What You Need to Know about Kidney Cancer

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... Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer ... Publications Reports What You Need To Know About™ Kidney Cancer This booklet is about cancer that starts in ...

Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

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Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

2017-08-08

Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

RLIP76 Targeted Therapy for Kidney Cancer.

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

2015-10-01

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

Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...SUBTITLE Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER...immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or enhance the abscopal in a kidney cancer

Renal cancer in recipients of kidney transplant

Directory of Open Access Journals (Sweden)

Prajwal Dhakal

2017-03-01

Full Text Available The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE ® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48 recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66; 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17- 73; 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days. Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

Drugs Approved for Kidney (Renal Cell) Cancer

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... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

Kidney Cancer Risk Questionnaire

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... NCI Cancer Information A to Z Treatment Roles Cancer Types Bladder Brain/Spine Breast Cervical Colorectal Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic ...

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

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Habib, Samy L; Liang, Sitai

2014-05-15

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

Urinary acylcarnitines are altered in human kidney cancer.

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

2012-06-15

Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

Urology and nephrology update: bladder and kidney cancer.

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Fiore, David C; Fox, Cara-Louise

2014-01-01

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

Renal cancer in kidney transplanted patients.

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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.

The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

NARCIS (Netherlands)

Huls, M.; Brown, C.D.; Windass, A.S.; Sayer, R.; Heuvel, J.J.M.W. van den; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R.

2008-01-01

The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney,

Kidney cancer in Lebanon: a specific histological distribution?

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Khafaja, Sarah; Kourie, Hampig Raphael; Matar, Dany; Sader-Ghorra, Claude; Kattan, Joseph

2015-01-01

Kidney cancer is the third most frequent urologic cancer in Lebanon after prostate and bladder cancer, accounting for 1.5% of all diagnosed cancers. In this paper, we report the histologic characteristics and distribution of kidney cancer, never described in Lebanon or the Middle East. Pathology results of operated kidney cancer were collected during a two year period (2010-2011) from two different Lebanese hospitals (Hotel-Dieu de France University Hospital and Saint Joseph Hospital). A total of 124 reports were reviewed and analyzed according to WHO classification of 2009. The 124 patients diagnosed with kidney cancer had a median age of 62.4 [18-86], 75% being men and 25% women. Some 71 % of the lesions were renal cell carcinoma (RCC), 25.8% had a urothelial histology, 1.6% were lymphomas and 1.6% were metastases to the kidney. Patients having RCC had a median age of 60.3 [18-85], 77.3% were men and 22.7% women. Of the RCCs, 59.1% were clear cell carcinoma, 22.7% papillary, 11.4% chromophobic, 3.4% rom the collecting ducts of Bellini and 3.4% were not otherwise classified. Histological distribution of Lebanese kidney cancer seems unusual when compared to the literature. The percentage of urothelial renal pelvis tumors is strikingly high. Moreover, clear cell carcinoma accounts for only 59.1% of RCCS in contrast to the 75% described elsewhere, while papillary carcinoma represents more than 22.7% compared to 10%.

PET/CT in kidney and bladder cancer

International Nuclear Information System (INIS)

Bochev, P.; Klisarova, A.

2013-01-01

Full text: FDG PET/CT has traditionally been considered a method of limited use in tumors of the kidneys and excretory system. Major shortcoming of the method in kidney cancer is considered variable fixation and a more general lack of significant therapeutic alternatives that require early diagnosis of recurrence after nephrectomy. In the context of the modern methods of systemic anticancer therapy in kidney cancer, marking a significant success in terms of time to progression, the need of more detailed selection of the patients and the search methods for the early diagnosis and assessment of therapeutic response arises. While CT remains the primary method for the diagnosis of parenchymal metastases (lung, liver), the use of FDG PET/CT has a significant advantage in detecting of nodal metastasis, locoregional recurrence and bone metastasis. Interesting direction in the use of PET/CT remains the monitoring of therapeutic response to systemic therapy of metastatic kidney cancer. Unlike kidney cancer in transitional cell carcinoma of bladder (TCC), the application of FDG PET/CT is non- systematic and based on the specific clinical indications. As the main indicator can be observed the distant staging in locally advanced tumors and recurrences in restading after cystectomy. Besides the general advantages of PET/CT in terms of nodal and peritoneal involvement it should be noted that the role of the PET/CT in TCC is discussible. Application of FDG PET / CT in kidney cancer and TCC at this stage can not be considered as established, but while in TCCs, the method has sporadically application, mostly for specific clinical questions, the application in kidney cancer is significantly more systemic and in the context of systemic anti-tumor therapy allows early diagnosis and therapeutic approach modulation

End Stage and Chronic Kidney Disease: Associations with Renal Cancer

International Nuclear Information System (INIS)

Russo, Paul

2012-01-01

There is a well known association between end stage renal disease and the development of kidney cancer in the native kidney of patients requiring renal replacement therapy. There is now emerging evidence that lesser degrees of renal insufficiency (chronic kidney disease, CKD) are also associated with an increased likelihood of cancer in general and kidney cancer in particular. Nephropathological changes are commonly observed in the non-tumor bearing portions of kidney resected at the time of partial and radical nephrectomy (RN). In addition, patients with renal cancer are more likely to have CKD at the time of diagnosis and treatment than the general population. The exact mechanism by which renal insufficiency transforms normal kidney cells into tumor cells is not known. Possible mechanisms include uremic immune inhibition or increased exposure to circulating toxins not adequately cleared by the kidneys. Surgeons managing kidney tumors must have an increased awareness of their patient’s renal functional status as they plan their resection. Kidney sparing approaches, including partial nephrectomy (PN) or active surveillance in older and morbidly ill patients, can prevent CKD or delay the further decline in renal function which is well documented with RN. Despite emerging evidence that PN provides equivalent local tumor control to RN while at the same time preventing CKD, this operation remains under utilized in the United States and abroad. Increased awareness of the bi directional relationship between kidney function and kidney cancer is essential in the contemporary management of kidney cancer.

Risk of a Second Kidney Carcinoma Following Childhood Cancer: Role of Chemotherapy and Radiation Dose to Kidneys.

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de Vathaire, Florent; Scwhartz, Boris; El-Fayech, Chiraz; Allodji, Rodrigue Sètchéou; Escudier, Bernard; Hawkins, Mike; Diallo, Ibrahima; Haddy, Nadia

2015-11-01

Kidney carcinoma is a rare second malignancy following childhood cancer. We sought to quantify risk and assess risk factors for kidney carcinoma following treatment for childhood cancer. We evaluated a cohort of 4,350 patients who were 5-year cancer survivors and had been treated for cancer as children in France and the United Kingdom. Patients were treated between 1943 and 1985, and were followed for an average of 27 years. Radiation dose to the kidneys during treatment was estimated with dedicated software, regardless of the site of childhood cancer. Kidney carcinoma developed in 13 patients. The cumulative incidence of kidney carcinoma was 0.62% (95% CI 0.27%-1.45%) at 40 years after diagnosis, which was 13.3-fold higher (95% CI 7.1-22.3) than in the general population. The absolute excess risk strongly increased with longer duration of followup (p kidney carcinoma was 5.7-fold higher (95% CI 1.4-14.7) if radiotherapy was not performed or less than 1 Gy had been absorbed by the kidney but 66.3-fold higher (95% CI 23.8-142.5) if the radiation dose to the kidneys was 10 to 19 Gy and 14.5-fold higher (95% CI 0.8-63.9) for larger radiation doses to the kidney. Treatment with chemotherapy increased the risk of kidney carcinoma (RR 5.1, 95% CI 1.1-22.7) but we were unable to identify a specific drug or drug category responsible for this effect. Moderate radiation dose to the kidneys during childhood cancer treatment increases the risk of a second kidney carcinoma. This incidence will be further increased when childhood cancer survivors reach old age. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

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Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth

2016-05-01

To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data

End Stage and Chronic Kidney Disease:Associations with Renal Cancer

Directory of Open Access Journals (Sweden)

Paul eRusso

2012-04-01

Full Text Available There is a well known association between end stage renal disease and the development of kidney cancer in the native kidney of patients requiring renal replacement therapy. There is now emerging evidence that lesser degrees of renal insufficiency (chronic kidney disease, CKD are also associated with an increased likelihood of cancer in general and kidney cancer in particular. Nephro pathological changes are commonly observed in the non tumor bearing portions of kidney resected at the time of partial and radical nephrectomy. In addition, patients with renal cancer are more likely to have CKD at the time of diagnosis and treatment than the general population. The exact mechanism by which renal insufficiency transforms normal kidney cells into tumor cells is not known. Possible mechanisms include uremic immune inhibition or increased exposure to circulating toxins not adequately cleared by the kidneys. Surgeons managing kidney tumors must have an increased awareness of their patient’s renal functional status as they plan their resection. Kidney sparing approaches, including partial nephrectomy or active surveillance in older and morbidly ill patients, can prevent CKD or delay the further decline in renal function which is well documented with radical nephrectomy. Despite emerging evidence that partial nephrectomy provides equivalent local tumor control to radical nephrectomy while at the same time preventing CKD, this operation remains under utilized in the United States and abroad. Increased awareness of the bi directional relationship between kidney function and kidney cancer is essential in the contemporary management of kidney cancer.

Trace elemental analysis of carcinoma kidney and stomach by PIXE method

International Nuclear Information System (INIS)

Reddy, S. Bhuloka; John Charles, M.; Naga Raju, G.J.; Vijayan, V.; Seetharami Reddy, B.; Ravi Kumar, M.; Sundareswar, B.

2003-01-01

Trace elemental analysis was carried out in the biological samples of carcinoma kidney and stomach using particle induced X-ray emission technique. A 2 MeV proton beam was employed to excite the samples. From the present results, the levels of elements K, Ca, Fe, Ni and Se are lower and those of the elements Ti, Co, Zn, As and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. In the case of stomach, the concentrations of elements Cl, K, Ca, Ti, Mn, Fe, Co, Cu and Zn are lower while concentrations of elements Cr, Ni, As and Br are higher in the cancer tissue of stomach than those observed in the normal tissue. The observed deficiency or excess of certain elements is correlated to carcinogenesis of that organ. The present results of carcinoma stomach support the previous observations that nickel and chromium are carcinogenic agents. The low levels of selenium observed in the carcinoma tissue of kidney and the low levels of manganese observed in the carcinoma tissue of stomach support the view that selenium and manganese inhibit the growth of cancer in kidney and stomach respectively. The observed high levels of zinc in the cancer tissue of kidney suggest that zinc is involved in the tumor growth and development of neoplastic transformation in kidney while the observed low levels of zinc in the carcinoma tissue of stomach suggest that zinc inhibits the growth of cancer in this organ. For correctly assessing the role played by the trace elements in initiating, promoting or inhibiting cancer in various organs, there is a need for acquisition of more data by trace elemental analysis from several investigations of this type undertaken in different regions

Radiotherapy for bladder cancer and kidney cancer

International Nuclear Information System (INIS)

Ishikawa, Hitoshi; Tanaka, Keiichi; Iizumi, Takashi; Shimizu, Shosei; Okumura, Toshiyuki; Sakurai, Hideyuki; Kimura, Tomokazu; Nishiyama, Hiroyuki

2017-01-01

This paper explained the current state of radiotherapy for bladder cancer and kidney cancer, and discussed the role of radiotherapy in curative treatment and the future development. In the diagnosis and treatment of bladder cancer, it is important to judge the existence of pathological muscular layer invasion based on transurethral resection of bladder tumor (TUR-BT). In surgical results in Japan, the U.S., and Switzerland, 5-year survival rate is about 60 to 70%. Standard treatment for bladder cancer with muscle layer invasion had been surgery, and radiotherapy had been applied to the cases without resistance to surgery. Three combined therapy with TUR-BT and simultaneous chemoradiotherapy is the current standard bladder conserving therapy. The 5-year survival rate is approximately 60%, which is superior to the treatment with irradiation alone. Radiotherapy for kidney cancer is most often used as perioperative treatment for locally advanced cancer or as symptomatic treatment for metastatic lesions. However, due to recent improvement in radiotherapy technology, correspondence to respiratory movement and high dose administration associated with improvement in dose concentration have been realized, and stereotactic irradiation using a high single dose for inoperable disease cases or surgery refusal disease cases has come to be clinically applied. (A.O.)

Cancer risk and mortality after kidney transplantation

DEFF Research Database (Denmark)

Engberg, Henriette; Wehberg, Sonja; Bistrup, Claus

2016-01-01

BACKGROUND: Kidney recipients receive immunosuppression to prevent graft rejection, and long-term outcomes such as post-transplant cancer and mortality may vary according to the different protocols of immunosuppression. METHODS: A national register-based historical cohort study was conducted......, the Danish National Cancer Registry and the Danish National Patient Register were used. A historical cohort of 1450 kidney recipients transplanted in 1995-2005 was followed up with respect to post-transplant cancer and death until 31 December 2011. RESULTS: Compared with Center 1 the adjusted post...

Blood pressure and kidney cancer risk: meta-analysis of prospective studies.

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Hidayat, Khemayanto; Du, Xuan; Zou, Sheng-Yi; Shi, Bi-Min

2017-07-01

Globally, kidney cancer is the twelfth most common cancer, accounting for 337 860 cases recorded in 2012. By 2020, this number has been estimated to reach 412 929 or increase by 22%. Over the past few decades, a number of prospective studies have investigated the association between blood pressure (BP) and risk of kidney cancer, using either recorded BP levels or reported hypertension as the principal exposure variable. However, the relation of BP to kidney cancer remains incompletely understood, and the data on sex-specific differences in risk estimates have been inconsistent. PubMed and Web of Science databases were searched for studies assessing the association between BP and kidney cancer through July 2016. The summary relative risk with 95% confidence intervals was calculated using a random-effects model. A total of 18 prospective studies with 8097 kidney cancer cases from 3 628 479 participants were included in our meta-analysis. History of hypertension was associated with 67% increased risk of kidney cancer. Significant heterogeneity and evidence of publication bias were observed. However, the results remain unchanged after introducing the trim and fill method to correct the publication bias. Accordingly, each 10-mmHg increase in SBP and DBP was associated with 10 and 22% increased risk of kidney cancer. Collectively, the present meta-analysis of 18 prospective studies provides further support for a positive association between hypertension and kidney cancer risk.

Acute kidney injury in the cancer patient.

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

2014-01-01

Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

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

Science.gov (United States)

Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

2017-04-01

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

Cabozantinib and lenvatinib for kidney cancer

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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.

Application of Hanging Drop Technique for Kidney Tissue Culture.

Science.gov (United States)

Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

2017-01-01

The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

Application of Hanging Drop Technique for Kidney Tissue Culture

Directory of Open Access Journals (Sweden)

Shaohui Wang

2017-05-01

Full Text Available Background/Aims: The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. Methods: In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. Results: The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. Conclusions: We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli.

Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer: Targeting the Warburg Effect in Cancer

Science.gov (United States)

Linehan, W. Marston; Rouault, Tracey A.

2015-01-01

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 cycle (TCA) 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 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 HIF1α, and increased expression of genes such as vascular endothelial growth factor (VEGF) and 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, LDH-A, the anti-oxidant 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 metabolic basis of a rare cancer such as fumarate hydratase

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

Science.gov (United States)

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

2015-09-01

Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20-0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

OpenAIRE

Linehan, W. Marston

2012-01-01

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF...

Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT-PCR, and logistic regression model to identify cancer cell biomarkers.

Directory of Open Access Journals (Sweden)

Halliday A Idikio

Full Text Available Cancer biomarkers are sought to support cancer diagnosis, predict cancer patient response to treatment and survival. Identifying reliable biomarkers for predicting cancer treatment response needs understanding of all aspects of cancer cell death and survival. Galectin-3 and Beclin1 are involved in two coordinated pathways of programmed cell death, apoptosis and autophagy and are linked to necroptosis/necrosis. The aim of the study was to quantify galectin-3 and Beclin1 mRNA in human cancer tissue cDNA panels and determine their utility as biomarkers of cancer cell survival.A panel of 96 cDNAs from eight (8 different normal and cancer tissue types were used for quantitative real-time polymerase chain reaction (qRT-PCR using ABI7900HT. Miner2.0, a web-based 4- and 3-parameter logistic regression software was used to derive individual well polymerase chain reaction efficiencies (E and cycle threshold (Ct values. Miner software derived formula was used to calculate mRNA levels and then fold changes. The ratios of cancer to normal tissue levels of galectin-3 and Beclin1 were calculated (using the mean for each tissue type. Relative mRNA expressions for galectin-3 were higher than for Beclin1 in all tissue (normal and cancer types. In cancer tissues, breast, kidney, thyroid and prostate had the highest galectin-3 mRNA levels compared to normal tissues. High levels of Beclin1 mRNA levels were in liver and prostate cancers when compared to normal tissues. Breast, kidney and thyroid cancers had high galectin-3 levels and low Beclin1 levels.Galectin-3 expression patterns in normal and cancer tissues support its reported roles in human cancer. Beclin1 expression pattern supports its roles in cancer cell survival and in treatment response. qRT-PCR analysis method used may enable high throughput studies to generate molecular biomarker sets for diagnosis and predicting cancer treatment response.

Multiple high-intensity focused ultrasound probes for kidney-tissue ablation.

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Häcker, Axel; Chauhan, Sunita; Peters, Kristina; Hildenbrand, Ralf; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2005-10-01

To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.

Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

Science.gov (United States)

Linehan, W. Marston

2012-01-01

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. PMID:23038766

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

International Nuclear Information System (INIS)

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

2014-01-01

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. (orig.)

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

Energy Technology Data Exchange (ETDEWEB)

Drubay, Damien; Ancelet, Sophie; Laurier, Dominique; Rage, Estelle [Institut de Radioprotection et de Surete Nucleaire (IRSN), Laboratory of Epidemiology, Fontenay-aux-Roses cedex (France); Acker, Alain [AREVA NC, Paris (France); Kreuzer, Michaela [Federal Office for Radiation Protection and Health, Department of Radiation Protection and Health, Neuherberg (Germany)

2014-08-15

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. (orig.)

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

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Izzedine, Hassan; Perazella, Mark A

2015-12-01

A bidirectional relationship has been observed for kidney disease and cancer. On the one hand, cancer is an important complication noted in kidney disease as well as a major cause of morbidity and mortality in this group. On the other hand, improved cancer treatment has prolonged survival, but also increased the development of acute and chronic kidney disease. The combination of cancer and kidney disease makes it challenging for clinicians to provide comprehensive and safe therapies for this group of patients. As such, clinicians caring for this group must develop expertise and become competent in the practice of a newly evolving subspecialty of nephrology known as 'onco-nephrology'. This brief narrative review will focus on the cancer risk in patients with underlying kidney disease, the therapies such as erythropoiesis-stimulating agents on cancer progression and other outcomes, and the appropriate dosing of anti-cancer agents in patients with underlying kidney disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Racial/Ethnic Differences in Cancer Risk After Kidney Transplantation

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Hall, EC; Segev, DL; Engels, EA

2014-01-01

Transplant recipients have elevated cancer risk, but it is unknown if cancer risk differs across race and ethnicity as in the general population. U.S. 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, pkidney (aIRR 2.09, pcancer (aIRR 2.14, pcancer (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

Sirolimus use and cancer incidence among US kidney transplant recipients.

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

2015-01-01

Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

Science.gov (United States)

Hasumi, Hisashi; Yao, Masahiro

2018-03-01

Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Medication use and kidney cancer risk: A population-based study.

Science.gov (United States)

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

2017-09-01

Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesised to modulate cancer risk was obtained using prescription claims data. We modelled exposure in four different fashions: (1) as continuous exposures using (a) fractional polynomials (which allow for a non-linear relationship between an exposure and outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures denoting (a) ≥3 years versus kidney cancer. The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis. When utilising fractional polynomials, increasing cumulative exposure to acetylsalicylic acid, selective serotonin reuptake inhibitors, and proton-pump inhibitors was associated with significantly reduced risk of kidney cancer, while increasing exposure to antihypertensive drugs was associated with significantly increased risk. Our study provides impetus to further explore the effect of commonly prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Recent Overview of Kidney Cancer Diagnostics and Treatment].

Science.gov (United States)

Marenčák, J; Ondrušová, M; Ondruš, D

The incidence of kidney cancer has increased in the majority of countries worldwide, and this disease has relatively high lethality. For many years, the Slovak Republic has been among the countries with the highest kidney cancer incidence, in particular in 2012 (according to global estimated values) in both genders, although mainly in females. In the last few years, the Czech Republic has had the highest incidence of kidney cancer worldwide. The use of imaging techniques such as ultrasound and computerized tomography has increased the detection of asymptomatic renal cell cancer. Etiological factors include lifestyle factors such as smoking, obesity, and hypertension. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged by pharmacotherapy with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain or osseal metastases that are painful or increase the risk of fracture. Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.Key words: kidney cancer - epidemiology - risk factors - pathology - diagnosis - therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 2. 12. 2016Accepted: 3. 1. 2017.

Heavy metals burden in Kidney and heart tissues of Scarus ...

African Journals Online (AJOL)

Levels of selected heavy metals (Pb, Co, Cu, Ni, Zn, Mn and Cd) in the heart and kidney tissues of parrot fish, collected from the Arabian Gulf, Eastern Province of Saudi Arabia, were determined by wet-digestion based atomic absorption method. The results showed that accumulation pattern of analyzed metals in the kidney ...

Researching the experience of kidney cancer patients.

Science.gov (United States)

Taylor, K

2002-09-01

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

Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

International Nuclear Information System (INIS)

Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2014-01-01

Introduction: The kidneys are one of the main dose limiting organs in 177 Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from 177 Lu-octreotate exposure. Methods: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq 177 Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. Results: Distinct transcriptional responses were observed following 177 Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. Conclusion: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues

Immunotherapy Combination Approved for Advanced Kidney Cancer

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FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

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

Science.gov (United States)

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

2016-05-01

Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention. Copyright © 2016 by the American Society of Nephrology.

Risk for cancer in living kidney donors and recipients.

Science.gov (United States)

Wang, Min; Zhang, Huai; Zhou, Dan; Qiao, Yong-Chao; Pan, Yan-Hong; Wang, Yan-Chao; Zhao, Hai-Lu

2018-03-01

Malignancy following renal transplantation remains inconsistent with the reported safety of kidney donation during the long-term follow-up. We conducted searches of the published literature which included healthy participants, recipients, living kidney donors (LKDs), and the availability of outcome data for malignancy. Eight from 938 potentially relevant studies were analyzed by means of fixed-effects model or random-effects model, as appropriately. In 48,950 participants, the follow-up range was 18 months to 20 years, and the mean age of the subjects was approximately 41 years. The incidence rate with 95% confidence interval (CI) for malignancy after kidney transplantation was 0.03 (0.01-0.05) in recipients and 0.03 (0.1-0.07) in LKDs, giving a pooled incidence rate of 0.03 (95% CI 0.02-0.04). LKDs contrasted nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69-2.92). Kidney transplantation was associated with an increased risk of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and kidney recipients should be monitored.

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

Science.gov (United States)

Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

Science.gov (United States)

Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

2013-10-01

Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

Breast cancer metastatic to the kidney with renal vein involvement.

Science.gov (United States)

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

2015-02-01

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

Long noncoding RNA in prostate, bladder, and kidney cancer.

Science.gov (United States)

Martens-Uzunova, Elena S; Böttcher, René; Croce, Carlo M; Jenster, Guido; Visakorpi, Tapio; Calin, George A

2014-06-01

Genomic regions without protein-coding potential give rise to millions of protein-noncoding RNA transcripts (noncoding RNA) that participate in virtually all cellular processes. Research over the last 10 yr has accumulated evidence that long noncoding RNAs (lncRNAs) are often altered in human urologic cancers. To review current progress in the biology and implication of lncRNAs associated with prostate, bladder, and kidney cancer. The PubMed database was searched for articles in the English language with combinations of the Medical Subject Headings terms long non coding RNA, long noncoding RNA, long untranslated RNA, cancer, neoplasms, prostate, bladder, and kidney. We summarise existing knowledge on the systematics, biology, and function of lncRNAs, particularly these involved in prostate, kidney, and bladder cancer. We also discuss the possible utilisation of lncRNAs as novel biomarkers and potential therapeutic targets in urologic malignancies and portray the major challenges and future perspectives of ongoing lncRNA research. LncRNAs are important regulators of gene expression interacting with the major pathways of cell growth, proliferation, differentiation, and survival. Alterations in the function of lncRNAs promote tumour formation, progression, and metastasis of prostate, bladder, and kidney cancer. LncRNAs can be used as noninvasive tumour markers in urologic malignancies. Increased knowledge of the molecular mechanisms by which lncRNAs perform their function in the normal and malignant cell will lead to a better understanding of tumour biology and could provide novel therapeutic targets for the treatment of urologic cancers. In this paper we reviewed current knowledge of long noncoding RNAs (lncRNAs) for the detection and treatment of urologic cancers. We conclude that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer. LncRNAs hold promise as future therapeutic targets, but more research is needed to gain a better

Association Between Kidney Cancer and Occupational Exposure to Trichloroethylene.

Science.gov (United States)

Buhagen, Morten; Grønskag, Anna; Ragde, Siri Fenstad; Hilt, Bjørn

2016-09-01

This study investigates the association between occupational exposure to trichloroethylene (TCE) and kidney cancer, as this correlation has been questioned. The incidence of cancers was studied in a dynamic cohort of 997 male workers who for many years had been occupationally exposed to TCE. During a 50-year observation period, 13 cases of kidney cancer were observed (7.5 expected) with a standardized incidence ratio of 1.7 and a 95% confidence interval of 1.0 to 3.0. Four other cases, not included in the SIR analysis, were also observed. Long-term TCE exposure was positively confirmed for 14 of the 17 incident cases. There is reason to assume that the remaining cases also had been exposed to TCE. The present study supports the view that TCE is a kidney carcinogen.

Managing cancer risk and decision making after kidney transplantation.

Science.gov (United States)

Webster, A C; Wong, G; Craig, J C; Chapman, J R

2008-11-01

Kidney transplant recipients are at higher risk of cancer at most sites, and cancer after transplantation causes considerable morbidity and mortality. To optimize long-term patient outcomes, clinicians balance the prospect of graft failure and dialysis, with competing risks of diabetes, cardiovascular and cerebrovascular disease and the risk of malignancy. In this paper we critically examine the assumptions underpinning primary prevention, immunization, chemoprevention and screening programs, and highlight considerations when applying evidence to the kidney transplant population, and suggest a clinical research agenda that aims to define a rational approach to managing posttransplant cancer risk.

Application of infrared spectroscopy for diagnosis of kidney tumor tissue

OpenAIRE

Bandzevičiūtė, Rimantė

2016-01-01

Application of Infrared Spectroscopy for Diagnosis of Kidney Tumor Tissue It is possible to apply the technique of an attenuated total reflection of infrared radiation (ATR IR) for the characterisation of the removed tissues during the surgery. Application of this method for interstitium of the removed tissue does not require any specific sample preparation. For this reason ATR IR technique applied for the interstitium allows to get information about tissues immediately after surgical operati...

Usefulness of CT in diagnosing and staging of kidney cancer

International Nuclear Information System (INIS)

Batycka-Ugorska, I.

1993-01-01

Article presents 170 patients with suspected kidney cancer and applicability of CT in the diagnosis. According to author CT imaging is better than others (ultrasonography, urography) in assessment of the tumor development and detection of metastases to lymphatic nodes of abdomen and other organs. The method is compared with angiography in diagnosis of metastases of kidney cancer to veins

Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

Science.gov (United States)

Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian

2017-05-01

The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

Potential role of genetic markers in the management of kidney cancer

NARCIS (Netherlands)

Junker, K.; Ficarra, V.; Kwon, E.D.; Leibovich, B.C.; Thompson, R.H.; Oosterwijk, E.

2013-01-01

CONTEXT: Kidney cancer is not a single entity but comprises a number of different types of cancer that occur in the kidney including renal cell tumours as the most common type. Four major renal cell tumour subtypes can be distinguished based on morphologic and genetic characteristics. To

Trends in kidney cancer among the elderly in Denmark, 1980-2012

DEFF Research Database (Denmark)

Azawi, Nessn H; Joergensen, Simon Moeller; Jensen, Niels Viggo

2016-01-01

Background The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Material and methods Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database...... of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than......-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in1980 to 4713 in 2012. Conclusion A challenge in managing...

Unexpected relevance of the hallmarks of cancer to the pathogenesis of polycystic kidney disease

Science.gov (United States)

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

2018-01-01

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 extrarenal 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 an 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

Concentration of uranium in human cancerous tissues of Southern Iraqi patients using fission track analysis

International Nuclear Information System (INIS)

Al-Hamzawi, A.A.; Al-Qadisiyah University, Qadisiyah; Jaafar, M.S.; Tawfiq, N.F.

2015-01-01

The technique of nuclear fission track analysis with solid state nuclear track detectors CR-39 has been applied to determine concentrations of uranium in cancerous samples of human tissues that excised from patients in the three key southern Iraqi governorates namely, Basrah, Dhi-Qar, and Muthanna. These provinces were the sites of intensive military events during the Gulf Wars in 1991 and 2003. The investigation was based on the study of 24 abnormal samples and 12 normal samples for comparing the results. These samples include four types of soft tissues (kidney, breast, stomach and uterus). The results show that uranium concentrations in the normal tissues ranged between (1.42-4.76 μg kg -1 ), whereas in the cancerous tissues ranged between (3.37-7.22 μg kg -1 ). The uranium concentrations in the normal tissues were significantly lower than in the abnormal tissues (P < 0.001). (author)

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

Science.gov (United States)

Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

2017-11-15

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

Polycystic kidney disease and cancer after renal transplantation.

Science.gov (United States)

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

2014-10-01

Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia. However, it is not known whether renal transplant recipients with PKD have an increased risk of cancer. Data from the Scientific Registry of Transplant Recipients, which contains information on all solid organ transplant recipients in the United States, were linked to 15 population-based cancer registries in the United States. For PKD recipients, we compared overall cancer risk with that in the general population. We also compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poisson regression, and we determined incidence rate ratios (IRRs) adjusted for age, sex, race/ethnicity, dialysis duration, and time since transplantation. The study included 10,166 kidney recipients with PKD and 107,339 without PKD. Cancer incidence in PKD recipients was 1233.6 per 100,000 person-years, 48% higher than expected in the general population (standardized incidence ratio, 1.48; 95% confidence interval [95% CI], 1.37 to 1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000 person-years. The unadjusted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01 to 1.20). However, PKD recipients were older (median age at transplantation, 51 years versus 45 years for non-PKD recipients), and after multivariable adjustment, cancer incidence was lower in PKD recipients than in others (IRR, 0.84; 95% CI, 0.77 to 0.91). The reason for the lower cancer risk in PKD recipients is not known but may relate to biologic characteristics of ADPKD or to cancer risk behaviors associated with ADPKD. Copyright © 2014 by the American Society of Nephrology.

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

Science.gov (United States)

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.

Radiological methods for diagnostics of kidney cancer

Directory of Open Access Journals (Sweden)

Popkov V.M.

2012-09-01

Full Text Available It is stated that kidney cancer takes one of the leading places in the cancer incidence. Particular attention should be paid to renal cell carcinoma. By means of modern methods of volume visualization it is possible to diagnose small renal tumors, to prognose the process of tumor development and to save organs by surgical intervention.

The incidence of kidney cancer in Iran: a systematic review and meta-analysis.

Science.gov (United States)

Hassanipour, Soheil; Namvar, Gholamreza; Fathalipour, Mohammad; Salehiniya, Hamid

2018-06-01

The incidence of kidney cancer from different areas of Iran was reported. Nevertheless, there is no available systematic reviews in this regard. Therefore, the present systematic review carried out to estimate the incidence rate of kidney cancer among Iranian people. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) in September 2017. A search was concluded using Medline/ PubMed, Scopus, ScienceDirect, and Google scholar for international papers and four national databases (Scientific Information Database, MagIran, IranMedex, and IranDoc) for Persian papers. The incidence rate of kidney cancer was calculated using random effect model. An aggregate of 159 papers were retrieved in the primary search of the databases. Further screening and advanced refinement of the retrieved studies produced 15 studies totally. The age-standardized rate (ASR) of kidney cancer was 1.94, 95% CI (1.62-2.55) and 1.36, 95 % CI (1.09-1.62) in males and females, respectively. In comparison to other parts of the world, the incidence of kidney cancer was lower in Iran. Afterwards, further studies are necessary to outline the exact incidence rate and the trend of kidney cancer in Iran. © Author(s) 2018. This article is published with open access by China Medical University.

Association Between Pretransplant Cancer and Survival in Kidney Transplant Recipients.

Science.gov (United States)

Dahle, Dag Olav; Grotmol, Tom; Leivestad, Torbjørn; Hartmann, Anders; Midtvedt, Karsten; Reisæter, Anna V; Mjøen, Geir; Pihlstrøm, Hege K; Næss, Hege; Holdaas, Hallvard

2017-10-01

Kidney transplantation in recipients with a previous malignancy is often deferred 2 to 5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year. We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression. From 1963 to 2010, 377 (6.4%) of 5867 recipients had a pretransplant cancer. During a median follow-up of 6.8 years, 256 recipients died, 35 (13.7%) from recurrent cancer and 27 (10.5%) from de novo cancer. Uncensored and death-censored graft loss occurred in 263 and 46 recipients, respectively. All-cause mortality was similar as in comparators (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.93-1.20]; P = 0.40), death-censored graft loss was lower (HR, 0.63; 95% CI, 0.47-0.84; P = 0.002), and uncensored graft loss was similar (HR, 0.99; 95% CI, 0.87-1.12; P = 0.87). Cancer mortality was higher than in comparators (HR, 1.97; 95% CI, 1.51-2.56; P cancer mortality or all-cause mortality (both P > 0.45). Results were similar within cancer subgroups, with most data in patients with a history of kidney cancer, prostate cancer, urothelial cancer, and skin squamous cell carcinoma. Kidney transplant recipients with a pretransplant cancer had a similar overall patient and graft survival as recipients without such cancer. Cancer mortality was increased, particularly during the first 5 years after transplantation. A short waiting period was not associated with mortality.

Immunotherapy using dendritic cells and cytokine-induced killer for kidney cancer

International Nuclear Information System (INIS)

Chen Lijun; Xu Yuanbin; Zhao Li; Qu Nan; Sun Zhenpeng; Li Xuechao; Zhao Jiyu; Wang Bin; Wang Huixian

2008-01-01

Objective: To investigate the clinical efficacy of immunotherapy using dendritic cells (DC) and cytokine-induced killer (CIK)in treatment of patients with kidney cancer. Methods: Sixty patients with kidney cancer were divided into 2 groups randomly: the control group and immunotherapy group. Peripheral blood mononuclear cells (PBMC) were seperated from the patients who received immunotherapy first, then DC and CIK were induced and cultured with GM-CSF and IL4 in vitro. The immunotherapy group received DC four times and CIK twice at an interval of 14 days after routine treatment. The control group received only chemotherapy. T lymphocyte subtypes and NK cells in peripheral blood, the white cells and the values of liver and kidney biochemistry of two group of patients were analyzed and clinical efficacy were ob- served, so were side effects. Results: Clinical efficacy showed significant statistical difference between the two groups (P + , CD4 + , CD4 + /CD8 + and NK cell in the immunotherapy group increased after treatment, which showed significant statistical difference compared with those before treatment(P value was 0.010, 0.026, 0.021, 0.016, respectively). Changes in cell immune indexes (CD3 + , CD4 + , CD4 + /CD8 + ) in immunotherapy group and Control group showed significant statistical difference (P value was 0.001,0.023,0.012, respectively). Conclusion: Immunotherapy using dendritic cells and cytokine-induced killer combined with routine treatment can improve T lymphocyte subtypes and NK cell ratio in peripheral blood of the patients with kidney cancer, and may play an important role in the treatment of kidney cancer. It can enhance clinical efficacy in patients with kidney cancer and can improve prognosis. (authors)

Nivolumab as the new standard of metastatic kidney cancer treatment

Directory of Open Access Journals (Sweden)

V. B. Matveev

2017-01-01

Full Text Available The last decade was marked by the rapid development of kidney cancer drug treatment and advent of targeted drugs aimed at inhibition of angiogenesis which plays a crucial role in tumor growth. Despite certain success, targeted antiangiogenetic therapy with tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR, and monoclonal antibodies against vascular endothelial growth factor (VEGF in most cases do not achieve long-term remission, are highly toxic, and never lead to full cure for the patients. Development of modern immunological approaches to application of inhibitors of the crucial immune response regulators opens up new possibilities in treatment of disseminated kidney cancer. In this review, results of the studies of nivolumab (PD-1 inhibitor, first checkpoint inhibitor registered for treatment of metastatic kidney cancer are presented.

Identification and characterization of angiogenesis targets through proteomic profiling of endothelial cells in human cancer tissues.

Directory of Open Access Journals (Sweden)

Mehdi Mesri

Full Text Available Genomic and proteomic analysis of normal and cancer tissues has yielded abundant molecular information for potential biomarker and therapeutic targets. Considering potential advantages in accessibility to pharmacological intervention, identification of targets resident on the vascular endothelium within tumors is particularly attractive. By employing mass spectrometry (MS as a tool to identify proteins that are over-expressed in tumor-associated endothelium relative to normal cells, we aimed to discover targets that could be utilized in tumor angiogenesis cancer therapy. We developed proteomic methods that allowed us to focus our studies on the discovery of cell surface/secreted proteins, as they represent key antibody therapeutic and biomarker opportunities. First, we isolated endothelial cells (ECs from human normal and kidney cancer tissues by FACS using CD146 as a marker. Additionally, dispersed human colon and lung cancer tissues and their corresponding normal tissues were cultured ex-vivo and their endothelial content were preferentially expanded, isolated and passaged. Cell surface proteins were then preferentially captured, digested with trypsin and subjected to MS-based proteomic analysis. Peptides were first quantified, and then the sequences of differentially expressed peptides were resolved by MS analysis. A total of 127 unique non-overlapped (157 total tumor endothelial cell over-expressed proteins identified from directly isolated kidney-associated ECs and those identified from ex-vivo cultured lung and colon tissues including known EC markers such as CD146, CD31, and VWF. The expression analyses of a panel of the identified targets were confirmed by immunohistochemistry (IHC including CD146, B7H3, Thy-1 and ATP1B3. To determine if the proteins identified mediate any functional role, we performed siRNA studies which led to previously unidentified functional dependency for B7H3 and ATP1B3.

HYPERTENSION AND OBESITY AND THE RISK OF KIDNEY CANCER IN TWO LARGE COHORTS OF US MEN AND WOMEN

Science.gov (United States)

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

2014-01-01

Kidney cancer incidence is increasing globally. Reasons for this rise are unclear, but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156,774 participants of the Women’s Health Initiative (WHI) clinical trials and observational studies over 10.8 years. In addition, we examined the impact of blood pressure (BP) on kidney cancer deaths over 25 years among the 353,340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the WHI, systolic SBP was categorized in 6 groups from 160 mmHg and body mass index (BMI) was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (p-value for trend kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer amongst the 353,340 participants aged 35–57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (HR=1.87 for SBP>160 versus kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk. PMID:24637660

Cabozantinib for Initial Treatment of Kidney Cancer

Science.gov (United States)

FDA has approved cabozantinib (Cabometyx®) as an initial treatment for patients with advanced renal cell carcinoma. The approval adds another tyrosine kinase inhibitor to the available options for patients with advanced kidney cancer.

Trends in kidney cancer among the elderly in Denmark, 1980-2012.

Science.gov (United States)

Azawi, Nessn H; Joergensen, Simon Moeller; Jensen, Niels Viggo; Clark, Peter E; Lund, Lars

2016-01-01

The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. The proportion of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than 70 years, the incidence rates started increasing around 2000. The incidence rates were lower in women but with a similar pattern as in men. Mortality rates remained stable over time in persons aged 70 years or more while they decreased with time in younger women. Both the one- and the five-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in 1980 to 4713 in 2012. A challenge in managing kidney cancer in the elderly is to establish interdisciplinary collaborations between different specialties, such as surgeons, clinical oncologists, and geriatricians to be able to deliver the best possible care in the future.

Modest improvement in 20 years of kidney cancer care in the Netherlands.

NARCIS (Netherlands)

Schans, S.A. van de; Aben, K.K.H.; Mulders, P.F.A.; Haanen, J.B.; Herpen, C.M. van; Verhoeven, R.H.A.; Karim-Kos, H.E.; Oosterwijk, E.; Kiemeney, L.A.L.M.

2012-01-01

AIM: For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. METHODS: All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N=32,545)

Kidney cancer progression linked to shifts in tumor metabolism

Science.gov (United States)

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.

Characterization and localization of 3H-arginine8-vasopressin binding to rat kidney and brain tissue

International Nuclear Information System (INIS)

Dorsa, D.M.; Majumdar, L.A.; Petracca, F.M.; Baskin, D.G.; Cornett, L.E.

1983-01-01

Anatomic, behavioral and pharmacologic evidence suggests that arginine8-vasopressin (AVP) serves as a CNS neurotransmitter or neuromodulator. AVP binding to membrane and tissue slice preparations from brain and kidney was characterized, and the anatomical distribution of these binding sites was examined. Conditions for the binding assay were optimized using kidney medullary tissue. Binding of 3 H-AVP (S.A. . 30-51 Ci/mmol, NEN) to brain and kidney membranes and tissue slices was saturable, temperature dependent, linearly related to protein concentration (or number of tissue slices), reversible, and specific since the ability of cold AVP to displace 3 H-AVP from binding was greater than oxytocin and other related peptide fragments. Autoradiographic localization of 3 H-AVP binding was restricted to kidney medullary tissue. In brain tissue, 3 H-AVP binding was found to occur in concentrated foci. Brainstem areas such as the nucleus tractus solitarius (NTS) showed a high density of AVP binding sites. Since local injections of AVP into the NTS have been shown to influence blood pressure, the present study presents the first anatomical evidence for the presence of AVP specific binding sites which might mediate this effect

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

Science.gov (United States)

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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

Tseng, Chin-Hsiao

2015-01-01

To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. 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 kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration 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, Pkidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.

Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Menno Pruijm

2013-01-01

Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Comparative Study of Experimentally Induced Cancer of the Kidney in Mice and Rats with X-Rays

Energy Technology Data Exchange (ETDEWEB)

Maldague, P. [Cancer Institute, University of Louvain (Belgium)

1969-11-15

Local irradiation of a kidney in rats and mice results in the development of radiation- induced cancers in the irradiated kidney. The production of these cancers is considerably greater in rats than in mice, and their frequency depends on: (1) The X-ray dose absorbed by the kidney; (2) The latency period which is longer for carcinomas than for sarcomas; and (3) The degree and extent of renal radiation- induced lesions. A study of the relationship between dose and carcinogenic effect has enabled us to define three types of X-ray dose: (a) An ineffective dose of 570 rads at which the inducement of cancer is zero; (b) An optimum dose of 1700 rads at which the frequency of renal tumours is maximal (85%); and (c) Excessive doses between 7000 and 14 000 rads after which the frequency of radiation-induced cancers of the kidney approaches zero. Studies of the latent period have shown that radiation-induced cancers of the kidney in mice do not appear until 790 days after irradiation, whereas in rats the first cancers appear after 280 days. As regards the mechanism of the inducement of renal cancer by radiation, we have been able to establish that cancers of the kidney only develop from visible renal lesions. Radiation-induced cancers have not been observed in rats or mice whose kidneys were morphologically and functionally normal. (author)

SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

Directory of Open Access Journals (Sweden)

S. V. Kostritsky

2014-07-01

Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

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S. V. Kostritsky

2013-01-01

Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

Genetic predisposition to kidney cancer.

Science.gov (United States)

Schmidt, Laura S; Linehan, W Marston

2016-10-01

Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes. Published by Elsevier Inc.

Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

Directory of Open Access Journals (Sweden)

Sundus Iqbal

2014-03-01

Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

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

Science.gov (United States)

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

2016-02-01

The frequency of malignancy is increasing in kidney transplant recipients. Posttransplant malignancy (PTM) is a major cause of long-term graft survival inhibition. In this study, we evaluated the frequency and prognosis of PTM at our center and examined the efficacy of cancer screening. Between 1972 and 2013, 750 patients were followed-up at our center. Annual physical examinations and screenings were performed to detect PTM. We investigated the detail of two distinctive cancer groups: screening-detected cancers and symptom-detected cancers. Seventy-seven PTM were identified during the follow-up period. The mean age at the initial PTM detection was 43.6 ± 12.8 years. The mean interval from transplantation to cancer diagnosis was 134.5 ± 11.3 months. Among the 77 patients, posttransplant lymphoproliferative disease (PTLD) was the most common cancer (19.5%, 15/77), followed by renal cell carcinoma (15.6%, 12/77). Of the cancer cases, 46.8% (36/77) were detected via screening. The most frequently screening-detected cancer was renal cell carcinoma of the native kidney and breast cancer (22.2%, 8/36). However, it was difficult to detect PTLD, urothelial carcinoma, and colorectal cancer via screening. Interestingly, Cox proportional regression analyses revealed nonscreened recipients to be a significant prognostic factor for PTM (P kidney transplant recipients. These findings support the provision of long-term appropriate screening for kidney transplant recipients. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Contrast-enhanced ultrasound for diagnosis of prostate cancer and kidney lesions

International Nuclear Information System (INIS)

Mitterberger, Michael; Pelzer, Alexandre; Colleselli, Daniela; Bartsch, Georg; Strasser, Hannes; Pallwein, Leo; Aigner, Friedrich; Gradl, Johann; Frauscher, Ferdinand

2007-01-01

Purpose of review: Conventional ultrasonography of both, kidney and prostate, is limited due to the poor contrast of B-mode imaging for parenchymal disease and limited sensitivity of colour Doppler for the detection of capillaries and deep pedicular vessels. Contrast-enhanced ultrasound (CEUS) overcomes these limitations. Recent findings: CEUS investigates the blood flow of the prostate, allows for prostate cancer visualization and for targeted biopsies. Comparisons between systematic and CEUS-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores and with higher Gleason scores compared with the systematic approach. Also the kidney offers promising applications as CEUS improves the detection of abnormal microvascular and macrovascular disorders. Summary: In recent literature CEUS has shown its value for diagnosis of both, prostate cancer and kidney lesions. This paper describes recent improvements and future perspectives of CEUS

The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis.

Science.gov (United States)

Li, Yang; Hu, Liyi; Xia, Qinghong; Yuan, Yongqiang; Mi, Yonghua

2017-06-01

The effects of metformin on the prognosis of kidney cancer patients with diabetes are in controversial. The present study is conducted to classify the association of metformin use with the survival of patients with kidney cancer. Electronic databases, namely PubMed and Web of Science, were used to search the eligible studies up to December, 2016. Pooled hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were calculated. It was considered as statistically significant when P value was kidney cancer patients. The combined HR suggested that the use of metformin could improve the overall survival (OS) (HR 0.643, 95% CI 0.520-0.795, P cancer-specific survival (CSS) (HR 0.618, 95% CI 0.446-0.858, P = 0.004) in kidney cancer patients. In subgroup analysis, positive associations were found between metformin use and OS/CSS of localized renal cell carcinoma patients (OS: HR 0.634, 95% CI 0.440-0.913, P = 0.014; CSS: HR 0.476, 95% CI 0.295-0.768, P = 0.002). Moreover, we also found that the use of metformin could reduce the risk of death in kidney cancer patients (HR 0.711, 95% CI 0.562-0.899, P = 0.004). Our findings suggest that the use of metformin is in favor of the prognosis of patients with kidney cancers. Further investigations are needed to evaluate the prognostic value of metformin on kidney cancer patients.

Cancer incidence in kidney transplant recipients: a study protocol

International Nuclear Information System (INIS)

Pita-Fernandez, Salvador; Valdes-Cañedo, Francisco; Pertega-Diaz, Sonia; Seoane-Pillado, Maria Teresa; Seijo-Bestilleiro, Rocio

2009-01-01

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

Kidney Function, Proteinuria, and Cancer Incidence: The Korean Heart Study.

Science.gov (United States)

Mok, Yejin; Matsushita, Kunihiro; Ballew, Shoshana H; Sang, Yingying; Jung, Keum Ji; Lee, Sunmi; Jee, Sun Ha; Coresh, Josef

2017-10-01

Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort. A prospective cohort study. 242,583 adults (30-74 years old) without a diagnosis of cancer at baseline in the Korean Heart Study, based on health checkups in 1996 to 2004 with follow-up until 2012. Creatinine-based eGFR (≥90, 60-89, 45-59, and cancer incidence based on ICD-10 codes. 15,165 cases of cancer were detected. The relationship between eGFR and incidence of any cancer was J shaped, with the lowest risk at 45 to 59mL/min/1.73m 2 . There was 44% higher risk for any cancer among those with eGFRscancer risk, showing a dose-response relationship (HRs of 1.24 [95% CI, 1.13-1.35], 1.38 [95% CI, 1.17-1.63], and 1.66 [95% CI, 1.30-2.12] for 1+, 2+, and ≥3+ vs undetectable/trace). Examining site-specific cancer, eGFRkidney and ureteral cancer, multiple myeloma, and leukemia, whereas proteinuria ≥ 1+ (vs undetectable/trace) was related to a broader set of cancers (ie, stomach, rectal, liver, lung, ovarian, kidney, bladder, and multiple myeloma). After excluding study participants with follow-up less than 3 years, the associations remained consistent for kidney cancer and myeloma with eGFR and for rectal, liver, lung, and ovarian cancer with proteinuria. Relatively small number of participants with severely reduced eGFR or 70 years or older. Kidney measures, particularly proteinuria, were associated with increased incidence of cancer. Future studies are needed to better understand the pathophysiologic mechanisms underlying these associations. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of extracorporeal shock wave lithotripsy on the kidney and perinephric tissues: CT evaluation

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Song, Kounn Sik; Kim, Kun Sang; Kim, Sae Chul [College of Medicine, Chung-Ang University, Seoul (Korea, Republic of)

1987-12-15

Since the first successful treatment of the patient with renal stone by extracorporeal shock wave lithotripsy at the Institute for Surgical Research, West Germany, on February 7, 1980, extracorporeal shock wave lithotripsy (ESWL) has been a non-invasive technique for the treatment of the renal and ureteral calculi. In spite of the fact that the acoustic energy of the focused shock waves must pass through the soft tissues of back, perinephric tissues and renal parenchyme before reaching calculi, little is known about the effects of ESWL in the renal parenchyme and perinephric soft tissues. So we analyzed a pre and post-ESWL computed tomography scans of the kidneys in 130 patients treated at our hospital during a three month period to evaluate the effects of ESWL on the kidney and perinephric soft tissues.

Effects of extracorporeal shock wave lithotripsy on the kidney and perinephric tissues: CT evaluation

International Nuclear Information System (INIS)

Song, Kounn Sik; Kim, Kun Sang; Kim, Sae Chul

1987-01-01

Since the first successful treatment of the patient with renal stone by extracorporeal shock wave lithotripsy at the Institute for Surgical Research, West Germany, on February 7, 1980, extracorporeal shock wave lithotripsy (ESWL) has been a non-invasive technique for the treatment of the renal and ureteral calculi. In spite of the fact that the acoustic energy of the focused shock waves must pass through the soft tissues of back, perinephric tissues and renal parenchyme before reaching calculi, little is known about the effects of ESWL in the renal parenchyme and perinephric soft tissues. So we analyzed a pre and post-ESWL computed tomography scans of the kidneys in 130 patients treated at our hospital during a three month period to evaluate the effects of ESWL on the kidney and perinephric soft tissues

Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

Science.gov (United States)

Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

2015-12-01

Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

Palliative nephrectomy until targeted therapy of disseminated kidney cancer patients

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A. V. Klimov

2015-01-01

Full Text Available Objective: to assess the role of palliative nephrectomy in disseminated kidney cancer patients planned to undergo targeted antiangiogenic treatment.Subjects and methods. The investigation included data on 83 patients with T1-4N0 / +M1 disseminated renal cell carcinoma (RCC who had received at least 2 targeted therapy cycles in 2009 to 2011. In 48 (57.8 % patients, the treatment was preceded by palliative nephrectomy that was not carried out in 35 (42.2 %. Before starting targeted therapy, all the cases were confirmed to be diagnosed with clear cell RCC, with a sarcomatoid component being in 7 (8.4 % patients. The median follow-up of all the patients was 21 (12–36 months.Results. The unremoved affected kidney in disseminated kidney cancer patients receiving targeted antiangiogenic therapy is an independent factor for the poor prognosis of progression-free (odds ratio (OR, 2.4; 95 % confidence interval (CI, 1.2–4.7 and overall (OR, 2.8; 95 % CI, 1.3–6.3 survival. Palliative nephrectomy does not improve the prognosis in patients with a low somatic status, the N+ category, and metastases into the bones and nonregional lymph nodes.Conclusion. Palliative nephrectomy in the selected patients with disseminated kidney cancer on targeted antiangiogenic therapy increases progression-free and overall survival.

Trace elements in the kidney tissue of Bluefin Tuna ( Thunnus ...

African Journals Online (AJOL)

Trace elements, namely lead (Pb), copper (Cu), manganese (Mn), nickel (Ni), zinc (Zn), and iron (Fe), found in kidney tissues were analyzed and compared between wild/fattened and female/male bluefin tuna (BFT) in the Eastern Mediterranean region of Turkey. One hundred (that is, 50 female and 50 male) individual ...

Patient function, long-term survival, and use of surgery in patients with kidney cancer.

Science.gov (United States)

Tan, Hung-Jui; Chamie, Karim; Daskivich, Timothy J; Litwin, Mark S; Hu, Jim C

2016-12-15

Beyond age and comorbidity, functionality can shape the long-term survival potential of patients with cancer. Accordingly, herein the authors compared mortality and receipt of cancer-directed surgery according to patient function among older adults with kidney cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 through 2009, the authors studied 28,326 elderly subjects with primary kidney cancer. Patient function was quantified using function-related indicators, claims indicative of dysfunction and disability. Adjusting for patient and cancer characteristics, competing risk regression was used to assess the relationship between function-related indicator count and cause-specific mortality and then generalized estimating equations were used to quantify the probability of surgery. A total of 13,619 adult patients (48.1%) with at least 1 function-related indicator were identified. A higher indicator category was associated with older age, greater comorbidity, female sex, unmarried status, lower socioeconomic status, and higher stage of disease (Pkidney cancer mortality varied minimally with patient function. Patients with ≥ 2 indicators received cancer-directed surgery less often than those without disability (odds ratio, 0.61; 95% CI, 0.56-0.66), although treatment probabilities remained high for patients with locoregional disease and low for those with metastatic cancer. Among older adults with kidney cancer, functional health stands as a significant predictor of long-term survival. However, receipt of cancer-directed surgery appears largely determined by cancer stage. Patient function should be considered more heavily when determining treatment for older adults with kidney cancer. Cancer 2016;122:3776-3784. © 2016 American Cancer Society. © 2016 American Cancer Society.

Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

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Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

2017-07-01

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

Preliminary Study on the Kidney Elasticity Quantification in Patients With Chronic Kidney Disease Using Virtual Touch Tissue Quantification

International Nuclear Information System (INIS)

Zheng, Xiao Zhi; Yang, Bin; Fu, Ning Hua

2015-01-01

Virtual touch tissue quantification (VTTQ) provides numerical measurements (shear wave velocity (SWV) values) of tissue stiffness. The purpose of this study was to describe the SWV values of the kidney by VTTQ and to examine the clinical usefulness of this procedure in the evaluation of elasticity changes in the kidneys of patients with chronic kidney disease (CKD). Sixty-five patients with CKD and seventy healthy participants were included in this study. A total of 270 kidneys were examined by VTTQ. The kidney elasticity was expressed as shear wave velocity. The SWV values, blood serum creatinine (Scr)/BUN and pathological findings were analyzed and compared between patients with CKD and healthy participants. In patients with CKD and healthy participants, the SWV values both gradually decreased from the renal cortex to the medulla and renal sinus The SWV value of the renal cortex in patients with CKD was less than that of healthy participants (P < 0.05), and the SWV value of the renal cortex in patients with renal insufficiency was significantly less than in those with normal renal function (2.46 ± 0.15 vs. 3.45 ± 0.26 m/s, P < 0.05). The best cutoff value for predicting renal insufficiency (Scr > 1.24 mg/dL or/and BUN > 21 mg/DL) was a SWV value of the renal cortex of less than 1.92 m/s with a sensitivity of 84.4% (95% CI: 67.2-94.7%) and a specificity of 96.8% (95% CI: 83.3-99.9%) (P < 0.001). VTTQ can sensitively detect the elasticity changes in patients with CKD, and it can effectively predict renal insufficiency. This technology provides a valuable tool for the assessment of CKD

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

OpenAIRE

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

2016-01-01

Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. ...

Cadmium and renal cancer

International Nuclear Information System (INIS)

Il'yasova, Dora; Schwartz, Gary G.

2005-01-01

Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

Increasing trends in kidney cancer over the last 2 decades in Saudi Arabia.

Science.gov (United States)

Alkhateeb, Sultan S; Alkhateeb, Jawaher M; Alrashidi, Eman A

2015-06-01

To examine the trends of kidney cancer over the last 2 decades in a subset of a Saudi Arabian population.   We conducted a retrospective study in a tertiary care center including all adult patients with primary kidney cancer who presented and were managed between 1990 and 2010. The time period was split into 4 quartiles, and variables tested and compared using chi-square, T-test, and Kaplan-Meier curves for survival.   The total was 215 patients with a mean age of 57.8 years. There was an increase in the number of kidney cancer cases over the last 2 decades. There was no significant difference in the mode of presentation or stage distribution between quartiles. A significant change was observed in the management towards minimally invasive and nephron-sparing surgeries (p less than 0.001). There was no change in recurrence-free and disease-specific survival over the last 20 years.   There have been an increasing number of kidney cancer patients over the last 2 decades with no observed migration towards more incidental and low stage tumors as compared with developed countries.

Kidney (Renal Cell) Cancer—Patient Version

Science.gov (United States)

Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

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.

Science.gov (United States)

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

2014-12-10

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. 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. 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. 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. © 2014 by American Society of Clinical Oncology.

Use of metformin and risk of kidney cancer in patients with type 2 diabetes.

Science.gov (United States)

Tseng, Chin-Hsiao

2016-01-01

The anticancer effect of metformin has been reported in the literature but requires additional confirmation in epidemiologic studies. With respect to kidney cancer scarce data are available. This study investigates whether metformin use in patients with type 2 diabetes mellitus (T2DM) might affect kidney cancer risk. The reimbursement database of the National Health Insurance in Taiwan was used. T2DM patients aged ≥ 40 years and newly treated with either metformin (n=171,753, "ever users of metformin") or other antidiabetic drugs (n=75,499, "never users of metformin") within 1998-2002 were followed for at least 6 months for kidney cancer until 31 December 2009. The treatment effect was estimated by Cox regression using propensity score weighting by inverse probability of treatment weighting approach. Hazard ratios were estimated for ever versus never users, and for tertiles of cumulative duration of metformin therapy. During follow-up, 917 ever users and 824 never users developed kidney cancer, with respective incidence of 80.09 and 190.30 per 100,000 person-years. The hazard ratio (95% confidence intervals) for ever versus never users is 0.279 (0.254-0.307); and is 0.598 (0.535-0.668), 0.279 (0.243-0.321) and 0.104 (0.088-0.124), respectively, for the first, second, and third tertile of cumulative duration of 45.8 months. In subgroup analyses, the lower risk of kidney cancer associated with metformin use is consistently observed in both sexes, and in patients with or without concomitant use of other antidiabetic drugs. Metformin use is associated with a decreased risk of kidney cancer in patients with T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regional geographic variations in kidney cancer incidence rates in European countries.

Science.gov (United States)

Li, Peng; Znaor, Ariana; Holcatova, Ivana; Fabianova, Eleonora; Mates, Dana; Wozniak, Magdalena B; Ferlay, Jacques; Scelo, Ghislaine

2015-06-01

Marked unexplained national variations in incidence rates of kidney cancer have been observed for decades in Europe. To investigate geographic variations at the regional level and identify European regions with high incidence rates of kidney cancer. Regional- and national-level incidence data were extracted from the Cancer Incidence in Five Continents databases, local cancer registry databases, and local published reports. World population age-standardised rates (ASRs) were calculated for the periods 2003-2007 and 1988-1992. Rates by period and sex were compared using map visualisation. During 2003-2007, the highest ASR was found in the Plzen region, Czech Republic (31.4/100,000 person-years in men). Other regions of the Czech Republic had ASRs of 18.6-27.5/100,000 in men, with a tendency for higher rates in regions south of Prague. Surrounding regions, including eastern Germany and regions of Slovakia and Austria, had medium-to-high incidence rates (13.0-16.8/100,000 in men). Three other areas in Europe showed higher incidence rates in men compared with the rest of the continent: Lithuania, Estonia, Latvia, and Belarus (15.0-17.6/100,000); Iceland (13.5/100,000), and northern Italy (up to 16.0/100,000). Similar regional differences were observed among women, with rates approximately half of those observed in men in the same region. In general, these regional geographic variations remained stable over the periods 1988-1992 and 2003-2007, although higher incidence rates were detected in the Baltic countries in 2003-2007. Several European regions show particularly high rates of kidney cancer incidence. Large variations were observed within countries covered by national health-care systems, implying that overdetection is not the major factor. We present regional geographic variations in kidney cancer incidence rates in Europe. We highlight several regions with high incidence rates where further studies should be conducted for cancer control and prevention. Copyright �

[Is there a link between the occurrence of Kidney cancer and hypertension in Tunisian population?].

Science.gov (United States)

Ferchichi, Imen; Kourda, Nadia; Derouiche, Amine; Baltagi, Sarra; Chebil, Mohamed; Benammar-Elgaaied, Amel

2012-05-01

Kidney cancer is generally asymptomatic and discovered incidentally at a late stage, which is a negative diagnosis because in most cases the disease is incurable at this stage. Some predisposing factors have been revealed by studies such high blood pressure, which is a frequent among the Tunisian population. A study among the Tunisian population to determine if there is a link between the occurrence of kidney cancer and the hypertension. Our work was conducted on 91 patients with confirmed renal cell carcinoma and 91 healthy subjects who consulted the Urology Department at the Charles Nicolle Hospital in Tunis. The study of clinical records has identified the clinical, pathological and therapeutic features of the 182 patients. 59% of individuals with hypertension have developed kidney cancer with a significant p-value equal to 0.03. The more the value of blood pressure increases the more the risk is (p = 0.03). Smoking in combination with hypertension is a factor favoring the occurrence of cancer with a value of p equal to 0.05. In the Tunisian population hypertension is a risk factor for developing kidney cancer, a factor compounded by the high incidence of this disease. What prompts us to make explorations of kidney lodges of hypertensive patients.

Description of a clinical case of synchronous cancer in the native and graft kidneys

Directory of Open Access Journals (Sweden)

A. V. Khaylenko

2017-01-01

Full Text Available Kidney transplantation is the most frequently performed organ transplant procedure in the world. The occurrence of malignant tumors is one of the well-known late complications of organ transplantation, which is induced by immunosuppressive therapy. In the vast majority of patients, kidney cancer occurs in the native organs; however, in a small percentage of cases, malignancies are found in the graft organ. The article describes a rare clinical case of a patient with synchronous cancer in the native and graft kidneys.

Somatic mutations in stilbene estrogen-induced Syrian hamster kidney tumors identified by DNA fingerprinting

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Roy Deodutta

2004-01-01

Full Text Available Abstract Kidney tumors from stilbene estrogen (diethylstilbestrol-treated Syrian hamsters were screened for somatic genetic alterations by Random Amplified Polymorphic DNA-polymerase chain-reaction (RAPD-PCR fingerprinting. Fingerprints from tumor tissue were generated by single arbitrary primers and compared with fingerprints for normal tissue from the same animal, as well as normal and tumor tissues from different animals. Sixty one of the arbitrary primers amplified 365 loci that contain approximately 476 kbp of the hamster genome. Among these amplified DNA fragments, 44 loci exhibited either qualitative or quantitative differences between the tumor tissues and normal kidney tissues. RAPD-PCR loci showing decreased and increased intensities in tumor tissue DNA relative to control DNA indicate that loci have undergone allelic losses and gains, respectively, in the stilbene estrogen-induced tumor cell genome. The presence or absence of the amplified DNA fragments indicate homozygous insertions or deletions in the kidney tumor DNA compared to the age-matched normal kidney tissue DNA. Seven of 44 mutated loci also were present in the kidney tissues adjacent to tumors (free of macroscopic tumors. The presence of mutated loci in uninvolved (non-tumor surrounding tissue adjacent to tumors from stilbene estrogen-treated hamsters suggests that these mutations occurred in the early stages of carcinogenesis. The cloning and sequencing of RAPD amplified loci revealed that one mutated locus had significant sequence similarity with the hamster Cyp1A1 gene. The results show the ability of RAPD-PCR to detect and isolate, in a single step, DNA sequences representing genetic alterations in stilbene estrogen-induced cancer cells, including losses of heterozygosity, and homozygous deletion and insertion mutations. RAPD-PCR provides an alternative molecular approach for studying cancer cytogenetics in stilbene estrogen-induced tumors in humans and experimental

Contemporary, age-based trends in the incidence and management of patients with early-stage kidney cancer.

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Tan, Hung-Jui; Filson, Christopher P; Litwin, Mark S

2015-01-01

Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, Pmanagement and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

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

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

2014-05-01

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

Growing kidney tissue from stem cells: how far from ‘party trick’ to medical application?

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Little, Melissa H

2016-01-01

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 towards clinical use. PMID:27257757

The study regarding effect of paraoxon on oxidative stress index in kidney tissue of rats

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Maryam Abbasnezhad1

2009-01-01

Full Text Available (Received 14 July, 2009 ; Accepted 23 December, 2009AbstractBackground and purpose: Paraoxon is the active form of parathion, which is an organophosphate pesticide (OP. The toxic effects of some OPs are not limited to inhibition of cholinesterase, they are capable to produce free radicals and induce disturbance in body antioxidant systems. The purpose of this study was to evaluate the effect of paraoxon on oxidative stress index in the kidney of rat.Materials and methods: Wistar male rats were randomly divided in four groups including: control (corn oil as paraoxon solvent and three paraoxon groups receiving different doses (0.3, 0.7 and 1mg/kg by intraperitoneal injection. 24 hours after injection, animal was given anesthesia and kidney tissue removed. After kidney tissue hemogenation, superoxide dismutase (SOD and catalase (CAT, lactate dehydrogenase (LDH and glutathione S- transferase (GST activities, glutathione (GSH and malondialdehyde (MDA levels were determined by biochemical methods.Results: At doses higher than 0.3 mg/kg paraoxon, kidney SOD and CAT activities were significantly increased, comparing with the control, while GSH level was significantly decreased. There were no significant changes observed in GST, LDH activities and MDA levels.Conclusion: The results suggest that paraoxon induces the production of free radicals and oxidative stress. The enhanced activity of antioxidant enzymes in kidney of rats probably was a function of the increased detoxification capacity. Depletion of tissue GSH is a prime factor, which can impair the cell’s defense against the toxic actions of free radicals.J Mazand Univ Med Sci 2009; 19(73: 17-26 (Persian.

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

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

2013-01-01

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 3 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 5 with other NSAIDs) that were performed in 6 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 to 1.44 and 1.25; 95% CI, 1.06 to 1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR, 1.10; 95% CI, 0.95 to 1.28), except for non-US studies (5 studies, pooled RR=1.17, 95% CI, 1.04 to 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

Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

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Jing Ma

2009-01-01

Full Text Available Perchloroethylene (PERC is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994–2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

International Nuclear Information System (INIS)

Ma, J.; Lessner, L.; Lessner, L.; Carpenter, D.O.; Schreiber, J.

2010-01-01

Perchloroethylene (PERC) is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994-2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

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

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

2017-01-01

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

Cancer-Specific and All-Cause Mortality in Kidney Transplant Recipients With and Without Previous Cancer.

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Viecelli, Andrea K; Lim, Wai H; Macaskill, Petra; Chapman, Jeremy R; Craig, Jonathan C; Clayton, Philip; Cohney, Solomon; Carroll, Robert; Wong, Germaine

2015-12-01

For dialysis patients with a cancer history, a period of surveillance is generally recommended before listing for transplantation. However, the outcomes of patients with cancer recurrence and/or a second primary cancer after transplantation are unknown. To determine the prognosis of kidney transplant recipients who developed cancer after transplantation and whether this varied with cancer types (first cancer, recurrence, second primary cancer). Using data from the Australian and New Zealand Dialysis and Transplant Registry, we compared the cancer-specific and all-cause mortality among recipients with different cancer types using adjusted Cox proportional hazard models. Of the 21,415 recipients transplanted between 1965 and 2012, 3% (651 of 21,415) had a previous cancer history. A total of 2840 (13%) recipients developed cancer after the first transplant, of whom 2760 (97.2%) developed a first cancer, 23 (0.8%) experienced cancer recurrence, and 57 (2%) developed a second primary cancer. There were no significant differences in the risks of cancer-specific and all-cause mortality between recipients who developed their first cancer after transplant, those with cancer recurrence (adjusted hazard ratios [aHRs], 0.79; 95% confidence interval [95% CI], 0.38-1.67; P = 0.54 and aHRs, 0.86; 95% CI, 0.45-1.66; P = 0.66, respectively) and recipients who developed a second primary cancer after transplantation (aHRs, 1.01; 95%CI, 0.63-1.62; P = 0.95 and aHRs, 1.16; 95% CI, 0.79-1.69; P = 0.45, respectively). Among patients with a previous history of malignancy, recurrent and second primary cancers are infrequent after renal transplantation. A history of previous malignancy does not have an additive effect on the cancer-specific and overall survival of kidney transplant recipients who develop cancer.

Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors

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Therland, Karina L; Stubbe, Jane; Thiesson, Helle C

2004-01-01

The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys (cancer specimens),...... feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction....

SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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A. S. Semkov

2010-01-01

Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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A. S. Semkov

2014-08-01

Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target.

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Chen, C-H; Fong, L W R; Yu, E; Wu, R; Trott, J F; Weiss, R H

2017-06-22

Targeted therapeutics, such as those abrogating hypoxia inducible factor (HIF)/vascular endothelial growth factor signaling, are initially effective against kidney cancer (or renal cell carcinoma, RCC); however, drug resistance frequently occurs via subsequent activation of alternative pathways. Through genome-scale integrated analysis of the HIF-α network, we identified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) as a potential target molecule for kidney cancer. In a screen of nephrectomy samples from 56 patients with RCC, we found that MARCKS expression and its phosphorylation are increased and positively correlate with tumor grade. Genetic and pharmacologic suppression of MARCKS in high-grade RCC cell lines in vitro led to a decrease in cell proliferation and migration. We further demonstrated that higher MARCKS expression promotes growth and angiogenesis in vivo in an RCC xenograft tumor. MARCKS acted upstream of the AKT/mTOR pathway, activating HIF-target genes, notably vascular endothelial growth factor-A. Following knockdown of MARCKS in RCC cells, the IC50 of the multikinase inhibitor regorafenib was reduced. Surprisingly, attenuation of MARCKS using the MPS (MARCKS phosphorylation site domain) peptide synergistically interacted with regorafenib treatment and decreased survival of kidney cancer cells through inactivation of AKT and mTOR. Our data suggest a major contribution of MARCKS to kidney cancer growth and provide an alternative therapeutic strategy of improving the efficacy of multikinase inhibitors.

Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

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Gimpel, Charlotte; Pohl, Martin; Jung, Bernd A.; Jung, Sabine; Brado, Johannes; Odening, Katja E.; Schwendinger, Daniel; Burkhardt, Barbara; Geiger, Julia; Arnold, Raoul

2017-01-01

Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

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

International Nuclear Information System (INIS)

Choi, Insup.

1989-01-01

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

Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

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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.

MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays.

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Powers, Thomas W; Neely, Benjamin A; Shao, Yuan; Tang, Huiyuan; Troyer, Dean A; Mehta, Anand S; Haab, Brian B; Drake, Richard R

2014-01-01

A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues. Formalin-fixed tissues from normal mouse kidney, human pancreatic and prostate cancers, and a human hepatocellular carcinoma tissue microarray were processed by antigen retrieval followed by on-tissue digestion with peptide N-glycosidase F. The released N-glycans were detected by MALDI-IMS analysis, and the structural composition of a subset of glycans could be verified directly by on-tissue collision-induced fragmentation. Other structural assignments were confirmed by off-tissue permethylation analysis combined with multiple database comparisons. Imaging of mouse kidney tissue sections demonstrates specific tissue distributions of major cellular N-linked glycoforms in the cortex and medulla. Differential tissue distribution of N-linked glycoforms was also observed in the other tissue types. The efficacy of using MALDI-IMS glycan profiling to distinguish tumor from non-tumor tissues in a tumor microarray format is also demonstrated. This MALDI-IMS workflow has the potential to be applied to any FFPE tissue block or tissue microarray to enable higher throughput analysis of the global changes in N-glycosylation associated with cancers.

The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

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Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

2015-01-01

The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

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Pu Duann

2016-05-01

Full Text Available 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.

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

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Amiri, Fateme Shamekhi

2016-01-01

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.

Molecular detection of Leptospira spp. from canine kidney tissues and its association with renal lesions

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Biswajit R. Dash

2018-04-01

Full Text Available Aim: The study aimed to detect the prevalence of Leptospira spp. in kidney tissues collected during necropsy and to establish its association with renal lesions in dogs of Mumbai region. Materials and Methods: Kidney tissues from 40 dogs were collected during necropsy after gross examination and then fixed in neutral buffered formalin and Bouin's fluid for histopathology and histochemistry, respectively. Kidney tissues were also collected for the detection of Leptospira spp. by polymerase chain reaction (PCR in a sterile container and stored at -80°C until further processing. Results: Of 40 cases studied, 13 (32.5% cases showed lesions of nephritis of varying histotype and severity. Glomerulonephritis was reported as the most common type of nephritis in 9 (69.23% cases, and interstitial nephritis was recorded in 4 (30.76% cases. Chronic and acute interstitial nephritis was observed in two cases each. Renal failure as a cause of death was found in 7 (17.5% dogs. Of a total of 40 cases, 9 were found positive for pathogenic Leptospira spp. genome by PCR. However, of nine PCR-positive cases, only four cases showed lesions in kidneys as glomerulonephritis and interstitial nephritis in two cases each. The rest five cases positive for Leptospira spp. by PCR did not show any appreciable lesions in the kidneys. Conclusion: Leptospiral DNA was detected in 9 (22.5% cases by PCR. Of these nine cases, only four cases showed renal lesions. Other five cases which were positive for Leptospira spp. by PCR did not show any appreciable gross and microscopic lesions in the kidneys which might be carriers for Leptospira spp. Considering variable reports on types of nephritis in Leptospira spp. infection and also the prevalence of non-pathogenic Leptospira spp., it is important to conduct an extensive study on the prevalence of Leptospira spp. and its association with renal lesions involving batteries of tests.

Protein signature of lung cancer tissues.

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Michael R Mehan

Full Text Available 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.

Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres

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Silva, Suresh de, E-mail: suresh.desilva@unsw.edu.au [Southern Radiology Group, Radiology Department Sutherland Hospital (Australia); Mackie, Simon [Western General Hospital, Department of Urology (United Kingdom); Aslan, Peter [St George Hospital, Department of Urology (Australia); Cade, David [Sirtex Technology Pty Ltd (Australia); Delprado, Warick [Douglass Hanly Moir Pathology (Australia)

2016-12-15

BackgroundIntra-arterial brachytherapy with yttrium-90 ({sup 90}Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of {sup 90}Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.MethodsIn each of six pigs, ~25–33 % of the kidney volume was embolized with {sup 90}Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extent of tissue necrosis from {sup 90}Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.ResultsKidneys embolized with {sup 90}Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the {sup 90}Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10{sup 6}) of bland microspheres.ConclusionThis study showed that radioembolization with {sup 90}Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of {sup 90}Y resin microspheres for the localized treatment of kidney tumors.

Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres

International Nuclear Information System (INIS)

Silva, Suresh de; Mackie, Simon; Aslan, Peter; Cade, David; Delprado, Warick

2016-01-01

BackgroundIntra-arterial brachytherapy with yttrium-90 ("9"0Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of "9"0Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.MethodsIn each of six pigs, ~25–33 % of the kidney volume was embolized with "9"0Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extent of tissue necrosis from "9"0Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.ResultsKidneys embolized with "9"0Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the "9"0Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10"6) of bland microspheres.ConclusionThis study showed that radioembolization with "9"0Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of "9"0Y resin microspheres for the localized treatment of kidney tumors.

Precision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics.

Science.gov (United States)

Kiryluk, Krzysztof; Bomback, Andrew S; Cheng, Yim-Ling; Xu, Katherine; Camara, Pablo G; Rabadan, Raul; Sims, Peter A; Barasch, Jonathan

2018-01-01

Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

Science.gov (United States)

Kao, C-C; Liu, J-S; Lin, M-H; Hsu, C-Y; Chang, F-C; Lin, Y-C; Chen, H-H; Chen, T-W; Hsu, C-C; Wu, M-S

2016-04-01

The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

Three-dimensional reconstruction volume: a novel method for volume measurement in kidney cancer.

Science.gov (United States)

Durso, Timothy A; Carnell, Jonathan; Turk, Thomas T; Gupta, Gopal N

2014-06-01

The role of volumetric estimation is becoming increasingly important in the staging, management, and prognostication of benign and cancerous conditions of the kidney. We evaluated the use of three-dimensional reconstruction volume (3DV) in determining renal parenchymal volumes (RPV) and renal tumor volumes (RTV). We compared 3DV with the currently available methods of volume assessment and determined its interuser reliability. RPV and RTV were assessed in 28 patients who underwent robot-assisted laparoscopic partial nephrectomy for kidney cancer. Patients with a preoperative creatinine level of kidney pre- and postsurgery overestimated 3D reconstruction volumes by 15% to 102% and 12% to 101%, respectively. In addition, volumes obtained from 3DV displayed high interuser reliability regardless of experience. 3DV provides a highly reliable way of assessing kidney volumes. Given that 3DV takes into account visible anatomy, the differences observed using previously published methods can be attributed to the failure of geometry to accurately approximate kidney or tumor shape. 3DV provides a more accurate, reproducible, and clinically useful tool for urologists looking to improve patient care using analysis related to volume.

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

Science.gov (United States)

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

2016-04-05

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

Advances in diagnosis and follow-up in kidney cancer

NARCIS (Netherlands)

Rioja, Jorge; de La Rosette, Jean J. M. C. H.; Wijkstra, Hessel; Laguna, M. Pilar

2008-01-01

PURPOSE OF REVIEW: To review the most recent data on preoperative diagnostic methods in kidney cancer and in follow-up and monitoring after ablation therapy. RECENT FINDINGS: Although the role of the percutaneous biopsy in the diagnostics of renal masses has been limited, new data suggest a high

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

Energy Technology Data Exchange (ETDEWEB)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

Energy Technology Data Exchange (ETDEWEB)

Gimpel, Charlotte; Pohl, Martin [Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Center for Pediatrics, Freiburg (Germany); Jung, Bernd A. [Inselspital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Jung, Sabine [Medical Center - University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Brado, Johannes; Odening, Katja E. [University Heart Center Freiburg, Department of Cardiology and Angiology I, Freiburg (Germany); Schwendinger, Daniel [University Children' s Hospital Zurich, Zurich (Switzerland); Burkhardt, Barbara [University Children' s Hospital Zurich, Pediatric Heart Center, Zurich (Switzerland); Geiger, Julia [University Children' s Hospital Zurich, Department of Radiology, Zurich (Switzerland); Northwestern University, Department of Radiology, Chicago, IL (United States); Arnold, Raoul [University Hospital Heidelberg, Department of Pediatric and Congenital Cardiology, Heidelberg (Germany)

2017-02-15

Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V{sub E}), late diastolic (V{sub A}) and peak systolic (V{sub S}) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz{sub base} -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz{sub mid} -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz{sub apex} -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr{sub base} -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr{sub mid} -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr{sub apex} -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

Hormonal treatment of obstructed kidneys in patients with prostatic cancer

DEFF Research Database (Denmark)

Honnens de Lichtenberg, M; Miskowiak, J; Rolff, H

1993-01-01

A review of 1288 patients with previously untreated prostatic cancer revealed 209 patients (16%) with ureteric obstruction; the obstruction was bilateral in 36%. The effect of hormonal treatment was assessed in 88 patients with 120 obstructed kidneys: 77 patients had androgen deprivation...... or hormonal medication alone and 11 patients needed percutaneous nephrostomy or ureteric catheters in addition. Drainage improved in 58% of the kidneys. The diverting catheter was withdrawn in 9 of the 11 patients after a median of 4 weeks. In all, 95% of patients were discharged. The patients with hormonal...

[Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic rat].

Science.gov (United States)

Chen, Weidong; Chang, Baochao; Zhang, Yan; Yang, Ping; Liu, Lei

2015-05-01

To observe the effect of rhein on the expression of SIRT1(Sirtuin 1) in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism. The type 2 diabetic rats were induced by high-glucose and high-fat diet combined with streptozotocin (35 mg/kg body mass). Seventy-five eight-week-old male SD rats were randomly divided into 6 groups: normal group, diabetic group, low-, medium- and high-dose (50, 100, 150 mg/kg) rhein treatment groups and 10 mg/kg pioglitazone treatment group. The rats were given corresponding substances intragastrically once a day. At the end of the 16th week, the fasting plasma glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), serum creatinine (Scr) and 24 hours urine protein (24 h U-PRO) were determined. The renal hypertrophy index (KM/BM), insulin resistance index (HOMA-IR) were calculated. The pathological changes in renal tissues were examined by PAS staining under a light microscopy. The mean glomerular area (MGA) and mean glomerular volume (MGV) were measured by pathological image analysis system. Western blotting and real-time quantitative PCR were used to determine the expression of SIRT1 in renal tissues at protein and mRNA levels, respectively. The expression of SIRT1 was down-regulated in the kidney of diabetic rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and MGV significantly decreased and the histopathology of renal tissues were significantly improved in all treatment groups compared with diabetic group. The expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups and pioglitazone treatment group compared with diabetic group. The indicators in high-dose rhein treatment group were improved more significantly than those in the other groups. Correlation analysis showed that the expression of SIRT1 was negatively correlated with 24 h U-PRO and MGV. The expression of SIRT1 was

Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

Directory of Open Access Journals (Sweden)

Navin Gupta

2017-08-01

Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

Cancerous tissue mapping from random lasing emission spectra

International Nuclear Information System (INIS)

Polson, R C; Vardeny, Z V

2010-01-01

Random lasing emission spectra have been collected from both healthy and cancerous tissues. The two types of tissue with optical gain have different light scattering properties as obtained from an average power Fourier transform of their random lasing emission spectra. The difference in the power Fourier transform leads to a contrast between cancerous and benign tissues, which is utilized for tissue mapping of healthy and cancerous regions of patients

Everolimus-associated acute kidney injury in patients with metastatic breast cancer

Directory of Open Access Journals (Sweden)

A Chandra

2017-01-01

Full Text Available Recently, everolimus (Evl has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

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

Energy Technology Data Exchange (ETDEWEB)

Taylor, M. L. [School of Applied Sciences and Health Innovation Research Institute, RMIT University, Melbourne 3000 (Australia); Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne 3001 (Australia) and Medical Physics, WBRC, Alfred Hospital, Melbourne 3000 (Australia)

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

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

International Nuclear Information System (INIS)

Taylor, M. L.

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Kong Xiangang

2011-03-01

Full Text Available Abstract 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.

Tissue expression and plasma levels of adrenomedullin in renal cancer patients

DEFF Research Database (Denmark)

Michelsen, Jens; Thiesson, Helle; Walter, Steen

2006-01-01

that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3-6 days after surgery and 4-5 weeks after surgery. AM m...... conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease....

The effect of extracorporeal shock wave lithotripsy on kidney and adjacent tissue detected by magnetic resonance imaging

International Nuclear Information System (INIS)

Saiko, Yasushi; Hirose, Tomonobu; Yoshida, Masahiko; Saito, Isao

1995-01-01

Etracorporeal shock wave lithotripsy (ESWL) using YACHIYODA SZ1 was performed on 12 patients with renal stones and the effect on the kidney and adjacent tissue was evaluated by magnetic resonance imaging(MRI) before and after treatment. Some changes were seen in 6 of the 12 (50%) patients; perirenal fluid collection in 2 of the 12 (16.7%) patients, subcapsular hematoma in 2 of the 12 (16.7%) patients, renal enlargement in 5 of the 12 (31.3%) patients, increased signal intensity in perirenal tissue in 6 of the 12 (50%) patients, and loss of the corticomedullary junction in 2 out of 9 patients (22%). These findings indicated fewer changes in the kidney after ESWL using YACHIYODA SZ1 than in the other reports. MRI is also concluded to be effective to detect the changes of the kidney after ESWL. (author)

The effect of extracorporeal shock wave lithotripsy on kidney and adjacent tissue detected by magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Saiko, Yasushi; Hirose, Tomonobu; Yoshida, Masahiko; Saito, Isao [Tokyo Kyosai Hospital (Japan)

1995-08-01

Etracorporeal shock wave lithotripsy (ESWL) using YACHIYODA SZ1 was performed on 12 patients with renal stones and the effect on the kidney and adjacent tissue was evaluated by magnetic resonance imaging(MRI) before and after treatment. Some changes were seen in 6 of the 12 (50%) patients; perirenal fluid collection in 2 of the 12 (16.7%) patients, subcapsular hematoma in 2 of the 12 (16.7%) patients, renal enlargement in 5 of the 12 (31.3%) patients, increased signal intensity in perirenal tissue in 6 of the 12 (50%) patients, and loss of the corticomedullary junction in 2 out of 9 patients (22%). These findings indicated fewer changes in the kidney after ESWL using YACHIYODA SZ1 than in the other reports. MRI is also concluded to be effective to detect the changes of the kidney after ESWL. (author).

The Dynamics of Acute Renal Impairment Markers During a Surgery for Kidney Cancer

Directory of Open Access Journals (Sweden)

E. M. Frantsiyants

2017-01-01

Full Text Available The purpose of the study is to investigate the effect of epidural block on the functional state of the kidneys in patients with localized cancer during kidney resection under the conditions of warm ischemia.Materials and methods. We examined 45 patients (25 men and 20 women with a localized kidney cancer (T1N0M0 aged 56.5±8.7 years. All the patients underwent kidney resection performed under conditions of warm ischemia (15—20 minutes. Patients were divided into 2 groups: the main group (25 subjects in which the perioperative epidural block was applied and the reference group (20 patients without the epidural block. The following parameters were tested in blood and urine using the ELISA technique: cystatin C, L-FABP, KIM-1 , IL-18, and GFR. The test was carried out 1 hour prior to surgery, 20 minutes after the warm ischemia stage, and on Days 1 and 3. Based on the baseline cystatin С level, the patients in each group were divided into 2 subgroups: subgroup 1 —cystatin C is 1000 ng/ml and lower; subgroup 2 — more than 1000 ng/ml. The statistical processing of the findings was performed using the Statistica 6.0 software based on the t-test for two independent samples. Differences were considered to be statistically significant at P<0.05.Results. It has been demonstrated that functional parameters of kidneys were recovered to the baseline values by the 3rd day after the kidney resection under the warm ischemia due to perioperative epidural block. Impairment of the tubulointerstitium and glomerular apparatus were observed in the reference group. GFR values in the patients of the main group were within normal limits by Day 3, whereas in the patients of the GFR was lower by 38.8% as compared to the baseline (P<0.05.Conclusion. The use of the perioperative epidural block in patients with localized kidney cancer who underwent the organ resection under the warm ischemia demonstrated the nephroprotective effect, while maintaining the functional

Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.

Science.gov (United States)

Vasselli, James R; Shih, Joanna H; Iyengar, Shuba R; Maranchie, Jodi; Riss, Joseph; Worrell, Robert; Torres-Cabala, Carlos; Tabios, Ray; Mariotti, Andra; Stearman, Robert; Merino, Maria; Walther, McClellan M; Simon, Richard; Klausner, Richard D; Linehan, W Marston

2003-06-10

To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.

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.

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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.

Differentiating cancerous from normal breast tissue by redox imaging

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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 (pcancerous tissues than in the normal ones (pcancer 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.

[Cancer cachexia and white adipose tissue browning].

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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.

Nonmuscle Tissues Contribution to Cancer Cachexia

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Josep M. Argilés

2015-01-01

Full Text Available 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.

Epidemiology of Kidney Cancer

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D. Pascual

2008-01-01

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

Diagnosis of breast cancer by tissue analysis

Institute of Scientific and Technical Information of China (English)

Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

2013-01-01

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

N-glycosylation of Colorectal Cancer Tissues

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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

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

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Yu SS

2016-09-01

Full Text Available Steven S Yu, David I Quinn, Tanya B Dorff Division of Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA Abstract: Clear cell (cc renal cell carcinoma (RCC is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC. Keywords: cabozantinib, renal cell carcinoma, kidney cancer, clear cell carcinoma, tyrosine kinase inhibitor

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.

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Piccoli, Giorgina Barbara; Bonino, Laura Davico; Campisi, Paola; Vigotti, Federica Neve; Ferraresi, Martina; Fassio, Federica; Brocheriou, Isabelle; Porpiglia, Francesco; Restagno, Gabriella

2012-02-21

MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.

Kidney (Renal Cell) Cancer—Health Professional Version

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Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

The Perspectives of Haematological Cancer Patients on Tissue Banking.

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Turon, Heidi; Waller, Amy; Clinton-McHarg, Tara; Boyes, Allison; Fleming, Jennifer; Marlton, Paula; Harrison, Simon J; Sanson-Fisher, Rob

2016-01-01

A high level of support for tissue banking has been identified amongst both the general public and patients. However, much debate remains about the regulatory framework of tissue banks. This study explored the views of haematological cancer patients regarding tissue banking and how tissue banks should operate. Haematological cancer patients from three outpatient clinics in Australia completed a questionnaire examining their preferences for tissue banking as well as items about their sociodemographic characteristics, disease and treatment history. The majority of participants (95%) reported being willing to allow their leftover tissue to be used for medical research. Three quarters (76%) supported the idea of their medical record being linked to their tissue sample, and 77% preferred a blanket (one-off) consent model for future research use of their tissue sample. Only 57 (27%) participants had been asked to give a tissue sample for research, 98% of whom gave permission. The majority of haematological cancer patients are willing to donate their leftover tissue to a tissue bank and have their medical records linked to tissue samples and prefer a one-off consent process. These novel data from potential donors inform the debate about how tissue banks might operate. Strategic Research Partnership Grant from the Cancer Council NSW to the Newcastle Cancer Control Collaborative (New-3C) and infrastructure funding from the Hunter Medical Research Institute (HMRI). A.W. is supported by an Australian Research Council DECRA fellowship (DE150101262). T.C.M. was supported by a Leukaemia Foundation of Queensland Post-Doctoral Fellowship. A.B. is supported by National Health and Medical Research Council (APP1073317) and Cancer Institute NSW (13/ECF/1-37) Early Career Fellowships.

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

International Nuclear Information System (INIS)

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 [ 3 H]yohimbine, whereas [ 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, [ 3 H] clonidine and [ 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 [ 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

Kidney compartment model

International Nuclear Information System (INIS)

Gullberg, G.T.

1976-09-01

A multiparameter kidney compartment model which quantitates the amount of iodohippurate concentration as a function of time in the blood, tissue, kidneys and bladder is developed from a system of differential equations which represent first order kinetics. The kinetic data are obtained using a gamma camera and an HP5407 computer system which allows one to delineate areas of interest for the blood and tissue, kidneys, and bladder thus separating the data into four data sets. The estimated tubular transit times have a high ratio of the signal to the variance whereas the estimates of the amount of iodohippurate in the blood, tissue and kidneys have a low ratio of the signal to the variance. Application of this model to patient data requires better statistics than available with conventional 131 I-hippurate doses; thus a true test of the efficacy awaits availability of 123 I-hippurate

Cancers Associated with Overweight and Obesity Infographic

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Overweight and obesity are linked to an increased risk of 13 types of cancer. See a diagram of the human body highlighting the organs or tissues at increased cancer risk, including the breast, colon and rectum, kidney, and liver.

Prediction of survival in patients with Stage IV kidney cancer

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L. V. Mirilenko

2015-01-01

Full Text Available The efficiency of treatment was evaluated and the predictors of adjusted survival (AS were identified in patients with disseminated kidney cancer treated at the Republican Research and Practical Center for Oncology and Medical Radiology in 1999 to 2011 (A.E. Okeanov, P.I. Moiseev, L.F. Levin. Malignant tumors in Belarus, 2001–2012. Edited by O.G. Sukonko. Seven factors (regional lymph node metastases; distant bone metastases; a high-grade tumor; sarcomatous tumor differentiation; hemoglobin levels of < 125 g/l in women and < 150 g/l in men; an erythrocyte sedimentation rate of 40 mm/h; palliative surgery were found to have an independent, unfavorable impact on AS. A multidimensional model was built to define what risk group low (no more than 2 poor factors, moderate (3–4 poor factors, and high (more than 4 poor factors the patients with Stage IV kidney cancer belonged to. In these groups, the median survival was 34.7, 17.2, and 4.0 months and 3-year AS rates were 48.6, 24.6, and 3.2 %, respectively. 

The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians.

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Jones, Jennifer; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

2017-12-01

It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

Tissue distribution of crizotinib and gemcitabine combination in a patient-derived orthotopic mouse model of pancreatic cancer

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Richard J. Honeywell

2016-12-01

Full Text Available Pharmacokinetics focuses on the question whether a drug actually reaches its target in therapeutic concentrations or accumulates elsewhere, potentially causing toxicological or unpredictable side effects. We determined tissue distribution of gemcitabine, an antimetabolite, and crizotinib, a tyrosine-kinase inhibitor targeted against the anaplastic lymphoma kinase (ALK and mesenchymal-epithelial transition factor (c-Met receptors, in a validated orthotopic mouse model for pancreatic cancer. Mice with pancreatic cancer were treated with either oral crizotinib at 25 mg/kg, gemcitabine at 100 mg/kg or with their combination. Two hours after the last gemcitabine dose mice were sacrificed and all available blood/organs/tissues were sampled. Tissue was subsequently analyzed for drug concentrations using a validated liquid chromatography-mass spectrometry (LC-MS/MS technique. In whole blood gemcitabine was about 1.0 µM and crizotinib 2.4 µM in the single treatment, whereas in the combination crizotinib increased the levels of gemcitabine. Crizotinib was found in all major tissues, being highest in the intestine. Comparison of crizotinib alone to the gemcitabine-crizotinib combination showed that crizotinib tissue concentrations were 3-6 fold lower in liver, lung, kidney and spleen, 30-fold lower in the skin, heart and pancreas and 200-fold lower in the brain. Tissue gemcitabine was highest in spleen and skin, being about 5-10 fold higher than in the other tissues, including brain, which still had a relatively high accumulation. In conclusion, both gemcitabine and crizotinib accumulate at clinically active but variable levels in tissues, possibly relating to the effects exerted by these drugs.

A study about trace element distribution in cancer tissue and serum of cancer patients

International Nuclear Information System (INIS)

Lee, Jong In; Lee, Eun Joo; Jung, Young Joo

1993-01-01

Authers analyzed the trace element distribution of cancer tissue and its corresponding normal tissue and serum of preoperative and postoperative stage in gastric, colon, breast cancer patients. Zinc and rubidium were higher in concentration in breast cancer tissue than in normal tissue. As for the distribution of trace element in serum, bromine became about 10 times higher after gastric resection. This result can be applied to experimental carcinogenesis and to relationship with other prognostic factors. (Author)

The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer.

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Alsaiari, Ahmed; Joury, Abdulaziz; Aljuaid, Mossab; Wazzan, Mohammed; Pines, Jesse M

2017-12-01

The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

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DONGZHI LI

2013-07-01

Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

Comparative trace elemental analysis of cancerous and non-cancerous tissues of rectal cancer patients using PIXE

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Naga Raju, G. J.; Sarita, P.; Murthy, K. S. R.

2017-08-01

Particle Induced X-ray Emission (PIXE), an accelerator based analytical technique has been employed in this work for the analysis of trace elements in the cancerous and non-cancerous tissues of rectal cancer patients. A beam of 3 MeV protons generated from 3 MV Pelletron accelerator at the Ion Beam Laboratory of Institute of Physics, Bhubaneswar, India was used as projectile to excite the atoms present in the tissues samples. PIXE technique, with its capability to detect simultaneously several elements present at very low concentrations, offers an excellent tool for trace element analysis. The characteristic X-rays emitted by the samples were recorded by a high resolution Si (Li) detector. On the basis of the PIXE spectrum obtained for each sample, the elements Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, and Br were identified and their relative concentrations were estimated in the cancerous and non-cancerous tissues of rectum. The levels of Mn, Fe, Co, Cu, Zn, and As were higher (p < 0.005) while the levels of Ca, Cr and Ni were lower (p < 0.005) in the cancer tissues relative to the normal tissues. The alterations in the levels of the trace elements observed in the present work are discussed in this paper with respect to their potential role in the initiation, promotion and inhibition of cancer of the rectum.

Time- and dose rate-related effects of internal 177Lu exposure on gene expression in mouse kidney tissue

International Nuclear Information System (INIS)

Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Spetz, Johan; Helou, Khalil; Forssell-Aronsson, Eva

2014-01-01

Introduction: The kidneys are the dose-limiting organs in some radionuclide therapy regimens. However, the biological impact of internal exposure from radionuclides is still not fully understood. The aim of this study was to examine the effects of dose rate and time after i.v. injection of 177 LuCl 3 on changes in transcriptional patterns in mouse kidney tissue. Methods: To investigate the effect of dose rate, female Balb/c nude mice were i.v. injected with 11, 5.6, 1.6, 0.8, 0.30, and 0 MBq of 177 LuCl 3 , and killed at 3, 6, 24, 48, 168, and 24 hours after injection, respectively. Furthermore, the effect of time after onset of exposure was analysed using mice injected with 0.26, 2.4, and 8.2 MBq of 177 LuCl 3 , and killed at 45, 90, and 140 days after injection. Global transcription patterns of irradiated kidney cortex and medulla were assessed and enriched biological processes were determined from the regulated gene sets using Gene Ontology terms. Results: The average dose rates investigated were 1.6, 0.84, 0.23, 0.11 and 0.028 mGy/min, with an absorbed dose of 0.3 Gy. At 45, 90 and 140 days, the absorbed doses were estimated to 0.3, 3, and 10 Gy. In general, the number of differentially regulated transcripts increased with time after injection, and decreased with absorbed dose for both kidney cortex and medulla. Differentially regulated transcripts were predominantly involved in metabolic and stress response-related processes dependent on dose rate, as well as transcripts associated with metabolic and cellular integrity at later time points. Conclusion: The observed transcriptional response in kidney tissue was diverse due to difference in absorbed dose, dose rate and time after exposure. Nevertheless, several transcripts were significantly regulated in all groups despite differences in exposure parameters, which may indicate potential biomarkers for exposure of kidney tissue

[Application of 3D soft print models of the kidney for treatment of patients with localized cancer of the kidney (a pilot study)].

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Alyaev, Yu G; Sirota, E S; Bezrukov, E A; Fiev, D N; Bukatov, M D; Letunovskii, A V; Byadretdinov, I Sh

2017-12-01

To evaluate the possibility of using 3D-printing in the management of patients with localized kidney cancer. The study comprised five patients with localized kidney cancer who were treated at the Urology Clinic of the I.M. Sechenov First Moscow State Medical University from January 2016 to April 2017. Along with the standard examination, the patients underwent multispiral computed tomography (MSCT) to produce patient-specific 3D-printed models of the kidney tumors using 3D modeling and 3D printing. To evaluate the effectiveness of using 3D-printed models, two-stage preoperative planning was conducted, and five surgeons were surveyed using a four-question multiple choice questionnaire. At the first stage, the planning of operations was carried out based on MSCT findings. At the second stage, the surgeons were given patient-specific soft 3D models of the kidney with a tumor for preoperative training. After preoperative training, patients underwent laparoscopic resection of the kidney with a tumor. According to the survey results, each of the participating surgeons at least once changed surgical plan based on data obtained with 3D printed models of the kidney with the tumor. The implementation of preoperative training using 3D printed models of the kidney turned out to be effective. All patients underwent laparoscopic surgery performed by a single surgeon with extensive experience in this type of surgery. The mean operative time was 187 minutes. All operations were performed with main renal artery occlusion. The men warm ischemia time was 19.5 minutes and the mean blood loss was 170 ml. There were no conversions to open surgery and organ-removing operations. There were no postoperative complications or deaths. All surgical margins were negative. Morphological examination showed that four patients had renal cell carcinoma one patient had the oncocytoma. The study demonstrated the promise of using 3D printing for preoperative planning and surgical performance due to a

[Morphological characteristics of kidneys connective tissue of mature fetuses and newborns from mothers, whose pregnancy was complicated by preeclampsia of varying degrees of severity].

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Sorokina, Iryna V; Myroshnychenko, Mykhailo S; Kapustnyk, Nataliia V; Khramova, Tetyana O; Dehtiarova, Oksana V; Danylchenko, Svitlana I

2018-01-01

Introduction: The kidneys connective tissue condition in the antenatal period affects the formation of tissues and it changes with the development of various general pathological processes in this organ. The aim of the study was to identify the morphological features of kidneys connective tissue of fetuses and newborns from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity. Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity (78 cases). Immunohistochemical study was performed by an indirect Coons method according to M. Brosman's technique using monoclonal antibodies to collagen type I, III and IV. Results: The kidneys connective tissue of fetuses and newborns developing under the maternal preeclampsia conditions is characterized by the qualitative and quantitative changes that indicate the development of sclerotic processes in this organ, the severity of which increase with the age and with the increase of the maternal preeclampsia severity. Qualitative changes are characterized by an increase of the fibrous component, thickening of the bundles of connective tissue fibers, and a decrease in the distance between them. Quantitative changes are characterized by a pronounced predominance of collagen fibers over elastic fibers, almost total absence in some field of view elastic fibers and the violation of the content of collagen type I, III and IV. Conclusion: Maternal preeclampsia underlies the development of qualitative and quantitative changes in kidneys connective tissue of fetuses and newborns, which as a result will lead to disruption of the functions of these organs in such children.

Statin use and kidney cancer outcomes: A propensity score analysis.

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

2016-11-01

Studies evaluating the association between statin use and survival outcomes in renal cell carcinoma have demonstrated conflicting results. Our objective was to evaluate this association in a large clinical cohort by using propensity score methods to reduce confounding from measured covariates. We performed a retrospective review of 893 patients undergoing nephrectomy for unilateral, M0 renal cell carcinoma between 2000 and 2014 at a tertiary academic center. Inverse probability of treatment weights were derived from a propensity score model based on clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between statin use and disease-free survival, cancer-specific survival, and overall survival in the sample weighted by the inverse probability of treatment weights. A secondary analysis was performed matching statin users 1:1 to statin nonusers on the propensity score. Of the 893 patients, 259 (29%) were on statins at the time of surgery. Median follow-up was 47 months (interquartile range: 20-80). Statin use was not significantly associated with disease-free survival (hazard ratio [HR] = 1.09, 95% CI: 0.65-1.81), cancer-specific survival (HR = 0.90, 95% CI: 0.40-2.01), or overall survival (HR = 0.89, 95% CI: 0.55-1.44). Similar results were observed when using propensity score matching. The present study found no significant association between statin use and kidney cancer outcomes. Population-based studies are needed to further evaluate the role of statins in kidney cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

The tissue injury and repair in cancer radiotherapy

International Nuclear Information System (INIS)

Matsuzawa, Taiju

1975-01-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed. (author)

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

Science.gov (United States)

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

2015-08-01

Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations.

Science.gov (United States)

Häcker, Axel; Peters, Kristina; Knoll, Thomas; Marlinghaus, Ernst; Alken, Peter; Jenne, Jürgen W; Michel, Maurice Stephan

2006-11-01

To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

Science.gov (United States)

Tan, Hung-Jui; Meyer, Anne-Marie; Kuo, Tzy-Mey; Smith, Angela B; Wheeler, Stephanie B; Carpenter, William R; Nielsen, Matthew E

2015-03-15

Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care. © 2014 American Cancer Society.

Kidney cancer and 2014: is innovation really over?

Science.gov (United States)

Ciccarese, Chiara; Modena, Alessandra; Tortora, Giampaolo; Massari, Francesco

2015-01-01

2014 has been a year of significant innovations on kidney cancer treatments, the most relevant of which will be shown below. In particular, we analyzed the consolidated knowledge regarding the role of surgery in localized and advanced renal cell carcinoma and the targeted therapies already approved for metastatic renal cell carcinoma. Furthermore, we examined the outstanding issues, with particular reference to the choice of the second-line and the role of adjuvant and neoadjuvant treatments. Finally, we outlined the future therapeutic perspectives and those definitely abandoned.

Optical redox imaging indices discriminate human breast cancer from normal tissues

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

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

Science.gov (United States)

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

Less overdiagnosis of kidney cancer? an age-period-cohort analysis of incidence trends in 16 populations worldwide.

Science.gov (United States)

Znaor, Ariana; Laversanne, Mathieu; Bray, Freddie

2017-09-01

The increasing rates of kidney cancer incidence, reported in many populations globally, have been attributed both to increasing exposures to environmental risk factors, as well as increasing levels of incidental diagnosis due to widespread use of imaging. To better understand these trends, we examine long-term cancer registry data worldwide, focusing on the roles of birth cohort and calendar period, proxies for changes in risk factor prevalence and detection practice respectively. We used an augmented version of the Cancer Incidence in Five Continents series to analyze kidney cancer incidence rates 1978-2007 in 16 geographically representative populations worldwide by sex for ages 30-74, using age-period-cohort (APC) analysis. The full APC model provided the best fit to the data in most studied populations. While kidney cancer incidence rates have been increasing in successive generations born from the early twentieth century in most countries, equivalent period-specific rises were observed from the late-1970s, although these have subsequently stabilized in certain European countries (the Czech Republic, Lithuania, Finland, Spain) as well as Japan from the mid-1990s, and from the mid-2000s, in Colombia, Costa Rica and Australia. Our results indicate that the effects of both birth cohort and calendar period contribute to the international kidney cancer incidence trends. While cohort-specific increases may partly reflect the rising trends in obesity prevalence and the need for more effective primary prevention policies, the attenuations in period-specific increases (observed in 8 of the 16 populations) highlight a possible change in imaging practices that could lead to mitigation of overdiagnosis and overtreatment. © 2017 UICC.

Time trend and age-period-cohort effect on kidney cancer mortality in Europe, 1981–2000

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López-Abente Gonzalo

2006-05-01

Full Text Available Abstract Background The incorporation of diagnostic and therapeutic improvements, as well as the different smoking patterns, may have had an influence on the observed variability in renal cancer mortality across Europe. This study examined time trends in kidney cancer mortality in fourteen European countries during the last two decades of the 20th century. Methods Kidney cancer deaths and population estimates for each country during the period 1981–2000 were drawn from the World Health Organization Mortality Database. Age- and period-adjusted mortality rates, as well as annual percentage changes in age-adjusted mortality rates, were calculated for each country and geographical region. Log-linear Poisson models were also fitted to study the effect of age, death period, and birth cohort on kidney cancer mortality rates within each country. Results For men, the overall standardized kidney cancer mortality rates in the eastern, western, and northern European countries were 20, 25, and 53% higher than those for the southern European countries, respectively. However, age-adjusted mortality rates showed a significant annual decrease of -0.7% in the north of Europe, a moderate rise of 0.7% in the west, and substantial increases of 1.4% in the south and 2.0% in the east. This trend was similar among women, but with lower mortality rates. Age-period-cohort models showed three different birth-cohort patterns for both men and women: a decrease in mortality trend for those generations born after 1920 in the Nordic countries, a similar but lagged decline for cohorts born after 1930 in western and southern European countries, and a continuous increase throughout all birth cohorts in eastern Europe. Similar but more heterogeneous regional patterns were observed for period effects. Conclusion Kidney cancer mortality trends in Europe showed a clear north-south pattern, with high rates on a downward trend in the north, intermediate rates on a more marked rising

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

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Schrem, Harald; Schneider, Valentin; Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (pKaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers.

Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

Science.gov (United States)

Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

2017-03-01

Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

Science.gov (United States)

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

2016-10-01

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

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

Science.gov (United States)

Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

2009-07-01

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

Directory of Open Access Journals (Sweden)

Mei-Yueh Lee

Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

Cancer incidence in kidney transplant recipients: a study protocol

OpenAIRE

Pita-Fernandez, Salvador; Valdes-Ca?edo, Francisco; Pertega-Diaz, Sonia; Seoane-Pillado, Maria Teresa; Seijo-Bestilleiro, Rocio

2009-01-01

Abstract Background Different publications show an increased incidence of neoplasms in renal transplant patients. The objective of this study is to determine the incidence of cancer in the recipients of renal transplants performed in the A Coruña Hospital (Spain) during the period 1981–2007. Methods/Design During the study period 1967 kidney transplants were performed, corresponding to 1710 patients. Patients with neoplasms prior to the transplant will be excluded (n = 38). A follow-up study ...

Observation of human tissue with phase-contrast x-ray computed tomography

Science.gov (United States)

Momose, Atsushi; Takeda, Tohoru; Itai, Yuji; Tu, Jinhong; Hirano, Keiichi

1999-05-01

Human tissues obtained from cancerous kidneys fixed in formalin were observed with phase-contrast X-ray computed tomography (CT) using 17.7-keV synchrotron X-rays. By measuring the distributions of the X-ray phase shift caused by samples using an X-ray interferometer, sectional images that map the distribution of the refractive index were reconstructed. Because of the high sensitivity of phase- contrast X-ray CT, a cancerous lesion was differentiated from normal tissue and a variety of other structures were revealed without the need for staining.

Expression of methionine adenosyltransferase 2A in renal cell carcinomas and potential mechanism for kidney carcinogenesis

International Nuclear Information System (INIS)

Wang, Xuliang; Guo, Xiaoqiang; Yu, Wenshui; Li, Cailing; Gui, Yaoting; Cai, Zhiming

2014-01-01

Methionine adenosyltransferase 2A (MAT2A) is an enzyme that catalyzes the formation of S-adenosylmethionine (SAMe) by joining methionine and ATP. SAMe is a methyl donor for transmethylation and has an important role for DNA and/or protein methylation. MAT2A is expressed widely in many tissues especially in kidney. Several studies have demonstrated that there are abnormal expressions of MAT2A in several kinds of cancers such as liver and colon cancers. But the relationship of MAT2A between renal cell carcinomas (RCC) is less understood. The mRNA expression level of the MAT2A gene was determined in 24 RCC patients and 4 RCC cell lines, using real-time quantitative-polymerase chain reaction (RT-PCR). The MAT2A protein content was measured by western blotting and immunohistochemical analysis in 55 RCC patients. The mRNA levels of heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) were also analysized in patients using RT-PCR. The correlations between the MAT2A and HO-1 as well as COX-2 were analyzed with nonparametric Spearman method. MAT2A transcript was significantly downregulated in cancer tissues compared to normal tissues (P < 0.05). Immunohistochemical analysis and western blotting indicated that level of MAT2A protein was decreased in cancer tissues. The statistical analysis reveals a negative correlation between MAT2A and HO-1 expression in RCC patients and cell lines (P < 0.01). This study demonstrated that MAT2A was lower expression in cancer tissues, suggesting that it may be involved in the development of RCC. MAT2A is a transcriptional corepressor for HO-1 expression by supplying SAM for methyltransferases, which may be one of potential mechanism of MAT2A as tumor suppressor in kidney carcinogenesis

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

Science.gov (United States)

Greiman, Alyssa K; Rosoff, James S; Prasad, Sandip M

2017-12-01

To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R 2 = 0.78), prostate (regression coefficient -1.56, R 2 = 0.85), kidney (regression coefficient -1.34, R 2 = 0.74), and bladder cancer (regression coefficient -1.01, R 2 = 0.80). While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

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

NARCIS (Netherlands)

Raaschou-Nielsen, Ole; Pedersen, Marie; Stafoggia, Massimo; Weinmayr, Gudrun; Andersen, Zorana J; Galassi, Claudia; Sommar, Johan; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Krog, Norun H; Aasvang, Gunn Marit; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Fratiglioni, Laura; Sørensen, Mette; Eriksen, Kirsten T; Tjønneland, Anne; Peeters, Petra H; Bueno-de-Mesquita, Bas; Plusquin, Michelle; Key, Timothy J; Jaensch, Andrea; Nagel, Gabriele; Föger, Bernhard; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Migliore, Enrica; Tamayo, Ibon; Amiano, Pilar; Dorronsoro, Miren; Sokhi, Ranjeet; Kooter, Ingeborg; de Hoogh, Kees; Beelen, Rob|info:eu-repo/dai/nl/30483100X; Eeftens, Marloes|info:eu-repo/dai/nl/315028300; Vermeulen, Roel|info:eu-repo/dai/nl/216532620; Vineis, Paolo; Brunekreef, Bert|info:eu-repo/dai/nl/067548180; Hoek, Gerard|info:eu-repo/dai/nl/069553475

2017-01-01

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air

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

DEFF Research Database (Denmark)

Raaschou-Nielsen, Ole; Pedersen, Marie; Stafoggia, Massimo

2017-01-01

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor ai...

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

Directory of Open Access Journals (Sweden)

Thorsten Schlomm

2013-03-01

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

Effect of preoperative neoadjuvant chemotherapy on the expression of malignant molecules in colon cancer tissue and the degree of trauma caused by radical operation

Directory of Open Access Journals (Sweden)

Yan-Cheng Wang

2017-09-01

Full Text Available Objective: To study the effect of preoperative neoadjuvant chemotherapy on the expression of malignant molecules in colon cancer tissue and the degree of trauma caused by radical operation. Methods: Patients who were diagnosed with colon cancer in Fengrun People’s Hospital between March 2014 and February 2017 were selected and randomly divided into the XELOX group who accepted XELOX neoadjuvant chemotherapy combined with radical operation for colon cancer and the control group who accepted radical operation for colon cancer alone. Surgically removed colon cancer tissue was collected to test the expression of proliferation, apoptosis and invasion genes, and serum was collected to detect the contents of liver and kidney function indicators as well as inflammatory factors. Results: Rac1, PLD2, CHD1L, Snail, Vimentin and N-cadherin mRNA expression levels in surgically removed colon cancer lesions of XELOX group were significantly lower than those of control group while MS4A12 and ASPP2 mRNA expression levels were significantly higher than those of control group; serum ALT, AST, β2-MG, Cys-C, sICAM-1, sVCAM-1, sTM and sE-selectin contents were not significantly different between the two groups of patients 1 day and 3 days after surgery. Conclusion: Preoperative neoadjuvant chemotherapy can inhibit the proliferation, apoptosis and invasion gene expression in colon cancer tissues without increasing the trauma of operation.

Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

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Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

EXPERIMENTAL RATIONALE FOR HEMOSTATIC SUTURES DURING RESECTION OF THE KIDNEY FOR ITS TUMOR

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V. M. Popkov

2014-08-01

Full Text Available The investigation deals with the study of the biomechanical properties of renal tissues and the comparison of different hemostatic suture procedures used during resection of the kidney for its tumor. The performed experimental study allows one to recommend that a renal capsule as the organ’s most stable and plastic part must be necessarily inserted into the hemostatic suture on both sides. The elastic modulus (Young’s modulus serves as an integral indicator of the deformation-strength properties of renal tissues, which enables it to be recommended for the wider use in experimental and clinical studies. The proposed modified suture can minimize the number of postoperative bleedings from the renal parenchyma and reduce the time of surgery, thereby improving the results of organ-saving treatment in patients with kidney cancer.

Cytotoxic assessment of silver nanoparticles in embryonic development and kidney tissue in pregnant mice

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Bagher seyedalipour

2015-10-01

Full Text Available Background and Aim: Regarding the widespread use of silver nanoparticles in medecine and lack of a detailed study of toxicity effects of these particles on fetus, this study was carried out to investigate histopathological changes of the kidneys and also embryonic development following exposure to silver nanoparticles. Materials and Methods: In this experimental study, thirty five female NMRI mice were randomly divided into five equal groups i.e. one control group and four experimental groups. The experimental groups intraperitoneally (IP received silver nanoparticles at concentrations of 50, 100, 200 and 400 mg/ kg . .every other day. On the 17th day  of pregnancy, the mice were dissected and  their kidneys and embryos tissues were separated and stained with hematoxylin and eosin for histopathological examinations. .Finally, the obtained data was fed into SPSS software (V:16 using statistical tests including Kolmogrof-Smearnof, one-way variance analysis, Dante, Mann-Whitney and Kruskal-Wallis and P<0.05 was taken as the significant level. Results: Histopathological assessment of kidney tissue following IP administration of silver nanoparticle indicated pathological changes including congestion, necrosis, inflammatory cell infiltration, vacuolar degeneration compared to the control group. Our findings showed that silver nanoparticles during the gestation period affects fetal organogenesis, evolution of neural structure, liver lobulation and fetal growth retardation. Mean number of somites in groups receiving doses of 200 and 400 mg kg, . significantly reduced compared to the control group (P<0.05. Conclusion: The obtained results suggest that  passing of silver nanoparticles through placenta is possible and damage caused by the particles  could lead to the deformity or developmental retardation of the fetus.

The tissue injury and repair in cancer radiotherapy. A concept of tissue architecture and radio sensitivity

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Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1975-06-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed.

The Protective Effects of Vitamins C and E on The Oxidative Stress Induced by Sodium Metabisulfite on The Kidney Tissue in Adult Rats

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Abdolnabi Peyravi

2016-09-01

Full Text Available Background & Objective: Sodium metabisulfite which is used as a food preservative in the food industry, has adverse effects on body organs such as kidney and body grouth rate. In this research we have studied the protective effect of Vitamin C and E as antioxidants, on the kidney tissue damage after the consumption of Sodium metabisulfite. Materials & methods: Forty-eight Adult male Wistar rats of 150-200 grams were divided into 6 groups of 8 each. Rats in the experimental groups received Sodium metabisulfite (520 mg / kg body weight by gavage feeding for 30 consecutive days. Also during this period, the experimental groups 2 and 3 received a daily dose of 100 mg / kg vitamins C and E, Respectively. The experimental group 4 received 50 mg / kg vitamin C plus 50 mg / kg of vitamin E by the same root. Control group received only normal diet and water. The placebo received vehicle (drug solvent as well as normal diet and water. At the end of the exprimental period the body growth rate was measured between the groups. The histhopatological examination was performed on the kidney tissue sections. by light microscope Results: The results showed sodium metabisulfite in daily dietary could lead to the kidney tissue damage and reduced body weight in rats (p <0.05. However, vitamins C and E can reduce the kidney tissue damage and allow a normal growth weight (p <0.05. Conclusion: With this study we could conclude that the antioxidant effect of that vitamins C and E have a protective effect on renal damage induced by sodium metabisulfite consumption

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

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Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

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

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

2016-02-09

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

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

Science.gov (United States)

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Kidney Tests: MedlinePlus Health Topic

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... Spanish Total protein (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Kidney Tests updates ... hour volume Show More Show Less Related Health Topics Kidney Cancer Kidney Diseases National Institutes of Health ...

Application of tissue mesodissection to molecular cancer diagnostics.

Science.gov (United States)

Krizman, David; Adey, Nils; Parry, Robert

2015-02-01

To demonstrate clinical application of a mesodissection platform that was developed to combine advantages of laser-based instrumentation with the speed/ease of manual dissection for automated dissection of tissue off standard glass slides. Genomic analysis for KRAS gene mutation was performed on formalin fixed paraffin embedded (FFPE) cancer patient tissue that was dissected using the mesodissection platform. Selected reaction monitoring proteomic analysis for quantitative Her2 protein expression was performed on FFPE patient tumour tissue dissected by a laser-based instrument and the MilliSect instrument. Genomic analysis demonstrates highly confident detection of KRAS mutation specifically in lung cancer cells and not the surrounding benign, non-tumour tissue. Proteomic analysis demonstrates Her2 quantitative protein expression in breast cancer cells dissected manually, by laser-based instrumentation and by MilliSect instrumentation (mesodissection). Slide-mounted tissue dissection is commonly performed using laser-based instruments or manually scraping tissue by scalpel. Here we demonstrate that the mesodissection platform as performed by the MilliSect instrument for tissue dissection is cost-effective; it functions comparably to laser-based dissection and which can be adopted into a clinical diagnostic workflow. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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Federica Marchesi

2011-12-01

Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

2011-12-28

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

International Nuclear Information System (INIS)

Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2011-01-01

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

Connective tissue: cancer patients’ attitudes towards medical research using excised (tumour) tissue

NARCIS (Netherlands)

Vermeulen, E.; Schmidt, M.K.; Cornel, M.C.; Knoppers, B.M.; van Leeuwen, F.E.; Aaronson, N.K.

2011-01-01

The objective of this article is to explore the views of Dutch cancer patients on the use of excised and stored (tumor) tissues in medical research. Excised tissues are routinely stored in hospitals for future diagnostic use. They are also important for scientific research. This article discusses

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

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Harald Schrem

Full Text Available The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers.1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences.Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21. Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46, post-transplant lymphoproliferative disorder (SIR = 8.36, prostate cancer (SIR = 2.22, bladder cancer (SIR = 3.24, thyroid cancer (SIR = 10.13 and melanoma (SIR = 3.08. Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29, polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD (p = 0.001, HR: 0.68, high body mass index in kg/m2 (p<0.001, HR: 1.04, ADPKD (p = 0.008, HR: 1.26 and diabetic nephropathy (p = 0.004, HR = 1.51. G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05.Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes

Genetic basis of cancer of the kidney: disease-specific approaches to therapy.

Science.gov (United States)

Linehan, W Marston; Vasselli, James; Srinivasan, Ramaprasad; Walther, McClellan M; Merino, Maria; Choyke, Peter; Vocke, Cathy; Schmidt, Laura; Isaacs, Jennifer S; Glenn, Gladys; Toro, Jorge; Zbar, Berton; Bottaro, Donald; Neckers, Len

2004-09-15

Studies during the past two decades have shown that kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in this organ. Clear cell renal carcinoma is characterized by mutation of the VHL gene. The VHL gene product forms a heterotrimeric complex with elongin C, elongin B, and Cul-2 to target hypoxia-inducible factors 1 and 2alpha for ubiquitin-mediated degradation. VHL-/- clear cell renal carcinoma overexpresses epidermal growth factor receptor and transforming growth factor alpha. Both hypoxia-inducible factor 1alpha and the epidermal growth factor receptor are potential therapeutic targets in clear cell renal carcinoma. Studies of the hereditary form of renal cell carcinoma (RCC) associated with hereditary papillary renal carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the gene for HPRC and for a number of sporadic papillary RCCs. The HPRC c-Met mutations are activating mutations in the tyrosine kinase domain of the gene. The gene for a new form of hereditary RCC (Birt Hogg Dubé syndrome) associated with cutaneous tumors, lung cysts, and colon polyps or cancer has recently been identified. Studies are currently under way to determine what type of gene BHD is and how damage to this gene leads to kidney cancer. Individuals affected with hereditary leiomyomatosis renal cell carcinoma are at risk for the development of cutaneous leiomyomas, uterine leiomyomas (fibroids), and type 2 papillary RCC. The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase. Studies are under way to understand the downstream pathway of this cancer gene.

Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS.

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Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili

2014-06-01

Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic profile of kidney tissue samples was observed in the model group and restoration of the profile was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic profiling of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue target metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.

Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study.

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Yi-Long Yang

Full Text Available Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD and the associated psychosocial factors among bladder/kidney cancer patients.A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early-stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates.The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (β sequence, patient's perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01. Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01.The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese medical settings

Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

Science.gov (United States)

Al-Muslet, Nafie A.; Ali, Essam E.

2012-03-01

Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

Science.gov (United States)

Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

2016-08-01

To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Evidence that breast tissue stiffness is associated with risk of breast cancer.

Science.gov (United States)

Boyd, Norman F; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J; Minkin, Salomon

2014-01-01

Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP

Science.gov (United States)

Viana, R. S.; Agasthya, G. A.; Yoriyaz, H.; Kapadia, A. J.

2013-09-01

This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work—32S, 12C, 23Na, 14N, 31P and 39K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in 31P, 39K and 23Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP.

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Viana, R S; Agasthya, G A; Yoriyaz, H; Kapadia, A J

2013-09-07

This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work - (32)S, (12)C, (23)Na, (14)N, (31)P and (39)K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in (31)P, (39)K and (23)Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

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Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

Long non-coding RNA expression profile in cervical cancer tissues

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Zhu, Hua; Chen, Xiangjian; Hu, Yan; Shi, Zhengzheng; Zhou, Qing; Zheng, Jingjie; Wang, Yifeng

2017-01-01

Cervical cancer (CC), one of the most common types of cancer of the female population, presents an enormous challenge in diagnosis and treatment. Long non-coding (lnc)RNAs, non-coding (nc)RNAs with length >200 nucleotides, have been identified to be associated with multiple types of cancer, including CC. This class of nc transcripts serves an important role in tumor suppression and oncogenic signaling pathways. In the present study, the microarray method was used to obtain the expression profile of lncRNAs and protein-coding mRNAs and to compare the expression of lncRNAs between CC tissues and corresponding adjacent non-cancerous tissues in order to screen potential lncRNAs for associations with CC. Overall, 3356 lncRNAs with significantly different expression pattern in CC tissues compared with adjacent non-cancerous tissues were identified, while 1,857 of them were upregulated. These differentially expressed lncRNAs were additionally classified into 5 subgroups. Reverse transcription quantitative polymerase chain reactions were performed to validate the expression pattern of 5 random selected lncRNAs, and 2lncRNAs were identified to have significantly different expression in CC samples compared with adjacent non-cancerous tissues. This finding suggests that those lncRNAs with different expression may serve important roles in the development of CC, and the expression data may provide information for additional study on the involvement of lncRNAs in CC. PMID:28789353

Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

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Yu, Hong; Bao, En-Dong; Zhao, Ru-Qian; Lv, Qiong-Xia

2007-11-01

To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. 24 pigs (mean weight, 20 +/- 1 kg). Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.

Pathway analysis of kidney cancer using proteomics and metabolic profiling

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Fiehn Oliver

2006-11-01

Full Text Available Abstract 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 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 of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

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

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Tatiane Klingelfus

2015-01-01

Full Text Available 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.

Suramin protects from cisplatin-induced acute kidney injury

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Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

CD4 T cell knockout does not protect against kidney injury and worsens cancer.

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Ravichandran, Kameswaran; Wang, Qian; Ozkok, Abdullah; Jani, Alkesh; Li, Howard; He, Zhibin; Ljubanovic, Danica; Weiser-Evans, Mary C; Nemenoff, Raphael A; Edelstein, Charles L

2016-04-01

Most previous studies of cisplatin-induced acute kidney injury (AKI) have been in models of acute, high-dose cisplatin administration that leads to mortality in non-tumor-bearing mice. The aim of the study was to determine whether CD4 T cell knockout protects against AKI and cancer in a clinically relevant model of low-dose cisplatin-induced AKI in mice with cancer. Kidney function, serum neutrophil gelatinase-associated lipocalin (NGAL), acute tubular necrosis (ATN), and tubular apoptosis score were the same in wild-type and CD4 -/- mice with AKI. The lack of protection against AKI in CD4 -/- mice was associated with an increase in extracellular signal-regulated kinase (ERK), p38, CXCL1, and TNF-α, mediators of AKI and fibrosis, in both cisplatin-treated CD4 -/- mice and wild-type mice. The lack of protection was independent of the presence of cancer or not. Tumor size was double, and cisplatin had an impaired therapeutic effect on the tumors in CD4 -/- vs. wild-type mice. Mice depleted of CD4 T cells using the GK1.5 antibody were not protected against AKI and had larger tumors and lesser response to cisplatin. In summary, in a clinically relevant model of cisplatin-induced AKI in mice with cancer, (1) CD4 -/- mice were not protected against AKI; (2) ERK, p38, CXCL1, and TNF-α, known mediators of AKI, and interstitial fibrosis were increased in CD4 -/- kidneys; and (3) CD4 -/- mice had faster tumor growth and an impaired therapeutic effect of cisplatin on the tumors. The data warns against the use of CD4 T cell inhibition to attenuate cisplatin-induced AKI in patients with cancer. A clinically relevant low-dose cisplatin model of AKI in mice with cancer was used. CD4 -/- mice were not functionally or histologically protected against AKI. CD4 -/- mice had faster tumor growth. CD4 -/- mice had an impaired therapeutic effect of cisplatin on the tumors. Mice depleted of CD4 T cells were not protected against AKI and had larger tumors.

Lysyl oxidase‑like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis.

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Choi, Sung-Eun; Jeon, Nara; Choi, Hoon Young; Shin, Jae Il; Jeong, Hyeon Joo; Lim, Beom Jin

2017-09-01

Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.

Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

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Kusaka, M; Okamoto, M; Takenaka, M; Sasaki, H; Fukami, N; Kataoka, K; Ito, T; Kenmochi, T; Hoshinaga, K; Shiroki, R

2017-06-01

Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system. Copyright © 2017 Elsevier Inc. All rights reserved.

Tissue preservation with mass spectroscopic analysis: Implications for cancer diagnostics.

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Hall, O Morgan; Peer, Cody J; Figg, William D

2018-05-17

Surgical intervention is a common treatment modality for localized cancer. Post-operative analysis involves evaluation of surgical margins to assess whether all malignant tissue has been resected because positive surgical margins lead to a greater likelihood of recurrence. Secondary treatments are utilized to minimize the negative effects of positive surgical margins. Recently, in Science Translational Medicine, Zhang et al describe a new mass spectroscopic technique that could potentially decrease the likelihood of positive surgical margins. Their nondestructive in vivo tissue sampling leads to a highly accurate and rapid cancer diagnosis with great precision between healthy and malignant tissue. This new tool has the potential to improve surgical margins and accelerate cancer diagnostics by analyzing biomolecular signatures of various tissues and diseases.

Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

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

2015-01-01

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

Increased technetium-99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism

DEFF Research Database (Denmark)

Enevoldsen, Lotte Hahn; Heaf, James Goya; Højgaard, Liselotte

2017-01-01

In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphata......In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and...... patients diagnosed with secondary hyperparathyroidism admitted for Tc-99 m-HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P-calcium and P-phosphate) taken 0-3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans....../or hyperphosphataemia. As human vascular smooth muscle cells produce hydroxyapatite during cell culture with increased phosphate levels and as Tc-99 m-HDP/MDP primarily binds to hydroxyapatite, we hypothesized that soft tissue accumulation would be found in patients with hyperphosphataemia. We identified 63 CKD...

Limitations of tissue micro array in Duke's B colon cancer

DEFF Research Database (Denmark)

Kjær-Frifeldt, Sanne; Lindebjerg, Jan; Brunner, Nils

2012-01-01

Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular distribu......Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular...

Tissue characterization using magnetic resonance elastography: preliminary results

International Nuclear Information System (INIS)

Kruse, S.A.; Smith, J.A.; Lawrence, A.J.; Dresner, M.A.; Manduca, A.; Greenleaf, J.F.; Ehman, R.L.

2000-01-01

The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for non-invasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves. (author)

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

DEFF Research Database (Denmark)

Baatrup, E; Nielsen, M G; Danscher, G

1987-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl2) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography......, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury......-exposed trout were subjected to selenium (as Na2SeO3), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested...

Tissue inhibitor of metalloproteinases-1 in breast cancer

DEFF Research Database (Denmark)

Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Sørensen, Nanna Møller

2005-01-01

Whether patients diagnosed with primary breast cancer are offered adjuvant systemic therapy following surgical removal of the tumor is based on prognosis. Prognosis is estimated in every patient using established prognostic variables. Unfortunately, when using the currently available prognostic...... parameters a significant proportion of patients are over-treated. Thus, in order to improve stratification of breast cancer patients, additional prognostic factors need to be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the promising candidates for new prognostic markers in breast...... cancer, as a number of studies have demonstrated an association between high tumor-tissue levels of TIMP-1 mRNA as well as TIMP-1 protein and a poor prognosis of breast cancer patients. TIMP-1 is a member of the TIMP family, currently comprising four members (TIMP-1-4), and its main function...

Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

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Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

2013-12-01

Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

Renoscintigraphic integral assessment of kidney functional state at chemotherapy for breast cancer

International Nuclear Information System (INIS)

Kamyins'ka, A.L.; Nyikolov, M.O.; Kovalenko, M.M.; Voronyina, Yi.A.

2009-01-01

The purpose of the work was quantitative integral assessment of functional state of the kidneys at analysis of the results of multi-purpose scintigraphy with phosphate compounds labeled with 99m Tc in patients with breast cancer. The obtained findings suggest significant aggravation of both renoscintigraphy parameters and integral indices irrespective of the type of chemotherapy especially in patients with the history of nephrourological disorders.

Extraintestinal Complications: Kidney Disorders

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... the ureters, bladder, and urethra for the passage, storage, and voiding of urine. Serious kidney complications associated with IBD are rare, ... Proteinuria, an elevated level of protein in the urine, is one sign of amyloidosis. A biopsy (tissue sample) of the kidney can confirm the diagnosis. Various ...

A study on the ultrastructure of the mouse kidney tissues affected by lead (Pb)

International Nuclear Information System (INIS)

Yoo, Chang Kyu; Choe, Rim Soon

1986-01-01

This study was made to investigate the ultrastructural changes of the male mouse(ICR strain) kidney tissue affected by lead(Pb). Pb, as a form of Pb(CH 3 COO) 2 was injected within the peritoneal cavity at the time interval of 24 hrs, 48 hrs and 72 hrs from injection time. In the meantime, electron microscopy was used to investigate the histologic changes occured in control animals, experimental animals. In kidney cells of experimental animals, changes of the nuclear chromatin were little, but cristae of mitochondria presented in cytoplasm was impaired, vacuolation was risen, thoseby many vacuole was formed. Especially, in the case of 5 mg/kg and 10 mg/kg Pb concentration, mitochondrial presented in cytoplasm was considerably deformed. While, with 20 mg/kg of Pb(CH 3 C00) 2 , it was observed that normal structure was presented in the nucleus electrodensity in cytoplasm was decreased mostly, but mitochondrial deform was slightly decreased. (Author)

The bioengineered kidney: science or science fiction?

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Oxburgh, Leif; Carroll, Thomas J

2016-07-01

This article gives an overview of important new advances relating to kidney bioengineering. Directed differentiation studies have shown that proximal tubules, distal tubules, podocytes, collecting ducts, interstitium and endothelial cells can be generated from patient-derived stem cells using standardized protocols. One caveat to the interpretation of these studies is that the physiological characteristics of differentiated cells remain to be defined. Another important area of progress is scaffolding. Both decellularized organs and polymeric materials are being used as platforms for three-dimensional growth of kidney tissue, and key distinctions between these approaches are discussed. In the past 3 years, it has become clear that building kidney tissue is feasible. The laboratory-grown kidney is an attainable goal if efforts are focused on refining directed differentiation procedures to optimize cell function and on developing scaffolding strategies that ensure physiological function at the tissue level.

¹H NMR-based metabolic profiling of human rectal cancer tissue

Science.gov (United States)

2013-01-01

Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

Study of Fe, Zn, Cu, Cd, Pb concentrations in liver, kidney and muscle tissue of cow and sheep marketed in Hamedan in 2011

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S Sobhanardakani

2012-11-01

Full Text Available Importance of heavy metals in food safety and detrimental effects of their high concentrations in food stuff is well documented. In this study, concentrations of Fe, Zn, Cu, Cd and Pb in kidney, liver and muscle tissues of cow and sheep at Hamedan retails were evaluated. A total number of 180 samples was assessed for the amount of heavy metals as ppb in wet weight. For this, wet-digestion method was used to determine the concentration of given elements by ICP (Varian ES-710. Results showed that the highest concentration of heavy metals was determined in the liver and kidney samples, while the lowest concentration was found in muscle tissue. Among the heavy metals, Fe in cow’s liver had the highest concentration (25507±879 ppb and Cd in muscle tissue of sheep has the lowest concentration (192±54 ppb. In overall, accumulation of heavy metals in tissues of cows was higher than sheep. Statistical comparison of accumulated metals concentration in various tissues of these two animal groups showed significant difference (P

Tissue metabolic profiling of human gastric cancer assessed by 1H NMR

International Nuclear Information System (INIS)

Wang, Huijuan; Zhang, Hailong; Deng, Pengchi; Liu, Chunqi; Li, Dandan; Jie, Hui; Zhang, Hu; Zhou, Zongguang; Zhao, Ying-Lan

2016-01-01

Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on 1 H nuclear magnetic resonance ( 1 H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping

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

Directory of Open Access Journals (Sweden)

Oluwafemi O. Oguntibeju

2016-01-01

Full Text Available 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.

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

Energy Technology Data Exchange (ETDEWEB)

Naga Raju, G.J. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); John Charles, M. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Bhuloka Reddy, S. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India)]. E-mail: sbr_r@yahoo.com; Sarita, P. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Seetharami Reddy, B. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Rama Lakshmi, P.V.B. [Pathology Department, Andhra Medical College, Visakhapatnam 530 002 (India); Vijayan, V. [Institute of Physics, Sachivalaya Marg, Bhubaneswar 751 001 (India)

2005-04-01

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

Breast cancer screening in Korean woman with dense breast tissue

International Nuclear Information System (INIS)

Shin, Hee Jung; Ko, Eun Sook; Yi, Ann

2015-01-01

Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results

Breast cancer screening in Korean woman with dense breast tissue

Energy Technology Data Exchange (ETDEWEB)

Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

2015-11-15

Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

High-intensity focused ultrasound for ex vivo kidney tissue ablation: influence of generator power and pulse duration.

Science.gov (United States)

Häcker, Axel; Köhrmann, Kai Uwe; Knoll, Thomas; Langbein, Sigrun; Steidler, Annette; Kraut, Oliver; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2004-11-01

The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size. The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds. The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power. This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.

Human tissue models in cancer research: looking beyond the mouse.

Science.gov (United States)

Jackson, Samuel J; Thomas, Gareth J

2017-08-01

Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

International Nuclear Information System (INIS)

Baatrup, E.; Nielsen, M.G.; Danscher, G.

1986-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl 2 ) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury-exposed trout were subjected to selenium (as Na 2 SeO 3 ), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested that the mercury visualized prior to selenium treatment represents inorganic mercury, while additional mercury visualized after selenium administration represents an organic form

DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

International Nuclear Information System (INIS)

Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

2006-01-01

Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

Energy Technology Data Exchange (ETDEWEB)

Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

2006-12-01

Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

Microfluidic extraction and microarray detection of biomarkers from cancer tissue slides

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Nguyen, H. T.; Dupont, L. N.; Jean, A. M.; Géhin, T.; Chevolot, Y.; Laurenceau, E.; Gijs, M. A. M.

2018-03-01

We report here a new microfluidic method allowing for the quantification of human epidermal growth factor receptor 2 (HER2) expression levels from formalin-fixed breast cancer tissues. After partial extraction of proteins from the tissue slide, the extract is routed to an antibody (Ab) microarray for HER2 titration by fluorescence. Then the HER2-expressing cell area is evaluated by immunofluorescence (IF) staining of the tissue slide and used to normalize the fluorescent HER2 signal measured from the Ab microarray. The number of HER2 gene copies measured by fluorescence in situ hybridization (FISH) on an adjacent tissue slide is concordant with the normalized HER2 expression signal. This work is the first study implementing biomarker extraction and detection from cancer tissue slides using microfluidics in combination with a microarray system, paving the way for further developments towards multiplex and precise quantification of cancer biomarkers.

Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

International Nuclear Information System (INIS)

Datta, Antara; Adelson, Martin E; Mogilevkin, Yakov; Mordechai, Eli; Sidi, Abraham A; Trama, Jason P

2011-01-01

Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test. We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals. The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK. Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic test for bladder cancer

Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue

DEFF Research Database (Denmark)

Usher, Pernille Autzen; Sieuwerts, A.M.; Bartels, Annette

2007-01-01

TIMP-1 is a promising new candidate as a prognostic marker in colorectal and breast cancer. We now describe the discovery of two alternatively spliced variants of TIMP-1 mRNA. The two variants lacking exon 2 (del-2) and 5 (del-5), respectively, were identified in human cancer cell lines by RT......-PCR. The del-2 variant was, furthermore, detected in extracts from 12 colorectal cancer tissue samples. By western blotting additional bands of lower molecular mass than full-length TIMP-1 were identified in tumor tissue, but not in plasma samples obtained from cancer patients. The two splice variants of TIMP...

The role of adipose tissue in cancer-associated cachexia.

Science.gov (United States)

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

Cancer - renal pelvis or ureter

Science.gov (United States)

... ureter; Kidney cancer - renal pelvis; Ureter cancer Images Kidney anatomy References National Cancer Institute website. Transitional cell cancer (kidney/ureter) treatment (PDQ) - health professional version. www.cancer. ...

Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

International Nuclear Information System (INIS)

Khlifi, Rim; Olmedo, Pablo; Gil, Fernando; Hammami, Bouthaina; Chakroun, Amine; Rebai, Ahmed; Hamza-Chaffai, Amel

2013-01-01

Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues. ► Heavy metal exposure via occupational exposures may increase the risk of HNC

Trace element load in cancer and normal lung tissue

International Nuclear Information System (INIS)

Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

1999-01-01

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

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

Science.gov (United States)

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...

Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

Science.gov (United States)

Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

2014-05-01

The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin- embedded breast cancer tissues.

Science.gov (United States)

Kalkan, Ahmet; Ozdarendeli, Aykut; Bulut, Yasemin; Yekeler, Hayrettin; Cobanoglu, Bengu; Doymaz, Mehmet Z

2005-01-01

To investigate etiological role of Epstein-Barr virus (EBV) DNA in breast cancer. The presence of EBV DNA in 57 breast cancer tissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular (n=28), lobular (n=20) and other miscellaneous carcinomas (n=9). Tissues from normal breasts and patients with various benign breast diseases (n=55): fibrocystic disease (n=34), fibroadenoma (n=16), hyperplasia, and granulomatous mastitis (n=5), were used as control samples. EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4 lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant (p>0.05). The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies. Copyright (c) 2005 S. Karger AG, Basel.

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

Directory of Open Access Journals (Sweden)

Kevin Tong

2017-12-01

Full Text Available Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2, stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

Science.gov (United States)

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. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Kidney cancer

International Nuclear Information System (INIS)

Rajer, M.

2007-01-01

The purpose of this paper is to present the epidemiology, diagnostic workup and treatment of renal cell carcinoma (RCC) with an emphasis on the Slovenian epidemiological data. RCC represents 2% of all cancers and is the third most common genitourinary tract tumour. It most frequently occurs among people of ages, between 50 and 60 years. Male patients are more prone to it than female. A number of environmental, occupational and genetic factors have been found to be associated with the development of RCC. Patients often have nonspecific symptoms and this is the reason why for half of them the disease is already metastatic when diagnosed. The most common sites of metastases are lungs (75%), followed by soft tissues (36%), bones (20%), liver (18%), skin (8%) and central nerve system (8%). In the evaluation of RCC multiple diagnostic procedures are needed with obligatory image diagnostics. Radical nephrectomy is still the mainstream treatment of localized disease. Nephron sparing techniques have been used in cases, where radical operation would result in an anephric patient. Efficient adjuvant therapy has not been discovered yet. Until recently interpherone and interleukin were the only known effective treatments for metastatic disease, but now new and more efficient biologic agents are being discovered. The most important prognostic factor for survival is stage at the beginning of treatment. The 5-year survival rate is 95% for patients with stage I disease, 88% for stage II, 59% for stage III and 20% for stage IV. (author)

Distinction of gastric cancer tissue based on surface-enhanced Raman spectroscopy

Science.gov (United States)

Ma, Jun; Zhou, Hanjing; Gong, Longjing; Liu, Shu; Zhou, Zhenghua; Mao, Weizheng; Zheng, Rong-er

2012-12-01

Gastric cancer is one of the most common malignant tumors with high recurrence rate and mortality rate in China. This study aimed to evaluate the diagnostic capability of Surface-enhanced Raman spectroscopy (SERS) based on gold colloids for distinguishing gastric tissues. Gold colloids were directly mixed with the supernatant of homogenized tissues to heighten the Raman signal of various biomolecule. A total of 56 samples were collected from normal (30) and cancer (26). Raman spectra were obtained with a 785nm excitation in the range of 600-1800 cm-1. Significant spectral differences in SERS mainly belong to nucleic acid, proteins and lipids, particularly in the range of 653, 726, 828, 963, 1004, 1032, 1088, 1130, 1243, 1369, 1474, 1596, 1723 cm-1. PCA-LDA algorithms with leave-one-patient-out cross validation yielded diagnostic sensitivities of 90% (27/30), specificities of 88.5% (23/26), and accuracy of 89.3% (50/56), for classification of normal and cancer tissues. The receiver operating characteristic (ROC) surface is 0.917, illustrating the diagnostic utility of SERS together with PCA-LDA to identify gastric cancer from normal tissue. This work demonstrated the SERS techniques can be useful for gastric cancer detection, and it is also a potential technique for accurately identifying cancerous tumor, which is of considerable clinical importance to real-time diagnosis.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

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Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

2015-08-07

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

International Nuclear Information System (INIS)

Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

2015-01-01

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

Human tissue models in cancer research: looking beyond the mouse

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Samuel J. Jackson

2017-08-01

Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

Tissue Specific Promoters in Colorectal Cancer

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A. R. Rama

2015-01-01

Full Text Available 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.

Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope.

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Wang, Ye; He, Honghui; Chang, Jintao; Zeng, Nan; Liu, Shaoxiong; Li, Migao; Ma, Hui

2015-12-01

Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

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Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2016-10-01

Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

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

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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.

The assay of estrogen receptors in three components of human breast cancer tissue

International Nuclear Information System (INIS)

Lu Hanping; Gui Zhining

1992-01-01

The binding capacities of estrogen receptors in nuclear matrix, nuclei and cytosol of human breast cancer tissue (EmR, EnR, EcR) were estimated with radioligand binding assay of receptors. The average B max values of these components in 21 breast cancer specimens are 417.54 ± 170.95, 147.75 ± 98.32, 7.34 ± 5.33 fmol/mg protein, and those in 10 normal breast tissue specimens are 42.33 ± 8.49, 25.05 ± 7.81, 5.91 ± 2.28 fmol/mg protein. Comparing the cancer and normal breast tissues, there is significant difference in B max values of EmR and EnR (P max values of EcR (P > 0.10). The EmR/EnR value of 21 breast cancer tissue is 0.65 ± 0.10, and that of 10 normal breast tissue is 0.42 ± 0.04. There is statistical difference between the cancer and normal. 10 of 13 (77%) patients, who are EcR-positive, have higher EmR/EnR values (≥0.50). The results suggest that estrogen receptors are mainly located at the nuclear matrix, ER levels in nucleus, especially in nuclear matrix of breast cancer tissue are valuable parameters and may be useful for predicting whether the patient will be responsible to endocrine therapy

Kidney and innate immunity.

Science.gov (United States)

Wang, Ying-Hui; Zhang, Yu-Gen

2017-03-01

Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Migration assay on primary culture isolated from patient's primary breast cancer tissue

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ED Yuliana

2014-12-01

Full Text Available Background: Migration is an essential component of breast cancer metastasis, which studyhas been concentrated on culture of established breast cancer cell lines that do not accuratelyrepresent the sophistication and heterogeneity of patient's breast cancer. An attempt toperform migration assay using Boyden Chamber Assay (BCA on primary culture originatingfrom patient's breast cancer tissue was developed to accommodate upcoming study of breastcancer migration in lndonesian patients.Methods: Pathologically proven primary breast cancer tissue samples were obtained fromCiptomangunkusumo Hospital during core (n=4 and incisional (n=3 biopsies of stage llAup to stage lllA breast cancer patients. Following biopsy, the breast cancer tissue samplesunderwent processings to isolate the cancer cells. These cancer cells were -then resuspendedwithin Dulbecco's modified Eagle's medium (DMEM ahd cultured in 12-well plate. The growthof primary culture were observed and compared between the core biopsy and the incisionalbiopsy specimens. Optimization of BCA method was later performed to investigate themigration of the breast cancer primary culture towards different experirnental conditions, whichwere control, Fetal Bovine Serum (FBS, and Stromal Derived Factor-l (SDF-1. Two differentnumber of breast cancer cells were tested for the optimization of the BCA, which were 1 x 105and3x105cells.Results: None of the culture performed on core biopsy specimens grew, while one out ofthree incisional biopsy specimens grew until confluence. The one primary culture that grewwas later assesed using BCA to assess its migration index towards different experimentalconditions. Using 1 x 10s breast cancer cells in the BCA , the result of the absorbance level ofmigrated cells showed that the migration towards SDF-1 (0.529 nearly doubled the migrationtowards controlmedium (0.239 and FBS (0.209. Meanwhile, the absorbance levelwas simiiarbetween the control medium (1.050, FBS (1 .103

Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

Science.gov (United States)

Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

2017-01-01

The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

The aluminium content of breast tissue taken from women with breast cancer.

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House, Emily; Polwart, Anthony; Darbre, Philippa; Barr, Lester; Metaxas, George; Exley, Christopher

2013-10-01

The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content

Effect of tissue and plasma factors on kidney proliferation.

Science.gov (United States)

Inda, A M; García, A L; Errecalde, A L; Badrán, A F

1997-04-01

Liver extract, plasma from intact mice, ES2 tumour extract and plasma from tumour bearing mice has an inhibiting effect on the mitotic activity of hepatocytes and duodenal enterocytes. In the present experiments, the effect of these treatments on the mitotic activity of renal tubular cells was studied. C3HS 28 day-old male mice, standardized for periodicity analysis were used. The determination of normal mitotic circadian curve of the renocytes was done. A second batch of mice were injected with 0.01 ml/gr of either liver extract, plasma from intact mice, ES2 tumour extract or plasma from tumour bearing mice, at 16:00 hours and controlled at 08:00, 12:00 and 16:00 hs during 2 consecutive days post treatment. Colchicine (2 micrograms/gr) was injected 4 hours before killing. Kidneys were processed for histology and mitotic index determinations. Results were expressed as colchicine metaphases per 1000 nuclei, and showed that mitotic activity values of treated animals were significantly lower than those of controls. In conclusion, mitotic activity inhibition of renocytes may be due to some non specific plasmatic and/or tissue factors.

Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

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Ai-Di Zhang

2013-01-01

Full Text Available With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases.

Concentration of gadolinium-diethylene triamine pentaacetic acid in human kidney

International Nuclear Information System (INIS)

Takeda, Masayuki; Katayama, Yasushi; Tsutsui, Toshiki; Komeyama, Takeshi; Mizusawa, Takaki; Tanikawa, Toshiki; Sato, Shotaro

1993-01-01

Although gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging, it is known that contrast enhancement effect disappears if the concentration of Gd-DTPA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic magnetic resonance imaging (MRI) in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA, and the signal intensity of MRI is the solution of several concentrations of Gd-DTPA was measured. In using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 μmol/g under saturation recovery sequences (flip angle was 60deg or 90deg). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 μmol/g under spin echo or gradient-echo sequences. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 μmol/g tissue at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight in 7 patients with adrenal tumor or renal cell cancer, and 1 patient with both urinary bladder cancer and prostatic cancer. Seven of them showed normal renal function and the other had renal insufficiency (GFR 25 ml/min/1.48 m 2 ). Gd-DTPA concentrations of renal medulla and renal cell cancer tissue were 0.123 and 0.108 μmol/g tissue, respectively, at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight. These results suggest that the signal intensity of renal cortex, renal medulla, and renal cell cancer tissue may linearly correlate with Gd-DTPA concentration of tissues at 5 min after intravenous injection of Gd-DTPA 0.5 mmol/kg body weight. (author)

Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney

International Nuclear Information System (INIS)

Castilho, Marcus S; Jacinto, Alexandre A; Viani, Gustavo A; Campana, Andre; Carvalho, Juliana; Ferrigno, Robson; Novaes, Paulo ERS; Fogaroli, Ricardo C; Salvajoli, Joao V

2006-01-01

Pelvic Radiotherapy (RT) as a postoperative treatment for endometrial cancer improves local regional control. Brachytherapy also improves vaginal control. Both treatments imply significant side effects that a fine RT technique can help avoiding. Intensity Modulated RT (IMRT) enables the treatment of the target volume while protecting normal tissue. It therefore reduces the incidence and severity of side effects. We report on a 50 year-old patient with a serous-papiliferous adenocarcinoma of the uterus who was submitted to surgical treatment without lymph node sampling followed by Brachytherapy, and Chemotherapy. The patient had a pelvic kidney, and was therefore treated with IMRT. So far, the patient has been free from relapse and with normal kidney function. IMRT is a valid technique to prevent the kidney from radiation damage

Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Khlifi, Rim, E-mail: rimkhlifi@yahoo.fr [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia); Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Olmedo, Pablo; Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada (Spain); Hammami, Bouthaina; Chakroun, Amine [Department of Otorhinolaryngology, HUC Habib Borguiba Hospital, Sfax (Tunisia); Rebai, Ahmed [Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Hamza-Chaffai, Amel [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia)

2013-05-01

Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p < 0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p < 0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (< 40, 51–60 and > 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues

ERC/mesothelin is expressed in human gastric cancer tissues and cell lines.

Science.gov (United States)

Ito, Tomoaki; Kajino, Kazunori; Abe, Masaaki; Sato, Koichi; Maekawa, Hiroshi; Sakurada, Mutsumi; Orita, Hajime; Wada, Ryo; Kajiyama, Yoshiaki; Hino, Okio

2014-01-01

ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

Robust multi-tissue gene panel for cancer detection

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Talantov Dmitri

2010-06-01

Full Text Available Abstract Background We have identified a set of genes whose relative mRNA expression levels in various solid tumors can be used to robustly distinguish cancer from matching normal tissue. Our current feature set consists of 113 gene probes for 104 unique genes, originally identified as differentially expressed in solid primary tumors in microarray data on Affymetrix HG-U133A platform in five tissue types: breast, colon, lung, prostate and ovary. For each dataset, we first identified a set of genes significantly differentially expressed in tumor vs. normal tissue at p-value = 0.05 using an experimentally derived error model. Our common cancer gene panel is the intersection of these sets of significantly dysregulated genes and can distinguish tumors from normal tissue on all these five tissue types. Methods Frozen tumor specimens were obtained from two commercial vendors Clinomics (Pittsfield, MA and Asterand (Detroit, MI. Biotinylated targets were prepared using published methods (Affymetrix, CA and hybridized to Affymetrix U133A GeneChips (Affymetrix, CA. Expression values for each gene were calculated using Affymetrix GeneChip analysis software MAS 5.0. We then used a software package called Genes@Work for differential expression discovery, and SVM light linear kernel for building classification models. Results We validate the predictability of this gene list on several publicly available data sets generated on the same platform. Of note, when analysing the lung cancer data set of Spira et al, using an SVM linear kernel classifier, our gene panel had 94.7% leave-one-out accuracy compared to 87.8% using the gene panel in the original paper. In addition, we performed high-throughput validation on the Dana Farber Cancer Institute GCOD database and several GEO datasets. Conclusions Our result showed the potential for this panel as a robust classification tool for multiple tumor types on the Affymetrix platform, as well as other whole genome arrays

Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening.

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Han, Guangchun; Zhao, Wei; Song, Xiaofeng; Kwok-Shing Ng, Patrick; Karam, Jose A; Jonasch, Eric; Mills, Gordon B; Zhao, Zhongming; Ding, Zhiyong; Jia, Peilin

2017-10-03

In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early-stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data. Through pan-cancer screening, we found that many protein biomarkers were prognostic for patients' survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These

Up-regulation of ALG-2 in hepatomas and lung cancer tissue

DEFF Research Database (Denmark)

la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

2003-01-01

, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

Science.gov (United States)

Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

2014-12-21

Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

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Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

2016-02-01

ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

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Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

2018-04-01

The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

Image-guided urologic surgery: intraoperative optical imaging and tissue interrogation (Conference Presentation)

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Liao, Joseph C.

2017-02-01

Emerging optical imaging technologies can be integrated in the operating room environment during minimally invasive and open urologic surgery, including oncologic surgery of the bladder, prostate, and kidney. These technologies include macroscopic fluorescence imaging that provides contrast enhancement between normal and diseased tissue and microscopic imaging that provides tissue characterization. Optical imaging technologies that have reached the clinical arena in urologic surgery are reviewed, including photodynamic diagnosis, near infrared fluorescence imaging, optical coherence tomography, and confocal laser endomicroscopy. Molecular imaging represents an exciting future arena in conjugating cancer-specific contrast agents to fluorophores to improve the specificity of disease detection. Ongoing efforts are underway to translate optimal targeting agents and imaging modalities, with the goal to improve cancer-specific and functional outcomes.

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

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Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

Prostate tissue metal levels and prostate cancer recurrence in smokers.

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Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

2014-02-01

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

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Lichtenberg, Shelly; Rahamimov, Ruth; Green, Hefziba; Fox, Benjamin D; Mor, Eytan; Gafter, Uzi; Chagnac, Avry; Rozen-Zvi, Benaya

2017-07-01

Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Distribution of Human papilloma virus genotypes in cervical cancer tissues

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Stamenković M.

2014-01-01

Full Text Available Cervical cancer incidence and mortality rates in Serbia are among the highest in Europe and data on Human papilloma virus (HPV type distribution are scarce. The aim of this study was to determine the prevalence of HPV types in archival specimens of cervical cancer tissues of women in the Serbian population. A total of 45 paraffin-embedded tissue samples of cervical carcinoma were used in this study. The procedure included deparaffinization of tissue samples, DNA extraction, PCR, gel electrophoresis and HPV genotyping by direct sequencing. HPV was detected in 32 samples (71%. Genotyping revealed the presence of 6 high-risk HPV types 16, 18, 33, 45, 53 and 58, where HPV type 16 was the most prevalent type (73.7%. The results of this study and further studies will provide more detailed information about HPV genotype distribution and may contribute to the formulation of national guidelines for the prevention of cervical cancer. [175073

Laparoscopic resection aided by preoperative 3-D CT angiography for rectosigmoid colon cancer associated with a horseshoe kidney: A case report.

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Maeda, Yoshiaki; Shinohara, Toshiki; Nagatsu, Akihisa; Futakawa, Noriaki; Hamada, Tomonori

2014-11-01

We herein report a case of laparoscopic high anterior resection with D3 lymph node dissection for rectosigmoid colon cancer with a horseshoe kidney. A 65-year-old Japanese man referred to our hospital for rectosigmoid colon cancer was found to have a horseshoe kidney on a CT scan. On 3-D CT angiography, an aberrant renal artery was visualized feeding the renal isthmus that arises from the aorta just below the root of the inferior mesenteric artery (IMA). Laparoscopic anterior rectal resection with D3 lymph node dissection was performed. During the operation, the IMA, left ureter, left gonadal vessels and hypogastric nerve plexus could be seen passing over the horseshoe kidney isthmus. With the aid of preoperative 3-D CT angiography, the root of the IMA was identified on the temporal side of the isthmus and divided safely just above the hypogastric nerve. As a horseshoe kidney is often accompanied by aberrant renal arteries and/or abnormal running of the ureter, 3-D CT angiography is useful for determining the location of these structures and avoiding intraoperative injury. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Complex pattern of colon cancer recurrence including a kidney metastasis: A case report

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Waleczek, Helfried; Wente, Moritz N; Kozianka, Jürgen

2005-01-01

We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancrea-toduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colo...

Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer.

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Bakalova, Rumiana; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

2013-05-01

The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. ©2013 AACR.

Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues.

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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 PointsExercise can induce increases in HSP70 in

Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

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Wenyan Hu

Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

Peroxisome proliferator-activated receptor α (PPARα mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

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Kurokawa Tsuyoshi

2011-12-01

Full Text Available Abstract Background Peroxisome proliferator-activated receptor α (PPARα regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer. Methods The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system. Results The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections. Conclusion The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.

Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease

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Yi-Wen Wang

2017-04-01

Full Text Available Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD. However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM, a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height2. An LTI of less than 10% of the normal value (low LTI indicates muscle wasting. Patients with low LTI (n = 40 tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.

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

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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.

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

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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.

Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.

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Danuta Martuszewska

Full Text Available The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4 are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC, as well as probed the biological function of Tensin3.Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001. Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration.Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary

Modeling Kidney Disease with iPS Cells

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Freedman, Benjamin S.

2015-01-01

Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and ‘disease in a dish’ laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field. PMID:26740740

Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

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Shiro Koizume

2015-01-01

Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

Intensity Modulated Radiotherapy (IMRT in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney

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Novaes Paulo ERS

2006-11-01

Full Text Available Abstract Background Pelvic Radiotherapy (RT as a postoperative treatment for endometrial cancer improves local regional control. Brachytherapy also improves vaginal control. Both treatments imply significant side effects that a fine RT technique can help avoiding. Intensity Modulated RT (IMRT enables the treatment of the target volume while protecting normal tissue. It therefore reduces the incidence and severity of side effects. Case We report on a 50 year-old patient with a serous-papiliferous adenocarcinoma of the uterus who was submitted to surgical treatment without lymph node sampling followed by Brachytherapy, and Chemotherapy. The patient had a pelvic kidney, and was therefore treated with IMRT. So far, the patient has been free from relapse and with normal kidney function. Conclusion IMRT is a valid technique to prevent the kidney from radiation damage.

Tissue Distribution Of Chloroaluminium Sulfonated Phthalocyanine In Dogs

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M. M.; H. C.; Newman

1989-06-01

Chloroaluminum sulfonated phthalocyanine (A1PCS) was administered intravenously to clinically normal dogs, and A1PCS levels were determined in tissues using a sensitive assay. A1PCS accumulated to high levels in liver, spleen, bone marrow, kidney, and lung. These tissue levels confirm previous determinations in mice and rats. Only a small amount of dye was retained in skin and very small amounts in muscle and brain. A1PCS was cleared from the blood within 24 h, and excreted primarily by urine. Serum clearance was faster in males than in females. There were also significant tissue distribution differences between the genders, particularly during the first 12 h. The low levels of A1PCS in skin suggest that cutaneous photosensitivity and toxic skin reactions using this photosensitizer in photodynamic therapy of cancer may be eliminated. The difference in tissue distribution between genders is not only intriguing, but indicates that the optimal time window for treatment of various tissue sites may vary by gender.

Methanolic effect of Clerodendrum myricoides root extract on blood, liver and kidney tissues of mice.

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Hayelom, K; Mekbeb, A; Eyasu, M; Wondwossen, E; Kelbesa, U

2012-12-01

The present study deals with the toxicological investigations of chronic treatment with methanol root extract of Clerodendrum myricoides on body weight, hematological and biochemical parameters, and liver and kidney tissue sections. Mice treated with 100mg/kg bw/day of methanol extract showed no behavioral changes. However, there was a general reduction of activity in mice treated with 400mg/kg bw/day methanol extract and LD50 treated mice showed hypoactivity, grooming, prostration, piloroerection and irritation during administration towards the last days of the treatment period. The body weight gain difference in the 100mg/kg bw/day methanol extract treated group was not significant, while those of the others were significant as compared with the controls. Hematological results for the RBC count, HCT, MCV, MCH and MCHC in methanol extract treated mice showed no significant changes at both doses of treatments as compared with the controls. However, the value of lymphocytes was found significantly increased at 100 and 400mg/kg bw/day methanol extract. Similarly, HGB was significantly increased at 100 and 400mg/kg bw/day of methanol extract treated groups. On the other hand, WBC and platelets count were significantly decreased after treatment with 400mg/kg bw/day methanol extract. ALT, ALP, AST and urea values were significantly increased respectively at 100mg/kg bw/day and 400mg/kg bw/day methanol extract. Several histopathological changes of liver and kidney were observed in the extract treated mice as compared to the controls. Such histopathological changes observed in both liver and kidneys were inflammations and hydropic degenerations of hepatocytes at both doses of methanol. In addition, in the LD50 treated mice of the extracts there were also hemorrhages and signs in congestion of glomeruli of the kidney. chronic treatment with Clerodendrum myricoides extracts in mice causes reduction in body weight gain, damage to liver & kidney and changes in some

Hyperspectral Imaging and SPA-LDA Quantitative Analysis for Detection of Colon Cancer Tissue

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Yuan, X.; Zhang, D.; Wang, Ch.; Dai, B.; Zhao, M.; Li, B.

2018-05-01

Hyperspectral imaging (HSI) has been demonstrated to provide a rapid, precise, and noninvasive method for cancer detection. However, because HSI contains many data, quantitative analysis is often necessary to distill information useful for distinguishing cancerous from normal tissue. To demonstrate that HSI with our proposed algorithm can make this distinction, we built a Vis-NIR HSI setup and made many spectral images of colon tissues, and then used a successive projection algorithm (SPA) to analyze the hyperspectral image data of the tissues. This was used to build an identification model based on linear discrimination analysis (LDA) using the relative reflectance values of the effective wavelengths. Other tissues were used as a prediction set to verify the reliability of the identification model. The results suggest that Vis-NIR hyperspectral images, together with the spectroscopic classification method, provide a new approach for reliable and safe diagnosis of colon cancer and could lead to advances in cancer diagnosis generally.

Growing indications for CEUS: The kidney, testis, lymph nodes, thyroid, prostate, and small bowel

International Nuclear Information System (INIS)

Cantisani, V.; Bertolotto, M.; Weskott, H.P.; Romanini, L.; Grazhdani, H.; Passamonti, M.; Drudi, F.M.; Malpassini, F.; Isidori, A.; Meloni, F.M.; Calliada, F.; D’Ambrosio, F.

2015-01-01

Highlights: • Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications. • There is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. • Updated knowledge for proper use of CEUS in uncommon fields is provided. - Abstract: Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications as well, so that nearly all organs have been investigated. Among them, there is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. The possibility to differentiate benign from malignant nodes in cancer patients has been investigated. A new application is in the detection of sentinel nodes after intradermal microbubble injection. The need to distinguish thyroid nodules eligible for fine needle aspiration cytology has led to the use of CEUS in thyroid examinations as well. The potential of CEUS for prostate cancer detection has been extensively investigated, with encouraging initial results. Early promise, however, has not been fulfilled. New perspective regards evaluation of the extent of prostate tissue devascularization following ablative treatments

Growing indications for CEUS: The kidney, testis, lymph nodes, thyroid, prostate, and small bowel

Energy Technology Data Exchange (ETDEWEB)

Cantisani, V., E-mail: vito.cantisani@uniroma1.it [Department of Radiology, Anatomopathology and Oncology, “Sapienza” University of Rome (Italy); Bertolotto, M. [Department of Radiology, University of Trieste (Italy); Weskott, H.P. [Central Ultrasound Department, Klinikum Siloah , Hannover (Germany); Romanini, L. [University Hospital of Pavia (Italy); Grazhdani, H. [Department of Radiology, Anatomopathology and Oncology, “Sapienza” University of Rome (Italy); Passamonti, M. [Dipartimento di Scienze Radiologiche, Ospedale di Lodi (Italy); Drudi, F.M.; Malpassini, F. [Department of Radiology, Anatomopathology and Oncology, “Sapienza” University of Rome (Italy); Isidori, A. [Department of Experimental Medicine, “Sapienza” University of Rome, Rome (Italy); Meloni, F.M. [Dipartimento servizi diagnostici, Ospedale Valduce, Como (Italy); Calliada, F. [University Hospital of Pavia (Italy); D’Ambrosio, F. [Department of Radiology, Anatomopathology and Oncology, “Sapienza” University of Rome (Italy)

2015-09-15

Highlights: • Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications. • There is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. • Updated knowledge for proper use of CEUS in uncommon fields is provided. - Abstract: Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications as well, so that nearly all organs have been investigated. Among them, there is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. The possibility to differentiate benign from malignant nodes in cancer patients has been investigated. A new application is in the detection of sentinel nodes after intradermal microbubble injection. The need to distinguish thyroid nodules eligible for fine needle aspiration cytology has led to the use of CEUS in thyroid examinations as well. The potential of CEUS for prostate cancer detection has been extensively investigated, with encouraging initial results. Early promise, however, has not been fulfilled. New perspective regards evaluation of the extent of prostate tissue devascularization following ablative treatments.

MFDFA and Lacunarity Analysis of Synthetic Multifractals and Pre-Cancerous Tissues

Science.gov (United States)

Roy, A.; Das, N.; Ghosh, N.

2017-12-01

Multifractal Detrended Fluctuation Analysis (MFDFA) has been employed for evaluating complex variations in the refractive index (RI) of human pre-cancerous tissues. While this was primarily aimed towards the early diagnosis of cancer in the human cervix, question remains whether multifractal analysis alone can be conclusively used for distinguishing between various grades of pre-cancerous tissues. Lacunarity is a parameter that was developed for multiscale analysis of data and has been shown to be theoretically related to the correlation dimension, D2, by dlog(L)/dlog(x) = D2 - 2. Further, research has proven that not only can Lacunarity be used as a preliminary indicator of multifractal behavior but it also distinguishes between images with similar correlation dimension values. In order to compare the efficacy of the two approaches namely, MFDFA and Lacunarity, in distinguishing between pre-cancerous tissues of various grades, we test these techniques on a set of 2-dimensional theoretical random multifractal fields. MFDFA is employed for computing the width of the singularity spectrum f(α), which is a measure of multifractal behavior. A weighted mean of the log-transformed lacunarity values at different scales is employed for differentiating between patterns with the same correlation dimension but differences in texture. The two different techniques are then applied to images containing RI values of biopsy samples from human cervical tissues that were histo-pathologically characterized as grade-I and grade-II pre-cancerous cells. The results show that the two approaches are complementary to one another when it comes to multi-scale analysis of complex natural patterns manifested in the images of such pre-cancerous cells.

Obesity and kidney disease

Directory of Open Access Journals (Sweden)

Geraldo Bezerra da Silva Junior

Full Text Available Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD. Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.

Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

Science.gov (United States)

Guo, Jilong; Gong, Guohua; Zhang, Bin

2017-07-01

Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p gradient protein 2 was significantly highly expressed in grade 1 + 2 (triple-negative breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall survival in patients with grade 1 and 2 tumours. Cox multivariate analysis revealed anterior gradient protein 2 as a putative independent indicator of unfavourable outcomes (p = 0.031). All these data clearly showed that anterior gradient protein 2 is highly expressed in breast cancer and can be regarded as a putative biomarker for

Fetal Kidney Anomalies: Next Generation Sequencing

DEFF Research Database (Denmark)

Rasmussen, Maria; Sunde, Lone; Nielsen, Marlene Louise

Aim and Introduction Identification of abnormal kidneys in the fetus may lead to termination of the pregnancy and raises questions about the underlying cause and recurrence risk in future pregnancies. In this study, we investigate the effectiveness of targeted next generation sequencing in fetuses...... with prenatally detected kidney anomalies in order to uncover genetic explanations and assess recurrence risk. Also, we aim to study the relation between genetic findings and post mortem kidney histology. Methods The study comprises fetuses diagnosed prenatally with bilateral kidney anomalies that have undergone...... postmortem examination. The approximately 110 genes included in the targeted panel were chosen on the basis of their potential involvement in embryonic kidney development, cystic kidney disease, or the renin-angiotensin system. DNA was extracted from fetal tissue samples or cultured chorion villus cells...

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

Science.gov (United States)

Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

Twist and YB-1 gene expression in cervical cancer and precancerous tissue and their correlation with cell invasion

Directory of Open Access Journals (Sweden)

Qin Tian

2017-04-01

Full Text Available Objective: To study the correlation of Twist and YB-1 gene expression in cervical cancer and precancerous tissue with cell invasion. Methods: Cervical cancer tissue, precancerous tissue and normal cervical tissue surgically removed in our hospital between May 2013 and April 2015 were collected; immunohistochemical staining kits were used to detect the positive protein expression rate of Twist and YB-1 gene; fluorescence quantitative PCR kits were used to detect Twist, YB-1 and invasion gene mRNA expression. Results: Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue were significantly higher than those in normal cervical tissue, Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue were significantly higher than those in precancerous tissue; USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue with positive Twist and YB-1 expression were significantly higher than those in cervical cancer tissue and precancerous tissue with negative Twist and YB-1 expression. Conclusion: Highly expressed Twist and YB-1 in cervical cancer and precancerous tissue can promote cell invasion.

The safety of transplanting cryopreserved ovarian tissue in cancer patients

DEFF Research Database (Denmark)

Rosendahl, Mikkel; Greve, Tine; Andersen, Claus Yding

2013-01-01

Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence...

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Prostate cancer outcome and tissue levels of metal ions

Science.gov (United States)

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

2011-01-01

BACKGROUNDThere 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.METHODSWe 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.RESULTSPatients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 µg/g vs. 111 µg/g; P = 0.04) and 21% lower zinc (279 µg/g vs. 346 µg/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 µg/g vs. 0.439 µg/g; 4% higher) and selenium (1.68 µg/g vs. 1.58 µg/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively).CONCLUSIONSThere 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. 

The magnitude of linear dichroism of biological tissues as a result of cancer changes

Science.gov (United States)

Bojchuk, T. M.; Yermolenko, S. B.; Fedonyuk, L. Y.; Petryshen, O. I.; Guminetsky, S. G.; Prydij, O. G.

2011-09-01

The results of studies of linear dichroism values of different types of biological tissues (human prostate, esophageal epithelial human muscle tissue in rats) both healthy and infected tumor at different stages of development are shown here. The significant differences in magnitude of linear dichroism and its spectral dependence in the spectral range λ = 330 - 750 nm both among the objects of study, and between biotissues: healthy (or affected by benign tumors) and cancer patients are established. It is researched that in all cases in biological tissues (prostate gland, esophagus, human muscle tissue in rats) with cancer the linear dichroism arises, the value of which depends on the type of tissue and time of the tumor process. As for healthy tissues linear dichroism is absent, the results may have diagnostic value for detecting and assessing the degree of development of cancer.

Obesity and kidney disease: hidden consequences of the epidemic ...

African Journals Online (AJOL)

Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating a healthy lifestyle and health policy measures that ...

Diffuse reflectance spectroscopy as a tool for real-time tissue assessment during colorectal cancer surgery

Science.gov (United States)

Baltussen, Elisabeth J. M.; Snaebjornsson, Petur; de Koning, Susan G. Brouwer; Sterenborg, Henricus J. C. M.; Aalbers, Arend G. J.; Kok, Niels; Beets, Geerard L.; Hendriks, Benno H. W.; Kuhlmann, Koert F. D.; Ruers, Theo J. M.

2017-10-01

Colorectal surgery is the standard treatment for patients with colorectal cancer. To overcome two of the main challenges, the circumferential resection margin and postoperative complications, real-time tissue assessment could be of great benefit during surgery. In this ex vivo study, diffuse reflectance spectroscopy (DRS) was used to differentiate tumor tissue from healthy surrounding tissues in patients with colorectal neoplasia. DRS spectra were obtained from tumor tissue, healthy colon, or rectal wall and fat tissue, for every patient. Data were randomly divided into training (80%) and test (20%) sets. After spectral band selection, the spectra were classified using a quadratic classifier and a linear support vector machine. Of the 38 included patients, 36 had colorectal cancer and 2 had an adenoma. When the classifiers were applied to the test set, colorectal cancer could be discriminated from healthy tissue with an overall accuracy of 0.95 (±0.03). This study demonstrates the possibility to separate colorectal cancer from healthy surrounding tissue by applying DRS. High classification accuracies were obtained both in homogeneous and inhomogeneous tissues. This is a fundamental step toward the development of a tool for real-time in vivo tissue assessment during colorectal surgery.

Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

Science.gov (United States)

Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

2015-03-01

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

Stages of Childhood Soft Tissue Sarcoma

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy is used to ...

DIFFERENTIAL RESPONSE OF HEAT SHOCK PROTEINS TO UPHILL AND DOWNHILL EXERCISE IN HEART, SKELETAL MUSCLE, LUNG AND KIDNEY TISSUES

Directory of Open Access Journals (Sweden)

Pablo C. B. Lollo

2013-09-01

Full Text Available 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

Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

OpenAIRE

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

Leiomyosarcoma: A rare soft tissue cancer arising from multiple organs

Directory of Open Access Journals (Sweden)

Zorawar Singh

2018-03-01

Full Text Available Leiomyosarcoma (LMS, a smooth muscle connective tissue tumor, is a rare form of cancer which accounts for 5–10% of soft tissue sarcomas. This type of cancer is highly unpredictable. LMS is a resistant type of cancer and can remain in the dormant state for long time. It can recur in the later stages of life. LMS has been reported in different animals including humans. A wide literature search was done. The PubMed database was used to search for journal articles on the occurrence of LMS in different organs from 1950 to 2016. LMS has been reported to be associated with different organs, including esophagus, stomach, intestine, anus and uterus. In this article, an attempt has been made to review the studies based on occurrence of LMS with respect to the organs affected and frequency of publications. Finding the organ-associated occurrence of LMS may be useful in assessing the overall risk and formulating future cancer preventive strategies.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

National Research Council Canada - National Science Library

O'Keefe, Denise

2002-01-01

Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver...