney cancer: A population-based cohort study.

    PubMed

    Nayan, Madhur; Macdonald, Erin M; Juurlink, David N; Austin, Peter C; Finelli, Antonio; Kulkarni, Girish S; Hamilton, Robert J

    2016-11-01

    Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes.

  3. Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer

    PubMed Central

    Trott, Josephine F.; Kim, Jeffrey; Aboud, Omran Abu; Wettersten, Hiromi; Stewart, Benjamin; Berryhill, Grace; Uzal, Francisco; Hovey, Russell C.; Chen, Ching-Hsien; Anderson, Katie; Graef, Ashley; Sarver, Aaron L; Modiano, Jaime F.; Weiss, Robert H.

    2016-01-01

    Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC. PMID:27572319

  4. Calcium and magnesium in drinking water and risk of death from kidney cancer.

    PubMed

    Chiu, Hui-Fen; Chang, Chih-Ching; Chen, Chih-Cheng; Yang, Chun-Yuh

    2011-01-01

    The possible association between the risk of kidney cancer development and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched cancer case-control study in Taiwan. All eligible kidney cancer deaths (1778 cases) of Taiwan residents from 1999 through 2008 were compared with deaths from other causes (1778 controls), and the levels of calcium and magnesium in drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of individuals who died from other causes, and the controls were pair-matched to the cancer cases by gender, year of birth, and year of death. The adjusted odd ratios for death attributed to kidney cancer for individuals with higher calcium levels in their drinking water, as compared to the lowest tertile, were 0.89 (95% CI = 0.72-1.11) and 0.78 (95% CI = 0.62-0.98), respectively. The adjusted odd ratios were not statistically significant for the relationship between magnesium levels in drinking water and kidney cancer development. The results of the present study demonstrate that there may be a significant protective effect of calcium intake from drinking water against the risk of death due to kidney cancer.

  5. Trace level determination of trichloroethylene from liver, lung and kidney tissues by gas chromatography - magnetic sector mass spectrometry

    SciTech Connect

    Stacy D. Brown; S. Muralidhara; James V. Bruckner, Michael G. Bartlett

    2002-07-30

    Trichloroethylene (TCE) is a common industrial chemical that has been heavily used as a metal degreaser and a solvent for the past 100 years. As a result of the extensive use and production of this compound, it has become prevalent in the environment, appearing at over 50% of the hazardous waste sites on the US EPA's National Priorities List (NPL). TCE exposure has been linked to neurological dysfunction as well as to several types of cancer in animals. This paper describes the development and validation of a gas chromatography-mass spectrometry (GC-MS) method for the quantitation of trace levels of TCE in its target tissues (i.e. liver, kidney and lungs). The limit of quantitation (5 ng/ml) is substantially lower than currently published methods for the analysis of TCE in tissues. The % RSD and % Error for the assay falls within the acceptable range (<15% for middle and high QC points and <20% for low QC points), and the recovery is high from all tissues (>79%).

  6. Lipidomic differentiation between human kidney tumors and surrounding normal tissues using HILIC-HPLC/ESI-MS and multivariate data analysis.

    PubMed

    Cífková, Eva; Holčapek, Michal; Lísa, Miroslav; Vrána, David; Melichar, Bohuslav; Študent, Vladimír

    2015-09-01

    The characterization of differences among polar lipid classes in tumors and surrounding normal tissues of 20 kidney cancer patients is performed by hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS). The detailed analysis of identified lipid classes using relative abundances of characteristic ions in negative- and positive-ion modes is used for the determination of more than 120 individual lipid species containing attached fatty acyls of different chain length and double bond number. Lipid species are described using relative abundances, providing a better visualization of lipidomic differences between tumor and normal tissues. The multivariate data analysis methods using unsupervised principal component analysis (PCA) and supervised orthogonal partial least square (OPLS) are used for the characterization of statistically significant differences in identified lipid species. Ten most significant up- and down-regulated lipids in OPLS score plots are also displayed by box plots. A notable increase of relative abundances of lipids containing four and more double bonds is detected in tumor compared to normal tissues.

  7. Assembling Kidney Tissues from Cells: The Long Road from Organoids to Organs

    PubMed Central

    Hariharan, Krithika; Kurtz, Andreas; Schmidt-Ott, Kai M.

    2015-01-01

    The field of regenerative medicine has witnessed significant advances that can pave the way to creating de novo organs. Organoids of brain, heart, intestine, liver, lung and also kidney have been developed by directed differentiation of pluripotent stem cells. While the success in producing tissue-specific units and organoids has been remarkable, the maintenance of an aggregation of such units in vitro is still a major challenge. While cell cultures are maintained by diffusion of oxygen and nutrients, three- dimensional in vitro organoids are generally limited in lifespan, size, and maturation due to the lack of a vascular system. Several groups have attempted to improve vascularization of organoids. Upon transplantation into a host, ramification of blood supply of host origin was observed within these organoids. Moreover, sustained circulation allows cells of an in vitro established renal organoid to mature and gain functionality in terms of absorption, secretion and filtration. Thus, the coordination of tissue differentiation and vascularization within developing organoids is an impending necessity to ensure survival, maturation, and functionality in vitro and tissue integration in vivo. In this review, we inquire how the foundation of circulation is laid down during the course of organogenesis, with special focus on the kidney. We will discuss whether nature offers a clue to assist the generation of a nephro-vascular unit that can attain functionality even prior to receiving external blood supply from a host. We revisit the steps that have been taken to induce nephrons and provide vascularity in lab grown tissues. We also discuss the possibilities offered by advancements in the field of vascular biology and developmental nephrology in order to achieve the long-term goal of producing transplantable kidneys in vitro. PMID:26618157

  8. Association of Kidney Tissue Barrier Disrupture and Renal Dysfunction in Resuscitated Murine Septic Shock.

    PubMed

    Stenzel, Tatjana; Weidgang, Clair; Wagner, Katja; Wagner, Florian; Gröger, Michael; Weber, Sandra; Stahl, Bettina; Wachter, Ulrich; Vogt, Josef; Calzia, Enrico; Denk, Stephanie; Georgieff, Michael; Huber-Lang, Markus; Radermacher, Peter; McCook, Oscar

    2016-10-01

    Septic shock-related kidney failure is characterized by almost normal morphological appearance upon pathological examination. Endothelial barrier disrupture has been suggested to be of crucial importance for septic shock-induced organ dysfunction. Therefore, in murine resuscitated cecal ligation and puncture (CLP)-induced septic shock, we tested the hypothesis whether there is a direct relationship between the kidney endothelial barrier injury and renal dysfunction. Anesthetized mice underwent CLP, and 15 h later, were anesthetized again and surgically instrumented for a 5-h period of intensive care comprising lung-protective mechanical ventilation, fluid resuscitation, continuous i.v. norepinephrine to maintain target hemodynamics, and measurement of creatinine clearance (CrCl). Animals were stratified according to low or high CrCl. Nitrotyrosine formation, expression of the inducible isoform of the nitric oxide synthase, and blood cytokine (tumor necrosis factor, interleukin-6, interleukin-10) and chemokine (monocyte chemoattractant protein-1, keratinocyte-derived chemokine) levels were significantly higher in animals with low CrCl. When plotted against CrCl and neutrophil gelatinase-associated lipocalin levels, extravascular albumin accumulation, and tissue expression of the vascular endothelial growth factor and angiopoietin-1 showed significant mathematical relationships related to kidney (dys)function. Preservation of the constitutive expression of the hydrogen sulfide producing enzyme cystathione-γ-lyase was associated with maintenance of organ function. The direct quantitative relation between microvascular leakage and kidney (dys)function may provide a missing link between near-normal tissue morphology and septic shock-related renal failure, thus further highlighting the important role of vascular integrity in septic shock-related renal failure.

  9. Up-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer Survival

    PubMed Central

    Zaman, Mohd Saif; Shahryari, Varahram; Deng, Guoren; Thamminana, Sobha; Saini, Sharonjot; Majid, Shahana; Chang, Inik; Hirata, Hiroshi; Ueno, Koji; Yamamura, Soichiro; Singh, Kamaldeep; Tanaka, Yuichiro; Tabatabai, Z. Laura; Dahiya, Rajvir

    2012-01-01

    Background MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically. Methods and Results We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation. Conclusions The current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21. PMID:22347428

  10. Engineering liver tissues under the kidney capsule site provides therapeutic effects to hemophilia B mice.

    PubMed

    Ohashi, Kazuo; Tatsumi, Kohei; Utoh, Rie; Takagi, Soichi; Shima, Midori; Okano, Teruo

    2010-01-01

    Recent advances in liver tissue engineering have encouraged further investigation into the evaluation of therapeutic benefits based on animal disease models. In the present study, liver tissues were engineered in coagulation factor IX knockout (FIX-KO) mice, a mouse model of hemophilia B, to determine if the tissue engineering approach would provide therapeutic benefits. Primary hepatocytes were isolated from the liver of wild-type mice and suspended in a mixture of culture medium and extracellular matrix components. The hepatocyte suspension was injected into the space under the bilateral kidney capsules of the FIX-KO mice to engineer liver tissues. The plasma FIX activities (FIX:C) of the untreated FIX-KO mice were undetectable at any time point. In contrast, the liver tissue engineered FIX-KO mice achieved 1.5-2.5% of plasma FIX activities (FIX:C) and this elevated FIX:C level persisted throughout the 90 day experimental period. Significant FIX mRNA expression levels were found in the engineered liver tissues at levels similar to the wild-type livers. The present study demonstrates that liver tissue engineering could provide therapeutic benefits in the treatment of hemophilia B.

  11. Risk of kidney cancer and chronic kidney disease in relation to hepatitis C virus infection: a nationwide register-based cohort study in Sweden

    PubMed Central

    Hofmann, Jonathan N; Törner, Anna; Chow, Wong-Ho; Ye, Weimin; Purdue, Mark P; Duberg, Ann-Sofi

    2011-01-01

    Chronic hepatitis C virus (HCV) infection is an established cause of liver cancer, and recent studies have suggested a link with kidney cancer. The aim of this study was to evaluate risk of kidney cancer in relation to HCV infection in a nationwide registry-based study of Swedish residents diagnosed with HCV between 1990 and 2006. A total of 43,000 patients with chronic HCV infection were included, and the mean follow-up time was 9.3 years. Observed kidney cancer incidence and mortality in the cohort were compared with expected values based on the age- and sex-adjusted rates in the general population. Risk of hospitalization for other chronic kidney disease was also evaluated using Cox proportional hazards regression. No association between HCV infection and risk of kidney cancer was observed [standardized incidence ratio with one-year lag = 1.2; 95% confidence interval (CI) 0.8–1.7]. Risk of hospitalization for non-cancer kidney disease was significantly elevated in the HCV cohort, with significantly stronger associations observed among women than among men [hazard ratio = 5.8 (95% CI 4.2–7.9) and 3.9 (95% CI 3.2–4.8) for women and men, respectively]. Results of this study do not support the hypothesis that chronic HCV infection confers an increased risk of kidney cancer. However, we did find an association between HCV infection and chronic kidney disease, particularly among women. Given inconsistent findings in the literature, it is premature to consider HCV infection to be a risk factor for kidney cancer. PMID:21386707

  12. Oral contraceptive use and kidney cancer risk among women: evidence from a meta-analysis

    PubMed Central

    Liu, Huan; Wang, Xing-Chun; Hu, Guang-Hui; Huang, Tian-Bao; Xu, Yun-Fei

    2014-01-01

    Previous studies have investigated the relationship between oral contraceptives (OCs) use and kidney cancer risk. However, they yielded inconsistent results. To our knowledge, a comprehensive assessment of the association between OC and kidney cancer risk has not been reported. Hence, we conducted a meta-analysis to quantify the association. We identified all relevant studies up to July 2014 through a literature search of using PubMed and EMBASE, and by reviewing the references from the retrieved articles. Fixed-effect and random-effect models were used to estimate summary relative risks (SRRs) and the corresponding 95% confidence intervals (CIs). A total of 12 studies were eligible and included in this meta-analysis, involving 4,206 kidney cancer cases and 638,677 participants. The SRR of kidney cancer for ever versus never OC use was 0.89 (95% CI: 0.82-0.98). The protection became stronger when compared the longest duration of OC use with never use (RR = 0.80; 95% CI: 0.68-0.94). In dose-response analysis, we found that the kidney cancer risk decreased by 2% for per 1 year increment in OC use (RR = 0.98; 95% CI: 0.96-0.99). No apparent heterogeneity was observed across studies included in this analysis. Egger’s and Begg’s test also indicated no publication bias. The present study suggested that OC may reduce the risk of kidney cancer, especially for long-term users. More well-conducted and large-scale prospective studies are warranted to confirm the effects of OC use on kidney cancer. PMID:25550903

  13. The Relationship between the Occupational Exposure of Trichloroethylene and Kidney Cancer

    PubMed Central

    2014-01-01

    Trichloroethylene (TCE) has been widely used as a degreasing agent in many manufacturing industries. Recently, the International Agency for Research on Cancer presented “sufficient evidence” for the causal relationship between TCE and kidney cancer. The aim of this study was to review the epidemiologic evidences regarding the relationship between TCE exposure and kidney cancer in Korean work environments. The results from the cohort studies were inconsistent, but according to the meta-analysis and case–control studies, an increased risk for kidney cancer was present in the exposure group and the dose–response relationship could be identified using various measures of exposure. In Korea, TCE is a commonly used chemical for cleaning or degreasing processes by various manufacturers; average exposure levels of TCE vary widely. When occupational physicians evaluate work-relatedness kidney cancers, they must consider past exposure levels, which could be very high (>100 ppm in some cases) and associated with jobs, such as plating, cleaning, or degreasing. The exposure levels at a manual job could be higher than an automated job. The peak level of TCE could also be considered an important exposure-related variable due to the possibility of carcinogenesis associated with high TCE doses. This review could be a comprehensive reference for assessing work-related TCE exposure and kidney cancer in Korea. PMID:24955246

  14. Super-resolution stimulated emission depletion imaging of slit diaphragm proteins in optically cleared kidney tissue.

    PubMed

    Unnersjö-Jess, David; Scott, Lena; Blom, Hans; Brismar, Hjalmar

    2016-01-01

    The glomerular filtration barrier, consisting of podocyte foot processes with bridging slit diaphragm, glomerular basement membrane, and endothelium, is a key component for renal function. Previously, the subtlest elements of the filtration barrier have only been visualized using electron microscopy. However, electron microscopy is mostly restricted to ultrathin two-dimensional samples, and the possibility to simultaneously visualize multiple different proteins is limited. Therefore, we sought to implement a super-resolution immunofluorescence microscopy protocol for the study of the filtration barrier in the kidney. Recently, several optical clearing methods have been developed making it possible to image through large volumes of tissue and even whole organs using light microscopy. Here we found that hydrogel-based optical clearing is a beneficial tool to study intact renal tissue at the nanometer scale. When imaging samples using super-resolution STED microscopy, the staining quality was critical in order to assess correct nanoscale information. The signal-to-noise ratio and immunosignal homogeneity were both improved in optically cleared tissue. Thus, STED of slit diaphragms in fluorescently labeled, optically cleared, intact kidney samples is a new tool for studying the glomerular filtration barrier in health and disease.

  15. Trypsinization of monkey-kidney tissue: an automatic method for the preparation of cell suspensions*

    PubMed Central

    Rappaport, Catherine

    1956-01-01

    A study of some of the factors which influenced the rate and amount of cells released from tissue fragments during trypsinization led to a revision of the method described by Youngner for monkey kidney. The revision includes the use of a glass mixing-chamber and magnetic stirrer in place of the Waring blendor. Simpler to use, the revised method has been found to yield, consistently, about 7 × 10 7 cells per g of kidney tissue, or from two to three times more than that obtained by the earlier method. The revised method may be done either manually or automatically. A simple glass apparatus which automatically regulates the continuous addition of trypsin and removal of cell suspension during trypsinization has been developed. It operates reliably over a threefold volume range and a varying flow rate. The yield of cells per gram of tissue treated in the automatic trypsinizer is about 30% greater than when the change of fluids is done manually. ImagesFIG. 1FIG. 3 PMID:13329843

  16. Characterization of a thyroid hormone receptor expressed in human kidney and other tissues

    SciTech Connect

    Nakai, A.; Seino, S.; Sakurai, A.; Szilak, I.; Bell, G.I.; DeGroot, L.J.

    1988-04-01

    A cDNA encoding a specific form of thyroid hormone receptor expressed in human liver, kidney, placenta, and brain was isolated from a human kidney library. Identical clones were found in human placenta and HepG2 cDNA libraries. The cDNA encodes a 490-amino acid protein. When expressed and translated in vitro, the protein products binds triiodothyronine with K/sub a/ of 2.3 /times/ 10/sup 9/ M/sup /minus/1/. This protein, designated human thyroid hormone receptor type ..cap alpha..2 (hTR..cap alpha..2), has the same domain structure as other members of the v-erbA-related superfamily of receptor genes. It is similar to thyroid hormone receptor type ..cap alpha.. described in chicken and rat and less similar to human thyroid hormone receptor type ..beta.. (formerly referred to as c-erbA..beta..) from placenta. However, it is distinguished from these receptors by an extension of the C-terminal hormone binding domain making it 80 amino acids longer than rat thyroid hormone receptor type ..cap alpha..1. Different sizes of mRNA found in liver and kidney suggest that there may be tissue-specific processing of the primary transcript of this gene. Identification of human thyroid hormone receptor type ..cap alpha..2 indicates that two or more forms of thyroid hormone receptor exist in human tissues and may explain the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in the thyroid hormone resistance syndromes.

  17. Acute changes of serum markers for tissue damage after ESWL of kidney stones.

    PubMed

    Apostolov, I; Minkov, N; Koycheva, M; Isterkov, M; Abadjyev, M; Ondeva, V; Trendafilova, T

    1991-01-01

    Seventeen serum markers (including 9 enzyme activities) for eventual tissue damage were studied after ESWL in 40 patients with unilateral kidney calculosis. No changes were established in the 8 non-enzymic parameters and the activities of amylase, lipase, AST (GOT), ALT (GPT) and CK-MB. A statistically significant increase was found in LDH, alpha-HBDH, CK (twice) and glutamate dehydrogenase (3 times). The slight elevation of LDH and alpha-HBDH could be due to haemolysis caused by the shock waves. Increased activity of CK suggested myolysis and that of GlDH a hepatocellular damage.

  18. [Visible light reflectance spectrum for measurement of cancerous tissue].

    PubMed

    Wang, Cheng; Fan, Jin; Ren, Qiu-Shi

    2008-01-01

    A goal the authors always pursue is to realize diagnosis of precancer in vivo, real-time and non-invasive. In the present paper, results of diagnosis of certain cancer were obtained by pathological analysis of several samples, and then the visible light reflectance spectrum property of cancerous tissue was acquired by the comparison with the reflectance spectrum of normal tissue in the same organ. It was found that the main result of change in the reflectance spectrum was caused by the increases in hemoglobin and deoxygenated hemoglobin. The cancerous tissue has a lower reflectance in visible spectrum and has the strongest change in the absorption at 630 nm. Absorption peaks in the reflectance spectrum indicated that there are abundant of oxygenated hemoglobin and deoxygenated hemoglobin in the cancerous tissue. It is the same characteristics as in the cancerous tissue. It was fully indicated experimentally that visible light reflectance spectrum can distinguish normal and cancerous tissue.

  19. Investigation of the thermal and tissue injury behavior in microwave thermal therapy of the porcine kidney

    NASA Astrophysics Data System (ADS)

    He, Xiaoming; Mcgee, Shawn; Coad, James E.; Schmidlin, Franz R.; Iaizzo, Paul; Swanlund, David J.; Rudie, Eric; Kluge, Stan; Bischof, John C.

    2003-06-01

    In this paper, we report the characterization of microwave therapy in normal porcine kidneys both in vitro and in vivo. This technology is being developed for eventual use in the treatment of small renal cell carcinomas (RCC) using minimally invasive procedures. Microwave energy was applied through an interstitial microwave probe (Urologix, Plymouth, MN) to the kidney cortex with involvement of the medulary region. The thermal histories at several locations were recorded. After treatment, the kidneys were bisected and tissue sections were prepared for histologic study at approximately the same depth as the thermal probe. Histologic cellular injury and microvascular stasis were quantitatively evaluated. Absolute rate kinetic models of cellular injury and vascular stasis were fit to the thermal and histologic data to determine the kinetic parameters. A 3-D finite element thermal model based on the Pennes Bioheat equation was developed and solved using a commercial software package (ANSYS, V5.7). The specific absorption rate (SAR) of the microwave probe was measured experimentally. This is the first thermal model validated using measured in vitro thermal histories and then used to determine the blood perfusion term in vivo.

  20. [Horseshoe kidney, stone disease and prostate cancer: a case presentation].

    PubMed

    Hermida Pérez, J A; Bermejo Hernández, A; Hernández Guerra, J S; Sobenes Gutierrez, R J

    2013-01-01

    The horseshoe kidney is the most common congenital renal fusion anomalies. It occurs in 0.25% of the population, or 1 in every 400 people. It is more frequent in males (ratio 2:1). The most observed complication of horseshoe kidney is stone disease, although there may be others such as, abdominal pain, urinary infections, haematuria, hydronephrosis, trauma and tumours (most commonly associated with hypernephroma and Wilms tumour). We describe a case of a male patient with horseshoe kidney, stone disease and adenocarcinoma of the prostate. One carrier of this condition who suffered a transitional cell carcinoma of the prostate was found in a review of the literature.

  1. B cell translocation gene 1 reduces the biological outcome of kidney cancer through induction of cell proliferation, cell cycle arrest, cell apoptosis and cell metastasis.

    PubMed

    Sun, Guogui; Liu, Qing; Cheng, Yunjie; Hu, Wanning

    2015-03-01

    The aim of the present study was to determine the expression and function of B cell translocation gene 1 (BTG1) in kidney carcinoma. Kidney samples were obtained from cancer lesions (n=85) and the adjacent normal tissue (n=40) in kidney cancer patients immediately following endoscopic biopsy. The effect of BTG1 overexpression was examined in vitro utilizing a human kidney cancer cell line, ACHN, stably transfected with a recombinant lentivirus (LeBTG1 cells) and compared to empty vector‑transfected controls (LeEmpty). BTG1 protein expression was significantly lower in kidney cancer tissue biopsies compared to normal tissue, as measured by immunohistochemistry (34.1 vs. 77.8% of tissues; P<0.05) and western blotting (0.481±0.051 vs. 0.857±0.081; P<0.05). In vitro analyses revealed that LeBTG1 cells had a reduced survival fraction compared to control LeEmpty cells, with higher rates of apoptosis (16.6±2.5 vs. 6.1±0.7%; P<0.05). The proportion of LeBTG1 cells in G(0)/G(1) stage and S phase was also significantly different from LeEmpty cells (66.8±5.3 and 22.2±1.5% vs. 44.4±3.1 and 34.5±2.3%, respectively; P<0.05), and the migration and invasion of LeBTG1 cells was significantly impaired with respect to LeEmpty cells (74.0±9.0 and 53.0±7.0 vs. 118.0±15.0 and 103.0±13.0, respectively; P<0.05). These effects were accompanied by decreased protein expression of cyclin D1, B‑cell lymphoma 2 and matrix metalloproteinase 9 in LeBTG1 cells (0.118±0.018, 0.169±0.015 and 0.207±0.027, respectively) compared to control LeEmpty cells (0.632±0.061, 0.651±0.063 and 0.443±0.042, respectively; P<0.05). Reduced BTG1 expression is associated with increased disease severity, suggesting it is a negative regulator of kidney cancer and can serve as a prognostic indicator. The results of the present study show that BTG1 protein levels were significantly reduced in kidney cancer biopsy specimens and were associated with disease progression and prognosis.

  2. Grade-Dependent Metabolic Reprogramming in Kidney Cancer Revealed by Combined Proteomics and Metabolomics Analysis.

    PubMed

    Wettersten, Hiromi I; Hakimi, A Ari; Morin, Dexter; Bianchi, Cristina; Johnstone, Megan E; Donohoe, Dallas R; Trott, Josephine F; Aboud, Omran Abu; Stirdivant, Steven; Neri, Bruce; Wolfert, Robert; Stewart, Benjamin; Perego, Roberto; Hsieh, James J; Weiss, Robert H

    2015-06-15

    Kidney cancer [or renal cell carcinoma (RCC)] is known as "the internist's tumor" because it has protean systemic manifestations, suggesting that it utilizes complex, nonphysiologic metabolic pathways. Given the increasing incidence of this cancer and its lack of effective therapeutic targets, we undertook an extensive analysis of human RCC tissue employing combined grade-dependent proteomics and metabolomics analysis to determine how metabolic reprogramming occurring in this disease allows it to escape available therapeutic approaches. After validation experiments in RCC cell lines that were wild-type or mutant for the Von Hippel-Lindau tumor suppressor, in characterizing higher-grade tumors, we found that the Warburg effect is relatively more prominent at the expense of the tricarboxylic acid cycle and oxidative metabolism in general. Further, we found that the glutamine metabolism pathway acts to inhibit reactive oxygen species, as evidenced by an upregulated glutathione pathway, whereas the β-oxidation pathway is inhibited, leading to increased fatty acylcarnitines. In support of findings from previous urine metabolomics analyses, we also documented tryptophan catabolism associated with immune suppression, which was highly represented in RCC compared with other metabolic pathways. Together, our results offer a rationale to evaluate novel antimetabolic treatment strategies being developed in other disease settings as therapeutic strategies in RCC.

  3. Observation of tissues in open aqueous solution by atmospheric scanning electron microscopy: Applicability to intraoperative cancer diagnosis

    PubMed Central

    MEMTILY, NASSIRHADJY; OKADA, TOMOKO; EBIHARA, TATSUHIKO; SATO, MARI; KURABAYASHI, ATSUSHI; FURIHATA, MUTSUO; SUGA, MITSUO; NISHIYAMA, HIDETOSHI; MIO, KAZUHIRO; SATO, CHIKARA

    2015-01-01

    In the atmospheric scanning electron microscope (ASEM), a 2- to 3-μm layer of the sample resting on a silicon nitride-film window in the base of an open sample dish is imaged, in liquid, at atmospheric pressure, from below by an inverted SEM. Thus, the time-consuming pretreatments generally required for biological samples to withstand the vacuum of a standard electron microscope are avoided. In the present study, various mouse tissues (brain, spinal cord, muscle, heart, lung, liver, kidney, spleen and stomach) were fixed, stained with heavy metals, and visualized in radical scavenger D-glucose solution using the ASEM. While some stains made the nuclei of cells very prominent (platinum-blue, phosphotungstic acid), others also emphasized cell organelles and membranous structures (uranium acetate or the NCMIR method). Notably, symbiotic bacteria were sometimes observed on stomach mucosa. Furthermore, kidney tissue could be stained and successfully imaged in <30 min. Lung and spinal cord tissue from normal mice and mice metastasized with breast cancer cells was also examined. Cancer cells present in lung alveoli and in parts of the spine tissue clearly had larger nuclei than normal cells. The results indicate that the ASEM has the potential to accelerate intraoperative cancer diagnosis, the diagnosis of kidney diseases and pathogen detection. Importantly, in the course of the present study it was possible to increase the observable tissue area by using a new multi-windowed ASEM sample dish and sliding the tissue across its eight windows. PMID:25707365

  4. Surgical treatment of patients with kidney and bladder cancer in case of severe concomitant cardiovascular diseases.

    PubMed

    Davydov, M I; Akchurin, R S; Gerasimov, S S; Belov, Yu V; Matveev, V B; Brand, Ya B; Cheban, O I

    2014-01-01

    It was operated 17 patients with kidney and bladder cancer against the background of severe concomitant coronary artery disease (52.9%), aortic aneurysm (35.3%) or combination of coronary artery disease with Leriche syndrome (5.9%) or hemodynamically significant stenosis of internal carotid artery (5.9%). Patients were operated for the period from 1998 to 2012. All patients were male at the age from 39 to 80 years (mean 62.1 years). The first stage of kidney cancer was diagnosed in 8 (53.3%) patients, the second stage - in 1 (6.7%) patient, the third stage - in 2 (13.3%) patients and the fourth stage was observed in 4 (26.7%) patients. Bladder cancer had 1 and 2 stages. Simultaneous operations were performed in 3 (17.6%) patients. 12 (70.6%) patients were operated consequentially. Surgery for kidney cancer was not done in 2 (11.8%) of 17 patients because of patient death after coronary bypass surgery or patient refusal of surgery after carotid arteries stenting. Intraoperative and postoperative complications have been developed in 9 (52.9%) of 17 patients. 2 (11.8%) patients died. The complications frequency and mortality after simultaneous operations were 25% (1 of 4) and 0. These parameters were 57.1% (8 of 14) and 14.3% respectively in case of consequent tactics. It was not observed myocardial infarction and aortic aneurysm rupture after surgeries for kidney and bladder cancer. Overall 1, 3, 5 - year survival of patients with kidney cancer and severe concomitant cardiovascular diseases was 100%, 73.3% and 52.4% respectively. It was concluded that surgical treatment of severe concomitant coronary artery disease and aortic aneurysm in patients with kidney and bladder cancer decreases risk of myocardial infarction and aortic aneurysm rupture in intraoperative and postoperative periods.

  5. Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

    PubMed Central

    2011-01-01

    Background Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic Escherichia coli (UPEC) infection within the kidney of a live rat. Results Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal Ifng induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections. Conclusion Our hypothesis-free approach identified

  6. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2015-08-01

    rights reserved.1. Introduction White adipose tissue (WAT) is a loose connective tissue that is crucial in the regulation of whole-body fatty-acid...AWARD NUMBER: W81XWH-10-1-0275 TITLE: Androgenic Regulation of White Adipose Tissue -Prostate Cancer Interactions PRINCIPAL INVESTIGATOR...2010-05/31/2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0275 Androgenic Regulation of White Adipose Tissue -Prostate Cancer

  7. Tissue imaging for cancer detection using NIR autofluorescence

    NASA Astrophysics Data System (ADS)

    Demos, Stavros G.; Staggs, Michael C.; Gandour-Edwards, Regina; Ramsamooj, Rajen; White, Ralph de Vere

    2002-05-01

    Near IR imaging using elastic light scattering and tissue fluorescence under long-wavelength laser excitation are explored for cancer detection. Various types of normal and malignant human tissue samples were utilized in this investigation. A set of images of each tissue sample is recorded. These images are then compared with the histopathology of the tissue sample to reveal the optical fingerprint characteristics suitable for cancer detection. The experimental results indicate that the above approaches can help image and differentiate cancer form normal tissue.

  8. Urine metabolomic analysis identifies potential biomarkers and pathogenic pathways in kidney cancer.

    PubMed

    Kim, Kyoungmi; Taylor, Sandra L; Ganti, Sheila; Guo, Lining; Osier, Michael V; Weiss, Robert H

    2011-05-01

    Kidney cancer is the seventh most common cancer in the Western world, its incidence is increasing, and it is frequently metastatic at presentation, at which stage patient survival statistics are grim. In addition, there are no useful biofluid markers for this disease, such that diagnosis is dependent on imaging techniques that are not generally used for screening. In the present study, we use metabolomics techniques to identify metabolites in kidney cancer patients' urine, which appear at different levels (when normalized to account for urine volume and concentration) from the same metabolites in nonkidney cancer patients. We found that quinolinate, 4-hydroxybenzoate, and gentisate are differentially expressed at a false discovery rate of 0.26, and these metabolites are involved in common pathways of specific amino acid and energetic metabolism, consistent with high tumor protein breakdown and utilization, and the Warburg effect. When added to four different (three kidney cancer-derived and one "normal") cell lines, several of the significantly altered metabolites, quinolinate, α-ketoglutarate, and gentisate, showed increased or unchanged cell proliferation that was cell line-dependent. Further evaluation of the global metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger sample size, will lead to new avenues of kidney cancer diagnosis and therapy.

  9. Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern

    PubMed Central

    Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

    2017-01-01

    Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. Materials and Methods This ecological study was based on GLOBOCAN data Asia for assessment the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. We use of correlation bivariate method for assessment the correlation between ASIR and ASMR with HDI and its components. Results A total of 121 099 kidney cancer cases were recorded in Asian countries in 2012.Overall, 80 080 cases (66.12%) were males. Sex ratio was 1.95. The three countries with the highest number of new patients were china (66 466 cases), Japan (16 830 cases), India(9658 cases), respectively. Positive correlation were seen between HDI and ASIR of kidney cancer 0.655 (P = 0.001), and HDI and ASMR of kidney cancer 0.285 (P = 0.055). Conclusions A positive relationship between ASIR and the HDI was seen. The relationship is due to risk factors in countries with high development such as older age, smoking, hypertension, obesity, and diet. However, ASMR showed no significant relationship with HDI. PMID:28042551

  10. Protein Array-Based Detection of Proteins in Kidney Tissues from Patients with Membranous Nephropathy

    PubMed Central

    Lu, Yang; Fan, Meng

    2017-01-01

    Membranous nephropathy (MN) is an autoimmune inflammatory disease in which proteins related with plenty of biological processes play an important role. However, the role of these proteins in the pathogenesis of MN is still unclear. This study aimed to screen differential proteins in kidney tissue samples from MN patients by using protein arrays and determine the pathways involved in the pathogenesis of MN. This study first tested a quantitative protein array (QAH-INF-3) and two semiquantitative protein arrays (L-493 and L-507) with normal renal tissue and identified L-493 as the most appropriate assay to compare protein levels between MN tissues and normal control tissues. The L-493 array identified 66 differentially expressed proteins (DEPs) that may be associated with MN. The gene oncology (GO) and protein-protein interaction (PPI) analyses revealed several processes potentially involved in MN, including extracellular matrix disassembly and organization, cell adhesion, cell-cell signaling, cellular protein metabolic process, and immune response (P < 0.05). We suggest that these different pathways work together via protein signaling and result in the pathogenesis and progression of MN. PMID:28337458

  11. The benefits of cancer screening in kidney transplant recipients: a single-center experience.

    PubMed

    Kato, Taigo; Kakuta, Yoichi; Abe, Toyofumi; Yamanaka, Kazuaki; Imamura, Ryoichi; Okumi, Masayoshi; Ichimaru, Naotsugu; Takahara, Shiro; Nonomura, Norio

    2016-02-01

    The frequency of malignancy is increasing in kidney transplant recipients. Posttransplant malignancy (PTM) is a major cause of long-term graft survival inhibition. In this study, we evaluated the frequency and prognosis of PTM at our center and examined the efficacy of cancer screening. Between 1972 and 2013, 750 patients were followed-up at our center. Annual physical examinations and screenings were performed to detect PTM. We investigated the detail of two distinctive cancer groups: screening-detected cancers and symptom-detected cancers. Seventy-seven PTM were identified during the follow-up period. The mean age at the initial PTM detection was 43.6 ± 12.8 years. The mean interval from transplantation to cancer diagnosis was 134.5 ± 11.3 months. Among the 77 patients, posttransplant lymphoproliferative disease (PTLD) was the most common cancer (19.5%, 15/77), followed by renal cell carcinoma (15.6%, 12/77). Of the cancer cases, 46.8% (36/77) were detected via screening. The most frequently screening-detected cancer was renal cell carcinoma of the native kidney and breast cancer (22.2%, 8/36). However, it was difficult to detect PTLD, urothelial carcinoma, and colorectal cancer via screening. Interestingly, Cox proportional regression analyses revealed nonscreened recipients to be a significant prognostic factor for PTM (P < 0.001). This study is the first to report that appropriate screening tests play a key role in early PTM diagnosis and lead to reduce the mortality rate in kidney transplant recipients. These findings support the provision of long-term appropriate screening for kidney transplant recipients.

  12. Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer.

    PubMed

    Kawakami, Kazumori; Yamamura, Soichiro; Hirata, Hiroshi; Ueno, Koji; Saini, Sharanjot; Majid, Shahana; Tanaka, Yuichiro; Kawamoto, Ken; Enokida, Hideki; Nakagawa, Masayuki; Dahiya, Rajvir

    2011-02-01

    Secreted frizzled-related protein-5 (sFRP-5) has been identified as 1 of the secreted antagonists that bind Wnt protein. However, the functional significance of sFRP-5 in renal cell cancer (RCC) has not been reported. We hypothesized that sFRP-5 may be epigenetically downregulated through DNA methylation and histone modification and function as a tumor suppressor gene in RCC. Using tissue microarray and real-time RT-PCR, we found that sFRP-5 was significantly downregulated in kidney cancer tissues and cell lines, respectively. DNA bisulfite sequencing of the sFRP-5 promoter region in RCC cell lines showed it to be densely methylated, whereas there was few promoter methylation in normal kidney. The sFRP-5 expression was restored and the acetylation of H3 and H4 histones associated with the sFRP-5 promoter region were significantly increased after treatment with demethylation agent (5-Aza-dc) and histone deacetylase inhibitor (TSA). When RCC cells were transfected with the sFRP-5 gene, significant inhibition of anchorage independent colony formation and cell invasion were observed compared to controls. The sFRP-5 transfection also significantly induced apoptosis in RCC cells. In conclusion, this is the first report documenting that the sFRP-5 is downregulated by promoter methylation and histone acetylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells.

  13. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jr; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2010-02-01

    In this work, we utilized multiphoton microscopy for the label-free diagnosis of non-cancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from human. Our results show that the combination of second harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from non-cancerous lung tissues. Specifically, non-cancerous lung tissues are largely fibrotic in structure while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI or SAAID) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55 +/-0.23 and 0.87+/-0.15 respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13 respectively. Intrinsic fluorescence ratio (FAD/NADH) of SCC and non-cancerous tissues are 0.40+/-0.05 and 0.53+/-0.05 respectively, the redox ratio of SCC diminishes significantly, indicating that increased cellular metabolic activity. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from non-cancerous tissues. With additional development, multiphoton microscopy may be used for the clinical diagnosis of lung cancers.

  14. Outcomes of acute kidney injury patients with and without cancer.

    PubMed

    Juwon, Lee; Jang, Gookhwan; Kim, Sunmin; Kim, Dajung; Lee, Jinwook; Park, Hyunjoon; Lee, Junyeob; Kim, Sangbin; Kim, Yunkyung; Kim, Soo Young; Yang, Joung Wook; Gwoo, Sangeon; Kim, Ye Na; Shin, Ho Sik; Jung, Yeonsoon; Rim, Hark

    2015-11-01

    Incidence of AKI in hospitalized patients with cancer is increasing, but there have been few studies on AKI in patients with cancer. We conducted a retrospective cohort study in a South Korean tertiary care hospital. A total of 2211 consecutive patients (without cancer 61.5%; with cancer 38.5%) were included over a 140-month period. Predictors of all-cause death were examined using the Kaplan-Meier method and the Cox proportional hazards model. The main contributing factors of AKI were sepsis (31.1%) and ischemia (52.7%). AKI was multifactorial in 78% of patients with cancer and in 71% of patients without cancer. Hospital mortality rates were higher in patients with cancer (42.8%) than in patients without cancer (22.5%) (p = 0.014). In multivariate analyses, diabetes mellitus (DM) and cancer diagnosis were associated with hospital mortality. Cancer diagnosis was independently associated with mortality [odds ratio = 3.010 (95% confidence interval, 2.340-3.873), p = 0.001]. Kaplan-Meier analysis revealed that subjects with DM and cancer (n = 146) had lower survival rates than subjects with DM and without cancer (n = 687) (log rank test, p = 0.001). The presence of DM and cancer was independently associated with mortality in AKI patients both with and without cancer. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.

  15. EXPRESSION MECHANISM AND CLINICAL SIGNIFICANCE OF NOB1 IN GASTRIC CANCER TISSUE AND ADJACENT NORMAL TISSUE.

    PubMed

    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F

    2015-01-01

    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  16. Cumulative Doses of T-Cell Depleting Antibody and Cancer Risk after Kidney Transplantation.

    PubMed

    Chen, Jenny H C; Wong, Germaine; Chapman, Jeremy R; Lim, Wai H

    2015-01-01

    T-cell depleting antibody is associated with an increased risk of cancer after kidney transplantation, but a dose-dependent relationship has not been established. This study aimed to determine the association between cumulative doses of T-cell depleting antibody and the risk of cancer after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant Registry between 1997-2012, we assessed the risk of incident cancer and cumulative doses of T-cell depleting antibody using adjusted Cox regression models. Of the 503 kidney transplant recipients with 2835 person-years of follow-up, 276 (55%), 209 (41%) and 18 (4%) patients received T-cell depleting antibody for induction, rejection or induction and rejection respectively. The overall cancer incidence rate was 1,118 cancers per 100,000 patient-years, with 975, 1093 and 1377 cancers per 100,000 patient-years among those who had received 1-5 doses, 6-10 doses and >10 doses, respectively. There was no association between cumulative doses of T cell depleting antibody and risk of incident cancer (1-5: referent, 6-10: adjusted hazard ratio (HR) 1.19, 95%CI 0.48-2.95, >10: HR 1.42, 95%CI 0.50-4.02, p = 0.801). This lack of association is contradictory to our hypothesis and is likely attributed to the low event rates resulting in insufficient power to detect significant differences.

  17. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  18. Effects of chytridiomycosis on hematopoietic tissue in the spleen, kidney and bone marrow in three diverse amphibian species.

    PubMed

    Brannelly, Laura A; Webb, Rebecca J; Skerratt, Lee F; Berger, Lee

    2016-10-01

    One of the major causes of amphibian population decline is the deadly fungal pathogen Batrachochytrium dendrobatidis, Bd Research on pathogenesis and host immunity aims to inform development of targeted conservation interventions. Studies examining global host immune responses as well as effects on lymphocytes in vitro suggest that Bd infection causes immunosuppression. However, it is unknown which hematopoietic tissues are affected and if these effects differ among host species. We investigated the effect of experimental Bd infection on three diverse amphibian species by quantifying the amount of hematopoietic tissue in the spleen, bone marrow and kidney. Upon Bd infection, hematopoietic tissue in the kidney tended to be depleted, while the spleen appeared unaffected. The bone marrow in highly susceptible species was depleted, whereas an increase in hematopoietic tissue was observed in the more resistant species. Our study demonstrates that species and hematopoietic tissues behave differently in response to Bd infection, and may be related to the species' susceptibility to infection.

  19. Regulation of Breast Cancer Stem Cells by Tissue Rigidity

    DTIC Science & Technology

    2015-06-01

    AD ____________ __ Award Number: W81XWH-13-1-0133 TITLE: Regulation of Breast Cancer Stem Cells by Tissue Rigidity PRINCIPAL INVESTIGATOR: Adam J...CONTRACT NUMBER Regulation of Breast Cancer Stem Cell by Tissue Rigidity W81XWH-13-1-0133 Sb. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...in breast tumors is associated with a 1 0-50-fold increase in tissue stiffness and correlates with distant metastasis and poor outcome. Recent studies

  20. Regulation of Breast Cancer Stem Cell by Tissue Rigidity

    DTIC Science & Technology

    2015-06-01

    AD_________________ Award Number: W81XWH-13-1-0132 TITLE: Regulation of Breast Cancer Stem Cell by Tissue Rigidity PRINCIPAL INVESTIGATOR: Jing...COVERED 4. TITLE AND SUBTITLE Regulation of Breast Cancer Stem Cell by Tissue Rigidity 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...fibrotic focus in breast tumors is associated with a 10-50-fold increase in tissue stiffness and correlates with distant metastasis and poor outcome. Recent

  1. Immunocytochemistry of band 3 protein in kidney and other tissues of control and cystic fibrosis patients.

    PubMed

    Hazen-Martin, D J; Pasternack, G; Hennigar, R A; Spicer, S S; Sens, D A

    1987-03-01

    Current evidence indicates that the underlying genetic defect in cystic fibrosis (CF) results in defective chloride transport, and more specifically, chloride impermeability. However, recent consideration has been given to a possible defect in band 3 protein at CF-affected sites. In an effort to determine a possible role for band 3, an anion exchange channel protein, a series of immunocytochemical localizations was performed. Immunocytochemical staining for the anion channel band 3, 43K, in normal and CF human kidney was confined to erythrocytes, glomerular podocytes, the basal region of half of the cells of the initial connecting segment of cortical collecting ducts, and a minority of cells in medullary ray-collecting ducts. Erythrocytes alone evidenced immunoreactivity for band 3 protein in human pancreas, submandibular gland, trachea, and lung. In all cases, specimens from patients with CF stained like those from control subjects for band 3. Abnormal Cl- transport in CF tissues is not reflected in altered band 3, 43K, localizations.

  2. Differentiation of tissue and kidney stones for laser lithotripsy using different spectroscopic approaches

    NASA Astrophysics Data System (ADS)

    Lange, Birgit; Cordes, Jens; Brinkmann, Ralf

    2015-07-01

    Holmium lasers are nowadays the gold standard for endoscopic laser lithotripsy. However, there is a risk of damaging or perforating the ureter or kidney tissue when the vision is poor. An automatic tissue/stone differentiation would improve the handling and safety of the procedure. To achieve this objective, an easy and robust real-time discrimination method has to be found which can be used to realize a feedback loop to control the laser system. Two possible approaches have been evaluated: White light reflectance and fluorescence spectroscopy. In both cases, we use the treatment fiber for detection and evaluate the possibility to decide whether the fiber is placed in front of tissue or calculus by the signal that is delivered by the surface in front of it. White light reflectance spectroscopy uses the standard light source for endourologic surgeries: Radiation of a Xenon light source is coupled to the ureteroscope via a liquid light guide. The part of the white light that is reflected back into the fiber is spectroscopically analyzed. In a clinical proof of concept study reflection signals were measured in vivo in 8 patients. For differentiation of stone and tissue via autofluorescence, excitation as well as detection was done via the treatment fiber. A suitable excitation wavelength was chosen with in vitro measurements (UV / visible) on several human renal calculi and porcine tissues. For verification of the positive results with green excitation in a clinical proof of concept study, a measurement set-up was realized which allows the recording of fluorescence signals during an endourological intervention.

  3. Analgesic use and the risk of kidney cancer: a meta-analysis of epidemiologic studies.

    PubMed

    Choueiri, Toni K; Je, Youjin; Cho, Eunyoung

    2014-01-15

    Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random-effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15-1.44 and 1.25; 95% CI: 1.06-1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95-1.28), except for non-US studies (five studies, pooled RR: 1.17; 95% CI: 1.04-1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings.

  4. Plumb as a cause of kidney cancer (case study: Iran from 2008-2010)

    PubMed Central

    Mazdak, Hamid; Rashidi, Maasoumeh; Zohary, Moien

    2015-01-01

    Background: The main threats to human health from heavy metals are associated with exposure to plumb (Pb), cadmium, mercury, and arsenic. Some hazards that threat human health are the results of environmental factors and the relevant pollutions. Some important categories of diseases including (cancers) have considerable differences in various places, as observed in their spatial prevalence and distribution maps. The present study sets out to investigate the correlation between kidney cancer and the concentration of Pb in Iran. Materials and Methods: In this study, the first challenge was to collect some relevant information. In this connection, the authors managed to gain access to data concerning kidney cancer in Iran. The data were collected by a health centre for the period of 2008-2010. Besides, a map of Pb distribution in soil, drawn by the Mineral Exploration Organization, and Plumb Concentration Information, collected by Agriculture Jihad Organization, were used. Using a geographic information system (GIS) software such as ArcGIS (USA), the researchers drew the map of the spatial distribution of kidney cancer in the Iran country. In the indirect methods, one measures vegetation stress caused by heavy metal soil contamination. In direct methods, target detection algorithms are used to detect a selected material on the basis of its unique spectral signature. In this research, we applied target detection algorithms on moderate resolution imaging spectroradiometer (MODIS) images to detect Pb. MODIS is a sensor placed on the Terra satellite that collects data in 35 spectral bands with 250-1,000 m special resolutions. Results: The spatial distribution of kidney cancer in Iran country delineated above revealed a positive correlation between the amount of lead and the high frequency of kidney cancer. Regression analyses also confirmed this relationship (R2 = 0.77 and R = 0.87). Conclusion: The findings of the current study underscore not only the importance of

  5. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-12-09

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  6. Examining the association of circulating 25-hydroxyvitamin D with kidney cancer risk: a meta-analysis

    PubMed Central

    Lin, Guangzheng; Ning, Ling; Gu, Di; Li, Shi; Yu, Zhe; Long, Qicheng; Hou, Li-Na; Tan, Wan-Long

    2015-01-01

    Objective: To examine the relationship between circulating 25-hydroxy-vitamin D (25 (OH) D) and risk of kidney cancer. Methods: We searched PubMed, EMBASE, and Web of Science databases through August 31, 2015 for eligible studies. Pooled ORs with 95% confidence interval were calculated using fixed effect models. All data analyses were performed with STATA version 12.0. Results: The final analysis included 2 prospective cohort studies and 7 nested case-control studies, with a total of 130, 609 participants and 1, 815 cases of kidney cancer. No obvious heterogeneity was observed between individual studies. The results of this study revealed that higher circulating 25-hydroxyvitamin D levels were associated with lower risk of kidney cancer (OR=0.79, 95% CI 0.69-0.91; P value for heterogeneity: 0.61, I2=0%). After stratified by geographical region, the similar association was detected in European studies (OR=0.81, 95% CI 0.69-0.94; P value for heterogeneity: 0.38, I2=0%), though no significant association was observed in the USA studies (OR=0.73, 95% CI 0.51-1.04; P value for heterogeneity: 0.44, I2=0%). Conclusion: Our present findings suggest that higher levels of circulating 25-hydroxyvitamin D could reduce the risk of kidney cancer by 21%. Further well-designed large-scaled prospective studies and randomized controlled trials are warranted to provide more conclusive evidence. PMID:26884966

  7. Sixth BHD Symposium and First International Upstate Kidney Cancer Symposium: latest scientific and clinical discoveries.

    PubMed

    Bratslavsky, Gennady; Woodford, Mark R; Daneshvar, Michael; Mollapour, Mehdi

    2016-03-29

    The Sixth BHD Symposium and First International Upstate Kidney Cancer Symposium concluded in September 2015, in Syracuse, NY, USA. The program highlighted recent findings in a variety of areas, including drug development, therapeutics and surgical management of patients with BHD and multi-focal renal tumors, as well as multidisciplinary approaches for patients with localized, locally advanced and metastatic renal cell carcinoma.

  8. A study of metal concentrations and metallothionein binding capacity in liver, kidney and brain tissues of three Arctic seal species.

    PubMed

    Sonne, Christian; Aspholm, Ole; Dietz, Rune; Andersen, Steen; Berntssen, Marc H G; Hylland, Ketil

    2009-12-01

    Arctic seals are known to accumulate relatively high concentrations of potential toxic heavy metals in their vital organs, such as livers and kidneys, as well as in their central nervous system. We therefore decided to determine whether mercury, copper, cadmium and zinc levels in liver, kidney and brain tissues of three Arctic seal species were associated with the intracellular metal-binding protein metallothionein (MT) as a sign of toxic exposure. Samples from four ringed (Phoca hispida), five harp (P.groenlandica) and five hooded (Cystophora cristata) seals taken during field trips to Central West Greenland (Godhavn) and the Barents Sea in the spring of 1999 were used for the present study. In all three seal species concentrations of mercury, zinc and copper were highest in the liver, except for cadmium which was highest in the kidneys. Metal concentrations increased significantly in the order: ringed sealkidney and liver tissues. MT concentrations were highest in the kidneys and the concentrations increased in the order: ringed sealkidneys for all three species and increased in the same order: ringed seals (2-10%)tissues (i.e. kidney) from metal toxicosis. MT with its binding capacity could be a useful marker for environmental exposure to metals and their potential toxicity in the Arctic.

  9. Current Status of Cryotherapy for Prostate and Kidney Cancer

    PubMed Central

    Cho, Seok

    2014-01-01

    In terms of treating diseases, minimally invasive treatment has become a key element in reducing perioperative complications. Among the various minimally invasive treatments, cryotherapy is often used in urology to treat various types of cancers, especially prostate cancer and renal cancer. In prostate cancer, the increased incidence of low-risk, localized prostate cancer has made minimally invasive treatment modalities an attractive option. Focal cryotherapy for localized unilateral disease offers the added benefit of minimal morbidities. In renal cancer, owing to the increasing utilization of cross-sectional imaging, nearly 70% of newly detected renal masses are stage T1a, making them more susceptible to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. This article reviews the various outcomes of cryotherapy compared with other treatments and the possible uses of cryotherapy in surgery. PMID:25512811

  10. An analysis of the expression of cyclophilin C reveals tissue restriction and an intriguing pattern in the mouse kidney.

    PubMed Central

    Friedman, J.; Weissman, I.; Friedman, J.; Alpert, S.

    1994-01-01

    Cyclophilin C (cyp C) is a cyclosporin A (CsA) binding protein originally isolated from a mouse bone marrow stromal cell line. We have compared the expression patterns of the mammalian cyclophilins A, B, and C in mouse tissues using in situ hybridization. These studies reveal that cyp C is expressed in a restricted subset of tissues including mouse ovary, testis, bone marrow, and kidney. Within the kidney, cyp C is highly expressed in a narrow zone in the outer medulla. Using monoclonal antibodies reactive against cyp C, we find that the kidney cells expressing cyp C correspond to the S3 segment of the nephron. The S3 segment has been shown to sustain histopathological damage from high dosages of CsA, raising the possibility that cyp C may be involved in mediating this damage. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8203464

  11. Cadmium and zinc in kidney, liver, muscle and mammary tissue from dairy cows in conventional and organic farming.

    PubMed

    Olsson, I M; Jonsson, S; Oskarsson, A

    2001-10-01

    Input of Cd to arable soils occurs mainly through atmospheric deposition and mineral fertilisers. Phosphate fertilisers are often contaminated with Cd. In organic farming the use of mineral fertilisers is restricted. The impact of conventional and organic farming on Cd and Zn levels in tissues from dairy cows was studied. Kidney, liver, muscle and mammary tissue samples were collected at slaughter from 67 cows, aged 30-95 months, in a project with conventional and organic production at the same farm. Samples were analysed by electrothermal atomic absorption spectrometry with a quality control programme. Significantly lower levels of Cd were found in cows from the organic system (n = 29) than from the conventional cows (n = 38) in kidney [330 +/- 100 (mean +/- s) micrograms kg-1 vs. 410 +/- 140], liver (33 +/- 15 vs. 44 +/- 19) and mammary tissue (0.38 +/- 0.14 vs. 0.59 +/- 0.37), while there were no differences in muscle (0.48 +/- 0.13 vs. 0.49 +/- 0.14). Organic cow kidneys had lower Zn levels than conventional cows (19 +/- 1.4 mg kg-1 vs. 20 +/- 2), whereas muscles had higher Zn levels than conventional cows (67 +/- 16 vs. 51 +/- 12). Cd and Zn in mammary tissue were positively related to age and milk production. There was a positive relationship between levels in kidney of Cd and metallothionein (MT) and a Cd/MT concentration ratio indicating protection from Cd-induced renal dysfunction. When older animals, that entered the project as milk-producing cows, were included the differences in kidney and liver Cd levels between the systems were no longer significant, while Cd in kidney became related to age- and production-related parameters. The change of significant relationships when older animals were included shows the importance of controlled conditions for environmental monitoring.

  12. Cigarette Smoking Prior to First Cancer and Risk of Second Smoking-Associated Cancers Among Survivors of Bladder, Kidney, Head and Neck, and Stage I Lung Cancers

    PubMed Central

    Shiels, Meredith S.; Gibson, Todd; Sampson, Joshua; Albanes, Demetrius; Andreotti, Gabriella; Beane Freeman, Laura; Berrington de Gonzalez, Amy; Caporaso, Neil; Curtis, Rochelle E.; Elena, Joanne; Freedman, Neal D.; Robien, Kim; Black, Amanda; Morton, Lindsay M.

    2014-01-01

    Purpose Data on smoking and second cancer risk among cancer survivors are limited. We assessed associations between smoking before first cancer diagnosis and risk of second primary smoking-associated cancers among survivors of lung (stage I), bladder, kidney, and head/neck cancers. Methods Data were pooled from 2,552 patients with stage I lung cancer, 6,386 with bladder cancer, 3,179 with kidney cancer, and 2,967 with head/neck cancer from five cohort studies. We assessed the association between prediagnostic smoking and second smoking-associated cancer risk with proportional hazards regression, and compared these estimates to those for first smoking-associated cancers in all cohort participants. Results Compared with never smoking, current smoking of ≥ 20 cigarettes per day was associated with increased second smoking-associated cancer risk among survivors of stage I lung (hazard ratio [HR] = 3.26; 95% CI, 0.92 to 11.6), bladder (HR = 3.67; 95% CI, 2.25 to 5.99), head/neck (HR = 4.45; 95% CI, 2.56 to 7.73), and kidney cancers (HR = 5.33; 95% CI, 2.55 to 11.1). These estimates were similar to those for first smoking-associated cancer among all cohort participants (HR = 5.41; 95% CI, 5.23 to 5.61). The 5-year cumulative incidence of second smoking-associated cancers ranged from 3% to 8% in this group of cancer survivors. Conclusion Understanding risk factors for second cancers among cancer survivors is crucial. Our data indicate that cigarette smoking before first cancer diagnosis increases second cancer risk among cancer survivors, and elevated cancer risk in these survivors is likely due to increased smoking prevalence. The high 5-year cumulative risks of smoking-associated cancers among current smoking survivors of stage I lung, bladder, kidney, and head/neck cancers highlight the importance of smoking cessation in patients with cancer. PMID:25385740

  13. Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues to the Kidney Inhibition Swab (KIS(TM)) from the Fast Antimicrobial Screen Test. A high dose of penicillin G procaine relative to a label dose is commonly used ...

  14. Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues from the Fast Antimicrobial Screen Test to the Kidney Inhibition Swab (KIS(TM)). Here, we describe the use of KIS(TM) test for the detection of penicillin G res...

  15. Development of breast cancer tissue phantoms for terahertz imaging

    NASA Astrophysics Data System (ADS)

    Walter, Alec; Bowman, Tyler; El-Shenawee, Magda

    2016-03-01

    The goal of this work was to develop phantoms that match the refractive indices and absorption coefficients between 0.15 and 2.0 THz of the freshly excised tissues commonly found in breast tumors. Since a breast cancer tumor can contain fibrous and fatty tissues alongside the cancerous tissues, a phantom had to be developed for each. In order to match the desired properties of the tissues, oil in water emulsions were solidified using the proven phantom component TX151. The properties of each potential phantom were verified through THz time-domain spectroscopy on a TPS Spectra 3000. Using this method, phantoms for fibrous and cancerous tissue were successfully developed while a commercially available material was found which matched the optical properties of fatty tissue.

  16. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jhih; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2009-07-01

    We utilize multiphoton microscopy for the label-free diagnosis of noncancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from humans. Our results show that the combination of second-harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from noncancerous lung tissues. Specifically, noncancerous lung tissues are largely fibrotic in structure, while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55+/-0.23 and 0.87+/-0.15, respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13, respectively. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from noncancerous tissues.

  17. TOF-SIMS analysis of adipose tissue from patients with chronic kidney disease

    NASA Astrophysics Data System (ADS)

    Sjövall, Peter; Johansson, Björn; Belazi, Dalila; Stenvinkel, Peter; Lindholm, Bengt; Lausmaa, Jukka; Schalling, Martin

    2008-12-01

    In this work, time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for detecting systematic variations in the spatial and compositional distributions of lipids in human tissue samples. Freeze-dried sections of subcutaneous adipose tissue from six chronic kidney disease (CKD) patients and six control subjects were analysed by TOF-SIMS using 25 keV Bi 3+ primary ions. Principal component analysis of signal intensities from different fatty acids, diacylglycerol and triacylglycerol ions showed evidence for systematic variations in the lipid distributions between different samples. The main observed difference in the spectra was a concerted variation in the signal intensities from the saturated lipids relative to the unsaturated lipids, while variations in the fatty acid chain lengths were considerably weaker. Furthermore, the three samples showing the lowest degree of saturation came from CKD patients, while three of the four samples with the highest degree of saturation were from control subjects, indicating that low saturation levels in the glycerol lipid distribution may be more frequent in patients with CKD. Systematic differences in the spatial distributions between saturated and unsaturated glycerol lipids were observed in several analysed areas.

  18. Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women.

    PubMed

    Sanfilippo, Kristen M; McTigue, Kathleen M; Fidler, Christian J; Neaton, James D; Chang, Yuefang; Fried, Linda F; Liu, Simin; Kuller, Lewis H

    2014-05-01

    Kidney cancer incidence is increasing globally. Reasons for this rise are unclear but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156 774 participants of the Women's Health Initiative clinical trials and observational studies over 10.8 years. In addition, we examined the effect of blood pressure (BP) on kidney cancer deaths for over 25 years among the 353 340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the Women's Health Initiative, systolic BP (SBP) was categorized in 6 groups from <120 to >160 mm Hg, and body mass index was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (P value for trend <0.0001) and body mass index categories (P value for trend <0.0001). In adjusted Cox proportional hazards models, both SBP levels and body mass index were predictors of kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer among the 353 340 participants aged 35 to 57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (hazard ratio, 1.87 for SBP>160 versus <120 mm Hg; 95% confidence interval, 1.38-2.53). Risk was increased among cigarette smokers. Further research is needed to determine the pathophysiologic basis of relationships between both higher BP and the risk of kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk.

  19. Functional life-long maintenance of engineered liver tissue in mice following transplantation under the kidney capsule.

    PubMed

    Ohashi, Kazuo; Koyama, Fumikazu; Tatsumi, Kohei; Shima, Midori; Park, Frank; Nakajima, Yoshiyuki; Okano, Teruo

    2010-02-01

    The ability to engineer biologically active cells and tissue matrices with long-term functional maintenance has been a principal focus for investigators in the field of hepatocyte transplantation and liver tissue engineering. The present study was designed to determine the efficacy and temporal persistence of functional engineered liver tissue following transplantation under the kidney capsule of a normal mouse. Hepatocytes were isolated from human alpha-1 antitrypsin (hA1AT) transgenic mouse livers. Hepatocytes were subsequently transplanted under the kidney capsule space in combination with extracellular matrix components (Matrigel) for engineering liver tissues. The primary outcome of interest was to assess the level of engineering liver tissue function over the experimental period, which was 450 days. Long-term survival by the engineered liver tissue was confirmed by measuring the serum level of hA1AT in the recipient mice throughout the experimental period. In addition, administration of chemical compounds at day 450 resulted in the ability of the engineered liver tissue to metabolize exogenously circulating compounds and induce drug-metabolizing enzyme production. Moreover, we were able to document that the engineered tissues could retain their native regenerative potential similar to that of naïve livers. Overall, these results demonstrated that liver tissues could be engineered at a heterologous site while stably maintaining its functionality for nearly the life span of a normal mouse.

  20. Tissue resident NK cells mediate ischemic kidney injury and are not depleted by anti-Asialo GM1 antibody

    PubMed Central

    Victorino, Francisco; Sojka, Dorothy K.; Brodsky, Kelley S.; McNamee, Eoin N.; Masterson, Joanne C.; Homann, Dirk; Yokoyama, Wayne M.; Eltzschig, Holger K.; Clambey, Eric T.

    2015-01-01

    NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. While conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. Here we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions. Kidney trNK cells developed independent of NFIL3 and Tbet, and expressed a distinct cell surface phenotype as compared to cNK cells. Among these, trNK cells had reduced asialo-GM1 (AsGM1) expression relative to cNK cells, a phenotype observed in trNK cells across multiple organs and mouse strains. Strikingly, anti-AsGM1 antibody treatment, commonly used as NK cell-depleting regimen, resulted in a robust and selective depletion of cNKs, leaving trNKs largely intact. Using this differential depletion, we tested the relative contribution of cNK and trNK cells in ischemic kidney injury. Whereas anti-NK1.1 antibody effectively depleted both trNK and cNK cells and protected against ischemic-reperfusion injury, anti-AsGM1 antibody preferentially depleted cNK cells and failed to protect against injury. These data demonstrate unanticipated specificity of anti-AsGM1 antibody depletion on NK cell subsets and reveal a new approach to study the contributions of cNK and trNK cells in vivo. In total, these data demonstrate that trNK cells play a key role in modulating local responses to ischemic tissue injury in the kidney and potentially other organs. PMID:26453755

  1. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    PubMed Central

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  2. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    PubMed

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  3. Tissue Kim-1 and urinary clusterin as early indicators of cisplatin-induced acute kidney injury in rats.

    PubMed

    Vinken, Petra; Starckx, Sofie; Barale-Thomas, Erio; Looszova, Adriana; Sonee, Manisha; Goeminne, Nick; Versmissen, Loes; Buyens, Kristel; Lampo, Ann

    2012-10-01

    The kidney is one of the main targets of drug toxicity, and early detection of renal damage is critical in preclinical drug development. A model of cisplatin-induced nephrotoxicity in male Sprague Dawley rats treated for 1, 3, 5, 7, or 14 days at 1 mg/kg/day was used to monitor the spatial and temporal expression of various indicators of kidney toxicity during the progression of acute kidney injury (AKI). As early as 1 day after cisplatin treatment, positive kidney injury molecule-1 (Kim-1) immunostaining, observed in the outer medulla of the kidney, and changes in urinary clusterin indicated the onset of proximal tubular injury in the absence of functional effects. After 3 days of treatment, Kim-1 protein levels in urine increased more than 20-fold concomitant with a positive clusterin immunostaining and an increase in urinary osteopontin. Tubular basophilia was also noted, while serum creatinine and blood urea nitrogen levels were elevated only after 5 days, together with tubular degeneration. In conclusion, tissue Kim-1 and urinary clusterin were the most sensitive biomarkers for detection of cisplatin-induced kidney damage. Thereafter, urinary Kim-1 and osteopontin, as well as clusterin immunostaining accurately correlated with the histopathological findings. When AKI is suspected in preclinical rat studies, Kim-1, clusterin, and osteopontin should be part of urinalysis and/or IHC can be performed.

  4. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.

    PubMed

    Ju, Wenjun; Nair, Viji; Smith, Shahaan; Zhu, Li; Shedden, Kerby; Song, Peter X K; Mariani, Laura H; Eichinger, Felix H; Berthier, Celine C; Randolph, Ann; Lai, Jennifer Yi-Chun; Zhou, Yan; Hawkins, Jennifer J; Bitzer, Markus; Sampson, Matthew G; Thier, Martina; Solier, Corinne; Duran-Pacheco, Gonzalo C; Duchateau-Nguyen, Guillemette; Essioux, Laurent; Schott, Brigitte; Formentini, Ivan; Magnone, Maria C; Bobadilla, Maria; Cohen, Clemens D; Bagnasco, Serena M; Barisoni, Laura; Lv, Jicheng; Zhang, Hong; Wang, Hai-Yan; Brosius, Frank C; Gadegbeku, Crystal A; Kretzler, Matthias

    2015-12-02

    Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages.

  5. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker

    PubMed Central

    Smith, Shahaan; Zhu, Li; Shedden, Kerby; Song, Peter X. K.; Mariani, Laura H.; Eichinger, Felix H.; Berthier, Celine C.; Randolph, Ann; Lai, Jennifer Yi-Chun; Zhou, Yan; Hawkins, Jennifer J.; Bitzer, Markus; Sampson, Matthew G.; Thier, Martina; Solier, Corinne; Duran-Pacheco, Gonzalo C.; Duchateau-Nguyen, Guillemette; Essioux, Laurent; Schott, Brigitte; Formentini, Ivan; Magnone, Maria C.; Bobadilla, Maria; Cohen, Clemens D.; Bagnasco, Serena M.; Barisoni, Laura; Lv, Jicheng; Zhang, Hong; Brosius, Frank C.; Gadegbeku, Crystal A.; Kretzler, Matthias

    2016-01-01

    Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages. PMID:26631632

  6. Emerging co-morbidities of obstructive sleep apnea: cognition, kidney disease, and cancer

    PubMed Central

    Gildeh, Nadia; Drakatos, Panagis; Higgins, Sean; Rosenzweig, Ivana

    2016-01-01

    Obstructive sleep apnea (OSA) causes daytime fatigue and sleepiness, and has an established relationship with cardiovascular and metabolic disease. Recent years have seen the emergence of an evidence base linking OSA with an increased risk of degenerative neurological disease and associated cognitive impairment, an accelerated rate of decline in kidney function with an increased risk of clinically significant chronic kidney disease (CKD), and with a significantly higher rate of cancer incidence and death. This review evaluates the evidence base linking OSA with these seemingly unrelated co-morbidities, and explores potential mechanistic links underpinning their development in patients with OSA, including intermittent hypoxia (IH), sleep fragmentation, sympathetic excitation, and immune dysregulation. PMID:27747026

  7. Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway Regulated-Circulating microRNA

    DTIC Science & Technology

    2016-05-01

    Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA PRINCIPAL...TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway- Regulated Circulating microRNA Sb. GRANT NUMBER...panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized that serum

  8. Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA

    DTIC Science & Technology

    2014-09-01

    Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA PRINCIPAL...31Aug2014 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway- Regulated Circulating microRNA Sb...identify a panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized

  9. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

    SciTech Connect

    Taouis, M.; Berlan, M.; Lafontan, M.

    1987-01-01

    The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with (/sup 3/H)yohimbine, whereas (/sup 3/H)clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, (/sup 3/H) clonidine and (/sup 3/H)yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of (/sup 3/H)clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations.

  10. Effects of anionic xenobiotics on rat kidney. I--Tissue and mitochondrial respiration.

    PubMed

    Pritchard, J B; Krall, A R; Silverthorn, S U

    1982-01-15

    The polar 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolite, 2,2-bis(p-chlorophenyl)acetic acid (DDA), and the phenoxyacetic acid herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), were previously shown to be accumulated to high levels in liver and kidney via the organic acid transport system, raising the possibility of organ-specific toxicity secondary to transport. In these studies, accumulation of DDA was shown to depress oxygen consumption by renal cortical slices at high doses (0.1 and 1mM). Isolated renal and hepatic mitochondria were uncoupled by low doses of DDA (5-10 nmoles/mg mitochondrial protein. Maximal uncoupling was seen at 50-70 nmoles/mg. 2,4-D and 2,4,5-T also produced uncoupling, but at doses of 70 nmoles/mg or higher. All agents were more effective with alpha-ketoglutarate or pyruvate-malate), all three agents also depressed State 3 (ADP-stimulated) respiration. Again, DDA was more effective than 2,4-D or 2,4,5-T. These results suggest that accumulation of these or other anionic xenobiotics may lead to toxicity in those tissues possessing the organic anion transport system.

  11. Immunohistochemical diagnosis of Fabry nephropathy and localisation of globotriaosylceramide deposits in paraffin-embedded kidney tissue sections.

    PubMed

    Valbuena, Carmen; Leitão, Dina; Carneiro, Fátima; Oliveira, João Paulo

    2012-02-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder of glycosphingolipids, mostly globotriaosylceramide (Gb3). Proteinuric chronic kidney disease develops frequently, and recognition of Fabry nephropathy on a kidney biopsy may be the first clue to the underlying diagnosis. Since the accumulated glycosphingolipids are largely extracted by the paraffin-embedding procedure, the most characteristic feature of Fabry nephropathy on routine light microscopy (LM) is nonspecific cell vacuolization. To test whether residual Gb3 in kidney tissue might be exploited for the specific diagnosis of Fabry nephropathy, paraffin-embedded kidney biopsies of nine FD patients (one boy, four men, four women) and of a female carrier of a mild genetic mutation, with no evidence of Fabry nephropathy, were immunostained with an anti-Gb3 antibody. The adult biopsies were additionally co-stained with a lysosomal marker (anti-lysosomal-associated membrane protein 2 (anti-LAMP2) antibody). The distribution of Gb3 deposits was scored per cell type and compared to the histological scorings of glycosphingolipid inclusions on semi-thin sections. FD patients had residual Gb3 in all types of glomerular, tubular, interstitial and vascular kidney cells. The highest expression of LAMP2 was seen in tubular cells, but there were no meaningful associations between LAMP2 expression and prevalence of Gb3 deposits on different kidney cell types. The histological scorings of glycosphingolipid inclusions were relatively higher than the corresponding immunohistochemical scorings of Gb3 deposits. In the mildly affected female, Gb3 expression was limited to tubular cells, a pattern similar to controls. Gb3 immunostaining allows the specific diagnosis of Fabry nephropathy even in kidney biopsies routinely processed for LM.

  12. Color-Doppler sonographic tissue perfusion measurements reveal significantly diminished renal cortical perfusion in kidneys with vesicoureteral reflux

    PubMed Central

    Scholbach, T. M.; Sachse, C.

    2016-01-01

    Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion and loss of renal function. Methods to describe and monitor tissue perfusion are needed. We investigated dynamic tissue perfusion measurement (DTPM) with the PixelFlux-software to measure microvascular changes in the renal cortex in 35 children with VUR and 28 healthy children. DTPM of defined horizontal slices of the renal cortex was carried out. A kidney was assigned to the “low grade reflux”-group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the “high grade reflux”-group if the reflux grade was 4 to 5. Kidneys with VUR showed a significantly reduced cortical perfusion. Compared to healthy kidneys, this decline reached in low and high grade refluxes within the proximal 50% of the cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in kidneys depending on the degree of VUR, which is most pronounced in the peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular perfusion, to help planning treatment decisions in children with VUR. PMID:27051133

  13. Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts.

    PubMed

    Raaschou-Nielsen, Ole; Pedersen, Marie; Stafoggia, Massimo; Weinmayr, Gudrun; Andersen, Zorana J; Galassi, Claudia; Sommar, Johan; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Krog, Norun H; Aasvang, Gunn Marit; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Fratiglioni, Laura; Sørensen, Mette; Eriksen, Kirsten T; Tjønneland, Anne; Peeters, Petra H; Bueno-de-Mesquita, H B As; Plusquin, Michelle; Key, Timothy J; Jaensch, Andrea; Nagel, Gabriele; Föger, Bernhard; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Migliore, Enrica; Tamayo, Ibon; Amiano, Pilar; Dorronsoro, Miren; Sokhi, Ranjeet; Kooter, Ingeborg; de Hoogh, Kees; Beelen, Rob; Eeftens, Marloes; Vermeulen, Roel; Vineis, Paolo; Brunekreef, Bert; Hoek, Gerard

    2017-04-01

    Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land-use regression models for particulate matter (PM10 , PM2.5 , PMcoarse , PM2.5 absorbance (soot)) and nitrogen oxides (NO2 , NOx ), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person-years at risk. During follow-up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta-analyses showed higher HRs in association with higher PM concentration, e.g. HR = 1.57 (95%CI: 0.81-3.01) per 5 μg/m(3) PM2.5 and HR = 1.36 (95%CI: 0.84-2.19) per 10(-5) m(-1) PM2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow-up showed stronger associations, but none were statistically significant. Our study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance.

  14. Tissue and serum sialidase levels in breast cancer.

    PubMed

    Sönmez, H; Süer, S; Güngör, Z; Baloglu, H; Kökoglu, E

    1999-02-08

    Breast cancer is both one of the most common and one of the most treatable of all human malignancies. It has been suggested by various investigators that sialic acid increases in the sera of cancerous patients. In cancer patients, an increase in the levels of serum sialic acid may also be due to an increase in the activity of serum or tissue sialidase. The purpose of the present investigation was to determine whether the concentration of sialidase in serum and breast tissue could be used as a tumor marker in breast cancer. In this study; serum sialidase levels in 26 patient with breast cancer and 31 controls were found to be 77.04+/-25.07 U/l and 55.56+/-7.50 U/l, respectively. The mean tissue sialidase levels in 26 breast cancer patients and 13 controls were 39.76+/-17.03 U/g protein and 14.30+/-7.09 U/g protein, respectively. Serum and tissue sialidase levels in breast cancer were significantly higher than those found in the control group (P < 0.001). The mean serum and tissue sialidase levels in 14 Grade I-II and 12 Grade III breast cancer patients were found to be 67.73+/-11.87 U/l and 33.41+/-12.17 U/g protein and 87.89+/-31.94 U/l and 47.17+/-19.30 U/g protein, respectively. Also we found a significant difference between the levels of serum and tissue sialidase in Grade I-II and III (P < 0.05).

  15. Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining.

    PubMed

    Xuan, Jiajia; Zhang, Yunfeng; Zhang, Xiujun; Hu, Fen

    2015-05-01

    Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis.

  16. Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining

    PubMed Central

    XUAN, JIAJIA; ZHANG, YUNFENG; ZHANG, XIUJUN; HU, FEN

    2015-01-01

    Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis. PMID:26137243

  17. Reductions in immunosuppression after haematological or solid organ cancer diagnosis in kidney transplant recipients.

    PubMed

    Hope, Christopher M; Krige, Alice J; Barratt, Alex; Carroll, Robert P

    2015-11-01

    Few data exist on how immunosuppression is altered in kidney transplant recipients (KTR) following a diagnosis of cancer. This study investigated how immunosuppression was altered in KTR after cancer diagnosis and its effect on patient and graft survival. All KTR diagnosed with cancer at our centre from 1990 to 2012 were assessed. Drug regime and serum creatinine levels were recorded 1 year before, at time of, and 1 year after cancer diagnosis. Of 87 KTR who developed cancer (7.3% of transplanted population, n = 1189), 30 developed haematological malignancies and 57 developed solid organ cancers (SOC). In total, 38% of KTR presented with nodal or metastatic disease and 23 of 87 (26%) KTR died within 6 months of cancer diagnosis. Fifty-five KTR had records of pre- and postcancer diagnosis drug regimes. Thirty-six KTR had a (>50%) dose reduction or cessation of 1 or more immunosuppressive agents, and 19 no reduction in immunosuppression. In total, 2 of 36 (6%) of KTR who underwent a dose reduction suffered acute rejection that was reversed with methylprednisolone. Dose reduction/cessation of immunosuppression did not impair graft function, but also did not affect cancer free survival. Further larger prospective studies are needed to determine whether dose reduction alters relapse free cancer survival in KTR.

  18. Risk factors for kidney cancer in New South Wales--I. Cigarette smoking.

    PubMed

    McCredie, M; Stewart, J H

    1992-01-01

    In a population-based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls confirmed an increased risk associated with cigarette smoking in both types of cancer. The risk among current smokers was consistently higher than among ex-smokers, and was nearly twice as great for CaRP than for RCC. Additional information provided by this study includes reduced risks following cessation of smoking within 12 years for CaRP, but only after 25 years for RCC. Starting to smoke before, rather than after, the age of 18 years is linked independently with almost twice the risk for CaRP, but does not affect the risk for RCC. No independent trend was found with number of cigarettes smoked per day.

  19. Tissue engineering a surrogate niche for metastatic cancer cells.

    PubMed

    Seib, F Philipp; Berry, Janice E; Shiozawa, Yusuke; Taichman, Russell S; Kaplan, David L

    2015-05-01

    In breast and prostate cancer patients, the bone marrow is a preferred site of metastasis. We hypothesized that we could use tissue-engineering strategies to lure metastasizing cancer cells to tissue-engineered bone marrow. First, we generated highly porous 3D silk scaffolds that were biocompatible and amenable to bone morphogenetic protein 2 functionalization. Control and functionalized silk scaffolds were subcutaneously implanted in mice and bone marrow development was followed. Only functionalized scaffolds developed cancellous bone and red bone marrow, which appeared as early as two weeks post-implantation and further developed over the 16-week study period. This tissue-engineered bone marrow microenvironment could be readily manipulated in situ to understand the biology of bone metastasis. To test the ability of functionalized scaffolds to serve as a surrogate niche for metastasis, human breast cancer cells were injected into the mammary fat pads of mice. The treatment of animals with scaffolds had no significant effect on primary tumor growth. However, extensive metastasis was observed in functionalized scaffolds, and the highest levels for scaffolds that were in situ manipulated with receptor activator of nuclear factor kappa-B ligand (RANKL). We also applied this tissue-engineered bone marrow model in a prostate cancer and experimental metastasis setting. In summary, we were able to use tissue-engineered bone marrow to serve as a target or "trap" for metastasizing cancer cells.

  20. Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease

    PubMed Central

    Kline, Timothy L.; Irazabal, Maria V.; Ebrahimi, Behzad; Hopp, Katharina; Udoji, Kelly N.; Warner, Joshua D.; Korfiatis, Panagiotis; Mishra, Prasanna K.; Macura, Slobodan I.; Venkatesh, Sudhakar K.; Lerman, Lilach O.; Harris, Peter C.; Torres, Vicente E.; King, Bernard F.

    2015-01-01

    Purpose Noninvasive imaging techniques that quantify renal tissue composition are needed to more accurately ascertain prognosis and monitor disease progression in polycystic kidney disease (PKD). Given the success of magnetization transfer (MT) imaging to characterize various tissue remodeling pathologies, it was tested on a murine model of autosomal dominant PKD. Methods C57Bl/6 Pkd1 R3277C mice at 9, 12, and 15 months were imaged with a 16.4T MR imaging system. Images were acquired without and with RF saturation in order to calculate MT ratio (MTR) maps. Following imaging, the mice were euthanized and kidney sections were analyzed for cystic and fibrotic indices, which were compared with statistical parameters of the MTR maps. Results The MTR‐derived mean, median, 25th percentile, skewness, and kurtosis were all closely related to indices of renal pathology, including kidney weight/body weight, cystic index, and percent of remaining parenchyma. The correlation between MTR and histology‐derived cystic and fibrotic changes was R2 = 0.84 and R2 = 0.70, respectively. Conclusion MT imaging provides a new, noninvasive means of measuring tissue remodeling PKD changes and may be better suited for characterizing renal impairment compared with conventional MR techniques. Magn Reson Med 75:1466–1473, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance. PMID:25974140

  1. Tissue/fluid correlation study for the depletion of sulfadimethoxine in bovine kidney, liver, plasma, urine, and oral fluid.

    PubMed

    Chiesa, O A; Li, H; Kijak, P J; Li, J X; Lancaster, V; Smith, M L; Heller, D N; Thomas, M H; Von Bredow, J

    2012-06-01

    Sulfonamides are among the oldest, but still effective, antimicrobial veterinary medicines. In steers and dairy cows, the sulfonamides are effective in the treatment of respiratory disease and general infections. Sulfadimethoxine (SDM) has been approved by US Food and Drug Administration (FDA) for use in steers and dairy cows with a tolerance of 100 ng/g (ppb) in edible tissues and 10 ppb in milk. The detection of SDM residue above tolerance in the animal slaughtered for food process will result in the whole carcass being discarded. This report describes a comprehensive depletion study of SDM (and its main metabolite) in plasma, urine, oral fluid, kidney, and liver. In this study, nine steers were injected intravenously with the approved dose of SDM; the loading dose was 55 mg/kg, followed by 27.5 mg/kg dose at 24 h and again at 48 h. Fluids (blood, urine, and saliva) and tissue (liver and kidney) samples were collected at intervals after the last dose of SMD. The combination of laparoscopic serial sampling technique with the liquid chromatography/mass spectrometry method provided the data to establish the tissue/fluid correlation in the depletion of SMD. A strong correlation and linearity of the log-scale concentration over time in the depletion stage has been confirmed for kidney, liver, and plasma.

  2. Characterization of MMP-9 gene from a normalized cDNA library of kidney tissue of yellow catfish (Pelteobagrus fulvidraco).

    PubMed

    Ke, Fei; Wang, Yun; Hong, Jun; Xu, Chen; Chen, Huan; Zhou, Shuai-Bang

    2015-08-01

    Matrix metalloproteinase-9 (MMP-9), one of members of the MMP family, is important for the cleaving of structural extracellular matrix (ECM) molecules and involved in inflammatory processes. In this study, MMP-9 cDNA was isolated and characterized from a normalized cDNA library of kidney tissue of yellow catfish (designated as YcMMP-9). The complete sequence of YcMMP-9 cDNA consisted of 2561 nucleotides. The open reading frame potentially encoded a protein of 685 amino acids with a calculated molecular mass of approximately 77.182 kDa. Amino acid sequence of YcMMP-9 have typical characteristics of MMP-9 family and showed highest identity (85.3%) to channel catfish MMP-9. The YcMMP-9 genomic DNA contains 13 exons and 12 introns. Quantitative RT-PCR (qRT-PCR) analysis showed that YcMMP-9 mRNA was constitutively expressed in all examined tissues in normal fish with high expression in head kidney, trunk kidney, blood, and spleen. However, expression of YcMMP-9 mRNA was induced by Aeromonas hydrophila stimulation, especially in these four tissues mentioned above. It indicated that YcMMP-9 was involved in innate immune responses against bacterial infection.

  3. Urine metabolomics for kidney cancer detection and biomarker discovery.

    PubMed

    Ganti, Sheila; Weiss, Robert H

    2011-01-01

    Renal cell carcinoma (RCC) is one of the few human cancers whose incidence is increasing. The disease regularly progresses asymptomatically and is frequently metastatic upon presentation, thereby necessitating the development of an early method of detection. A metabolomic approach for biomarker detection using urine as a biofluid is appropriate since the tumor is located in close proximity to the urinary space. By comparing the composition of urine from individuals with RCC to control individuals, differences in metabolite composition of this biofluid can be identified, and these data can be utilized to create a clinically applicable and, possibly, bedside assay. Recent studies have shown that sample handling and processing greatly influences the variability seen in the urinary metabolome of both cancer and control patients. Once a standard method of collection is developed, identifying metabolic derangements associated with RCC will also lead to the investigation of novel targets for therapeutic intervention. The objective of this review is to discuss existing methods for sample collection, processing, data analysis, and recent findings in this emerging field.

  4. Proliferation and tissue remodeling in cancer: the hallmarks revisited.

    PubMed

    Markert, E K; Levine, A J; Vazquez, A

    2012-10-04

    Although cancers are highly heterogeneous at the genomic level, they can manifest common patterns of gene expression. Here, we use gene expression signatures to interrogate two major processes in cancer, proliferation and tissue remodeling. We demonstrate that proliferation and remodeling signatures are partially independent and result in four distinctive cancer subtypes. Cancers with the proliferation signature are characterized by signatures of p53 and PTEN inactivation and concomitant Myc activation. In contrast, remodeling correlates with RAS, HIF-1α and NFκB activation. From the metabolic point of view, proliferation is associated with upregulation of glycolysis and serine/glycine metabolism, whereas remodeling is characterized by a downregulation of oxidative phosphorylation. Notably, the proliferation signature correlates with poor outcome in lung, prostate, breast and brain cancer, whereas remodeling increases mortality rates in colorectal and ovarian cancer.

  5. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-20

    ..., Gastric Cancer, Kidney Cancer, Liver Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer and Pancreatic..., gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer and...

  6. Differentiating cancerous tissues from noncancerous tissues using single-fiber reflectance spectroscopy with different fiber diameters

    NASA Astrophysics Data System (ADS)

    Sircan-Kuçuksayan, Aslinur; Denkceken, Tuba; Canpolat, Murat

    2015-11-01

    Elastic light-scattering spectra acquired with single-fiber optical probes with diameters of 100, 200, 400, 600, 800, 1000, 1200, and 1500 μm were used to differentiate cancerous from noncancerous prostate tissues. The spectra were acquired ex vivo on 24 excised prostate tissue samples collected from four patients. For each probe, the spectra and histopathology results were compared in order to investigate the correlation between the core diameters of the single-fiber optical probe and successful differentiation between cancerous and noncancerous prostate tissues. The spectra acquired using probes with a fiber core diameter of 400 μm or smaller successfully differentiated cancerous from noncancerous prostate tissues. Next, the spectra were acquired from monosized polystyrene microspheres with a diameter of 5.00±0.01 μm to investigate the correlation between the core diameters of the probes and the Mie oscillations on the spectra. Monte Carlo simulations of the light distribution of the tissue phantoms were run to interrogate whether the light detected by the probes with different fiber core diameters was in the ballistic or diffusive regime. If the single-fiber optical probes detect light in the ballistic regime, the spectra can be used to differentiate between cancerous and noncancerous tissues.

  7. Diabetes and kidney cancer outcomes: a propensity score analysis.

    PubMed

    Nayan, Madhur; Finelli, Antonio; Jewett, Michael A S; Juurlink, David N; Austin, Peter C; Kulkarni, Girish S; Hamilton, Robert J

    2017-02-01

    There is conflicting evidence whether diabetes is associated with survival outcomes in patients undergoing a nephrectomy for renal cell carcinoma. We performed a retrospective review of 1034 patients undergoing nephrectomy for unilateral, M0, renal cell carcinoma between 2000 and 2016 at a tertiary academic center. Inverse probability of treatment weights were derived from a propensity score model based on various clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between diabetes and disease-free survival, cancer-specific survival, and overall survival in the sample weighted by the inverse probability of treatment weights. Furthermore, to evaluate whether severity of diabetes was associated with survival outcomes, we performed separate analyses where inverse probability of treatment weights were computed based on the probability of having diabetes that was controlled by medication. Of the 1034 patients, 180 (17 %) had diabetes. Of these, 139 (77 %) patients required medications for diabetes control while the remaining 41 (23 %) had diet controlled diabetes. Median follow-up was 50 months (IQR 17-86). Diabetes at the time of surgery was not significantly associated with disease-free survival (HR 1.11, 95 % CI 0.64 -1.91), cancer-specific survival (HR 0.96, 95 % CI 0.49-1.91), or overall survival (HR 1.28, 95 % CI 0.84-1.95). We found similar results when we compared diabetics controlled with medication vs. non-diabetics or diet controlled diabetics. In summary, we found no significant association between diabetes and survival outcomes in patients undergoing nephrectomy for M0 renal cell carcinoma. These results suggest that diabetics should be treated and followed in a similar manner to non-diabetics.

  8. Risk factors for kidney cancer in New South Wales. IV. Occupation.

    PubMed

    McCredie, M; Stewart, J H

    1993-04-01

    In a population based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP), and 523 controls from the electoral roles were obtained about employment in certain industries or occupations, and exposure to particular chemicals chosen because of suspected associations with kidney cancer. A low level of education increased the risk for CaRP but not RCC. After adjustment for known risk factors, exposure to asbestos significantly increased the risk for RCC (relative risk (RR) = 1.62; 95% confidence interval (95% CI) 1.04-2.53). Working in the dry cleaning industry had a stronger link with CaRP (RR = 4.68; 95% CI 1.32-16.56) than with RCC (RR = 2.49; 95% CI 0.97-6.35). Working in the iron and steel industry doubled the risk for CaRP (RR = 2.13; 95% CI 1.04-4.39) whereas employment in the petroleum refining industry had a non-significant association with CaRP (RR = 2.60; 95% CI 0.88-7.63) and none with RCC.

  9. Risk factors for kidney cancer in New South Wales. IV. Occupation.

    PubMed Central

    McCredie, M; Stewart, J H

    1993-01-01

    In a population based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP), and 523 controls from the electoral roles were obtained about employment in certain industries or occupations, and exposure to particular chemicals chosen because of suspected associations with kidney cancer. A low level of education increased the risk for CaRP but not RCC. After adjustment for known risk factors, exposure to asbestos significantly increased the risk for RCC (relative risk (RR) = 1.62; 95% confidence interval (95% CI) 1.04-2.53). Working in the dry cleaning industry had a stronger link with CaRP (RR = 4.68; 95% CI 1.32-16.56) than with RCC (RR = 2.49; 95% CI 0.97-6.35). Working in the iron and steel industry doubled the risk for CaRP (RR = 2.13; 95% CI 1.04-4.39) whereas employment in the petroleum refining industry had a non-significant association with CaRP (RR = 2.60; 95% CI 0.88-7.63) and none with RCC. PMID:8494775

  10. Autofluorescence polarization spectroscopy of cancerous and normal colorectal tissues

    NASA Astrophysics Data System (ADS)

    Genova, Ts.; Borisova, E.; Penkov, N.; Vladimirov, B.; Terziev, I.; Zhelyazkova, Al.; Avramov, L.

    2016-01-01

    The wide spread of colorectal cancer and high mortality rate among the patients, brings it to a level of high public health concern. Implementation of standard endoscopic surveillance proves to be effective for reduction of colorectal cancer patients' mortality, since its early diagnosis allows eradication of the disease prior to invasive cancer development, but its application in common clinical practice is still limited. Therefore the development of complimentary diagnostic techniques of the standard white-light endoscopy is on high demand. The non-invasive and highly informative nature of the fluorescence spectroscopy allow to use it as the most realistic prospect of an add-on "red flag" technique for early endoscopy detection of colorectal cancer. Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that is used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues in our studies. The feasibility of polarization fluorescence technique to enhance the contrast between normal and cancerous tissues was investigated as well. Additional linear polarizing optics was used on the way of the excitation and emission fluorescence light beams. The polarizing effects were investigated in parallel and perpendicular linear polarization modes respectively. The excitation applied was in the region of 280 - 440 nm, with 10 nm scanning step, and the fluorescence emission was detected in the region of 300 - 800 nm. Our previous experience with SFS technique showed its great potential for accurate, highly sensitive and specific discrimination between cancerous and normal colorectal tissue. Since one of the major sources of endogenous fluorescence with diagnostic meaning is the structural protein - collagen, which is characterized with high anisotropy, we've expected and observed an enhancement of the spectral differences between cancerous and normal colorectal tissue, which could be beneficial for the colorectal tumour' diagnostics

  11. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

    PubMed

    Pompas-Veganzones, N; Sandonis, V; Perez-Lanzac, Alberto; Beltran, M; Beardo, P; Juárez, A; Vazquez, F; Cozar, J M; Alvarez-Ossorio, J L; Sanchez-Carbayo, Marta

    2016-10-01

    Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed

  12. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    NASA Astrophysics Data System (ADS)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  13. Trihalomethanes in drinking water and the risk of death from kidney cancer: does hardness in drinking water matter?

    PubMed

    Liao, Yen-Hsiung; Chen, Chih-Cheng; Chang, Chih-Ching; Peng, Chiung-Yu; Chiu, Hui-Fen; Wu, Trong-Neng; Yang, Chun-Yuh

    2012-01-01

    The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of development of kidney cancer and (2) determine whether hardness levels in drinking water modify the effects of TTHM on risk of kidney cancer induction. A matched case-control study was used to investigate the relationship between the risk of death attributed to kidney cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from 1998 through 2007 were obtained. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels and levels of hardness in drinking water were also collected. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and hardness exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77-1.25) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. However, evidence of an interaction was noted between the use of soft water and drinking water TTHM concentrations. Increased knowledge of the interaction between hardness and TTHM levels in reducing risk of kidney cancer development will aid in public policy decision and establishing standards to prevent disease occurrence.

  14. Investigation of the thermal and tissue injury behaviour in microwave thermal therapy using a porcine kidney model.

    PubMed

    He, X; McGee, S; Coad, J E; Schmidlin, F; Iaizzo, P A; Swanlund, D J; Kluge, S; Rudie, E; Bischof, J C

    2004-09-01

    Minimally invasive microwave thermal therapies are being developed for the treatment of small renal cell carcinomas (RCC, d<3 cm). This study assessed the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex. Three groups of kidneys were evaluated: (1) in vitro treated, (2) in vivo with 2-h post-treatment perfusion (acute) and (3) in vivo with 7-day post-treatment perfusion (chronic). The kidneys were treated with an interstitial water-cooled microwave probe (Urologix, Plymouth, MN) that created a lesion centered in the renal cortex (50 W for 10 min). The thermal histories were recorded at 0.5 cm radial intervals from the probe axis for correlation with the histologic cellular and vascular injury. The kidneys showed a reproducible 2 cm chronic lesion with distinct histologic injury zones identified. The thermal histories at the edge of these zones were found using Lagrangian interpolation. The threshold thermal histories for microvascular injury and stasis appeared to be lower than that for renal epithelial cell injury. The Arrhenius kinetic injury models were fit to the thermal histories and injury data to determine the kinetic parameters (i.e. activation energy and frequency factor) for the thermal injury processes. The resultant activation energies are consistent in magnitude with those for thermally induced protein denaturation. A 3-D finite element thermal model based on the Pennes bioheat equation was developed and solved using ANSYS (V7.0). The real geometry of the kidneys studied and temperature dependent thermal properties were used in this model. The specific absorption rate (SAR) of the microwave probe required for the thermal modelling was experimentally determined. The results from the thermal modelling suggest that the complicated change of local renal blood perfusion with temperature and time during microwave thermal therapy can be predicted, although a first order kinetic model may

  15. Trace element load in cancer and normal lung tissue

    NASA Astrophysics Data System (ADS)

    Kubala-Kukuś , A.; Braziewicz, J.; Banaś , D.; Majewska, U.; Góź Dź , S.; Urbaniak, A.

    1999-04-01

    Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described.

  16. Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-regulated Circulating microRNA

    DTIC Science & Technology

    2013-09-01

    Cancer via VHL /HIF Pathway-regulated Circulating microRNA PRINCIPAL INVESTIGATOR: Allan Pantuck, MD...SUBTITLE Early Diagnosis of Clear Cell Kidney Cancer via VHL /HIF Pathway-regulated Circulating microRNA 5a. CONTRACT NUMBER 5b. GRANT NUMBER

  17. Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues

    PubMed Central

    Carlson, Grady E.; Martin, Eric W.; Shirure, Venktesh S.; Malgor, Ramiro; Resto, Vicente A.; Goetz, Douglas J.; Burdick, Monica M.

    2017-01-01

    A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue. PMID:28282455

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  19. Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

    SciTech Connect

    Wendler, Johann Jakob; Pech, Maciej; Blaschke, Simon; Porsch, Markus; Janitzky, Andreas; Ulrich, Matthias; Dudeck, Oliver; Ricke, Jens; Liehr, Uwe-Bernd

    2012-04-15

    Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE. Methods: Results of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys. Results: In the dedicated investigation, no acute vascular destruction of the renal parenchyma and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave. Conclusion: The NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.

  20. Kidney Dysplasia

    MedlinePlus

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  1. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    PubMed Central

    2012-01-01

    Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration. Conclusions Our

  2. Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

    PubMed Central

    Yu, Steven S; Quinn, David I; Dorff, Tanya B

    2016-01-01

    Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC. PMID:27713636

  3. Non-Invasive Measurement of the Temperature Rise in Tissue Surrounding a Kidney Stone Subjected to Ultrasonic Propulsion*

    PubMed Central

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

    2016-01-01

    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. PMID:26736818

  4. Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B-deoxycholate.

    PubMed Central

    Collette, N; van der Auwera, P; Lopez, A P; Heymans, C; Meunier, F

    1989-01-01

    We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection. Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts. The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillus fumigatus. Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 micrograms/g. A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs. Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates. Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys. The median concentration in bile was 7.3 micrograms/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose. Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC. In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive. PMID:2658785

  5. A nested case-control study of kidney cancer among refinery/petrochemical workers

    SciTech Connect

    Gamble, J.F.; Pearlman, E.D.; Nicolich, M.J.

    1996-06-01

    A nested case-control study was designed to evaluate whether a nearly twofold excess of kidney cancer among workers at a refinery/petrochemical plant was associated with cumulative exposure to C{sub 2}-C{sub 5} saturated, C{sub 2}-C{sub 5} unsaturated, C{sub 6}-C{sub 10} aliphatic saturated, C{sub 6}-C{sub 10} aliphatic unsaturated, and C{sub 6}-C{sub 10} aromatic process streams. Nonoccupational risk factors were body mass index association with cumulative exposure or tenure as estimated by conditional logistic regression and adjusted for nonoccupational risk factors. Categorical analysis showed increased odds ratios only in the second (low) and fourth (high) quartiles compared to the first quartile reference group of lowest exposed workers, and a three-quarter-fold increased odds ratio for >32 years` tenure compared to the <25-year reference group. The number of cases was small with wide confidence intervals around estimate of risk, so the possibility of an exposure-response trend cannot be ruled out. Multivariate analysis identified overweight (high BMI; p<0.01) as the most important risk factor in this data set, followed by tenure and increased blood pressure. There was a weak association with current smoking, but not with pack-years smoked. The risk of kidney cancer for a nonsmoker with normal blood pressure but 25% overweight was increased about 2.6-fold (95% CI = 1.2-5.4). The risk of kidney cancer for a nonsmoker of normal weight with high blood pressure (e.g., 150/110), was increased about 4.5 (95% CI, 0.8-26). 49 refs., 3 figs., 8 tabs.

  6. Detection of cancerous biological tissue areas by means of infrared absorption and SERS spectroscopy of intercellular fluid

    NASA Astrophysics Data System (ADS)

    Velicka, M.; Urboniene, V.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.

    2015-08-01

    We present a novel approach to the detection of cancerous kidney tissue areas by measuring vibrational spectra (IR absorption or SERS) of intercellular fluid taken from the tissue. The method is based on spectral analysis of cancerous and normal tissue areas in order to find specific spectral markers. The samples were prepared by sliding the kidney tissue over a substrate - surface of diamond ATR crystal in case of IR absorption or calcium fluoride optical window in case of SERS. For producing the SERS signal the dried fluid film was covered by silver nanoparticle colloidal solution. In order to suppress fluorescence background the measurements were performed in the NIR spectral region with the excitation wavelength of 1064 nm. The most significant spectral differences - spectral markers - were found in the region between 400 and 1800 cm-1, where spectral bands related to various vibrations of fatty acids, glycolipids and carbohydrates are located. Spectral markers in the IR and SERS spectra are different and the methods can complement each other. Both of them have potential to be used directly during surgery. Additionally, IR absorption spectroscopy in ATR mode can be combined with waveguide probe what makes this method usable in vivo.

  7. Mechanisms of Chemical Carcinogenesis in the Kidneys

    PubMed Central

    Radford, Robert; Frain, Helena; Ryan, Michael P.; Slattery, Craig; McMorrow, Tara

    2013-01-01

    Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney to perform its vital roles in maintaining tissue homeostasis may in fact increase the risk of carcinogen exposure and contribute to the organ specific carcinogenicity observed with numerous kidney carcinogens. This review will address the numerous mechanisms which play a role in the concentration, bioactivation, and uptake of substances from both the urine and blood which significantly increase the risk of cancer in the kidney. PMID:24071941

  8. The analysis of microRNA-34 family expression in human cancer studies comparing cancer tissues with corresponding pericarcinous tissues.

    PubMed

    Wang, Liguang; Yu, Jianyu; Xu, Jun; Zheng, Chunlong; Li, Xiaowei; Du, Jiajun

    2015-01-01

    Recently many studies have focused on the microRNA-34 (miR-34) family expression in various cancers; nevertheless, the controversial results of these studies still exist in identifying miR-34 members as new biomarkers of cancers. Therefore, we carried out this comprehensive meta-analysis of published studies that compared the miR-34 family expression profiles between cancer tissues and paired neighboring noncancerous tissues to systemically evaluate the findings globally and address the inconsistencies of pertinent literatures. The data included in this article were collected from Embase, PubMed and Web of Science up to December 2013. To overcome the difficulties that many raw data were unavailable and study methods were different, a vote-counting strategy was adopted to identify consistent markers in our analysis. Ultimately, a total of 23 cancers were reported in the 61 eligible studies, of which 46 studies provided fold-change value information. In the consistently reported cancer types, non-small cell lung cancer (NSCLC), glioma and nasopharyngeal carcinoma (NPC) ranked at the top with down-regulated feature. Cervical neoplasm was consistently reported to be over-expressed in the panel of each member of miR-34s. Subgroup analysis of miR-34 family expression demonstrated that colorectal cancer (CRC), gastric cancer (GC), hepatocellular carcinoma (HCC) and prostate cancer (PCa) were most frequently reported with inconsistent regulations. Our meta-analysis showed that miR-34 family members could be expected to become potential diagnostic and prognostic biomarkers in some types of human cancers. Further well-designed and larger sample studies are surely warranted to identify the role of the miR-34 family in the occurrence and development of tumors.

  9. Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer.

    PubMed

    Pampalakis, Georgios; Sotiropoulou, Georgia

    2007-09-01

    Human tissue kallikreins (KLKs or kallikrein-related peptidases) are a subgroup of extracellular serine proteases that act on a wide variety of physiological substrates, while they display aberrant expression patterns in certain types of cancer. Differential expression patterns lead to the exploitation of these proteins as new cancer biomarkers for hormone-dependent malignancies, in particular. The prostate-specific antigen or kallikrein-related peptidase 3 (PSA/KLK3) is an established tumor marker for the diagnosis and monitoring of prostate cancer. It is well documented that specific KLK genes are co-expressed in tissues and in various pathologies suggesting their participation in complex proteolytic cascades. Here, we review the currently established knowledge on the involvement of KLK proteolytic cascades in the regulation of physiological and pathological processes in prostate tissue and in skin. It is well established that the activity of KLKs is often regulated by auto-activation and subsequent autolytic internal cleavage leading to enzymatic inactivation, as well as by inhibitory serpins or by allosteric inhibition by zinc ions. Redistribution of zinc ions and alterations in their concentration due to physiological or pathological reasons activates specific KLKs initiating the kallikrein cascade(s). Recent studies on kallikrein substrate specificity allowed for the construction of a kallikrein interaction network involved in semen liquefaction and prostate cancer, as well as in skin pathologies, such as skin desquamation, psoriasis and cancer. Furthermore, we discuss the crosstalks between known proteolytic pathways and the kallikrein cascades, with emphasis on the activation of plasmin and its implications in prostate cancer. These findings may have clinical implications for the underlying molecular mechanism and management of cancer and other disorders in which KLK activity is elevated.

  10. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2016-05-06

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

  11. DNA damage in the kidney tissue cells of the fish Rhamdia quelen after trophic contamination with aluminum sulfate

    PubMed Central

    Klingelfus, Tatiane; da Costa, Paula Moiana; Scherer, Marcos; Cestari, Marta Margarete

    2015-01-01

    Abstract Even though aluminum is the third most common element present in the earth's crust, information regarding its toxicity remains scarce. It is known that in certain cases, aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of the fish Rhamdia quelen after trophic contamination for 60 days. Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50 mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The three types of chromosomal abnormalities (CA) found were categorized as chromatid breaks, decondensation of telomeric region, and early separation of sister chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum sulfate had genotoxic potential. Under these treatments, early separation of the sister chromatids was observed more frequently and decondensation of the telomeric region tended to increase in frequency. We suggest that structural changes in the proteins involved in DNA compaction may have led to the decondensation of the telomeric region, making the DNA susceptible to breaks. Moreover, early separation of the sister chromatids may have occurred due to changes in the mobility of chromosomes or proteins that keep the sister chromatids together. The comet assay confirmed the genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia quelen at the three doses of exposure. PMID:26692157

  12. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    PubMed Central

    Oguntibeju, Oluwafemi O.; Meyer, Samantha; Aboua, Yapo G.; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  13. Effect of preservation solutions UW and EC on the expression of matrix metalloproteinase II and tissue inhibitor of metalloproteinase II genes in rat kidney.

    PubMed

    Sulikowski, Tadeusz; Domanski, Leszek; Zietek, Zbigniew; Adler, Grażyna; Pawlik, Andrzej; Ciechanowicz, Andrzej; Ciechanowski, Kazimierz; Ostrowski, Marek

    2012-01-30

    Matrix metalloproteinases and tissue inhibitor of metalloproteinases play an important role in the regulation of mesangial cell proliferation and may be involved in ischemia-reperfusion injuries. Preservation solutions are thought to diminish the ischemic injury and appropriate choice of the solution should guarantee a better graft function and good prognosis for graft survival. The aim of the study was to examine the effect of preservation solutions UW and EC on the expression of matrix metalloproteinase II and tissue inhibitor of metalloproteinase II genes in rat kidney. The study was carried out on Wistar rat kidneys divided into 3 groups: kidneys perfused with 0.9% NaCl (control group), with UW, and with EC preservation solution. The results show an enhancement of MMP-2 and TIMP-2 gene expression after 12 min of cold ischemia. This increase was more expressed in kidneys preserved with UW solution in comparison with kidneys perfused with EC solution and 0.9% NaCl. After 24 h of cold ischemia the expression of MMP-2 and TIMP-2 genes in kidney perfused with UW solution decreased, while in kidneys perfused with EC it was increased. After warm ischemia the MMP-2 and TIMP-2 gene expression increased, whereas it was significantly lower in kidneys perfused with EC solution.

  14. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues

    PubMed Central

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J.; Sirota, Marina

    2016-01-01

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery. PMID:27142790

  15. Classifications of Multispectral Colorectal Cancer Tissues Using Convolution Neural Network

    PubMed Central

    Haj-Hassan, Hawraa; Chaddad, Ahmad; Harkouss, Youssef; Desrosiers, Christian; Toews, Matthew; Tanougast, Camel

    2017-01-01

    Background: Colorectal cancer (CRC) is the third most common cancer among men and women. Its diagnosis in early stages, typically done through the analysis of colon biopsy images, can greatly improve the chances of a successful treatment. This paper proposes to use convolution neural networks (CNNs) to predict three tissue types related to the progression of CRC: benign hyperplasia (BH), intraepithelial neoplasia (IN), and carcinoma (Ca). Methods: Multispectral biopsy images of thirty CRC patients were retrospectively analyzed. Images of tissue samples were divided into three groups, based on their type (10 BH, 10 IN, and 10 Ca). An active contour model was used to segment image regions containing pathological tissues. Tissue samples were classified using a CNN containing convolution, max-pooling, and fully-connected layers. Available tissue samples were split into a training set, for learning the CNN parameters, and test set, for evaluating its performance. Results: An accuracy of 99.17% was obtained from segmented image regions, outperforming existing approaches based on traditional feature extraction, and classification techniques. Conclusions: Experimental results demonstrate the effectiveness of CNN for the classification of CRC tissue types, in particular when using presegmented regions of interest.

  16. Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells.

    PubMed

    Kato, Taigo; Inoue, Hiroyuki; Imoto, Seiya; Tamada, Yoshinori; Miyamoto, Takashi; Matsuo, Yo; Nakamura, Yusuke; Park, Jae-Hyun

    2016-04-05

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.

  17. Role of Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by ho...

  18. Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes.

    PubMed

    Flechner, Stuart M; Kurian, Sunil M; Head, Steven R; Sharp, Starlette M; Whisenant, Thomas C; Zhang, Jie; Chismar, Jeffrey D; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J; Kay, Steven A; Walker, John R; Salomon, Daniel R

    2004-09-01

    A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients.

  19. A COMPARISON OF THE GROWTH OF SELECTED MYCOBACTERIA IN HELA, MONKEY KIDNEY, AND HUMAN AMNION CELLS IN TISSUE CULTURE

    PubMed Central

    Shepard, Charles C.

    1958-01-01

    HeLa, monkey kidney, and human amnion cells in tissue cultures were compared as sites for the multiplication of strains of tubercle bacilli or original and reduced pathogenicity, and for several other species of mycobacteria capable of causing disease in humans. The arrangement of the pathogenic species inorder of their growth rates in HeLa cells was Mycobacterium fortuitum, Mycobacterium balnei, and the "yellow bacillus," followed closely by the tubercle bacillus. This order was also correct for these species in monkey kidney and human amnion cells, and is the same as that seen in bacteriological media. The arrangement of the strains of tubercle bacilli in order of their growth rates in all three types of cells was: H37Rv, then R1Rv, and lastly H37Ra, which multiplied about as slowly as BCG. An INH-resistant strain grew about as rapidly as H37Rv. Growth of the pathogenic species occurred at about the same rates in HeLa and monkey kidney cells, but was distinctly slower in human amnion cells, which are less active metabolically. Irradiation of the cells in doses up to 5000 r did not affect the subsequent growth of mycobacteria in them. Preliminary experiments with human leprosy bacilli indicate that they can be introduced into these cells in high numbers and that the bacilli then persist for the life of the cells. PMID:13491759

  20. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    PubMed

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  1. Kidney, Lung, Ovarian, and Prostate Cancer - Treatment Summary Table | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  2. Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile.

    PubMed

    Ferreccio, Catterina; Smith, Allan H; Durán, Viviana; Barlaro, Teresa; Benítez, Hugo; Valdés, Rodrigo; Aguirre, Juan José; Moore, Lee E; Acevedo, Johanna; Vásquez, María Isabel; Pérez, Liliana; Yuan, Yan; Liaw, Jane; Cantor, Kenneth P; Steinmaus, Craig

    2013-09-01

    Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007-2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of <400, 400-1,000, and >1,000 µg/day (median water concentrations of 60, 300, and 860 µg/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (Ptrend < 0.001), respectively. Odds ratios were not elevated for renal cell cancer. With these new findings, including evidence of dose-response, we believe there is now sufficient evidence in humans that drinking-water arsenic causes renal pelvis and ureter cancer.

  3. Case-Control Study of Arsenic in Drinking Water and Kidney Cancer in Uniquely Exposed Northern Chile

    PubMed Central

    Ferreccio, Catterina; Smith, Allan H.; Durán, Viviana; Barlaro, Teresa; Benítez, Hugo; Valdés, Rodrigo; Aguirre, Juan José; Moore, Lee E.; Acevedo, Johanna; Vásquez, María Isabel; Pérez, Liliana; Yuan, Yan; Liaw, Jane; Cantor, Kenneth P.; Steinmaus, Craig

    2013-01-01

    Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007–2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of <400, 400–1,000, and >1,000 µg/day (median water concentrations of 60, 300, and 860 µg/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (Ptrend < 0.001), respectively. Odds ratios were not elevated for renal cell cancer. With these new findings, including evidence of dose-response, we believe there is now sufficient evidence in humans that drinking-water arsenic causes renal pelvis and ureter cancer. PMID:23764934

  4. Inflammatory Kidney and Liver Tissue Response to Different Hydroxyethylstarch (HES) Preparations in a Rat Model of Early Sepsis

    PubMed Central

    Schimmer, Ralph C.; Urner, Martin; Voigtsberger, Stefanie; Booy, Christa; Roth Z’Graggen, Birgit; Beck-Schimmer, Beatrice; Schläpfer, Martin

    2016-01-01

    Background Tissue hypoperfusion and inflammation in sepsis can lead to organ failure including kidney and liver. In sepsis, mortality of acute kidney injury increases by more than 50%. Which type of volume replacement should be used is still an ongoing debate. We investigated the effect of different volume strategies on inflammatory mediators in kidney and liver in an early sepsis model. Material and Methods Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) and assigned to three fluid replenishment groups. Animals received 30mL/kg of Ringer’s lactate (RL) for 2h, thereafter RL (75mL/kg), hydroxyethyl starch (HES) balanced (25mL/kg), containing malate and acetate, or HES saline (25mL/kg) for another 2h. Kidney and liver tissue was assessed for inflammation. In vitro rat endothelial cells were exposed to RL, HES balanced or HES saline for 2h, followed by stimulation with tumor necrosis factor-α (TNF-α) for another 4h. Alternatively, cells were exposed to malate, acetate or a mixture of malate and acetate, reflecting the according concentration of these substances in HES balanced. Pro-inflammatory cytokines were determined in cell supernatants. Results Cytokine mRNA in kidney and liver was increased in CLP animals treated with HES balanced compared to RL, but not after application of HES saline. MCP-1 was 3.5fold (95% CI: 1.3, 5.6) (p<0.01) and TNF-α 2.3fold (95% CI: 1.2, 3.3) (p<0.001) upregulated in the kidney. Corresponding results were seen in liver tissue. TNF-α-stimulated endothelial cells co-exposed to RL expressed 3529±1040pg/mL MCP-1 and 59±23pg/mL CINC-1 protein. These cytokines increased by 2358pg/mL (95% CI: 1511, 3204) (p<0.001) and 29pg/ml (95% CI: 14, 45) (p<0.01) respectively when exposed to HES balanced instead. However, no further upregulation was observed with HES saline. PBS supplemented with acetate increased MCP-1 by 1325pg/mL (95% CI: 741, 1909) (p<0.001) and CINC-1 by 24pg/mL (95% CI: 9, 38) (p<0

  5. Clinical features of kidney cancer in primary care: a case-control study using primary care records

    PubMed Central

    Shephard, Elizabeth; Neal, Richard; Rose, Peter; Walter, Fiona; Hamilton, William T

    2013-01-01

    Background Kidney cancer accounts for over 4000 UK deaths annually, and is one of the cancer sites with a poor mortality record compared with Europe. Aim To identify and quantify all clinical features of kidney cancer in primary care. Design Case-control study, using General Practice Research Database records. Method A total of 3149 patients aged ≥40 years, diagnosed with kidney cancer between 2000 and 2009, and 14 091 age, sex and practice-matched controls, were selected. Clinical features associated with kidney cancer were identified, and analysed using conditional logistic regression. Positive predictive values for features of kidney cancer were estimated. Results Cases consulted more frequently than controls in the year before diagnosis: median 16 consultations (interquartile range 10–25) versus 8 (4–15): P<0.001. Fifteen features were independently associated with kidney cancer: visible haematuria, odds ratio 37 (95% confidence interval [CI] = 28 to 49), abdominal pain 2.8 (95% CI = 2.4 to 3.4), microcytosis 2.6 (95% CI = 1.9 to 3.4), raised inflammatory markers 2.4 (95% CI = 2.1 to 2.8), thrombocytosis 2.2 (95% CI = 1.7 to 2.7), low haemoglobin 1.9 (95% CI = 1.6 to 2.2), urinary tract infection 1.8 (95% CI = 1.5 to 2.1), nausea 1.8 (95% CI = 1.4 to 2.3), raised creatinine 1.7 (95% CI = 1.5 to 2.0), leukocytosis 1.5 (95% CI = 1.2 to 1.9), fatigue 1.5 (95% CI = 1.2 to 1.9), constipation 1.4 (95% CI = 1.1 to 1.7), back pain 1.4 (95% CI = 1.2 to 1.7), abnormal liver function 1.3 (95% CI = 1.2 to 1.5), and raised blood sugar 1.2 (95% CI = 1.1 to 1.4). The positive predictive value for visible haematuria in patients aged ≥60 years was 1.0% (95% CI = 0.8 to 1.3). Conclusion Visible haematuria is the commonest and most powerful single predictor of kidney cancer, and the risk rises when additional symptoms are present. When considered alongside the risk of bladder cancer, the overall risk of urinary tract cancer from haematuria warrants referral. PMID:23540481

  6. Delivering kidney cancer care in rural Central and Southern Illinois: a telemedicine approach.

    PubMed

    Alanee, S; Dynda, D; LeVault, K; Mueller, G; Sadowski, D; Wilber, A; Jenkins, W D; Dynda, M

    2014-11-01

    There is a growing body of experience and research suggesting that telemedicine (video conferencing, smart phones and online patient portals) could be the solution to addressing gaps in the provision of specialised healthcare in rural areas. The proposed role of telemedicine in providing needed services in hard to reach areas is not new. The United States Telecommunication Act of 1996 provided the initial traction for telemedicine by removing important economic and legal obstacles regarding the use of technology in healthcare delivery. This initial ruling has been supplemented by the availability of federal funding to support efforts aimed at developing telemedicine in underserved areas. In this paper, we explore one aspect of disease disparity pertinent to rural Illinois (kidney cancer incidence and mortality) and describe how we are planning to use an existing telemedicine program at Southern Illinois University School of Medicine (SIUSOM) to improve kidney cancer (Kca) care in rural Illinois. This represents an example of the possible role of telemedicine in addressing healthcare disparities in rural areas/communities and provides a description of general challenges and barriers to the implementation and maintenance of such systems.

  7. Rat Kidney Cancers Determined by Dietary Ochratoxin A in the First Year of Life

    PubMed Central

    2016-01-01

    An experiment to explore renal carcinogenic efficacy of male rat exposure to dietary ochratoxin A (OTA) only in the first year of life has been made in comparison to lifetime exposure. Ten months exposure to OTA at 300 µg/kg b.w. was sufficient to cause high incidence of tumours which became apparent clinically after a latency of up to a year. As a putative model for human kidney cancer, the study shows a silent organ-specific carcinogenic effect through protracted exposure up to middle age and focused probably on very few nephrons. So far, tumourigenesis has not been recognised until in the last quarter of natural rat life, but for OTA, rat renal carcinogenesis requires both long exposure and only during the first year of normal longevity. The present findings offer an experimental framework within which systematic histopathology during tumourigenesis might show whether findings of mechanistic studies in key focal neoplasms can reasonably be applied to OTA as a putative renal carcinogen for idiopathic kidney cancer in humans. Already, the rat tumours mimic those occurring spontaneously in the Eker rat, and there is disparity between the large necessary OTA exposure in the rat and the trace amounts of OTA consumed by humans. In all such complex considerations it is important to adhere rigorously to established principles of disease epidemiology. PMID:28326281

  8. Birt-Hogg-Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome.

    PubMed

    Hasumi, Hisashi; Baba, Masaya; Hasumi, Yukiko; Furuya, Mitsuko; Yao, Masahiro

    2016-03-01

    Birt-Hogg-Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt-Hogg-Dubé syndrome patients. The folliculin gene (FLCN) that is responsible for Birt-Hogg-Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer.

  9. Secreted frizzled-related protein-5 (sFRP-5) is epigenetically downregulated and functions as a tumor suppressor in kidney cancer

    PubMed Central

    Kawakami, Kazumori; Yamamura, Soichiro; Hirata, Hiroshi; Ueno, Koji; Saini, Sharanjot; Majid, Shahana; Tanaka, Yuichiro; Kawamoto, Ken; Enokida, Hideki; Nakagawa, Masayuki; Dahiya, Rajvir

    2014-01-01

    Secreted frizzled-related protein-5 (sFRP-5) has been identified as one of the secreted antagonists that bind Wnt protein. However, the functional significance of sFRP-5 in renal cell cancer (RCC) has not been reported. We hypothesized that sFRP-5 may be epigenetically downregulated through DNA methylation and histone modification and function as a tumor suppressor gene in RCC. Using tissue microarray and real-time RT-PCR, we found that sFRP-5 was significantly downregulated in kidney cancer tissues and cell lines, respectively. DNA bisulfite sequencing of the sFRP-5 promoter region in RCC cell lines showed it to be densely methylated whereas there was few promoter methylation in normal kidney. The sFRP-5 expression was restored and the acetylation of H3 and H4 histones associated with the sFRP-5 promoter region were significantly increased after treatment with demethylation agent (5-Aza-dc) and histone deacetylase inhibitor (TSA). When RCC cells were transfected with the sFRP-5 gene, significant inhibition of anchorage independent colony formation and cell invasion were observed compared to controls. The sFRP-5 transfection also significantly induced apoptosis in RCC cells. In conclusion, this is the first report documenting that the sFRP-5 is downregulated by promoter methylation and histone acetylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells. PMID:20340127

  10. Zinc deficiency in chronic kidney disease: is there a relationship with adipose tissue and atherosclerosis?

    PubMed

    Lobo, Julie Calixto; Torres, João Paulo Machado; Fouque, Denis; Mafra, Denise

    2010-06-01

    Cardiovascular complications caused by an accelerated atherosclerotic disease consist the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). These patients present multiple atherosclerotic risk factors, considered traditional, as well as nontraditional risk factors such as inflammation and oxidative stress. These complications are also seen in obesity, in which endothelial dysfunction is one of the early stages of atherosclerosis. The impact of trace metal deficiencies on this process is not well studied in patients with CKD and in obese people, although the influence of trace elements depletion, particularly zinc (Zn), may have significant clinical implications. This brief review describes the functions of Zn as well as the respective role of this trace element in atherosclerosis processes, with a particular emphasis on obese patients with chronic kidney disease.

  11. An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

    PubMed Central

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-01-01

    Background Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Methods Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Results Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for

  12. A role of active brown adipose tissue in cancer cachexia?

    PubMed

    Beijer, Emiel; Schoenmakers, Janna; Vijgen, Guy; Kessels, Fons; Dingemans, Anne-Marie; Schrauwen, Patrick; Wouters, Miel; van Marken Lichtenbelt, Wouter; Teule, Jaap; Brans, Boudewijn

    2012-03-05

    Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT). Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and so-called brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using (18)F-fluoro- deoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  13. A role of active brown adipose tissue in cancer cachexia?

    PubMed Central

    Beijer, Emiel; Schoenmakers, Janna; Vijgen, Guy; Kessels, Fons; Dingemans, Anne-Marie; Schrauwen, Patrick; Wouters, Miel; van Marken Lichtenbelt, Wouter; Teule, Jaap; Brans, Boudewijn

    2012-01-01

    Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT). Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and so-called brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluoro- deoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity. PMID:25992201

  14. Malarial infection of female BWF1 lupus mice alters the redox state in kidney and liver tissues and confers protection against lupus nephritis.

    PubMed

    Al-Quraishy, Saleh; Abdel-Maksoud, Mostafa A; El-Amir, Azza; Abdel-Ghaffar, Fathy A; Badr, Gamal

    2013-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

  15. Prostate cancer outcome and tissue levels of metal ions

    USGS Publications Warehouse

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Michael A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUND There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome. METHODS We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case-control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se. RESULTS Patients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 ??g/g vs. 111 ??g/g; P = 0.04) and 21% lower zinc (279 ??g/g vs. 346 ??g/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 ??g/g vs. 0.439 ??g/g; 4% higher) and selenium (1.68 ??g/g vs. 1.58 ??g/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively). CONCLUSIONS There is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. Copyright ?? 2011 Wiley-Liss, Inc.

  16. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2012-05-01

    androgen-dependent cell population; activation of oncogenes; inactivation of tumor suppression genes ; and interaction between cancer cells and tumor...BODY STATEMENT OF WORK Aim 1: Identify castration-affected and/or Glipr1-regulated genes in ventral prostate (VP) tissue, epididymal white...WAT, and ASCs on days 3, 14, and 35 after castration (6–9 months). 3. Isolate RNA and perform microarray analyses to characterize genes affected by

  17. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

    PubMed

    Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

    2015-06-01

    Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

  18. Personalising pancreas cancer treatment: When tissue is the issue

    PubMed Central

    Sjoquist, Katrin M; Chin, Venessa T; Chantrill, Lorraine A; O’Connor, Chelsie; Hemmings, Chris; Chang, David K; Chou, Angela; Pajic, Marina; Johns, Amber L; Nagrial, Adnan M; Biankin, Andrew V; Yip, Desmond

    2014-01-01

    The treatment of advanced pancreatic cancer has not moved much beyond single agent gemcitabine until recently when protocols such as FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) and nab-paclitaxel-gemcitabine have demonstrated some improved outcomes. Advances in technology especially in massively parallel genome sequencing has progressed our understanding of the biology of pancreatic cancer especially the candidate signalling pathways that are involved in tumourogenesis and disease course. This has allowed identification of potentially actionable mutations that may be targeted by new biological agents. The heterogeneity of pancreatic cancer makes tumour tissue collection important with the aim of being able to personalise therapies for the individual as opposed to a one size fits all approach to treatment of the condition. This paper reviews the developments in this area of translational research and the ongoing clinical studies that will attempt to move this into the everyday oncology practice. PMID:24976722

  19. Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells.

    PubMed

    Emlet, David R; Pastor-Soler, Nuria; Marciszyn, Allison; Wen, Xiaoyan; Gomez, Hernando; Humphries, William H; Morrisroe, Seth; Volpe, Jacob K; Kellum, John A

    2017-02-01

    We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin. In human kidney tissue, strong staining of IGFBP7 was seen in the luminal brush-border region of a subset of proximal tubule cells, and TIMP-2 stained intracellularly in distal tubules. Additionally, while some tubular colocalization of both biomarkers was identified with the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, both biomarkers could also be seen alone, suggesting the possibility for differential mechanistic and/or temporal profiles of regulation of these early AKI biomarkers from known markers of injury. Last, an in vitro model of ischemia-reperfusion demonstrated enhancement of secretion of both markers early after reperfusion. This work provides a rationale for further investigation of these markers for their potential role in the pathogenesis of acute kidney injury.

  20. Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice.

    PubMed

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Góralska, Marta; Piotrowska, Joanna

    2011-01-01

    The biological action ofN-acetyl-p-aminophenol - paracetamol (acetaminophen) has been demonstrated to involve different mechanisms and is still not clear. Hydrogen sulfide (H2S) has been shown to play an important role in many physiological and pathological processes including nociception. The interaction between acetaminophen and endogenous H2S is unknown. Twenty four female CBA strain mice were administered intraperitoneal injections of N-acetyl-p-aminophenol solution: paracetemol in doses of 30 mg/kg b.w. per day (group D1, n = 8) or 100 mg/kg b.w. per day (group D2, n = 8).. The control group (n = 8) received physiological saline in portions of the same volume--0.2 ml. The measurements of tissue H2S concentration were performed with the Siegel spectrophotometric modified method. In the brain, the H2S tissue level decreased, but more significantly in the lower drug dose group. Conversely, there was a significant rise in the H2S tissue concentration in D1 and D2 groups in heart and kidney with the increase more pronounced in the group with the lower paracetamol dose. In the liver only the higher acetaminophen dose elicited a change in H2S concentration, increasing after administration of acetaminophen at 100 mg/kg. Our study demonstrates that paracetamol induces H2S tissue concentration changes in different mouse organs.

  1. Risk factors for kidney cancer in New South Wales, Australia. II. Urologic disease, hypertension, obesity, and hormonal factors.

    PubMed

    McCredie, M; Stewart, J H

    1992-07-01

    In a population-based case-control study of kidney cancer in New South Wales, Australia, data from structured interviews with 489 cases of renal cell cancer (RCC) and 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls, confirmed the link between obesity and RCC. In addition, regular consumption of 'diet' pills independently increased the risk for this cancer. A diagnosis of hypertension at least two years before interview raised the risk for RCC, and regular use of beta-blockers, a class of antihypertensive drug, independently increased the risk for RCC and CaRP (risk ratio = 1.5-1.8). No independent effect was found for use of diuretics. Additional information provided by this study includes increased risks associated with kidney injury (RCC, CaRP)--possibly attributed to recall bias--and kidney infection (CaRP), as well as a nonsignificantly raised risk linked with kidney stones (RCC, CaRP) and a significantly reduced risk for RCC in persons giving a history of lower urinary tract infection. No significant association of RCC was found with hormonal factors (age at menarche or menopause; child-bearing; regular use of oral contraceptives or estrogens; hysterectomy or oophorectomy).

  2. PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

    PubMed

    Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

    2016-02-09

    Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia.

  3. Quantification of differences in the effective atomic numbers of healthy and cancerous tissues: A discussion in the context of diagnostics and dosimetry

    SciTech Connect

    Taylor, M. L.

    2012-09-15

    Purpose: There are a range of genetic and nongenetic factors influencing the elemental composition of different human tissues. The elemental composition of cancerous tissues frequently differs from healthy tissue of the same organ, particularly in high-Z trace element concentrations. For this reason, one could suggest that this may be exploited in diagnostics and perhaps even influence dosimetry. Methods: In this work, for the first time, effective atomic numbers are computed for common cancerous and healthy tissues using a robust, energy-dependent approach between 10 keV and 100 MeV. These are then quantitatively compared within the context of diagnostics and dosimetry. Results: Differences between effective atomic numbers of healthy and diseased tissues are found to be typically less than 10%. Fibrotic tissues and calcifications of the breast exhibit substantial (tens to hundreds of percent) differences to healthy tissue. Expectedly, differences are most pronounced in the photoelectric regime and consequently most relevant for kV imaging/therapy and radionuclides with prominent low-energy peaks. Cancerous tissue of the testes and stomach have lower effective atomic numbers than corresponding healthy tissues, while diseased tissues of the other organ sites typically have higher values. Conclusions: As dose calculation approaches improve in accuracy, there may be an argument for the explicit inclusion of pathologies. This is more the case for breast, penile, prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidney cancer. The calculated data suggest dual-energy computed tomography could potentially improve lesion identification in the aforementioned organs (with the exception of testicular cancer), with most import in breast imaging. Ultimately, however, the differences are very small. It is likely that the assumption of a generic 'tissue ramp' in planning will be sufficient for the foreseeable future, and that the Z differences do not

  4. Mass Spectrometry Imaging of Kidney Tissue Sections of Rat Subjected to Unilateral Ureteral Obstruction

    PubMed Central

    Liu, Huihui; Li, Wan; He, Qing; Xue, Jinjuan; Wang, Jiyun; Xiong, Caiqiao; Pu, Xiaoping; Nie, Zongxiu

    2017-01-01

    Chronic kidney disease (CKD) poses a serious threat to the quality of human life and health with an increasing incidence worldwide. Renal fibrosis is closely related to CKD and regarded as the final common pathophysiological pathway in most cases of end-stage renal diseases. Elucidating the mechanisms underlying renal fibrosis and developing novel therapeutic strategies are of great importance. Herein, matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) based on 1, 5-diaminonaphthalene hydrochloride was applied to the rat model of unilateral ureteral obstruction (UUO) to investigate metabolic changes during renal fibrosis. Among identified endogenous compounds, twenty-one metabolites involved in metabolic networks such as glycolysis, tricarboxylic acid (TCA) cycle, ATP metabolism, fatty acids metabolism, antioxidants, and metal ions underwent relatively obvious changes after 1 and 3 weeks of UUO. Unique distribution of the metabolites was obtained, and metabolic changes of kidneys during renal fibrosis were investigated simultaneously for the first time. These findings once again highlighted the promising potential of the organic salt matrix for application in small molecule in situ MSI and in the field of biomedical research. PMID:28157191

  5. Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

    PubMed Central

    Tseng, Chin-Hsiao

    2015-01-01

    Purpose To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. Methods A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively. Results The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2

  6. Tissue Refractive Index Fluctuations Report on Cancer Development

    NASA Astrophysics Data System (ADS)

    Popescu, Gabriel

    2012-02-01

    The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it will allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin (H&E). We found that cancer progression significantly alters the tissue organization, as exhibited in our refractive index maps. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. We found that these scattering parameters are able to distinguish between two adjacent grades, which is a difficult task and relevant for determining patient treatment. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis. [4pt] [1] Z. Wang, K. Tangella, A. Balla and G. Popescu, Tissue refractive index as marker of disease, Journal of Biomedical Optics, in press).[0pt] [2] Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette and G. Popescu, Spatial light interference microscopy (SLIM), Optics Express, 19, 1016 (2011).[0pt] [3] Z. Wang, D. L. Marks, P. S. Carney, L. J. Millet, M. U. Gillette, A. Mihi, P. V. Braun, Z. Shen, S. G. Prasanth and G. Popescu, Spatial light interference tomography (SLIT), Optics Express, 19, 19907-19918 (2011

  7. Another small molecule in the oncometabolite mix: L-2-Hydroxyglutarate in kidney cancer.

    PubMed

    Shim, Eun-Hee; Sudarshan, Sunil

    2015-01-01

    Alterations in metabolism are now considered a hallmark of cancer. One of the clearest links between metabolism and malignancy are oncometabolites. To date, several putative oncometabolites with transforming properties have been identified in the context of tumors due to both gain and loss of function mutations in genes encoding enzymes of intermediary metabolism. Through an unbiased metabolomics approach, we identified elevations of the metabolite 2-hydroxyglutarate (2-HG) in the most common histology of kidney cancer that is among the most common malignancies in both men and women. Subsequent analyses demonstrate that the predominant enantiomer of 2-HG elevated in renal cancer is the L(S) form. Notably, elevations of L-2HG are due in part to loss of expression of the L-2HG dehydrogenase (L2HGDH) which normally serves as an enzyme of "metabolite repair" to keep levels of this metabolite from accumulating. Lowering L-2HG levels in RCC through re-expression of L2HGDH mitigates tumor phenotypes and reverses epigenetic alterations known to be targeted by oncometabolites. These data add to the growing body of evidence that metabolites, similarly to oncogenes and oncoproteins, can play a role in tumor development and/or progression. As such, they represent a unique opportunity to utilize these findings in the clinic setting.

  8. FGF-23 regulates CYP27B1 transcription in the kidney and in extra-renal tissues.

    PubMed

    Chanakul, Ankanee; Zhang, Martin Y H; Louw, Andrew; Armbrecht, Harvey J; Miller, Walter L; Portale, Anthony A; Perwad, Farzana

    2013-01-01

    The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to the biological active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). Renal 1α-hydroxylase activity is the principal determinant of the circulating 1,25(OH)2D concentration and enzyme activity is tightly regulated by several factors. Fibroblast growth factor-23 (FGF-23) decreases serum 1,25(OH)2D concentrations by suppressing CYP27B1 mRNA abundance in mice. In extra-renal tissues, 1α-hydroxylase is responsible for local 1,25(OH)2D synthesis, which has important paracrine actions, but whether FGF-23 regulates CYP27B1 gene expression in extra-renal tissues is unknown. We sought to determine whether FGF-23 regulates CYP27B1 transcription in the kidney and whether extra-renal tissues are target sites for FGF-23-induced suppression of CYP27B1. In HEK293 cells transfected with the human CYP27B1 promoter, FGF-23 suppressed promoter activity by 70%, and the suppressive effect was blocked by CI-1040, a specific inhibitor of extracellular signal regulated kinase 1/2. To examine CYP27B1 transcriptional activity in vivo, we crossed fgf-23 null mice with mice bearing the CYP27B1 promoter-driven luciferase transgene (1α-Luc). In the kidney of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity was increased by 3-fold compared to that in wild-type/1α-Luc mice. Intraperitoneal injection of FGF-23 suppressed renal CYP27B1 promoter activity and protein expression by 26% and 60% respectively, and the suppressive effect was blocked by PD0325901, an ERK1/2 inhibitor. These findings provide evidence that FGF-23 suppresses CYP27B1 transcription in the kidney. Furthermore, we demonstrate that in FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA abundance are increased in several extra-renal sites. In the heart of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA were 2- and 5-fold higher, respectively, than in control mice. We also

  9. Investigation of biochemical and histopathological effects of Mentha piperita L. and Mentha spicata L. on kidney tissue in rats.

    PubMed

    Akdogan, Mehmet; Kilinç, Ibrahim; Oncu, Meral; Karaoz, Erdal; Delibas, Namik

    2003-04-01

    Peppermint plants have been used as a herbal medicine for many conditions, including loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, vomiting and indigestion. This study is aimed at investigating the biochemical and histological effects of Mentha piperita L., growing in the Yenisar Bademli town of Isparta City, and Mentha spicata L., growing on the Anamas high plateau of Isparta City, on rat kidney tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Animals were divided into four experimental groups, each with 12 rats, as follows: control group (group I); 20 g/L M. piperita tea (group II); 20 g/L M. spicata tea (group III); 40 g/L M. spicata tea (group IV). The control group rats were given commercial drinking water (Hayat DANONESA water). The tea for the other groups was prepared daily and provided at all times to the rats during 30 days as drinking water. Plasma urea and creatinine levels were determined, and the levels of thiobarbituric acid reactive substance (TBARS) and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. The levels of plasma urea and creatinine were increased significantly (P < 0.0033) in groups III and IV when compared with group I. The activities of SOD and GSH-Px were decreased significantly (P < 0.0033) in group IV when compared with group I. The activities of CAT were decreased significantly in groups III and IV (P < 0.033, P < 0.0033, respectively) when compared with group I. TBARS levels were increased significantly (P < 0.0033) in groups III and IV when compared with group I. In groups II, III and IV, hydropic degeneration of tubular epithelial cells, the epithelial cells with picnotic nuclei and eosinophilic cytoplasm, tubular dilatation and enlargements in Bowman capsules were observed histologically. However, in group II histopathological changes were more slight than in groups III

  10. Regulation of aromatase expression in breast cancer tissue.

    PubMed

    Bulun, S E; Lin, Z; Zhao, H; Lu, M; Amin, S; Reierstad, S; Chen, D

    2009-02-01

    Epithelial-stromal interactions play key roles for aromatase expression and estrogen production in breast cancer tissue. Upregulated aromatase expression in breast fibroblasts increases the tissue concentration of estradiol (E2), which then activates a large number of carcinogenic genes via estrogen receptor-alpha (ERalpha) in malignant epithelial cells. This clinically pertains, since aromatase inhibitors (AIs) are the most effective hormonal treatment of ERalpha-positive breast tumors. A single gene encodes aromatase, the key enzyme in estrogen biosynthesis, the inhibition of which by an AI effectively eliminates E2 production. Since alternative promoters regulated by distinct signaling pathways control aromatase expression, it is possible to target these pathways and inhibit estrogen production in a tissue-selective fashion. We and others previously found that the majority of estrogen production in breast cancer tissue was accounted for by the aberrant activation of the proximal promoter I.3/II region. PGE(2) that is secreted in large amounts by malignant breast epithelial cells is the most potent known natural inducer of this promoter region in breast adipose fibroblasts. Signaling effectors/transcriptional regulators that mediate PGE(2) action include the activator pathways p38/CREB-ATF and JNK/jun and the inhibitory factor BRCA1 in breast adipose fibroblasts. Selective inhibition of this promoter region may treat breast cancer while permitting aromatase expression via alternative promoters in the brain and bone and thus obviate the key side effects of the current AIs. The signaling pathways that mediate the regulation of the promoter I.3/II region in undifferentiated fibroblasts in malignant breast tumors are reviewed.

  11. Texture analysis of tissues in Gleason grading of prostate cancer

    NASA Astrophysics Data System (ADS)

    Alexandratou, Eleni; Yova, Dido; Gorpas, Dimitris; Maragos, Petros; Agrogiannis, George; Kavantzas, Nikolaos

    2008-02-01

    Prostate cancer is a common malignancy among maturing men and the second leading cause of cancer death in USA. Histopathological grading of prostate cancer is based on tissue structural abnormalities. Gleason grading system is the gold standard and is based on the organization features of prostatic glands. Although Gleason score has contributed on cancer prognosis and on treatment planning, its accuracy is about 58%, with this percentage to be lower in GG2, GG3 and GG5 grading. On the other hand it is strongly affected by "inter- and intra observer variations", making the whole process very subjective. Therefore, there is need for the development of grading tools based on imaging and computer vision techniques for a more accurate prostate cancer prognosis. The aim of this paper is the development of a novel method for objective grading of biopsy specimen in order to support histopathological prognosis of the tumor. This new method is based on texture analysis techniques, and particularly on Gray Level Co-occurrence Matrix (GLCM) that estimates image properties related to second order statistics. Histopathological images of prostate cancer, from Gleason grade2 to Gleason grade 5, were acquired and subjected to image texture analysis. Thirteen texture characteristics were calculated from this matrix as they were proposed by Haralick. Using stepwise variable selection, a subset of four characteristics were selected and used for the description and classification of each image field. The selected characteristics profile was used for grading the specimen with the multiparameter statistical method of multiple logistic discrimination analysis. The subset of these characteristics provided 87% correct grading of the specimens. The addition of any of the remaining characteristics did not improve significantly the diagnostic ability of the method. This study demonstrated that texture analysis techniques could provide valuable grading decision support to the pathologists

  12. FTIR study of protective action of deferoxamine and deferiprone on the kidney tissues of aluminum loaded mice

    NASA Astrophysics Data System (ADS)

    Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

    2014-01-01

    The present study was designed to evaluate the FTIR spectra of the aluminum exposed kidney tissues and recovered by chelating agents DFO and DFP then showed significant alteration on the major biochemical constituents such as lipids, proteins and glycogen at molecular level. The significant increased in the peak area of glycogen from 0.006 ± 0.001 to 0.187 ± 0.032 may be the interruption of aluminum in the calcium metabolism and the reduced level of calcium. The peak area value of amide A significantly decreased from control (4.931 ± 1.446) to aluminum (1.234 ± 0.052), but improved by DFP and DFO + DFP from 2.658 ± 0.153 to 3.252 ± 0.070 respectively. Amide I and amide II peak area values also decreased from 1.690 ± 0.133 to 0.811 ± 0.192 and 1.158 ± 0.050 to 0.489 ± 0.047 but treated with DFP and DFO + DFP significantly improved. This result suggests an alteration in the protein profile. The absence of Olefinicdbnd CH stretching band, Cdbnd O stretching of triglycerides and ring breathing mode in the DNA bases in aluminum exposure kidney suggests an altered lipid levels. Treated with DFP and DFO + DFP mice were considerably increased in lipid peroxidative markers. Further, assessed the activities of enzymatic antioxidants and measured the levels of nonenzymatic antioxidants. Concentrations of trace elements were found by ICP-OES. Histopathology of chelating agents treated kidney showed reduced renal damage in aluminum induced mice. Thus, histopathological findings confirmed the biochemical observations of this study. This results demonstrated that FTIR spectroscopy can be successfully applied to toxicological and biotoxicology studies.

  13. Management of kidney cancer in Asia: resource-stratified guidelines from the Asian Oncology Summit 2012.

    PubMed

    Chiong, Edmund; Tay, Miah Hiang; Tan, Min Han; Kumar, Santosh; Sim, Hong Gee; Teh, Bin Tean; Umbas, Rainy; Chau, Noan Minh

    2012-11-01

    Treatment of renal-cell carcinoma has progressed over the past decade, in terms of surgical and systemic therapy. Current treatment guidelines are based on clinical evidence, but do not take into account resource limitations among different countries. These limitations, which include financial and logistical challenges and lack of skilled health-care professionals, have the greatest effect in low-income countries. This consolidated statement gives treatment recommendations for renal-cell carcinoma that are based on clinical evidence and stratified according to extent of resource availability. The statement was formulated by a panel of urologists, medical oncologists, and clinical oncologists from Asian countries, at a consensus session on kidney cancer that was held as part of the 2012 Asian Oncology Summit in Singapore. Resource levels are defined according to a four-tier system (basic, limited, enhanced, and maximum), and treatment recommendations are specified based on availability of financial, skill, and logistical resources.

  14. An intelligent knowledge mining model for kidney cancer using rough set theory.

    PubMed

    Durai, M A Saleem; Acharjya, D P; Kannan, A; Iyengar, N Ch Sriman Narayana

    2012-01-01

    Medical diagnosis processes vary in the degree to which they attempt to deal with different complicating aspects of diagnosis such as relative importance of symptoms, varied symptom pattern and the relation between diseases themselves. Rough set approach has two major advantages over the other methods. First, it can handle different types of data such as categorical, numerical etc. Secondly, it does not make any assumption like probability distribution function in stochastic modeling or membership grade function in fuzzy set theory. It involves pattern recognition through logical computational rules rather than approximating them through smooth mathematical functional forms. In this paper we use rough set theory as a data mining tool to derive useful patterns and rules for kidney cancer faulty diagnosis. In particular, the historical data of twenty five research hospitals and medical college is used for validation and the results show the practical viability of the proposed approach.

  15. Proteomic analysis of formalin-fixed prostate cancer tissue.

    PubMed

    Hood, Brian L; Darfler, Marlene M; Guiel, Thomas G; Furusato, Bungo; Lucas, David A; Ringeisen, Bradley R; Sesterhenn, Isabell A; Conrads, Thomas P; Veenstra, Timothy D; Krizman, David B

    2005-11-01

    Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

  16. Acute Kidney Injury Classified by Serum Creatinine and Urine Output in Critically Ill Cancer Patients.

    PubMed

    Córdova-Sánchez, Bertha M; Herrera-Gómez, Ángel; Ñamendys-Silva, Silvio A

    2016-01-01

    Acute kidney injury (AKI) is common in critically ill patients and is associated with higher mortality. Cancer patients are at an increased risk of AKI. Our objective was to determine the incidence of AKI in our critically ill cancer patients, using the criteria of serum creatinine (SCr) and urine output (UO) proposed by the Kidney Disease: Improving Global Outcomes (KDIGO). Methods. We performed a retrospective cohort analysis of a prospectively collected database at the intensive care unit (ICU) of the Instituto Nacional de Cancerología from January 2013 to March 2015. Results. We classified AKI according to the KDIGO definition. We included 389 patients; using the SCr criterion, 192 (49.4%) had AKI; using the UO criterion, 219 (56.3%) had AKI. Using both criteria, we diagnosed AKI in 69.4% of patients. All stages were independently associated with six-month mortality; stage 1 HR was 2.04 (95% CI 1.14-3.68, p = 0.017), stage 2 HR was 2.73 (95% CI 1.53-4.88, p = 0.001), and stage 3 HR was 4.5 (95% CI 2.25-8.02, p < 0.001). Patients who fulfilled both criteria had a higher mortality compared with patients who fulfilled just one criterion (HR 3.56, 95% CI 2.03-6.24, p < 0.001). Conclusion. We diagnosed AKI in 69.4% of patients. All AKI stages were associated with higher risk of death at six months, even for patients who fulfilled just one AKI criterion.

  17. Computer-Aided Detection of Prostate Cancer on Tissue Sections

    PubMed Central

    Peng, Yahui; Jiang, Yulei; Chuang, Shang-Tian; Yang, Ximing J.

    2009-01-01

    We report an automated computer technique for detection of prostate cancer in prostate tissue sections processed with immunohistochemistry. Two sets of color optical images were acquired from prostate tissue sections stained with a double-chromogen triple-antibody cocktail combining alpha-methylacyl-CoA racemase (AMACR), p63, and high-molecular-weight cytokeratin (HMWCK). The first set of images consisted of 20 training images (10 malignant) used for developing the computer technique and 15 test images (7 malignant) used for testing and optimizing the technique. The second set of images consisted of 299 images (114 malignant) used for evaluation of the performance of the computer technique. The computer technique identified image segments of AMACR-labeled malignant epithelial cells (red), p63-and HMWCK-labeled benign basal cells (brown), and secretory and stromal cells (blue) for identifying prostate cancer automatically. The sensitivity and specificity of the computer technique were 94% (16/17) and 94% (17/18), respectively, on the first (training and test) set of images, and 88% (79/90) and 97% (136/140), respectively, on the second (validation) set of images. If high-grade prostatic intraepithelial neoplasia (HGPIN), which is a precursor of cancer, and atypical cases were included, the sensitivity and specificity were 85% (97/114) and 89% (165/185), respectively. These results show that the novel automated computer technique can accurately identify prostatic adenocarcinoma in the triple-antibody cocktail-stained prostate sections. PMID:19417626

  18. Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

    PubMed Central

    JIANG, JIONG; DONG, LEI; QIN, BIN; SHI, HAITAO; GUO, XIAOYAN; WANG, YAN

    2016-01-01

    The present study aimed to determine the expression of Toll-like receptor 7 (TLR7) in gastric cancer tissues and investigate the effects of its activation on gastric cancer cells. Patients with gastric cancer (n=30) and patients without gastric cancer (control; n=14) who underwent gastroscopy were enrolled in the study. Gastric cancer and cancer-adjacent tissues were obtained from the patients with gastric cancer, and normal gastric epithelial tissues were obtained from the control patients. The TLR7 mRNA and protein expressions in different tissues were investigated by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The present study also determined the effects of TLR7 activation by the agonist imiquimod on TLR7 protein expression, proinflammatory cytokine secretion and viability in SGC-7901 gastric cancer cells. The mRNA and protein expression levels of TLR7 were significantly downregulated in gastric cancer tissues compared with cancer-adjacent and normal gastric epithelial tissues (P<0.01). Imiquimod significantly increased TLR7 protein expression levels, and promoted the secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 in SGC-7901 cells. Furthermore, imiquimod inhibited the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Thus, the present study identified that the expression of TLR7 was decreased in gastric cancer tissues, and TLR7 activation enhanced TLR7 expression, promoted the production of proinflammatory cytokines and inhibited the growth of gastric cancer cells. PMID:27347192

  19. Trace elements in human cancerous and healthy tissues from the same individual: A comparative study by TXRF and EDXRF

    NASA Astrophysics Data System (ADS)

    Magalhães, T.; von Bohlen, A.; Carvalho, M. L.; Becker, M.

    2006-11-01

    In this work we studied the elemental distribution of P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Ni, Se, Br, Rb, Sr, I and Pb in normal and cancerous tissues of the same individual along several contiguous thin sections (up to 10 μm thick) of each tissue. Samples of healthy and carcinoma tissues, of colon, breast and uterus on a total of 7 citizens from German population, were analysed directly by total-reflection X-ray fluorescence (TXRF). The tissues were also analysed by normal energy-dispersive X-ray fluorescence (EDXRF). An additional application was performed by studying, by the same processes, 10 carcinoma samples of 10 Portuguese citizens from: rectum, sigmoid, thyroid, kidney, larynx and lung, in order to find out a similar correlation pattern in the studied elements in carcinoma tissues. As major conclusion of this work a similar pattern for almost all the analysed tissues were obtained for all the studied samples: increased or constant levels of P, S, K, Ca, Fe and Cu, and decreased levels of Zn and Br were found in carcinoma tissues, when compared with the corresponding healthy ones. Some exceptions were found in some samples for a few numbers of elements. When comparing the results obtained for both techniques, the patterns were the same, however not always the results did coincide. This can be explained by considering that the analysed samples were not exactly the same and the differences can be explained by inhomogeneities.

  20. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  1. Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines.

    PubMed

    Mas, E; Pasqualini, E; Caillol, N; El Battari, A; Crotte, C; Lombardo, D; Sadoulet, M O

    1998-06-01

    Human pancreatic cancer is characterized by an alteration in fucose-containing surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl-Lewis. These carbohydrate determinants can be synthesized by sequential action of alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains. Therefore, the expression and the function of seven fucosyltransferases were investigated in normal and cancer pancreatic tissues and in four pancreatic carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral tissues. Interestingly, the FUT6 message was only detected in tumoral tissues. Analysis of the acceptor substrate specificity for fucosyltransferases indicated that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and alpha(1,4) Fuc-T were expressed in microsome preparations of all tissues as demonstrated by fucose incorporation into phenyl beta-d-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl-N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T activity was observed in tumoral tissues and cell lines compared to normal tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell lines. These increases correlated with an enhanced expression of Lewis a, sialyl-Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which participates in the synthesis of the sialyl-Lewis x structure, was not significantly modified in cell lines compared to normal tissues. However, the sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and BxPC-3 cell lines but was not detected on Panc-1

  2. Serum and tissue markers in colorectal cancer: State of art.

    PubMed

    Berretta, Massimiliano; Alessandrini, Lara; De Divitiis, Chiara; Nasti, Guglielmo; Lleshi, Arben; Di Francia, Raffaele; Facchini, Gaetano; Cavaliere, Carla; Buonerba, Carlo; Canzonieri, Vincenzo

    2017-03-01

    Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade, the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. bevacizumab, cetuximab, panitumab, aflibercept and regorafenib), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future, the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment. Moreover, molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumors may have different long-term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of serum and tissue markers according to the recently published English literature. This paper is an extension of the article "Biological and clinical markers in colorectal cancer: state of art" by Cappellani A published in Jan 2010.

  3. [MicroRNAs and kidneys].

    PubMed

    Stříteská, Jana; Nekvindová, Jana; Cerný, Vladimír; Palička, Vladimír

    2014-01-01

    MicroRNAs are short non-coding ribonucleic acid molecules that regulate gene expression at the post-transcriptional level thus affecting important physiological as well as pathophysiological processes in the organism, for example cell differentiation, proliferation, apoptosis, and metabolism. They are involved in pathogenesis of many diseases including cancer. Many microRNAs are tissue or organ-specific which implies their possible potential as biomarkers or maybe even therapeutical agents as documented by microRNA research interest rising exponentially during last years. Among all, microRNAs are important also for physiological function of the kidney and they are involved in various renal disorders. Today research is focused mainly on renal and urinary tract carcinogenesis, acute kidney injury, chronic renal diseases (polycystic kidney disease) or renal complications of systemic diseases such as diabetic or hypertension nephropathy and autoimmune kidney injury including acute allograft rejection after kidney transplantation. The review summarizes current information about microRNA effect on kidney development and function and also on the most common kidney diseases.

  4. Conkiss: Conformal Kidneys Sparing 3D Noncoplanar Radiotherapy Treatment for Pancreatic Cancer As an Alternative to IMRT

    SciTech Connect

    Sebestyen, Zsolt; Kovacs, Peter; Gulyban, Akos; Farkas, Robert; Bellyei, Szabolcs; Liposits, Gabor; Szigeti, Andras; Esik, Olga; Derczy, Katalin; Mangel, Laszlo

    2011-04-01

    When treating pancreatic cancer using standard (ST) 3D conformal radiotherapy (3D-CRT) beam arrangements, the kidneys often receive a higher dose than their probable tolerance limit. Our aim was to elaborate a new planning method that-similarly to IMRT-effectively spares the kidneys without compromising the target coverage. Conformal kidneys sparing (CONKISS) 5-field, noncoplanar plans were compared with ST plans for 23 consecutive patients retrospectively. Optimal beam arrangements were used consisting of a left- and right-wedged beam-pair and an anteroposterior beam inclined in the caudal direction. The wedge direction determination (WEDDE) algorithm was developed to adjust the adequate direction of wedges. The aimed organs at risk (OARs) mean dose limits were: kidney <12 Gy, liver <25 Gy, small bowels <30 Gy, and spinal cord maximum <45 Gy. Conformity and homogeneity indexes with z-test were used to evaluate and compare the different planning approaches. The mean dose to the kidneys decreased significantly (p < 0.05): left kidney 7.7 vs. 10.7 Gy, right kidney 9.1 vs. 11.7 Gy. Meanwhile the mean dose to the liver increased significantly (18.1 vs. 15.0 Gy). The changes in the conformity, homogeneity, and in the doses to other OARs were not significant. The CONKISS method balances the load among the OARs and significantly reduces the dose to the kidneys, without any significant change in the conformity and homogeneity. Using 3D-CRT the CONKISS method can be a smart alternative to IMRT to enhance the possibility of dose escalation.

  5. Tissue sodium storage: evidence for kidney-like extrarenal countercurrent systems?

    PubMed Central

    Hofmeister, Lucas H.; Perisic, Stojan; Titze, Jens

    2015-01-01

    Recent evidence from chemical analysis of tissue electrolyte and water composition has shown that body Na+ content in experimental animals is not constant, does not always readily equilibrate with water, and cannot be exclusively controlled by the renal blood purification process. Instead, large amounts of Na+ are stored in the skin and in skeletal muscle. Quantitative non-invasive detection of Na+ reservoirs with 23NaMRI suggests that this mysterious Na+ storage is not only an animal research curiosity, but also exists in humans. In clinical studies, tissue Na+ storage is closely associated with essential hypertension. In animal experiments, modulation of reservoir tissue Na+ content leads to predictable blood pressure changes. The available evidence thus suggests that the patho(?)-physiological process of Na+ storage might be even of relevance for human health and disease. PMID:25600900

  6. Proteomic analysis of tissue samples in translational breast cancer research.

    PubMed

    Gromov, Pavel; Moreira, José M A; Gromova, Irina

    2014-06-01

    In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis, and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens.

  7. [Identification of the primary lesion in a patient with concomitant breast and kidney cancer following fracture of the femur].

    PubMed

    Sato, Yasufumi; Okishiro, Masatsugu; Ishida, Tomo; Morimoto, Yoshihiro; Kusama, Hiroki; Matsusita, Katsunori; Hashimoto, Tadayoshi; Kimura, Kei; Katsura, Yoshiteru; Nitta, Kanae; Kagawa, Yoshinori; Takeno, Atsushi; Sakisaka, Hideki; Nakahira, Shin; Taniguchi, Hirokazu; Egawa, Chiyomi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki; Takatsuka, Yuichi; Oku, Kazuko; Goto, Takayoshi; Nagano, Teruaki; Nakatsuka, Shinichi

    2014-11-01

    A 61-year-old woman was diagnosed with breast cancer [T3N3cM0: Stage IIIC, estrogen receptor [ER] (+), progesterone receptor [PgR] (+), human epidermal growth factor receptor 2[HER2] (-)]at the time of initial presentation. Following diagnosis, combined modality therapy including hormone therapy and chemotherapy were initiated, but hemorrhage from the primary lesion and bone metastases were observed. Priority was given to treatment of the breast cancer, and chemotherapy was administered, after which, right mastectomy and axillary lymph node sampling were performed to assess local disease control. In addition, concurrent right kidney enucleation was performed for a renal lesion. The renal neoplasm was diagnosed as T1aN0M0, Stage I. After this intervention, treatment of the breast cancer was continued, but pain of the right femoral region developed, and bone metastasis was diagnosed on close inspection. The bone metastasis was considered to derive from the breast cancer. During hospitalization, the patient fell and broke her right femur. Open reduction and internal fixation was performed immediately, and bone metastasis of kidney cancer was diagnosed via perioperative cytodiagnosis. Pulmonary metastasis, local recurrence, and metastasis to the shoulder blade have been detected. The metastases are considered to derive from the breast cancer, for which treatment has been continued. In the case of concomitant cancers, biopsy for metastatic foci can be considered essential, whenever it can be performed safely.

  8. Confocal Microscopy of thick tissue sections: 3D Visualization of rat kidney glomeruli

    EPA Science Inventory

    Confocal laser scanning microscopy (CLSM) as a technique capable of generating serial sections of whole-mount tissue and then reassembling the computer-acquired images as a virtual 3-dimentional structure. In many ways CLSM offers an alternative to traditional sectioning approac...

  9. Confocal microscopy of thick tissue sections: 3D visualizaiton of rat kidney glomeruli

    EPA Science Inventory

    Confocal laser scanning microscopy (CLSM) as a technique capable of generating serial sections of whole-mount tissue and then reassembling the computer-acquired images as a virtual 3-dimentional structure. In many ways CLSM offers an alternative to traditional sectioning approac...

  10. Organochlorine-induced histopathology in kidney and liver tissue from Arctic fox (Vulpes lagopus).

    PubMed

    Sonne, Christian; Wolkers, Hans; Leifsson, Pall S; Jenssen, Bjørn Munro; Fuglei, Eva; Ahlstrøm, Oystein; Dietz, Rune; Kirkegaard, Maja; Muir, Derek C G; Jørgensen, Even

    2008-04-01

    The effects of persistent organic pollutants on renal and liver morphology in farmed arctic fox (Vulpes lagopus) were studied under experimental conditions. Control animals received a diet containing pork (Sus scrofa) fat with low amounts of persistent organic pollutants, while the diet of the exposed animals contained whale blubber, 'naturally' contaminated with persistent organic pollutants. Polychlorinated biphenyls (PCB) and organochlorine pesticide (OCP) concentrations in the whale blubber were 488 and 395 ng/g wet weight, respectively. Animals were sacrificed and sampled when they were at their fattest (winter) as well as their lowest body weight (summer). The results show that PCB and OCP exposure causes renal (and probably also liver) lesions in arctic foxes. The prevalence of glomerular, tubular and interstitial lesions was significantly highest in the exposed group (chi-square: all p<0.05). The frequency of liver lesions (steatosis, intravascular granulocyte accumulations, interstitial cell infiltrations, lipid granulomas, portal fibrosis and bile duct hyperplasia) were also highest in the exposed group, although not significantly (chi-square: all p>0.05). The prevalence of lesions was not significantly different between lean (winter) and fat (summer) foxes for any of the lesions (chi-square: all p>0.05). We suggest that wild arctic foxes exposed to an environmental cocktail of persistent organic pollutants, such as PCBs and OCPs, in their natural diet are at risk for developing chronic kidney and liver damage. Whether such lesions may have an impact on age and health of the animals remains uncertain.

  11. The isolated perfused kidney: an in vitro test system for evaluation of renal tissue damage induced by high-energy shockwaves sources.

    PubMed

    Bergsdorf, Th; Thüroff, S; Chaussy, Ch

    2005-09-01

    Most of our knowledge of shockwave-induced renal damage is based on animal experiments and clinical observation. We developed a tissue model using isolated porcine kidneys perfused with Berliner Blau dye in physiologic saline using a Ureteromat Perez-Castro peristaltic pump connected to the renal artery. Reproducible results were obtained under a variety of experimental conditions. Further refinements of the model might consist of interposition of tissue layers in the shockwave path or simulation of ventilatory movements.

  12. Use of a panel of novel genes for differentiating breast cancer from non-breast tissues.

    PubMed

    O'Brien, Neil; O'Donovan, Norma; Foley, Deirdre; Hill, Arnold D K; McDermott, Enda; O'Higgins, Niall; Duffy, Michael J

    2007-01-01

    Existing serum markers for breast cancer such as CA 15-3, BR 27.29 and CEA lack sensitivity and specificity. The aim of this study was to evaluate the value of new putative breast-specific markers for differentiating breast cancer from non-breast tissues. Expression of mammaglobin A (MGA), B726P, small breast epithelial mucin (SBEM) and MUC1 was measured by RT-PCR. MGA mRNA was detected in 86/162 (60%) breast cancers but in only 1/32 (3%) non-breast tissues; B726P was detected in 44/108 (41%) breast cancers but in none of 20 non-breast tissues, while SBEM was present in 52/103 (51%) breast cancers but in only 1/26 non-breast cancer tissues. In contrast to these novel markers, the established breast cancer marker MUC1 was detected in 72/99 (73%) breast cancers and in 22/32 (59%) of non-breast tissues. Combining MGA with B726P separated breast cancer from non-breast tissue with a sensitivity of 71% and a specificity of 95% while combining MGA with SBEM differentiated breast cancer from non-breast tissues with a sensitivity of 76% and a specificity of 89%. Genes such as MGA, B726P and SBEM that are expressed relatively exclusively in breast tissue are potential new markers for breast cancer.

  13. Fluorescent imaging of cancerous tissues for targeted surgery

    PubMed Central

    Bu, Lihong; Shen, Baozhong; Cheng, Zhen

    2014-01-01

    To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

  14. Waves of ratcheting cancer cells in growing tumor tissue layer

    NASA Astrophysics Data System (ADS)

    Yang, Taeseok; Kwon, Tae; Kim, Hyun; Lee, Kyoung; CenterCell Dynamics Team

    2015-03-01

    Over many years researchers have shown that the mechanical forces generated by, and acting on, tissues influence the way they grow, develop and migrate. As for cancer research goes, understanding the role of these forces may even be as influential as deciphering the relevant genetic and molecular basis. Often the key issues in the field of cancer mechanics are to understand the interplay of mechanics and chemistry. In this study, we discuss very intriguing population density waves observed in slowly proliferating of tumor cell layers. The temporal periods are around 4 hr and their wavelength is in the order of 1 mm. Tumor cell layer, which is initially plated in a small disk area, expands as a band of tumor cells is ``ratcheting'' in concert in radially outward direction. By adding Cytochalasin D and Latrunculin B, an inhibitor of actin polymerization, or Mytomycin, a chemotherapeutic agent, we could halt and modulate the wave activities reversibly. The observed waves are visually quite similar to those of chemotaxing dictyostelium discodium amoeba population, which are driven by nonlinear chemical reaction-diffusion waves of cAMP. So far, we have not been able to show any relevant chemo-attractants inducing the collective behavior of these tumor cells. Researchers have been investigating how forces from both within and outside developing cancer cells interact in intricate feedback loops. This work reports the example of periodic density waves of tumor cells with an explanation purely based on nonlinear mechanics.

  15. Impact of Transient and Persistent Acute Kidney Injury on Chronic Kidney Disease Progression and Mortality after Gastric Surgery for Gastric Cancer

    PubMed Central

    Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Kweon, Sun-Seog; Kim, Soo Wan

    2016-01-01

    Acute kidney injury (AKI) is common after gastric surgery for gastric cancer and associated with adverse outcomes. However, the impact of transient or persistent AKI on clinical outcomes after gastric surgery for gastric cancer has not been described. We performed a retrospective study of 4,886 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2012. AKI patients were classified as transient and persistent AKI based on the return of serum creatinine to the level indicating no AKI within 7 days. Our outcomes included occurrence of new-onset chronic kidney disease (CKD) and mortality 1 year after gastric surgery. AKI occurred in 638 (13.1%) after gastric surgery. Transient AKI was documented in 574 (90%). Use of diuretics and contrast agents was a common risk factor for persistent and transient AKI. Length of intensive care unit (ICU) and hospital stay, and ICU admission rate were higher in patients with transient AKI than in those without AKI. Although patients with persistent AKI had a higher new-onset CKD 1 year after gastric surgery after adjusting for multiple covariates, transient AKI was not associated with new-onset CKD. The 1-year mortality rates were significantly higher in patients with transient and persistent AKI. Not only persistent AKI but transient AKI is associated with increased risk of hospital complications and a significantly higher risk of long-term mortality than patients without AKI after gastric surgery. Moreover, persistent AKI, but not transient AKI, is associated with CKD progression at 1 year. PMID:27936153

  16. Ectopic Pelvic Kidney Mimicking Sacral Metastasis on Post-Therapy Iodine-131 Scan of a Thyroid Cancer Patient

    PubMed Central

    Soyluoğlu Demir, Selin; Ege Aktaş, Gül; Polat, Ahmet; Sarıkaya, Ali

    2017-01-01

    A 25-year-old woman had total thyroidectomy and iodine-131 ablation therapy for papillary thyroid carcinoma. Whole body imaging on the 7th day of therapeutic activity demonstrated radioiodine uptake in the remnant tissue and intense heterogeneous uptake at the sacral region prominently in the posterior image. Initial interpretation was suspicious for sacral metastasis. Technetium-99m-methylene diphosphonate bone scan demonstrated normal bone uptake and the absence of left kidney. On blood-pool phase of bone scan, the absence of left renal activity and an extra area of uptake in the sacral region suggestive of pelvic kidney were noticed. Magnetic resonance imaging scan confirmed the ectopic pelvic kidney overlying the sacrum. PMID:28291010

  17. Palliation of Soft Tissue Cancer Pain With Radiofrequency Ablation

    PubMed Central

    Locklin, Julia K.; Mannes, Andrew; Berger, Ann; Wood, Bradford J.

    2008-01-01

    The purpose of this study was to analyze the feasibility, safety, and efficacy of radiofrequency ablation (RFA) to treat pain from soft tissue neoplasms. RFA was performed on 15 painful soft tissue tumors in 14 patients. Tumors varied in histology and location and ranged in size from 2 to 20 cm. Patient pain was assessed using the Brief Pain Inventory (BPI) at baseline and 1 day, 1 week, 1 month, and 3 months post RFA. All patients had unresectable tumors or were poor operative candidates whose pain was poorly controlled by conventional treatment methods. BPI scores were divided into two categories: pain severity and interference of pain. Although not all scores were statistically significant, all mean scores trended down with increased time post ablation. Based on these outcomes, RFA appears to be a low-risk and well-tolerated procedure for pain palliation in patients with unresectable, painful soft tissue neoplasms. RFA is effective for short-term local pain control and may provide another option for failed chemotherapy or radiation therapy in patients with cancer. However, pain may transiently worsen, and relief is often temporary. PMID:15524075

  18. A Minimum Spanning Forest Based Hyperspectral Image Classification Method for Cancerous Tissue Detection.

    PubMed

    Pike, Robert; Patton, Samuel K; Lu, Guolan; Halig, Luma V; Wang, Dongsheng; Chen, Zhuo Georgia; Fei, Baowei

    2014-03-21

    Hyperspectral imaging is a developing modality for cancer detection. The rich information associated with hyperspectral images allow for the examination between cancerous and healthy tissue. This study focuses on a new method that incorporates support vector machines into a minimum spanning forest algorithm for differentiating cancerous tissue from normal tissue. Spectral information was gathered to test the algorithm. Animal experiments were performed and hyperspectral images were acquired from tumor-bearing mice. In vivo imaging experimental results demonstrate the applicability of the proposed classification method for cancer tissue classification on hyperspectral images.

  19. A Minimum Spanning Forest Based Hyperspectral Image Classification Method for Cancerous Tissue Detection

    PubMed Central

    Pike, Robert; Patton, Samuel K.; Lu, Guolan; Halig, Luma V.; Wang, Dongsheng; Chen, Zhuo Georgia; Fei, Baowei

    2014-01-01

    Hyperspectral imaging is a developing modality for cancer detection. The rich information associated with hyperspectral images allow for the examination between cancerous and healthy tissue. This study focuses on a new method that incorporates support vector machines into a minimum spanning forest algorithm for differentiating cancerous tissue from normal tissue. Spectral information was gathered to test the algorithm. Animal experiments were performed and hyperspectral images were acquired from tumor-bearing mice. In vivo imaging experimental results demonstrate the applicability of the proposed classification method for cancer tissue classification on hyperspectral images. PMID:25426272

  20. Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.

    PubMed

    Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona; Hansen, Mie R; Stæhr, Mette; Svenningsen, Per; Jacobsen, Ib A; Hansen, Pernille B; Thuesen, Anne D; Toft, Anja; Hinrichs, Gitte R; Bistrup, Claus; Jensen, Boye L

    2017-02-24

    The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS(-/-)) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS(-/-) and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS(-/-) mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.

  1. Cancer detection using NIR elastic light scattering and tissue fluorescence imaging

    SciTech Connect

    Demos, S G; Staggs, M; Radousky, H B; Gandour-Edwards, R; deVere White, R

    2000-12-04

    Near infrared imaging using elastic light scattering and tissue fluorescence under long-wavelength laser excitation are explored for cancer detection. Various types of normal and malignant human tissue samples were utilized in this investigation.

  2. Direct infusion mass spectrometry or liquid chromatography mass spectrometry for human metabonomics? A serum metabonomic study of kidney cancer.

    PubMed

    Lin, Lin; Yu, Quan; Yan, Xiaomei; Hang, Wei; Zheng, Jiaxin; Xing, Jinchun; Huang, Benli

    2010-11-01

    Serum samples from kidney cancer patients and healthy controls were analyzed by both direct infusion mass spectrometry (DIMS) and liquid chromatography-mass spectrometry (LC-MS) with a high resolution ESI-Q-TOFMS. The classification and biomarker discovery capacities of the two methods were compared, and MS/MS experiments were carried out to identify potential biomarkers. DIMS had comparable classification and prediction capabilities to LC-MS but consumed only ~5% of the analysis time. With regard to biomarker discovery, twenty-three variables were found as potential biomarkers by DIMS, and 48 variables were obtained by LC-MS. DIMS is recommended to be a fast diagnostic method for kidney cancer, while LC-MS is necessary when comprehensive screening of biomarkers is required.

  3. Metabolic substrate utilization by tumour and host tissues in cancer cachexia.

    PubMed Central

    Mulligan, H D; Tisdale, M J

    1991-01-01

    Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3-hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3-hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state. PMID:1859359

  4. Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

    2013-01-01

    The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

  5. FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis

    PubMed Central

    Atsuta, Yuji; Takahashi, Yoshiko

    2015-01-01

    When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static (‘rear’) cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth. PMID:26130757

  6. Time trend and age-period-cohort effect on kidney cancer mortality in Europe, 1981–2000

    PubMed Central

    Pérez-Farinós, Napoleón; López-Abente, Gonzalo; Pastor-Barriuso, Roberto

    2006-01-01

    Background The incorporation of diagnostic and therapeutic improvements, as well as the different smoking patterns, may have had an influence on the observed variability in renal cancer mortality across Europe. This study examined time trends in kidney cancer mortality in fourteen European countries during the last two decades of the 20th century. Methods Kidney cancer deaths and population estimates for each country during the period 1981–2000 were drawn from the World Health Organization Mortality Database. Age- and period-adjusted mortality rates, as well as annual percentage changes in age-adjusted mortality rates, were calculated for each country and geographical region. Log-linear Poisson models were also fitted to study the effect of age, death period, and birth cohort on kidney cancer mortality rates within each country. Results For men, the overall standardized kidney cancer mortality rates in the eastern, western, and northern European countries were 20, 25, and 53% higher than those for the southern European countries, respectively. However, age-adjusted mortality rates showed a significant annual decrease of -0.7% in the north of Europe, a moderate rise of 0.7% in the west, and substantial increases of 1.4% in the south and 2.0% in the east. This trend was similar among women, but with lower mortality rates. Age-period-cohort models showed three different birth-cohort patterns for both men and women: a decrease in mortality trend for those generations born after 1920 in the Nordic countries, a similar but lagged decline for cohorts born after 1930 in western and southern European countries, and a continuous increase throughout all birth cohorts in eastern Europe. Similar but more heterogeneous regional patterns were observed for period effects. Conclusion Kidney cancer mortality trends in Europe showed a clear north-south pattern, with high rates on a downward trend in the north, intermediate rates on a more marked rising trend in the east than in the

  7. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    PubMed

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency.

  8. Sunitinib Malate and Bevacizumab in Treating Patients With Kidney Cancer or Advanced Solid Malignancies

    ClinicalTrials.gov

    2014-04-01

    Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage I Renal Cell Cancer; Stage II Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  9. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis

    PubMed Central

    Honore, Patrick M.; Nguyen, H. Bryant; Gong, Michelle; Chawla, Lakhmir S.; Bagshaw, Sean M.; Artigas, Antonio; Shi, Jing; Joannes-Boyau, Olivier; Vincent, Jean-Louis

    2016-01-01

    Objectives: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. Method: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2–3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)2/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Results: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin

  10. DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer

    PubMed Central

    Teschendorff, Andrew E; Gao, Yang; Jones, Allison; Ruebner, Matthias; Beckmann, Matthias W.; Wachter, David L.; Fasching, Peter A.; Widschwendter, Martin

    2016-01-01

    Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis. PMID:26823093

  11. DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer.

    PubMed

    Teschendorff, Andrew E; Gao, Yang; Jones, Allison; Ruebner, Matthias; Beckmann, Matthias W; Wachter, David L; Fasching, Peter A; Widschwendter, Martin

    2016-01-29

    Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis.

  12. Sonohistology - ultrasonic tissue characterization for prostate cancer diagnostics.

    PubMed

    Scheipers, U; König, K; Sommerfeld, H-J; Garcia-Schürmann, M; Senge, T; Ermert, H

    2008-01-01

    A computer-aided diagnostic system for imaging prostate cancer has been developed in order to supplement today's conventional methods for the early detection of prostate carcinoma. The system is based on analysis of the spectral content of radiofrequency ultrasonic echo data in combination with evaluations of textural, contextual, morphological and clinical features in a multiparameter approach. A state-of-the-art, non-linear classifier, the so-called adaptive network-based fuzzy inference system, is used for higher-order classification of the underlying tissue-describing parameters. The system has been evaluated on radio-frequency ultrasound data originating from 100 patients using histological specimens obtained after prostatectomy as the gold standard. Leave-one-out cross-validation over patient data sets results in areas under the ROC curve of 0.86 +/- 0.01 for hypoechoic and hyperechoic tumors and of 0.84 +/- 0.02 for isoechoic tumors, respectively.

  13. Functional significance of Wnt inhibitory factor-1 gene in kidney cancer.

    PubMed

    Kawakami, Kazumori; Hirata, Hiroshi; Yamamura, Soichiro; Kikuno, Nobuyuki; Saini, Sharanjot; Majid, Shahana; Tanaka, Yuichiro; Kawamoto, Ken; Enokida, Hideki; Nakagawa, Masayuki; Dahiya, Rajvir

    2009-11-15

    Wnt inhibitory factor-1 (WIF-1) has been identified as one of the secreted antagonists that bind Wnt protein. WIF-1 has been described as a tumor suppressor in various types of cancer. However, the molecular function of WIF-1 gene has never been examined in human renal cell carcinoma (RCC). Therefore, we hypothesized that WIF-1 functions as a tumor suppressor gene and overexpression of this gene may induce apoptosis and inhibit tumor growth in RCC cells. Immunohistochemistry and real-time reverse transcription-PCR revealed that WIF-1 was significantly downregulated in RCC samples and RCC cell lines, respectively. Bisulfite sequencing of the WIF-1 promoter region in RCC cell lines showed it to be densely methylated, whereas there was no methylation of WIF-1 promoter in normal kidney. Significant inhibition of cell growth and colony formation in WIF-1-transfected cells compared with controls were observed. WIF-1 transfection significantly induced apoptosis and suppressed in vivo tumor growth. Also, Wnt signaling activity and beta-catenin expression were reduced by WIF-1 transfection. In conclusion, this is the first report documenting that the WIF-1 is downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells.

  14. Clinic application of tissue engineered bronchus for lung cancer treatment

    PubMed Central

    Liu, Ruijun; Chen, Xiaoke; Wu, Jingxiang; Pan, Yinggen; Lu, Shun; Weder, Walter; Luo, Qingquan

    2017-01-01

    Background Delayed revascularization process and substitute infection remain to be key challenges in tissue engineered (TE) airway reconstruction. We propose an “in-vivo bioreactor” design, defined as an implanted TE substitutes perfused with an intra-scaffold medium flow created by an extracorporeal portable pump system for in situ organ regeneration. The perfusate keeps pre-seeded cells alive before revascularization. Meanwhile the antibiotic inside the perfusate controls topical infection. Methods A stage IIIA squamous lung cancer patient received a 5-cm TE airway substitute, bridging left basal segment bronchus to carina, with the in-vivo bioreactor design to avoid left pneumonectomy. Continuous intra-scaffold Ringer’s-gentamicin perfusion lasted for 1 month, together with orthotopic peripheral total nucleated cells (TNCs) injection twice a week. Results The patient recovered uneventfully. Bronchoscopy follow-up confirmed complete revascularization and reepithelialization four months postoperatively. Perfusate waste test demonstrated various revascularization growth factors secreted by TNCs. The patient received two cycles of chemotherapy and 30 Gy radiotherapy thereafter without complications related to the TE substitute. Conclusions In-vivo bioreactor design combines the traditionally separated in vitro 3D cell-scaffold culture system and the in vivo regenerative processes associated with TE substitutes, while treating the recipients as bioreactors for their own TE prostheses. This design can be applied clinically. We also proved for the first time that TE airway substitute is able to tolerate chemo-radiotherapy and suitable to be used in cancer treatment. PMID:28203403

  15. Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease

    PubMed Central

    Belmonte, Julio M.; Clendenon, Sherry G.; Oliveira, Guilherme M.; Swat, Maciej H.; Greene, Evan V.; Jeyaraman, Srividhya; Glazier, James A.; Bacallao, Robert L.

    2016-01-01

    In autosomal dominant polycystic kidney disease (ADPKD), cysts accumulate and progressively impair renal function. Mutations in PKD1 and PKD2 genes are causally linked to ADPKD, but how these mutations drive cell behaviors that underlie ADPKD pathogenesis is unknown. Human ADPKD cysts frequently express cadherin-8 (cad8), and expression of cad8 ectopically in vitro suffices to initiate cystogenesis. To explore cell behavioral mechanisms of cad8-driven cyst initiation, we developed a virtual-tissue computer model. Our simulations predicted that either reduced cell–cell adhesion or reduced contact inhibition of proliferation triggers cyst induction. To reproduce the full range of cyst morphologies observed in vivo, changes in both cell adhesion and proliferation are required. However, only loss-of-adhesion simulations produced morphologies matching in vitro cad8-induced cysts. Conversely, the saccular cysts described by others arise predominantly by decreased contact inhibition, that is, increased proliferation. In vitro experiments confirmed that cell–cell adhesion was reduced and proliferation was increased by ectopic cad8 expression. We conclude that adhesion loss due to cadherin type switching in ADPKD suffices to drive cystogenesis. Thus, control of cadherin type switching provides a new target for therapeutic intervention. PMID:27193300

  16. Supersonic shear wave elastography of in vivo pig kidney: influence of blood pressure, urinary pressure and tissue anisotropy.

    PubMed

    Gennisson, Jean-Luc; Grenier, Nicolas; Combe, Christian; Tanter, Mickaël

    2012-09-01

    The in vivo influence of renal anisotropy and of urinary and vascular pressure on elasticity values using ultrasonic supersonic shear wave elastography was studied in pigs. Experiments were conducted in agreement with the European Commission guidelines and directives of the French Research Ministry. Six kidneys in three pigs were studied in vivo. Elasticity of renal cortex and medulla was quantified through the shear modulus (μ) by using the supersonic shear imaging technique with an 8 MHz linear ultrasound probe. All measurements were done peroperatively both in the axis and perpendicular to the main axis of pyramids, in normal condition, after progressive increase of urinary pressure, and after renal artery and renal vein ligation. In normal conditions, cortical (C) and medullary (M) elasticity values were always higher when acquisitions were realized with the ultrasound main axis perpendicular to main pyramid axis (C(//): 7.7 ± 2.3 kPa; M(//): 8.7 ± 2.5 kPa) than parallel (C(⊥): 6.9 ± 1.4 kPa; M(⊥): 6.6 ± 2.3 kPa), demonstrating an effect of renal anisotropy. In renal cortex, two bands were separated, inner cortex showing higher elasticity values (IC(⊥): 8.1 ± 1.9 kPa) than outer cortex (OC(⊥): 6.9 ± 1.4 kPa). Renal artery and renal vein ligation induced a decrease and an increase of elasticity respectively. Parenchymal elasticity increased linearly with elevation of urinary pressure. Intrarenal elasticity values vary with tissue anisotropy and, with vascular and urinary pressure levels. These parameters have to be taken into account for interpretation of tissue changes. Separation of outer and inner cortex could be attributable to perfusion differences.

  17. Solitary Kidney

    MedlinePlus

    ... How They Work Kidney Disease A-Z Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

  18. Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study

    PubMed Central

    Yang, Yi-Long; Liu, Li; Li, Meng-Yao; Shi, Meng; Wang, Lie

    2016-01-01

    Purpose Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD) and the associated psychosocial factors among bladder/kidney cancer patients. Methods A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early-stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience) anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates. Results The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (β) sequence, patient’s perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01). Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01). Conclusions The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese

  19. Molecular Imaging of the Kidneys

    PubMed Central

    Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

    2010-01-01

    Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer

  20. Optical redox imaging indices discriminate human breast cancer from normal tissues

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-11-01

    Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (p<0.05). The redox ratio Fp/(NADH + Fp) was ˜27% higher in the cancerous tissues (p<0.05). Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients.

  1. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage

    PubMed Central

    Vermeulen Windsant, Iris C.; de Wit, Norbert C. J.; Sertorio, Jonas T. C.; van Bijnen, Annemarie A.; Ganushchak, Yuri M.; Heijmans, John H.; Tanus-Santos, Jose E.; Jacobs, Michael J.; Maessen, Jos G.; Buurman, Wim A.

    2014-01-01

    Introduction: Acute kidney injury (AKI) and intestinal injury negatively impact patient outcome after cardiac surgery. Enhanced nitric oxide (NO) consumption due to intraoperative intravascular hemolysis, may play an important role in this setting. This study investigated the impact of hemolysis on plasma NO consumption, AKI, and intestinal tissue damage, after cardiac surgery. Methods: Hemolysis (by plasma extracellular (free) hemoglobin; fHb), plasma NO-consumption, plasma fHb-binding capacity by haptoglobin (Hp), renal tubular injury (using urinary N-Acetyl-β-D-glucosaminidase; NAG), intestinal mucosal injury (through plasma intestinal fatty acid binding protein; IFABP), and AKI were studied in patients undergoing off-pump cardiac surgery (OPCAB, N = 7), on-pump coronary artery bypass grafting (CABG, N = 30), or combined CABG and valve surgery (CABG+Valve, N = 30). Results: FHb plasma levels and NO-consumption significantly increased, while plasma Hp concentrations significantly decreased in CABG and CABG+Valve patients (p < 0.0001) during surgery. The extent of hemolysis and NO-consumption correlated significantly (r2 = 0.75, p < 0.0001). Also, NAG and IFABP increased in both groups (p < 0.0001, and p < 0.001, respectively), and both were significantly associated with hemolysis (Rs = 0.70, p < 0.0001, and Rs = 0.26, p = 0.04, respectively) and NO-consumption (Rs = 0.55, p = 0.002, and Rs = 0.41, p = 0.03, respectively), also after multivariable logistic regression analysis. OPCAB patients did not show increased fHb, NO-consumption, NAG, or IFABP levels. Patients suffering from AKI (N = 9, 13.4%) displayed significantly higher fHb and NAG levels already during surgery compared to non-AKI patients. Conclusions: Hemolysis appears to be an important contributor to postoperative kidney injury and intestinal mucosal damage, potentially by limiting NO-bioavailability. This observation offers a novel diagnostic and therapeutic target to improve patient outcome after

  2. Metabolism of [1-14C]glyoxylate, [1-14C]-glycollate, [1-14C]glycine and [2-14C]-glycine by homogenates of kidney and liver tissue from hyperoxaluric and control subjects

    PubMed Central

    Dean, Betty M.; Watts, R. W. E.; Westwick, Wendy J.

    1967-01-01

    1. The metabolism of [1-14C]glyoxylate to carbon dioxide, glycine, oxalate, serine, formate and glycollate was investigated in hyperoxaluric and control subjects' kidney and liver tissue in vitro. 2. Only glycine and carbon dioxide became significantly labelled with 14C, and this was less in the hyperoxaluric patients' kidney tissue than in the control tissue. 3. Liver did not show this difference. 4. The metabolism of [1-14C]glycollate was also studied in the liver tissue; glyoxylate formation was demonstrated and the formation of 14CO2 from this substrate was likewise unimpaired in the hyperoxaluric patients' liver tissue in these experiments. 5. Glycine was not metabolized by human kidney, liver or blood cells under the conditions used. 6. These observations show that glyoxylate metabolism by the kidney is impaired in primary hyperoxaluria. PMID:5584012

  3. T 1 Relaxation Measurement of Ex-Vivo Breast Cancer Tissues at Ultralow Magnetic Fields

    PubMed Central

    Lee, Seong-Joo; Shim, Jeong Hyun; Kim, Kiwoong; Hwang, Seong-min; Yu, Kwon Kyu; Lim, Sanghyun; Han, Jae Ho; Yim, Hyunee; Kim, Jang-Hee; Jung, Yong Sik; Kim, Ku Sang

    2015-01-01

    We investigated T1 relaxations of ex-vivo cancer tissues at low magnetic fields in order to check the possibility of achieving a T1 contrast higher than those obtained at high fields. The T1 relaxations of fifteen pairs (normal and cancerous) of breast tissue samples were measured at three magnetic fields, 37, 62, and 122 μT, using our superconducting quantum interference device-based ultralow field nuclear magnetic resonance setup, optimally developed for ex-vivo tissue studies. A signal reconstruction based on Bayesian statistics for noise reduction was exploited to overcome the low signal-to-noise ratio. The ductal and lobular-type tissues did not exhibit meaningful T1 contrast values between normal and cancerous tissues at the three different fields. On the other hand, an enhanced T1 contrast was obtained for the mucinous cancer tissue. PMID:25705658

  4. Ex vivo label-free microscopy of head and neck cancer patient tissues

    NASA Astrophysics Data System (ADS)

    Shah, Amy T.; Skala, Melissa C.

    2015-03-01

    Standard methods to characterize patient tissue rely on histology. This technique provides only anatomical information, so complementary imaging methods could provide beneficial phenotypic information. Cancer cells exhibit altered metabolism, and metabolic imaging could be applied to better understand cancer tissue. This study applies redox ratio, fluorescence lifetime, and second harmonic generation (SHG) imaging to ex vivo tissue from head and neck cancer patients. This high-resolution imaging technique has unique advantages of utilizing intrinsic tissue contrast, which eliminates the need for sample processing or staining, and multiphoton microscopy, which provides depth sectioning in intact tissue. This study demonstrates feasibility of these measurements in patient tissue from multiple anatomical sites and carcinoma types of head and neck cancer.

  5. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

    Templeton, Zach S.; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V.; Tamaresis, John S.; Bachmann, Michael H.; Lee, Kitty; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

    2015-01-01

    BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. PMID:26696367

  6. Tissue-specific alterations of PRL-1 and PRL-2 expression in cancer.

    PubMed

    Dumaual, Carmen M; Sandusky, George E; Soo, Han Weng; Werner, Sean R; Crowell, Pamela L; Randall, Stephen K

    2012-01-01

    The PRL-1 and PRL-2 phosphatases have been implicated as oncogenic, however the involvement of these molecules in human neoplasms is not well understood. To increase understanding of the role PRL-1 and PRL-2 play in the neoplastic process, in situ hybridization was used to examine PRL-1 and PRL-2 mRNA expression in 285 normal, benign, and malignant human tissues of diverse origin. Immunohistochemical analysis was performed on a subset of these. PRL-1 and PRL-2 mRNA expression was also assessed in a small set of samples from a variety of diseases other than cancer. Where possible, associations with clinicopathological characteristics were evaluated. Alterations in PRL-1 or -2 expression were a frequent event, but the nature of those alterations was highly tumor type specific. PRL-1 was significantly overexpressed in 100% of hepatocellular and gastric carcinomas, but significantly under-expressed in 100% of ovarian, 80% of breast, and 75% of lung tumors. PRL-2 expression was significantly increased in 100% of hepatocellular carcinomas, yet significantly downregulated in 54% of kidney carcinomas. PRL-1 expression was correlated to patient gender in the bladder and to patient age in the brain and skeletal muscle. PRL-1 expression was also associated with tumor grade in the prostate, ovary, and uterus. These results suggest a pleiotropic role for PRL-1 and PRL-2 in the neoplastic process. These molecules may associate with tumor progression and serve as clinical markers of tumor aggressiveness in some tissues, but be involved in inhibition of tumor formation or growth in others.

  7. In experimental chronic kidney disease or cancer, parathyroid hormone is a novel mediator of cachexia.

    PubMed

    Wyatt, Christina M; Mitch, William E

    2016-05-01

    Hyperparathyroidism plays a central role in the disordered bone mineral metabolism of chronic kidney disease, and has been associated with increased cardiovascular morbidity and mortality in that setting. A recent study suggests a novel role for parathyroid hormone and its receptor in muscle wasting and cachexia occurring in advanced chronic kidney disease.

  8. Determination of optical coefficients and fractal dimensional parameters of cancerous and normal prostate tissues.

    PubMed

    Pu, Yang; Wang, Wubao; Al-Rubaiee, Mohammad; Gayen, Swapan Kumar; Xu, Min

    2012-07-01

    Optical extinction and diffuse reflection spectra of cancerous and normal prostate tissues in the 750 to 860 nm spectral range were measured. Optical extinction measurements using thin ex vivo prostate tissue samples were used to determine the scattering coefficient (μ(s)), while diffuse reflection measurements using thick prostate tissue samples were used to extract the absorption coefficient (μ(a)) and the reduced scattering coefficient (μ'(s)). The anisotropy factor (g) was obtained using the extracted values of μ(s) and μ'(s). The values of fractal dimension (D(f)) of cancerous and normal prostate tissues were obtained by fitting to the wavelength dependence of μ'(s). The number of scattering particles contributing to μ(s) as a function of particle size and the cutoff diameter d(max) as a function of g were investigated using the fractal soft tissue model and Mie theory. Results show that d(max) of the normal tissue is larger than that of the cancerous tissue. The cutoff diameter d(max) is observed to agree with the nuclear size for the normal tissues and the nucleolar size for the cancerous tissues. Transmission spectral polarization imaging measurements were performed that could distinguish the cancerous prostate tissue samples from the normal tissue samples based on the differences between their absorption and scattering parameters.

  9. Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues

    NASA Astrophysics Data System (ADS)

    Yermolenko, Sergey; Ivashko, Pavlo; Gruia, Ion; Gruia, Maria; Peresunko, Olexander; Zelinska, Natalia; Voloshynskyi, Dmytro; Fedoruk, Olexander; Zimnyakov, Dmitry; Alonova, Marina

    2015-02-01

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  10. The role of cryosurgery in palliative care for cancer.

    PubMed

    Niu, Lizhi; Zhou, Liang; Xu, Kecheng; Mu, Feng

    2013-01-01

    Cryosurgery as one of the ablation methods is performed intraoperatively, laparoscopically or percutaneously, is especially adapted for ablation of prostate cancer, liver cancer, lung cancer, kidney cancer, breast cancer, benign fibroadenomas of breast, uterine tumors and neoplasms of soft tissue. Compared with other ablation methods (such as radiofrequency and microwave ablation), cryoablation has several advantages on therapeutic efficacy, imaging guidance and modality.

  11. Local tumour ablation for localized kidney cancer: Practice patterns in Canada

    PubMed Central

    Trudeau, Vincent; Larcher, Alessandro; Dell’Oglio, Paolo; Boehm, Katharina; Bishr, Mohamed; Karakiewicz, Pierre I.

    2015-01-01

    Introduction: Local tumour ablation (LTA) is a recommended option for the treatment of localized kidney cancer in nonsurgical candidates. We performed a survey to describe the practice patterns of this procedure in Canada. Methods: An electronic survey was sent by email to all urologists registered to the Canadian Urological Association (CUA). Urologists were queried about general demographic information, LTA availability at their institution (and reasons for non-availability, if it was the case), as well as the type and context of LTA use. Results: Overall, 103 individual responses were obtained (response rate of 19.5%). Of those, 58 (56.3%) had access to LTA at their institution. Urologists who had access to LTA were more likely to work at an academic institution (69 vs. 16%, p<0.001). Among individuals who did not use LTA, the main reasons were lack of staff, such as radiologists, who can assist and/or perform the procedure (64%); and lack of expertise with the procedure (62%). Among urologists who had access to LTA, percutaneous radiofrequency and cryoablation were the most commonly used (72% and 21%, respectively); however, urologists were rarely involved in those procedures (12%). Conclusions: In this national survey, we found that a significant proportion of Canadian urologists did not have access to LTA. We also found that when LTA was performed, urologists were rarely involved in the procedures. Those findings represent significant areas for improvement in the access to LTA. The conclusions of this study are limited by the low response rate. PMID:26788232

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

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

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

  13. Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia.

    PubMed

    Iannacone, Michelle R; Sinnya, Sudipta; Pandeya, Nirmala; Isbel, Nikky; Campbell, Scott; Fawcett, Jonathan; Soyer, Peter H; Ferguson, Lisa; Davis, Marcia; Whiteman, David C; Green, Adèle C

    2016-07-01

    The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

  14. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    SciTech Connect

    Nichols, Romaine C.; Huh, Soon N.; Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K.; Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng; Regine, William F.

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  15. An attempt to diagnose cancer by PIXE

    NASA Astrophysics Data System (ADS)

    Uda, M.; Maeda, K.; Sasa, Y.; Kusuyama, H.; Yokode, Y.

    1987-03-01

    PIXE is suitable especially for trace elemental analysis for atoms with high atomic numbers, which are contained in matrices composed mainly of light elements such as biological materials. An attempt has been made to distinguish elemental concentrations of cancer tissues from those of normal ones. Kidney, testis and urinary bladder cancer tissues were examined by PIXE. Key elements to diagnose these cancers were Ca, Ti, Cr, Fe and Zn. Enrichment of Fe and Ti, and deficiency of Zn could be seen in the kidney cancer. An opposite tendency was observed in the testicular cancer. Imbalance of these elemental concentrations in characteristic organs might give us a possibility for cancer diagnosis.

  16. Is chronic kidney disease an adverse factor in lung cancer clinical outcome? A propensity score matching study

    PubMed Central

    Lu, Ming‐Shian; Chen, Miao‐Fen; Lin, Chien‐Chao; Tseng, Yuan‐Hsi; Huang, Yao‐Kuang; Liu, Hui‐Ping

    2017-01-01

    Background Comorbidity has a great impact on lung cancer survival. Renal function status may affect treatment decisions and drug toxicity. The survival outcome in lung cancer patients with coexisting chronic kidney disease (CKD) has not been fully evaluated. We hypothesized that CKD is an independent risk factor for mortality in patients with lung cancer. Methods A retrospective, propensity‐matched study of 434 patients diagnosed between June 2004 and May 2012 was conducted. CKD was defined as estimated glomerular filtration rate <60 mL/minute. Lung cancer and coexisting CKD patients were matched 1:1 to patients with lung cancer without CKD. Results Age, gender, smoking status, histology, and lung cancer stage were not statistically significantly different between the CKD and non‐CKD groups. Kaplan–Meier survival analysis demonstrated a median survival of 7.26 months (95% confidence interval [CI] 6.06–8.46) in the CKD group compared with 7.82 months (95% CI 6.33–9.30) in the non‐CKD group (P = 0.41). Lung cancer stage‐specific survival is not affected by CKD. Although lung cancer patients with CKD presented with an increased risk of death of 6%, this result was not statistically significant (hazard ratio 1.06, 95% CI 0.93–1.22; P = 0.41). Conclusion According to our limited experience, CKD is not an independent risk factor for survival in lung cancer patients. Clinicians should not be discouraged to treat lung cancer patients with CKD. PMID:28207203

  17. Analysis of altered microRNA expression profiles in the kidney tissues of ethylene glycol-induced hyperoxaluric rats

    PubMed Central

    Liu, Zhuo; Jiang, Hongyang; Yang, Jun; Wang, Tao; Ding, Yufeng; Liu, Jihong; Wang, Shaogang; Ye, Zhangqun

    2016-01-01

    Calcium oxalate stones account for >80% of urinary stones, however the mechanisms underlying their formation remains to be elucidated. Hyperoxaluria serves an important role in the pathophysiological process of stone formation. In the present study, differences in the miRNA expression profiles between experimental hyperoxaluric rats and normal rats were analyzed, in order to identify target genes and signaling pathways involved in the pathogenesis of hyperoxaluria. Ethylene glycol and ammonium chloride was fed to male hyperoxaluric rats (EXP) and normal age-matched male rats (CON). The oxalate concentration in the urine of each experimental rat was collected every 24 h and measured on day 14. Three rats exhibiting the highest concentrations were selected for microarray analysis. Microarray analysis was performed to evaluate differences in the expression of microRNA (miRNA) in the kidney tissues from EXP and CON groups, and miRNAs that exhibited a >2-fold or a <0.5-fold alteration in expression between these groups were screened for differential expression patterns according to the threshold P-values. Reverse transcription-quantitative polymerase chain reaction analysis was employed to confirm the microarray results. In order to predict the potential role of miRNAs in pathophysiological processes, gene ontology (GO), pathway and target prediction analyses were conducted. A total of 28 miRNAs were observed to be differentially expressed (>2-fold change) between EXP and CON groups. Among these miRNAs, 20 were upregulated and 8 were downregulated. GO and pathway analyses revealed that the insulin resistance and phosphatidylinositol-bisphosphonate 3-kinase/AKT serine threonine kinase signaling pathways were potentially associated with miRNA regulation in this setting. In conclusion, the results of the present study identified differentially expressed miRNAs in hyperoxaluric rats, and provided a novel perspective for the role of miRNAs in the formation of calcium oxalate

  18. Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue.

    PubMed

    Luo, Jian-Hua; Liu, Silvia; Zuo, Ze-Hua; Chen, Rui; Tseng, George C; Yu, Yan P

    2015-07-01

    Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail gene fusion protein product and the roles that these fusions may play in cancer development.

  19. The Analysis of Phenylbutazone and Its Active Metabolite, Oxyphenbutazone, in Equine Tissues (Muscle, Kidney, and Liver), Urine, and Serum by LC-MS/MS.

    PubMed

    Boison, Joe O; Dowling, Patricia; Matus, Johanna L; Kinar, Jana; Johnson, Ron

    2017-02-01

    This study reports the use of two validated LC with tandem MS (MS/MS) methods to study the residue depletion profile ofphenylbutazone (PBZ) and its metabolite oxyphenbutazone (OXPBZ) from equine serum, urine, and muscle, kidney, and liver tissues. One LC-MS/MS method, with an LOQ of 1.0 ng/mL for PBZ and 2.0 ng/mL for OXPBZ, was used for the analysis of the two drugs in the biological fluids (equine urine and serum); the other LC-MS/MS method, with an LOQ of 0.5 ng/g for PBZ and OXPBZ, was used for the analysis of the drugs in the equine tissue samples. PBZ was administered intravenously to two horses dosed with 8.8 mg/kg PBZ once daily for 4 days and sacrificed humanely at a slaughter plant 7 days after the last drug administration. Urine, serum, and kidney, liver, and muscle tissues were collected from the two horses and shipped on ice to the laboratory and stored at −20°C until analysis. The concentrations of PBZ and OXPBZ residues in the biological fluid and tissue samples collected at slaughter were measured with the two validated LC-MS/MS methods using deuterated internal standards. The results demonstrate that the validated methods are fit for studying the depletion kinetics of PBZ residues in equine tissues and biological fluids.

  20. Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

    2015-03-01

    With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

  1. Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues.

    PubMed

    Takahashi, Kazuto; Hosokawa, Masashi; Kasajima, Hiroyuki; Hatanaka, Kazuteru; Kudo, Kazuhiro; Shimoyama, Norihiko; Miyashita, Kazuo

    2015-09-01

    Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fucoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCT116, and DLD-1 cell lines at doses of 20 µM. Fucoxanthinol also decreased the T/C (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the T/C (%) of Caco-2 and WiDr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 µM fucoxanthinol for 24 h, was markedly decreased to 1.4±0.2 and 12.0±0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the T/C (%) in colorectal cancer tissue samples. Notably, 20 µM fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of <50% (13/20, 65%) compared with samples treated with 20 µM fucoxanthin (2/20, 10%). The median T/C (%) value of 35.1% for the 20 cancers specimens treated with 20 µM fucoxanthinol was lower than the median T/C (%) values of 86.3% and 75.8% for those treated with fluorouracil and paclitaxel, respectively. These results suggested that fucoxanthin and fucoxanthinol may be of use as chemotherapeutic agents in colorectal cancer.

  2. Expression and clinicopathological implication of DcR3 in lung cancer tissues: a tissue microarray study with 365 cases

    PubMed Central

    Zhang, Yu; Luo, Jie; He, Rongquan; Huang, Wenting; Li, Zuyun; Li, Ping; Dang, Yiwu; Chen, Gang; Li, Shikang

    2016-01-01

    Background Decoy receptor 3 (DcR3) has been reported to be involved in different cancers. However, few related researches have been accomplished on the role of DcR3 in lung cancer. Objective To explore the expression level and clinicopathological implication of DcR3 protein in lung cancer tissues. Materials and methods Immunohistochemistry was used to examine DcR3 protein expression in lung cancer (n=365) and normal lung tissues (n=26). The relationships between DcR3 expression and clinical parameters were further investigated. Furthermore, the diagnostic and clinicopathological value of DcR3 mRNA was analyzed based on The Cancer Genome Atlas database in lung cancer patients. Results Compared to normal lung tissues, DcR3 expression was significantly higher in lung cancer (P=0.007) tissues, including small-cell lung cancer (P=0.001) and non-small-cell lung cancer (P=0.008). In addition, DcR3 expression was related to tumor-node-metastasis (TNM) stage (P<0.001), tumor diameter (P=0.007), distant metastasis (P<0.001), and lymph node metastasis (P<0.001) in lung cancers. When concerning non-small-cell lung cancer, consistent correlations between DcR3 expression and TNM stage (P<0.001), tumor diameter (P=0.019), distant metastasis (P<0.001), and lymph node metastasis (P<0.001) were found. Simultaneously, in small-cell lung cancer, TNM stage (P=0.004) and lymph node metastasis (P=0.005) were also associated with DcR3 expression. Additionally, receiver operator characteristic curve revealed that the area under curve (AUC) of DcR3 was 0.637 (95% confidence interval [CI] 0.531–0.742) for lung cancer. Furthermore, DcR3 was overexpressed in both adenocarcinoma and squamous cell carcinoma tissues than in noncancerous lung tissues (all P<0.0001) based on the data from The Cancer Genome Atlas. AUC of DcR3 was 0.726 (95% CI 0.644–0.788) for lung adenocarcinoma patients and 0.647 (95% CI 0.566–0.728) for squamous cell carcinoma patients. DcR3 expression was also related to

  3. RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both normal and cancer tissues.

    PubMed

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

    2013-01-01

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

  4. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers

    NASA Astrophysics Data System (ADS)

    Brozek-Pluska, B.; Kopec, M.

    2016-12-01

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.

  5. Comparing the micro-vascular structure of cancerous and healthy tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Lang, Sabrina; Beckmann, Felix; Dominietto, Marco; Rudin, Markus; Zanette, Irene; Weitkamp, Timm; Rack, Alexander; Hieber, Simone Elke

    2012-10-01

    Basic research is required to develop more powerful approaches to prevent, diagnose, and above all to treat cancer, although the clever combination of surgery, chemical, pharmacological, and radiation therapies is well established. Our research activity concentrates on the quantification of the three-dimensional micro-morphology of vessel trees formed in cancerous and healthy tissues of a mouse model post mortem. While in several cases it is possible to extract the vessel tree from corrosion casts, phase contrast imaging modalities are needed for cancerous tissues with a significant amount of damaged vessel walls. Differences between cancerous and healthy tissues could be identified. The sum-of-angle metrics is found to be constant for vessel segments in cancerous and healthy tissues with lengths between 12 and 220 μm and corresponds to (0.62 +/- 0.10) rad/μm.

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  7. A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer

    PubMed Central

    Tessem, May-Britt; Bertilsson, Helena; Angelsen, Anders; Bathen, Tone F.; Drabløs, Finn; Rye, Morten Beck

    2016-01-01

    Molecular analysis of patient tissue samples is essential to characterize the in vivo variability in human cancers which are not accessible in cell-lines or animal models. This applies particularly to studies of tumor metabolism. The challenge is, however, the complex mixture of various tissue types within each sample, such as benign epithelium, stroma and cancer tissue, which can introduce systematic biases when cancers are compared to normal samples. In this study we apply a simple strategy to remove such biases using sample selections where the average content of stroma tissue is balanced between the sample groups. The strategy is applied to a prostate cancer patient cohort where data from MR spectroscopy and gene expression have been collected from and integrated on the exact same tissue samples. We reveal in vivo changes in cancer-relevant metabolic pathways which are otherwise hidden in the data due to tissue confounding. In particular, lowered levels of putrescine are connected to increased expression of SRM, reduced levels of citrate are attributed to upregulation of genes promoting fatty acid synthesis, and increased succinate levels coincide with reduced expression of SUCLA2 and SDHD. In addition, the strategy also highlights important metabolic differences between the stroma, epithelium and prostate cancer. These results show that important in vivo metabolic features of cancer can be revealed from patient data only if the heterogeneous tissue composition is properly accounted for in the analysis. PMID:27100877

  8. Cell type-specific properties and environment shape tissue specificity of cancer genes

    PubMed Central

    Schaefer, Martin H.; Serrano, Luis

    2016-01-01

    One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer. PMID:26856619

  9. Trends in net survival from kidney cancer in six European Latin countries: results from the SUDCAN population-based study.

    PubMed

    Mangone, Lucia; Bossard, Nadine; Marcos-Gragera, Rafael; Pezzarossi, Annamaria; Roncaglia, Francesca; Giorgi Rossi, Paolo

    2017-01-01

    Kidney cancer is a frequent malignant disease. To date, there is no evidence on the effectiveness of early detection and, in most cases, surgery represents the only standard treatment. So far, there is no standardized therapy for localized and locally advanced renal tumors; however, the recent introduction of target therapy has significantly improved the prognosis of metastatic disease. Therefore, survival differences in Europe are deemed to involve differences in diagnostic and therapeutic approaches. The aim of the SUDCAN collaborative study was to compare the net survival from kidney cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analysis, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland, and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modeling strategy. In 2000-2004, the 5-year net survival ranged between 59% (Spain) and 67% (France and Italy) in men and between 60% (Spain) and 73% (Portugal) in women. There was an increase in the age-standardized net survival between 1992 and 2004 at 1 year, as well as at 5 years, in all age groups and countries. Irrespective of the year of diagnosis, the excess mortality rate decreased with time elapsed since diagnosis. There are some differences in survival from kidney cancer between European Latin countries, but a considerable improvement was observed in most countries.

  10. IL-15/sIL-15Rα gene transfer suppresses Lewis lung cancer growth in the lungs, liver and kidneys.

    PubMed

    Sun, H; Liu, D

    2016-01-01

    Nearly 40% of people with lung cancer have tumor growth in other organs at the time of diagnosis. Current treatment strategies for patients with late-stage lung cancer are primarily palliative and only showed modest efficacy. The current study takes advantage of the hydrodynamic gene delivery technique to evaluate the antitumor activity of interleukin (IL)-15/sIL-15Rα on lung tumors growing in the lungs, liver and kidneys. We demonstrate that hydrodynamic tail vein injection of 2 μg of AG209 DP muIL-15sRα+IL-15 plasmid resulted in serum IL-15/sIL-15Rα reaching a peak level of ~10 μg ml(-1) 1 day after the injection and gradually declined to ~5 ng ml(-1) within 3 days. Quantitative PCR analysis revealed that overexpression of IL-15/sIL-15Rα induced the activation of natural killer and T cells, evidenced by increased mRNA levels of marker genes including granzyme B, perforin, Ifn-γ, T-bet and Cd8 in the lungs, liver and kidneys. Importantly, transfer of the Il-15/sIl-15Rα gene alone, or in combination with gemcitabine chemotherapy, significantly inhibited the tumor growth in these three organs and prolonged median survival time of treated mice by 1.7- and 3.3-fold, respectively. The therapeutic benefits are principally blockade and elimination of tumor growth in the liver and kidneys. Taken together, these results suggest that IL-15/sIL-15Rα-based gene therapy could be an effective approach to treat late-stage lung cancer with metastases in other organs.

  11. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer

    PubMed Central

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors. PMID:26876567

  12. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer.

    PubMed

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-02-15

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors.

  13. Raman spectra of normal and cancerous mouse mammary gland tissue using near infrared excitation energy

    NASA Astrophysics Data System (ADS)

    Naik, Vaman; Serhatkulu, G. K.; Dai, H.; Shukla, N.; Weber, R.; Thakur, J. S.; Freeman, D. C.; Pandya, A. K.; Auner, G. W.; Naik, R.; Miller, R. F.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra of normal mammary gland tissues, malignant mammary gland tumors, and lymph nodes have been recorded using fresh tissue from mice. Tumors were induced in mice by subcutaneously injecting 4T1 BALB/c mammary tumor (a highly malignant) cell line. The Raman spectra were collected using the same tissues that were examined by histopathology for determining the cancerous/normal state of the tissue. Differences in various peak intensities, peak shifts and peak ratios were analyzed to determine the Raman spectral features that differentiate mammary gland tumors from non-tumorous tissue. Tissues that were confirmed by pathology as cancerous (tumors) show several distinctive features in the Raman spectra compared to the spectra of the normal tissues. For example, the cancerous tissues show Raman peaks at 621, 642, 1004, 1032, 1175 and 1208 cm-1 that are assignable to amino acids containing aromatic side-chains such as phenylalanine, tryptophan and tyrosine. Further, the cancerous tissues show a greatly reduced level of phospholipids compared to the normal tissues. The Raman spectral regions that are sensitive to pathologic alteration in the tissue will be discussed.

  14. Transperitoneal Robot-Assisted Radical Prostatectomy Should Be Considered in Prostate Cancer Patients with Pelvic Kidneys

    PubMed Central

    Plagakis, Sophie; Foreman, Darren; Sutherland, Peter

    2016-01-01

    Abstract We highlight two cases of transperitoneal robot-assisted radical prostatectomy (RARP) in patients with pelvic kidneys because of congenital development and renal transplant. These uncommon cases present a challenge to the surgeon contemplating surgery because of access and anomalous vascular and ureteral anatomy. We describe the technical considerations that are paramount in effectively completing transperitoneal RARP, and believe it should be considered as a treatment option in men with pelvic kidneys. PMID:27579412

  15. Incidence and characteristics of chronic renal replacement therapy in patients with cancer: data from kidney and cancer registries in Basse-Normandie.

    PubMed

    Béchade, Clémence; Dejardin, Olivier; Bara, Simona; Bouvier, Véronique; Guizard, Anne-Valérie; De Mil, Rémy; Troussard, Xavier; Lobbedez, Thierry; Launoy, Guy

    2016-11-04

    Aims To estimate the incidence of chronic dialysis in patients with a history of cancer and assess how renal replacement therapy is initiated in this population. Methods We merged data from cancer registries and hospital databases in one French region to identify patients with an incident cancer between 2001 and 2008 who started chronic dialysis. Results Mean participation time was 3.4 ± 2.7 years. Males comprised 58.5 % of participants. During the study period, 74 chronic dialysis treatments were initiated. Chronic interstitial nephritis was the leading cause of end-stage renal disease (21.6 %), and 46.6 % of dialysis initiation cases were unplanned. The incidence rate of chronic dialysis initiation in the population of incident cancer patients was 370 per million population/year (74 events/199,809 person-years). After age-adjustment, the standardized incidence ratio was 1.26, 95 % confidence interval 0.98-1.57, p = 0.55. Conclusion Cancer patients are known to be at risk of chronic kidney disease. However, the standardized incidence ratio of chronic dialysis initiation did not differ significantly between cancer patients and the general population. Further studies should be performed to identify the barriers to starting renal replacement therapy in cancer patients.

  16. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    SciTech Connect

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; Boreham, Douglas R.

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average

  17. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice.

    PubMed

    Taylor, Kristina; Lemon, Jennifer A; Phan, Nghi; Boreham, Douglas R

    2014-07-01

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy (18)F-FDG, 4 Gy γ-rays, 10 mGy (18)F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from (18)F-FDG, with respect to malignancy, is approximately 1. However; when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.

  18. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  19. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    PubMed

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  20. Investigating Breast Cancer Cell Behavior Using Tissue Engineering Scaffolds

    PubMed Central

    Guiro, Khadidiatou; Patel, Shyam A.; Greco, Steven J.; Rameshwar, Pranela; Arinzeh, Treena L.

    2015-01-01

    Despite early detection through the use of mammograms and aggressive intervention, breast cancer (BC) remains a clinical dilemma. BC can resurge after >10 years of remission. Studies indicate that BC cells (BCCs) with self-renewal and chemoresistance could be involved in dormancy. The majority of studies use in vitro, two-dimensional (2-D) monolayer cultures, which do not recapitulate the in vivo microenvironment. Thus, to determine the effect of three-dimensional (3-D) microenvironment on BCCs, this study fabricated tissue engineering scaffolds made of poly (ε-caprolactone) (PCL) having aligned or random fibers. Random and aligned fibers mimic, respectively, the random and highly organized collagen fibers found in the tumor extracellular matrix. Chemoresistant BCCs were obtained by treating with carboplatin. Western blot analysis of carboplatin resistant (treated) MDA-MB-231 (highly invasive, basal-like) and T47D (low-invasive, luminal) BCCs showed an increase in Bcl-2, Oct-4 and Sox-2, suggesting protection from apoptosis and increase in stem-like markers. Further studies with MDA-MB-231 BCCs seeded on the scaffolds showed little to no change in cell number over time for non-treated BCCs whereas on tissue culture polystyrene (TCP), non-treated BCCs displayed a significant increase in cell number at days 4 and 7 as compared to day 1 (p<0.05). Treated BCCs did not proliferate on TCP and the fibrous scaffolds. Little to no cyclin D1 was expressed for non-treated BCCs on TCP. On fibrous scaffolds, non-treated BCCs stained for cyclin D1 during the 7-day culture period. Treated BCCs expressed cyclin D1 on TCP and fibrous scaffolds during the 7-day culture period. Proliferation, viability and cell cycle analysis indicated that this 3-D culture prompted the aggressive BCCs to adopt a dormant phenotype, while the treated BCCs retained their phenotype. The findings indicate that random and aligned fibrous PCL scaffolds may provide a useful system to study how the 3-D

  1. Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis.

    PubMed

    Ping, An; Zhendong, Su; Rongmei, Qu; Jingxing, Dai; Wei, Chen; Zhongyin, Zhou; Hesheng, Luo; Soh, Kwang-Sup

    2015-01-01

    Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis.

  2. Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis

    PubMed Central

    Ping, An; Zhendong, Su; Rongmei, Qu; Jingxing, Dai; Wei, Chen; Zhongyin, Zhou; Hesheng, Luo; Soh, Kwang-Sup

    2015-01-01

    Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis. PMID:26379752

  3. Visualization of basement membranes in normal breast and breast cancer tissues using multiphoton microscopy

    PubMed Central

    WU, XIUFENG; CHEN, GANG; QIU, JINGTING; LU, JIANPING; ZHU, WEIFENG; CHEN, JIANXIN; ZHUO, SHUANGMU; YAN, JUN

    2016-01-01

    Since basement membranes represent a critical barrier during breast cancer progression, timely imaging of these signposts is essential for early diagnosis of breast cancer. A label-free method using multiphoton microscopy (MPM) based on two-photon excited fluorescence signals and second harmonic generation signals for analyzing the morphology of basement membrane in normal and cancerous breast tissues is likely to enable a better understanding of the pathophysiology of breast cancer and facilitate improved clinical management and treatment of this disease. The aim of this study was to determine whether MPM has the potential for label-free assessment of the morphology of basement membrane in normal and cancerous breast tissues. A total of 60 tissue section samples (comprising 30 fresh breast cancer specimens and 30 normal breast tissues) were first imaged (fresh, unfixed and unstained) with MPM and are then processed for routine hematoxylin and eosin (H&E) histopathology. Comparisons were made between MPM imaging and gold standard sections for each specimen stained with H&E. Simply by visualizing morphological features appearing on multiphoton images, cancerous lesions may be readily identified by the loss of basement membrane and tumor cells characterized by irregular size and shape, enlarged nuclei and increased nuclear-cytoplasmic ratio. These results suggest that MPM has potential as a label-free method of imaging the morphology of basement membranes and cell features to effectively distinguish between normal and cancerous breast tissues. PMID:27313695

  4. Fucosyltransferase 8 expression in breast cancer patients: A high throughput tissue microarray analysis.

    PubMed

    Yue, Liling; Han, Cuicui; Li, Zubin; Li, Xin; Liu, Deshui; Liu, Shulin; Yu, Haitao

    2016-05-01

    The aim of this study was to compare the expression of fucosyltransferase 8 (FUT8) in breast cancer tissue and to investigate the relationship between this marker with tumor progression and its applicability to differential diagnosis. An immunohistochemical study was performed for FUT8 using the tissue microarray technique. In addition, the mRNA and protein levels of FUT8 in the tissue were also tested by real-time PCR and Western blot. There was a significant difference in cytoplasmic expression of FUT8 between breast cancer tissue and matched normal tissue (p<0.001). The percent of FUT8 staining in breast cancer tissues ranging from negative, weak positive, positive and strong positive were 2.7%, 40.2%, 54% and 3.2%, respectively. High FUT8 protein expression correlated with lymphatic metastasis (p=0.008) and with stage status (p=0.039). We detected that reduced FUT8 expression correlated with disease-free survival (p=0.02) and overall survival (p=0.04) of breast cancer patients. Expression of FUT8 can stratify breast cancer tissue and may be considered a prognostic marker for breast cancer patients.

  5. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    PubMed

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  6. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  7. Accurate Characterization of Benign and Cancerous Breast Tissues: Aspecific Patient Studies using Piezoresistive Microcantilevers

    PubMed Central

    PANDYA, HARDIK J.; ROY, RAJARSHI; CHEN, WENJIN; CHEKMAREVA, MARINA A.; FORAN, DAVID J.; DESAI, JAYDEV P.

    2014-01-01

    Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316 X 10−3 Ω-cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression. PMID:25128621

  8. The nanomechanical signature of liver cancer tissues and its molecular origin

    NASA Astrophysics Data System (ADS)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-07-01

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  9. Spatial Moran models, II: cancer initiation in spatially structured tissue

    PubMed Central

    Foo, J; Leder, K

    2016-01-01

    We study the accumulation and spread of advantageous mutations in a spatial stochastic model of cancer initiation on a lattice. The parameters of this general model can be tuned to study a variety of cancer types and genetic progression pathways. This investigation contributes to an understanding of how the selective advantage of cancer cells together with the rates of mutations driving cancer, impact the process and timing of carcinogenesis. These results can be used to give insights into tumor heterogeneity and the “cancer field effect,” the observation that a malignancy is often surrounded by cells that have undergone premalignant transformation. PMID:26126947

  10. Comparison of the viscoelastic properties of cells from different kidney cancer phenotypes measured with atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Rebelo, L. M.; de Sousa, J. S.; Mendes Filho, J.; Radmacher, M.

    2013-02-01

    The viscoelastic properties of human kidney cell lines from different tumor types (carcinoma (A-498) and adenocarcinoma (ACHN)) are compared to a non-tumorigenic cell line (RC-124). Our methodology is based on the mapping of viscoelastic properties (elasticity modulus E and apparent viscosity η) over the surface of tens of individual cells with atomic force microscopy (AFM). The viscoelastic properties are averaged over datasets as large as 15000 data points per cell line. We also propose a model to estimate the apparent viscosity of soft materials using the hysteresis observed in conventional AFM deflection-displacement curves, without any modification to the standard AFM apparatus. The comparison of the three cell lines show that the non-tumorigenic cells are less deformable and more viscous than cancerous cells, and that cancer cell lines have distinctive viscoelastic properties. In particular, we obtained that ERC-124 > EA-498 > EACHN and ηRC-124 > ηA-498 > ηACHN.

  11. Diabetes-induced alterations in tissue collagen and carboxymethyllysine in rat kidneys: Association with increased collagen-degrading proteinases and amelioration by Cu(II)-selective chelation.

    PubMed

    Brings, Sebastian; Zhang, Shaoping; Choong, Yee S; Hogl, Sebastian; Middleditch, Martin; Kamalov, Meder; Brimble, Margaret A; Gong, Deming; Cooper, Garth J S

    2015-08-01

    Advanced glycation end-products (AGEs) comprise a group of non-enzymatic post-translational modifications of proteins and are elevated in diabetic tissues. AGE-modification impairs the digestibility of collagen in vitro but little is known about its relation to collagen-degrading proteinases in vivo. N(ε)-carboxymethyllysine (CML) is a stable AGE that forms on lysyl side-chains in the presence of glucose, probably via a transition metal-catalysed mechanism. Here, rats with streptozotocin-induced diabetes and non-diabetic controls were treated for 8weeks with placebo or the Cu(II)-selective chelator, triethylenetetramine (TETA), commencing 8weeks after disease induction. Actions of diabetes and drug treatment were measured on collagen and collagen-degrading proteinases in kidney tissue. The digestibility and CML content of collagen, and corresponding levels of mRNAs and collagen, were related to changes in collagen-degrading-proteinases. Collagen-degrading proteinases, cathepsin L (CTSL) and matrix metalloproteinase-2 (MMP-2) were increased in diabetic rats. CTSL-levels correlated strongly and positively with increased collagen-CML levels and inversely with decreased collagen digestibility in diabetes. The collagen-rich mesangium displayed a strong increase of CTSL in diabetes. TETA treatment normalised kidney collagen content and partially normalised levels of CML and CTSL. These data provide evidence for an adaptive proteinase response in diabetic kidneys, affected by excessive collagen-CML formation and decreased collagen digestibility. The normalisation of collagen and partial normalisation of CML- and CTSL-levels by TETA treatment supports the involvement of Cu(II) in CML formation and altered collagen metabolism in diabetic kidneys. Cu(II)-chelation by TETA may represent a treatment option to rectify collagen metabolism in diabetes independent of alterations in blood glucose levels.

  12. Breast tissue phantoms to assist compression study for cancer detection using microwave radiometry.

    PubMed

    Akki, Rachana S; Arunachalam, Kavitha

    2014-01-01

    Microwave radiometry is a passive imaging modality proposed for breast cancer detection without the need for ionizing radiation. Detection of breast tumor using radiometry is challenging as the intensity of thermal radiation received by the antenna is influenced by tumor stage, location, physiological conditions and the imaging setup. The controllable parameters for setting up a good imaging modality for early detection of breast cancer are ambient temperature (Ta), convection cooling of tissue surface (h), and tissue compression (c). Amongst these parameters tissue compression plays an important role since reducing the breast thickness increases visibility. In this work, fabrication of hydrogel breast tissue phantoms with varying concentrations of polyvinyl alcohol (PVAL) is carried out to mimic breast fat and glandular tissue properties for compression study. The phantoms were subjected to compression to investigate the mechanical properties for varying PVAL concentrations. A 3D numerical model was developed for phantom tissue compression simulations. Simulated tissue compression results were compared with phantom measurements for model validation.

  13. Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7,12-dimethylbenz[a]anthracene.

    PubMed

    Lakshmi, Arivazhagan; Subramanian, Sorimuthu Pillai

    2014-09-02

    Tangeretin, a citrus polymethoxyflavone, is an antioxidant modulator which has been shown to exhibit a surfeit of pharmacological properties. The present study was hypothesized to explore the therapeutic activity of tangeretin against 7,12-dimethylbenz[a]anthracene (DMBA) induced kidney injury in mammary tumor bearing rats. Recently, we have reported the chemotherapeutic effect of tangeretin in the breast tissue of DMBA induced rats. Breast cancer was induced by "air pouch technique" with a single dose of 25mg/kg of DMBA. Tangeretin (50mg/kg/day) was administered orally for four weeks. The renoprotective nature of tangeretin was assessed by analyzing the markers of oxidative stress, proinflammatory cytokines and antioxidant competence in DMBA induced rats. Tangeretin treatment revealed a significant decline in the levels of lipid peroxides, inflammatory cytokines and markers of DNA damage, and a significant improvement in the levels of enzymatic and non-enzymatic antioxidants in the kidney tissue. Similarly, mRNA, protein and immunohistochemical analysis substantiated that tangeretin treatment notably normalizes the renal expression of Nrf2/Keap1, its downstream regulatory proteins and the inflammatory cytokines in the DMBA induced rats. Histological and ultrastructural observations also evidenced that the treatment with tangeretin effectively protects the kidney from DMBA-mediated oxidative damage, hence, proving its nephroprotective nature.

  14. NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer

    Cancer.gov

    Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes. The genetic alterations identified in this malignancy could be useful

  15. [Regulatory mechanism of p38MAPK signaling pathway on renal tissue inflammation in chronic kidney disease and interventional effect of traditional Chinese medicine].

    PubMed

    Zhao, Qing; Wan, Yigang; Wang, Chaojun; Wei, Qingxue; Chen, Haoli; Meng, Xianjie; Yao, Jian

    2012-06-01

    The inflammatory reaction of renal tissues and its relevant tissue damages (such as glomerulosclerosis and renal interstitial fibrosis) are important factors for the development of chronic kidney diseases (CKD) to end-state renal diseases. Of them, p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in regulating expression and bioactivity of multiple nuclear transcription factors, impacting synthesis of downstream inflammatory mediators and activating inflammatory cells. Some monomer traditional Chinese medicines and their extracts (such as emodin and berberine) and some traditional Chinese medicine compound prescriptions (such as Yishen Huoxue decoction) can affect inflammatory reaction of renal tissues by regulating p38MAPK signaling pathway, thas improving reduce glomerulus and renal interstitial inflammatory injury.

  16. Prostate specific membrane antigen (PSM) is expressed in various human tissues: implication for the use of PSM reverse transcription polymerase chain reaction to detect hematogenous prostate cancer spread.

    PubMed

    Renneberg, H; Friedetzky, A; Konrad, L; Kurek, R; Weingärtner, K; Wennemuth, G; Tunn, U W; Aumüller, G

    1999-01-01

    Detection of prostate-specific membrane antigen (PSM)-mRNA expression in blood samples using reverse transcription polymerase chain reaction (RT-PCR) is discussed as a new diagnostic marker of circulating micrometastases in prostate cancer patients. We applied the RT-PCR technique to different human tissues and obtained positive signals for PSM transcripts in human genital and multiple extra-genital tissue sites. The cDNAs were prepared from different human tissues and prostatic cell lines. RT-PCR and nested RT-PCR for PSM was performed with primers derived from the published PSM cDNA. The RT-PCR fragments obtained were cloned and showed 100% sequence homology to PSM. Southern blot hybridization with labeled probes was used to confirm the specificity of the amplicons. In addition to the known PSM expression in the human brain, PSM-mRNA was detected in cDNA isolated from human testis, epididymis and seminal vesicles and in the PC-3 prostatic cancer cell line. Furthermore, we found PSM-mRNA in heart, liver, lung, kidney, spleen, and thyroid gland. The results indicate that PSM expression is not restricted to the prostate gland, but represents a more general component of genital and extra-genital human tissues. This must be considered when RT-PCR and nested RT-PCR screening for PSM expression is performed as a diagnostic measure in blood from prostate cancer patients.

  17. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    PubMed Central

    2010-01-01

    Background Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. Methods The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Results Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm3 vs. 1195 ± 84 mm3, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. Conclusions CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis. PMID:20509933

  18. Preliminary evidence of different selection pressures on cancer cells as compared to normal tissues

    PubMed Central

    2012-01-01

    Background Cancer is characterized by both a high mutation rate as well as high rates of cell division and cell death. We postulate that these conditions will result in the eventual mutational inactivation of genes not essential to the survival of the cancer cell, while mutations in essential genes will be eliminated by natural selection leaving molecular signatures of selection in genes required for survival and reproduction. By looking for signatures of natural selection in the genomes of cancer cells, it should therefore be possible to determine which genes have been essential for the development of a particular cancer. Methods We provide a proof of principle test of this idea by applying a test of neutrality (Nei-Gojobori Z-test of selection) to 139 cancer-related nucleotide sequences obtained from GenBank representing 46 cancer-derived genes. Results Among cancer associated sequences, 10 genes showed molecular evidence of selection. Of these 10 genes, four showed molecular evidence of selection in non-cancer transcripts. Among non-cancer associated sequences, eight genes showed molecular evidence of selection, with four of these also showing selection in the cancer associated sequences. Conclusions These results provide preliminary evidence that the same genes may experience different selection pressures within normal and cancer tissues. Application of this technique could identify genes under unique selection pressure in cancer tissues and thereby indicate possible targets for therapeutic intervention. PMID:23146329

  19. Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2014-01-01

    Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII (fVII) is produced in the liver and secreted into the blood stream. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fVII complex may be formed in the absence of injury, because fVII potentially exists in the tissue fluid within cancer tissues. The active form of this complex (TF-fVIIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fVII pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mechanisms by which TF-fVII signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fVII synthesis and regulation in breast cancer cells. Our current understanding of the TF-fVII pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies. PMID:25493229

  20. [Management of High-Risk Prostate Cancer and Left Ectopic Ureter Inserting into Seminal Vesicle with Ipsilateral Hypoplastic Kidney of a Young Patient : A Case Report].

    PubMed

    Matsumoto, Teppei; Koie, Takuya; Soma, Osamu; Kusaka, Ayumu; Hosogoe, Shogo; Hamano, Itsuto; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

    2016-06-01

    A 44-year-old male patient visited our hospital with a chief complaint of macroscopic hematuria. Prostate biopsies were performed due to prostate specific antigen (PSA) 11.6 ng/ml, and he was diagnosed with Gleason score 5+4 prostate cancer. Computed tomography showed a left hypoplastic kidney. T2- weighted magnetic resonance imaging showed the left ureter stump with ectopic insertion into the dilated left seminal vesicle. He was diagnosed with high-risk prostate cancer and left ectopic ureter inserting into the seminal vesicle with ipsilateral hypoplastic kidney. Laparoscopic left nephroureterectomy and open radical prostatectomy were performed.

  1. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

    PubMed

    Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2015-03-30

    Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

  2. Quantification of nucleic acid quality in postmortem tissues from a cancer research autopsy program

    PubMed Central

    Fan, Jun; Khanin, Raya; Sakamoto, Hitomi; Zhong, Yi; Michael, Chelsea; Pena, Derwin; Javier, Breanna; Wood, Laura D.; Iacobuzio-Donahue, Christine A.

    2016-01-01

    The last decade has seen a marked rise in the use of cancer tissues obtained from research autopsies. Such resources have been invaluable for studying cancer evolution or the mechanisms of therapeutic resistance to targeted therapies. Degradation of biomolecules is a potential challenge to usage of cancer tissues obtained in the post-mortem setting and remains incompletely studied. We analysed the nucleic acid quality in 371 different frozen tissue samples collected from 80 patients who underwent a research autopsy, including eight normal tissue types, primary and metastatic tumors. Our results indicate that RNA integrity number (RIN) of normal tissues decline with the elongation of post-mortem interval (PMI) in a tissue-type specific manner. Unlike normal tissues, the RNA quality of cancer tissues is highly variable with respect to post-mortem interval. The kinetics of DNA damage also has tissue type-specific features. Moreover, while DNA degradation is an indicator of low RNA quality, the converse is not true. Finally, we show that despite RIN values as low as 5.0, robust data can be obtained by RNA sequencing that reliably discriminates expression signatures. PMID:27602498

  3. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    DOE PAGES

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; ...

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancermore » risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

  4. Exploring the Presence of microDNAs in Prostate Cancer Cell Lines, Tissue, and Sera of Prostate Cancer Patients and its Possible Application as Biomarker

    DTIC Science & Technology

    2015-08-01

    AWARD NUMBER: W81XWH-13-1-0088 TITLE: Exploring the Presence of microDNAs in Prostate Cancer Cell Lines, Tissue , and Sera of Prostate Cancer...the Presence of microDNAs in Prostate Cancer Cell Lines, Tissue , and Sera of Prostate Cancer Patients and its Possible Application as Biomarker 5c...extra chromosomal circular DNA present in normal mammalian somatic cells. To find the prostate tissue -specific microDNA a panel of human prostrate

  5. Quantification of effects of cancer on elastic properties of breast tissue by Atomic Force Microscopy.

    PubMed

    Ansardamavandi, Arian; Tafazzoli-Shadpour, Mohammad; Omidvar, Ramin; Jahanzad, Iisa

    2016-07-01

    Different behaviors of cells such as growth, differentiation and apoptosis widely differ in case of diseases. The mechanical properties of cells and tissues can be used as a clue for diagnosis of pathological conditions. Here, we implemented Atomic Force Microscopy to evaluate the extent of alteration in mechanical stiffness of tissue layers from patients affected by breast cancer and investigated how data can be categorized based on pathological observations. To avoid predefined categories, Fuzzy-logic algorithm as a novel method was used to divide and categorize the derived Young׳s modulus coefficients (E). Such algorithm divides data among groups in such way that data of each group are mostly similar while dissimilar with other groups. The algorithm was run for different number of categories. Results showed that three (followed by two with small difference) groups categorized data best. Three categories were defined as (E<3000Pa, 30007000Pa) among which data were allocated. The first cluster was assumed as the cellular region while the last cluster was referred to the fibrous parts of the tissue. The intermediate region was due to other non-cellular parts. Results indicated 50% decline of average Young׳s modulus of cellular region of cancerous tissues compared to healthy tissues. The average Young׳s modulus of non-cellular area of normal tissues was slightly lower than that of cancerous tissues, although the difference was not statistically different. Through clustering, the measured Young׳s moduli of different locations of cancerous tissues, a quantified approach was developed to analyze changes in elastic modulus of a spectrum of components of breast tissue which can be applied in diagnostic mechanisms of cancer development, since in cancer progression the softening cell body facilitates the migration of cancerous cells through the original tumor and endothelial junctions.

  6. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

    PubMed Central

    2012-01-01

    Background Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for

  7. Analysis of blood and tissue in gallbladder cancer

    NASA Astrophysics Data System (ADS)

    Rautray, T. R.; Vijayan, V.; Sudarshan, M.; Panigrahi, S.

    2009-09-01

    Particle induced X-ray emission, particle induced γ-ray emission studies has been carried out to analyse normal and carcinoma tissues and blood samples of gallbladder of both sexes and seventeen trace elements namely Na, Mg, Al, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br and Pb were estimated in the tissue and blood samples. In the present study, concentration of Zn in the carcinoma gallbladder tissue is less than that of the normal gallbladder tissue. Tobacco habit could be one of the important factors to decrease the elemental concentrations in blood and tissue samples.

  8. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects.

    PubMed

    Yoo, Hong Sik; Bradford, Blair U; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B; Bodnar, Wanda M; Ball, Louise M; Gold, Avram; Rusyn, Ivan

    2015-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal-cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, interspecies and interindividual differences, and the mode of action for kidney carcinogenicity. It was postulated that TCE renal metabolite levels are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In subacute study, interstrain differences in renal TCE metabolite levels were observed. In addition, data showed that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In subchronic study, peroxisome proliferator-marker gene induction and renal toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ but not C57BL/6J mice. Overall, data demonstrated that renal TCE metabolite levels are associated with kidney-specific toxicity and that these effects are strain dependent.

  9. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  10. Molecular interaction of a kinase inhibitor midostaurin with anticancer drug targets, S100A8 and EGFR: transcriptional profiling and molecular docking study for kidney cancer therapeutics.

    PubMed

    Mirza, Zeenat; Schulten, Hans-Juergen; Farsi, Hasan Ma; Al-Maghrabi, Jaudah A; Gari, Mamdooh A; Chaudhary, Adeel Ga; Abuzenadah, Adel M; Al-Qahtani, Mohammed H; Karim, Sajjad

    2015-01-01

    The S100A8 and epidermal growth factor receptor (EGFR) proteins are proto-oncogenes that are strongly expressed in a number of cancer types. EGFR promotes cellular proliferation, differentiation, migration and survival by activating molecular pathways. Involvement of proinflammatory S100A8 in tumor cell differentiation and progression is largely unclear and not studied in kidney cancer (KC). S100A8 and EGFR are potential therapeutic biomarkers and anticancer drug targets for KC. In this study, we explored molecular mechanisms of interaction profiles of both molecules with potential anticancer drugs. We undertook transcriptional profiling in Saudi KCs using Affymetrix HuGene 1.0 ST arrays. We identified 1478 significantly expressed genes, including S100A8 and EGFR overexpression, using cut-off p value <0.05 and fold change ≥2. Additionally, we compared and confirmed our findings with expression data available at NCBI's GEO database. A significant number of genes associated with cancer showed involvement in cell cycle progression, DNA repair, tumor morphology, tissue development, and cell survival. Atherosclerosis signaling, leukocyte extravasation signaling, notch signaling, and IL-12 signaling were the most significantly disrupted signaling pathways. The present study provides an initial transcriptional profiling of Saudi KC patients. Our analysis suggests distinct transcriptomic signatures and pathways underlying molecular mechanisms of KC progression. Molecular docking analysis revealed that the kinase inhibitor "midostaurin" has amongst the selected drug targets, the best ligand properties to S100A8 and EGFR, with the implication that its binding inhibits downstream signaling in KC. This is the first structure-based docking study for the selected protein targets and anticancer drug, and the results indicate S100A8 and EGFR as attractive anticancer targets and midostaurin with effective drug properties for therapeutic intervention in KC.

  11. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival

    PubMed Central

    Gaude, Edoardo; Frezza, Christian

    2016-01-01

    Cancer cells undergo a multifaceted rewiring of cellular metabolism to support their biosynthetic needs. Although the major determinants of this metabolic transformation have been elucidated, their broad biological implications and clinical relevance are unclear. Here we systematically analyse the expression of metabolic genes across 20 different cancer types and investigate their impact on clinical outcome. We find that cancers undergo a tissue-specific metabolic rewiring, which converges towards a common metabolic landscape. Of note, downregulation of mitochondrial genes is associated with the worst clinical outcome across all cancer types and correlates with the expression of epithelial-to-mesenchymal transition gene signature, a feature of invasive and metastatic cancers. Consistently, suppression of mitochondrial genes is identified as a key metabolic signature of metastatic melanoma and renal cancer, and metastatic cell lines. This comprehensive analysis reveals unexpected facets of cancer metabolism, with important implications for cancer patients' stratification, prognosis and therapy. PMID:27721378

  12. Distribution of inorganic mercury in liver and kidney of beluga and bowhead whales through autometallographic development of light microscopic tissue sections.

    PubMed

    Woshner, Victoria M; Ohara, Todd M; Eurell, Jo Ann; Wallig, Matthew A; Bratton, Gerald R; Suydam, Robert S; Beasley, Val R

    2002-01-01

    Inorganic mercury was localized through autometallography (AMG) in kidney and liver of free-ranging, subsistence-harvested beluga (Delphinapterus leucus: n = 20) and bowhead (Balaena mysticetrus: n = 5) whales. AMG granules were not evident in bowhead tissues, confirming nominal mercury (Hg) concentrations (range = 0.011 to 0.038 microg/g ww for total Hg). In belugas, total Hg ranged from 0.30 to 17.11 and from 0.33 to 82.47 microg/g ww in liver and kidney, respectively. AMG granules were restricted to cortical tubular epithelial cytoplasm in belugas with lower tissue burdens; whales with higher tissue burdens had granules throughout the uriniferous tubular epithelium. In liver, AMG granular densities differed between lobular zones, concentrating in stellate macrophages and bile cannalicular domains of hepatocytes. AMG granules aggregated in periportal regions in belugas with lower hepatic Hg concentrations, yet among whales with higher Hg, AMG granule deposition extended to pericentral and midzonal regions of liver lobules. Mean areas occupied by AMG granules correlated well with hepatic Hg concentrations and age. In beluga livers, AMG staining density was not associated with lipofuscin quantity (an index of oxidative damage). Occasionally, AMG granules and lipofuscin were colocalized, but more often were not, implying that Hg was not a prominent factor in hepatic lipofuscin deposition in belugas.

  13. Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

    PubMed Central

    Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

  14. Trace elemental analysis of carcinoma kidney and stomach by PIXE method

    NASA Astrophysics Data System (ADS)

    Reddy, S. Bhuloka; John Charles, M.; Naga Raju, G. J.; Vijayan, V.; Seetharami Reddy, B.; Ravi Kumar, M.; Sundareswar, B.

    2003-07-01

    Trace elemental analysis was carried out in the biological samples of carcinoma kidney and stomach using particle induced X-ray emission technique. A 2 MeV proton beam was employed to excite the samples. From the present results, the levels of elements K, Ca, Fe, Ni and Se are lower and those of the elements Ti, Co, Zn, As and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. In the case of stomach, the concentrations of elements Cl, K, Ca, Ti, Mn, Fe, Co, Cu and Zn are lower while concentrations of elements Cr, Ni, As and Br are higher in the cancer tissue of stomach than those observed in the normal tissue. The observed deficiency or excess of certain elements is correlated to carcinogenesis of that organ. The present results of carcinoma stomach support the previous observations that nickel and chromium are carcinogenic agents. The low levels of selenium observed in the carcinoma tissue of kidney and the low levels of manganese observed in the carcinoma tissue of stomach support the view that selenium and manganese inhibit the growth of cancer in kidney and stomach respectively. The observed high levels of zinc in the cancer tissue of kidney suggest that zinc is involved in the tumor growth and development of neoplastic transformation in kidney while the observed low levels of zinc in the carcinoma tissue of stomach suggest that zinc inhibits the growth of cancer in this organ. For correctly assessing the role played by the trace elements in initiating, promoting or inhibiting cancer in various organs, there is a need for acquisition of more data by trace elemental analysis from several investigations of this type undertaken in different regions.

  15. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2012-10-01

    prostate cancer ." Am J Pathol 181(1): 34-42. Li, M. and L. A. Cannizzaro (1999). "Identical clonal origin of synchronous and metachronous low-grade...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue PRINCIPAL INVESTIGATOR...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue 5a. CONTRACT NUMBER 5b. GRANT

  16. miRNA-Target Gene Regulatory Networks: A Bayesian Integrative Approach to Biomarker Selection with Application to Kidney Cancer

    PubMed Central

    Chekouo, Thierry; Stingo, Francesco C.; Doecke, James D.; Do, Kim-Anh

    2015-01-01

    Summary The availability of cross-platform, large-scale genomic data has enabled the investigation of complex biological relationships for many cancers. Identification of reliable cancer-related biomarkers requires the characterization of multiple interactions across complex genetic networks. MicroRNAs are small non-coding RNAs that regulate gene expression; however, the direct relationship between a microRNA and its target gene is difficult to measure. We propose a novel Bayesian model to identify microRNAs and their target genes that are associated with survival time by incorporating the microRNA regulatory network through prior distributions. We assume that biomarkers involved in regulatory networks are likely associated with survival time. We employ non-local prior distributions and a stochastic search method for the selection of biomarkers associated with the survival outcome. We use KEGG pathway information to incorporate correlated gene effects within regulatory networks. Using simulation studies, we assess the performance of our method, and apply it to experimental data of kidney renal cell carcinoma (KIRC) obtained from The Cancer Genome Atlas. Our novel method validates previously identified cancer biomarkers and identifies biomarkers specific to KIRC progression that were not previously discovered. Using the KIRC data, we confirm that biomarkers involved in regulatory networks are more likely to be associated with survival time, showing connections in one regulatory network for five out of six such genes we identified. PMID:25639276

  17. Extensive adipose tissue necrosis following pfannenstiel incision for endometrial cancer.

    PubMed

    Lavoie, Maryse Céline; Plante, Marie; Lemieux, Marie-Carine; Roberge, Céline; Renaud, Marie-Claude; Grégoire, Jean; Roy, Michel; Sebastianelli, Alexandra

    2014-03-01

    Contexte : Les hématomes sont des complications postopératoires qui peuvent en venir à se manifester à la suite du recours à des incisions de Pfannenstiel. Habituellement, ils se résorbent de façon spontanée ou font l’objet d’un drainage (en fonction de leur ampleur). Des facteurs de risque importants (comme l’obésité et le diabète) pourraient mener à des complications surajoutées et aggraver davantage l’issue. Cas : Dix jours après avoir subi une hystérectomie abdominale totale par incision de Pfannenstiel en raison d’un cancer de l’endomètre, une femme de 73 ans a présenté un gros hématome sous-cutané. L’hématome en question a évolué et a mené à une nécrose étendue du tissu adipeux sous-cutané. La mise en œuvre d’un débridement de grande envergure s’est avérée nécessaire et la plaie a été traitée par pression négative au moyen de gaze afin de permettre une cicatrisation par deuxième intention. Une guérison satisfaisante a été constatée après 82 jours de traitement, sans greffe cutanée. Conclusion : Ce cas souligne l’utilité du traitement de plaie par pression négative au moyen de gaze, ainsi que la nécessité d’avoir recours à une approche multidisciplinaire au moment d’assurer la prise en charge de complications de plaie d’une telle complexité.

  18. Electrophoretic separation and analysis of living cells from solid tissues by several methods - Human embryonic kidney cell cultures as a model

    NASA Technical Reports Server (NTRS)

    Todd, Paul; Plank, Lindsay D.; Kunze, M. Elaine; Lewis, Marian L.; Morrison, Dennis R.

    1986-01-01

    The use of free-fluid electrophoresis methods to separate tissue cells having a specific function is discussed. It is shown that cells suspended by trypsinization from cultures of human embryonic kidney are electrophoretically heterogeneous and tolerate a wide range of electrophoresis buffers and conditions without significant attenuation of function. Moreover, these cells do not separate electrophoretically on the basis of size or cell position alone and can be separated according to their ability to give rise to progeny that produce specific plasminogen activators.

  19. The nanomechanical signature of liver cancer tissues and its molecular origin.

    PubMed

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-08-14

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.

  20. TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney | Office of Cancer Genomics

    Cancer.gov

    Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified.

  1. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues

    PubMed Central

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    Objective: To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Methods: One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. Results: The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (P<0.05). Spearman’s correlation analysis showed that the expressions of COX-2 and GLUT-1 (r=0.207, P<0.05), COX-2 and VEGF (r=0.243, P<0.05), as well as GLUT-1 and VEGF (r=0.758, P<0.05) were positively correlated. Conclusion: COX-2, GLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer. PMID:26101475

  2. Biomimetic tissue-engineered systems for advancing cancer research: NCI Strategic Workshop report.

    PubMed

    Schuessler, Teresa K; Chan, Xin Yi; Chen, Huanhuan Joyce; Ji, Kyungmin; Park, Kyung Min; Roshan-Ghias, Alireza; Sethi, Pallavi; Thakur, Archana; Tian, Xi; Villasante, Aranzazu; Zervantonakis, Ioannis K; Moore, Nicole M; Nagahara, Larry A; Kuhn, Nastaran Z

    2014-10-01

    Advanced technologies and biomaterials developed for tissue engineering and regenerative medicine present tractable biomimetic systems with potential applications for cancer research. Recently, the National Cancer Institute convened a Strategic Workshop to explore the use of tissue biomanufacturing for development of dynamic, physiologically relevant in vitro and ex vivo biomimetic systems to study cancer biology and drug efficacy. The workshop provided a forum to identify current progress, research gaps, and necessary steps to advance the field. Opportunities discussed included development of tumor biomimetic systems with an emphasis on reproducibility and validation of new biomimetic tumor models, as described in this report.

  3. A 3D biomimetic model of tissue stiffness interface for cancer drug testing.

    PubMed

    Lam, Chee Ren Ivan; Wong, Hui Kian; Nai, Spencer; Chua, Chee Kai; Tan, Nguan Soon; Tan, Lay Poh

    2014-07-07

    Contrary to oversimplified preclinical drug screens that derive treatment responses of cancer cells grown on plastic cell culturing surfaces, the actual in vivo scenario for cancer cell invasion is confronted with a diversity of tissue stiffness. After all, the packing of organs and tissues in the body translates to the abundant presence of tissue stiffness interfaces. The invasive dissemination of cancer cells in vivo might be encouraged by favorable tissue stiffness gradients, likely explaining the preferential spread of cancer cells which is subjective to the cancer type and origin of the primary site. Yet these critical tumor microenvironmental influences cannot be recapitulated in 2D preclinical drug screens, hence omitting potentially invaluable in vivo patterns of drug responses that may support safer clinical dosage implementation of cancer drugs. Current attempts to study stiffness implications on cancer cells are largely confined to 2D surfaces of tunable stiffness. While these studies collectively show that cancer cells migrate better on a stiffer matrix, the generation of a biomimetic 3D tissue stiffness interface for cancer cell migration would clearly give a more definitive understanding on the probable push and pull influences of the 3D ECM. Herein, we developed a biomimetic platform which enables the precise placement of spheroids at tissue stiffness interfaces constructed with natural ECM collagen type I. This enables a standardized comparison of spheroid invasion under a 3D stiffness gradient influence. We found that cancer cells in 3D infiltrated more extensively into a softer matrix of 300 Pa while showing significantly reduced invasion into stiffer matrix of 1200 and 6000 Pa. These biomimetic spheroid cultures postinvasion were suitably subjected to paclitaxel treatment and subsequent daily live quantification of apoptotic cells to evaluate the implications of tissue stiffness on chemotherapeutic treatment. We importantly found that cancer

  4. Kidney Diseases

    MedlinePlus

    ... Infections Your doctor can do blood and urine tests to check if you have kidney disease. If your kidneys fail, you will need dialysis or a kidney transplant. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  5. Kidney Failure

    MedlinePlus

    ... upcoming screening events. Kidney Action Day Kidney Action Day Learn about our signature outreach event. About AKF ... support of AKF. Kidney Action Day Kidney Action Day Learn about our signature outreach event. Free health ...

  6. Kidney Transplant

    MedlinePlus

    Kidney transplant Overview By Mayo Clinic Staff A kidney transplant is a surgical procedure to place a healthy kidney ... bloodstream via a machine (dialysis) or a kidney transplant to stay alive. Mayo Clinic's approach . Mayo Clinic ...

  7. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  8. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease A A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  9. Your Kidneys

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Kidneys KidsHealth > For Kids > Your Kidneys A A A ... and it will be lighter. What Else Do Kidneys Do? Kidneys are always busy. Besides filtering the ...

  10. Kidney Cysts

    MedlinePlus

    ... common type of PKD end up with kidney failure. PKD also causes cysts in other parts of ... and lifestyle changes, and if there is kidney failure, dialysis or kidney transplants. Acquired cystic kidney disease ( ...

  11. The distribution of tissue fibronectin and sialic acid in human breast cancer.

    PubMed

    Süer, S; Baloğlu, H; Güngör, Z; Sönmez, H; Kökoğlu, E

    1998-06-01

    Our findings indicate that sialic acid and fibronectin levels in breast tumors are higher than those in normal tissues. The mean tissue fibronectin and sialic acid concentrations for patients with breast cancer were 30.90 +/- 9.68 microg/mg protein and 21.60 +/- 9.35 microg/mg protein, respectively, and for normal controls were 12.47 +/- 5.69 microg/mg protein, respectively. Tissue fibronectin and sialic acid can be important markers for human breast cancer.

  12. Proteogenomic Analysis of Human Chromosome 9-Encoded Genes from Human Samples and Lung Cancer Tissues

    PubMed Central

    Ahn, Jung-Mo; Kim, Min-Sik; Kim, Yong-In; Jeong, Seul-Ki; Lee, Hyoung-Joo; Lee, Sun Hee; Paik, Young-Ki; Pandey, Akhilesh; Cho, Je-Yoel

    2014-01-01

    The Chromosome-centric Human Proteome Project (C-HPP) was recently initiated as an international collaborative effort. Our team adopted chromosome 9 (Chr 9) and performed a bioinformatics and proteogenomic analysis to catalog Chr 9-encoded proteins from normal tissues, lung cancer cell lines and lung cancer tissues. Approximately 74.7% of the Chr 9 genes of the human genome were identified, which included approximately 28% of missing proteins (46 of 162) on Chr 9 compared with the list of missing proteins from the neXtProt master table (2013-09). In addition, we performed a comparative proteomics analysis between normal lung and lung cancer tissues. Based on the data analysis, 15 proteins from Chr 9 were detected only in lung cancer tissues. Finally, we conducted a proteogenomic analysis to discover Chr 9-residing single nucleotide polymorphisms (SNP) and mutations described in the COSMIC cancer mutation database. We identified 21 SNPs and 4 mutations containing peptides on Chr 9 from normal human cells/tissues and lung cancer cell lines, respectively. In summary, this study provides valuable information of the human proteome for the scientific community as part of C-HPP. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD. PMID:24274035

  13. Renal (pro)renin receptor contributes to development of diabetic kidney disease through transforming growth factor-β1-connective tissue growth factor signalling cascade.

    PubMed

    Huang, Jiqian; Matavelli, Luis C; Siragy, Helmy M

    2011-04-01

    1. Transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) are expressed in renal glomeruli, and contribute to the development of diabetic nephropathy. Recently, we showed that (pro)renin receptor (PRR) is upregulated in the kidneys of the streptozocin (STZ)-induced diabetes rat model. We hypothesized that in the presence of hyperglycaemia, increased renal PRR expression contributes to enhanced TGF-β1-CTGF signalling activity, leading to the development of diabetic kidney disease. 2. In vivo and in vitro studies were carried out in Sprague-Dawley rats and rat mesangial cells (RMC). PRR blockade was achieved in vivo by treating STZ induced diabetes rats with the handle region peptide (HRP) of prorenin and in vitro by HRP or PRR siRNA in RMC. Angiotensin AT1 receptor blockade was achieved by valsartan treatment. 3. Results showed that expression of PRR, TGF-β1 and CTGF were upregulated in diabetic kidneys and RMC exposed to high glucose. Glucose exposure also induced PRR phosphorylation, a process that was inhibited by HRP, valsartan or PRR siRNA. HRP and valsartan significantly attenuated renal TGF-β1 and CTGF expression in diabetic animals and high glucose treated RMC. Similar results were observed in high glucose exposed RMC in response to PRR siRNA. TGF-β receptor blockade decreased CTGF expression in RMC. Combined administration of valsartan and PRR siRNA showed further reduction of TGF-β1 and CTGF expression in RMC. 4. In conclusion, PRR contributes to kidney disease in diabetes through an enhanced TGF-β1-CTGF signalling cascade.

  14. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

    NASA Astrophysics Data System (ADS)

    Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

    2015-07-01

    Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

  15. Study on nasopharyngeal cancer tissue using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Ge, Xiaosong; Lin, Xueliang; Xu, Zhihong; Wei, Guoqiang; Huang, Wei; Lin, Duo

    2016-10-01

    Surface-enhanced Raman spectroscopy (SERS) can provide detailed molecular structure and composition information, and has demonstrated great potential in biomedical filed. This spectroscopy technology has become one of the most important optical techniques in the early diagnosis of cancer. Nasopharyngeal cancer (NPC) is a malignant neoplasm arising in the nasopharyngeal epithelial lining, which has relatively high incidence and death rate in Southeast Asia and southern China. This paper reviews the current progress of SERS in the field of cancer diagnostics, including gastric cancer, colorectal cancer, cervical cancer and nasopharyngeal cancer. In addition to above researches, we recently develop a novel NPC detection method based on tissue section using SERS, and obtain primary results. The proposed method has promising potential for the detection of nasopharyngeal carcinoma.

  16. Characterization of human breast cancer tissues by infrared imaging.

    PubMed

    Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

    2016-01-21

    Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

  17. Differential MicroRNA Expression Between Gastric Cancer Tissue and Non-cancerous Gastric Mucosa According to Helicobacter pylori Status

    PubMed Central

    Lee, Jung Won; Kim, Nayoung; Park, Ji Hyun; Kim, Hee Jin; Chang, Hyun; Kim, Jung Min; Kim, Jin-Wook; Lee, Dong Ho

    2017-01-01

    Background MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n = 8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status. PMID:28382284

  18. The Microbiota of Breast Tissue and Its Association with Breast Cancer

    PubMed Central

    Urbaniak, Camilla; Gloor, Gregory B.; Brackstone, Muriel; Scott, Leslie; Tangney, Mark

    2016-01-01

    ABSTRACT In the United States, 1 in 8 women will be diagnosed with breast cancer in her lifetime. Along with genetics, the environment contributes to disease development, but what these exact environmental factors are remains unknown. We have previously shown that breast tissue is not sterile but contains a diverse population of bacteria. We thus believe that the host's local microbiome could be modulating the risk of breast cancer development. Using 16S rRNA amplicon sequencing, we show that bacterial profiles differ between normal adjacent tissue from women with breast cancer and tissue from healthy controls. Women with breast cancer had higher relative abundances of Bacillus, Enterobacteriaceae and Staphylococcus. Escherichia coli (a member of the Enterobacteriaceae family) and Staphylococcus epidermidis, isolated from breast cancer patients, were shown to induce DNA double-stranded breaks in HeLa cells using the histone-2AX (H2AX) phosphorylation (γ-H2AX) assay. We also found that microbial profiles are similar between normal adjacent tissue and tissue sampled directly from the tumor. This study raises important questions as to what role the breast microbiome plays in disease development or progression and how we can manipulate this for possible therapeutics or prevention. IMPORTANCE This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria that had the ability to cause DNA damage in vitro were detected in breast cancer patients, as was a decrease in some lactic acid bacteria, known for their beneficial health effects, including anticarcinogenic properties. This study raises important questions as to the role of the mammary microbiome in modulating the risk of breast cancer development. PMID:27342554

  19. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2011-05-01

    cytochrome P450 , family 2, subfamily F, polypeptide 1 4.8 HBD hemoglobin, delta 4.6 Down-regulated SPAG11B sperm associated antigen 11B –12.3 DEFB129... Cancer Interactions PRINCIPAL INVESTIGATOR: Timothy Thompson, Ph.D. CONTRACTING ORGANIZATION: University of Texas M.D. Anderson... Cancer Center Houston, TX 77030 REPORT DATE: May 2011 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical

  20. Levels of metals in kidney, liver and muscle tissue and their relation to the occurrence of parasites in the red fox in the Lower Silesian Forest in Europe.

    PubMed

    Binkowski, Łukasz J; Merta, Dorota; Przystupińska, Anna; Sołtysiak, Zenon; Pacoń, Jarosław; Stawarz, Robert

    2016-04-01

    Together with the occurrence of parasites, increased concentrations of xenobiotics, to which scavengers are greatly exposed, may significantly influence the physiology of red foxes. It is also suspected that these two factors interact. The accumulation of various metals (Ca, Cd, Cu, Fe, Hg, K, Mg, Ni, Pb, Zn) in kidney, liver and muscle tissue was investigated, as well as the occurrence of parasites, and the potential link to the presence of metals. Generally speaking, neither sex nor age influenced these concentrations. K, Mg and Fe were found in the highest concentrations and Hg was found in the lowest. Various relationships between the concentrations of metals were observed in the tissues. 34% of the specimens studied were hosts to parasites. No clear, significant connection between the concentrations and the occurrence of parasites was noted, but the discernible trend confirmed by the logistic regression, needs further study.

  1. Transcriptomic molecular markers for screening human colon cancer in stool and tissue.

    PubMed

    Ahmed, Farid E; Vos, Paul; iJames, Stephanie; Lysle, Donald T; Allison, Ron R; Flake, Gordon; Sinar, Dennis R; Naziri, Wade; Marcuard, Stefan P; Pennington, Rodney

    2007-01-01

    There is a need for sensitive and specific diagnostic molecular markers that can be used to monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and in situ in adenoma-carcinoma epithelium of the colon. RNA-based detection methods are more comprehensive than either DNA-, protein- or methylation-based screening methods. By routinely and systematically being able to perform quantitative gene expression studies on these samples using less than ten colon cancer genes selected by the enormous resources of the National Cancer Institute's Cancer Genome Anatomy Project, we were able to monitor changes at various stages in the neoplastic process, allowing for reliable diagnostic screening of colon cancer particularly at the early, pre-malignant stages. Although the expression of some of the genes tested in tissue showed less variability in normal or cancerous patients than in stool, the stool by itself is suitable for screening. Thus, a transcriptomic approach using stool or tissue samples promises to offer more sensitivity and specificity than currently used molecular screening methods for colon cancer. A larger prospective clinical study utilizing stool and tissue samples derived from many control and colon cancer patients, to allow for a statistically valid analysis, is now urgently required to determine the true sensitivity and specificity of the transcriptomic screening approach for this preventable cancer.

  2. Cancer Detection in Human Tissue Samples Using a Fiber-Tip pH Probe.

    PubMed

    Schartner, Erik P; Henderson, Matthew R; Purdey, Malcolm; Dhatrak, Deepak; Monro, Tanya M; Gill, P Grantley; Callen, David F

    2016-12-01

    Intraoperative detection of tumorous tissue is an important unresolved issue for cancer surgery. Difficulty in differentiating between tissue types commonly results in the requirement for additional surgeries to excise unremoved cancer tissue or alternatively in the removal of excess amounts of healthy tissue. Although pathologic methods exist to determine tissue type during surgery, these methods can compromise postoperative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis, and are restricted to excised tissue. In this work, we report the development of an optical fiber probe that could potentially find use as an aid for margin detection during surgery. A fluorophore-doped polymer coating is deposited on the tip of an optical fiber, which can then be used to record the pH by monitoring the emission spectra from this dye. By measuring the tissue pH and comparing with the values from regular tissue, the tissue type can be determined quickly and accurately. The use of a novel lift-and-measure technique allows for these measurements to be performed without influence from the inherent autofluorescence that commonly affects fluorescence-based measurements on biological samples. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration, which could find use in the operating theater. Use of this probe in surgery either on excised or in vivo tissue has the potential to improve success rates for complete removal of cancers. Cancer Res; 76(23); 6795-801. ©2016 AACR.

  3. Astragaloside effect on TGF-β1, SMAD2/3, and α-SMA expression in the kidney tissues of diabetic KKAy mice.

    PubMed

    Wang, Yaning; Lin, Chao; Ren, Qiang; Liu, Yunqi; Yang, Xiangdong

    2015-01-01

    Numerous cytokines participate in the occurrence and development of inflammation and renal interstitial fibrosis. Previous studies confirmed that TGF-β1 overexpressed in diabetic nephropathy. As a downstream signal protein of TGF-β1 family, SMAD has an important role in the process of α-SMA mediated renal interstitial fibrosis. This study aimed to study astragaloside effect on TGF-β1, SMAD2/3, and α-SMA expression in the kidney tissue of diabetic KKAy mice, to reveal its potential impact on renal interstitial fibrosis. 20 type II diabetic KKAy mice were randomly equally divided into model group and astragaloside group, while 10 male C57BL/6J mice were selected as the control. Astragaloside at 40 mg/(kg•d) was given when the KKAy mice fed with high-fat diet to 14 weeks old. The mice were killed at 24 weeks old and the kidney tissue samples were collected. Pathology morphological changes were observed. TGF-β1, SMAD2/3, and α-SMA expression levels were determined by immunohistochemistry. Compared with control, mice kidney in model group appeared obvious fibrosis and up-regulated blood glucose level, TGF-β1, SMAD2/3, and α-SMA expression (P < 0.05). Mice in astragaloside group exhibited alleviated renal interstitial fibrosis compared with the model. Its blood glucose level, TGF-β1, SMAD2/3, and α-SMA expression levels were significantly lower than the model group (P < 0.05). Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-β/SMADS signaling pathway and down-regulating TGF-β1, SMAD2/3, and α-SMA expression.

  4. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    PubMed

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  5. A Regulatory miRNA–mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury

    PubMed Central

    de Almeida, Danilo Candido; Bassi, Ênio Jose; Azevedo, Hatylas; Anderson, Letícia; Origassa, Clarice Silvia Taemi; Cenedeze, Marcos Antônio; de Andrade-Oliveira, Vinicius; Felizardo, Raphael José Ferreira; da Silva, Reinaldo Correia; Hiyane, Meire Ioshie; Semedo, Patricia; dos Reis, Marlene Antônia; Moreira-Filho, Carlos Alberto; Verjovski-Almeida, Sergio; Pacheco-Silva, Álvaro; Câmara, Niels Olsen Saraiva

    2017-01-01

    Mesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidenced in vivo and in vitro by modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-β, fibrosis, and epithelial–mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA–mRNA network. PMID:28096802

  6. In vivo optical analysis of pancreatic cancer tissue in living model mice using fluorescence and Raman spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Suzuki, Toshiaki; Hattori, Yusuke; Katagiri, Takashi; Mitsuoka, Hiroki; Sato, Ken-ichi; Asakura, Toru; Shimosegawa, Toru; Sato, Hidetoshi

    2009-02-01

    Living pancreatic cancer tissues grown subcutaneously in nude mice are studied by in vivo Raman spectroscopy and autofluorescence imaging. Comparing the same point spectra of alive pancreatic cancer tissue to that of the dead tissue, it is found that they are different each other. The results suggest that the spectral changes reflect the protein conformational changes in the tumor tissue with death of the host animal. From the result of autofluorescence study, in vivo autofluorescence imaging has potential as a method to assign the histological elements of the pancreatic cancer tissue without any staining. These results strongly suggest that combination of these techniques is very important to study biological tissue.

  7. ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

    PubMed Central

    Sheng, Wei-Zhong; Chen, Yu-Sheng; Tu, Chuan-Tao; He, Juan; Zhang, Bo; Gao, Wei-Dong

    2016-01-01

    AIM To explore expression of angiopoietin-like protein 2 (ANGPTL2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression of ANGPTL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and PAMC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells. RESULTS Compared to normal tissues, ANGPTL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGPTL2 mRNA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and PAMC82. The expression of ANGPTL2 in highly malignant gastric cancer cell lines BGC823 and PAMC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank control cells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells. CONCLUSION ANGPTL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGPTL2 may become a new target for treatment of gastric cancer. PMID:28058016

  8. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control

    PubMed Central

    Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

    2016-01-01

    Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Conclusions Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm

  9. Cytotoxic effect of microbial biosurfactants against human embryonic kidney cancerous cell: HEK-293 and their possible role in apoptosis.

    PubMed

    Pradhan, Arun Kumar; Pradhan, Nilotpala; Mohapatra, Purusottam; Kundu, Chanakya Nath; Panda, Prasanna Kumar; Mishra, Barada Kanta

    2014-11-01

    Two different microbial biosurfactants S9BS and CHBS were isolated from Lysinibacillus fusiformis S9 and Bacillus tequilensis CH. Cytotoxicity effect of these biosurfactants on human embryonic kidney cancerous cell (HEK-293) were studied with the help of 3-(4,5-dimethylthiazol-2yl-)-2, 5-diphenyl tetrazolium bromide (MTT) assay and morphological changes were observed under inverted microscope. The biosurfactants exhibited positive cytotoxic effect on HEK-293 cell line. It was found that LC50 of S9BS and CHBS were 75 and 100 μg ml(-1), respectively. Further cell cycle and apoptosis analysis of biosurfactant-treated HEK-293 cell line were done by FACS. In this study, cytotoxic effect of glycolipid biosurfactant against HEK-293 cell lines is reported for the first time. Mechanism towards increased membrane permeability of biosurfactant-treated cancer cell may be the incorporation of its lipid moiety into the plasma membrane leading to formation of pores and membrane disruption. Hence, these microbial biosurfactants can prove to be significant biomolecule for cancer treatment.

  10. Radiofrequency Ablation in Combination with Embolization in Metachronous Recurrent Renal Cancer in Solitary Kidney after Contralateral Tumor Nephrectomy

    SciTech Connect

    Gebauer, Bernhard Werk, Michael; Lopez-Haenninen, Enrique; Felix, Roland; Althaus, Peter

    2007-07-15

    Purpose. To evaluate the feasibility and safety of minimally invasive, percutaneous techniques in metachronous recurrent renal cell cancers (RCCs) in solitary kidneys. Methods. In 4 patients, recurrent RCC was treated by radiofrequency ablation (RFA) (RITA, StarBurst) alone, and in 2 patients by RFA in combination with superselective transarterial particle-lipiodol embolization using 3 Fr microcatheters. RFA was guided by computed tomography in 5 patients, and by magnetic resonance imaging in 1 patient. Mean tumor diameter was 26.7 mm (range 10-45 mm). All interventions were technically successful; during follow-up 1 patient developed recurrent RCC, which was retreated by RFA after embolization. Results. No major peri- or postprocedural complications occurred. Changes in creatinine (pre- vs. post-intervention, 122 vs. 127 {mu}mol/l) and calculated creatinine clearance (pre- vs. post-intervention, 78 vs. 73 ml/min) after ablation were minimal. Conclusion. In single kidneys, percutaneous, minimally invasive techniques are safe and feasible. In large tumors, or where there are adjacent critical structures, we prefer a combination of embolization and thermal ablation (RFA)

  11. The Light Propagation in Biological Tissue for Cancer Treatment

    DTIC Science & Technology

    2007-11-02

    For the effective PDT , we should controlled the value of photosensitizer , power density of laser and supplied oxygen to tissue. Increasing the power...by means of light action on photosensitizer in tissue. It is considered that destroying effect is mainly due to the formation of singlet oxygen...resulting from the interaction of light excited photosensitizer with molecular oxygen (triplet state in the ground state). So the destroying effect

  12. A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

    PubMed Central

    2016-01-01

    Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis), but also in the situations when a hypercoagulable state is presumed. The unspecific presenting symptoms often mask the true etiology of the patient's complaints. We present here a rare case of renal infarction that occurred in the setting of a hypercoagulable state, in a female patient with a history of breast cancer and documented hepatic metastases. PMID:27293927

  13. Distinct mutation accumulation rates among tissues determine the variation in cancer risk

    PubMed Central

    Hao, Dapeng; Wang, Li; Di, Li-jun

    2016-01-01

    Cancer is believed to be a result of accumulated mutations. However, this concept has not been fully confirmed owing to the impossibility of tracking down the ancestral somatic cell. We sought to verify the concept by exploring the correlation between cancer risk and mutation accumulation among different tissues. We hypothesized that the detected mutations through bulk tumor sequencing are commonly shared in majority, if not all, of tumor cells and are therefore largely a reflection of the mutations accumulated in the ancestral cell that gives rise to tumor. We collected a comprehensive list of mutation frequencies revealed by bulk tumor sequencing, and investigated its correlation with cancer risk to mirror the correlation between mutation accumulation and cancer risk. This revealed an approximate 1:1 relationship between mutation frequency and cancer risk in 41 different cancer types based on the sequencing data of 5,542 patients. The correlation strongly suggests that variation in cancer risk among tissues is mainly attributable to distinct mutation accumulation rates. Moreover, the correlation establishes a baseline to evaluate the effect of non-mutagenic carcinogens on cancer risk. Finally, our mathematic modeling provides a reasonable explanation to reinforce that cancer risk is predominantly determined by the first rate-limiting mutation. PMID:26785814

  14. Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

    PubMed

    Crowell, Ed; Wang, Gufeng; Cox, Jason; Platz, Charles P; Geng, Lei

    2005-03-01

    Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer

  15. Exome enrichment and SOLiD sequencing of formalin fixed paraffin embedded (FFPE) prostate cancer tissue.

    PubMed

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study's aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing.

  16. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE) Prostate Cancer Tissue

    PubMed Central

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing. PMID:22942743

  17. [Determination of thirty three elements in lung cancer tissues of patients with lung cancer by microwave digestion-ICP-MS].

    PubMed

    Zhang, Lin-Lin; Ma, Qian-Li; Huang, Yun-Chao; Wu, Guo-Ping; Wei, Fu-Sheng

    2009-12-01

    A method for determining 33 elements in lung tissues of patients with lung cancer was developed by using vacuum freeze-drying microwave digestion-ICP-MS. The lung tissue samples were treated by vacuum freeze-drying equipment. After microwave digestion in HNO3-H2O2 solution system, the samples were diluted with the method of constant volume. Under the optimized conditions the samples were analyzed by ICP-MS. The double internal standard elements Rh and Re were used to compensate for matrix suppression effect and sensitivity drift. The analytical results showed that the detection limits of the 33 elements were 0.01-0.45 ng x mL(-1). The national standard reference material GBW(E)080193 bovine liver was analyzed by the described method and the measured element values accorded with the standard values or the reference values. The relative standard deviation (RSD) of the method was 2.1%-14.3%. The recovery rates of the studied elements were 90.1%-117.5%. The contents of 33 elements in lung cancer tissues, paracancerous lung tissues and benign lung tissues of 6 patients with lung cancer were determined by the method. It was indicated that the method is rapid, simple and accurate for determining multi-elements in human lung tissue and other biological samples.

  18. Distinction of gastric cancer tissue based on surface-enhanced Raman spectroscopy