Science.gov

Sample records for cancer kidney tissues

  1. 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.

  2. 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.

  3. 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 ...

  4. Fluorescence polarization spectroscopy and time-resolved fluorescence kinetics of native cancerous and normal rat kidney tissues.

    PubMed Central

    Tata, D B; Foresti, M; Cordero, J; Tomashefsky, P; Alfano, M A; Alfano, R R

    1986-01-01

    Steady state fluorescence polarization spectra and time-resolved emission decay kinetics have been measured in vitro from malignant and normal rat kidney tissue. The degrees of polarization and emission lifetimes from the cancerous and normal systems are different. The spectroscopic differences are attributed to environmental transformations local to the native flavin and porphyrin fluorophors' binding sites. PMID:3489490

  5. 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.

  6. 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.

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

    MedlinePlus

    ... the key statistics 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 ...

  8. 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. PMID:26134528

  9. Infrared spectroscopic imaging of kidney tumor tissue

    NASA Astrophysics Data System (ADS)

    Sablinskas, V.; Steiner, G.; Koch, E.; Ceponkus, J.; Pucetaite, M.; Strazdaite, S.; Urboniene, V.; Jankevicius, F.

    2011-02-01

    Infrared spectroscopic imaging of cancerous kidney tissue was performed by means of FTIR microscopy. The spectra of thin tissue cryosections were collected with 64x64 MCT FPA detector and imaging area was increased up to 5.4×5.4 mm by mapping by means of PC controlled x,y stage. Chemical images of the samples were constructed using statistical treatment of the raw spectra. Several unsupervised and supervised statistical methods were used. The imaging results are compared with results of the standard histopathological analysis. It was concluded that application of method of cluster analysis ensures the best contrast of the images. It was found that border between cancerous and normal tissues visible in the infrared spectroscopic image corresponds with the border visible in histopathological image. Closer examination of the infrared spectroscopic image reveals that small domains of cancerous cells are found beyond the border in areas distant from the border up to 3 mm. Such domains are not visible in the histopathological images. The smallest domains found in the infrared images are approx. 60 μm.

  10. 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) ...

  11. 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.

  12. 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

    2015-01-01

    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. PMID:25426679

  13. Biologic Therapy (Immunotherapy) for Kidney Cancer

    MedlinePlus

    ... articles window. My Saved Articles » My ACS » Kidney Cancer (Adult) - Renal Cell Carcinoma + - Text Size Download Printable Version [PDF] » Treating Kidney Cancer TOPICS Document Topics GO » SEE A LIST » How ...

  14. Generating kidney tissue from pluripotent stem cells

    PubMed Central

    Little, MH

    2016-01-01

    With the isolation of human pluripotent stem cells came the possibility of generating specific cell types for regenerative medicine. This has required the development of protocols for directed differentiation into many distinct cell types. One of the more complicated tissue types to recreate is the kidney. Here we review recent progress towards the recreation of not only specific kidney cell types but complex kidney organoids, models of the developing human organ, in vitro. We will also discuss potential short and long term applications of these approaches. PMID:27551541

  15. Laser capture microdissection of kidney tissue.

    PubMed

    Woroniecki, Robert P; Bottinger, Erwin P

    2009-01-01

    Kidney tissue laser capture microdissection (LCM) is of great clinical relevance since genome wide studies on total kidney messenger RNA (mRNA) potentially miss important factors involved in the pathogenesis of the disease in glomeruli and tubules. This technique is readily applicable to study mRNA from isolated glomeruli and tubules of human kidney biopsy material. In this chapter we present a "cook-book" practical approach of utilizing LCM in combination with RNA isolation technique in downstream applications in nephrology. PMID:19148600

  16. Therapeutic Strategies for Hereditary Kidney Cancer.

    PubMed

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers. PMID:27325049

  17. What Are the Risk Factors for Kidney Cancer?

    MedlinePlus

    ... kidney cancer? 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. Tissue-Engineered Kidney Disease Models

    PubMed Central

    DesRochers, Teresa M.; Palma, Erica; Kaplan, David L.

    2014-01-01

    Renal disease represents a major health problem that often results in end-stage renal failure necessitating dialysis and eventually transplantation. Historically these diseases have been studied with patient observation and screening, animal models, and two-dimensional cell culture. In this review, we focus on recent advances in tissue engineered kidney disease models that have the capacity to compensate for the limitations of traditional modalities. The cells and materials utilized to develop these models are discussed and tissue engineered models of polycystic kidney disease, drug-induced nephrotoxicity, and the glomerulus are examined in detail. The application of these models has the potential to direct future disease treatments and preclinical drug development. PMID:24361391

  19. 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

  20. What Are the Key Statistics about Kidney Cancer?

    MedlinePlus

    ... factors for 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. Last Medical Review: ...

  1. Cancer of the Kidney and Renal Pelvis

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 62,700 % of All New Cancer Cases 3.7% Estimated Deaths in 2016 14,240 % of All Cancer ... of This Cancer : In 2013, there were an estimated 394,336 people living with kidney and renal ...

  2. Do We Know What Causes Kidney Cancer?

    MedlinePlus

    ... kidney cells to become cancerous. Changes (mutations) in genes Researchers are starting to understand how certain changes ... oncogenes or turn off tumor suppressor genes. Inherited gene mutations Certain inherited DNA changes can lead to ...

  3. Drugs Approved for Wilms Tumor and Other Childhood Kidney Cancers

    MedlinePlus

    ... Drugs Approved for Wilms Tumor and Other Childhood Kidney Cancers This page lists cancer drugs approved by ... Drugs Approved for Wilms Tumor and Other Childhood Kidney Cancers Cosmegen (Dactinomycin) Dactinomycin Doxorubicin Hydrochloride Vincasar PFS ( ...

  4. 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.

  5. 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 ...

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

    MedlinePlus

    ... Next Topic Additional resources for 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 ( ...

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

    MedlinePlus

    ... for kidney cancer? What should you ask your doctor about kidney cancer? It’s important to have frank, ... on treatment? Do I need to see other doctors? How much experience do you have treating this ...

  8. 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. PMID:26202137

  9. [Cystic cancer of the kidney].

    PubMed

    el Moussaoui, A; Dakir, M; Sarf, I; Aboutaeib, R; el Mrini, M; Benjelloun, S

    1997-01-01

    Cystic renal cancer is uncommon and raises real preoperative diagnostic problems, requiring the use of medical imaging, and sometimes even surgery. The authors report 3 cases of cystic renal cancer in 2 men and 1 woman, aged 87, 67 and 20 years, respectively. Three patients presented with the urological triad (haematuria, pain and lumbar mass). Ultrasonography suggested the diagnosis of cystic cancer in all 3 cases. Computed tomography was performed in 2 patients and more precisely confirmed the ultrasound findings. Selective arteriography, performed in one patient, confirmed the hypothesis of malignancy. Surgical exploration resulted in radical total nephrectomy. Histology confirmed the diagnosis of adenocarcinoma. The course was favourable in 2 cases after a follow-up of 4 years. One patient presented a local recurrence with pulmonary metastases 6 months after the operation. A review of the literature illustrates the diagnostic difficulties of this form of renal cancer. PMID:9509236

  10. 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 Central

    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. PMID:26244343

  11. 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. PMID:26244343

  12. 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.

  13. Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer

    ClinicalTrials.gov

    2016-04-18

    Carcinoma of the Collecting Ducts of Bellini; Chromophobe Renal Cell Carcinoma; Kidney Medullary Carcinoma; Kidney Oncocytoma; Papillary Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Renal Cell Cancer

  14. International cancer seminars: a focus on kidney cancer.

    PubMed

    Scelo, G; Hofmann, J N; Banks, R E; Bigot, P; Bhatt, R S; Cancel-Tassin, G; Chew, S K; Creighton, C J; Cussenot, O; Davis, I J; Escudier, B; Frayling, T M; Häggström, C; Hildebrandt, M A T; Holcatova, I; Johansson, M; Linehan, W M; McDermott, D F; Nathanson, K L; Ogawa, S; Perlman, E J; Purdue, M P; Stattin, P; Swanton, C; Vasudev, N S; Wu, X; Znaor, A; Brennan, P; Chanock, S J

    2016-08-01

    Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research. PMID:27130845

  15. Decade in Review-Kidney Cancer Kidney cancer's decade—discoveries, therapies and opportunities

    PubMed Central

    Linehan, W. Marston; Ricketts, Christopher J.

    2015-01-01

    Advances in kidney cancer have occurred over the past decade, including the discovery of mutations in chromatin remodeling genes and genomic heterogeneity in clear cell renal cell carcinoma (ccRCC), altered metabolic patterns in ccRCC and papillary renal cell carcinoma and the approval of drugs for patients with ccRCC. PMID:25287783

  16. 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.

  17. What You Need to Know about Kidney Cancer

    MedlinePlus

    ... This booklet is not about transitional cell cancer (TCC) of the kidney. TCC is a different disease with different treatment options. For the latest information about TCC, visit: http://www.cancer.gov/cancertopics/types/transitionalcell ...

  18. Thyroxine monodeiodination in normal human kidney tissue in vitro.

    PubMed

    Boye, N

    1986-08-01

    The present study deals with thyroxine monodeiodination in normal human kidney. To allow for comparison with previous reports, the present methods are similar to those used by others in rat tissue studies. The microsomal cell fraction of normal human kidney tissue was obtained by differential ultracentrifugation. The microsomes were incubated under various conditions and the deiodination products assayed with radioimmunoassay. A type I 5'-monodeiodinase was demonstrated, pH optimum around 6.5. Competitive inhibition was observed of T3 generation from T4 by rT3 with a Km of 3.0 microM and a Ki of 4 microM. Vmax was 26.1 pmol/min/mg protein. Likewise rT3 was generated from added T4, but it was rapidly degraded, while T3 was relatively stable as is the case in rat tissue preparations. Propylthiouracil inhibited 5'-deiodination in a dose dependent fashion with complete abolishment of deiodination at propylthiouracil concentration of 10(-4) M. Ipodate inhibited the reaction with complete inhibition at 10(-2) M. The data demonstrate that a human kidney particulate cell-fraction contained considerable amounts of T4 deiodinases, very similar to the type I deiodinase of various rat tissue, although the handling of rT3 and the inhibitory action of this iodothyronine on T4 to T3 conversion seem to be slightly different in the two species. PMID:3751464

  19. Do Overweight People Fare Better Than Others with Kidney Cancer?

    MedlinePlus

    ... Overweight People Fare Better Than Others With Kidney Cancer? Study suggests they do, giving insights into potential new treatments To use the ... We plan to test FASN inhibitors in an animal model as a possible therapy for kidney cancer," he said. The study findings were published online ...

  20. 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.

  1. Obesity, interrelated mechanisms, and exposures and kidney cancer.

    PubMed

    Moyad, M A

    2001-11-01

    Obesity has been shown to increase the risk or be associated with numerous conditions from cardiovascular disease and type II diabetes to erectile dysfunction and osteoarthritis. Obesity may also be associated with numerous cancers, and kidney cancer or renal-cell cancer (RCC) may have one of the strongest correlations to obesity compared with cancer at any other site. Almost every epidemiologic investigation has demonstrated an association that tends to affect women more than men, but both genders are impacted. In general, past studies suggest that with increasing weight, a threshold point exists whereby a certain range of body mass index dramatically changes risk. Men and women at the most extreme ends of obesity tend to have the highest risk or only risk in past studies. Individuals at the more extreme ends of obesity may be affected by an almost indefinite number of mechanisms and exposures that could determine incidence and possibly prognosis. For example, higher estrogen levels, elevated insulin levels, a greater concentration of growth factors in adipose tissue, hypertension, cholesterol metabolism abnormalities, and immune malfunction are just some of the potential mechanisms that may increase kidney cancer risk. Obese individuals may also have lower serum levels of vitamin D and engage in less physical activity. Smoking or genetic predisposition to RCC may synergistically contribute to the effect of obesity on risk. The potential mechanisms and associations are numerous and complex. Regardless of the actual cancer risk now and in the future, the overall effect of obesity on general health is clear, and this should be kept in mind in the discussion between health professional and patient. PMID:11769879

  2. Skin manifestations associated with kidney cancer.

    PubMed

    Amin, Asim; Burgess, Earle F

    2016-06-01

    Kidney cancer is a heterogenous disease encompassing several distinct clinicopathologic entities with different underlying molecular aberrations and clinical outcomes. Renal cell carcinoma (RCC) has been shown to evoke immunologic responses that can impact the natural history of disease and clinical presentation. It is important to recognize atypical presentations of disease, including cutaneous manifestations. The incidence of skin metastases from RCC is low, yet needs to be appreciated in the appropriate setting; clinical presentation for these lesions is reviewed briefly. There are several hereditary syndromes that present with well characterized cutaneous lesions and are associated with an increased risk for RCC, including Von Hippel-Lindau and Birt-Hogg-Dubé syndromes. Given that these skin lesions may be the first presenting sign for RCC, timely recognition is of essence and both are discussed in some detail. Several therapeutic options based on immunomodulation are approved for the treatment of advanced RCC. Dermatologic toxicities observed with these agents are also briefly discussed. PMID:27178696

  3. 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.

  4. NIH scientists provide new insight into rare kidney cancer

    Cancer.gov

    NIH scientists have discovered a unique feature of a rare, hereditary form of kidney cancer that may provide a better understanding of its progression and metastasis, possibly laying the foundation for the development of new targeted therapies.

  5. Some Advanced Kidney Cancer Patients May Postpone Treatment

    MedlinePlus

    ... advanced kidney cancer that has spread require immediate, aggressive treatment, a small new study suggests. "A subset ... them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some ...

  6. 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

  7. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury.

    PubMed

    Duann, Pu; Lianos, Elias A; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  8. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    PubMed Central

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  9. [Cancer in ectopic breast tissue].

    PubMed

    Røikjer, Johan; Lindmark, Ida; Knudsen, Thor

    2015-06-15

    Two different forms of ectopic breast tissue exist in human beings: supernumerary and aberrant. Both forms are usually seen alongside the milk lines, which extend from the upper limbs to the inguinal region where they give rise to mammary glands, areolas and nipples. Although ectopic- and orthotopic breast tissue are placed in different areas of the body, they still share the same ability to undergo pathological degeneration. The focus of this case report is to shed light on this unusual form of breast cancer, and raise the level of awareness in cases with lumps located in the milk lines. PMID:26101129

  10. [Molecular biological predictors for kidney cancer].

    PubMed

    Vtorushin, S V; Tarakanova, V O; Zavyalova, M V

    2016-01-01

    The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely; Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Berclin 1 that is an authophagy indicator in intact tissues gives rise to t high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC. PMID:27077146

  11. 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. PMID:23331953

  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. Protein profiling of microdomains purified from renal cell carcinoma and normal kidney tissue samples.

    PubMed

    Raimondo, F; Morosi, L; Chinello, C; Perego, R; Bianchi, C; Albo, G; Ferrero, S; Rocco, F; Magni, F; Pitto, M

    2012-04-01

    Renal cell carcinoma (RCC) is representing about 3% of all adult cancers. A promising strategy for cancer biomarker discovery is subcellular comparative proteomics, allowing enriching specific cell compartments and assessing differences in protein expression patterns. We investigated the proteomic profile of a peculiar RCC subcellular compartment, plasma membrane microdomains (MD), involved in cell signalling, transport, proliferation and in many human diseases, such as cancer. Subcellular fractions were prepared by differential centrifugation from surgical samples of RCC and adjacent normal kidney (ANK). MD were isolated from plasma-membrane-enriched fractions after Triton X-100 treatment and sucrose density gradient ultracentrifugation. MD derived from RCC and ANK tissues were analyzed after SDS-PAGE separation by LC-ESI-MS/MS. We identified 93 proteins from MD isolated from RCC tissue, and 98 proteins from ANK MD. About 70% of the identified proteins are membrane-associated and about half of these are known as microdomain-associated. GRAVY scores assignment shows that most identified proteins (about 70%) are in the hydrophobic range. We chose a panel of proteins to validate their differential expression by WB. In conclusion, our work shows that RCC microdomain proteome is reproducibly different from ANK, and suggests that mining into such differences may support new biomarker discovery. PMID:22159573

  14. Development of flexible-heteroarotinoids for kidney cancer

    PubMed Central

    Liu, Tongzu; Masamha, Chioniso Patience; Chengedza, Shylet; Berlin, K. Darrell; Lightfoot, Stan; He, Feng; Benbrook, Doris Mangiaracina

    2009-01-01

    Potential chemopreventive and therapeutic value of the lead Flexible Heteroarotinoid (Flex-Het), SHetA2, was indicated by growth inhibition of multiple cancer cell lines. The objective of this study was to evaluate the SHetA2 mechanism and in vivo activity in kidney cancer. SHetA2 induced apoptosis in the Caki-1 kidney cancer cell line through reduction of Bcl-2 protein and induction of PARP-1 and caspase 3 cleavages, whereas normal kidney epithelial cells exhibited resistance. Both normal and cancerous cells underwent G1 arrest and loss of Cyclin D1. Tubule differentiation was induced in organotypic cultures and xenograft tumors in association with increases in E-Cadherin mRNA and protein expression. SHetA2 repressed activity of nuclear factor-κB, a transcription factor that regulates apoptosis, Bcl-2, growth, Cyclin D1, differentiation, and E-Cadherin in the opposite manner as SHetA2. Glutathione binding and generation of reactive oxygen species were not required for these activities. Oral SHetA2 inhibited growth in one of two renal cancer xenograft models without causing mortality or weight loss. Structure function analysis of related Flex-Hets for potential improvement of SHetA2 pharmaceutical properties showed that compounds with increased hydrophilicity slightly reduced the growth inhibition efficacy, but retained the differential effect on cancer over normal cells. Flex-Hets and metabolites were not mutagenic in the Ames test. In conclusion, SHetA2 regulates growth, differentiation, and apoptosis in kidney cancer cells through multiple molecular events downstream of nuclear factor-κB repression. Increasing the hydrophilicity of Flex-Hets does not attenuate the differential effect on cancer cells over normal cells, thus offering alternatives for improvement of therapeutic value. PMID:19417155

  15. Epidemiologic evidence for an association between gasoline and kidney cancer.

    PubMed Central

    Enterline, P E; Viren, J

    1985-01-01

    A recent animal experiment suggests that gasoline exposure may be a cause of human kidney cancer. This is a literature review to see whether there is any epidemiologic support for these animal findings. Trends and geographic patterns in gasoline consumption and kidney cancer mortality are moderately supportive of a relationship, although this cannot be considered important evidence for a causal relationship. Most other ecological correlations are not supportive of a relationship. Eleven oil refinery populations and one population of petroleum products distribution workers have been studied. These studies taken as a group do not appear to support the notion of a relationship between gasoline exposure and kidney cancer. However, most were not designed or analyzed with this hypothesis in mind. An examination of these data which attempts to consider the ages of the populations studied provides some evidence of a small kidney cancer excess among older workers or among workers exposed for long periods. Because of the importance of gasoline and the potential for exposure by the public further study of exposed populations is needed. PMID:4085434

  16. Adipose tissue immunity and cancer

    PubMed Central

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

    2013-01-01

    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. PMID:24106481

  17. Hereditary kidney cancer: unique opportunity for disease-based therapy.

    PubMed

    Linehan, W Marston; Pinto, Peter A; Bratslavsky, Gennady; Pfaffenroth, Elizabeth; Merino, Maria; Vocke, Cathy D; Toro, Jorge R; Bottaro, Donald; Neckers, Len; Schmidt, Laura S; Srinivasan, Ramaprasad

    2009-05-15

    Kidney cancer is not a single disease; it is comprised of several different types of cancer, each with a different histology, with a different clinical course, caused by a different gene, and responding differently to therapy. The VHL gene is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for the common form of sporadic, noninherited, clear cell kidney cancer. Understanding the VHL-hypoxia inducible factor (HIF) pathway has provided the foundation for the development of several agents targeting this pathway, such as sunitinib, sorafenib, and temsirolimus. Hereditary papillary renal carcinoma (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary renal cell carcinoma. The genetic defect underlying HPRC is MET, the cell surface receptor for hepatocyte growth factor. Mutations of MET also have been identified in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma (RCC). Clinical trials targeting the MET pathway are currently underway in patients with HPRC and in patients with sporadic (nonhereditary) papillary kidney cancer. The BHD gene (also known as folliculin or FLCN) is the gene for Birt-Hogg-Dube syndrome, an autosomal-dominant genodermatosis associated with a hereditary form of chromophobe and oncocytic, hybrid RCC. Preclinical studies are underway targeting the BHD gene pathway in preparation for clinical trials in Birt-Hogg-Dube and sporadic chromophobe RCC. Patients with hereditary leiomyomatosis RCC (HLRCC) are at risk for developing cutaneous and uterine leiomyomas and a very aggressive type of RCC. HLRCC is characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH). Studies of the tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic

  18. 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. PMID:25539049

  19. Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer.

    PubMed

    Cherkasova, Elena; Scrivani, Claire; Doh, Susan; Weisman, Quinn; Takahashi, Yoshiyuki; Harashima, Nanae; Yokoyama, Hisayuki; Srinivasan, Ramaprasad; Linehan, W Marston; Lerman, Michael I; Childs, Richard W

    2016-04-15

    VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript-stimulated CD8(+) T cells, which could recognize HLA-A*0201-positive HERV-E-expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell-based immunotherapy of kidney cancer. Cancer Res; 76(8); 2177-85. ©2016 AACR. PMID:26862115

  20. 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.

  1. Growing Kidney Tissue from Stem Cells: How Far from "Party Trick" to Medical Application?

    PubMed

    Little, Melissa H

    2016-06-01

    The successful generation of kidney-like structures from human pluripotent stem cells, although slower to come than other tissue types, brings the hope of new therapies. While the demand for alternative treatments for kidney failure is acute, huge challenges remain to move these exciting but preliminary results toward clinical use. PMID:27257757

  2. Reduced Risk of Incident Kidney Cancer from Walking and Running

    PubMed Central

    Williams, Paul T.

    2013-01-01

    Purpose Test whether incident kidney cancer risk is associated with exercise energy expenditure (i.e., metabolic equivalents, 1 MET) when calculated from distance walked or run. Methods Hazard ratios (HR) and 95% confidence intervals (95%CI) from Cox proportional hazard analyses of self-reported physician-diagnosed incident kidney cancer vs. MET-hours/wk in 91,820 subjects recruited between 1991 and 1993 (7.7 yr follow-up of 42,833 subjects) and between 1998 and 1999 (6.4 yr follow-up of 33,053 subjects) as part of the National Runners' Health Study and between 1998 and 1999 as part of the National Walkers' Health Study (5.7 yr follow-up of 15,934 subjects). Results Fifty-two incident cancers were reported. Age- and sex-adjusted risk declined 1.9% per MET-hour/wk run or walked (HR: 0.981; 95%CI: 0.964 to 0.997, P=0.02). Compared to walking or running below guidelines levels (<7.5 MET-hours/wk), the risk for incident kidney cancer was 61% lower for meeting the guidelines (HR: 0.39, 95%CI: 0.11 to 1.08, P=0.07 for 7.5 to 12.5 MET-hours/wk), 67% lower for exercising one to two-times the recommended level (HR: 0.33; 95%CI: 0.15 to 0.72, P=0.005 for 12.6 to 25.1 MET-hours/wk), and 76.3% lower for exercising ≥2-times the recommended level (HR: 0.24; 95%CI: 0.11 to 0.52, P=0.0005 for ≥25.2 MET-hours/wk). Incident kidney cancer risk also increased in association with baseline BMI (P=0.002), smoking (P=0.02), and hypertensive (P=0.007) and diabetes medication use (P=0.01), however, exercise-associated reductions in kidney cancer risk persisted for 12.6 to 25.1 MET-hours/wk (HR: 0.35, P=0.01), and ≥ 25.2 MET-hours/wk (HR: 0.29, P=0.004) vis-à-vis <7.5 MET-hours/wk when also adjusted for BMI, hypertension, diabetes, and pack-years smoked. Conclusion Running and walking may reduce incident kidney cancer risk independent of its other known risk factors. PMID:23863620

  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. 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.

  5. Logic Regression for Provider Effects on Kidney Cancer Treatment Delivery

    PubMed Central

    Banerjee, Mousumi; Filson, Christopher; Xia, Rong; Miller, David C.

    2014-01-01

    In the delivery of medical and surgical care, often times complex interactions between patient, physician, and hospital factors influence practice patterns. This paper presents a novel application of logic regression in the context of kidney cancer treatment delivery. Using linked data from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program and Medicare we identified patients diagnosed with kidney cancer from 1995 to 2005. The primary endpoints in the study were use of innovative treatment modalities, namely, partial nephrectomy and laparoscopy. Logic regression allowed us to uncover the interplay between patient, provider, and practice environment variables, which would not be possible using standard regression approaches. We found that surgeons who graduated in or prior to 1980 despite having some academic affiliation, low volume surgeons in a non-NCI hospital, or surgeons in rural environment were significantly less likely to use laparoscopy. Surgeons with major academic affiliation and practising in HMO, hospital, or medical school based setting were significantly more likely to use partial nephrectomy. Results from our study can show efforts towards dismantling the barriers to adoption of innovative treatment modalities, ultimately improving the quality of care provided to patients with kidney cancer. PMID:24795774

  6. 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 ...

  7. [Cancer cachexia and white adipose tissue browning].

    PubMed

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research. PMID:27531474

  8. Kidney cancer and hydrocarbon exposures among petroleum refinery workers.

    PubMed Central

    Poole, C; Dreyer, N A; Satterfield, M H; Levin, L; Rothman, K J

    1993-01-01

    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. To 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 "present" or "absent" 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 refinery 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). PMID:8020449

  9. Acute kidney injury in critically ill cancer patients: an update.

    PubMed

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

    2016-01-01

    Patients with cancer represent a growing group among actual ICU admissions (up to 20 %). Due to their increased susceptibility to infectious and noninfectious complications related to the underlying cancer itself or its treatment, these patients frequently develop acute kidney injury (AKI). A wide variety of definitions for AKI are still used in the cancer literature, despite existing guidelines on definitions and staging of AKI. Alternative diagnostic investigations such as Cystatin C and urinary biomarkers are discussed briefly. This review summarizes the literature between 2010 and 2015 on epidemiology and prognosis of AKI in this population. Overall, the causes of AKI in the setting of malignancy are similar to those in other clinical settings, including preexisting chronic kidney disease. In addition, nephrotoxicity induced by the anticancer treatments including the more recently introduced targeted therapies is increasingly observed. However, data are sometimes difficult to interpret because they are often presented from the oncological rather than from the nephrological point of view. Because the development of the acute tumor lysis syndrome is one of the major causes of AKI in patients with a high tumor burden or a high cell turnover, the diagnosis, risk factors, and preventive measures of the syndrome will be discussed. Finally, we will briefly discuss renal replacement therapy modalities and the emergence of chronic kidney disease in the growing subgroup of critically ill post-AKI survivors. PMID:27480256

  10. 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

  11. 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

  12. Kidney Cysts

    MedlinePlus

    ... fluid-filled sac. There are two types of kidney cysts. Polycystic kidney disease (PKD) runs in families. In PKD, the ... place of the normal tissue. They enlarge the kidneys and make them work poorly, leading to kidney ...

  13. 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

  14. 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 ...

  15. 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 ...

  16. 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. PMID:25573057

  17. Biomimetic Porous PLGA Scaffolds Incorporating Decellularized Extracellular Matrix for Kidney Tissue Regeneration.

    PubMed

    Lih, Eugene; Park, Ki Wan; Chun, So Young; Kim, Hyuncheol; Kwon, Tae Gyun; Joung, Yoon Ki; Han, Dong Keun

    2016-08-24

    Chronic kidney disease is now recognized as a major health problem, but current therapies including dialysis and renal replacement have many limitations. Consequently, biodegradable scaffolds to help repairing injured tissue are emerging as a promising approach in the field of kidney tissue engineering. Poly(lactic-co-glycolic acid) (PLGA) is a useful biomedical material, but its insufficient biocompatibility caused a reduction in cell behavior and function. In this work, we developed the kidney-derived extracellular matrix (ECM) incorporated PLGA scaffolds as a cell supporting material for kidney tissue regeneration. Biomimetic PLGA scaffolds (PLGA/ECM) with different ECM concentrations were prepared by an ice particle leaching method, and their physicochemical and mechanical properties were characterized through various analyses. The proliferation of renal cortical epithelial cells on the PLGA/ECM scaffolds increased with an increase in ECM concentrations (0.2, 1, 5, and 10%) in scaffolds. The PLGA scaffold containing 10% of ECM has been shown to be an effective matrix for the repair and reconstitution of glomerulus and blood vessels in partially nephrectomized mice in vivo, compared with only PLGA control. These results suggest that not only can the tissue-engineering techniques be an effective alternative method for treatment of kidney diseases, but also the ECM incorporated PLGA scaffolds could be promising materials for biomedical applications including tissue engineered scaffolds and biodegradable implants. PMID:27456613

  18. Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

    NASA Astrophysics Data System (ADS)

    Heinert, G.; Mondorf, W.

    1982-11-01

    High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

  19. Aerobic glycolysis: a novel target in kidney cancer.

    PubMed

    Shuch, Brian; Linehan, W Marston; Srinivasan, Ramaprasad

    2013-06-01

    Renal cell carcinoma (RCC) is a heterogenous group of cancers that arise from the nephron. While there are distinct histologic subtypes associated with common genetic alterations, most forms of RCC are linked by a common pathway of dysregulated metabolism. Reliance on aerobic glycolysis, a feature of cancer first hypothesized by Warburg, is a common feature in sporadic and hereditary forms of kidney cancer. Two hereditary forms of RCC, succinate dehydrogenase (SDH) and hereditary leiomyomatosis and RCC (HLRCC), are characterized by mutations in Krebs cycle enzymes, rendering them dependent on glycolysis for energy requirements. The reliance on these pathways may make them vulnerable to novel metabolic strategies, including inhibition of glycolysis, glucose uptake and macromolecule biosynthesis. PMID:23773105

  20. Twist2 promotes kidney cancer cell proliferation and invasion via regulating ITGA6 and CD44 expression in the ECM-Receptor-Interaction pathway.

    PubMed

    Zhang, Hao-Jie; Tao, Jing; Sheng, Lu; Hu, Xin; Rong, Rui-Ming; Xu, Ming; Zhu, Tong-Yu

    2016-07-01

    Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence proves that Twist2 involves in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. RT-PCR 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 was measured by the Cell Count Kit-8 (CCK8), flow cytometry, wound healing and transwell analysis, respectively. Gene set enrichment analysis (GSEA) was used to identify correlation of Twist2 with ECM-Receptor-Interaction pathway. In this report, we show that Twist2 up-regulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promotes cell proliferation, inhibits cell apoptosis, augments cell migration and invasion in human kidney cancer-derived cell in vitro, and promotes tumor growth in vivo. Moreover, we found that knockdown of Twist2 decreased the levels of ITGA6 and CD44 which contribute to cell migration and invasion correlated with ECM-Receptor-Interaction pathway. This result indicates Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 involves in kidney cancer progression. The identification of the role Twist2 on the migration and invasion of kidney cancer provides a potential appropriate treatment after radical nephrectomy to get a better prognosis that reducing recurrence. PMID:27261625

  1. 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. PMID:25870008

  2. 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

  3. 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. PMID:27194718

  4. Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

    PubMed

    Diamond, G L; Cohen, J J; Weinstein, S L

    1986-11-01

    Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution. PMID:3777178

  5. Clearing the Air: Summarizing the Smoking-related Relative Risks of Bladder and Kidney Cancer.

    PubMed

    Purdue, Mark P; Silverman, Debra T

    2016-09-01

    This Platinum Priority editorial discusses the strengths and limitations of a recent meta-analysis summarizing the published smoking-related relative risks for bladder cancer and kidney cancer. PMID:27130147

  6. Nonmuscle Tissues Contribution to Cancer Cachexia

    PubMed Central

    Argilés, Josep M.; Stemmler, Britta; López-Soriano, Francisco J.; Busquets, Silvia

    2015-01-01

    Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia. PMID:26523094

  7. Protein Signature of Lung Cancer Tissues

    PubMed Central

    Mehan, Michael R.; Ayers, Deborah; Thirstrup, Derek; Xiong, Wei; Ostroff, Rachel M.; Brody, Edward N.; Walker, Jeffrey J.; Gold, Larry; Jarvis, Thale C.; Janjic, Nebojsa; Baird, Geoffrey S.; Wilcox, Sheri K.

    2012-01-01

    Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment. PMID:22509397

  8. 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 ...

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

    PubMed

    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

  10. 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

  11. Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

    PubMed Central

    Huang, Chang-Shuo; Tang, Shye-Jye; Chung, Ling-Yen; Yu, Cheng-Ping; Ho, Jar-Yi; Cha, Tai-Lung; Hsieh, Chii-Cheng; Wang, Hsiao-Hsien

    2014-01-01

    Galectin-1, a β-galactoside–binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1–silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-κB (NF-κB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. PMID:24511119

  12. Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

    PubMed Central

    Connors, Bret A.; Evan, Andrew P.; Blomgren, Philip M.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Wang, Yak-Nam; Simon, Julianna C.; Paun, Marla; Starr, Frank; Cunitz, Bryan W.; Bailey, Michael R.; Lingeman, James E.

    2013-01-01

    Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters. PMID:23917165

  13. Continuous infusion interleukin-2 and antihistamines in metastatic kidney cancer.

    PubMed

    Walker, Paul R; Khuder, Sadik A; Quan, Walter D Y

    2005-10-01

    A prior randomized trial suggested a possible survival advantage favoring the combination of histamine and subcutaneous interleukin-2 (IL-2), compared to IL-2 alone in patients with metastatic melanoma. It has been postulated previously that antihistamines may, therefore, actually be antagonistic to IL-2 and thus interfere with its antitumor activity. We have previously shown no such antagonistic effect in patients with melanoma receiving IL-2 and antihistamines when reviewing the known literature. We sought to determine whether there was any negative effect of the combination in patients with metastatic kidney cancer. A PubMed literature search between 1985 and 2005 was done. High-dose continuous (or constant) infusion (CIV) interleukin-2 was used as the reference therapy because of the relatively constant IL-2 levels generated by this approach. Studies in which cimetidine, ranitidine, or famotidine were regularly scheduled and administered concurrently with IL-2 were included. Thirteen studies were identified. A total of 47 patients responded to therapy. Total response rate = 22%; 95%; Confidence Interval: 17%-28%. Eleven complete responses were noted. Complete response rate = 5%; 95% Confidence Interval: 3%-9%. These response rates are consistent with previously noted IL-2 response rates. In this study of CIV IL-2 and antihistamines, this combination appears to be active in metastatic kidney cancer. There appears to be no negative effect of antihistamine on the CIV IL-2 response rate in this disease. PMID:16248764

  14. Continuous infusion interleukin-2 and famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter D Y; Vinogradov, Mikhail; Quan, Francine M; Khan, Nawazish; Liles, Darla K; Walker, Paul R

    2006-10-01

    Infusional interleukin-2 (IL-2) is able to elicit lymphokine-activated killer cell (LAK) cytotoxicity against kidney cancer in vitro and in vivo. Famotidine may be able to augment LAK cytotoxicity against neoplastic cells. Fifteen (15) patients were treated with continuous-infusion IL-2 (9-18 MIU/m2/24 hours) for 72 hours and famotidine 20 mg intravenously twice per day. Cycles were repeated every 3 weeks. These patients had a median age of 60 years (range, 29-72), had a median performance status of 1 (range, 0-1), and had metastatic sites, including lung, bone, lymph node, and liver. The most common toxicities of this regimen were hypophosphatemia, fever, nausea/emesis, rigors, elevated creatinine, and hypomagnesemia. One (1) complete and 6 partial responses have been seen (47% response rate). The median duration of response is 9 months. The median survival for all patients is 20 months. Five (5) patients are alive at a median of 36+ months. This combination of infusional IL-2 with famotidine is active in metastatic kidney cancer. PMID:17105423

  15. 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

  16. 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.

  17. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease.

    PubMed

    Ow, Connie P C; Abdelkader, Amany; Hilliard, Lucinda M; Phillips, Jacqueline K; Evans, Roger G

    2014-11-15

    Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney. PMID:25209412

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

    PubMed Central

    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

  19. TISSUE ENGINEERING PERFUSABLE CANCER MODELS

    PubMed Central

    Fong, E.L.; Santoro, M.; Farach-Carson, M.C.; Kasper, F.K.; Mikos, A.G.

    2014-01-01

    The effect of fluid flow on cancer progression is currently not well understood, highlighting the need for perfused tumor models to close this gap in knowledge. Enabling biological processes at the cellular level to be modeled with high spatiotemporal control, microfluidic tumor models have demonstrated applicability as platforms to study cell-cell interactions, effect of interstitial flow on tumor migration and the role of vascular barrier function. To account for the multi-scale nature of cancer growth and invasion, macroscale models are also necessary. The consideration of fluid dynamics within tumor models at both the micro- and macroscopic levels may greatly improve our ability to more fully mimic the tumor microenvironment. PMID:24634812

  20. Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

    PubMed

    Benjachat, Thitima; Tongyoo, Pumipat; Tantivitayakul, Pornpen; Somparn, Poorichaya; Hirankarn, Nattiya; Prom-On, Santitham; Pisitkun, Prapaporn; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Townamchai, Natavudh

    2015-01-01

    The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy. PMID:26110394

  1. ISOTONICITY OF LIVER AND OF KIDNEY TISSUE IN SOLUTIONS OF ELECTROLYTES

    PubMed Central

    Opie, Eugene L.

    1959-01-01

    Solutions of a wide variety of electrolytes, isotonic with liver or with kidney tissue, have approximately the same osmotic pressure as solutions of sodium chloride isotonic with tissues of the two organs respectively; that is, with solutions approximately twice as concentrated as the sodium chloride of mammalian blood plasma. The molar concentration of various electrolytes isotonic with liver or with kidney tissue immediately after its removal from the body is determined by the molecular weight, valency, and ion-dissociation of these electrolytes in accordance with the well known conditions of osmosis. The plasma membranes of liver and of kidney cells are imperfectly semipermeable to electrolytes, and those that enter the cell, though retarded in so doing, bring about injury which increases permeability to water. The osmotic activity of cells of mammalian liver and kidney immediately after their removal from the body resembles that of plant cells, egg cells of marine invertebrates, and mammalian red blood corpuscles and presumably represents a basic property of living cells by which osmotic pressure may be adjusted to functional need. PMID:13664872

  2. Isotonicity of liver and of kidney tissue in solutions of electrolytes.

    PubMed

    OPIE, E L

    1959-07-01

    Solutions of a wide variety of electrolytes, isotonic with liver or with kidney tissue, have approximately the same osmotic pressure as solutions of sodium chloride isotonic with tissues of the two organs respectively; that is, with solutions approximately twice as concentrated as the sodium chloride of mammalian blood plasma. The molar concentration of various electrolytes isotonic with liver or with kidney tissue immediately after its removal from the body is determined by the molecular weight, valency, and ion-dissociation of these electrolytes in accordance with the well known conditions of osmosis. The plasma membranes of liver and of kidney cells are imperfectly semipermeable to electrolytes, and those that enter the cell, though retarded in so doing, bring about injury which increases permeability to water. The osmotic activity of cells of mammalian liver and kidney immediately after their removal from the body resembles that of plant cells, egg cells of marine invertebrates, and mammalian red blood corpuscles and presumably represents a basic property of living cells by which osmotic pressure may be adjusted to functional need. PMID:13664872

  3. [Transurethral prostate resection prior to kidney transplantation leading to urethral cicatricial tissue].

    PubMed

    Schou-Jensen, Katrine; Mohammad, Wael

    2015-01-26

    In Denmark, kidney transplantations in patients above 50 years have increased during the last decade. Consequently, the number of patients with lower urinary tract symptoms due to prostate hypertrophy increases accordingly. We describe two patients, who both had a resection of the prostate while having anuria and waiting for a kidney transplantation from a deceased donor. In both cases it was impossible to place a urethral catheter during the following transplantation due to total urethral occlusion, so a suprapubic catheter was inserted until the scar tissue was dilated or resected by a later transurethral intervention. PMID:25612989

  4. 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

  5. N-glycosylation of Colorectal Cancer Tissues

    PubMed Central

    Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2012-01-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871

  6. The effects of refractive index heterogeneity within kidney tissue on multiphoton fluorescence excitation microscopy.

    PubMed

    Young, P A; Clendenon, S G; Byars, J M; Dunn, K W

    2011-05-01

    Although multiphoton fluorescence excitation microscopy has improved the depth at which useful fluorescence images can be collected in biological tissues, the reach of multiphoton fluorescence excitation microscopy is nonetheless limited by tissue scattering and spherical aberration. Scattering can be reduced in fixed samples by mounting in a medium whose refractive index closely matches that of the fixed material. Using optical 'clearing', the effects of refractive index heterogeneity on signal attenuation with depth are investigated. Quantitative measurements show that by mounting kidney tissue in a high refractive index medium, less than 50% of signal attenuates in 100 μm of depth. PMID:21118239

  7. Segmentation of prostate cancer tissue microarray images

    NASA Astrophysics Data System (ADS)

    Cline, Harvey E.; Can, Ali; Padfield, Dirk

    2006-02-01

    Prostate cancer is diagnosed by histopathology interpretation of hematoxylin and eosin (H and E)-stained tissue sections. Gland and nuclei distributions vary with the disease grade. The morphological features vary with the advance of cancer where the epithelial regions grow into the stroma. An efficient pathology slide image analysis method involved using a tissue microarray with known disease stages. Digital 24-bit RGB images were acquired for each tissue element on the slide with both 10X and 40X objectives. Initial segmentation at low magnification was accomplished using prior spectral characteristics from a training tissue set composed of four tissue clusters; namely, glands, epithelia, stroma and nuclei. The segmentation method was automated by using the training RGB values as an initial guess and iterating the averaging process 10 times to find the four cluster centers. Labels were assigned to the nearest cluster center in red-blue spectral feature space. An automatic threshold algorithm separated the glands from the tissue. A visual pseudo color representation of 60 segmented tissue microarray image was generated where white, pink, red, blue colors represent glands, epithelia, stroma and nuclei, respectively. The higher magnification images provided refined nuclei morphology. The nuclei were detected with a RGB color space principle component analysis that resulted in a grey scale image. The shape metrics such as compactness, elongation, minimum and maximum diameters were calculated based on the eigenvalues of the best-fitting ellipses to the nuclei.

  8. 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

  9. 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. PMID:24858911

  10. Grading Breast Cancer Tissues Using Molecular Portraits*

    PubMed Central

    Olsson, Niclas; Carlsson, Petter; James, Peter; Hansson, Karin; Waldemarson, Sofia; Malmström, Per; Fernö, Mårten; Ryden, Lisa; Wingren, Christer; Borrebaeck, Carl A. K.

    2013-01-01

    Tumor progression and prognosis in breast cancer patients are difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessments of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, determined using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grades 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of the tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the likelihood of long-term metastasis-free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer. PMID:23982162

  11. 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

  12. Tissue Specific Promoters in Colorectal Cancer

    PubMed Central

    Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.

    2015-01-01

    Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599

  13. 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. PMID:26255999

  14. Aurora a Overexpression and pVHL Reduced Expression Are Correlated with a Bad Kidney Cancer Prognosis

    PubMed Central

    Ferchichi, Imen; Kourda, Nadia; Sassi, Samia; Romdhane, Khaled Ben; Balatgi, Sarra; Cremet, Jean Yves; Prigent, Claude; Elgaaied, Amel Benammar

    2012-01-01

    We investigate the expression and localization of the tumor suppressor protein pVHL as well as the oncoprotein Aurora A kinase in kidney cancer. Both Aurora A kinase and pVHL protein status were evaluated using immunohistochemistry. The Aurora A expression is correlated with the Fuhrman grade and the TNM stage, while the pVHL expression is correlated with the capsule rupture and the TNM stage. Aurora A kinase expression increases in malignant tissue comparing to the non-malignant one. And there is a decrease in pVHL expression from the adjacent healthy tissues to the tumor`s ones. The two kinds of opposite tumor profiles display significant distribution difference according to TNM stages. It could be proposed that the absence of Aurora A protein associated with a strong expression of pVHL in clear cells kidney carcinoma are of good prognosis for the disease. PMID:23151618

  15. [Penetration of polyene antibiotics into human embryonic kidney tissue cell cultures].

    PubMed

    Kravchenko, L S; Sokolov, V N; Vaĭnshteĭn, V A; Diment, A V; Tereshin, I M

    1977-12-01

    Penetration of 14C-amphotericin AM-2 into the cells of the tissue culture of the human embryon kidneys was studied by means of light autoradiography after incubation with the antibiotic. Microscopic examination of the autographs of the cell slices revealed the presence of the radioactive label in the cytoplasm and nucleoplasm of the cells. The revealed intracellular localization of the label was evident of the antibiotic penetration into the cells. PMID:596858

  16. 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.

  17. Benefit of a Second Opinion for Lung Cancer: No Metastasis to the Kidney but a Synchronous Primary Renal Neoplasm

    PubMed Central

    ter Avest, Marleen J.; Schook, Romane M.; Koudstaal, Lyan G.; Grünberg, Katrien; Paul, Marinus A.; Smit, Egbert F.; Postmus, Pieter E.

    2014-01-01

    Background The finding of a renal mass on imaging is suggestive of metastatic non-small cell lung cancer in the presence of a lung tumor but can also have another origin. Case Report We describe the case of a patient diagnosed with stage IV lung cancer based on a renal metastasis. A second opinion including review of histopathological data and additional imaging followed by lung surgery and cryoablation of the kidney lesion revealed two tumors of different origins, non-small cell lung cancer and a renal cell carcinoma. Discussion The presence of a renal mass diagnosed on a CT scan in a patient with lung cancer is not always synonymous with metastatic disease. Confirmation of diagnosis by tissue sampling is mandatory, especially if a synchronous primary tumor is possible. PMID:24707259

  18. Molecular Mechanisms of Chronic Kidney Transplant Rejection via Large-Scale Proteogenomic Analysis of Tissue Biopsies

    PubMed Central

    Nakorchevsky, Aleksey; Hewel, Johannes A.; Kurian, Sunil M.; Mondala, Tony S.; Campbell, Daniel; Head, Steve R.; Marsh, Christopher L.; Yates, John R.

    2010-01-01

    The most common cause of kidney transplant failure is the poorly characterized histopathologic entity interstitial fibrosis and tubular atrophy (IFTA). There are no known unifying mechanisms, no effective therapy, and no proven preventive strategies. Possible mechanisms include chronic immune rejection, inflammation, drug toxicity, and chronic kidney injury from secondary factors. To gain further mechanistic insight, we conducted a large-scale proteogenomic study of kidney transplant biopsies with IFTA of varying severity. We acquired proteomic data using tandem mass spectrometry with subsequent quantification, analysis of differential protein expression, validation, and functional annotations to known molecular networks. We performed genome-wide expression profiling in parallel. More than 1400 proteins with unique expression profiles traced the progression from normal transplant biopsies to biopsies with mild to moderate and severe disease. Multiple sets of proteins were mapped to different functional pathways, many increasing with histologic severity, including immune responses, inflammatory cell activation, and apoptosis consistent with the chronic rejection hypothesis. Two examples include the extensive population of the alternative rather than the classical complement pathway, previously not appreciated for IFTA, and a comprehensive control network for the actin cytoskeleton and cell signaling of the acute-phase response. In summary, this proteomic effort using kidney tissue contributes mechanistic insight into several biologic processes associated with IFTA. PMID:20093355

  19. Tissue culture correlational study of genetic cholangiopathy of autosomal recessive polycystic kidney disease.

    PubMed

    Nakanuma, Yasuni; Sato, Yasunori; Harada, Kenichi

    2013-01-01

    Cholangiocytes are epithelial cells that line the biliary tract and are also known as biliary epithelial cells (BECs). In vitro culture studies of BECs in correlation with tissue section examination may give us a comprehensive analysis of biliary tract diseases. Herein, we discuss genetic cholangiopathy of autosomal recessive polycystic kidney disease (ARPKD), mainly using a polycystic kidney (PCK) rat, an animal model of ARPKD. The hepatobiliary lesions in ARPKD patients (Caroli's disease and congenital hepatic fibrosis) and in PCK rats are speculated to be related to mutations to polycystic kidney and hepatic disease 1 (PKHD1) which have been recently demonstrated, though the exact causal relation between these mutations and hepatobiliary pathology remain to be clarified. Recently we clarified that BECs of PCK rat showed increased cell proliferation followed by irregular dilatation of intrahepatic bile ducts. We also identified the essential involvement of the MEK5-ERK5 pathway in the abnormal proliferation of BECs in the PCK rat. The degradation of laminin and type IV collagen (basal membrane components of bile ducts) was closely related to the biliary dysgenesis and cystogenesis in the PCK rats. BECs also showed mesenchymal phenotype followed by progressive portal tract fibrosis, indicating TGF-β1 may be involved in this acquisition of mesenchymal phenotype. Detailed tissue culture correlation studies of ARPKD and PCK rats are mandatory to evaluate the pathogenesis of this genetic cholangiopathy. PMID:23097114

  20. 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

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

    PubMed

    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

  2. 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%).

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

    PubMed

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

    2003-01-15

    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%). PMID:12482474

  4. The development of a real-time PCR to detect pathogenic Leptospira species in kidney tissue.

    PubMed

    Fearnley, C; Wakeley, P R; Gallego-Beltran, J; Dalley, C; Williamson, S; Gaudie, C; Woodward, M J

    2008-08-01

    A LightCycler real-time PCR hybridization probe-based assay that detects a conserved region of the16S rRNA gene of pathogenic but not saprophytic Leptospira species was developed for the rapid detection of pathogenic leptospires directly from processed tissue samples. In addition, a differential PCR specific for saprophytic leptospires and a control PCR targeting the porcine beta-actin gene were developed. To assess the suitability of these PCR methods for diagnosis, a trial was performed on kidneys taken from adult pigs with evidence of leptospiral infection, primarily a history of reproductive disease and serological evidence of exposure to pathogenic leptospires (n=180) and aborted pig foetuses (n=24). Leptospire DNA was detected by the 'pathogenic' specific PCR in 25 tissues (14%) and the control beta-actin PCR was positive in all 204 samples confirming DNA was extracted from all samples. No leptospires were isolated from these samples by culture and no positives were detected with the 'saprophytic' PCR. In a subsidiary experiment, the 'pathogenic' PCR was used to analyse kidney samples from rodents (n=7) collected as part of vermin control in a zoo, with show animals with high microagglutination titres to Leptospira species, and five were positive. Fifteen PCR amplicons from 1 mouse, 2 rat and 14 pig kidney samples, were selected at random from positive PCRs (n=30) and sequenced. Sequence data indicated L. interrogans DNA in the pig and rat samples and L. inadai DNA, which is considered of intermediate pathogenicity, in the mouse sample. The only successful culture was from this mouse kidney and the isolate was confirmed to be L. inadai by classical serology. These data suggest this suite of PCRs is suitable for testing for the presence of pathogenic leptospires in pig herds where abortions and infertility occur and potentially in other animals such as rodents. PMID:17961617

  5. Tissue components of weight loss in cancer patients. A new method of study and preliminary observations.

    PubMed

    Heymsfield, S B; McManus, C B

    1985-01-01

    A new approach using anthropometric, radiographic, biochemical, and ultrasonic methods allowed partition of body weight into fat, fat-free mass, skeletal muscle, and volume of heart, liver, kidneys, spleen, and tumor. These methods were used to evaluate body composition longitudinally in a pilot group of nine cancer patients, seven of whom lost weight (greater than 2.5 kg) during the study period. Two control groups also underwent the protocol: (1) healthy subjects (+/- 10% IBW) of similar age, sex, and height; and (2) patients with weight loss due to anorexia nervosa. Weight loss in both the cancer and anorexia nervosa groups could be accounted for primarily by loss in fat and skeletal muscle; although the relative magnitude of these tissue losses were approximately the same in both groups, cancer patients lost relatively less body weight. This was because (1) overt or occult ascites (detected radiographically) was present in cancer patients (3 of 9); (2) tumor bulk increased fat-free mass by up to 1 to 2 kg; and (3) the proportional loss in visceral organ volume was less in cancer patients than in anorexia nervosa patients. In the latter group, heart, liver, kidneys, and spleen were reduced in proportion to body weight, whereas in the cancer group as a whole, these organs (when uninvolved with tumor) lost little (heart and kidneys) or no volume (liver and spleen). This initial study suggests that the principal endogenous energy and nitrogen sources during evolution of weight loss in cancer are primarily adipose tissue triglycerides and skeletal muscle proteins. In some cancer patients, fluid accumulation, a large tumor burden, and the slow rate of visceral organ atrophy make body weight an unreliable index of available energy-nitrogen reserves. PMID:3965090

  6. Tissue doses from radiotherapy of cancer of the uterine cervix

    SciTech Connect

    Stovall, M.; Smith, S.A. ); Rosenstein, M.

    1989-09-01

    For use in an epidemiologic study of subsequent tumors, absorbed doses from brachytherapy and external beam radiotherapy were measured and calculated for various tissues of patients treated for cancer of the uterine cervix. External beams included orthovoltage x rays (1.9 and 3.0 mm Cu half-value layer), cobalt-60 gamma rays, 2 MV x rays, and 25 MV x rays. The brachytherapy sources were encapsulated radium. Measurements were made in an Alderson anthropomorphic phantom and a water phantom; calculations were made using a Monte Carlo technique or standard radiotherapy methods. Depending upon stage of disease and radiation energy, the absorbed doses (cGy) from typical treatment regimes to tissues of interest were: ovaries, 1400--5200; stomach, 130--320; kidneys, 120--310; pancreas, 100--260; lungs, 22--48; breasts, 19--52; thyroid, 6--17; salivary glands, 4--11; brain, 2--7, and total active bone marrow, 320--1100. The lower values of each range were for stage I of the disease.

  7. 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.

  8. 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

  9. Reproductive Factors and Kidney Cancer Risk in 2 US Cohort Studies, 1993–2010

    PubMed Central

    Karami, Sara; Daugherty, Sarah E.; Schonfeld, Sara J.; Park, Yikyung; Hollenbeck, Albert R.; Grubb, Robert L.; Hofmann, Jonathan N.; Chow, Wong-Ho; Purdue, Mark P.

    2013-01-01

    Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health–AARP Diet and Health Study (NIH-AARP), 1995–2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993–2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend = 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation. PMID:23624999

  10. [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. PMID:24315083

  11. Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma

    PubMed Central

    Han, Won K.; Alinani, Anwar; Wu, Chin-Lee; Michaelson, Dror; Loda, Massimo; McGovern, Francis J.; Thadhani, Ravi; Bonventre, Joseph V.

    2005-01-01

    Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at high levels in human and rodent kidneys with dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Therefore, it was hypothesized that renal tumors express hKIM-1 and release this protein into the urine. Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy tissue samples were collected from an additional 42 patients with renal tumors, from 30 normal control subjects, and also from 10 patients with prostate carcinoma (group 2). In five additional patients with RCC, urine was collected before and after nephrectomy (group 3). Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA. Urinary hKIM-1 was normalized to the urinary creatinine concentration (UCr). Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly higher in patients with clear cell RCC (0.39 ± 0.08 ng/mg UCr; n = 21), compared with levels in patients with prostate carcinoma (0.12 ± 0.03 ng/mg UCr; P < 0.02; n = 10), or normal control subjects (0.05 ± 0.01 ng/mg UCr; P < 0.005; n = 30). Tissue sections from 28 (82%) of 34 primary RCC stained positively for the expression of hKIM-1. In all patients with a detectable prenephrectomy urinary hKIM-1 level, there was either complete disappearance or marked reduction after nephrectomy (group 3). In conclusion, the cleaved ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may serve as a new biomarker for early detection of RCC. PMID:15744000

  12. 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

  13. Association between pesticide exposure and risk of kidney cancer: a meta-analysis

    PubMed Central

    Xie, Bo; Hu, Yingfang; Liang, Zhen; Liu, Ben; Zheng, Xiangyi; Xie, Liping

    2016-01-01

    This meta-analysis aimed to evaluate the correlation between pesticide exposure and kidney cancer. We conducted a systematic search of the Cochrane Library, Embase, Web of Knowledge, and Medline (updated to March 1, 2015) to identify all relevant studies. References of the retrieved articles were also identified. Fixed- or random-effect models were used to summarize the estimates of relative risk (RR) with 95% confidence interval for the association between exposure of pesticide and risk of kidney cancer. The pooled RR estimate indicated that pesticide exposure might have an elevated risk for kidney cancer (RR =1.10, 95% confidence interval 1.01–1.19). In a subgroup analysis of high quality articles, we detected that pesticide exposure is a significant risk factor for kidney cancer in a subgroup analysis of case-control studies, (Newcastle–Ottawa Quality Assessment Scale score >6) (RR =1.31, 95% confidence interval 1.12–1.51). North America studies, odds ratio studies, and studies with effect estimate adjusted for more than two confounder studies. In conclusion, pesticide exposure may be a risk factor for kidney cancer. PMID:27418833

  14. Grade-dependent metabolic reprogramming in kidney cancer revealed by combined proteomics and metabolomics analysis

    PubMed Central

    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.

    2015-01-01

    Kidney cancer (or renal cell carcinoma [RCC]) is known as “the internist’s tumor” because it has protean systemic manifestations suggesting it utilizes complex, non-physiologic 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 VHL 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, while the β-oxidation pathway is inhibited leading to increased fatty acyl-carnitines. 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 to other metabolic pathways. Together, our results offer a rationale to evaluate novel anti-metabolic treatment strategies being developed in other disease settings as therapeutic strategies in RCC. PMID:25952651

  15. 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

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

    PubMed

    Memtily, Nassirhadjy; Okada, Tomoko; Ebihara, Tatsuhiko; Sato, Mari; Kurabayashi, Atsushi; Furihata, Mutsuo; Suga, Mitsuo; Nishiyama, Hidetoshi; Mio, Kazuhiro; Sato, Chikara

    2015-05-01

    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

  17. Radiation May Help After Surgery for 'Soft-Tissue' Cancers

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158322.html Radiation May Help After Surgery for 'Soft-Tissue' Cancers ... called soft-tissue sarcomas may benefit more from radiation therapy after surgery than younger patients do, a ...

  18. 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. PMID:21348635

  19. Accumulation of heavy metals in kidney and heart tissues of Epinephelus microdon fish from the Arabian Gulf.

    PubMed

    Ashraf, Waqar

    2005-02-01

    Levels of Pb, Co, Cu, Ni, Zn, Mn and Cd in the kidney and heart tissues of Epinephelus Microdon collected from the Arabian Gulf, Eastern province of Saudi Arabia, were determined by wet digestion-based atomic absorption method. The results indicated that accumulation pattern of analyzed metals in the kidney tissues followed the order; Zn > Cu > Pb > Ni > Co > Mn > Cd, with Zn at 47.73 +/- 13.26 ppm and Cd at 0.41 +/- 0.16 ppm. Cu, Mn, Co and Ni levels in the kidney tissues were significantly lower or within the ranges reported previously. In the heart tissue the analyzed metals followed almost the same pattern of metal accumulation; Zn > Cu > Pb > Co > Ni > Mn > Cd. The average lead (3.19 +/- 2.03 ppm), nickel (1.69 +/- 0.52 ppm), cobalt (1.75 +/- 0.44 ppm), copper (3.96 +/- 0.98 ppm) and cadmium (0.34 +/- 0.23 ppm) concentrations were found high in the heart tissues whereas zinc and manganese levels were found high in kidney tissues. In general, the data indicated that marine fish from the sampling site of Arabian Gulf are comparatively clean and unpolluted. PMID:15736888

  20. Resistant arterial hypertension: association with syncronous kidney cancer and adrenal adenoma.

    PubMed

    Pittavini, Loretta; De Gaetano, Andrea; Solano, Giuseppe; Losito, Attilio

    2010-01-01

    The coexistence of renal cancer and adrenal adenoma is rare. We report the case of a 60-year-old patient with synchronous hypernephroma and adrenal adenoma. The patient presented with resistant hypertension, high plasma renin activity and aldosterone and target organ damage. Removal of the affected kidney cured the hypertension and normalized the plasma renin activity (PRA) and circulating aldosterone. This suggests that the coexistence of kidney cancer and adrenal adenoma may be a curable cause of resistant hypertension. The potential mechanisms accounting for the lack of suppression of PRA are discussed. PMID:20383873

  1. Quantitative proteomics in resected renal cancer tissue for biomarker discovery and profiling

    PubMed Central

    Atrih, A; Mudaliar, M A V; Zakikhani, P; Lamont, D J; Huang, J T-J; Bray, S E; Barton, G; Fleming, S; Nabi, G

    2014-01-01

    Background: Proteomics-based approaches for biomarker discovery are promising strategies used in cancer research. We present state-of-art label-free quantitative proteomics method to assess proteome of renal cell carcinoma (RCC) compared with noncancer renal tissues. Methods: Fresh frozen tissue samples from eight primary RCC lesions and autologous adjacent normal renal tissues were obtained from surgically resected tumour-bearing kidneys. Proteins were extracted by complete solubilisation of tissues using filter-aided sample preparation (FASP) method. Trypsin digested proteins were analysed using quantitative label-free proteomics approach followed by data interpretation and pathways analysis. Results: A total of 1761 proteins were identified and quantified with high confidence (MASCOT ion score threshold of 35 and P-value <0.05). Of these, 596 proteins were identified as differentially expressed between cancer and noncancer tissues. Two upregulated proteins in tumour samples (adipose differentiation-related protein and Coronin 1A) were further validated by immunohistochemistry. Pathway analysis using IPA, KOBAS 2.0, DAVID functional annotation and FLink tools showed enrichment of many cancer-related biological processes and pathways such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. Conclusions: Our study identified a number of differentially expressed proteins and pathways using label-free proteomics approach in RCC compared with normal tissue samples. Two proteins validated in this study are the focus of on-going research in a large cohort of patients. PMID:24548857

  2. 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.

  3. Terahertz imaging diagnostics of cancer tissues with a chemometrics technique

    NASA Astrophysics Data System (ADS)

    Nakajima, Sachiko; Hoshina, Hiromichi; Yamashita, Masatsugu; Otani, Chiko; Miyoshi, Norio

    2007-01-01

    Terahertz spectroscopic images of paraffin-embedded cancer tissues have been measured by a terahertz time domain spectrometer. For the systematic identification of cancer tumors, the principal component analysis and the clustering analysis were applied. In three of the four samples, the cancer tissue was recognized as an aggregate of the data points in the principal component plots. By the agglomerative hierarchical clustering, the data points were well categorized into cancer and the other tissues. This method can be also applied to various kinds of automatic discrimination of plural components by terahertz spectroscopic imaging.

  4. 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.

  5. Ablation and Other Local Therapy for Kidney Cancer

    MedlinePlus

    ... how the procedure is being done. Possible side effects include bleeding and damage to the kidneys or other nearby organs. Radiofrequency ablation (RFA) This technique uses high-energy radio waves to heat the tumor. A thin, needle-like probe is ...

  6. 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.

  7. 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. PMID:19773017

  8. 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

  9. 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. PMID:23400756

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

    PubMed Central

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

    2016-01-01

    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. PMID:26933819

  11. Molecular and immunologic markers of kidney cancer-potential applications in predictive, preventive and personalized medicine.

    PubMed

    Mickley, Amanda; Kovaleva, Olga; Kzhyshkowska, Julia; Gratchev, Alexei

    2015-01-01

    Kidney cancer is one of the deadliest malignancies due to frequent late diagnosis (33 % or renal cell carcinoma are metastatic at diagnosis) and poor treatment options. There are two major subtypes of kidney cancer: renal cell carcinoma (RCC) and renal pelvis carcinoma. The risk factors for RCC, accounting for more than 90 % of all kidney cancers, are smoking, obesity, hypertension, misuse of pain medication, and some genetic diseases. The most common molecular markers of kidney cancer include mutations and epigenetic inactivation of von Hippel-Lindau (VHL) gene, genes of vascular endothelial growth factor (VEGF) pathway, and carbonic anhydrase IX (CIAX). The role of epigenetic pathways, including DNA methylation and chromatin structure remodeling, was also demonstrated. Immunologic properties of RCC enable this type of tumor to escape immune response effectively. An important role in this process is played by tumor-associated macrophages that demonstrate mixed M1/M2 phenotype. In this review, we discuss molecular and cellular aspects for RCC development and current state of knowledge allowing personalized approaches for diagnostics and prognostic prediction of this disease. A set of macrophage markers is suggested for the analysis of the association of macrophage phenotype and disease prognosis. PMID:26500709

  12. 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. PMID:26933819

  13. Cancer of the Soft Tissue including Heart

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 12,310 % of All New Cancer Cases 0.7% Estimated Deaths in 2016 4,990 % of All Cancer ... heart cancer is rare. Common Types of Cancer Estimated New Cases 2016 Estimated Deaths 2016 1. Breast ...

  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 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 ...

  15. 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...

  16. RNA-Seq accurately identifies cancer biomarker signatures to distinguish tissue of origin.

    PubMed

    Wei, Iris H; Shi, Yang; Jiang, Hui; Kumar-Sinha, Chandan; Chinnaiyan, Arul M

    2014-11-01

    Metastatic cancer of unknown primary (CUP) accounts for up to 5% of all new cancer cases, with a 5-year survival rate of only 10%. Accurate identification of tissue of origin would allow for directed, personalized therapies to improve clinical outcomes. Our objective was to use transcriptome sequencing (RNA-Seq) to identify lineage-specific biomarker signatures for the cancer types that most commonly metastasize as CUP (colorectum, kidney, liver, lung, ovary, pancreas, prostate, and stomach). RNA-Seq data of 17,471 transcripts from a total of 3,244 cancer samples across 26 different tissue types were compiled from in-house sequencing data and publically available International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Robust cancer biomarker signatures were extracted using a 10-fold cross-validation method of log transformation, quantile normalization, transcript ranking by area under the receiver operating characteristic curve, and stepwise logistic regression. The entire algorithm was then repeated with a new set of randomly generated training and test sets, yielding highly concordant biomarker signatures. External validation of the cancer-specific signatures yielded high sensitivity (92.0% ± 3.15%; mean ± standard deviation) and specificity (97.7% ± 2.99%) for each cancer biomarker signature. The overall performance of this RNA-Seq biomarker-generating algorithm yielded an accuracy of 90.5%. In conclusion, we demonstrate a computational model for producing highly sensitive and specific cancer biomarker signatures from RNA-Seq data, generating signatures for the top eight cancer types responsible for CUP to accurately identify tumor origin. PMID:25425966

  17. Comparative analysis of differential network modularity in tissue specific normal and cancer protein interaction networks

    PubMed Central

    2013-01-01

    Background Large scale understanding of complex and dynamic alterations in cellular and subcellular levels during cancer in contrast to normal condition has facilitated the emergence of sophisticated systemic approaches like network biology in recent times. As most biological networks show modular properties, the analysis of differential modularity between normal and cancer protein interaction networks can be a good way to understand cancer more significantly. Two aspects of biological network modularity e.g. detection of molecular complexes (potential modules or clusters) and identification of crucial nodes forming the overlapping modules have been considered in this regard. Methods In the current study, the computational analysis of previously published protein interaction networks (PINs) has been conducted to identify the molecular complexes and crucial nodes of the networks. Protein molecules involved in ten major cancer signal transduction pathways were used to construct the networks based on expression data of five tissues e.g. bone, breast, colon, kidney and liver in both normal and cancer conditions. MCODE (molecular complex detection) and ModuLand methods have been used to identify the molecular complexes and crucial nodes of the networks respectively. Results In case of all tissues, cancer PINs show higher level of clustering (formation of molecular complexes) than the normal ones. In contrast, lower level modular overlapping is found in cancer PINs than the normal ones. Thus a proposition can be made regarding the formation of some giant nodes in the cancer networks with very high degree and resulting in reduced overlapping among the network modules though the predicted molecular complex numbers are higher in cancer conditions. Conclusion The study predicts some major molecular complexes that might act as the important regulators in cancer progression. The crucial nodes identified in this study can be potential drug targets to combat cancer. PMID

  18. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer.

    PubMed

    Sudarshan, Sunil; Pinto, Peter A; Neckers, Len; Linehan, W Marston

    2007-02-01

    Renal cell carcinoma (RCC) represents a group of diseases linked by their primary site of origin, the kidney. Studies of families with a genetic predisposition to the development of kidney cancer have revealed that multiple genes are involved in the molecular pathogenesis of RCC. Germline mutations in a gene that encodes a Krebs cycle enzyme have been found to result in a distinct clinical entity referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is inherited in an autosomal-dominant fashion. Affected individuals in HLRCC families are at risk for the development of leiomyomas of the skin and uterus as well as renal cancers. HLRCC-associated kidney tumors are often biologically aggressive. Linkage analysis has identified germline alterations in the fumarate hydratase (FH) gene associated with HLRCC. While the mechanisms of molecular carcinogenesis are not entirely understood, several lines of evidence derived from clinical and basic research suggest that pseudohypoxia might drive cellular transformation. The role of FH mutations in sporadic tumors seems to be limited. Nevertheless, continued investigation of HLRCC should provide further insight into the mechanisms of kidney cancer development, and could potentially identify targets for new therapeutic approaches to RCC. PMID:17287871

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

    ClinicalTrials.gov

    2016-01-12

    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

  20. Mueller matrix polarimetry for differentiating characteristic features of cancerous tissues

    NASA Astrophysics Data System (ADS)

    Du, E.; He, Honghui; Zeng, Nan; Sun, Minghao; Guo, Yihong; Wu, Jian; Liu, Shaoxiong; Ma, Hui

    2014-07-01

    Polarization measurements allow one to enhance the imaging contrast of superficial tissues and obtain new polarization sensitive parameters for better descriptions of the micro- and macro- structural and optical properties of complex tissues. Since the majority of cancers originate in the epithelial layer, probing the morphological and pathological changes in the superficial tissues using an expended parameter set with improved contrast will assist in early clinical detection of cancers. We carry out Mueller matrix imaging on different cancerous tissues to look for cancer specific features. Using proper scattering models and Monte Carlo simulations, we examine the relationship between the microstructures of the samples, which are represented by the parameters of the scattering model and the characteristic features of the Mueller matrix. This study gives new clues on the contrast mechanisms of polarization sensitive measurements for different cancers and may provide new diagnostic techniques for clinical applications.

  1. 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.

  2. Activity of continuous infusion plus pulse interleukin-2 with famotidine in patients with metastatic kidney cancer or melanoma previously treated with interleukin-2.

    PubMed

    Quan, Walter D Y; Walker, Paul R; Quan, Francine M; Ramirez, Maria; Elsamaloty, Haitham M; Ghai, Vikas; Vinogradov, Mikhail; Liles, Darla K

    2006-10-01

    Lymphokine-activated killer (LAK) cells generated by high-dose continuous infusion interleukin-2 (IL-2) are able to nonspecifically lyse melanoma and kidney cancer cells. In vitro famotidine enhances cytotoxicity of LAK against tumor cells, possibly by increasing IL-2 uptake at the IL-2 receptor on lymphocytes. Outpatient IL-2 regimens typically have response rates of 15% or less, with most patients eventually experiencing progressive disease. Second-line therapy is, therefore, needed. We treated 11 patients (6 with metastatic melanoma; 5 having metastatic kidney cancer) who had previously experienced progressive disease on prior IL-2 regimens, with a combination of famotidine 20 mg intravenously (i.v.) twice per day and continuous-infusion IL-2 18 MIU/M2/24 hours x 72 hours, followed 24 hours later by a pulse IL-2 dose (18 MIU/M2 over 15 minutes). Cycles were repeated every 3 weeks. Patient characteristics were: 9 males, median age 63 years (range, 57-75), median Eastern Cooperative Oncology Group (ECOG) performance status: 1; most common metastatic sites: lungs, lymph nodes, and soft tissue/subcutaneous (s.c.); median number of cycles received: 4; most common toxicities were fever, nausea/emesis, hypophosphatemia, and hypomagnesemia. Five (5) patients (3 with melanoma, 2 with kidney cancer) have had partial responses. Two (2) patients with kidney cancer have been converted to complete responders with resection of residual disease, remaining without relapse at 5+ and 20+ months. Responding sites are lungs, lymph nodes, abdominal mass, and s.c. Median duration of response was 9.5 months. Median survival was 12 months. This combination has activity in patients with metastatic kidney cancer or melanoma who have received prior IL-2. PMID:17105418

  3. Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Shen, Chongxing; Huang, Ying; Yi, Shanhong; Fang, Zhenqiang; Li, Longkun

    2015-01-01

    Background Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. Material/Methods A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. Results A total of 13 observational studies (7 case-control and 6 cohort) were included. The pooled RR (95%CI) of kidney cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.69–0.94). In subgroup-analysis, this study found an inverse relationship between vitamin E intake and kidney cancer risk, which was not significantly modified by study design, study population, or sex distribution except in the cohort studies. Conclusions Results of the present study suggest an inverse relationship between vitamin E intake and kidney cancer risk. However, additional well designed cohort studies and randomized controlled trials that focus on the relationship between vitamin E intake and kidney cancer risk are needed. PMID:26547129

  4. 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

  5. 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

    2015-12-01

    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. 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

  7. Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus

    PubMed Central

    2011-01-01

    Background Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS). Results 17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection. Conclusions To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection. PMID:21385394

  8. Genomic characterisation of two cancers of unknown primary cases supports a kidney cancer origin.

    PubMed

    Wei, Elizabeth Y; Chen, Ying-Bei; Hsieh, James J

    2015-01-01

    Cancer of unknown primary (CUP) comprises of 3-5% of new cancer diagnoses in the USA. Diagnostic work up typically includes CT of the chest, abdomen and pelvis, and histopathological review of tissue specimens. These measures are neither sensitive nor specific in determining tissue of origin (ToO) of primary tumours and, therefore, are unable to guide therapy. We present two cases of CUP for which we utilised ultra-deep genomic sequencing to identify the candidate ToO and to propose treatment. Patient 1 presented with metastases involving the lung, lymph nodes and bone. Patient 2 presented with an acute pathological fracture of the T7 vertebral body and metastases involving the bone, lymph nodes and soft tissue. No primary renal mass was found. Sequencing revealed SETD2 and NF2 mutations, and heterozygous loss of the short arm of chromosome 3 (3p). Mutations in conjunction with clinicopathological features strongly support a diagnosis of renal cell carcinoma. Both patients initially responded to mTORC1 inhibition therapy. PMID:26494726

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

    PubMed Central

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

    2016-01-01

    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. PMID:26771139

  11. 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

    2016-02-01

    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. PMID:26771139

  12. Certain Biopsy Method Tied to Better Outcomes After Kidney Cancer

    MedlinePlus

    ... adults. Researchers led by Dr. Rosaleen Parsons, of Fox Chase Cancer Center in Philadelphia, noted that incidence ... treatment decisions, Parsons, chair of diagnostic imaging at Fox Chase, said in a center news release. However, ...

  13. Complex permittivities of breast tumor tissues obtained from cancer surgeries

    NASA Astrophysics Data System (ADS)

    Sugitani, Takumi; Kubota, Shin-ichi; Kuroki, Shin-ichiro; Sogo, Kenta; Arihiro, Koji; Okada, Morihito; Kadoya, Takayuki; Hide, Michihiro; Oda, Miyo; Kikkawa, Takamaro

    2014-06-01

    The variability in measurements of complex permittivities of tumor tissues between multiple samples could be attributed to the volume fraction of cancer cells in the excised tumor tissue. By the use of a digital photomicrograph image and hematoxylin-eosin staining, it was found that the malignant tumor tissue was not fully occupied by the cancer cells, but the cells were distributed locally in the stroma cells depending on the growth of cancer. The results showed that the volume fraction of cancer cells in the tumor tissue had a correlation to the measured conductivity and dielectric constant in the frequency range from 1 GHz to 6 GHz. It introduces a method to understand and gauge variability in measurements between different tumors.

  14. Association of Antibody Induction Immunosuppression with Cancer After Kidney Transplantation1

    PubMed Central

    Hall, Erin C; Engels, Eric A; Pfeiffer, Ruth M; Segev, Dorry L

    2014-01-01

    Background Induction immunosuppression is a mainstay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. Methods We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. 111,857 kidney recipients (1987–2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. cancer registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL)and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). Results 2,763 cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR=1.37, 95% CI 1.06–1.76). Alemtuzumab was associated with increased NHL (aIRR=1.79, 95% CI 1.02-1-3.14), colorectal cancer (aIRR=2.46, 95% CI 1.03–5.91), and thyroid cancer (aIRR=3.37, 95% CI 1.55–7.33). Polyclonal induction was associated with increased melanoma (aIRR=1.50, 95% CI 1.06–2.14). Conclusions Our findings highlight the relative safety with regard to cancer risk of the most common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T cell induction. PMID:25340595

  15. Qualitative and Quantitative Analysis of Histone Deacetylases in Kidney Tissue Sections.

    PubMed

    Ververis, Katherine; Marzully, Selly; Samuel, Chrishan S; Hewitson, Tim D; Karagiannis, Tom C

    2016-01-01

    Fluorescent microscope imaging technologies are increasing in their applications and are being used on a wide scale. However methods used to quantify the level of fluorescence intensity are often not utilized-perhaps given the result may be immediately seen, quantification of the data may not seem necessary. However there are a number of reasons given to quantify fluorescent images including the importance of removing potential bias in the data upon observation as well as quantification of large numbers of images gives statistical power to detect subtle changes in experiments. In addition discreet localization of a protein could be detected without selection bias that may not be detectable by eye. Such data will be deemed useful when detecting the levels of HDAC enzymes within cells in order to develop more effective HDAC inhibitor compounds for use against multiple diseased states. Hence, we discuss a methodology devised to analyze fluorescent images using Image J to detect the mean fluorescence intensity of the 11 metal-dependent HDAC enzymes using murine kidney tissue sections as an example. PMID:26676140

  16. Checkmate: kidney injury associated with targeted cancer immunotherapy.

    PubMed

    Perazella, Mark A

    2016-09-01

    Immune checkpoint inhibitors are a class of drugs that utilizes immunotherapy to target various cancers. Included are the anti-CTLA-4 and anti-PD-1 receptor antibodies. By reprogramming the immune system, these agents provide a therapy that destroys cancer cells. However, this approach runs the risk of allowing pathologic autoimmunity and organ injury to develop. Unsurprisingly, immune-related adverse effects are described including pneumonitis, colitis, and various endocrinopathies. Now added to this list is AKI, primarily due to ATIN. PMID:27521108

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

    PubMed Central

    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. PMID:26555791

  18. Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction.

    PubMed

    Keller, Frieder; Schröppel, Bernd; Ludwig, Ulla

    2015-07-01

    Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations. PMID:26167456

  19. Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction

    PubMed Central

    Keller, Frieder; Schröppel, Bernd; Ludwig, Ulla

    2015-01-01

    Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations. PMID:26167456

  20. 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

  1. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors*

    PubMed Central

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Background Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. Objectives To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Methods Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. Results We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Conclusion Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies. PMID:27579740

  2. Repeated cycles with 72-hour continuous infusion interleukin-2 in kidney cancer and melanoma.

    PubMed

    Quan, Walter; Brick, Wendy; Vinogradov, Mikhail; Taylor, W Chris; Khan, Nawazish; Burgess, Russell

    2004-06-01

    While high-dose bolus inpatient interleukin-2 is generally given on 8-week cycles, continuous infusion interleukin-2 could potentially allow for more rapidly repeated cycles. Fourteen (14) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, having either kidney cancer (6) or melanoma (8), have been treated with continuous infusion (CIV) interleukin-2 (IL-2) 18 MIU/m(2)/24 hours for 72 hours. Cycles were repeated every 3 weeks up to 4 cycles, then every 3-4 weeks for 2 cycles, then every 6-8 weeks, until progression or intolerable toxicity. All patients received famotidine 20 mg intravenously (i.v.) twice per day during the 72-hour infusions. Patient characteristics included a median ECOG performance status of 1; median age = 63 (range: 25-79); most common metastatic sites: lung (9), bone (5), lymph nodes (5), and the liver (3). No patients with metastatic kidney cancer underwent a nephrectomy prior to interleukin-2. Median number of cycles received = 5 (1-9). No patients required Intensive Care Unit (ICU) admission. There have been no treatment-related deaths. Most common toxicities have been rigors, fever, nausea/emesis, and the reversible elevation of creatinine. One complete response and three partial responses (67% response rate; 95% confidence interval: 30%-90%) have been seen in kidney cancer, and two partial responses (25% response rate; 95% confidence interval: 7%-60%) have occurred in melanoma. Median survival has not been reached at >9+ months. Responding sites include the liver, bone, lung, lymph node and subcutaneous sites. Inpatient 72-hour continuous infusion interleukin-2 at this dose and schedule is well tolerated by patients with an ECOG performance status of 0 or 1 and has activity in kidney cancer and melanoma. PMID:15285881

  3. Location of type XV collagen in human tissues and its accumulation in the interstitial matrix of the fibrotic kidney.

    PubMed Central

    Hägg, P. M.; Hägg, P. O.; Peltonen, S.; Autio-Harmainen, H.; Pihlajaniemi, T.

    1997-01-01

    An antipeptide antibody was produced against the carboxyl-terminal noncollagenous domain of human type XV collagen and used to localize this recently described collagen in a number of human tissues. The most conspicuous findings were powerful staining of most of the capillaries and staining of the basement membrane (BM) zones of muscle cells. Not all of the BM zones were positive, however, as shown by the lack of staining in the developing fetal alveoli and some of the tubules in developing kidney. Nor was type XV collagen staining restricted to the BM zones, as some could be observed in the fibrillar collagen matrix of the papillary dermis and placental villi, for example. Interestingly, differences in the expression of type XV collagen could be observed during kidney development, and staining of fetal lung tissue suggested that changes in its expression may also occur during the formation of vascular structures. Another intriguing finding was pronounced renal interstitial type XV collagen staining in patients with kidney fibrosis due to different pathological processes. This suggests that the accumulation of type XV collagen may accompany fibrotic processes. Full-length human type XV collagen chains with an apparent molecular mass of approximately 200 kd were produced in insect cells using a baculovirus expression system. The fact that these had a markedly higher molecular mass than the 100- to 110-kd type XV collagen chains found in homogenates of heart and kidney tissue suggests either proteolytic processing during the synthesis of type XV collagen or an inability to solubilize complete molecules from tissues. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9176399

  4. High-dose intensity pulse interleukin-2 with famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter D Y; Quan, Francine M

    2009-04-01

    Lymphokine-activated killer cell (LAK) activity against tumor cell lines may be induced by intravenous (i.v.) interleukin-2 (IL-2). Daily short infusions (pulses) have been developed to decrease toxicity while maintaining the anticancer activity of this agent against kidney cancer. The anthihistamine, famotidine, may increase IL-2 uptake by the IL-2 receptor on lymphocytes. We have treated 12 patients with metastatic kidney cancer, using pulse IL-2 (18 million IU/M(2) i.v.) over 15-30 minutes, preceded by famotidine (20 mg I.V. daily for 5 days) on an oncology inpatient unit. Cycles were repeated every 3 weeks until disease progression. Patient characteristics were as follows: 9 males with a median age of 66 years (range, 48-74), and median Eastern Cooperative Oncology Group performance status of 1; common metastatic sites included in the lungs 9 and lymph nodes 3. Median number of cycles received was 2 (range, 1-5). The most common toxicities were fever, rigors, and hypomagnesemia. Two (2) patients had partial responses (17% response rate). Responses occurred in the liver (11.5 months) and lung, pleura, and lymph nodes (3 months). Pulse IL-2 with famotidine shows activity in kidney cancer. PMID:19409039

  5. Activity of outpatient intravenous interleukin-2 and famotidine in metastatic clear cell kidney cancer.

    PubMed

    Quan, Walter D Y; Quan, Francine Marie

    2014-03-01

    Outpatient daily intravenous infusions of interleukin-2 (IL-2) have been developed to maintain anticancer activity and decrease toxicity of this agent against kidney cancer. Lymphokine activated killer cell (LAK) numbers are increased with these IL-2 schedules. Famotidine may enhance the LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. Fifteen patients with metastatic clear cell kidney cancer received IL-2 18 million IU/M² intravenously over 15-30 minutes preceded by famotidine 20 mg IV daily for 3 days for 6 consecutive weeks as outpatients. Cycles were repeated every 8 weeks. Patient characteristics were seven males/eight females, median age 59 (range: 28-70), median Eastern Cooperative Oncology Group (ECOG) performance status-1; common metastatic sites were lungs (14), lymph nodes (9), liver (4), bone (4), and pancreas (4). Prior systemic therapies were oral tyrosine kinase inhibitor (8), IL-2 (6), and mTor inhibitor (2). Most common toxicities were rigors, arthralgia/myalgia, nausea/emesis, fever, and hypotension. All episodes of hypotension were reversible with intravenous fluid. No patients required hospitalization due to toxicity. One complete response (7%) and four partial responses (26%) were seen (total response rate=33%; 95% confidence interval: 15%-59%). Responses occurred in the lungs, liver, lymph nodes, and bone. Outpatient intravenous IL-2 with famotidine has activity in metastatic clear cell kidney cancer. PMID:24251758

  6. Optical transillumination spectroscopy of breast tissue for cancer risk assessment

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar; Blyschak, Kristina; Simick, Michelle; Jong, Roberta A.

    2003-10-01

    Breast cancer is the most commonly occurring cancer in women. The lifetime risk of being diagnosed with breast cancer is approximately 1 in 10 thereby the highest out of all cancers. Breast cancer screening programs have been shown to decrease the mortality rates of women between ages 50-69, since cancers are detected at an earlier, more favourable stage. It is apparent that the development of breast cancer is a slow process following initial transformation of the breast tissue. Hence, there has been a strong effort within the research community to understand risk factors for the disease. Risk factors are defined as those characteristics that are more common in people with the disease when compared to the normal population. Quantification of an individual's breast cancer rate may lead that individual to modify her lifestyle and/or diet. Lifestyle changes could lead to a reduction in the incidence of breast cancer. Anatomically, the presence of increased amounts of fibroglandular tissue raises the estimated risk by up to 6 fold (correct for age), hence representing one of the strongest known risk factors pertaining to the entire female population. In this study the relative area of mammographic densities within a mammogram will be used as a global risk assessment tool. It has been shown previously that quantification of water, lipids, haemoglobin and other tissue chromophores of the optically interrogated breast tissue, which also gives rise to the mammographic densities, is feasible through near-infrared spectroscopy. Thus, the hypothesis for this study is that optical transillumination spectroscopy provides consistent and/or complementary information to conventional mammography in quantifying breast tissue density.

  7. 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

  8. Gender differences in incidence and outcomes of urothelial and kidney cancer.

    PubMed

    Lucca, Ilaria; Klatte, Tobias; Fajkovic, Harun; de Martino, Michela; Shariat, Shahrokh F

    2015-10-01

    A gender discrepancy exists in the incidence of both urothelial and kidney carcinomas, with more men presenting with these cancers than women. Men have a threefold greater risk of developing bladder cancer than women, but female gender has been identified as an independent adverse prognostic factor for both recurrence and progression of this disease. In particular, women with bladder cancer are often diagnosed with a higher tumour stage than men. Conclusive data on the influence of gender on outcomes of patients with upper tract urothelial carcinoma are currently lacking, although men seem to have a higher disease incidence, whereas survival outcomes might be independent of gender. Patients with renal cell carcinoma are more often men and they typically have larger tumours and higher stage and grade disease than women with this cancer. Smoking habits, tumour biology, occupational risk factors and sex steroid hormones and their receptors could have a role in these observed gender disparities. The majority of data support the theory that gender influences incidence and prognosis of urothelial and kidney cancers; men and women are different genetically and socially, making the consideration of gender a key factor in the clinical decision-making process. Thus, the inclusion of this variable in validated prognostic tables and nomograms should be discussed as a matter of importance. PMID:26436686

  9. Diagnostics of cancer tissues by fiber optic evanescent wave Fourier transform IR (FEW-FTIR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Letokhov, Vladilen S.; Golovkina, Viktoriya N.

    1997-08-01

    Fiber optic evanescent wave Fourier transform infrared (FEW- FTIR) spectroscopy using fiberoptic sensors operated in the attenuated total reflection (ATR) regime in the middle infrared (IR) region of the spectrum (850 - 1850 cm-1) has recently found application in the diagnostics of tissues. The method is suitable for noninvasive and rapid (seconds) direct measurements of the spectra of normal and pathological tissues in vitro, ex vivo and in vivo. The aim of our studies is the express testing of various tumor tissues at the early stages of their development. The method is expected to be further developed for endoscopic and biopsy applications. We measured in vivo the skin normal and malignant tissues on surface (directly on patients) in various cases of basaloma, melanoma and nevus. The experiments were performed in operating room for measurements of skin in the depth (under/in the layers of epidermis), human breast, stomach, lung, kidney tissues. The breast and skin tissues at different stages of tumor or cancer were distinguished very clearly in spectra of amide, side cyclic and noncyclic hydrogen bonded fragments of aminoacid residuals, phosphate groups and sugars. Computer monitoring is being developed for diagnostics.

  10. Innovations in preclinical biology: ex vivo engineering of a human kidney tissue microperfusion system

    PubMed Central

    2013-01-01

    Kidney disease is a public health problem that affects more than 20 million people in the US adult population, yet little is understood about the impact of kidney disease on drug disposition. Consequently there is a critical need to be able to model the human kidney and other organ systems, to improve our understanding of drug efficacy, safety, and toxicity, especially during drug development. The kidneys in general, and the proximal tubule specifically, play a central role in the elimination of xenobiotics. With recent advances in molecular investigation, considerable information has been gathered regarding the substrate profiles of the individual transporters expressed in the proximal tubule. However, we have little knowledge of how these transporters coupled with intracellular enzymes and influenced by metabolic pathways form an efficient secretory and reabsorptive mechanism in the renal tubule. Proximal tubular secretion and reabsorption of xenobiotics is critically dependent on interactions with peritubular capillaries and the interstitium. We plan to robustly model the human kidney tubule interstitium, utilizing an ex vivo three-dimensional modular microphysiological system with human kidney-derived cells. The microphysiological system should accurately reflect human physiology, be usable to predict renal handling of xenobiotics, and should assess mechanisms of kidney injury, and the biological response to injury, from endogenous and exogenous intoxicants. PMID:24564863

  11. 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. PMID:25771021

  12. Tissue engineering a surrogate niche for metastatic cancer cells

    PubMed Central

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

    2015-01-01

    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 for metastasizing cancer cells. PMID:25771021

  13. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    PubMed

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. PMID:26529279

  14. Serum tumor markers in chronic kidney disease: as clinical tool in diagnosis, treatment and prognosis of cancers.

    PubMed

    Amiri, Fateme Shamekhi

    2016-05-01

    Cancer is singled out as the biggest cause of death in the world, predicted to reach 13.1 million cancer-related deaths by the year 2030. Although there are no specific tumor markers used in cancer screening, some markers can be used to assist in making a diagnosis and determining a prognosis. They can be used to follow in cases where the diagnosis is cancer through monitoring of the disease recurrence and/or evaluating the response to therapy. These markers are not specific as the number increases in multiple cases of cancer. Some markers are positive in a single type of cancer; others are detectable in more than one type. An ideal tumor marker should be highly sensitive, specific, and reliable with high prognostic value. Other characteristics of an ideal tumor marker are organ specificity and correlation of it with tumor stages. However, none of the tumor markers reported to date has all these characteristics. Influence of different stages of chronic kidney function on serum tumor markers is variable. Furthermore, hemodialysis, peritoneal dialysis, and kidney transplantation affect on tumor markers differently. Sometimes, no study has been found in the literature review. Combined serum tumor markers may also be valuable. This literature review points the role of serum tumor markers in screening, diagnosis, and follow-up of cancer patients in chronic kidney disease patients and renal allograft recipients. In addition, impact of chronic kidney disease and kidney transplantation on different serum tumor markers is briefly explored. PMID:26907957

  15. Podocyte-associated mRNA profiles in kidney tissue and in urine of patients with active lupus nephritis

    PubMed Central

    dos Santos, Mariane; Bringhenti, Rafael N; Rodrigues, Patrícia G; do Nascimento, Jonathan F; Pereira, Sane V; Zancan, Rafael; Monticielo, Odirlei A; Gasparin, Andrese A; de Castro, Waldir P; Veronese, Francisco V

    2015-01-01

    Aim: Glomerular deposition of immune complexes and inflammation induce podocyte injury in lupus nephritis (LN). This study hypothesized that the severity of the histological lesions of LN affects podocyte-associated mRNAs profiles in kidney tissue and in urine. Methods: Thirty-three patients with LN were grouped according to the presence of mild mesangial (classes I and II) or moderate-to-severe immune complex deposition, proliferation and/or inflammation (classes III, IV and V) in kidney biopsy. Tissue and urine mRNA of nephrin, podocin, podocalyxin, α-actinin-4, transient receptor potential cation channel 6, and of growth factors VEGF-A and TGF-β1 and the transcription factor FOXP3 were measured using real time polymerase chain reaction. These mRNAs were correlated with histological severity of LN, extent of glomerular immune deposits, and tissue infiltrating cells. Results: Podocyte-associated mRNAs were inhibited in renal tissue of patients with LN irrespective of histological class when compared to controls. However, significantly higher expression of podocyte mRNAs in urine, including those of growth factors and FOXP3, were found in patients with moderate-to-severe nephritis, mostly in class III and IV proliferative forms. The number of invading CD8+ T cells, B cells and macrophages correlated positively with urine podocyte-associated mRNAs. Urine podocyte mRNAs also correlated with proteinuria. Conclusions: Inhibition of podocyte-associated mRNAs in kidney tissue suggests that podocyte injury occurs regardless of class severity of LN. Increased urinary excretion of podocyte mRNAs, mostly in patients with moderate-to-severe lesions, may reflect a greater burden of glomerular damage with detachment of podocytes into the urine. PMID:26191151

  16. ANALYSIS FOR B-LACTAM ANTIBIOTICS IN KIDNEY TISSUE BY LIQUID CHROMATOGRAPHY WITH ELECTROSPRAY IONIZATION AND SELECTIVE REACTION MONITORING/TANDEM ION TRAP MASS SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eleven B-lactams antibiotics were analyzed in fortified and incurred beef kidney tissue using high-performance liquid chromatography/selective reaction monitoring/tandem ion trap mass spectrometry. The analytes included: deacetylcephapirin, amoxicillin, cephapirin, desfuroylceftiofur cysteine disul...

  17. Cadmium and lead in animal tissue (muscle, liver and kidney), cow milk and dairy products in Korea.

    PubMed

    Kim, Dong-Gyu; Kim, MeeKyung; Shin, Jin Young; Son, Seong-Wan

    2016-03-01

    A survey of Cd and Pb in animal tissue, milk and dairy products was conducted. Muscle, liver and kidney of domestically produced cows, pigs, chickens and ducks were collected from eight regions in Korea. Raw cow milk was collected from 9 regions, and imported dairy products (butter, cheese, cream and powdered milk) were collected from 15 countries. Cd and Pb were analysed by inductively coupled plasma mass spectrometry (ICP-MS) after microwave digestion. Concentrations of Cd and Pb did not exceed the Korean legal maximum levels in any of the samples. Correlation coefficients were estimated between concentration of Cd or Pb and animal age and between muscle, liver and kidney. In cows, there were good correlations between age and Cd in kidney (r = 0.748) and between Cd in liver and in kidney (r = 0.878). Continuous monitoring will be an important role to safeguard consumers in the event of a food contamination incident. PMID:26588172

  18. 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.

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

    PubMed

    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. PMID:26590218

  20. Inhibition of Macrophage Migration Inhibitory Factor Protects against Inflammation and Matrix Deposition in Kidney Tissues after Injury

    PubMed Central

    Lu, Hong; Bai, Yongyu; Wu, Lianfeng; Hong, Weilong; Liang, Yong; Chen, Bicheng; Bai, Yongheng

    2016-01-01

    Background. Macrophage migration inhibitory factor (MIF) is an important immunoregulatory cytokine involved in inflammation, which may be one important reason resulting in matrix deposition in renal tissues after injury. However, the underlying mechanisms have not yet been elucidated. Methods and Results. We uncovered a crucial role of MIF in inflammation and collagen deposition in vivo and in vitro. In rats, ureteral obstruction induced tubular injury, matrix accumulation, and inflammatory cell infiltration. Additionally, enhanced MIF levels in the obstructed kidneys were closely related to the increasing numbers of CD68-positive macrophages. These obstruction-induced injuries can be relieved by recanalization, consequently resulting in downregulated expression of MIF and its receptor CD74. Similarly, ischemia reperfusion induced renal injury, and it was accompanied by elevated MIF levels and macrophages infiltration. In cultured tubular epithelial cells (TECs), aristolochic acid (AA) promoted matrix production and increased MIF expression, as well as the release of macrophage-related factors. Inhibition of MIF with an antagonist ISO-1 resulted in the abolishment of these genotypes in AA-treated TECs. Conclusion. MIF plays an important role in macrophage-related inflammation and matrix deposition in kidney tissues following injury. MIF as a specific inhibitor may have therapeutic potential for patients with inflammatory and fibrotic kidney diseases. PMID:27313397

  1. Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management

    PubMed Central

    Shuch, Brian; Vourganti, Srinivas; Ricketts, Christopher J.; Middleton, Lindsay; Peterson, James; Merino, Maria J.; Metwalli, Adam R.; Srinivasan, Ramaprasad; Linehan, W. Marston

    2014-01-01

    Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer. Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing. Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was ≤ 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity. Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines. PMID:24378414

  2. Polarimetric phenomenology of photons with lung cancer tissue

    NASA Astrophysics Data System (ADS)

    Giakos, G. C.; Marotta, S.; Narayan, C.; Petermann, J.; Shrestha, S.; Baluch, J.; Pingili, D.; Sheffer, D. B.; Zhang, L.; Zervakis, M.; Livanos, G.; Kounelakis, M.

    2011-11-01

    The objective of this study is to explore the polarimetric phenomenology of light interaction with healthy and early-stage lung cancer tissue samples by applying efficient polarimetric backscattering detection techniques combined with polarimetric exploratory data analysis. Preliminary results indicate that enhanced discrimination signatures can be obtained for certain types of early-stage lung cancers based on their depolarization, backscattered intensity and retardance characteristics.

  3. Safety of Ovarian Tissue Autotransplantation for Cancer Patients

    PubMed Central

    Bockstaele, Laurence; Tsepelidis, Sophie; Dechene, Julie; Englert, Yvon; Demeestere, Isabelle

    2012-01-01

    Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance. PMID:22253631

  4. 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.

  5. Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction

    ClinicalTrials.gov

    2013-05-15

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  6. 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.

  7. Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

    PubMed Central

    Campanholle, Gabriela; Ligresti, Giovanni; Gharib, Sina A.

    2013-01-01

    Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process. PMID:23325411

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

    PubMed

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

    2015-08-01

    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

  9. 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

  10. 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.

  11. 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

  12. High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Vinogradov, Mikhail; Quan, Francine; Khan, Nawazish

    2005-02-01

    High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate. PMID:15778577

  13. 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

  14. 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.

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

    PubMed Central

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

    1996-01-01

    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 C2-C5 saturated, C2-C5 unsaturated, C6-C10 aliphatic saturated, C6-C10 aliphatic unsaturated, and C6-C10 aromatic process streams. Nonoccupational risk factors were body mass index (BMI), blood pressure (both measured at about age 28), and smoking. There was no significant 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). Images Figure 1. Figure 2. Figure 3. PMID:8793353

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

    PubMed

    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 C2-C5 saturated, C2-C5 unsaturated, C6-C10 aliphatic saturated, C6-C10 aliphatic unsaturated, and C6-C10 aromatic process streams. Nonoccupational risk factors were body mass index (BMI), blood pressure (both measured at about age 28), and smoking. There was no significant 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). PMID:8793353

  17. 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

  18. 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.

  19. Nectin 4 Overexpression in Ovarian Cancer Tissues and Serum

    PubMed Central

    DeRycke, Melissa S.; Pambuccian, Stefan E.; Gilks, C. Blake; Kalloger, Steve E.; Ghidouche, Abderrezak; Lopez, Marc; Bliss, Robin L.; Geller, Melissa A.; Argenta, Peter A.; Harrington, Katherine M.; Skubitz, Amy P.N.

    2011-01-01

    Early detection of ovarian cancer is difficult owing to the lack of specific and sensitive tests available. Previously, we found expression of nectin 4 to be increased in ovarian cancer compared with normal ovaries. Reverse transcriptase–polymerase chain reaction (RT-PCR) and quantitative RT-PCR validated the overexpression of nectin 4 messenger RNA in ovarian cancer compared with normal ovarian cell lines and tissues. Protein levels of nectin 4 were elevated in ovarian cancer cell lines and tissue compared with normal ovarian cell lines as demonstrated by Western immunoblotting, flow cytometry, and immunohistochemical staining of tissue microarray slides. Cleaved nectin 4 was detectable in a number of patient serum samples by enzyme-linked immunosorbent assay. In patients with benign gynecologic diseases with high serum CA125 levels, nectin 4 was not detected in the majority of cases, suggesting that nectin 4 may serve as a potential biomarker that helps discriminate benign gynecologic diseases from ovarian cancer in a panel with CA125. PMID:20959669

  20. 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

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

    PubMed

    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

  2. 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...

  3. Tissue-Based Metabolomics to Analyze the Breast Cancer Metabolome.

    PubMed

    Budczies, Jan; Denkert, Carsten

    2016-01-01

    Mass spectrometry and nuclear magnetic resonance-based metabolomics have been developed into mature technologies that can be utilized to analyze hundreds of biological samples in a high-throughput manner. Over the past few years, both technologies were utilized to analyze large cohorts of fresh frozen breast cancer tissues. Metabolite biomarkers were shown to separate breast cancer tissues from normal breast tissues with high sensitivity and specificity. Furthermore, the metabolome differed between hormone receptor positive (HR+) and hormone receptor negative (HR-) breast cancer, but was unchanged in HER2+ tumors compared to HER2- tumors. New metabolism-related biomarkers were discovered including the 4-aminobutyrate aminotransferase ABAT, where low mRNA expression led to an accumulation of beta-alanine and shortened relapse-free survival. The glutamate-to-glutamine ratio (GGR) represents another new biomarker that was increased in 88 % of HR- tumors and 56 % of HR+ tumors compared to normal breast tissues. The GGR might help to stratify patients for the treatment with specific glutaminase inhibitors that were recently developed and are currently being tested in phase I clinical studies. Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. In summary, metabolomics analysis of breast cancer tissues is a reliable method and has produced many new biological insights that may impact breast cancer diagnostics and treatment over the coming years. PMID:27557538

  4. 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

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

    PubMed

    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

  6. 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

  7. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26933922

  9. Integration of multimodal RNA-seq data for prediction of kidney cancer survival

    PubMed Central

    Schwartzi, Matt; Parkl, Martin; Phanl, John H.; Wang., May D.

    2016-01-01

    Kidney cancer is of prominent concern in modern medicine. Predicting patient survival is critical to patient awareness and developing a proper treatment regimens. Previous prediction models built upon molecular feature analysis are limited to just gene expression data. In this study we investigate the difference in predicting five year survival between unimodal and multimodal analysis of RNA-seq data from gene, exon, junction, and isoform modalities. Our preliminary findings report higher predictive accuracy-as measured by area under the ROC curve (AUC)-for multimodal learning when compared to unimodal learning with both support vector machine (SVM) and k-nearest neighbor (KNN) methods. The results of this study justify further research on the use of multimodal RNA-seq data to predict survival for other cancer types using a larger sample size and additional machine learning methods. PMID:27532026

  10. 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. PMID:26608100

  11. Genetic instability in epithelial tissues at risk for cancer.

    PubMed

    Hittelman, W N

    2001-12-01

    Epithelial tumors develop through a multistep process driven by genomic instability frequently associated with etiologic agents such as prolonged tobacco smoke exposure or human papilloma virus (HPV) infection. The purpose of the studies reported here was to examine the nature of genomic instability in epithelial tissues at cancer risk in order to identify tissue genetic biomarkers that might be used to assess an individual's cancer risk and response to chemopreventive intervention. As part of several chemoprevention trials, biopsies were obtained from risk tissues (i.e., bronchial biopsies from chronic smokers, oral or laryngeal biopsies from individuals with premalignancy) and examined for chromosome instability using in situ hybridization. Nearly all biopsy specimens show evidence for chromosome instability throughout the exposed tissue. Increased chromosome instability was observed with histologic progression in the normal to tumor transition of head and neck squamous cell carcinomas. Chromosome instability was also seen in premalignant head and neck lesions, and high levels were associated with subsequent tumor development. In bronchial biopsies of current smokers, the level of ongoing chromosome instability correlated with smoking intensity (e.g., packs/day), whereas the chromosome index (average number of chromosome copies per cell) correlated with cumulative tobacco exposure (i.e., pack-years). Spatial chromosome analyses of the epithelium demonstrated multifocal clonal outgrowths. In former smokers, random chromosome instability was reduced; however, clonal populations appeared to persist for many years, perhaps accounting for continued lung cancer risk following smoking cessation. PMID:11795428

  12. 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

  13. Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide.

    PubMed

    Jung, Jin Woo; Lee, Mi Suk; Choi, Hyo-Jung; Jung, Sunhee; Lee, Yu-Jung; Hwang, Geum-Sook; Kwon, Tae-Hwan

    2016-06-01

    In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg·day(-1)·rat(-1) of furosemide. Vehicle-treated (n = 14) and furosemide-treated (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g·220 g body wt(-1)·day(-1) for each rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mosmol/kgH2O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by ultraperformance liquid chromatography coupled with quadrupole time-of-flight (TOF) mass spectrometry, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetylcarnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI-TOF/TOF and IMS. Their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Carnitine compounds were increased in COR and IM, whereas carnitine and acetylcarnitine were decreased in OM. Choline compounds were increased in COR and OM but decreased in IM from furosemide rats. Betaine and GPC were decreased in OM and IM. Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. PMID:26962105

  14. Structural mass spectrometry of tissue extracts to distinguish cancerous and non-cancerous breast diseases

    PubMed Central

    Hines, K. M.; Ballard, B. R.

    2014-01-01

    Breast cancer is well-known to broadly impact cellular metabolism and aberrant metabolism in breast cancer tumors has been widely studied by both targeted and untargeted analyses to characterize the affected metabolic pathways. In this work, we utilize ultra-performance liquid chromatography (UPLC) in tandem with ion mobility-mass spectrometry (IM-MS), which provides chromatographic, structural, and mass information, to characterize the aberrant metabolism associated with breast diseases such as cancer. In a double-blind analysis of matched control (n=3) and disease tissues (n=3), tissues were homogenized, polar metabolites were extracted, and the extracts were characterized by UPLC-IM-MS/MS. Principle component analysis revealed a strong separation between disease tissues, with one diseased tissue clustering with the control tissues along PC1 and two others separated along PC2. Using postion mobility MS/MS spectra acquired by data-independent acquisition, the features giving rise to the observed grouping were determined to be biomolecules associated with aggressive breast cancer tumors, including glutathione, oxidized glutathione, thymosins β4 and β10, and choline-containing species. Pathology reports revealed the outlier of the disease tissues to be a benign fibroadenoma, whereas the other disease tissues represented highly metabolic benign and aggressive tumors. This IM-MS-based workflow bridges the transition from untargeted metabolomic profiling to tentative identifications of key descriptive molecular features using data acquired in one analysis, with additional experiments performed only for validation. The ability to resolve cancerous and non-cancerous tissues at the biomolecular level demonstrates UPLC-IM-MS/MS as a robust and sensitive platform for metabolomic profiling of tissues. PMID:25212505

  15. Differential Response of Heat Shock Proteins to Uphill and Downhill Exercise in Heart, Skeletal Muscle, Lung and Kidney Tissues

    PubMed Central

    Lollo, Pablo C. B.; Moura, Carolina S.; Morato, Priscila N.; Amaya-Farfan, Jaime

    2013-01-01

    Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP), but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric) and downhill (predominantly eccentric) muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7%) and downhill (-7% of inclination). At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK) and lactate dehydrogenase (LDH) were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal). When the contraction was concentric (uphill) and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL−1) in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively). The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus. Key Points Exercise can induce increases in HSP70 in

  16. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum

    PubMed Central

    2011-01-01

    Background The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl4) is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals. Methods 36 albino rats were divided into six groups of 6 animals each, all animals were allowed food and water ad libitum. Group I (control) was given olive oil, while the rest groups were injected intraperitoneally with a single dose of CCl4 (1 ml/kg) as a 50% (v/v) solution in olive oil. Group II received CCl4 only. Group III animals received vitamin E at a concentration of 50 mg/kg body weight and animals of groups IV, V and VI were given extract of Podophyllum hexandrum at concentration dose of 20, 30 and 50 mg/kg body weight. Antioxidant status in both kidney and lung tissues were estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and superoxide dismutase (SOD); as well as by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). In addition, superoxide and hydrogen peroxide radical scavenging activity of the extract was also determined. Results Results showed that the extract possessed strong superoxide and hydrogen peroxide radical scavenging activity comparable to that of known antioxidant butylated hydroxy toluene (BHT). Our results also showed that CCl4 caused a marked increase in TBARS levels whereas GSH, SOD, GR, GPX and GST levels were decreased in kidney and lung tissue homogenates of CCl4 treated rats. Aqueous extract of Podophyllum hexandrum successfully prevented the alterations of these effects

  17. 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

  18. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25810260

  20. Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers

    PubMed Central

    Senda, Motohiro; Ito, Akihiro; Tsuchida, Akiko; Hagiwara, Tomoko; Kaneda, Tsuguhiro; Nakamura, Yoko; Kasama, Kenji; Kiso, Makoto; Yoshikawa, Kazuhiro; Katagiri, Yoko; Ono, Yoshinari; Ogiso, Manabu; Urano, Takeshi; Furukawa, Keiko; Oshima, Shinichi; Furukawa, Koichi

    2006-01-01

    Although disialyl glycosphingolipids such as GD3 and GD2 have been considered to be associated with malignant tumours, whether branched-type disialyl glycosphingolipids show such an association is not well understood. We investigated the sialyltransferases responsible for the biosynthesis of DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside). Among six GalNAc:α2,6-sialyltransferases cloned to date, we focused on ST6GalNAc III, V and VI, which utilize sialylglycolipids as substrates. In vitro enzyme analyses revealed that ST6GalNAc III and VI generated DSGG from MSGG with Vmax/Km values of 1.91 and 4.16 respectively. Transfection of the cDNA expression vectors for these enzymes resulted in DSGG expression in a renal cancer cell line. Although both ST6GalNAc III and VI genes were expressed in normal kidney cells, the expression profiles of ST6GalNAc VI among 20 renal cancer cell lines correlated clearly with those of DSGG, suggesting that the sialyltransferase involved in the synthesis of DSGG in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and DSGG were found in proximal tubule epithelial cells in normal kidney tissues, while they were downregulated in renal cancer cell lines and cancer tissues. All these findings indicated that DSGG was suppressed during the malignant transformation of the proximal tubules as a maturation arrest of glycosylation. PMID:17123352

  1. 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

  2. Photo diagnosis of early pre cancer (LSIL) in genital tissue

    NASA Astrophysics Data System (ADS)

    Vaitkuviene, A.; Andersen-Engels, S.; Auksorius, E.; Bendsoe, N.; Gavriushin, V.; Gustafsson, U.; Oyama, J.; Palsson, S.; Soto Thompson, M.; Stenram, U.; Svanberg, K.; Viliunas, V.; De Weert, M. J.

    2005-11-01

    Permanent infections recognized as oncogenic factor. STD is common concomitant diseases in early precancerous genital tract lesions. Simple optical detection of early regressive pre cancer in cervix is the aim of this study. Hereditary immunosupression most likely is risk factor for cervical cancer development. Light induced fluorescence point monitoring fitted to live cervical tissue diagnostics in 42 patients. Human papilloma virus DNR in cervix tested by means of Hybrid Capture II method. Ultraviolet (337 nm) laser excited fluorescence spectra in the live cervical tissue analyzed by Principal Component (PrC) regression method and spectra decomposition method. PCr method best discriminated pathology group "CIN I and inflammation"(AUC=75%) related to fluorescence emission in short wave region. Spectra decomposition method suggested a few possible fluorophores in a long wave region. Ultraviolet (398 nm) light excitation of live cervix proved sharp selective spectra intensity enhancement in region above 600nm for High-grade cervical lesion. Conclusion: PC analysis of UV (337 nm) light excitation fluorescence spectra gives opportunity to obtain local immunity and Low-grade cervical lesion related information. Addition of shorter and longer wavelengths is promising for multi wave LIF point monitoring method progress in cervical pre-cancer diagnostics and utility for cancer prevention especially in developing countries.

  3. Detection and Localization of Pre-Cancerous Lesions and Early Lung Cancer Using Tissue Autofluorescence.

    NASA Astrophysics Data System (ADS)

    Hung, Jaclyn Yip-Chan

    In this work, two different yet related hypotheses were tested by experimental means as follows: (i) pre-cancerous and non-invasive (early) lung cancer can be detected and localized using the fluorescence properties of tumour localizing drugs at non-photosensitizing doses to skin tissue; (ii) significant differences exist in laser-induced autofluorescence between normal, pre-cancerous and cancerous tissues such that these differences alone can be exploited to detect and delineate early lung cancer without using exogenous drug(s). Exogenous fluorescent tumour markers such as hematoporphyrin derivatives (e.g. Photofrin) have been used to enhance to detection of occult lung lesions. Photofrin is preferentially retained in tumor tissues compared to the surrounding normal tissues; it fluoresces at 630 nm and 690 nm when excited at -405 nm. Based on this principle several imaging and non-imaging devices have been developed. However, wider clinical applications were limited due to the skin photosensitivity property of Photofrin. We have postulated that this could be solved by employing a much lower dose of Photofrin (0.25 mg/kg) which was believed to be less photosensitizing to human patients. This postulate was experimentally tested by ratio fluorometry and early lung cancers were detected with no false negative results and no apparent skin photosensitivity. An important finding in this study was that the mechanism for detection of early cancer was mainly due to the differences in the green autofluorescence between normal and malignant tissues, rather than fluorescence of tumour localizing drug. This discovery led to the second postulate of this thesis that tissue autofluorescence alone can be exploited for the detection of early lung cancer. The results indicated that algorithm(s) could be developed to clearly delineate early lesions from the normal tissues. Several algorithms were then tested using a non-imaging ratio fluorometer device and a prototype imaging

  4. 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.

  5. 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

    2016-02-01

    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. PMID:26669699

  6. Antibody levels against BK virus and prostate, kidney and bladder cancers in the EPIC-Oxford cohort

    PubMed Central

    Newton, R; Ribeiro, T; Casabonne, D; Alvarez, E; Touzé, A; Key, T; Coursaget, P

    2005-01-01

    In a case–control study nested within the EPIC-Oxford cohort, there were no statistically significant differences in the prevalence or titre of antibodies against BK virus measured in plasma taken prior to diagnosis between cases with cancer of the prostate (n=31), kidney (n=5) or bladder (n=9) and controls (n=45). PMID:16304559

  7. 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

  8. [Revision of therapeutic index for targeted treatment in kidney cancer: What if toxicity could predict efficacy?].

    PubMed

    Grellety, Thomas; Brugères-Chakiba, Camille; Chaminade, Axel; Roubaud, Guilhem; Ravaud, Alain; Gross-Goupil, Marine

    2014-06-01

    Since 2006, new treatments as targeted therapies (anti angiogenic and mTOR inhibitors) are prescribed in renal cell cancer. Toxicity of these treatments is well known by clinicians. Occurrence of these side effects has been associated with anti tumoral efficacy. High blood pressure, hypothyroïdie and hand foot syndrome were reported to be predictive of anti tumoral response. Fatigue and hyponatremia are still largely discussed. Moreover, non infectious pneumonia, which frequently occurs with mTOR inhibitors, is associated with clinical benefit. The main objective of treatment of advanced kidney cancer, specially renal cell cancer, is obtaining clinical benefit (stabilization and response) with a chronic evolution of the disease. This prolong exposure to drugs, according to their toxicity profile, often contributes to dose reduction, moreover interruption of treatment, potentially associated with a loss of control of disease. Thus, the adverse effects, described hereby, may be considered as « positive events », predicting efficacy, and thus looked for… Moreover, the sequential approach, with new drugs, emphasizes the need of defining the optimal sequence. Thus, because of the lack of molecular biomarkers to date, this predictives secondary effects may help for selecting the therapeutic strategy. PMID:24977449

  9. 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

  10. 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