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Sample records for human renal tumor

  1. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  2. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  3. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

    Science.gov (United States)

    Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

  4. Teratoid Wilms′ tumor - A rare renal tumor

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    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  5. Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.

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    Zhang, Xiao-Fei; Weng, De-Sheng; Pan, Ke; Zhou, Zi-Qi; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Jiang, Shan-Shan; Chen, Chang-Long; Li, Yong-Qiang; Zhang, Hong-Xia; Chang, Alfred E; Wicha, Max S; Zeng, Yi-Xin; Li, Qiao; Xia, Jian-Chuan

    2017-11-01

    Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC. © 2017 Wiley Periodicals, Inc.

  6. A 3D Human Renal Cell Carcinoma-on-a-Chip for the Study of Tumor Angiogenesis.

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    Miller, Chris P; Tsuchida, Connor; Zheng, Ying; Himmelfarb, Jonathan; Akilesh, Shreeram

    2018-06-01

    Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system. Specifically, we have combined primary human clear cell renal cell carcinoma (ccRCC) cells from six independent donors with human endothelial cells in a vascularized, flow-directed, 3D culture system ("ccRCC-on-a-chip"). The upregulation of key angiogenic factors in primary human ccRCC cells, which exhibited unique patterns of donor variation, was further enhanced when they were cultured in 3D clusters. When embedded in the matrix surrounding engineered human vessels, these ccRCC tumor clusters drove potent endothelial cell sprouting under continuous flow, thus recapitulating the critical angiogenic signaling axis between human ccRCC cells and endothelial cells. Importantly, this phenotype was driven by a primary tumor cell-derived biochemical gradient of angiogenic growth factor accumulation that was subject to pharmacological blockade. Our novel 3D system represents a vascularized tumor model that is easy to image and quantify and is fully tunable in terms of input cells, perfusate, and matrices. We envision that this ccRCC-on-a-chip will be valuable for mechanistic studies, for studying tumor-vascular cell interactions, and for developing novel and personalized antitumor therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  8. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

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    Sandy Azzi

    2015-06-01

    Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

  9. Activation of Stat3 in renal tumors.

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    Guo, Charles; Yang, Guanyu; Khun, Kyle; Kong, Xiantian; Levy, David; Lee, Peng; Melamed, Jonathan

    2009-02-28

    Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target.

  10. Usefulness of MR angiography in renal tumor

    International Nuclear Information System (INIS)

    Oka, Toshitsugu; Morimoto, Kouji; Nishimura, Kenji; Tsujimura, Akira; Yasunaga, Yutaka; Matsumiya, Kiyomi; Takaha, Minato

    1992-01-01

    MR angiography using a gradient-echo, pulse sequence FLASH (fast, low-angle shot) method during breath-hold with a 'MAGNETOM H-15' scanner (1.5 Tesla; Siemens Medical System) was performed on 27 patients with renal tumor at our clinic between Feburary 20, 1990 and September 30, 1991 and we studied to evaluate its usefulness. Of these 27 patients, 22 patients including one patient under hemodialysis treatment had renal cell carcinoma and one patient had oncocytoma pathologically proven from the excised specimens. The remaining four patients including two patients associated with inferior vena cava tumor thrombus were clinically diagnosed as renal cell carcinoma based on the result of imaging examinations such as excretory urography, ultrasonography, computed tomography and conventional angiography. However, they could not be operated on because their tumors were too advanced. By reconstruction of the data of consecutive coronal scans of the abdominal blood vessels such as the abdominal aorta, inferior vena cava and renal arteries and veins simultaneously without any intravenous contrast materials. Our present study revealed that MR angiography has some advantages, especially with regard to preoperative angiographic information about the abdomen of patients with renal tumor. That is, MR angiography can delineate many kinds of arteries and veins of the abdomen simultaneously and in a broader range, as well as it can be performed on the patients with hypersensitivity to iodinate contrast materials or renal insufficiency in a usual fashion. Furthermore, our present study suggested that the MR angiography is useful for assessing the presence and extent of inferior vena caval tumor thrombus of renal cell carcinoma and for clearly distinguishing tumor lesion and the surrounding normal renal parenchyma in the patients with renal tumor. (author)

  11. Usefulness of MR angiography in renal tumor

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    Oka, Toshitsugu; Morimoto, Kouji; Nishimura, Kenji; Tsujimura, Akira; Yasunaga, Yutaka; Matsumiya, Kiyomi; Takaha, Minato (Osaka National Hospital (Japan))

    1992-11-01

    MR angiography using a gradient-echo, pulse sequence FLASH (fast, low-angle shot) method during breath-hold with a MAGNETOM H-15 scanner (1.5 Tesla; Siemens Medical System) was performed on 27 patients with renal tumor at our clinic between Feburary 20, 1990 and September 30, 1991 and we studied to evaluate its usefulness. Of these 27 patients, 22 patients including one patient under hemodialysis treatment had renal cell carcinoma and one patient had oncocytoma pathologically proven from the excised specimens. The remaining four patients including two patients associated with inferior vena cava tumor thrombus were clinically diagnosed as renal cell carcinoma based on the result of imaging examinations such as excretory urography, ultrasonography, computed tomography and conventional angiography. However, they could not be operated on because their tumors were too advanced. By reconstruction of the data of consecutive coronal scans of the abdominal blood vessels such as the abdominal aorta, inferior vena cava and renal arteries and veins simultaneously without any intravenous contrast materials. Our present study revealed that MR angiography has some advantages, especially with regard to preoperative angiographic information about the abdomen of patients with renal tumor. That is, MR angiography can delineate many kinds of arteries and veins of the abdomen simultaneously and in a broader range, as well as it can be performed on the patients with hypersensitivity to iodinate contrast materials or renal insufficiency in a usual fashion. Furthermore, our present study suggested that the MR angiography is useful for assessing the presence and extent of inferior vena caval tumor thrombus of renal cell carcinoma and for clearly distinguishing tumor lesion and the surrounding normal renal parenchyma in the patients with renal tumor. (author).

  12. Radiofrequency ablation for renal tumors. Our experience

    International Nuclear Information System (INIS)

    Hiraoka, Kenji; Kawauchi, Akihiro; Nakamura, Terukazu; Soh, Jintetsu; Mikami, Kazuya; Miki, Tsuneharu

    2009-01-01

    The objective of this study was to report our results of percutaneous radiofrequency ablation (RFA) for renal tumors and to assess predictors of therapeutic efficacy. Forty patients (median age 73 years) with renal tumors were treated with RFA under local or epidural anesthesia. All of them had high surgical risk or refused radical surgery. Tumors were punctured percutaneously using the Radionics Cool-tip RF System under computed tomography or ultrasonographic guidance. Median tumor diameter was 24 mm. After RFA, contrast-enhanced computed tomography or magnetic resonance imaging was performed within 1 month. Complete response (CR) was defined as no enhancement inside the tumor. Factors related to the outcome and to renal function were assessed. Median follow up was 16 months. CR was observed in 34 cases (85.0%). A significant difference in CR rate was observed between tumors ≤30 mm and those >30 mm. Outcomes tended to be better for tumors in the mid to lower kidney, and those away from the renal hilum. Recurrence was observed in one case (2.9%), but a CR was obtained again by additional RFA. Out of a total of 77 RFA procedures, complications occurred in only three cases (3.9%), and conservative treatment was possible in all cases. Serum creatinine levels 3 months after RFA did not differ from those before RFA. Percutaneous RFA is a safe and effective treatment for small renal tumors in patients with high surgical risk or who refuse radical surgery. (author)

  13. Conservative management of small renal tumors

    International Nuclear Information System (INIS)

    Matsuzaki, Masato; Kawano, Yoshiyuki; Morikawa, Hirofumi; Shiga, Yoshiyuki; Murata, Hirokatsu; Komatsu, Hideki

    2007-01-01

    With the widespread use of imaging modalities, incidentally discovered small renal cell carcinomas have increased. Some patients, however, are too old or weak due to various diseases to undergo surgery and other patients occasionally refuse surgery. To investigate the natural history of small renal cell carcinoma, we retrospectively reviewed patients with small renal tumors suggestive of carcinoma. We retrospectively reviewed 15 patients with contrast-enhancing renal masses less than 4.0 cm in diameter who were observed without treatment. The mean follow-up period was 38 months (range, 8-91). The average patient age was 67 years (range, 44-87). The initial average tumor diameter was 2.2 cm (range, 1.0-3.9). The average growth rate was 0.06 cm per year (range, -0.09-0.28). Only 4 tumors grew obviously during the follow-up period. Three tumors were removed surgically by radical nephrectomy, and all tumors were pathologically diagnosed as renal cell carcinoma. None of the patients developed metastases during the follow-up period or after surgery. Two patients died of other causes. Nonsurgical watchful waiting may be an acceptable treatment option for elderly or severely comorbid patients; however, it is not known whether this conservative management can he applied to young or otherwise healthy patients. (author)

  14. Contemporary treatment of renal tumors

    DEFF Research Database (Denmark)

    Nisen, Harry; Järvinen, Petrus; Fovaeus, Magnus

    2017-01-01

    Objective: The five Nordic countries comprise 25 million people, and have similar treatment traditions and healthcare systems. To take advantage of these similarities, a collaborative group (Nordic Renal Cancer Group, NORENCA) was founded in 2015. Materials and methods: A questionnaire of 17...

  15. CT staging of renal pelvis tumor

    International Nuclear Information System (INIS)

    Yoon, Soo Woong; Cho, Kyoung Sik; Lee, Jong Hwa; Ham, Su Yeon; Won, Yeong Cheol; Ji, Eun Kyung; Choi, Seong Hun; Shin, Byung Suck

    1999-01-01

    To assess the value of computed tomography (CT) in the preoperative staging of transitional cell carcinoma (TCC) of the renal pelvis. We retrospectively evaluated the CT TNM staging of 38 patients with TCC of the renal pelvis who had undergone preoperative abdominal CT examination between January 1990 and January 1998. In CT staging for differentiation between early-stage (T0-2) and advanced-stage disease (T3-T4), three criteria were used, namely the presence or obliteration of the renal sinus fat layer, the smoothness or irregularity of margin between the tumor and renal parenchyma, and the presence or absence of hydronephrosis proximal to the tumor. CT staging was performed by two genitourinary radiologists blinded to the pathologic results, and was compared with pathologic staging. Pathologic results revealed 19 cases of early stage disease (T0=8, T1=9, T2=2) and 19 of advanced stage (T3=12, T4=7). Overall CT staging accuracy was 82%(31/38) ; four cases were overstaged and three were understaged. In early-stage disease, sensitivity and specificity were 79%, and 84%, and in advanced stage disease were 83% and 80%. Three of four overstaged cases showed hydronephrosis proximal to the tumor. In the second CT staging, using proximal hydronephrosis of the tumor as a criterion for early-stage disease, the sensitivity and specificity of early-stage disease were 95% and 75%, respectively, and the specificity of advanced-stage disease was 95%. When hydronephrosis proximal to a tumor was considered to be a sign of early stage disease, the CT staging of renal pelvic TCC was highly accurate

  16. CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

    International Nuclear Information System (INIS)

    Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

    1994-01-01

    It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

  17. The clinical factors associated with benign renal tumors

    International Nuclear Information System (INIS)

    Yamashita, Ryo; Nakamura, Masafumi; Matsuzaki, Masato; Matsui, Takashi; Yamaguchi, Raizo; Niwakawa, Masashi; Tobisu, Kenichi; Asakura, Koiku; Ito, Ichiro

    2009-01-01

    In this study, we sought to define the incidence of benign renal tumors in our institute and to clarify the clinical factors associated with benign renal tumors, in order to assist in forming preoperative differential diagnoses. From October 2002 to July 2007, we performed 157 nephrectomies in patients preoperatively diagnosed with renal cell carcinoma. We chose 81 tumors, all of which were less than 5 cm, for further study. We reviewed double-phase helical CT imaging retrospectively, specifically focusing on attenuation patterns and homogeneity. We also compared clinical factors, including age, sex and tumor size, between the benign and malignant renal tumors. The patient's median age was 67 years (mean age, 63 years), and the median tumor diameter was 3.0 cm (mean, 3.2 cm). Benign renal tumors were found in 10 (12%) of the 81 tumors; these included seven cases of oncocytoma and three cases of angiomyolipoma with minimal fat. Several factors were significant clinical determinants of differentiation between benign and malignant renal tumors: homogeneity in CT, female gender, and small tumor size all predominated in cases of benign tumors. Attenuation pattern in CT, however, was not a significant factor (p=0.344). When a patient, especially a female, presents with a small and homogeneous renal tumor, careful consideration should be given to the possibility of a benign process, which needs further consideration before performing excessive surgery. (author)

  18. New percutaneous ablative modalities in nephron-sparing surgery of small renal tumors

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    de Riese, Werner T. W.; Nelius, Thomas; Aronoff, David R.; Mittemeyer, Bernhard T.

    2004-07-01

    Renal tumors are increasingly detected on abdominal imaging studies. Standard treatment of small renal tumors includes partial or radical nephrectomy, done either open or laparoscopically. Several in situ ablative techniques to treat small renal lesions are currently in various phases of evolution. All involve imparting destructive energy to the tumor while minimizing injury to adjacent normal tissue. Cryotherapy (CryoT), radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFUS) and high-intensity radiation (HIR) are all being evaluated as tools to ablate renal tumors. The goal with these modalities is to minimize the blood loss, tissue manipulation, and morbidity associated with excisional approaches. Animal studies have shown that large, reproducible lesions can be ablated in normal kidney tissue by these new techniques. Studies of human renal tissue response to RFA are just beginning. Ex vivo studies reveal large, reproducible controlled lesions in normal renal tissue, similar to animal studies. In vivo studies have shown no significant toxicity, while efficacy is currently under evaluation. Preliminary clinical studies in humans have revealed that renal tumors are slow to regress after treatment, but about 75% of these small renal tumors appeared well treated. Mixed responses have been observed in the remaining cases. This paper presents a concise review of efficacy, advantages and disadvantages of these new minimal invasive techniques and their possible clinical implication in the future.

  19. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

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    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  20. Robotic partial nephrectomy for complex renal tumors: surgical technique.

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    Rogers, Craig G; Singh, Amar; Blatt, Adam M; Linehan, W Marston; Pinto, Peter A

    2008-03-01

    Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.

  1. Bone-metastasizing primary renal tumors in children

    International Nuclear Information System (INIS)

    Lamego, C.M.B.; Zerbini, M.C.N.

    1984-01-01

    Seven cases of childhood renal tumor with extensive bone involvement are reported. These neoplasms had been classified originally as wills tumors with atypical clinical and pathologic features. Subsequent to a retrospective histologic analysis, the lesions were reclassified as follows: three cases as bone-metastasizing renal tumors of childhood, one as rhabdomyosarcoma, two as indifferentiated Sarcomas and one case as indifferentiated malignant neoplasm. (Author) [pt

  2. Computerized tomography for diagnosis and staging of renal pelvic tumor

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    Fukuoka, Hiroshi; Goto, Akihiko; Kitamura, Hajime

    1985-01-01

    Although we have no definite criteria available yet for clinical staging of renal pelvic tumor, the preoperative staging of this disease is nevertheless important in view of the current tendency that the necessity for renal conservative operation is considered. CT is now a routine work also for diagnosing renal pelvic tumor. The present study was performed in order to validate its usefulness for diagnosing and staging the disease. Our series consisted of 8 patients with renal pelvic tumor, in 6 of whom a definite diagnosis was established after demonstrating filling defect on pyelogram, but in the remaining two with extensive infiltration, and squamous cell carcinoma associated with staghorn calculus respectively, CT failed to provide a definite diagnosis. CT findings of an extension of the mass in the renal pelvis or renal calyces into adipose tissue of the renal sinus or renal parenchyma were judged to indicate an invasive type (Stage III), while a non-invasive type (Stage I or II) was defined on the basis of otherwise CT findings. Consistency with pathological stages was noted in 7 of the 8 cases (87.5 %). It was difficult to differentiate Stage I and Stage II on CT findings. CT was considered to be extremely useful tool for preoperative staging of renal pelvic tumor. (author)

  3. Lin28 sustains early renal progenitors and induces Wilms tumor

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    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  4. Metanephric stromal tumor: A novel pediatric renal neoplasm

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    Rajalakshmi V

    2009-07-01

    Full Text Available Metanephric stromal tumor of kidney is a novel pediatric benign stromal specific renal neoplasm. A few cases have been reported in adults also. This tumor is usually centered in the renal medulla with a characteristic microscopic appearance which differentiates this lesion from congenital mesoblastic nephroma and clear cell sarcoma of the kidney. In most cases complete excision alone is curative. The differentiation of metanephric stromal tumor from clear cell sarcoma of the kidney will spare the child from the ill effects of adjuvant chemotherapy. In this communication we describe the gross and microscopic features of metanephric stromal tumor in a one-month-old child with good prognosis.

  5. Gonadal vein tumor thrombosis due to renal cell carcinoma

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    Hamidreza Haghighatkhah

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

  6. Superselective renal artery embolization with lipiodol and absolute alcohol emulsion for renal tumor

    International Nuclear Information System (INIS)

    Yu Miao; Li Jiakai; Sun Minglu; Wang Huixian

    2008-01-01

    Objective: To evaluate the efficacy of the renal arterial embolization with lipidol and absolute alcohol emulsion in the treatment of renal tumors. Methods: The superselective renal arterial embolization by using coaxial-cathaterization with infusion of lipiodol and absolute alcohol (in proportion of 2 :1) emulsion was performed in twenty patients with malignant and benign kidney tumors. 4 weeks later, the renal arteriography was taken routinely and repeated embolization was performed in case of necessary; and follow up was carried out periodically. Results: The imaging findings showed thorough tumor necrosis and feeding vessel abruption in 18 cases after one session of treatment. The volume of tumors decreased more than a half in 13 patients (82.25%, 13/18) associated with a well-distributed lipidol inside the tumors. The second session of treatment was performed in other 2 patients and the clinical symptoms relieved obviously. Conclusions: The superselective renal artery embolization with lipidol and absolute alcohol emulsion can permanently embolize all tumor feeding arteries in capillary vessel level with maximum reservation of renal function, providing definitively efficacy and worthwhile to be recommended widely. (authors)

  7. Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

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    Lopes Vendrami, Camila; Parada Villavicencio, Carolina; DeJulio, Todd J; Chatterjee, Argha; Casalino, David D; Horowitz, Jeanne M; Oberlin, Daniel T; Yang, Guang-Yu; Nikolaidis, Paul; Miller, Frank H

    2017-01-01

    Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

  8. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  9. Rapidly enlarging renal tumor during pregnancy: diagnostic and management dilemma

    Directory of Open Access Journals (Sweden)

    Kor Wei Tiang

    2014-04-01

    Full Text Available Urological tumors diagnosed during pregnancy are rare. However, the incidence seems to be increasing largely due to advancements in modern imaging techniques and improved antenatal care. The diagnosis and management of renal tumors during pregnancy poses a dilemma to clinicians. This case report highlights the challenges in managing a large chromophobe renal cell carcinoma in a young primigravida patient. Proper antenatal assessment, a multidisciplinary team approach and appropriate discussion with patient are important determinants to achieve the best clinical outcomes for both the mother and the baby. 

  10. LEFT RENAL TUMOR: A RARE CADAVERIC FINDINGS

    Directory of Open Access Journals (Sweden)

    Siva Prasad

    2015-08-01

    Full Text Available A benign tumour is a non - cancerous growth that does not spread (metastasize to other parts of the body and is not usually life - threatening. Many researchers believe that most of the following types of kidney tumours are benign. However, others feel that some of these tumours have the potential to develop into renal cell carcinoma. There are no diagnostic tests that can confirm if a benign tumour has the potential to become cancerous. Benign tumours are sometimes found along with renal cell carcinoma when a removed kidney is examined by a pathologist. For these reasons, benign kidney tumours are treated like malignant tumours. In this case we have observed a male cadaver with a large tumour in the left kidney during our routine dissections of undergraduates .

  11. Radiological features of progressive tumoral calcinosis in chronic renal failure.

    LENUS (Irish Health Repository)

    Hodnett, P

    2012-02-03

    We present the case of a young adult patient with chronic renal failure who developed painful subcutaneous nodules after failed renal transplant and recommencing dialysis. These nodules were juxta-articular in location and initially located over both shoulders. Radiological evaluation suggested tumoral calcinosis. The patient was placed on a strict dialysis and dietary regimen but was suboptimally compliant with same. The patient developed progressive disease with an increase in size and number of juxta-articular calcified soft-tissue masses. However, 6 months following a second renal transplant clinical and radiological follow up demonstrated marked resolution both in symptomatology and radiographic findings. We present the plain radiographic, CT and MRI findings which demonstrate the typical radiological features of tumoral calcinosis. We correlate these findings with clinical course and histological findings following surgical excision of one of these masses.

  12. Tumoral calcinosis in a dog with chronic renal failure

    International Nuclear Information System (INIS)

    Spotswood, T.C.

    2003-01-01

    A 2-year-old male German shepherd dog in poor bodily condition was evaluated for thoracic limb lameness due to a large, firm mass medial to the left cranial scapula. Radiography revealed several large cauliflower-like mineralized masses in the craniomedial left scapula musculature, pectoral region and bilaterally in the biceps tendon sheaths. Urinalysis, haematology and serum biochemistry showed that the dog was severely anaemic, hyperphosphataemic and in chronic renal failure. The dog was euthanased and a full post mortem performed. A diagnosis of chronic renal failure with secondary hyperparathyroidism was confirmed. The mineralised masses were grossly and histopathologically consistent with a diagnosis of tumoral calcinosis. Tumoral calcinosis associated with chronic renal failure that does not involve the foot pads is rarely seen

  13. Radio frequency ablation of small renal tumors:: intermediate results.

    Science.gov (United States)

    Hwang, J J; Walther, M M; Pautler, S E; Coleman, J A; Hvizda, J; Peterson, James; Linehan, W M; Wood, B J

    2004-05-01

    With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean +/- standard mean of error) were 243 +/- 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic

  14. END STAGE RENAL DISEASE IN PATIENTS WITH WILMS TUMOR: RESULTS FROM THE NATIONAL WILMS TUMOR STUDY GROUP AND THE U.S. RENAL DATA SYSTEM

    OpenAIRE

    Breslow, Norman E.; Grigoriev, Yevgeny A.; Peterson, Susan M.; Collins, Allan J.; Ritchey, Michael L.; Green, Daniel M.

    2005-01-01

    Purpose: To accurately assess the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the U.S. Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in those with the Wilms tumor-aniridia (WAGR) syndrome.

  15. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

    DEFF Research Database (Denmark)

    Turajlic, Samra; Xu, Hang; Litchfield, Kevin

    2018-01-01

    The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show...... that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors...... outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance....

  16. DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.

    Directory of Open Access Journals (Sweden)

    Hitomi Ueno

    Full Text Available A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms' tumor, clear cell sarcoma of the kidney (CCSK, congenital mesoblastic nephroma (CMN, rhabdoid tumor of the kidney (RTK, and the Ewing's sarcoma family of tumors (ESFT. By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK, and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms' tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors.

  17. Treatment of caval vein thrombosis associated with renal tumors.

    Science.gov (United States)

    Jiménez-Romero, Carlos; Conde, María; de la Rosa, Federico; Manrique, Alejandro; Calvo, Jorge; Caso, Óscar; Muñoz, Carlos; Marcacuzco, Alberto; Justo, Iago

    2017-03-01

    Renal carcinoma represents 3% of all solid tumors and is associated with renal or inferior caval vein (IVC) thrombosis between 2-10% of patients, extending to right atrial in 1% of cases. This is a retrospective study that comprises 5 patients who underwent nephrectomy and thrombectomy by laparotomy because of renal tumor with IVC thrombosis level iii. Four patients were males and one was female, and the mean age was 57,2 years (range: 32-72). Most important clinical findings were hematuria, weight loss, weakness, anorexia, and pulmonary embolism. Diagnostic confirmation was performed by CT scanner. Metastatic disease was diagnosed before surgery in 3 patients. Suprahepatic caval vein and hepatic hilium (Pringle's maneouver) were clamped in 4 patients, and ligation of infrarrenal caval vein was carry out in one patient. Five patients developed mild complications (Clavien I/II). No patient died and the mean hospital stay was 8,6 days. All patients were treated with chemotherapy, and 3 died because distant metastasis, but 2 are alive, without recurrence, at 5 and 60 months, respectively. Nephrectomy and thrombectomy in renal tumors with caval thrombosis can be curative in absence of metastasis or, at less, can increase survival or quality of live. Then these patients must be treated in liver transplant units because major surgical and anesthesiologic expertise. Adjuvant treatment with tyrosin kinase inhibitors must be validate in the future with wider experiences. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

    International Nuclear Information System (INIS)

    Sabharwal, Rohan; Vladica, Philip

    2006-01-01

    Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 ± 10.43 years. Mean tumor size was 1.95 ± 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors

  19. Management of Renal Tumors by Image-Guided Radiofrequency Ablation: Experience in 105 Tumors

    International Nuclear Information System (INIS)

    Breen, David J.; Rutherford, Elizabeth E.; Stedman, Brian; Roy-Choudhury, Shuvro H.; Cast, James E. I.; Hayes, Matthew C.; Smart, Christopher J.

    2007-01-01

    Aims. In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. Materials and Methods. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Results. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson χ 2 ) Five patients had complications. There have been no local recurrences. Conclusion. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors

  20. Stereotactic Body Radiotherapy for the Treatment of Renal Tumors

    Directory of Open Access Journals (Sweden)

    Michael Hanzly

    2014-09-01

    Full Text Available The purpose of this study was to evaluate the response of actively growing renal masses to stereotactic body radiation therapy (SBRT. We retrospectively reviewed our institutional review board–approved kidney database and identified 4 patients who underwent SBRT, 15 Gy dose, for their rapidly growing renal masses. Three patients had a decreased tumor size after radiation treatment by 20.8%, 38.1%, and 20%. The other patient had a size gain of 5.6%. This patient maintained a similar tumor growth rate before and after SBRT. Mean follow-up time was 13.8 months. SBRT represents an effective management option in select patients with larger rapidly growing kidney masses.

  1. Renal tumor leading to acute respiratory distress syndrome – a rare ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    renal cell carcinoma (RCC). KEY WORDS: ARDS; Renal tumor; Adult respiratory distress syndrome. INTRODUCTIONᴪ. ARDS due to ... unable to maintain saturation in spite of high flow ... Blood investigations showed mild leukocytosis.

  2. Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

    OpenAIRE

    Turker Acar; Mustafa Harman; Serkan Guneyli; Sait Sen; Nevra Elmas

    2014-01-01

    Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this...

  3. THE EPIGENETICS OF RENAL CELL TUMORS: FROM BIOLOGY TO BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Rui eHenrique

    2012-05-01

    Full Text Available Renal cell tumors (RCT collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling / histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided.

  4. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Affect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  5. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Effect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  6. Integrated imaging (ultrasound, computed tomography, intravenous urography) in diagnosing renal tumors and tumor-like formations

    International Nuclear Information System (INIS)

    Drudi, F.M.; Capanna, G.; Poggi, R.; Occhiato, R.; Iannicelli, E.; Nardo, R.; di Passariello, R.

    1994-01-01

    This is an assessment of semiologic imaging criteria based on computerised tomography, ultrasound diagnosis and intravenous urography in renal tumors. The purpose is to obtain differential diagnostic data capable to modify the treatment approach. Over the last three years, a total of 570 cases of kidney tumors are observed. In 490 of them (86%) the imaging patterns obtained by either of the three techniques leads to correct diagnosis. In 62 of the remaining 80 patients, the integration of two techniques allows to unveil the neoplastic nature of the disease (27 cases), or the presence of a benign process (35 cases). In 15 of the remaining 18 cases only integration of the three techniques results in diagnosing renal tumors or tumor-like conditions (3 adeno-carcinomas, 5 abscesses, 3 cases of tuberculosis, 2 - pyeloxanthogranulomatosis, 2 dysmorphisms). In the last three cases definite diagnosis is made on the basis of needle biopsy. The radiological diagnosis is confirmed intraoperatively or during clinical follow-up study. The obtained data underscore the clinical relevance of imaging integration in evaluating renal lesions. This is particularly valid whenever the clinical data are nonspecific or misleading. 15 refs., 3 figs., 5 tabs. (orig.)

  7. Establishment of a large panel of patient-derived preclinical models of human renal cell carcinoma

    OpenAIRE

    Lang, Herv?; B?raud, Claire; Bethry, Audrey; Danilin, Sabrina; Lindner, V?ronique; Coquard, Catherine; Rothhut, Sylvie; Massfelder, Thierry

    2016-01-01

    The objective of the present work was to establish a large panel of preclinical models of human renal cell carcinoma (RCC) directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues (all stages/subtypes) were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were ...

  8. Evaluation of morphologically unclassified renal cell carcinoma with electron microscopy and novel renal markers: implications for tumor reclassification.

    Science.gov (United States)

    Talento, Romualdo; Hewan-Lowe, Karlene; Yin, Ming

    2013-02-01

    Despite progress in the classification of renal cell carcinomas (RCC), a subset of these carcinomas remains unclassified (RCC-U). Patients with RCC-U usually present at a late stage and have a poor prognosis. Several studies have attempted to extract new classifications of newly recognized renal carcinomas from the group of RCC-U. However, to date, no studies in the literature have attempted to characterize the RCC-U with unrecognizable cell types beyond the morphologic evaluation on H&E-stained sections. The purpose of this study was to evaluate this group of RCC-U using electron microscopy and novel renal markers. Ten cases of such RCC-U were identified for this study. At the ultrastructural level, they did not show typical morphology that resembled any of the well-studied, recognizable subtypes of RCC. However, they did reveal features of renal tubular epithelial differentiation. The histologic, ultrastructural, and immunophenotypic features indicated that these tumors are poorly differentiated renal epithelial tumors, possibly derived from the proximal nephron, with an immunohistochemical profile similar to high-grade clear cell RCC. It is, therefore, proposed that this group of renal carcinomas be renamed "poorly differentiated renal cell carcinoma, not otherwise specified." The current study showed that PAX-8 and carbonic anhydrase IX are reliable markers for this novel group of renal carcinoma, and that electron microscopy is an important adjunct in the evaluation of new and unusual renal entities.

  9. CT diagnosis of tumor thrombus of the renal vein and inferior vena cava

    International Nuclear Information System (INIS)

    Masuda, Fujio; Chen, Zuicho; Oishi, Yukihiko; Machida, Toyohei

    1980-01-01

    We used computed tomography (CT) for diagnosis in 4 cases of renal tumor associated with tumor thrombus of the renal vein and inferior vana cava. The results obtained are described below: A total of 4 cases consisting of 3 cases of renal cell carcinoma and one case of squamous cell carcinoma of the renal pelvis, treated at the Jikei University Hospital during the six months period from January to June of 1979, were studied. The affected side was right in 3 cases and left in one case. In all of the former cases the tumor thrombus was extending from the renal vein to the inferior vena cava, while in the latter case it was confined in the renal vein. All these 4 cases received CT together with renal arteriography and inferior venacavography, followed by nephrectomy, and were confirmed of the presence of tumor thrombus in the renal vein and inferior vena cava operatively. CT findings revealed a pronounced enlargement of the renal vein, and tumor thrombus of the renal vein was diagnosed in all of the 4 cases. In 2 of 3 cases in which tumor thrombus extended to the inferior vena cava, the dilated renal vein was found to be connected to the slightly dilated inferior vena cava, while in the remaining one case the outline of the inferior vena cava was obscure, showing no clear dilatation. After contrast enhancement, a filling defect was seen in the inferior vena cava. CT findings of tumor thrombus in the vein indicated a dilatation of the renal vein and inferior vena cava. In addition, a filling defect was found after contrast enhancement, suggesting that CT is helpful as a diagnostic aid. (author)

  10. Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

    Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

  11. Renal sinus fat invasion and tumoral thrombosis of the inferior vena cava-renal vein: only confined to renal cell carcinoma.

    Science.gov (United States)

    Acar, Turker; Harman, Mustafa; Guneyli, Serkan; Sen, Sait; Elmas, Nevra

    2014-01-01

    Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

  12. Review of laparoscopic partial nephrectomy in the treatment of renal tumors, T1 stadium in adults

    International Nuclear Information System (INIS)

    Zamora Montes de Oca, Maria Jose

    2012-01-01

    The T1 renal cancer in adults is made known; incidence, characteristics and management. Renal cell carcinoma has been the most common malignancy of the kidney, percentage is close to three percent of solid tumors of adults. The treatments for this tumor are analyzed: open radical nephrectomy, laparoscopic radical nephrectomy, open partial nephrectomy and laparoscopic partial nephrectomy. Laparoscopic partial nephrectomy has represented an alternative option acceptable, safely and with good oncological and surgical outcomes for patients, as it is used to conserve nephrons and simultaneously to resect the tumor of a complete form promoting in the future the patient present a good renal function. Additionally, a adequate oncological control has reduced the risk of submit postoperative renal failure. An evolution of laparoscopic partial nephrectomy is presented determining the procedure for renal tumors in state T1 in the adults [es

  13. Fine mapping of the human renal oncocytoma-associated translocation (5;11)(q35;q13) breakpoint

    NARCIS (Netherlands)

    Sinke, RJ; Dijkhuizen, T; Janssen, B; Weghuis, DO; Merkx, G; vandenBerg, E; Schuuring, E; Meloni, AM; deJong, B; vanKessel, AG

    1997-01-01

    Recent cytogenetic analysis of a series of human renal oncocytomas revealed the presence of a recurring chromosomal translocation (5;11)(q35;q13) as sole anomaly in a subset of the tumors. The molecular characterization of this translocation was initiated using two primary t(5;11)-positive renal

  14. [{sup 18}F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing α{sub v}β{sub 3} and α{sub v}β{sub 5} integrins

    Energy Technology Data Exchange (ETDEWEB)

    Mena, Esther; Turkbey, Baris; Choyke, Peter; Kurdziel, Karen [NCI, NIH, Molecular Imaging Program, Bethesda, MD (United States); Owenius, Rikard [GE Healthcare, Life Sciences, Uppsala (Sweden); Sherry, Richard [NCI, NIH, Surgery Branch, Bethesda, MD (United States); Bratslavsky, Gennady [NCI, NIH, Urologic Oncology Branch, Bethesda, MD (United States); Macholl, Sven; Miller, Matthew P.; Somer, Ed J. [GE Healthcare, Life Sciences, Amersham (United Kingdom); Lindenberg, Liza [NCI, NIH, Molecular Imaging Program, Bethesda, MD (United States); National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Adler, Stephen [Clinical Research Directorate/CMRP SAIC-Frederick Inc., NCI-Frederick, Bethesda, MD (United States); Shih, Joanna [DCTD, NCI, NIH, Biometric Research Branch, Rockville, MD (United States)

    2014-10-15

    [{sup 18}F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α{sub v}β{sub 3} and α{sub v}β{sub 5} are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [{sup 18}F]fluciclatide (formerly known as [{sup 18}F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression. Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [{sup 18}F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV{sub 80%} {sub max}, and Patlak influx rate constant (K{sub i}) data, tumor by tumor. Tumors from all 18 patients demonstrated measurable [{sup 18}F ]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV{sub 80%} {sub max} of 6.4 ± 2.0 (range 3.8 - 10.0), while the average SUV{sub 80%} {sub max} for metastatic melanoma lesions (in 6 patients) was 3.0 ± 2.0 (range 0.7 - 6.5). There was a statistically significant difference in [{sup 18}F ]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs), with SUV{sub 80%} {sub max} of 8.2 ± 1.8 and 5.4 ± 1.4 (P = 0.020) and tumor-to-normal kidney (T/N) ratios of 1.5 ± 0.4 and 0.9 ± 0.2, respectively (P = 0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K{sub i} and α{sub v}β{sub 5} OD when segregating the patient population between melanoma and RCC (r = 0.83 for K{sub i} vs. melanoma and r = 0.91 for K{sub i} vs. RCC). SUV{sub 80%} {sub max} showed a moderate correlation with α{sub v}β{sub 5} and α{sub v}β{sub 3

  15. Excisional treatment of renal hydatid cyst mimicking renal tumor with diode laser technique: A case report.

    Science.gov (United States)

    Uçar, Murat; Karagözlü Akgül, Ahsen; Çelik, Fatih; Kılıç, Nizamettin

    2016-08-01

    Cystic echinococcosis, which is one of the most important helminthic infestations, is a serious life-threatening health problem in developing countries. Hydatid cyst of the kidney is a rare condition in children that can be treated with medical therapy or surgical treatment in some resistant cases. Here, we present a case of renal hydatid cyst that was treated with laparoscopic excision with diode laser. A 15-year-old female patient was admitted with abdominal pain. Abdominal ultrasonography revealed a 32 × 23 × 19-mm solid mass with cystic component at lower pole of right kidney. An indirect hemagglutination (IHA) test for echinococcosis granulosus was positive at a 1:320 titer. Other laboratory tests were within normal limits. The patient received albendazole therapy for 3 months. The follow-up magnetic resonance imaging showed a solitary lesion with exophytic extensions that contained large separations. No contrast enhancement could be detected after gadolinium injection. As no regression could be detected radiologically, surgical treatment was planned. Laparoscopic renal lower pole mass cyst excision with diode laser was performed (Figure). The patient was hospitalized for 1 day without any blood transfusion. Histopathological examination was consistent with hydatid cyst of the kidney. Diagnosis of hydatid cyst of the kidney is generally made incidentally and can be misdiagnosed as a primary kidney tumor. Radiological studies may be insufficient for accurate diagnosis. In our case, laparoscopic excision of cyst and histopathological examination confirmed the diagnosis of cyst hydatid. At the postoperative second month the ultrasonography of kidneys were normal. For patients from endemic areas, hydatid cyst should always be included in the differential diagnosis. Laparoscopic excision of renal hydatid cysts with diode laser is a feasible and safe technique for resistant cases. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier

  16. Percutaneous radiofrequency and microwave ablation in the treatment of renal tumors - 10 years of experience.

    Science.gov (United States)

    Dvorak, Petr; Hoffmann, Petr; Brodak, Milos; Kosina, Josef; Pacovsky, Jaroslav; Raupach, Jan; Krajina, Antonin

    2017-12-01

    The standard radical treatment of renal cell carcinoma is surgical resection, but it is not suitable for patients with serious medical comorbidities and solitary kidney tumors. Minimally invasive ablation techniques could be an appropriate therapeutic alternative. To retrospectively evaluate the technical success, mid-term and long-term efficacy and safety of radiofrequency and microwave ablation in patients with small renal tumors. Over the course of 10 years, 91 ablation procedures in 64 patients for 68 tumors, of size 12-60 mm, were performed using only conscious sedation. These ablations were done under the guidance of computed tomography. We treated 41 males and 23 females with solitary kidney tumors (14 cases) and tumors in non-surgical candidates (54 cases). In 50 (73.5%) tumors single treatment was successful; in 13 (19.1%) cases a second procedure was used successfully, and in the 5 largest tumors (sizes 45-60 mm, 7.4%) a third treatment was necessary. Within the follow-up 10 (15.6%) patients died, but none due to metastatic renal cell carcinoma. Only 1 serious complication was observed - retroperitoneal and psoatic hematoma. Early recurrence occurred in 18 (26.5%) tumors. Late recurrence was detected in 5 (7.4%) cases. In all cases complete local control of the renal tumors was reached. Percutaneous ablation is a very effective treatment for patients with small renal tumors of the T1a group with a minimal complication rate.

  17. Intra-arterial digital subtraction angiography in the diagnosis and treatment of renal tumors

    International Nuclear Information System (INIS)

    Yashiro, Naobumi; Itai, Yuji; Iio, Masahiro

    1985-01-01

    Nine patients with renal tumors were studied by IADSA. Embolization was performed in six patients. IADSA were evaluated on the practical points: vascular mapping, visualization of renal veins, and embolization. Vascular mapping with IADSA was satisfactory in eight patients. The limitation of the field of view was the major restricting factor in two. One with multiple renal arteries was unacceptable. Visualization of renal veins by IADSA with renal artery injections was not reliable because of misregistration. Conventional arteriography with large dose was thought to be preferrable. Embolization with IADSA was satisfactory. Significant reduction of contrast load and procedure time was achieved. (author)

  18. Renal transplantation-related risk factors for the development of uterine adenomatoid tumors.

    Science.gov (United States)

    Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

    2016-08-01

    •We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.•Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.•The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors.

  19. Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

    Science.gov (United States)

    Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

    2013-01-01

    Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

  20. Massive hematuria due to a congenital renal arteriovenous malformation mimicking a renal pelvis tumor: a case report

    Directory of Open Access Journals (Sweden)

    Sountoulides P

    2008-05-01

    Full Text Available Abstract Introduction Congenital renal arteriovenous malformations (AVMs are very rare benign lesions. They are more common in women and rarely manifest in elderly people. In some cases they present with massive hematuria. Contemporary treatment consists of transcatheter selective arterial embolization which leads to resolution of the hematuria whilst preserving renal parenchyma. Case presentation A 72-year-old man, who was heavy smoker, presented with massive hematuria and flank pain. CT scan revealed a filling defect caused by a soft tissue mass in the renal pelvis, which initially led to the suspicion of a transitional cell carcinoma (TCC of the upper tract, in view of the patient's age and smoking habits. However a subsequent retrograde study could not depict any filling defect in the renal pelvis. Selective right renal arteriography confirmed the presence of a renal AVM by demonstrating abnormal arterial communication with a vein with early visualization of the venous system. At the same time successful selective transcatheter embolization of the lesion was performed. Conclusion This case highlights the importance of careful diagnostic work-up in the evaluation of upper tract hematuria. In the case presented, a congenital renal AVM proved to be the cause of massive upper tract hematuria and flank pain in spite of the initial evidence indicating the likely diagnosis of a renal pelvis tumor.

  1. Crioterapia de tumores renales: estado actual y desarrollos contemporáneos [= Cryotherapy for renal tumors: Current status and contemporary developments

    NARCIS (Netherlands)

    Rioja, J.; Tzortzis, V.; Mamoulakis, C.; Laguna, M. P.

    2010-01-01

    The proportion of renal tumors found incidentally dramatically increased in the past decade. More than half of them were diagnosed in patients over 70 years of age, a population with high associated comorbidity. Nephron-sparing minimally invasive surgical procedures are aimed at treating patients

  2. Consideration on the diagnostic ability of various imaging techniques in relation to renal tumor

    International Nuclear Information System (INIS)

    Ike, Katsushi

    1984-01-01

    Radiological diagnosis of renal tumors is being improved with the increased imaging accuracy which has resulted from advancement in the various equipment used and improvement in techniques. However, at the clinical level, diagnostic procedures based on the characteristics of the delineated images are not yet established and the diverse diagnostic procedures are being conducted currently in a stereotyped manner. In this study, the images of 61 cases diagnosed as renal tumor were analysed retrospectively with the purpose of establishing the imaging accuracy, capacity for diagnosis based on image characteristics and a subseguent proper diagnostic procedure. It was found that CT and Angio gave similar diagnostic accuracy. It was further revealed that US images enabled to differentiate renal tumors from the more commonly experienced renal cystic disease. For determination of tunica involucrum infiltration, which is essential to diagnose Stage I and II renal tumors, CT was proved to be superior to Angio. CT and US were also to be so in the determination of metastasis to para-aortic lymph nodes which is a Stage III criterion. In recent years, CT and US imaging accuracies have increased, hence the improvement in the capacity to diagnose non-observable renal tumors is highly expected. (author)

  3. Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

    Directory of Open Access Journals (Sweden)

    Juan Ruiz-Bañobre

    2016-11-01

    Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

  4. Brown tumor of lumber spint in patient with chronic renal failure ...

    African Journals Online (AJOL)

    Brown tumors are erosive bone lesions caused by increased osteoclastic activity. They usually occur in the severe forms of secondary hyperparathyroidism, as in patients with hemodialysis-dependent chronic renal disease. Involvement of the lumbar spine with this tumor causing neural compression is extremely rare.

  5. Diagnostic problems in the subtyping of renal tumors encountered by five pathologists

    DEFF Research Database (Denmark)

    Kümmerlin, Intan; ten Kate, Fiebo; Smedts, Frank

    2009-01-01

    was reached for all 28 cases after examination of more slides from different tumor areas and IHC-stained sections. An accurate histologic distinction between benign and malignant renal tumors is possible on one HE-stained section. Correct assignment of the subtype is difficult on one slide alone and relies...

  6. Melanotic Xp11 Translocation Renal Cancer Managed With Radical Nephrectomy and IVC Tumor Thrombectomy

    Directory of Open Access Journals (Sweden)

    Iyad S. Khourdaji

    2017-01-01

    Full Text Available Melanotic Xp11 translocation renal cancer is a rarely observed neoplasm primarily affecting adolescents and young adults. Given the paucity of data describing this malignancy, its natural history and subsequent long-term management are not well understood. We report a case of melanotic Xp11 translocation with tumor thrombus extension managed with radical nephrectomy and inferior vena cava (IVC tumor thrombectomy. To our knowledge, this is the first case report to describe use of conventional tumor thrombectomy techniques in a patient with melanotic Xp11 translocation renal cancer.

  7. Aging augments renal vasoconstrictor response to orthostatic stress in humans.

    Science.gov (United States)

    Clark, Christine M; Monahan, Kevin D; Drew, Rachel C

    2015-12-15

    The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (-15 and -30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects (P aging augments the renal vasoconstrictor response to orthostatic stress in humans. Copyright © 2015 the American Physiological Society.

  8. Percutaneous radiofrequency ablation of renal tumors: Midterm results in 16 patients

    International Nuclear Information System (INIS)

    Memarsadeghi, Mazda; Schmook, Theresia; Remzi, Mesut; Weber, Michael; Poetscher, Gerda; Lammer, Johannes; Kettenbach, Joachim

    2006-01-01

    Purpose: To evaluate the outcome of 16 patients after percutaneous radiofrequency ablation of renal tumors. Materials and methods: Sixteen patients (nine women, seven men; mean age, 61 ± 9 years) with 24 unresectable renal tumors (mean volume, 4.3 ± 4.3 cm 3 ) underwent CT-guided (n = 20) or MR imaging-guided (n = 4) percutaneous radiofrequency ablation using an expandable electrode (Starburst XL TM , RITA Medical Systems, Mountain View, CA) with a 150-W generator. The initial follow-up imaging was performed within 1-30 days after RF ablation, then at 3-6 month intervals using either CT or MRI. Residual tumor volume and coagulation necrosis was assessed, and statistical correlation tests were obtained to determine the strength of the relationship between necrosis volume and number of ablations. Results: Overall, 97 overlapping RF ablations were performed (mean, 3.5 ± 1.5 ablations per tumor) during 24 sessions. Five or more RF ablations per tumor created significant larger necrosis volumes than 1-2 (p .034) or 3-4 ablations (p = .020). A complete ablation was achieved in 20/24 tumors (primary technical success, 83%; mean volume of coagulation necrosis: 10.2 ± 7.2 cm 3 ). Three of four residual tumors were retreated and showed complete necrosis thereafter. Three major complications (one percuatneous urinary fistula and two ureteral strictures) were observed after RF ablation. No further clinically relevant complications were observed and renal function remained stable. During a mean follow-up of 11.2 months (range, 0.2-31.5), 15/16 patients (94%) were alive. Only one patient had evidence of local recurrent tumor. Conclusion: The midterm results of percutaneous RF ablation for renal tumors are promising and show that RF ablation is well-suited to preserve renal function

  9. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  10. Metastatic malignant tumor in native kidney with acquired cystic disease after renal transplantation

    International Nuclear Information System (INIS)

    Garcia de la Oliva, T.; Gonzalez Molina, M.

    1990-01-01

    Patients on long-term hemodialysis frequently develop Acquired Cystic Renal Disease (ARCD). When hematuria or flank pain occurs, the possibility of malignant renal tumors should be investigated. The authors present an ARCD patient who received a kidney transplant and developed malignancy in a native kidney, the first manifestation being bone metastases, and discuss the role of CT in evaluating these patients. (authors). 9 refs.; 2 figs

  11. MR imaging of renal cell carcinoma: associations among signal intensity, tumor enhancement, and pathologic findings.

    OpenAIRE

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

    2003-01-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics ...

  12. Zonal NePhRO scoring system: a superior renal tumor complexity classification model.

    Science.gov (United States)

    Hakky, Tariq S; Baumgarten, Adam S; Allen, Bryan; Lin, Hui-Yi; Ercole, Cesar E; Sexton, Wade J; Spiess, Philippe E

    2014-02-01

    Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system. The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size. One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only. The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes.

    Science.gov (United States)

    George, Arvin K; Herati, Amin S; Rais-Bahrami, Soroush; Waingankar, Nikhil; Kavoussi, Louis R

    2014-01-01

    To present our experience with laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate oncologic and renal functional outcomes. A retrospective review of LPN cases performed in 488 patients was performed. Hilar lesions were defined as renal cortical tumors in direct physical contact with the renal artery, vein, or both, as identified on preoperative imaging and confirmed intraoperatively. The clinicopathologic parameters, perioperative course, complications, and oncologic and 6-month renal functional outcomes were analyzed. A total of 488 patients underwent LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL). There were no statistically significant differences noted in any of the perioperative parameters investigated despite a higher nephrometry complexity score in the hilar group. Change in estimated glomerular filtration rate at 6 months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar tumors, respectively (P = NS). There was 1 recurrence detected in the hilar group, with a median follow-up of 41.6 months. In the hands of an experienced laparoscopist, LPN can safely be performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Skull metastasis revealing a renal tumor: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Mohamed Badri

    Full Text Available Background: Renal cell carcinomas represent 85% of malignant renal tumors. Typically, the tumor remains asymptomatic a long time before the appearance of urologic clinical signs. In some cases, metastasis can precede the manifestations of the primary tumor. Different sites are potential metastatic localizations for renal tumors, including skull metastases who represent a very rare location. Case description: We report the case of a 65-year-old man presented after the appearance of a skull mass. This tumefaction developed and had progressively grown up during 9 months. Neurological examination was normal. Brain imaging showed a soft tissue lesion in the left parietal bone with marked osteolysis. Peroperative was found a huge oval-shape hemorrhagic and firm mass associated with scalp invasion and bone destruction that was totally resected. Histopathology revealed renal cell carcinoma (RCC. Pelvic and abdominal CT scan was performed, revealing a large mass on the left kidney with irregular contours and poor definition. The patient was then transferred to urology where he underwent nephrectomy. The patient went then through adjuvant chemotherapy. Clinical and radiological follow up of 12 months did not bring to light tumor recurrence. Conclusions: Although metastases to the head and neck occur infrequently, they should be considered when evaluating any unusual subcutaneous mass in the head and neck. RCC should not be discounted when sites as unlikely as the calvaria are evaluated. Treatment of metastatic renal cell carcinoma is complex, and the optimal regimen for achieving a lasting response without severe toxicity has not yet been defined. Keywords: Renal tumor, Skull metastasis, Neurosurgery

  15. Infestation of the human kidney with Dioctophyma renale.

    Science.gov (United States)

    Ignjatovic, Ivan; Stojkovic, Ivica; Kutlesic, Cedo; Tasic, Suzana

    2003-01-01

    Human infestation with Dioctophyma renale is presented. Clinical signs and diagnostic findings are unspecific. They are discussed and a conservative therapeutic approach is suggested. Copyright 2003 S. Karger AG, Basel

  16. Morphometric scores for renal tumors: What does the radiologist need to know?

    Energy Technology Data Exchange (ETDEWEB)

    Millet, Ingrid; Doyon, Fernanda Curros; Pages, Emma [Department of Imaging, CHU Montpellier (France); Thuret, Rodolphe [Department of Urology, CHU Montpellier (France); Taourel, Patrice, E-mail: p-taourel@chu-montpellier.fr [Department of Imaging, CHU Montpellier (France)

    2014-08-15

    Numerous therapeutic options are possible in the treatment of renal carcinomas including radical nephrectomy, partial nephrectomy, cryoablation, radiofrequency, active follow-up and among surgical treatments, different approaches may be used such as laparotomy, laparoscopy, robotic-assisted intervention. The choice between these different procedures is partially based on the anatomic conditions of the tumors. Different anatomic scores determined from cross-sectional imaging have been built to predict the complexity of the surgical procedure. The goals of this article are to review the relevant morphologic pattern for management of patients with renal tumors, to know how to calculate these different scores and to understand the clinical applications of these scores.

  17. Morphometric scores for renal tumors: What does the radiologist need to know?

    International Nuclear Information System (INIS)

    Millet, Ingrid; Doyon, Fernanda Curros; Pages, Emma; Thuret, Rodolphe; Taourel, Patrice

    2014-01-01

    Numerous therapeutic options are possible in the treatment of renal carcinomas including radical nephrectomy, partial nephrectomy, cryoablation, radiofrequency, active follow-up and among surgical treatments, different approaches may be used such as laparotomy, laparoscopy, robotic-assisted intervention. The choice between these different procedures is partially based on the anatomic conditions of the tumors. Different anatomic scores determined from cross-sectional imaging have been built to predict the complexity of the surgical procedure. The goals of this article are to review the relevant morphologic pattern for management of patients with renal tumors, to know how to calculate these different scores and to understand the clinical applications of these scores

  18. Brown tumor: clinical findings of secondary hyperparathyroidism in patients with renal osteodystrophy.

    Science.gov (United States)

    Silva, Mairaira Teles Leão E; Cedraz, Juliana Silva Barros; Pontes, Caetano Guilherme Carvalho; Trento, Cleverson Luciano; Brasileiro, Bernardo Ferreira; Piva, Marta Rabello; Pereira, Fabiano Alvim

    2017-01-01

    A brown tumor, or osteoclastoma, is a nonneoplastic bony lesion associated with hyperparathyroidism and directly related to increased levels of parathyroid hormone. These tumors result from excessive osteoclastic activity. This article presents 3 cases of brown tumor localized in facial bones. The lesions were the result of secondary hyperparathyroidism associated with chronic renal failure. The patients were two 42-year-old men and a 39-year-old woman. All patients had been treated systemically by hemodialysis for more than 10 years. This article highlights the importance of proper diagnosis and management of dental patients presenting with a brown tumor.

  19. Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.

    Science.gov (United States)

    Joshi, Shreyas S; Uzzo, Robert G

    2017-05-01

    Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

    International Nuclear Information System (INIS)

    Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.; Lichtenberg, T.

    1984-01-01

    Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, β-HCG, and β/sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serum the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and β/sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum β-HCG was normal in all patients. According to these results serum ferritin, TPA, and β/sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum β/sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and β/sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases

  1. Biomarkers of Renal Tumor Burden and Progression in TSC

    Science.gov (United States)

    2013-09-01

    implications. Standard of care should include routine genotyping and regular creatinine measurement in all TSC patients to help guide clinical...pressure, serum chemistries, urinalysis and urine chemistries). (B) Measure soluble growth factors, angiogenesis factors and renal injury molecules in...ELISA was unacceptably limited compared to the standard curve. This limitation restricts its ability to discriminate between samples from TSC patients

  2. Prognostic Factors Influencing the Development of an Iatrogenic Pneumothorax for Computed Tomography-Guided Radiofrequency Ablation of Upper Renal Tumor

    International Nuclear Information System (INIS)

    Park, B.K.; Kim, C.K.

    2008-01-01

    Background: Percutaneous radiofrequency (RF) ablation of upper renal tumors is considered a minimally invasive treatment, but this technique may cause pneumothorax. Purpose: To assess retrospectively the prognostic factors influencing the development of iatrogenic pneumothorax for RF ablation of upper renal tumors. Material and Methods: Computed tomography (CT)-guided RF ablation was performed in 24 patients (21 men, three women; age range 31-77 years, mean age 53.3 years) with 28 upper renal tumors. Various factors for pneumothorax-complicated (PC) upper renal tumors and non-pneumothoracic (NP) upper renal tumors were compared during RF ablation to determine which of the factors were involved in the development of pneumothorax. Results: Among 28 upper renal tumors in 24 patients, a pneumothorax occurred accidentally in six patients with eight tumors and intentionally in two patients with two tumors. This complication was treated with conservative management, instead of tube drainage. PC upper renal tumors had shorter distance from the lung or from the costophrenic line to the tumor, a larger angle between the costophrenic line and the tumor, and a higher incidence of intervening lung tissue than NP upper renal tumors (P<0.01). Intervening lung tissue was more frequently detected on CT images obtained with the patient in the prone position than on CT images obtained with the patient in the supine position. Conclusion: The presence of intervening lung tissue and the close proximity between an upper renal tumor and the lung are high risk factors for developing an iatrogenic pneumothorax. Pre-ablation CT scan should be performed in the prone position to exactly evaluate intervening lung tissue

  3. Radiological classification of renal angiomyolipomas based on 127 tumors

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    Prando Adilson

    2003-01-01

    Full Text Available PURPOSE: Demonstrate radiological findings of 127 angiomyolipomas (AMLs and propose a classification based on the radiological evidence of fat. MATERIALS AND METHODS: The imaging findings of 85 consecutive patients with AMLs: isolated (n = 73, multiple without tuberous sclerosis (TS (n = 4 and multiple with TS (n = 8, were retrospectively reviewed. Eighteen AMLs (14% presented with hemorrhage. All patients were submitted to a dedicated helical CT or magnetic resonance studies. All hemorrhagic and non-hemorrhagic lesions were grouped together since our objective was to analyze the presence of detectable fat. Out of 85 patients, 53 were monitored and 32 were treated surgically due to large perirenal component (n = 13, hemorrhage (n = 11 and impossibility of an adequate preoperative characterization (n = 8. There was not a case of renal cell carcinoma (RCC with fat component in this group of patients. RESULTS: Based on the presence and amount of detectable fat within the lesion, AMLs were classified in 4 distinct radiological patterns: Pattern-I, predominantly fatty (usually less than 2 cm in diameter and intrarenal: 54%; Pattern-II, partially fatty (intrarenal or exophytic: 29%; Pattern-III, minimally fatty (most exophytic and perirenal: 11%; and Pattern-IV, without fat (most exophytic and perirenal: 6%. CONCLUSIONS: This proposed classification might be useful to understand the imaging manifestations of AMLs, their differential diagnosis and determine when further radiological evaluation would be necessary. Small (< 1.5 cm, pattern-I AMLs tend to be intra-renal, homogeneous and predominantly fatty. As they grow they tend to be partially or completely exophytic and heterogeneous (patterns II and III. The rare pattern-IV AMLs, however, can be small or large, intra-renal or exophytic but are always homogeneous and hyperdense mass. Since no renal cell carcinoma was found in our series, from an evidence-based practice, all renal mass with detectable

  4. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  5. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    International Nuclear Information System (INIS)

    Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

    2007-01-01

    Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses

  6. Can selective pharmaco-angiography of renal tumor replace the examination under surgery?

    International Nuclear Information System (INIS)

    Will, C.H.; Bach, D.; Koop, H.; Impekoven, P.

    1996-01-01

    Can primary nephrectomy be performed without preliminary sample excision of the tumor if pharmaco-angiography of the kidney has demonstrated the typical tumor vascularization? To clarify this question in 32 patients with 'displacing mass' of the kidney, verified in sonography and computer-tomography, or hematuria of unknown origin, we prospectively performed an additional pharmaco-angiography of the respective kidney. In 18 patients with tumor vascularization in the pharmaco-angiography, intraoperatively we found 15 malignant renal cell carcinomas, 1 patient with transitional cell carcinoma of the renal pelvis, 1 leiomyosarcoma, and 1 high-differentiated tumor of only 2 cm in diameter with unclear dignity, which was treated by enucleation. In cases of an intrarenal lesion of more than 3 cm in diameter and additional tumor vascularization seen in selective pharmaco-angiography, the kidney undoubtedly can be removed by primary nephrectomy without a preliminary sample excision to confirm the diagnosis. For tumors with a diameter of less than 3 cm and additional tumor-vascularization, the option should be enucleation. If there is a 'tumor' without typical malignant vascularization, the exploration by sample excision should be performed. Depending on the histological result the tumor should be removed by enucleation or nephrectomy. (orig.) [de

  7. Spontaneous rupture of renal pelvis secondary to ureteral obstruction by urothelial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Daniel Alvarenga; Palma, Ana Laura Gatti; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago Jose; Caserta, Nelson Marcio Gomes, E-mail: daniel_alvafer@yahoo.com.br, E-mail: daniel_alvafer@icloud.com [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Medicina. Dept. de Radiologia

    2014-09-15

    Partial spontaneous rupture of the upper urinary tract is rare and usually associated with nephrolithiasis. Other reported causes, apart from instrumentation and trauma, involve obstructive ureteral tumor in the pelvic cavity, retroperitoneal fibrosis, fluid overload, and pregnancy. We report a case of spontaneous rupture of renal pelvis secondary to ureteral obstruction caused by urothelial tumor, clinically suspected and evaluated by CT scans and MRIs, discussing the relevant findings for diagnosis.(author)

  8. Value of T2-weighted MR imaging in differentiating low-fat renal angiomyolipomas from other renal tumors

    International Nuclear Information System (INIS)

    Choi, Hyuck Jae; Kim, Jeong Kon; Kim, Mi-Hyun; Cho, Kyoung-Sik; Ahn, Hanjong; Kim, Choung-Soo

    2011-01-01

    Background: Accurate preoperative diagnosis of fat scanty angiomyolipomas is an important clinical issue. By evaluating the low signal intensity of angiomyolipomas in MR T2-weighted images the diagnostic accuracy can be elevated. Purpose: To retrospectively assess the usefulness of T2-weighted MR imaging for differentiating low-fat angiomyolipomas (AMLs) from other renal tumors. Material and Methods: We retrospectively evaluated 71 patients with surgically proven renal masses (10 AMLs, 57 renal cell carcinomas [RCCs], and four oncocytomas), all of which showed no visible fat as well as gradual enhancement patterns on contrast-enhanced CT. Signal intensity was measured in each renal mass and in the spleen on T2-weighted images, and each signal intensity ratio (SIR) was calculated; SIR values were then compared in the AML and non-AML groups. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of the two parameters for differentiating the two groups. Results: The SIR values (77 ± 24% vs. 162 ± 79%, p = 0.002) were significantly lower in the AML than in the non-AML group. The area under the ROC curve was 0.926 for SIR. The sensitivity and specificity in the diagnosis of AMLs were 90% and 90.2%, using SIR cut-off of 92.5%. Conclusion: Signal intensity measurements on T2-weighted MR images can differentiate AML from non-AML in the kidney

  9. Hyperdiagnostic of renal tumor by intravenous urography in patient with adult polycystic disease

    International Nuclear Information System (INIS)

    Djerassi, R.; Lubomirova, M.; Mutafova, I.; Bogov, B.; Gavrikova, V.; Garvanska, G.

    2005-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the often seen (from 1:400 to 1:1000) inherited renal diseases with serious prognosis. The exact diagnosis, earlier treatment of the urinary tract infections and hypertension were the steps for prevention of the renal disease progression. The abdominal ultrasound is method used for screening. The frequency of the renal tumors in general population was not higher compared to those in patients with ADPKD. We described and discussed the results obtained by different imaging techniques in 23 years old female with family history for ADPKD. She was admitted to the 'Alexandrovska' University Hospital Nephrology Clinic because of the recurrence of the urinary tract infection. The diagnosis of renal tumor was suspected by renal intravenous pyelography (IVP). All the others imaging techniques - Triplex sonography-B-mode, Color, Pulse, Power Doppler, Tissue Doppler as well as contrast computer tomography showed the polycystic kidney disease, without focal changes, with several small cysts based in the medulla near distal calyces. This was probably the reason for the false-positive image made by IVP. The diagnostic values of the different imaging techniques in making the exact diagnosis in patients with polycystic kidney disease were comment, as well as a peculiar ultrasound image of the polycystic kidney in young patients, aged less then 30 years. To make the correct diagnosis of ADPKD the combination of all known imaging techniques was needed. The small kidney tumors were better visualized by tissue-harmonic ultrasound

  10. Spontaneous renal tumors suspected of being familial in sprague-dawley rats.

    Science.gov (United States)

    Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

    2012-12-01

    Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.

  11. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio [Okayama Univ. (Japan). Graduate School of Medicine and Dentistry

    2003-08-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  12. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    International Nuclear Information System (INIS)

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

    2003-01-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  13. pH distribution in human tumors

    International Nuclear Information System (INIS)

    Thistlethwaite, A.J.; Leeper, D.B.; Moylan, D.J.; Nerlinger, R.E.

    1984-01-01

    pH distribution in human tumors is being determined to evaluate this parameter as a prognostic indicator of hyperthermia response. pH is measured by a modified glass pH electrode (21g, model MI 408, Microelectrodes, Inc., Londonderry, NH) inserted through an 18g open-ended Angiocath. Eight tumors have been evaluated to date; and of those, 3 were also assayed after the first heat treatment coincident with determination of blood flow. Tumors were between 2-5 cm, of various histologies, and of primary, recurrent, or metastatic origin. 2-4 measurements were made per tumor. Pretreatment readings were between 6.4 and 7.2 pH units. As tumor blood flow increased after 1 hr heating (41.5 - 43 0 ) pH rose 0.1 - 0.3 units. Normal rat muscle yields pH readings of 7.35 - 7.45. Although there was considerable heterogeneity of pH within tumors, accuracy and drift were not a problem. 5-15 min were required for pH stabilization after catheter insertion and <5 min after electrode insertion. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Patient tolerance has not been a problems. This study suggests that human tumor tissue has a preponderance of areas more acidic than normal tissue. This may serve to sensitize tumor cells to hyperthermia and provide a prognostic indicator of tumor response

  14. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    Science.gov (United States)

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-11-01

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

  15. Tumoral calcinosis in a dog with chronic renal failure : clinical communication

    Directory of Open Access Journals (Sweden)

    T.C. Spotswood

    2003-06-01

    Full Text Available A 2-year-old male German shepherd dog in poor bodily condition was evaluated for thoracic limb lameness due to a large, firm mass medial to the left cranial scapula. Radiography revealed several large cauliflower-like mineralized masses in the craniomedial left scapula musculature, pectoral region and bilaterally in the biceps tendon sheaths. Urinalysis, haematology and serum biochemistry showed that the dog was severely anaemic, hyperphosphataemic and in chronic renal failure. The dog was euthanased and a full post mortem performed. A diagnosis of chronic renal failure with secondary hyperparathyroidism was confirmed. The mineralized masses were grossly and histopathologically consistent with a diagnosis of tumoral calcinosis. Tumoral calcinosis associated with chronic renal failure that does not involve the foot pads is rarely seen.

  16. The contemporary role of renal mass biopsy in the management of small renal tumors

    International Nuclear Information System (INIS)

    Lim, Amy; O'Neil, Brock; Heilbrun, Marta E.; Dechet, Christopher; Lowrance, William T.

    2012-01-01

    The selective use of percutaneous biopsy for diagnosis in renal masses is a relatively uncommon approach when compared to the management of other solid neoplasms. With recent advancements in imaging techniques and their widespread use, the incidental discovery of asymptomatic, small renal masses (SRM) is on the rise and a substantial percentage of these SRM are benign. Recent advances in diagnostics have significantly improved accuracy rates of renal mass biopsy (RMB), making it a potentially powerful tool in the management of SRM. In this review, we will discuss the current management of SRM, problems with the traditional view of RMB, improvements in the diagnostic power of RMB, cost-effectiveness of RMB, and risks associated with RMB. RMB may offer important information enabling treating clinicians to better risk-stratify patients and ultimately provide a more personalized treatment approach for SRM.

  17. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    International Nuclear Information System (INIS)

    Mellas, J.; Hammerman, M.R.

    1986-01-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

  18. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies.

    Science.gov (United States)

    Neri, G; Martini-Neri, M E; Katz, B E; Opitz, J M

    1984-09-01

    We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed.

  19. Brown tumors in patients with chronic renal failure and secondary hyperparathyroidism: Report of 12 cases

    Directory of Open Access Journals (Sweden)

    Fatma Lilia

    2010-01-01

    Full Text Available Brown tumors are unusual but serious complications of renal osteodystrophy. We retrospectively studied 12 patients presenting with chronic renal failure and brown tumor related to secondary hyperparathyroidism. Eleven patients were on chronic hemodialysis. The median duration between renal failure and end stage renal failure was 36 months (range: 12-190 months and the median duration in dialysis for 11 cases: 92 months (range: 72-252 months. The bone pain was noted in all cases (100%, pathological fracture in one case (8% and a palpable bone tumor in 10 cases (83%. Elevated serum Calcium (> 2.35 mmol/L was noted in four cases (33%, elevated serum Phosphate (> 1.78 mmol/L in ten cases (80%, elevated serum Alkaline Phosphate (> 290 UI/L in all cases and intact PTH was > 300 pg/mL in all cases with a serum median rate at 1475 pg/mL (range: 682-3687 pg/L. Subtotal parathyroidectomy was performed in all cases with a resultant decrease in size of brown tumors. We report here patient with CKD with unusual frequency and variable locations. This may be attributed tothe lack of the new calcium free phosphate binders and calcimimetics.

  20. Utilization and perioperative complications of laparoscopic cryoablation vs. robotic partial nephrectomy for localized renal tumors

    Directory of Open Access Journals (Sweden)

    Aaron C. Weinberg

    2015-06-01

    Full Text Available ABSTRACTObjective:To compare the utilization, perioperative complications and predictors of LCA versus RPN in the treatment of localized renal tumors.Methods:From the Nationwide Inpatient Sample we identified patients undergoing RPN or LCA for the treatment of localized renal tumors from October 2008 through 2010. Patient and hospital-specific factors which predict postoperative complications and use of LCA were investigated.Results:14,275 patients with localized renal tumors were identified: 70.3% had RPN and 29.7% had LCA. LCA was more common in older patient and at hospitals without robotic consoles. No difference was identified in perioperative complications (0.2% vs. 0.2%, transfusion (5.1% vs. 6.2%, length of stay (2.9 vs. 3.0 days or median cost ($41,753 vs. $44,618 between the groups, LCA vs. RPN. On multivariate analysis sicker patients were more likely to have LCA (OR 1.34, p=0.048 and sicker patients had greater postoperative complications (OR 3.30, pConclusions:More patients had RPN vs. LCA; surgical technique was not predictive of postoperative complications. As technology develops to treat localized renal tumors, it will be important to continue to track outcomes and costs for procedures including RPN and LCA.

  1. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  2. Renal tumors in adult Saudi patients: A review of 43 cases

    International Nuclear Information System (INIS)

    Talic, Riyadh F.; El-Faqih, Salah R.

    1996-01-01

    Seventy-nine patients with renal tumors were seen at King Khalid Univ. Hospital (KKUH) over a 10-year period from 1985 to November 1995. In a retrospective study, we analyzed the records of 43 Saudi patients from all over the Kingdom; they represented 54% of all patients encountered. Fourteen percent of the patients had benign renal tumors in the form of angiomyolipoma and oncocytoma. Eighty-six percent of the patients had malignant renal tumors. The largest subset of 33 patients (76.7%) had renal cell carcinoma (RCC). The mean age of this group was 50.9, with a male-to-female ratio of 1.3:1. The duration of symptoms varied widely from a few months to a few years and the most common presenting symptom was loin pain. Only four patients were smokers and one patient had Von Hippel Lindaus syndrome; no other risk factors could be identified in this group. This study shows a large percentage of angiomyolipoma among the tumors encountered. It also shows a high percentage of Saudi female patients in the RCC group; otherwise the pattern and clinicopathological features resemble those presented in the international literature. (author)

  3. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  4. T3 receptors in human pituitary tumors.

    Science.gov (United States)

    Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

    2009-11-01

    The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

  5. Is percutaneous microwave ablation of liver tumor safe for patients with renal dysfunction

    International Nuclear Information System (INIS)

    Liu Cun; Wang Yang; Yu Xiaoling; Dong Baowei; Zhou Pei; Ren He; Liang Ping

    2011-01-01

    Purpose: To determine the safety of percutaneous microwave ablation of primary and metastatic liver tumor for patients with renal dysfunction. Materials and methods: Fifty primary and metastatic liver tumors in 23 patients with renal dysfunction were retrospectively reviewed at our institution. Renal function was determined by measuring serum creatinine and serum urea before MWA as baseline, within 1 week and at last follow-up. The mean creatinine was 1.69 ± 0.32 mg/dL, 1.71 ± 0.33 mg/dL, and 1.71 ± 0.26 mg/dL respectively, there was not a statistically significant difference between baseline and at last follow-up (P = 0.26). The mean serum urea was 52.52 ± 6.48 mg/dL, 56.55 ± 14.72 mg/dL, and 57.90 ± 16.39 mg/dL respectively, there was not a statistically significant difference between baseline and within 1 week (P = 0.119), between within baseline and at last follow-up (P = 0.090). At the last follow-up examination, all patients had adequately functioning kidneys and did not require any form of renal replacement therapy. This is a small retrospectively study including highly selected patients treated. Therefore, further study should to determine the safety of percutaneous MWA for patients with renal dysfunction in the future. Conclusions: Percutaneous microwave ablation of primary and metastatic liver tumor is no adverse influence on renal function for patients with renal dysfunction in this preliminary series, which can be a minimally invasive alternative therapy.

  6. Review of laparoscopic partial nephrectomy in the treatment of renal tumors, T1 stadium in adults; Revision de la nefrectomia parcial laparoscopica en el tratamiento de los tumores renales, estadio T1 en adultos

    Energy Technology Data Exchange (ETDEWEB)

    Zamora Montes de Oca, Maria Jose

    2012-07-01

    The T1 renal cancer in adults is made known; incidence, characteristics and management. Renal cell carcinoma has been the most common malignancy of the kidney, percentage is close to three percent of solid tumors of adults. The treatments for this tumor are analyzed: open radical nephrectomy, laparoscopic radical nephrectomy, open partial nephrectomy and laparoscopic partial nephrectomy. Laparoscopic partial nephrectomy has represented an alternative option acceptable, safely and with good oncological and surgical outcomes for patients, as it is used to conserve nephrons and simultaneously to resect the tumor of a complete form promoting in the future the patient present a good renal function. Additionally, a adequate oncological control has reduced the risk of submit postoperative renal failure. An evolution of laparoscopic partial nephrectomy is presented determining the procedure for renal tumors in state T1 in the adults [Spanish] El cancer renal T1 en adultos es dado a conocer; su incidencia, caracteristicas y manejo. El carcinoma de celulas renales ha sido la malignidad mas comun de los rinones, su porcentaje se acerca al tres porciento de los tumores solidos de los adultos. Los tratamientos para combatir ese tumor son analizados: nefrectomia radical abierta, nefrectomia radical laparoscopica, nefrectomia parcial abierta y nefrectomia parcial laparoscopica. La nefrectonomia parcial laparoscopica ha representado una opcion alternativa aceptable, segura y con buenos resultados oncologicos y quirurgicos para los pacientes, ya que es utilizada para conservar nefronas y a la vez poder resecar el tumor de una forma completa promoviendo en el futuro que el paciente presente un buen funcionamiento renal. Ademas, un adecuado control oncologico ha reducido el riesgo de presentar insuficiencia renal postoperatoria. Una evolucion de la nefrectonomia parcial laparoscopica es presentada determinando el procedimiento para tumores renales en estado T1 en los adultos.

  7. CT-Guided Microwave Ablation of 45 Renal Tumors: Analysis of Procedure Complexity Utilizing a Percutaneous Renal Ablation Complexity Scoring System.

    Science.gov (United States)

    Mansilla, Alberto V; Bivins, Eugene E; Contreras, Francisco; Hernandez, Manuel A; Kohler, Nathan; Pepe, Julie W

    2017-02-01

    To develop a scoring system that stratifies complexity of percutaneous ablation of renal tumors. Analysis was performed of 36 consecutive patients (mean age, 64 y; range, 30-89 y) who underwent CT-guided microwave (MW) ablation of 45 renal tumors (mean tumor diameter, 2.4 cm; range, 1.2-4.0 cm). Technical success and effectiveness were determined based on intraprocedural and follow-up imaging studies. The RENAL score and the proposed percutaneous renal ablation complexity (P-RAC) score were calculated for each tumor. Technical success was 93.3% (n = 42). Biopsy of 38 of 45 renal tumors revealed 23 renal cell carcinomas. Median follow-up period was 9.7 months (range, 2.9-46.8 months). There were no tumor recurrences. One major complication, ureteropelvic junction stricture, occurred (2.6%). The P-RAC score was found to differ statistically from the RENAL score (t = 3.754, df = 44, P = .001). A positive correlation was found between the P-RAC score and number of antenna insertions (r = .378, n = 45, P = .011) and procedure duration (r = .328, n = 45, P = .028). No correlation was found between the RENAL score and number of MW antenna insertions (r = .110, n = 45, P = .472) or procedure duration (r = .263, n = 45, P = .081). Hydrodissection was significantly more common in the P-RAC high-complexity category than in low-complexity category (χ 2 = 12.073, df = 2, P = .002). The P-RAC score may be useful in stratifying percutaneous renal ablation complexity. Further studies with larger sample sizes are necessary to validate the P-RAC score and to determine if it can predict risk of complications. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  8. Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

    Science.gov (United States)

    Scalici Gesolfo, Cristina; Serretta, Vincenzo; Di Maida, Fabrizio; Giannone, Giulio; Barresi, Elisabetta; Franco, Vito; Montironi, Rodolfo

    2017-02-01

    Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory. Copyright © 2016. Published by Elsevier GmbH.

  9. Prognostic factors in urothelial renal pelvis and ureter tumors: a multicenter rare cancer network study

    International Nuclear Information System (INIS)

    Ozsahin, M.; Zouhair, A.; Villa, S.; Storme, G.; Chauvet, B.; Taussky, D.; Houtte, P. van; Ries, G.; Bontemps, P.; Coucke, P.; Mirimanoff, R.O.

    1997-01-01

    Purpose: To assess the prognostic factors and the outcome in patients with transitional-cell carcinoma of the renal pelvis and/or ureter. Materials and Methods: A series of 138 patients treated between 1971 and 1996 for transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicenter study of the Rare Cancer Network. Twelve patients with distant metastases were excluded from the statistical evaluation. In the remaining 126 patients, median age was 66 years (range: 41-87). The male to female ratio was 2.5 ((90(36))). All but 3 patients underwent a radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 8), and ureterectomy (n = 4). There were 6 stage pTa, 22 pT1, 17 pT2, 37 pT3, 37 pT4, and 7 pTx tumors. The pN-stage distribution was as follows: 69 pN0, 8 pN1, 14 pN2, 4 pN3, and 31 pNx. Sixty-one percent (n = 77) of the tumors were located in the renal pelvis, and 21% (n = 27) in the ureter. Renal pelvis and ureter localization was present together in 22 (17%) patients. There were 4 grade 1, 37 grade 2, 42 grade 3 tumors (grade was not registered in 43). Following surgery, microscopic (n = 16) or macroscopic (n = 17) tumor rest was detected in 33 patients. Postoperative radiotherapy was given in 45 (36%) patients with a median total dose of 50 Gy (range: 20-66) in median 25 fractions (range: 4-33). Adjuvant systemic chemotherapy was administered in 12 (10%) patients. The median follow-up period was 39 months (range: 5-220). Results: In a median period of 9 months (range: 1-141), 66% (n = 81) of the patients relapsed (local in 34, locoregional in 7, regional in 16, and distant in 24). The 5- and 10-year overall survival (Kaplan-Meier product-limit estimates) was respectively 29% (± 5) and 19% (± 5) in all patients. In univariate analyses (logrank test), statistically significant

  10. Value of percutaneous needle biopsy of small renal tumors in patients referred for cryoablation.

    Science.gov (United States)

    Iguchi, Toshihiro; Hiraki, Takao; Gobara, Hideo; Fujiwara, Hiroyasu; Sakurai, Jun; Matsui, Yusuke; Araki, Motoo; Nasu, Yasutomo; Kanazawa, Susumu

    2017-04-01

    To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment. Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared. After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p = .01). Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

  11. Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

    Science.gov (United States)

    2015-12-01

    production in the presence of oxygen (11, 12). Increased glycolysis facilitates the uptake and incorporation of nutrients and biomass needed for cell... shell coil; (d) Hyperpolarized lactate images overlaid on T2 weighted anatomical images, clearly depicting the tumor voxels (Figure 5). As shown in

  12. Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

    Science.gov (United States)

    Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

    2017-05-01

    To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p renal parenchyma volume preservation (89.19 vs 84.27%, p renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

  13. Development and Validity of a Silicone Renal Tumor Model for Robotic Partial Nephrectomy Training.

    Science.gov (United States)

    Monda, Steven M; Weese, Jonathan R; Anderson, Barrett G; Vetter, Joel M; Venkatesh, Ramakrishna; Du, Kefu; Andriole, Gerald L; Figenshau, Robert S

    2018-04-01

    To provide a training tool to address the technical challenges of robot-assisted laparoscopic partial nephrectomy, we created silicone renal tumor models using 3-dimensional printed molds of a patient's kidney with a mass. In this study, we assessed the face, content, and construct validity of these models. Surgeons of different training levels completed 4 simulations on silicone renal tumor models. Participants were surveyed on the usefulness and realism of the model as a training tool. Performance was measured using operation-specific metrics, self-reported operative demands (NASA Task Load Index [NASA TLX]), and blinded expert assessment (Global Evaluative Assessment of Robotic Surgeons [GEARS]). Twenty-four participants included attending urologists, endourology fellows, urology residents, and medical students. Post-training surveys of expert participants yielded mean results of 79.2 on the realism of the model's overall feel and 90.2 on the model's overall usefulness for training. Renal artery clamp times and GEARS scores were significantly better in surgeons further in training (P ≤.005 and P ≤.025). Renal artery clamp times, preserved renal parenchyma, positive margins, NASA TLX, and GEARS scores were all found to improve across trials (P <.001, P = .025, P = .024, P ≤.020, and P ≤.006, respectively). Face, content, and construct validity were demonstrated in the use of a silicone renal tumor model in a cohort of surgeons of different training levels. Expert participants deemed the model useful and realistic. Surgeons of higher training levels performed better than less experienced surgeons in various study metrics, and improvements within individuals were observed over sequential trials. Future studies should aim to assess model predictive validity, namely, the association between model performance improvements and improvements in live surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Comparison of renal function following donor nephrectomy versus radical nephrectomy for renal tumor

    Directory of Open Access Journals (Sweden)

    Mohamed Etafy

    2015-01-01

    Full Text Available In this study, we compared renal function in patients after donor nephrectomy (DN and radical nephrectomy (RN. We retrospectively reviewed 68 patients (mean follow-up 15 months, including 30 patients who had undergone DN and 38 patients who had undergone RN. The study was performed between April 2006 and July 2010 at a single institute. Patients were matched for age and co-morbidities (hypertension and diabetes mellitus. We calculated the estimated glomerular filtration rate (eGFR using the Modification of Diet in Renal Disease study group equation. Parameters studied included GFR (≥60 to 2.0 mg/dL, metabolic acidosis (serum bicarbonate 30 mg. There were no significant demographic differences between the two study groups. After a mean follow-up of 15 months, low eGFR (<60 mL/min/1.73 m 2 was seen in 28% and 6.7% of patients in the RN and DN groups, respectively (P = 0.03. Similarly, proteinuria was seen in 21% vs 0%, P = 0.007, and de novo elevated creatinine was seen in 13% vs 0%, respectively P = 0.04; thus the changes were greater in the RN group. Our study shows that undergoing RN had a significantly greater risk of developing renal insufficiency and proteinuria compared with age-and co-morbidity-matched patients undergoing DN. We concluded that patients undergoing RN show a significantly greater risk of developing renal insufficiency and proteinuria compared with the patients undergoing DN.

  15. Subtype differentiation of renal tumors using voxel-based histogram analysis of intravoxel incoherent motion parameters.

    Science.gov (United States)

    Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh

    2015-03-01

    The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [σ(Dt)] differentiated ccRCC (0.362 ± 0.136 × 10 mm/s) from AML (0.199 ± 0.043 × 10 mm/s) (P = 0

  16. Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea); Lee, Hyun Moo [Sungkyunkwan University School of Medicine, Department of Urology, Samsung Medical Center, Seoul (Korea)

    2008-07-15

    The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 {+-} 0.6 cm before ablation to 1.7 {+-} 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size. (orig.)

  17. Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

    International Nuclear Information System (INIS)

    Park, Byung Kwan; Kim, Chan Kyo; Lee, Hyun Moo

    2008-01-01

    The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 ± 0.6 cm before ablation to 1.7 ± 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size. (orig.)

  18. Radioimmunodetection of human melanoma tumor xenografts with human monoclonal antibodies

    International Nuclear Information System (INIS)

    Gomibuchi, Makoto; Saxton, R.E.; Lake, R.R.; Katano, Mitsuo; Irie, R.F.

    1986-01-01

    A human IgM monoclonal antibody has been established that defines a tumor-associated membrane antigen expressed on human melanoma cells. The antigen has been identified as the ganglioside GD2. In this paper, the authors describe the potential usefulness of the human monoclonal antibody for radioimaging. Nude mice bearing tumors derived from a human melanoma cell line were used as a model. Antibody activity was degradated significantly after labeling with 131 I by the use of a modified chloramine-T method. After testing various concentrations, labeled antibody of a specific activity of 2.8μCi/μg produced the best results. Balb/c nude mice bearing a GD2-positive M14 melanoma cell line were injected with 10-30μg of labeled antibody, and its radiolocalization in different organs and in the whole body were evaluated. The best tumor image was obtained on Day 6. The labeled antibody uptake ratio between tumor and muscle was 9.2:1; the ratio between tumor and liver was 1.4:1. These studies represent the first report of experimental tumor imaging with human monoclonal antibody. Human monoclonals will probably prove to be superior reagents for tumor imaging in melanoma patients if the problem of anti-body radiolysis is resolved. (author)

  19. Is anatomic complexity associated with renal tumor growth kinetics under active surveillance?

    Science.gov (United States)

    Mehrazin, Reza; Smaldone, Marc C; Egleston, Brian; Tomaszewski, Jeffrey J; Concodora, Charles W; Ito, Timothy K; Abbosh, Philip H; Chen, David Y T; Kutikov, Alexander; Uzzo, Robert G

    2015-04-01

    Linear growth rate (LGR) is the most commonly employed trigger for definitive intervention in patients with renal masses managed with an initial period of active surveillance (AS). Using our institutional cohort, we explored the association between tumor anatomic complexity at presentation and LGR in patients managed with AS. Enhancing renal masses managed expectantly for at least 6 months were included for analysis. The association between Nephrometry Score and LGR was assessed using generalized estimating equations, adjusting for the age, Charlson score, race, sex, and initial tumor size. Overall, 346 patients (401 masses) met the inclusion criteria (18% ≥ cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44% patients showed progression to definitive intervention with a median duration of 27 months (range: 6-130). On comparing patients managed expectantly to those requiring intervention, no difference was seen in median tumor size at presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74 vs. 65 y, P anatomic tumor complexity at presentation and renal masses of LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor individual patient radiographic surveillance schedules and warrants further evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

    Science.gov (United States)

    Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

    2017-03-01

    Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

  1. Microwave ablation of renal tumors: state of the art and development trends.

    Science.gov (United States)

    Floridi, Chiara; De Bernardi, Irene; Fontana, Federico; Muollo, Alessandra; Ierardi, Anna Maria; Agostini, Andrea; Fonio, Paolo; Squillaci, Ettore; Brunese, Luca; Fugazzola, Carlo; Carrafiello, Gianpaolo

    2014-07-01

    In the last decades an increased incidence of new renal tumor cases has been for clinically localized, small tumors elderly patients, with medical comorbidities whom the risk of surgical complications may pose a greater risk of death than that due to the tumor itself. In these patients, unsuitable for surgical approach, thermal ablation represents a valid alternative to traditional surgery. Thermal ablation is a less invasive, less morbid treatment option thanks to reduced blood loss, lower incidence of complications during the procedure and a less long convalescence. At present, the most widely used thermal ablative techniques are cryoablation, radiofrequency ablation and microwave ablation (MWA). MWA offers many benefits of other ablation techniques and offers several other advantages: higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times, the ability to use multiple applicators simultaneously, optimal heating of cystic masses and tumors close to the vessels and less procedural pain. This review aims to provide the reader with an overview about the state of the art of microwave ablation for renal tumors and to cast a glance on the new development trends of this technique.

  2. Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

    International Nuclear Information System (INIS)

    Meloni, Maria Franca; Smolock, Amanda; Cantisani, Vito; Bezzi, Mario; D'Ambrosio, Ferdinando; Proiti, Maria; Lee, Fred; Aiani, Luca; Calliada, Fabrizio; Ferraioli, Giovanna

    2015-01-01

    Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors

  3. Mini-flank supra-12th rib incision for open partial nephrectomy for renal tumor with RENAL nephrometry score ≥10: an innovation of traditional open surgery.

    Science.gov (United States)

    Wang, Hang; Sun, Li-an; Wang, Yiwei; Xiang, Zhuoyi; Zhou, Lin; Guo, Jianming; Wang, Guomin

    2015-04-01

    The skill of supra-12th rib mini-flank approach for open partial nephrectomy (MI-OPN) provides an advanced operative method for renal tumor. Compared with laparoscopic and robotic surgery, it may be a feasible selection for the complex renal tumors. We describe our techniques and results of MI-OPN in complex renal tumors with high RENAL nephrometry score (RENAL nephrometry score ≥10). Fifty-five patients diagnosed with renal tumors between January 2009 and July 2013 were included in this study. Eligibility criteria comprised of patients with complex renal tumor (RENAL score ≥10) being candidates for partial nephrectomy (PN). All patients received MI-OPN and all surgeries were performed by a single urologist. The preoperative workup comprised of medical history, physical examination, and routine laboratory tests. Serum creatinine was recorded preoperatively and 2 to 3 months after operation. Operative time, ischemia time, blood loss, operative and postoperative complications, renal function, and pathology parameters were recorded. MI-OPN was successfully performed in all cases. Mean tumor size was 4.7 cm (range: 2.5-8.1). Mean warm ischemia time was 28.1 minutes (range: 21-39), mean operative time was 105 minutes (range: 70-150) and mean estimated blood loss was 68 mL (range: 10-400). Mean postoperative hospital stay was 6.5 days (range: 5-12). Postoperative complications were found in 3 patients (5.5%). The mean pre- and postoperative serum creatinine levels were 76.2 μmol/L (range: 47-132) and 87.1 μmol/L (range: 61-189) with significant difference (P = 0.004). The mean pre- and postoperative estimated glomerular filtration rate (eGFR) were 91.5 (range: 34-133) and 82.5 (range: 22-126.5), respectively with significant difference (P = 0.024). In an average follow-up of 19.9 months (range: 8-50), no local recurrence or systemic progression occurred. In conclusion, MI-OPN can combine the benefits of both minimal invasive and traditional open

  4. Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

    Science.gov (United States)

    Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

    2017-12-18

    Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

  5. Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

    Science.gov (United States)

    Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun

    2017-09-11

    To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

  6. Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model.

    Science.gov (United States)

    Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O

    2017-07-04

    Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

  7. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  8. Structure and chromosomal localization of the human renal kallikrein gene

    International Nuclear Information System (INIS)

    Evans, B.A.; Yun, Z.X.; Close, J.A.

    1988-01-01

    Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7

  9. Efficiency and Reliability of Laparoscopic Partial Nephrectomy for Renal Tumors Larger than 4 cm

    Directory of Open Access Journals (Sweden)

    Faruk Özgör

    2015-03-01

    Full Text Available Aim: To evaluate safety and efficiency of laparoscopic partial nephrectomy for renal tumors larger than 4 cm. Methods: We retrospectivelly evaluated the medical records of 65 patients who underwent laparascopic partial nephrectomy between May 2009 and June 2013 in our clinic. The patients were divided into two groups according to tumor size. Patients with a tumor 4 cm were included in group 1 (n=45 and group 2 (n=20, respectively. Demographic, perioperative and postoperative parameters were compared between the groups. Histopathological examination and surgical margin status were also evaluated. Results: The mean age of the patients was 59.2±10.9 (range: 26- 81 years. The mean tumor size and the mean RENAL nephrometry score were significantly higher in group 2 than in group 1. The mean operation time and warm ischemia time were similar between groups but estimated blood loss and transfusion requirement were significantly higher in group 2. Convertion to open surgery was seen two patients in group 2 and one patient in group 1. Only one patient underwent radical nephrectomy for uncontrolled bleeding in group 2. There was no difference in preoperative and 3-month postoperative serum creatinine levels between the groups. The incidence of positive surgical margin was 0% and 5% in group 1 and group 2, respectively. Conclusion: Laparoscopic partial nephrectomy for renal tumors is an effective and feasible procedure with acceptable oncologic results. However, tranfusion rate and requiremet of pelvicaliceal system repair were more common in patients with tumor >4 cm. (The Medical Bulletin of Haseki 2015; 53:30-5

  10. Lithium and renal and upper urinary tract tumors - results from a nationwide population-based study

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Gerds, Thomas Alexander; Feldt-Rasmussen, Bo

    2015-01-01

    OBJECTIVES: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions...... for lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals. METHODS: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all...... individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii...

  11. A case of a desmoid tumor with an uretertumoral fisttula detected on renal scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun Woo; Lee, Kyu Taek; Lee, Sang Mi [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2016-11-15

    Desmoid tumors are rare benign tumors with aggressive fibroblastic proliferation. Although desmoid tumors do not metastasize, they have locally aggressive features and can cause a urinary fistula. Here, we report a case of a 35-year-old woman with Gardner syndrome who was diagnosed with an intra-abdominal desmoid tumor 1 year previously and who presented with a newly developed cystic mass lesion on a computed tomography scan. The cystic mass lesion was clinically diagnosed as an urinoma from the right ureterotumoral fistula; thus, surgical resection of the mass lesion was planned. However, Tc-99m diethylenetriamine pentaacetic acid renal scintigraphy revealed bilateral ureterotumoral fistulas; hence, the treatment plan was changed to conservative management.

  12. Spontaneous Renal Tumors Suspected of Being Familial in Sprague-Dawley Rats

    OpenAIRE

    Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

    2012-01-01

    Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carci...

  13. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

    Directory of Open Access Journals (Sweden)

    Rowland Randall G

    2008-04-01

    Full Text Available Abstract Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy.

  14. A rare case of retroperitoneal malignant triton tumor invading renal vein and small intestine

    Directory of Open Access Journals (Sweden)

    Mijović Žaklina

    2013-01-01

    Full Text Available Introduction. Malignant Triton tumor is a very rare malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation. Most of those tumors occur in patients with von Recklinghausen’s disease or as a late complication of irradiation and commonly seen in the head, neck, extremities and trunk. Case report. We reported retroperitoneal malignant Triton tumor in a 57-year-old female patient. Skin lesions were not present, and there was no family history of neurofibromatosis or previous irradiation. The presented case is one of a few recorded in the specialized literature that occurs in the retroperitoneal space in sporadic form. In this case, tumor consisted of a multilobular mass was in close relation with the abdominal aorta and inferior vena cava and involved the renal vein with gross invasion of the small intestine. The patient underwent total resection of the tumor and left nefrectomy was performed. The small intestine 10 cm in length was also resected and end-to-end anastomosis was conducted. The postoperative course was uneventful and the patient was discharged from the hospital ten days after the surgery. Conclusion. Diagnostically, it is crucial to recognize this uncommon histological variant because malignant Triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does. The use of the immunohistochemistry is essential in making the correct diagnosis. Only appropriate pathological evaluation supported by immunostaining with S-100 protein and desmin confirmed the diagnosis. Aggressive surgical management treatment improves the prognosis of such cases with adjuvant radiotherapy.

  15. Epigenetic inactivation of CHFR in human tumors

    OpenAIRE

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J.; Jair, Kam-Wing; Schuebel, Kornel E.; Imai, Kohzoh; Tokino, Takashi

    2003-01-01

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin–ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, w...

  16. Activation of the lectin complement pathway on human renal ...

    African Journals Online (AJOL)

    This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

  17. The Human Cell Surfaceome of Breast Tumors

    Science.gov (United States)

    da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

    2013-01-01

    Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

  18. Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation

    Energy Technology Data Exchange (ETDEWEB)

    McEachen, James C., E-mail: james.mceachen2@gmail.com [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Leng, Shuai; Atwell, Thomas D. [Mayo Clinic, Department of Radiology (United States); Tollefson, Matthew K. [Mayo Clinic, Department of Urology (United States); Friese, Jeremy L. [Mayo Clinic, Department of Radiology (United States); Wang, Zhen; Murad, M. Hassan [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Schmit, Grant D. [Mayo Clinic, Department of Radiology (United States)

    2016-02-15

    IntroductionOnce reserved solely for non-surgical cases, percutaneous ablation is becoming an increasingly popular treatment option for a wider array of patients with small renal masses and the radiation risk needs to be better defined as this transition continues.Materials and MethodsRetrospective review of our renal tumor ablation database revealed 425 patients who underwent percutaneous ablation for treatment of 455 renal tumors over a 5-year time period. Imparted radiation dose information was reviewed for each procedure and converted to effective patient dose and skin dose using established techniques. Statistical analysis was performed with each ablative technique.ResultsFor the 331 cryoablation procedures, the mean DLP was 6987 mGycm (SD = 2861) resulting in a mean effective dose of 104.7 mSv (SD = 43.5) and the mean CTDI{sub vol} was 558 mGy (SD = 439) resulting in a mean skin dose of 563.2 mGy (SD = 344.1). For the 124 RFA procedures, the mean DLP was 3485 mGycm (SD = 1630) resulting in a mean effective dose of 50.3 mSv (SD = 24.0) and the mean CTDI{sub vol} was 232 mGy (SD = 149) resulting in a mean skin dose of 233.2 mGy (SD = 117.4). The difference in patient radiation exposure between the two renal ablation techniques was statistically significant (p < 0.001).ConclusionBoth cryoablation and RFA imparted an average skin dose that was well below the 2 Gy deterministic threshold for appreciable sequela. Renal tumor cryoablation resulted in a mean skin and effective radiation dose more than twice that for RFA. The radiation exposure for both renal tumor ablation techniques was at the high end of the medical imaging radiation dose spectrum.

  19. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  20. Hemorrhagic Complications of Percutaneous Cryoablation for Renal Tumors: Results from a 7-year Prospective Study

    International Nuclear Information System (INIS)

    Kakarala, Bharat; Frangakis, Constantine E.; Rodriguez, Ron; Georgiades, Christos S.

    2016-01-01

    PurposeCryoablation of renal tumors is assumed to have a higher risk of hemorrhagic complications compared to other ablative modalities. Our purpose was to establish the exact risk and to identify hemorrhagic risk factors.Materials and MethodsThis IRB approved, 7-year prospective study included 261 renal cryoablations. Procedures were under conscious sedation and CT guidance. Pre- and postablation CT was obtained, and hemorrhagic complications were CTCAE tabulated. Age, gender, tumor size, histology, and probes number were tested based on averages or proportions using their exact permutation distribution. “High-risk” subgroups (those exceeding the thresholds of all variables) were tested for each variable alone, and for all combinations of variable threshold values. We compared the subgroup with the best PPV using one variable, with the subgroup with the best PPV using all variables (McNemmar test).ResultsThe hemorrhagic complication rate was 3.5 %. Four patients required transfusions, two required emergent angiograms, one required both a transfusion and angiogram, and two required bladder irrigation for outlet obstruction. Perirenal space hemorrhage was more clinically significant than elsewhere. Univariate risks were tumor size >2 cm, number of probes >2, and malignant histology (P = 0.005, 0.002, and 0.033, respectively). Multivariate analysis showed that patients >55 years with malignant tumors >2 cm requiring 2 or more probes yielded the highest PPV (7.5 %).ConclusionsAlthough older patients (>55 years old) with larger (>2 cm), malignant tumors have an increased risk of hemorrhagic complications, the low PPV does not support the routine use of embolization. Percutaneous cryoablation has a 3.5 % risk of significant hemorrhage, similar to that reported for other types of renal ablative modalities.

  1. Hemorrhagic Complications of Percutaneous Cryoablation for Renal Tumors: Results from a 7-year Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Kakarala, Bharat, E-mail: bkakara1@jhmi.edu, E-mail: bharat.kakarala@gmail.com [Johns Hopkins University, Vascular and Interventional Radiology (United States); Frangakis, Constantine E., E-mail: cfrangak@jhsph.edu [Johns Hopkins University, Biostatistics and Epidemiology, Bloomberg School of Public Health (United States); Rodriguez, Ron, E-mail: rodriguezr32@uthscsa.edu [University of Texas Health Science Center, Urologic Surgery (United States); Georgiades, Christos S., E-mail: g-christos@hotmail.com [Johns Hopkins University (United States)

    2016-11-15

    PurposeCryoablation of renal tumors is assumed to have a higher risk of hemorrhagic complications compared to other ablative modalities. Our purpose was to establish the exact risk and to identify hemorrhagic risk factors.Materials and MethodsThis IRB approved, 7-year prospective study included 261 renal cryoablations. Procedures were under conscious sedation and CT guidance. Pre- and postablation CT was obtained, and hemorrhagic complications were CTCAE tabulated. Age, gender, tumor size, histology, and probes number were tested based on averages or proportions using their exact permutation distribution. “High-risk” subgroups (those exceeding the thresholds of all variables) were tested for each variable alone, and for all combinations of variable threshold values. We compared the subgroup with the best PPV using one variable, with the subgroup with the best PPV using all variables (McNemmar test).ResultsThe hemorrhagic complication rate was 3.5 %. Four patients required transfusions, two required emergent angiograms, one required both a transfusion and angiogram, and two required bladder irrigation for outlet obstruction. Perirenal space hemorrhage was more clinically significant than elsewhere. Univariate risks were tumor size >2 cm, number of probes >2, and malignant histology (P = 0.005, 0.002, and 0.033, respectively). Multivariate analysis showed that patients >55 years with malignant tumors >2 cm requiring 2 or more probes yielded the highest PPV (7.5 %).ConclusionsAlthough older patients (>55 years old) with larger (>2 cm), malignant tumors have an increased risk of hemorrhagic complications, the low PPV does not support the routine use of embolization. Percutaneous cryoablation has a 3.5 % risk of significant hemorrhage, similar to that reported for other types of renal ablative modalities.

  2. Molecular sub-classification of renal epithelial tumors using meta-analysis of gene expression microarrays.

    Directory of Open Access Journals (Sweden)

    Thomas Sanford

    Full Text Available To evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures.A search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets.We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%. The correct classification by subtype was 19/20 (95% for clear cell, 14/14 (100% for papillary, 17/19 (89% for chromophobe, 18/19 (95% for oncocytomas.Through the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors.

  3. Human Tumor Antigens Yesterday, Today, and Tomorrow.

    Science.gov (United States)

    Finn, Olivera J

    2017-05-01

    The question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES. Most were identified through spontaneous antitumor humoral and cellular immune responses found in cancer patients and include peptides, glycopeptides, phosphopeptides, viral peptides, and peptides resulting from common mutations in oncogenes and tumor-suppressor genes, or common gene fusion events. Many have been extensively tested as candidates for anticancer vaccines. More recently, attention has been focused on the potentially large number of unique tumor antigens, mutated neoantigens, that are the predicted products of the numerous mutations revealed by exome sequencing of primary tumors. Only a few have been confirmed as targets of spontaneous immunity and immunosurveillance, and even fewer have been tested in preclinical and clinical settings. The field has been divided for a long time on the relative importance of shared versus mutated antigens in tumor surveillance and as candidates for vaccines. This question will eventually need to be answered in a head to head comparison in well-designed clinical trials. One advantage that shared antigens have over mutated antigens is their potential to be used in vaccines for primary cancer prevention. Cancer Immunol Res; 5(5); 347-54. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Evaluation of Renal Function in Pediatric Patients After Treatment for Wilms' Tumor.

    Science.gov (United States)

    Janeczko, Małgorzata; Niedzielska, Ewa; Pietras, Wojciech

    2015-01-01

    Wilms' tumor is the most common kidney cancer in children. Treatment consists of pre- and post-operative chemotherapy, surgery and in some cases radiotherapy. The treatment of nephroblastomas is very effective. Hence, the population of adult patients cured of this cancer in their childhood is steadily growing, generating a need for long-term health assessment, including renal function, due to the specifications of the therapy and the location of the tumor. The aim of the study was to evaluate nephrological complications after treatment for nephroblastoma. The study group consisted of 50 children treated in the Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation at Wroclaw Medical University (Poland) from 2002 to 2012. An analysis of the patients' medical histories was carried out. The glomerular filtration rate estimated by the Schwartz formula (GFR by Schwartz), serum creatinine levels, urea and electrolyte concentrations; the results of urinalysis and blood pressure were assessed. Each of these analyses was performed at the time of diagnosis, at the end of therapy, as well as 6 months, one year and two years after its completion. The study showed that, in most cases, implemented therapy had no significant impact on the deterioration of renal parameters in the two-year period following treatment for Wilms' tumor. However, the group of patients treated with cyclophosphamide and carboplatin required more careful monitoring, due to a higher risk of renal function deterioration. The study shows that the problem of nephrotoxicity after treatment for Wilms' tumor is more frequent than indicated in other studies; however, the deterioration of kidney function in most cases is not serious. Additional attention should be paid to patients treated with cyclophosphamide and carboplatin. Assessment of the early and late effects of the treatment is a key element in improving the quality of the patients' life.

  5. Fractionation parameters for human tissues and tumors

    International Nuclear Information System (INIS)

    Thames, H.D.; Turesson, I.; Bogaert, W. van den

    1989-01-01

    Time-dose factors such as fractionation sensitivity (α/β) can sometimes be estimated from clinical data, when there is a wide variation in dose, fraction size, treatment time, etc. This report summarizes estimates of fractionation parameters derived from clinical results. Consistent with the animal data, α/β is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high α/β values, there are exceptions (e.g. melanomas). Repair kinetics may be slower in human than in rodent skin and mucosa, but there are no hard and fast estimates of the repair halftime. Regeneration in head and neck tumors is equivalent to a daily dose of 1 Gy or less, while in the mucosa it is equivalent to approximately 1.8 Gy/day. (author)

  6. Laparoscopic Non-clamping Tumor Enucleation of Renal Hilum Schwannoma in a Single Kidney: A Case Report

    Directory of Open Access Journals (Sweden)

    Fuminari Hanashima

    2015-11-01

    Full Text Available A 56-year-old woman underwent laparoscopic right nephrectomy due to pyonephrosis associated with right ureteral stones. Moreover, the patient developed a brain stem hemorrhage and became bedridden. At the time of nephrectomy, a renal tumor, with a size of 24 × 24 × 20 mm, was observed in the left renal hilum; the tumor did not show contrast enhancement on computed tomography. After 3 years, the tumor gradually grew to a size of 45 × 35 × 34 mm, and therefore, laparoscopic non-clamping tumor enucleation was performed. Pathological examination confirmed a diagnosis of renal schwannoma.

  7. Robotic partial nephrectomy for renal cell carcinomas with venous tumor thrombus.

    Science.gov (United States)

    Abaza, Ronney; Angell, Jordan

    2013-06-01

    To describe the first report of robotic partial nephrectomies (RPNs) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Partial nephrectomy for RCC extending into the renal vein has been described in limited fashion, but such a complex procedure has not previously been reported in minimally-invasive fashion. We demonstrate the feasibility of robotic nephron-sparing surgery despite vein thrombi and the results of the initial four highly-selected patients to have undergone this novel procedure. Two patients underwent RPN for RCC with VTT involving intraparenchymal vein branches, and 2 others had VTT involving the main renal vein. Mean patient age was 65 years (range 50-74 years). Mean tumor size was 7.75 cm (range 4.3-12.8 cm) with mean RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score of 9.75 (range 8-12). Mean warm ischemia time was 24.2 minutes (range 19-27 minutes) and mean estimated blood loss was 168.8 mL (range 100-300 mL). No patients required transfusion, and there were no intraoperative complications. No patients required conversion to open or standard laparoscopic surgery. All 4 patients were discharged home on the first postoperative day. A single postoperative complication occurred in 1 patient who was readmitted with an ileus that resolved spontaneously. All patients had negative surgical margins. Two patients developed metastatic disease on surveillance imaging. RPN in patients with VTT is safe and feasible in selected patients. Given the risk of metastatic disease in patients with pathologic stage T3a RCC, the role of nephron sparing requires further evaluation such that radical nephrectomy remains the standard of care. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma.

    Science.gov (United States)

    Budak-Alpdogan, T; Sauter, C T; Bailey, C P; Biswas, C S; Panis, M M; Civriz, S; Flomenberg, N; Alpdogan, O

    2013-08-01

    Allogeneic hematopoietic SCT (HSCT) has been shown to be an effective treatment option for advanced renal cell cancer (RCC). However, tumor resistance/relapse remains as the main post transplant issue. Therefore, enhancing graft-versus-tumor (GVT) activity without increasing GVHD is critical for improving the outcome of HSCT. We explored the GVT effect of haploidentical-SCT (haplo-SCT) against RCC in murine models. Lethally irradiated CB6F1 (H2K(b/d)) recipients were transplanted with T-cell-depleted BM cells from B6CBAF1 (H2K(b/k)) mice. Haplo-SCT combined with a low-dose haploidentical (HI) T-cell infusion (1 × 10(5)) successfully provided GVT activity without incurring GVHD. This effect elicited murine RCC growth control and consequently displayed a comparative survival advantage of haplo-SCT recipients when compared with MHC-matched (B6D2F1CB6F1) and parent-F1 (B6CB6F1) transplant recipients. Recipients of haplo-SCT had an increase in donor-derived splenic T-cell numbers, T-cell proliferation and IFN-γ-secreting donor-derived T-cells, a critical aspect for anti-tumor activity. The splenocytes from B6CBAF1 mice had a higher cytotoxicity against RENCA cells than the splenocytes from B6 and B6D2F1 donors after tumor challenge. These findings suggest that haplo-SCT might be an innovative immunotherapeutic platform for solid tumors, particularly for renal cell carcinoma.

  9. Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

    Science.gov (United States)

    Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

    To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Renal lymph nodes for tumor staging: appraisal of 871 nephrectomies with examination of hilar fat.

    Science.gov (United States)

    Mehta, Vikas; Mudaliar, Kumaran; Ghai, Ritu; Quek, Marcus L; Milner, John; Flanigan, Robert C; Picken, Maria M

    2013-11-01

    Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases

  11. Radioimmunoassay of renin in human renal tissues

    International Nuclear Information System (INIS)

    Wowra, B.

    1981-01-01

    A method has been developed to quantitatively determine renin in human kidney tissue. The angiotensin I split off angiotensinogs by renin was radioimmunologically determined. The renin-renin substrate reaction rate followed a saturation kinetics, as it increased the larger the substrate content in the incubation medium until it acquired a maximum value; the reaction rate decreased with substrate concentrations over 40 mg/ml incubation medium. The discontinuance of the renin reaction after incubation by adding acid, boiling and neutralizing again, gave highest renin values. The RIA scattering was 8.3% for double determination of the same sample, for the determination in different RIA additions 7.0%. The detection limit was 20 pg angiotensin I. A direct comparison of radioimmunoassay and bioassay exhibited a very significant agreement of both methods, where the radioimmunologically measured renin values were on average four times larger than those obtained using biological technique. The definition of the so-called normal values for absolute and specific renin concentration in human kidney tissue enabled one to assess the renin values in various syndromes. (orig./MG) [de

  12. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma.

    Science.gov (United States)

    Kremer, Veronika; Ligtenberg, Maarten A; Zendehdel, Rosa; Seitz, Christina; Duivenvoorden, Annet; Wennerberg, Erik; Colón, Eugenia; Scherman-Plogell, Ann-Helén; Lundqvist, Andreas

    2017-09-19

    Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer. Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays. We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells. To increase the success of NK

  13. The perioperative outcomes between renal hilar and non-hilar tumors following robotic-assisted partial nephrectomy (RAPN).

    Science.gov (United States)

    Lu, Shih-Yen; Chung, Hsiao-Jen; Huang, Eric Yi-Hsiu; Lin, Tzu-Pin; Lin, Alex T L

    2018-03-15

    The aim of this study was to compare the perioperative outcomes between renal hilar tumors and non-hilar tumors after robotic-assisted partial nephrectomy (RAPN). A retrospective review of consecutive patients who underwent RAPN from December 2009 to September 2015 at our institution was recruited. Perioperative outcomes including demographic characteristics, perioperative, pathological and renal function outcomes were compared between the hilar group (n = 30) and non-hilar group (n = 170). In characteristics, hilar group was younger (52.4 vs. 58 years, p = 0.04) and had less body mass index (23.7 vs. 25.4 kg/m 2 , p = 0.018). Hilar group had larger tumor size (4.8 vs. 3.7 cm, p = 0.009), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (10.7 vs. 8.5, p Hilar tumor was associated with longer operative time (293.6 vs. 240.5 min, p = 0.001) and warm ischemia time (39.9 vs. 21.8 min, p hilar tumor patients had no difference of the change of creatinine and estimated glomerular filtration rate (eGFR) at postoperative 6 and 12 month as compared with non-hilar tumor patients. For renal hilar tumor, RAPN could provide acceptable results of perioperative, pathological and renal function outcome as compared with non-hilar tumor group. Thus RAPN is a safe and effective nephron-sparing surgery technique for renal hilar tumors. Copyright © 2018. Published by Elsevier Taiwan LLC.

  14. Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.

    Science.gov (United States)

    Gu, Yi-Feng; Cohn, Shannon; Christie, Alana; McKenzie, Tiffani; Wolff, Nicholas; Do, Quyen N; Madhuranthakam, Ananth J; Pedrosa, Ivan; Wang, Tao; Dey, Anwesha; Busslinger, Meinrad; Xie, Xian-Jin; Hammer, Robert E; McKay, Renée M; Kapur, Payal; Brugarolas, James

    2017-08-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl ) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1 -deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1 -deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1 , in Pbrm1 -deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells. Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900-17. ©2017 AACR. See related commentary by Leung and Kim, p. 802 This article is highlighted in the In This Issue feature, p. 783 . ©2017 American Association for Cancer Research.

  15. Epigenetic inactivation of CHFR in human tumors.

    Science.gov (United States)

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J; Jair, Kam-Wing; Schuebel, Kornel E; Imai, Kohzoh; Tokino, Takashi

    2003-06-24

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

  16. Successful Endovascular Control of Renal Artery in a Transplant Kidney During Nephron Sparing Surgery (NSS) for Large Centrally Located Tumor.

    Science.gov (United States)

    Shprits, Sagi; Moskovits, Boaz; Sachner, Robert; Nativ, Ofer

    2016-05-01

    Renal cell carcinoma in a transplant kidney is a rare condition. Nephron Sparing Surgery (NSS) is the treatment of choice. One of the main technical challenges is obtaining adequate vascular control. We present a rare case of large centrally located hillar tumor in a kidney 18 years after transplantation treated with NSS. Vascular control was achieved by using a novel approach. Post-operative course was uneventful with minimal decrease in renal function. We believe that this unique choice of treatment can be used in cases of NSS where the access to the renal pedicle is limited.

  17. Supra-Acetabular Brown Tumor due to Primary Hyperparathyroidism Associated with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Rosaria M. Ruggeri

    2010-01-01

    Full Text Available A 63-year-old woman presented to the Orthopedic Unit of our hospital complaining of right hip pain of 6 months'duration associated with a worsening limp. Her past medical history included chronic renal insufficiency. Physical examination revealed deep pain in the iliac region and severe restriction of the right hip's articular function in the maximum degrees of range of motion. X-rays and CT scan detected an osteolytic and expansive lesion of the right supra-acetabular region with structural reabsorption of the right iliac wing. 99mTc-MDP whole-body bone scan showed an abnormal uptake in the right iliac region. Bone biopsy revealed an osteolytic lesion with multinucleated giant cells, indicating a brown tumor. Serum intact PTH was elevated (1020 pg/ml; normal values, 12 62 pg/ml, but her serum calcium was normal (total = 9.4 mg/dl, nv 8.5–10.5; ionized = 5.0 mg/dl, nv 4.2–5.4 due to the coexistence of chronic renal failure. 99mTc-MIBI scintigraphy revealed a single focus of sestamibi accumulation in the left retrosternal location, which turned out to be an intrathoracic parathyroid adenoma at surgical exploration. After surgical removal of the parathyroid adenoma, PTH levels decreased to 212 pg/ml. Three months after parathyroidectomy, the imaging studies showed complete recovery of the osteolytic lesion, thus avoiding any orthopedic surgery. This case is noteworthy because (1 primary hyperparathyroidism was not suspected due to the normocalcemia, likely attributable to the coexistence of chronic renal failure; and (2 it was associated with a brown tumor of unusual location (right supra-acetabular region.

  18. Renal Tumor Cryoablation Planning. The Efficiency of Simulation on Reconstructed 3D CT Scan

    Directory of Open Access Journals (Sweden)

    Ciprian Valerian LUCAN

    2010-12-01

    Full Text Available Introduction & Objective: Nephron-sparing surgical techniques risks are related to tumor relationships with adjacent anatomic structures. Complexity of the renal anatomy drives the interest to develop tools for 3D reconstruction and surgery simulation. The aim of the article was to assess the simulation on reconstructed 3D CT scan used for planning the cryoablation. Material & Method: A prospective randomized study was performed between Jan. 2007 and July 2009 on 27 patients who underwent retroperitoneoscopic T1a renal tumors cryoablation (RC. All patients were assessed preoperatively by CT scan, also used for 3D volume rendering. In the Gr.A, the patients underwent surgery planning by simulation on 3D CT scan. In the Gr.B., patients underwent standard RC. The two groups were compared in terms of surgical time, bleeding, postoperative drainage, analgesics requirement, hospital stay, time to socio-professional reintegration. Results: Fourteen patients underwent preoperative cryoablation planning (Gr.A and 13 patients underwent standard CR (Gr.B. All parameters analyzed were shorter in the Gr.A. On multivariate logistic regression, only shortens of the surgical time (138.79±5.51 min. in Gr.A. vs. 140.92±5.54 min in Gr.B. and bleeding (164.29±60.22 mL in Gr.A. vs. 215.38±100.80 mL in Gr.B. achieved statistical significance (p<0.05. The number of cryoneedles assessed by simulation had a 92.52% accuracy when compared with those effectively used. Conclusions: Simulation of the cryoablation using reconstructed 3D CT scan improves the surgical results. The application used for simulation was able to accurately assess the number of cryoneedles required for tumor ablation, their direction and approach.

  19. Chemosensitivity testing of primary human renal cell carcinoma by a tetrazolium based microculture assay (MTT).

    Science.gov (United States)

    Mickisch, G; Fajta, S; Keilhauer, G; Schlick, E; Tschada, R; Alken, P

    1990-01-01

    MTT staining procedures have been used in chemosensitivity testing of established cell lines of human and other sources as well as of human leukaemias, but only limited information on its application in primary solid human tumors is presently available. We have evaluated MTT staining in primary human Renal Cell Carcinomas (RCCs), studied various factors interfering with the optimal use, and finally applied it in subsequent chemosensitivity testing. The method depends on the conversion of a water-soluble tetrazolium salt (MTT) to a purple colored formazan precipitate, a reaction effected by enzymes active only in living cells. Single cell suspensions of RCCs were obtained either by enzymatic dispersion or by mechanical dissagregation, filtered through gauze, and purified by Ficoll density centrifugation. Tests were carried out in 96-well microculture plates. 10(4) viable tumor cells per well at 4 h incubation time with 20 micrograms MTT/100 microliters total medium volume yielded best results. Formazan crystals were dissolved with DMSO, and the plates were immediately measured on a microculture plate reader at 540 nm. Under these criteria, linearity of the system could be demonstrated. For chemosensitivity testing, cells were continuously exposed to a number of drugs prior to the MTT staining procedure. Reproducibility of results was assessed and confirmed by culturing RCCs in flasks additionally, resubmitting them after 1, 2, and 4 weeks to the MTT assay. We conclude that the semiautomated MTT assay offers a valid, rapid, reliable and simple method to determine the degree of chemoresistance in primary human RCCs.

  20. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  1. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  2. A case of huge colon carcinoma and right renal angiomyolipoma accompanied by proximal deep venous thrombosis, pulmonary embolism and tumor thrombus in the renal vein.

    Science.gov (United States)

    Ban, Daisuke; Yamamoto, Seiichiro; Kuno, Hirofumi; Fujimoto, Hiroyuki; Fujita, Shin; Akasu, Takayuki; Moriya, Yoshihiro

    2008-10-01

    A preoperative inferior vena cava (IVC) filter is reported to be effective in surgical cases with proximal deep venous thrombosis (DVT) or in which pulmonary embolism (PE) has already developed, and considered to be at high risk of developing secondary fatal PE during or after surgery. However, guidelines for using an IVC filter have yet to be established. The patient in the present report had two huge tumors, ascending colon cancer and renal angiomyolipoma, which occupied the entire right half of the abdomen, coexisting PE, DVT and tumor thrombus in the right renal vein. Secondary PE is fatal in the perioperative period, therefore, the vena cava filters were preoperatively inserted into the supra- and the infrarenal IVC. We successfully removed the tumors without complications. The patient is alive without tumor recurrence and PE or recurrent DVT 1 year and 6 months after surgery. The coexistence of two huge abdominal tumors as potential causes of PE and DVT is extremely rare, and we could have safely undergone the operation, using two vena cava filters in the supra- and infrarenal IVC.

  3. Why should survivors of childhood renal tumor and others with only one kidney be denied the chance to play contact sports?

    Science.gov (United States)

    Spreafico, Filippo; Terenziani, Monica; van den Heuvel-Eibrink, Marry M; Pritchard-Jones, Kathy; Levitt, Gill; Graf, Norbert; Bergeron, Christophe; Massimino, Maura

    2014-04-01

    Over the last few decades advances in the treatment of childhood and young adult cancer have greatly improved survival. As a result most children diagnosed with Wilms' tumor (the most common renal tumor in childhood) or other renal tumors become long-term survivors, living with surgically solitary kidneys. As physical activity is gaining credibility as a therapy enhancing well-being, encouraging cancer survivors do exercise during adolescence and adulthood is advisable. Discussing current evidence-based information would help to provide a framework for the harmonization of guidelines for sport participation of childhood and young adult renal tumor survivors.

  4. 159. Trombectomía de Vena Cava Inferior Por Invasión de Tumor Renal

    Directory of Open Access Journals (Sweden)

    N. Miranda

    2012-04-01

    Conclusiones: en casos seleccionados, el carcinoma de célula renal extendiéndose a VCI puede ser resecado sin dificultad sin necesidad de esternotomía, CBP o PCHP, constituyendo una alternativa curativa en el tratamiento de dichos tumores.

  5. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

    Science.gov (United States)

    Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

    2013-11-01

    The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

  6. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    OpenAIRE

    Nestor Moisés Tineo Araque; Helen Daniela Uzcátegui Camacaro; Henrry Ramirez; Humberto Ruz

    2011-01-01

    El cáncer de riñón representa entre el 2 y 3% del total de las neoplasias malignas, encontrándose entre ellas el tumor neuroectodérmico (1,1% dentro del cáncer renal). En muchos casos el diagnóstico es tardío y se describe la triada clásica: dolor, hematuria y masa palpable. El ultrasonido y la tomografía axial computarizada son los métodos de diagnóstico más importantes y el éxito terapéutico se basa en la cirugía radical. Se presenta caso de paciente femenina de 23 años quien inicia enferm...

  7. Preoperative radiotherapy of renal adenocarcinomas from the point of view of tumor biology

    Energy Technology Data Exchange (ETDEWEB)

    Kob, D; Kriester, A; Hacker, I; Kloetzer, K H [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Radiologische Klinik und Poliklinik

    1982-05-01

    26 patients with pulmonary metastases of renal adenocarcinomas were examined under the aspect of tumor biology. Growth functions were used to calculate the time at which the metastases began to grow, in relation to the time of operation and with the aim to get information on the indication for preoperative radiotherapy. In 3 patients (11.5%) there was an indication for preoperative irradiation. For comparative clinical tests as to the value of preoperative irradiation a minimum of 871 patients are needed in each group for comparison to evaluate the 3-year survival rate and 489 patients to evaluate the 5-year survival rate in order to be certain of the positive effect of preoperative irradiation with 1% statistical probability. The investigations are to be considered a model.

  8. POSSIBILITIES OF ORGAN-PRESERVING TREATMENT OF PATIENTS WITH MULTIPLE RENAL TUMORS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2017-01-01

    Full Text Available Renal cell carcinoma (RCC occupies one of the leading places in the world for morbidity among malignant neoplasms of the genitourinary system. The frequency of occurrence of bilateral RCC according to different authors is 2–6% of the total population of patients with RCC. Currently, the only effective method of treatment of bilateral RCC is surgical treatment. Patients with bilateral RCC are at high risk of dev eloping of local recurrence or progression of the disease after organ-preserving surgeries, which is why the surgeon is faced with a choice between a high risk of developing renal failure or relapse and/or progression of the disease, depending on the extent of the surgical intervention. According to the literature, in patients with bilateral RCC there was an increase in the incidence of papillary variant of RCC up to 19% and the presence of multifocal lesion. Surgical treatment of bilateral RCC is the only effective method to achieve satisfactory oncological results at a low incidence of complications. The m ost justified option for the treatment of bilateral RCC is the implementation of bilateral organ-preserving treatment, which allows achieving the optimal functional results. This article presents a clinical case of successful surgical treatment of a patient with bilateral RCC with multiple tumors.

  9. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

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    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  10. Expression of CD44 and P53 in renal cell carcinoma: Association with tumor subtypes

    Directory of Open Access Journals (Sweden)

    Farahnaz Noroozinia

    2014-01-01

    Full Text Available Renal cell carcinoma (RCC is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3% specimens were P53 positive, 30/64 (46.9% were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5. A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5 and age (P = 0.07, sex (P= 0.3, tumor size (P = 0.7, grade (P = 0.23, vascular invasion (P = 1.00 and ureteral invasion (P = 1.00. Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3, sex (P = 0.7, tumor size (P = 0.7, grade (P = 0.1, vascular inva-sion (P = 1.00 and ureteral invasion (P = 1.00. According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.

  11. Transcriptional response to hypoxia in human tumors.

    NARCIS (Netherlands)

    Lal, A.; Peters, H.; Croix, B. St.; Haroon, Z.A.; Dewhirst, M.W.; Strausberg, R.L.; Kaanders, J.H.A.M.; Kogel, A.J. van der; Riggins, G.J.

    2001-01-01

    BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy.

  12. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    Energy Technology Data Exchange (ETDEWEB)

    Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp [St. Marianna University School of Medicine, Department of Radiology (Japan); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp [Mie University School of Medicine, Department of Interventional Radiology (Japan); Sone, Miyuki, E-mail: msone@me.com; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Miki, Tsuneharu, E-mail: tmiki@koto.kpu-m.ac.jp [Kyoto Prefectural University of Medicine, Department of Urology (Japan); Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan); Sakuhara, Yusuke, E-mail: yusaku@med.hokudai.ac.jp [Hokkaido University School of Medicine, Department of Diagnostic and Interventional Radiology (Japan); Yamamoto, Takanobu, E-mail: tyamamot@tcc.pref.tochigi.lg.jp [Tochigi Cancer Center, Department of Radiology (Japan); Sato, Yozo, E-mail: ysato@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kanazawa, Susumu, E-mail: susumu@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan)

    2016-05-15

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  13. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    International Nuclear Information System (INIS)

    Mimura, Hidefumi; Arai, Yasuaki; Yamakado, Koichiro; Sone, Miyuki; Takeuchi, Yoshito; Miki, Tsuneharu; Gobara, Hideo; Sakuhara, Yusuke; Yamamoto, Takanobu; Sato, Yozo; Kanazawa, Susumu

    2016-01-01

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  14. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

    Science.gov (United States)

    Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

    2011-06-13

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  15. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

    International Nuclear Information System (INIS)

    Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

    2011-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  16. Tumor-Like Liver Abscess Mimicking Malignancy With Lung Metastases in a Patient With Acute Renal Failure: A Case Report.

    Science.gov (United States)

    Wang, Chih Hsin; Sun, Cheuk-Kay; Jiang, Jiunn-Song; Tsai, Ming Hsien

    2016-03-01

    The worldwide incidence of Klebsiella pneumoniae liver abscess (KLA) is increasing. It is important to accurately diagnose this life-threatening disease to provide timely and appropriate treatment. Here we report the case of a 38-year-old man with acute renal failure and a tumor-like liver abscess and septic pulmonary embolism. Initially, his clinical symptoms, laboratory tests, and radiological findings presented equivocal results of malignancy with metastases. Fine needle aspiration of liver tumor was performed, which showed purulent material with a culture positive for K pneumoniae. KLA symptoms are atypical, and radiological findings may mimic a malignancy with tumor necrosis. In some circumstances, liver aspiration biopsy may be necessary to confirm the real etiology, leading to prompt and timely treatment. Moreover, we should be alert for the impression of KLA when facing a diabetic patient with liver mass lesion and acute renal failure.

  17. Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

    Science.gov (United States)

    de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

    2016-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

  18. Chemosensitization of Human Renal Cell Cancer Using Antisense Oligonucleotides Targeting the Antiapoptotic Gene Clusterin

    Directory of Open Access Journals (Sweden)

    Tobias Zellweger

    2001-01-01

    Full Text Available BACKGROUND: Renal cell cancer (RCC is a chemoresistant disease with no active chemotherapeutic agent achieving objective response rates higher than 15%. Clusterin is a cell survival gene that increases in human renal tubular epithelial cells after various states of injury and disease. Downregulation of clusterin, using antisense oligonucleotides (ASO, has recently been shown to increase chemosensitivity in several prostate cancer models. The objectives in this study were to evaluate clusterin expression levels in human RCC and normal kidney tissue, and to test whether clusterin ASO could also enhance chemosensitivity in human RCC Caki-2 cells both in vitro and in vivo. METHODS: Immunohistochemical staining was used to characterize clusterin expression in 67 RCC and normal kidney tissues obtained from radical nephrectomy specimens. Northern blot analysis was used to assess changes in clusterin mRNA expression after ASO and paclitaxel treatment. The effects of combined clusterin ASO and paclitaxel treatment on Caki-2 cell growth was examined using an MTT assay. Athymic mice bearing Caki-2 tumors were treated with clusterin ASO alone, clusterin ASO plus paclitaxel, and mismatch control oligonucleotides plus paclitaxel, over a period of 28 days with measurement of tumor volumes once weekly over 8 weeks. RESULTS: Immunohistochemistry of normal and malignant kidney tissue sections of 67 patients demonstrated positive clusterin staining for almost all RCC (98% and an overexpression, compared to normal tissue, in a majority of RCC (69%. Clusterin ASO, but not mismatch control oligonucleotides, decreased clusterin mRNA expression in Caki-2 cells in a dosedependent and sequence-specific manner. Pretreatment of Caki-2 cells with clusterin ASO significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo

  19. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  20. Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

    2018-01-01

    Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

  1. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  2. Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using cytokeratin gating

    International Nuclear Information System (INIS)

    Haustermans, K.; Hofland, I.; Ramaekers, M.; Ivanyi, D.; Balm, A.J.M.; Geboes, K.; Lerut, T.; Schueren, E. van der; Begg, A.C.

    1996-01-01

    Purpose: To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies. Material and methods: A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor. Results: The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. >From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors. Conclusions: We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements

  3. Deletions of 16q in Wilms tumors localize to blastemal-anaplastic cells and are associated with reduced expression of the IRXB renal tubulogenesis gene cluster

    NARCIS (Netherlands)

    Mengelbier, Linda Holmquist; Karlsson, Jenny; Lindgren, David; Øra, Ingrid; Isaksson, Margareth; Frigyesi, Ildiko; Frigyesi, Attila; Bras, Johannes; Sandstedt, Bengt; Gisselsson, David

    2010-01-01

    Wilms tumor is the most common pediatric renal neoplasm, but few molecular prognostic markers have been identified for this tumor. Somatic deletion in the long arm of chromosome 16 (16q) is known to predict a less favorable outcome in Wilms tumor, but the underlying molecular mechanisms are not

  4. MRI-guided percutaneous cryoablation of renal tumors: Use of external manual displacement of adjacent bowel loops

    International Nuclear Information System (INIS)

    Tuncali, Kemal; Morrison, Paul R.; Tatli, Servet; Silverman, Stuart G.

    2006-01-01

    Purpose: We sought to investigate retrospectively the safety and effectiveness of using external hand compression to displace adjacent bowel loops during MRI-guided percutaneous cryoablation of renal tumors. Materials and methods: Fourteen patients (six women, eight men; mean age: 72 years) with 15 renal tumors (mean diameter: 2.4 cm; range: 1.4-4.6 cm) adjacent to bowel were treated with MRI-guided percutaneous cryoablation during which bowel was displaced manually. Bowel loop of concern was ascending colon (n 5), descending colon (n = 8), descending colon and small bowel (n = 1), ascending colon and small bowel (n = 1). To analyze effectiveness of the maneuver, mean distance between tumor margin and bowel before and after the maneuver were compared and analyzed using paired Student's t-test. Minimum distance between iceball edge and adjacent bowel with external manual displacement during freezing was also measured. Safety was assessed by analyzing post-procedural MR imaging for adjacent bowel wall thickening and focal fluid collections as well as patients' clinical and imaging follow-up. Results: Mean distance between tumor margin and closest adjacent bowel increased from 0.8 cm (range: 0-2 cm) before external manual compression to 2.6 cm (range: 1.6-4.1 cm) with manual displacement (p < 0.01). Mean minimum distance between iceball edge and closest adjacent bowel during the procedures was 1.6 cm (range: 0.5-3.5 cm). No evidence of bowel injury was encountered. Twelve of 15 tumors had follow-up (mean: 10 months) that showed no tumor recurrence. Conclusion: MRI-guided percutaneous cryoablation of renal tumors adjacent to bowel can be done safely and effectively using external hand compression to displace bowel loops

  5. A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

    Science.gov (United States)

    Hsieh, Po-Fan; Wang, Yu-De; Huang, Chi-Ping; Wu, Hsi-Chin; Yang, Che-Rei; Chen, Guang-Heng; Chang, Chao-Hsiang

    2016-07-01

    We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

    Science.gov (United States)

    van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

    2016-06-01

    Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

  7. Tumor-Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2017-10-01

    markers in humans. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research also act to discourage such...Mouse models of cancer. Annu. Rev. Pathol 6, 95–119 52. Merlo, L.M. et al. (2006) Cancer as an evolutionary and ecological process. Nat. Rev. Cancer...some effect on the phenotype and function of TANs. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research

  8. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    International Nuclear Information System (INIS)

    Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

    2008-01-01

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOα on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOα at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 ± 4.7 mg and 34.9 ± 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

  9. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Science.gov (United States)

    2002-01-01

    Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Matrix Organization and Adhesion. Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data. PMID:12356337

  10. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Directory of Open Access Journals (Sweden)

    Madore Steven J

    2002-09-01

    Full Text Available Abstract Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.

  11. NMR relaxation times in human brain tumors (preliminary results)

    International Nuclear Information System (INIS)

    Benoist, L.; Certaines, J. de; Chatel, M.; Menault, F.

    1981-01-01

    Since the early work of Damadian in 1971, proton NMR studies of tumors has been well documented. Present study concerns the spin-lattice T 1 and spin-spin T 2 relaxation times of normal dog brain according to the histological differentiation and of 35 human benignant or malignant tumors. The results principally show T 2 important variations between white and gray substance in normal brain but no discrimination between malignant and benignant tumors [fr

  12. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  13. Metallothioneins in human tumors and potential roles in carcinogenesis

    International Nuclear Information System (INIS)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-01-01

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  14. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    tumor innate immune response. anti-tumor adaptive immune response, neutrophil and T cell interaction. ACCOMPLISHMENTS There were no significant...and by producing factors to recruit and acti- vate cells of the innate and adaptive immune system (Mantovani et al., 2011). Given these varying effects...vivo effects on neutro- phil activation (Figure 2, A and B) and cleavage of myeloid and lymphoid cell markers (Supplemental Figure 1, C–G). Once opti

  15. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

  16. Renal malignant solitary fibrous tumor with single lymph node involvement: report of unusual metastasis and review of the literature

    Directory of Open Access Journals (Sweden)

    Mearini E

    2014-05-01

    Full Text Available Ettore Mearini,1 Giovanni Cochetti,1 Francesco Barillaro,1 Sonia Fatigoni,2 Fausto Roila2 1Department of Medical-Surgical Specialties and Public Health, Division of Urological Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Terni, Italy; 2Medical Oncology, S Maria Hospital, Terni, Italy Abstract: Solitary fibrous tumors are rare mesenchymal spindle cell neoplasms that are usually found in the pleura. The kidneys are an uncommon site and only few cases of renal solitary fibrous tumor exhibit malignant behavior metastasizing to the liver, lung, and bone through the hematogenous pathway. Purpose: To describe the first case of lymph node metastasis from renal solitary fibrous tumor in order to increase the knowledge about the malignant behavior of these tumors. Patients and methods: A 19-year-old female patient had intermittent hematuria for several months without flank pain or other symptoms. A chest and abdomen CT scan was performed and showed a multi-lobed bulky solid mass of 170 × 98 × 120 mm in the left kidney. One day before the surgery, the left renal artery was catheterized and the kidney embolization was performed using a Haemostatic Absorbable Gelatin Sponge and polyvinyl alcohol. We then performed a radical nephrectomy with hilar, para-aortic, and inter-aortocaval lymphadenectomy. Results: Estimated intraoperative blood loss was 200 mL and the operative time was 100 minutes. No postoperative complications occurred. The hospital stay was 7 days long. The histological examination was malignant solitary fibrous tumor of the kidney. Cancerous tissue showed cellular atypia, with an increased mitotic index (up to 7 × 10 hpf. Immunohistochemical analysis showed positive results for CD34, BCL2, partial expression of HBME1, and occasionally of synaptophysin. Histological evaluation confirmed the presence of metastasis in one hilar node. The patient did not receive any other therapy. At 30-month follow-up, the

  17. NSS for an RCC in a patient with renal insufficiency after heart transplant because of right ventricular tumor.

    Science.gov (United States)

    Prokopowicz, Grzegorz; Zyczkowski, Marcin; Nowakowski, Krzysztof; Bryniarski, Piotr; Paradysz, Andrzej

    2013-01-01

    The effect of the immunosuppressive therapy on the development of neoplasms has become the object of an ever increasing interest for clinicians all over the world. The literature on neoplasms development in the course of therapy following transplants has confirmed a considerable increase in the incidence of neoplasms of the skin and lymph nodes. Organ neoplasms developing in patients after transplants are characterized by increased progression, poor cellular diversification and a more unfavorable prognosis than in the general population The aim of the study is to present the case of a nephron-sparing surgery of a renal tumor (NSS) without any intraoperative ischaemia in a 55-year-old female patient with an orthotopic heart transplant and renal insufficiency following a prolonged immune suppression. It is estimated that the patients at the highest risk of neoplasm development are those in the first months after transplant, especially heart transplant. They require maximum doses of immunosuppressive drugs. In the case of patients with initial renal insufficiency the duration of ischaemia of the organ operated on should be minimized, and if possible, surgery should be conducted without clamping the renal pedicle. The surgical treatment of RCC (renal cell carcinoma) in transplant patients does not require any reduction in the amount of the immunosuppressive drugs.

  18. Surgical treatment of Renal Cell Carcinoma (RCC with level III–IV tumor venous thrombosis

    Directory of Open Access Journals (Sweden)

    M. I. Davydov

    2016-01-01

    Full Text Available Objective: to assess the results of nephrectomy, thrombectomy in RCC patients with level III–IV tumor venous thrombosis with and without cardiopulmonary bypass.Materials and methods. Medical data of 167 consecutive RCC patients with level III–IV tumor venous thrombosis underwent nephrectomy thrombectomy in N.N. Blokhin Russian Cancer Research Center between 1998 and 2012 were collected. Right side tumor was in 122 (73.1 %, left side – in 42 (25.1 %, bilateral – in 3 (1.8 % cases. The extent of thrombus was defined as intrahepatic in 82 (49.1 %, supradiaphragmatic – in 85 (50.9 % (intrapericardial – in 44 (26.3 %, intraatrial – in 39 (23.4 %, intraventricular – in 2 (1.2 % cases. Nephrectomy, thrombectomy with cardiopulmonary bypass was used in 9 (5.4 %, 158 (94.6 % patients underwent radical nephrectomy with thrombectomy without CPBP and sternotomy. Intrapericardial IVC and right atrium were exposed through transdiaphragmatic approach and providing vascular control over infradiaphragmatic IVC and renal veins.Results. Median blood loss was 6000 (600–27 000 ml. Complications rate was 62.8 %, 90-day mortality – 13.2 %. Intraoperative complications were registered in 80 (47.9 %, postoperative – in 66 (40.5 % (grade II – 16 (9.8 %, grade IIIb – 1 (0.6 %, grade IVа – 28 (17.2 %, grade IVb – 3 (1.8 %, grade V – 18 (11.1 % patients. Modified thrombectomy technique insignificantly decreased blood loss compared to thrombectomy with CPB, did nоt increase complications rate including pulmonary vein thromboembolism, or mortality. Five-year overall, cancer-specific and recurrence-free survival was 46.2, 58.3 and 47.1 %, respectively. Thrombectomy technique did nоt affect survival.Conclusion. In selected patients with mobile thrombi transdiaphragmatic approach allows to avoid the use of CPBP and decrease surgical morbidity without survival compromising.

  19. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

  20. Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo.

    Science.gov (United States)

    Chang, De-Kuan; Moniz, Raymond J; Xu, Zhongyao; Sun, Jiusong; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

    2015-06-11

    Carbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). Therapeutic approaches targeting CAIX have focused on the development of CAIX inhibitors and specific immunotherapies including monoclonal antibodies (mAbs). However, current in vivo mouse models used to characterize the anti-tumor properties of fully human anti-CAIX mAbs have significant limitations since the role of human effector cells in tumor cell killing in vivo is not directly evaluated. The role of human anti-CAIX mAbs on CAIX(+) RCC tumor cell killing by immunocytes or complement was tested in vitro by antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) as well as on CAIX(+) RCC cellular motility, wound healing, migration and proliferation. The in vivo therapeutic activity mediated by anti-CAIX mAbs was determined by using a novel orthotopic RCC xenograft humanized animal model and analyzed by histology and FACS staining. Our studies demonstrate the capacity of human anti-CAIX mAbs that inhibit CA enzymatic activity to result in immune-mediated killing of RCC, including nature killer (NK) cell-mediated ADCC, CDC, and macrophage-mediated ADCP. The killing activity correlated positively with the level of CAIX expression on RCC tumor cell lines. In addition, Fc engineering of anti-CAIX mAbs was shown to enhance the ADCC activity against RCC. We also demonstrate that these anti-CAIX mAbs inhibit migration of RCC cells in vitro. Finally, through the implementation of a novel orthotopic RCC model utilizing allogeneic human peripheral blood mononuclear cells in NOD/SCID/IL2Rγ(-/-) mice, we show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in

  1. The Target of 5-Lipoxygenase is a Novel Strategy over Human Urological Tumors than the Target of Cyclooxygenase-2

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2008-01-01

    Full Text Available The metabolism of arachidonic acid by either the cyclooxygenase (COX or lipoxygenase (LOX pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer. It is now considered that they play important roles in tumor promotion, progression, and metastasis, also, the involvement of COX and LOX expression and function in tumor growth and metastasis has been reported in human tumor cell lines. In this study, we examined the expression of COX and LOX in human urological tumors (renal cell carcinoma, bladder tumor, prostate cancer, testicular cancer by immunohistochemistry and RT-PCR, and we also examined the effects of COX and LOX (5- and 12-LOX inhibitors in those cells by MTT assay, hoechest staining, and flow cytometry. COX-2, 5-LOX and 12-LOX expressions were significantly more extensive and intense in malignant tissues than in normal tissues. Furthermore, 5-LOX inhibitor induced the reduction of malignant cell viability through early apoptosis. These results demonstrated COX-2 and LOX were induced in urological tumors, and 5-LOX inhibitor may mediate potent antiproliferative effects against urological tumors cells. Thus, 5-LOX may become a new target in the treatment of urological tumors.

  2. Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell carcinoma patient-derived xenografts.

    Directory of Open Access Journals (Sweden)

    Kiersten Marie Miles

    Full Text Available The Notch ligand Delta-like 4 (Dll4 is highly expressed in vascular endothelium and has been shown to play a pivotal role in regulating tumor angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has been associated with non-productive angiogenesis and reduced tumor growth. Given the cross-talk between the vascular endothelial growth factor (VEGF and Delta-Notch pathways in tumor angiogenesis, we examined the activity of a function-blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy in renal cell carcinoma (RCC.Severe combined immunodeficiency (SCID mice bearing patient-derived clear cell RCC xenografts were treated with REGN1035 and in combination with the multi-targeted tyrosine kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept. Immunohistochemical and immunofluorescent analyses were carried out, as well as magnetic resonance imaging (MRI examinations pre and 24 hours and 2 weeks post treatment. Single agent treatment with REGN1035 resulted in significant tumor growth inhibition (36-62% that was equivalent to or exceeded the single agent anti-tumor activity of the VEGF pathway inhibitors sunitinib (38-54% and ziv-aflibercept (46%. Importantly, combination treatments with REGN1035 plus VEGF inhibitors resulted in enhanced anti-tumor effects (72-80% growth inhibition, including some tumor regression. Magnetic resonance imaging showed a marked decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in a sunitinib resistant ccRCC model.Overall, these findings demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient-derived tumors and a combination benefit for the simultaneous targeting of the Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this treatment modality in RCC.

  3. Perioperative outcomes of zero ischemia radiofrequency ablation-assisted tumor enucleation for renal cell carcinoma: results of 182 patients.

    Science.gov (United States)

    Zhang, Chengwei; Zhao, Xiaozhi; Guo, Suhan; Ji, Changwei; Wang, Wei; Guo, Hongqian

    2018-05-15

    To evaluate the perioperative outcomes of zero ischemia radiofrequency ablation-assisted tumor enucleation. Patients undergoing zero ischemia radiofrequency ablation-assisted tumor enucleation were retrospectively identified from July 2008 to March 2013. The tumor was enucleated after RFA treatment. R.E.N.A.L., PADUA and centrality index (C-index) score systems were used to assess each tumor case. We analyzed the correlation of perioperative outcomes with these scores. Postoperative complications were graded with Clavien-Dindo system. Multivariate logistic regression analyses were used to assess risk of complications. Among 182 patients assessed, median tumor size, estimated blood loss, hospital stay and operative time were 3.2 cm (IQR 2.8-3.4), 80 ml (IQR 50-120), 7 days (IQR 6-8) and 100 min (IQR 90-120), respectively. All three scoring systems were strongly correlated with estimated blood loss, hospital stay and operative time. We found 3 (1.6%) intraoperative and 23 (12.6%, 13 [7.1%] Grade 1 and 10 [5.5%] Grade 2 & 3a) postoperative complications. The median follow-up was 55.5 months (IQR 45-70). Additionally, the complexities of R.E.N.A.L., PADUA and C-index scores were significantly correlated with complication grades (P radiofrequency ablation-assisted tumor enucleation is considered an effective nephron-sparing treatment. Scoring systems could be useful for predicting perioperative outcomes of radiofrequency ablation-assisted tumor enucleation.

  4. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  5. X-ray sensitivity of human tumor cells in vitro

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1980-01-01

    Clonally-derived cells from ten human malignant tumors considered radiocurable (breast, neuroblastoma, medulloblastoma) or non-radiocurable (osteosarcoma, hypernephroma, glioblastoma, melanoma) were studied in cell culture and their in vitro x-ray survival curve parameters determined (anti n, D 0 ). There were no significant differences among the tumor cell lines suggesting that survival parameters in vitro do not explain differences in clinical radiocurability. Preliminary investigation with density inhibited human tumor cells indicate that such an approach may yield information regarding inherent cellular differences in radiocurability

  6. A bioartificial renal tubule device embedding human renal stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Giovanna Sciancalepore

    Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

  7. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  8. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

    2016-02-19

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

  9. Prospective Evaluation of (99m)Tc-sestamibi SPECT/CT for the Diagnosis of Renal Oncocytomas and Hybrid Oncocytic/Chromophobe Tumors.

    Science.gov (United States)

    Gorin, Michael A; Rowe, Steven P; Baras, Alexander S; Solnes, Lilja B; Ball, Mark W; Pierorazio, Phillip M; Pavlovich, Christian P; Epstein, Jonathan I; Javadi, Mehrbod S; Allaf, Mohamad E

    2016-03-01

    Nuclear imaging offers a potential noninvasive means of determining the histology of renal tumors. The aim of this study was to evaluate the accuracy of technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) for the differentiation of oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. In total, 50 patients with a solid clinical T1 renal mass were imaged with (99m)Tc-sestamibi SPECT/CT prior to surgical resection. Preoperative SPECT/CT scans were reviewed by two blinded readers, and their results were compared with centrally reviewed surgical pathology data. Following surgery, 6 (12%) tumors were classified as renal oncocytomas and 2 (4%) as HOCTs. With the exception of 1 (2%) angiomyolipoma, all other tumors were renal cell carcinomas (82%). (99m)Tc-sestamibi SPECT/CT correctly identified 5 of 6 (83.3%) oncocytomas and 2 of 2 (100%) HOCTs, resulting in an overall sensitivity of 87.5% (95% confidence interval [CI], 47.4-99.7%). Only two tumors were falsely positive on SPECT/CT, resulting in a specificity of 95.2% (95% CI, 83.8-99.4%). In summary, (99m)Tc-sestamibi SPECT/CT is a promising imaging test for the noninvasive diagnosis of renal oncocytomas and HOCTs. We found that the imaging test (99m)Tc-sestamibi SPECT/CT can be used to accurately diagnose two types of benign kidney tumors. This test may be eventually used to help better evaluate patients diagnosed with a renal tumor. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Laparoscopic resection of tumor recurrence after radical nephrectomy for localized renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lessandro Curcio

    2014-06-01

    Full Text Available Introduction Local recurrence of Renal Cell Carcinoma (RCC after radical nephrectomy is a rare event. Some known risk factors are: clinical/pathological stage, locorregional disease and lyimph node positivity. Since up to 30-40% of patients can achieve a disease-free status, we show a case (video in which we performed a laparoscopic excision of a local RCC, taking advantage of all the well-known benefits of laparoscopy.Case report A 56 years old female with a history of open radical nephrectomy two years before was diagnosed with a mass at the time of surveillance CT imaging during follow-up. The suspected local recurrence was 12cm, and vascularized predominantly by tributaries originating from the iliac vessels. There was no other site of disease (i.e. brain, lung, liver, bones and laboratory tests were normal. Laparoscopic approach was approached, by inserting 4 trocars (2 of 10 and 2 of 5mm with the patient in the lateral position.Result The procedure lasted 130 minutes, with 220mL of estimated bleeding; the larger vessels were ligated with polymer clips (Hem-o-lok and the smaller handled by ultrasonic clamp. The specimen was removed by a small incision below the umbilicus in an appropriate bag. The patient was feed in the first postoperative day and discharged on the third day. Histopathology revealed sarcoma, with a high degree of mitosis, and negative surgical margins. She was referred to medical oncology for adjuvant therapy consideration.Conclusion The laparoscopic resection of recurrent tumor should be encouraged in highly selected cases. The minimally invasive method, with its known advantages, especially for more debilitated patients, can be advantageous when applied to suitable cases.

  11. Laparoscopic resection of tumor recurrence after radical nephrectomy for localized renal cell carcinoma.

    Science.gov (United States)

    Curcio, Lessandro; Cunha, Antonio Claudio; Renteria, Juan; Presto, Daniel

    2014-01-01

    Local recurrence of Renal Cell Carcinoma (RCC) after radical nephrectomy is a rare event. Some known risk factors are: clinical/pathological stage, locorregional disease and lyimph node positivity. Since up to 30-40% of patients can achieve a disease-free status, we show a case (video) in which we performed a laparoscopic excision of a local RCC, taking advantage of all the well-known benefits of laparoscopy. A 56 years old female with a history of open radical nephrectomy two years before was diagnosed with a mass at the time of surveillance CT imaging during follow-up. The suspected local recurrence was 12 cm, and vascularized predominantly by tributaries originating from the iliac vessels. There was no other site of disease (i.e. brain, lung, liver, bones) and laboratory tests were normal. Laparoscopic approach was approached, by inserting 4 trocars (2 of 10 and 2 of 5mm) with the patient in the lateral position. The procedure lasted 130 minutes, with 220 mL of estimated bleeding; the larger vessels were ligated with polymer clips (Hem-o-lok) and the smaller handled by ultrasonic clamp. The specimen was removed by a small incision below the umbilicus in an appropriate bag. The patient was feed in the first postoperative day and discharged on the third day. Histopathology revealed sarcoma, with a high degree of mitosis, and negative surgical margins. She was referred to medical oncology for adjuvant therapy consideration. The laparoscopic resection of recurrent tumor should be encouraged in highly selected cases. The minimally invasive method, with its known advantages, especially for more debilitated patients, can be advantageous when applied to suitable cases.

  12. Use of Recombinant Human Erythropoietin in Renal Anemia in Children

    Directory of Open Access Journals (Sweden)

    Habibur Rahman

    2009-11-01

    Full Text Available Erythropoietin is a hormone highly effective as like as natural erythropoietin to maintain target hemoglobin and hematocrit level in renal anemia. Its advantage over blood transfusion has been proved by improving the quality of life and decreasing morbidity and mortality in ESRD patients. Effectiveness of r-erythropoietin depends on absences of infection, inflammation and vitamin deficiency and iron status. Iron supplementation is needed before r-erythropoietin administration and sub-cutaneous rout is better in renal anemia because of slow and sustained releases of r-erythropoietin from the site of administration. Target hemoglobin level is 11-12.5 gm/dl and hematocrit is 33% which can be achieved by this hormone therapy. Key words- Recombinant erythropoietin, renal anemia, end stage renal disease.DOI: 10.3329/bsmmuj.v2i1.3713 BSMMU J 2009; 2(1: 50-53  

  13. Mitochondrial DNA mutations in human tumor cells

    OpenAIRE

    LI, HUI; HONG, ZE-HUI

    2012-01-01

    Mitochondria play significant roles in cellular energy metabolism, free radical generation and apoptosis. The dysfunction of mitochondria is correlated with the origin and progression of tumors; thus, mutations in the mitochondrial genome that affect mitochondrial function may be one of the causal factors of tumorigenesis. Although the role of mitochondrial DNA (mtDNA) mutations in carcinogenesis has been investigated extensively by various approaches, the conclusions remain controversial to ...

  14. Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

    Science.gov (United States)

    Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

    2017-03-01

    Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

  15. Renal lactate elimination is maintained during moderate exercise in humans

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Dawson, Ellen A; Dalsgaard, Mads

    2012-01-01

    (2) (CaO(2)-CvO(2)) and lactate concentration differences were 0.8 ± 0.2 and 0.02 ± 0.02 mmol x L(-1), respectively. During exercise, arterial lactate and CaO(2)-CvO(2) increased to 7.1 ± 1.1 and 2.6 ± 0.8 mmol x L(-1), respectively (P renal blood flow...... with no significant change in the renal venous erythropoietin concentration (0.8 ± 1.4 U x L(-1)). The a-v lactate concentration difference increased to 0.5 ± 0.8 mmol x L(-1), indicating similar lactate elimination as at rest. In conclusion, a -70% reduction in renal blood flow does not provoke critical renal......Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference...

  16. The frequency of tumor-infiltrating Tie-2-expressing monocytes in renal cell carcinoma: its relationship to angiogenesis and progression.

    Science.gov (United States)

    Ji, Jindong; Zhang, Guangbo; Sun, Bo; Yuan, Hexing; Huang, Yuhua; Zhang, Jianglei; Wei, Xuedong; Zhang, Xuefeng; Hou, Jianquan

    2013-10-01

    To examine the frequency of tumor-infiltrating Tie-2-expressing monocytes (TEMs) in renal cell carcinoma (RCC) and its association with microvessel density (MVD) and other clinical-pathologic features. This study enrolled 65 consecutive patients with RCC treated with radical nephrectomy. The frequency of tumor-infiltrating TEMs, which was defined as CD14(+) Tie-2(+) cells, was assessed using flow cytometry. MVD was measured by immunohistochemistry using anti-CD34 antibody. The association between clinicopathologic parameters, MVD, and the frequency of tumor-infiltrating TEMs in RCC was assessed. High frequency of tumor-infiltrating TEMs was significantly associated with advanced stage (P = .018), positive lymph nodes (P = .013), high grade (P = .019), and metastases (P = .006). Correlation analysis revealed that the frequency of TEMs was positively correlated with MVD. Our findings revealed a significant association between prognostic tumor features, MVD, and the frequency of tumor-infiltrating TEMs in RCC and indicated that TEMs may play an important role in angiogenesis and progression of RCC. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin.

    Science.gov (United States)

    Shiomi, Kazu; Shiomi, Satoko; Ishinaga, Yuji; Sakuraba, Motoki; Hagiwara, Yoshiaki; Miyashita, Kazuya; Maeda, Masahiro; Suzuki, Kenji; Takahashi, Kazuhisa; Hino, Okio

    2011-04-01

    Knowledge of the characteristics and effective use of tumour markers for mesothelioma is essential for early-stage diagnosis of mesothelioma. We examined whether renal dysfunction influences blood concentrations of promising new tumour markers, N-ERC/mesothelin (N-ERC) and osteopontin (OPN), to an important degree. Levels of serum N-ERC and plasma OPN in 32 patients with chronic renal dysfunction, 22 of whom were on hemodialysis (CKD group), and 102 healthy volunteers were measured. Serum concentrations of N-ERC and plasma concentrations of OPN in the CKD group were significantly higher than those in volunteers, regardless of diabetes status and age. Blood concentrations of these markers increased as renal function decreased. N-ERC and OPN concentrations are significantly influenced by renal function. Therefore, the extent of renal failure must be considered when inferring the existence of tumours and chemotherapeutic response from the values of these markers in routine practice.

  18. Mining the human urine proteome for monitoring renal transplant injury

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; Gao, Yuqian; He, Jintang; Wang, Anyou; Nicora, Carrie D.; Fillmore, Thomas L.; Shi, Tujin; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Qian, Wei-Jun; Salvatierra, Oscar; Camp, David G.; Sarwal, Minnie M.

    2016-06-01

    The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used in the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.

  19. A Big Bang model of human colorectal tumor growth.

    Science.gov (United States)

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  20. A renal epithelioid angiomyolipoma/perivascular epithelioid cell tumor with TFE3 gene break visualized by FISH.

    Science.gov (United States)

    Ohe, Chisato; Kuroda, Naoto; Hes, Ondrej; Michal, Michal; Vanecek, Tomas; Grossmann, Petr; Tanaka, Yukichi; Tanaka, Mio; Inui, Hidekazu; Komai, Yoshihiro; Matsuda, Tadashi; Uemura, Yoshiko

    2012-12-01

    We present a case of renal epithelioid angiomyolipoma (eAML)/perivascular epithelioid cell tumor (PEComa) with a TFE3 gene break visible by fluorescence in situ hybridization (FISH). Histologically, the tumor was composed of mainly epithelioid cells forming solid arrangements with small foci of spindle cells. In a small portion of the tumor, neoplastic cells displayed nuclear pleomorphism, such as polygonal and enlarged vesicular nuclei with prominent nucleoli. Marked vascularity was noticeable in the background, and perivascular hyaline sclerosis was also seen. Immunohistochemically, neoplastic cells were diffusely positive for α-smooth muscle actin and melanosome in the cytoplasm. Nuclei of many neoplastic cells were positive for TFE3. FISH analysis of the TFE3 gene break using the Poseidon TFE3 (Xp11) Break probe revealed positive results. Reverse transcriptase-polymerase chain reactions (RT-PCR) for ASPL/TFE3, PRCC/TFE3, CLTC/TFE3, PSF/TFE3, and NonO/TFE3 gene fusions all revealed negative results. This is the first reported case of renal eAML/PEComa with a TFE3 gene break, and it has unique histological findings as compared to previously reported TFE3 gene fusion-positive PEComas. Pathologists should recognize that PEComa with TFE3 gene fusion can arise even in the kidney.

  1. Cardiovascular, endocrine and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M.H.; Olsen, N.V.; Christensen, P.

    1999-01-01

    remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate......Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7......-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood...

  2. Radiobiological parameters of a human tumor parent line and four tumor clones of a human epidermoid carcinoma

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.; Dahlberg, W.

    1987-01-01

    The authors examined the radiobiological parameters of a parent tumor line and four tumor clones of a human squamous cell carcinoma of the skin. The parent line and clones have a tumor morphology, aneuploid karyotype, and the ability to passage continuously in vitro. With the exception of clone F2A, all cell lines form tumors in nude mice. The parent line, SCC-12 has a D/sub o/ of 154 and an n 7.5 In four tumor clones, D/sub o/ ranges from 131 (clone V) to 266 (clone B2); n ranges from 22.8 in clone V to 2.1 in clone B2. PLDR following 1100 rad ranges from 1.7 in clone B2 to 13.1 in clone V. However, PLDR following equitoxic doses of radiation is similar in the parent and all sub-clones. Radiobiological heterogeneity may complicate predictive assays for clinical radiotherapy

  3. A Case Report of Human Infection with Dioctophyma Renale from Iran.

    Science.gov (United States)

    Norouzi, Roghayeh; Manochehri, Arman; Hanifi, Mustafa

    2017-03-16

    A 75-year-old man from Kurdistan province, western part of Iran was diagnosed with a mass in the right kidney by ultrasound and computed tomography. In operation, a parasitic helminth, 30 cm long and 1.2 cm in diameter consistent with D. renale was found in the right kidney. Microscopic examination revealed that the male Dioctophyma renale. Following removal of worm, the symptoms completely resolved within a few hours. Generally, parasitism by D. renale in human is a necropsy finding, nevertheless imaging techniques as ultrasound and computed tomography have been proven to be important tool to achieve diagnosis.

  4. Renal cortical and medullary blood flow responses to altered NO availability in humans

    DEFF Research Database (Denmark)

    Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L

    2010-01-01

    The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were......-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which...... the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans....

  5. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model.

    Science.gov (United States)

    Suarez, Eloah Rabello; Chang, De Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

    2016-06-07

    Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50-80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.

  6. Cardiovascular, endocrine and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M.H.; Olsen, N.V.; Christensen, P.

    1999-01-01

    remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate...... highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including...

  7. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  8. Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor

    Directory of Open Access Journals (Sweden)

    Agnes Shuk-Yee Lo

    2014-01-01

    Full Text Available Carbonic anhydrase IX (CAIX is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs that utilize a carbonic anhydrase (CA domain mapped, human single chain antibody (scFv G36 as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX+ RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX+ RCC.

  9. KITENIN is associated with tumor progression in human gastric cancer.

    Science.gov (United States)

    Ryu, Ho-Seong; Park, Young-Lan; Park, Su-Jin; Lee, Ji-Hee; Cho, Sung-Bum; Lee, Wan-Sik; Chung, Ik-Joo; Kim, Kyung-Keun; Lee, Kyung-Hwa; Kweon, Sun-Seog; Joo, Young-Eun

    2010-09-01

    KAI1 COOH-terminal interacting tetraspanin (KITENIN) promotes tumor cell migration, invasion and metastasis in colon, bladder, head and neck cancer. The aims of current study were to evaluate whether KITENIN affects tumor cell behavior in human gastric cancer cell line and to document the expression of KITENIN in a well-defined series of gastric tumors, including complete long-term follow-up, with special reference to patient prognosis. To evaluate the impact of KITENIN knockdown on behavior of a human gastric cancer cell line, AGS, migration, invasion and proliferation assays using small-interfering RNA were performed. The expression of activator protein-1 (AP-1) target genes and AP-1 transcriptional activity were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and luciferase reporter assay. The expression of KITENIN and AP-1 target genes by RT-PCR and Western blotting or immunohistochemistry was also investigated in human gastric cancer tissues. The knockdown of KITENIN suppressed tumor cell migration, invasion and proliferation in AGS cells. The mRNA expression of matrix metalloproteinase-1 (MMP-1), MMP-3, cyclooxygenase-2 (COX-2), and CD44 was reduced by knockdown of KITENIN in AGS. AP-1 transcriptional activity was significantly decreased by knockdown of KITENIN in AGS cells. KITENIN expression was significantly increased in human cancer tissues at RNA and protein levels. Expression of MMP-1, MMP-3, COX-2 and CD44 were significantly increased in human gastric cancer tissues. Immunostaining of KITENIN was predominantly identified in the cytoplasm of cancer cells. Expression of KITENIN was significantly associated with tumor size, Lauren classification, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN plays an important role in human gastric cancer progression by AP-1 activation.

  10. A Rare Renal Epithelial Tumor: Mucinous Cystadenocarcinoma Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Abdulkadir Tepeler

    2011-01-01

    Full Text Available Primary renal mucinous cystadenocarcinoma is a very rare lesion of kidney which originates from the metaplasia of the renal pelvic uroepithelium. Only one case with primary mucinous cystadenocarcinoma has been reported in the English literature. We report second case of mucinous cystadenocarcinoma which was radiologically classified as type-IIF Bosniak cyst in peripheral localization. We aimed to present this extreme and unusual entity with its radiological, surgical, and pathologic aspects under the light of literature.

  11. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  12. Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study.

    Science.gov (United States)

    Atherton, Daniel S; Deep, Nicholas L; Mendelsohn, Farrell O

    2012-07-01

    Hypertension remains an epidemic uncontrolled with pharmacologic therapies. A novel catheter inserted into the renal artery has been shown to lower blood pressure by ablating the renal sympathetic nerves with radiofrequency energy delivered through the arterial wall. We report a histologic study describing the anatomic substrate for this technique, specifically the renal sympathetic nervous system. Histological sections from proximal, middle, and distal renal artery segments from nine renal arteries (five human autopsies) were analyzed. Nerves were manually counted and their distance from the lumen-intima interface was measured using a micrometer. The nerves were then categorized by location into 0.5-mm-wide "rings" that were arranged circumferentially around the renal artery lumen. Of all nerves detected, 1.0% was in the 0-0.5 mm ring, 48.3% were in the 0.5-1.0 mm ring, 25.6% were in the 1.0-1.5 mm ring, 15.5% were in the 1.5-2.0 mm ring, and 9.5% were in the 2.0-2.5 mm ring. Beyond 0.5 mm, the proportion of nerves tended to decrease as the distance from the lumen increased. Totally, 90.5% of all nerves in this study existed within 2.0 mm of the renal artery lumen. Additionally, the number of nerves tended to increase along the length of the artery from proximal to distal segments (proximal = 216; middle = 323; distal = 417). In conclusion, our analysis indicates that a great proportion of renal sympathetic nerves have close proximity to the lumen-intima interface and should thus be accessible via renal artery interventional approaches such as catheter ablation. This data provides important anatomic information for the development of ablation and other type devices for renal sympathetic denervation. © 2011 Wiley Periodicals, Inc.

  13. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  14. Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways

    Directory of Open Access Journals (Sweden)

    Ma YL

    2018-03-01

    Full Text Available Ya-Li Ma,* Fang Chen,* Jun ShiDepartment of Nephrology, Huaihe Hospital Henan University, Kaifeng, People’s Republic of China*These authors contributed equally to this workBackground: Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC.Materials and methods: Three RCC cell lines (A489, 786-O and ACHN were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro. The therapeutic efficacy of Rhein was further evaluated by intraperitoneal administrations in tumor formation of mice. Western blot was used to investigate the underlying mechanisms of action of Rhein.Results: Rhein inhibited RCC cell proliferation in a dose- and time-dependent manner. It also suppressed RCC cell migration and invasion in vitro. Moreover, Rhein was able to inhibit tumor growth in nude mice by intraperitoneal administration in vivo. Mechanistically, the protein levels of phosphorylated MAPK (mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase, phosphorylated Akt and two targets of NF-κB (nuclear factor kappa-light-chain enhancer of activated B cells pathway, matrix metalloproteinase 9 and CCND1 were all markedly reduced by Rhein treatment.Conclusion: Rhein processed the antitumor effects in RCC cells by inhibiting cell proliferation, migration and invasion, and these tumor-suppressing functions might be mediated by MAPK/NF-κB signaling pathways.Keywords: Rhein, renal cell carcinoma, antitumor effects, MAPK, NF-κB

  15. Thymidine analogues to assess microperfusion in human tumors

    International Nuclear Information System (INIS)

    Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C.

    2005-01-01

    Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation

  16. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  17. Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

    Science.gov (United States)

    Grisk, Olaf

    2017-05-01

    Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors.

    Science.gov (United States)

    Zhao, Y-K; Jia, C-M; Yuan, G-J; Liu, W; Qiu, Y; Zhu, Q-G

    2015-06-29

    We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

  19. siRNA-mediated Erc gene silencing suppresses tumor growth in Tsc2 mutant renal carcinoma model.

    Science.gov (United States)

    Imamura, Osamu; Okada, Hiroaki; Takashima, Yuuki; Zhang, Danqing; Kobayashi, Toshiyuki; Hino, Okio

    2008-09-18

    Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery of siRNAs for stable treatment except short hairpin RNAs (shRNAs). On the other hand, there are many reports of systemic delivery of siRNAs for transient treatment using liposome carriers and others. With regard to shRNAs, a report showed fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Therefore, we decided to use original siRNA microspheres instead of shRNA for stable treatment of disease. In this study, we designed rat-specific siRNA sequences for Erc/mesothelin, which is a tumor-specific gene expressed in the Eker (Tsc2 mutant) rat model of hereditary renal cancer and confirmed the efficacy of gene silencing in vitro. Then, by using siRNA microspheres, we found that the suppression of Erc/mesothelin caused growth inhibition of Tsc2 mutant renal carcinoma cells in tumor implantation experiments in mice.

  20. Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

    Science.gov (United States)

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

    2016-08-01

    The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

  1. C-reactive Protein in Patients with Metastatic Clear Cell Renal Carcinoma: An Important Biomarker for Tumor-associated Inflammation

    Directory of Open Access Journals (Sweden)

    Albrecht Reichle

    2006-01-01

    Full Text Available Two consecutive multi-center phase II trials were designed to prove the hypothesis, whether therapeutic modeling of tumor-associated infl ammatory processes could result in improved tumor response. Therapy in both trials consisted of low-dose capecitabine 1g/m2 twice daily p.o. for 14 days, every 3 weeks, day 1+, and rofecoxib 25 mg daily p.o., day 1+ (from 11/04 etoricoxib 60 mg daily instead plus pioglitazone 60 mg daily p.o., day 1+. In study II low-dose IFN-a 4.5 MU sc. three times a week, week 1+, was added until disease progression. Eighteen, and 33 patients, respectively, with clear cell renal carcinoma and progressive disease were enrolled. Objective response (48% was exclusively observed in study II (PR 35%, CR 13%, and paralleled by a strong CRP response after 4 weeks on treatment, p = 0.0005, in all 29 pts (100% with elevated CRP levels. Median progression-free survival could be more than doubled from a median of 4.7 months (95% CI, 1.0 to 10.4 to 11.5 months (6.8 to 16.2 in study II, p = 0.00001. Median overall survival of population II was 26 months. Efficacious negative regulation of tumor-associated infl ammation by transcription modulators may result in a steep increase of tumor response and survival.

  2. Tumores renais e adrenais com invasão cardíaca: resultados cirúrgicos imediatos em 14 pacientes Tumores renales y adrenales con invasión cardiaca: resultados quirúrgicos inmediatos en 14 pacientes Renal and adrenal tumors with cardiac invasion: immediate surgical results in 14 patients

    Directory of Open Access Journals (Sweden)

    Rafael Fagionato Locali

    2009-03-01

    Full Text Available FUNDAMENTO: A ressecção do trombo tumoral em veia cava inferior (VCI e átrio direito (AD aumenta a sobrevida do paciente com câncer renal/supra-renal. OBJETIVO: Avaliar a conduta cirúrgica do trombo da VCI e AD no tratamento dos tumores renais e supra-renais. MÉTODOS:De janeiro de 1997 a junho de 2007 foram avaliados, retrospectivamente, 14 pacientes tratados cirurgicamente para retirada de trombo em VCI e/ou AD decorrente de tumor renal ou supra-renal. Desses, 64,2% eram do sexo masculino, e havia 42,8% de casos de tumor de Wilms (TW, 28,5% de adenocarcinoma de supra-renal (AS e 28,5% de carcinoma de células claras (CC, com idades médias de 4,5, 60,5 e 2,5 anos, respectivamente. Aspectos epidemiológicos e parâmetros intra e pós-operatórios hospitalar foram avaliados. RESULTADOS: Em todos os casos encontrou-se trombo tumoral em VCI supra-hepática, e em 62,4% o trombo invadiu o AD. A trombectomia foi realizada com o emprego da circulação extracorpórea associada à hipotermia profunda e parada circulatória total em 85,7% dos casos e moderada no restante. Ligou-se a VCI em 7,1% dos pacientes, e reconstruiu-se por rafia em 92,9%. Os tempos de intubação orotraqueal e internação variaram conforme o tipo de tumor. Ocorreram dois óbitos hospitalares no grupo de AS, por parada cardiorrespiratória intra-operatória. CONCLUSÃO: Existe maior número de casos de trombo tumoral em VCI e AD decorrente de TW. Os casos de AS evoluem com mais complicações no pós-operatório, e o prognóstico no pós-operatório hospitalar dos pacientes com TW é melhor.FUNDAMENTO: La resección del trombo tumoral en vena cava inferior (VCI y atrio derecho (AD aumenta la sobrevida del paciente con cáncer renal/ suprarrenal. OBJETIVO: Evaluar la conducta quirúrgica frente al trombo de la VCI y AD en el tratamiento de los tumores renales y suprarrenales. MÉTODOS: De enero de 1997 a junio de 2007, se evaluaron, retrospectivamente, a 14 pacientes tratados

  3. Is oxygen important in the radiocurability of human tumors

    International Nuclear Information System (INIS)

    Withers, H.R.; Suit, H.D.

    1974-01-01

    It is quite likely that untreated human tumors contain hypoxic cells. Frequently, perhaps usually, the presence of these hypoxic cells does not influence radiocurability. If hypoxia limits radiocurability, it is more likely to do so in the treatment of large tumors and maybe with greater likelihood in tumors in certain sites. Hypoxia would also be more likely to affect response to a small number of fractions, since reoxygenation would need to be more complete in order that cell killing by the larger dose fractions used would not be prejudiced by the hypoxia of a small proportion of cells. Hyperbaric oxygen is disappointing as an adjuvant to radiotherapy. Results obtained are not better than those obtained using the best conventional fractionation regimes in air. This does not prove, however, that hypoxia is not a cause of failure to control tumors locally, since physiological adaptive mechanisms against HPO such as vasoconstriction may prevent better oxygenation of the tumor. If other methods such as high LET beams are to be used to reduce any effect hypoxia may have on radiocurability, their greatest benefit would be expected in the local control of late-stage disease and this benefit may be greater in some tumor sites than others. (U.S.)

  4. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  5. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

    2014-07-15

    Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

  6. Induction and regulation of tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand-mediated apoptosis in renal cell carcinoma.

    Science.gov (United States)

    Griffith, Thomas S; Fialkov, Jonathan M; Scott, David L; Azuhata, Takeo; Williams, Richard D; Wall, Nathan R; Altieri, Dario C; Sandler, Anthony D

    2002-06-01

    The lack of effective therapy for disseminated renal cell carcinoma (RCC) has stimulated the search for novel treatments including immunotherapeutic strategies. However, poor therapeutic responses and marked toxicity associated with immunological agents has limited their use. The tumor necrosis factor family member tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2 ligand induces apoptosis in a variety of tumor cell types, while having little cytotoxic activity against normal cells. In this study the activation and regulation of TRAIL-induced apoptosis and TRAIL receptor expression in human RCC cell lines and pathologic specimens was examined. TRAIL induced caspase-mediated apoptotic death of RCC cells with variable sensitivities among the cell lines tested. Compared with TRAIL-sensitive RCC cell lines (A-498, ACHN, and 769-P), the TRAIL-resistant RCC cell line (786-O) expressed lesser amounts of the death-inducing TRAIL receptors, and greater amounts of survivin, an inhibitor of apoptosis. Incubation of 786-O with actinomycin D increased the expression of the death-inducing TRAIL receptors and, concomitantly, decreased the intracellular levels of survivin, resulting in TRAIL-induced apoptotic death. The link between survivin and TRAIL regulation was confirmed when an increase in TRAIL resistance was observed after overexpression of survivin in the TRAIL-sensitive, survivin-negative RCC line A-498. These findings, along with our observation that TRAIL receptors are expressed in RCC tumor tissue, suggest that TRAIL may be useful as a therapeutic agent for RCC and that survivin may partially regulate TRAIL-induced cell death.

  7. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

    Science.gov (United States)

    Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

    2004-01-01

    von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

  8. Upregulation of Peroxideroxin-6 in human renal adenocarcinoma cells 786-0, after ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Evelin Caroline da; Bellini, Maria Helena [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Renal cell carcinoma (RCC) accounts for 3% of human malignancies and approximately 90% of renal malignancies and among urological tumors. RCC is quite resistant to conventional radiotherapy. This technique allows the dose of radiation, in a single fraction, to be precisely applied to the tumor and the tissues adjacent to it, most of the time, are spared. Proteomics has allowed large-scale studies of protein expression in different tissues and body fluids, under different conditions and / or times. Mass spectrometry allows the identification and quantification of thousands of proteins and peptides in a biological fluid or lysed cells, and is analyzed on a platform to identify differences in the expression of proteins associated with cancer cell proliferation and to establish potential biomarkers predictive of the response therapy. The peroxideroxin- 6 (PRDX 6) protein encoded by this gene is a member of the antioxidant protein family. The PRDX family contains six members that function in detoxifying ROS and providing cytoprotection from internal and It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. Aim: To analyze the expression of PRDX6 in 786-0 cells, after radiation. Methods: A cell culture of the 786-0 cells was performed and to evaluate the mitotic potential, the clonogenic assay was performed with doses of 2 to 10 Gy irradiated in GammaCell (CTR, IPEN) and incubated for 10 days in normoxia conditions. After 10 days, the colonies of the respective doses were stained with methanol 20% and crystal violet 0,5% and counted, and the multiple comparisons was analyzed by One-way ANOVA followed by Bonferroni's test and at the defined dose the cells were irradiated and the cytoplasmic proteins were extracted by the PE kit Subcellular proteome extraction (Merck, USA), dosed by the Lowry method and stored at -20 °. For the qualitative analysis of proteins, SDS-PAGE was performed

  9. Upregulation of Peroxideroxin-6 in human renal adenocarcinoma cells 786-0, after ionizing radiation

    International Nuclear Information System (INIS)

    Silva, Evelin Caroline da; Bellini, Maria Helena

    2017-01-01

    Full text: Introduction: Renal cell carcinoma (RCC) accounts for 3% of human malignancies and approximately 90% of renal malignancies and among urological tumors. RCC is quite resistant to conventional radiotherapy. This technique allows the dose of radiation, in a single fraction, to be precisely applied to the tumor and the tissues adjacent to it, most of the time, are spared. Proteomics has allowed large-scale studies of protein expression in different tissues and body fluids, under different conditions and / or times. Mass spectrometry allows the identification and quantification of thousands of proteins and peptides in a biological fluid or lysed cells, and is analyzed on a platform to identify differences in the expression of proteins associated with cancer cell proliferation and to establish potential biomarkers predictive of the response therapy. The peroxideroxin- 6 (PRDX 6) protein encoded by this gene is a member of the antioxidant protein family. The PRDX family contains six members that function in detoxifying ROS and providing cytoprotection from internal and It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. Aim: To analyze the expression of PRDX6 in 786-0 cells, after radiation. Methods: A cell culture of the 786-0 cells was performed and to evaluate the mitotic potential, the clonogenic assay was performed with doses of 2 to 10 Gy irradiated in GammaCell (CTR, IPEN) and incubated for 10 days in normoxia conditions. After 10 days, the colonies of the respective doses were stained with methanol 20% and crystal violet 0,5% and counted, and the multiple comparisons was analyzed by One-way ANOVA followed by Bonferroni's test and at the defined dose the cells were irradiated and the cytoplasmic proteins were extracted by the PE kit Subcellular proteome extraction (Merck, USA), dosed by the Lowry method and stored at -20 °. For the qualitative analysis of proteins, SDS-PAGE was performed

  10. Effects of alpha-2 agonists on renal function in hypertensive humans.

    Science.gov (United States)

    Goldberg, M; Gehr, M

    1985-01-01

    Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.

  11. A Retroperitoneal Extra-Renal Wilms' Tumour: A Case Report

    African Journals Online (AJOL)

    2017-03-06

    Mar 6, 2017 ... renal origin might have arisen from totipotent germ cells and hence may consist of ... The exact embryonic origin of extrarenal Wilms' tumor is not certain,[12] but ... Stiller CA, Parkin DM. Human cancer: international variations.

  12. Critical appraisal of first-generation renal tumor complexity scoring systems: Creation of a second-generation model of tumor complexity.

    Science.gov (United States)

    Tobert, Conrad M; Shoemaker, Allen; Kahnoski, Richard J; Lane, Brian R

    2015-04-01

    To investigate whether a combination of variables from each nephrometry system improves performance. There are 3 first-generation systems that quantify tumor complexity: R.E.N.A.L. nephrometry score (RNS), preoperative aspects and dimensions used for an anatomical (PADUA) classification (PC), and centrality index (CI). Although each has been subjected to validation and comparative analysis, to our knowledge, no work has been done to combine variables from each method to optimize their performance. Scores were assigned to each of 276 patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN). Individual components of all 3 systems were evaluated in multivariable logistic regression analysis of surgery type (PN vs. RN) and combined into a "second-generation model." In multivariable analysis, each scoring system was a significant predictor of PN vs. RN (Psystems, CI was most highly correlated with surgery type (area under the curve [AUC] = 0.91), followed by RNS (AUC = 0.90) and PC (AUC = 0.88). Each individual component of these scoring systems was also a predictor of surgery type (Psystem (RNS), location along the lateral rim (PC), and centrality (CI). A novel model in which these 4 variables were rescaled outperformed each first-generation system (AUC = 0.91). Optimization of first-generation models of renal tumor complexity results in a novel scoring system, which strongly predicts surgery type. This second-generation model should aid comprehension, but future work is still needed to establish the most clinically useful model. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Decoding NADPH oxidase 4 expression in human tumors

    Directory of Open Access Journals (Sweden)

    Jennifer L. Meitzler

    2017-10-01

    Full Text Available NADPH oxidase 4 (NOX4 is a redox active, membrane-associated protein that contributes to genomic instability, redox signaling, and radiation sensitivity in human cancers based on its capacity to generate H2O2 constitutively. Most studies of NOX4 in malignancy have focused on the evaluation of a small number of tumor cell lines and not on human tumor specimens themselves; furthermore, these studies have often employed immunological tools that have not been well characterized. To determine the prevalence of NOX4 expression across a broad range of solid tumors, we developed a novel monoclonal antibody that recognizes a specific extracellular region of the human NOX4 protein, and that does not cross-react with any of the other six members of the NOX gene family. Evaluation of 20 sets of epithelial tumors revealed, for the first time, high levels of NOX4 expression in carcinomas of the head and neck (15/19 patients, esophagus (12/18 patients, bladder (10/19 patients, ovary (6/17 patients, and prostate (7/19 patients, as well as malignant melanoma (7/15 patients when these tumors were compared to histologically-uninvolved specimens from the same organs. Detection of NOX4 protein upregulation by low levels of TGF-β1 demonstrated the sensitivity of this new probe; and immunofluorescence experiments found that high levels of endogenous NOX4 expression in ovarian cancer cells were only demonstrable associated with perinuclear membranes. These studies suggest that NOX4 expression is upregulated, compared to normal tissues, in a well-defined, and specific group of human carcinomas, and that its expression is localized on intracellular membranes in a fashion that could modulate oxidative DNA damage.

  14. Core biopsies of renal tumors: A study on diagnostic accuracy, interobserver, and intraobserver variability

    DEFF Research Database (Denmark)

    Kummerlin, I.; Kate, F. ten; Smedts, F.

    2008-01-01

    and interobserver agreement were calculated. Results: Five tumors were benign and 57 malignant. Eight percent to 16% of the CBs were considered inadequate for diagnosis. In 0-8% of the cases, the pathologist could not discriminate between a benign or malignant tumor. Overall accuracy ranged from 77% to 90...

  15. T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

    Directory of Open Access Journals (Sweden)

    Kim Tae-Sik

    2011-06-01

    Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

  16. Sigma and opioid receptors in human brain tumors

    International Nuclear Information System (INIS)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J.

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [ 3 H] 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: μ, [D-ala 2 , mePhe 4 , gly-ol 5 ] enkephalin (DAMGE); κ, ethylketocyclazocine (EKC) or U69,593; δ, [D-pen 2 , D-pen 5 ] enkephalin (DPDPE) or [D-ala 2 , D-leu 5 ] enkephalin (DADLE) with μ suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. κ opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed

  17. Sigma and opioid receptors in human brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  18. Piggy-back Hepatic Transplant Technique and Veno-venous Bypass Without Cardiac Arrest: A Multidisciplinary Approach in Borderline T3b/T3c Renal Tumors

    Directory of Open Access Journals (Sweden)

    Nechifor-Boila IA

    2015-06-01

    Full Text Available Surgery for renal cell carcinomas with tumor thrombus extending in the Inferior Vena Cava (IVC can be particularly challenging, especially in the retrohepatic and intraatrial situations (T3b and T3c. Classically, these tumors require the intraoperative use of cardio-pulmonary by-pass (CPB and deep hypothermic circulatory arrest (DHCA, that can result in specific complications (stroke, platelet dysfunction, with increased postoperative morbidity rates.

  19. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. A Case of Renal Primitive Neuroectodermal Tumor Confirmed by Fluorescence in situ Hybridization

    Directory of Open Access Journals (Sweden)

    Toshiki Etani

    2015-04-01

    Full Text Available Primitive neuroectodermal tumor (PNET is a member of the Ewing's sarcoma family of tumors (ESFT. We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.

  1. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report

    OpenAIRE

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-01-01

    Background Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the fie...

  2. Complications of percutaneous renal tumor biopsy: An analysis of 340 consecutive biopsies

    DEFF Research Database (Denmark)

    René Rasmussen, Lars; Loft, Martina; Høyer, Søren

    Purpose Ultrasound Guided Percutaneous Kidney Biopsy (UGPKB) plays a major role in diagnosis of renal tumours. There seems to be little consensus regarding post-biopsy observation period. We aim to identify complications in UGPKB among outpatients with a suspected malignant renal lesion as well...... as the timing of onset of these complications, helping to clarify the optimal observation period. Many studies in this field suggest a lower complication risk for outpatients compared to hospitalized patients. In the latter group, an observation period of 24h after biopsy is often recommended. Material...... discrepancy. Results As for one third of the patients, analysed up until now, we find a total of one major complication and a few minor, all arisen within less than 6 hours after biopsy. Conclusions Rates of both major and minor complications in UGPKB are very low suggesting a shorter observation period...

  3. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  4. CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

    NARCIS (Netherlands)

    Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

  5. Retroperitoneal Laparoscopic Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1 Renal Hilar Tumor: Comparison of Perioperative Characteristics and Short-Term Functional and Oncologic Outcomes.

    Science.gov (United States)

    Yang, Chuance; Wang, Zhenlong; Huang, Shanlong; Xue, Li; Fu, Delai; Chong, Tie

    2018-04-18

    To present our single-center experience with retroperitoneal laparoscopic partial nephrectomy (LPN) and retroperitoneal laparoscopic radical nephrectomy (LRN) for T1 renal hilar tumors and evaluate which one is better. A retrospective review of 63 patients with hilar tumors undergoing retroperitoneal LPN or LRN was performed. The perioperative characteristics, change in estimated glomerular filtration rate (eGFR) from baseline to month 3, and oncologic outcomes were summarized. In total, 25 patients underwent LPN, and 38 patients underwent LRN. The mean tumor size in the LPN and LRN groups was 4.5 and 4.9 cm, respectively. The mean operation time was longer in the LPN group than that in the LRN group (212.5 minutes versus 160.7 minutes, respectively; P  .05). In experienced hands, although retroperitoneal LRN can result in shorter operation times and shorter lengths of stay, retroperitoneal LPN can preserve renal function better than LRN. Retroperitoneal LPN should be the priority in selected patients with T1 renal hilar tumors, especially for patients with renal insufficiency.

  6. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  7. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  8. Síndrome de lisis tumoral en un paciente con cáncer de riñón tratado con sunitinib Tumor lysis syndrome in a patient with a renal carcinoma treated with sunitinib

    Directory of Open Access Journals (Sweden)

    Ezequiel Rodríguez-Reimúndes

    2011-04-01

    Full Text Available El síndrome de lisis tumoral (SLT es un trastorno metabólico que ocurre como consecuencia de una destrucción celular masiva. Se caracteriza por la presencia de hiperuricemia, hiperfosfatemia, hipocalcemia e hiperkalemia, y predispone al desarrollo de insuficiencia renal aguda. En la mayoría de los casos el SLT ocurre luego de instaurarse un tratamiento antitumoral y es más frecuente en tumores de alto grado de malignidad y alta sensibilidad a la quimioterapia. Presentamos el caso de un paciente con diagnóstico de cáncer de riñón recidivado que presenta un SLT e insuficiencia renal aguda luego de iniciar tratamiento con sunitinib.The tumor mor lysis syndrome (TLS is a metabolic disorder resulting from a massive tumor breakdown. It is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia and hyperkalemia and predisposes to acute renal failure. TLS usually occurs after the initiation of cytotoxic therapy and is more frequent in the case of neoplasias with a high proliferative rate or that are highly chemo-sensitive. We report the case of a man with a recurrent kidney cancer who presented with a TLS and acute renal failure after initiation of sunitinib.

  9. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    Science.gov (United States)

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

  10. Renal tumors: evaluation of prognostic factors in 98 cases from a reference hospital in Porto Alegre, Brazil

    Directory of Open Access Journals (Sweden)

    Alexandra Medeiros Souza de Freitas

    2014-02-01

    Full Text Available Introduction: Renal cell carcinoma (RCC is an aggressive disease worldwide. Objective: Study traditional prognostic factors associated with pathological reports and the novel markers survivin and B7-H1 by immunohistochemistry. Methods: In a reference hospital of Porto Alegre, Brazil, we conducted a cross-sectional study of RCC in patients who underwent radical nephrectomy between 2006 and 2009. We selected those who were diagnosed with the most common histologic subtypes: clear cell and papillary RCC. We retrospectively reviewed pathological data to determine traditional prognostic factors, like size, presence of coagulative necrosis, Fuhrman grade and tumor-node metastasis (TNM system. Besides, we performed an immunohistochemistry (IHC study with survivin and B7-H1. Results: Our sample had 98 cases, 90% of the cases were composed by clear cell histologic subtype, 73% were tumors classified as T1 and T2 in the TNM system, most were Fuhrman nuclear grade 2 or 3, and 70% were positive for necrosis. In relation to the new prognostic markers, we found 50 cases positive to survivin and 38 to B7-H1. In this investigation of traditional prognostic markers and new markers we observed that only necrosis was associated with positive results of biomarkers. < 0.001. Conclusion: This finding confirms previous studies that necrosis is an important factor to consider in the prognosis of RCC.

  11. Triparanol suppresses human tumor growth in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Xinyu [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China); Han, Xingpeng [Department of Pathology, Tianjin Chest Hospital, Tianjin 300051 (China); Zhang, Fang [Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang (China); He, Miao [Life Sciences School, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhi, Xiu-Yi, E-mail: xiuyizhi@yahoo.com.cn [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  12. Triparanol suppresses human tumor growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Bi, Xinyu; Han, Xingpeng; Zhang, Fang; He, Miao; Zhang, Yi; Zhi, Xiu-Yi; Zhao, Hong

    2012-01-01

    Highlights: ► Demonstrate Triparanol can block proliferation in multiple cancer cells. ► Demonstrate Triparanol can induce apoptosis in multiple cancer cells. ► Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. ► Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  13. Laparoscopic radical nephrectomy versus open radical nephrectomy in T1-T3 renal tumors: An outcome analysis

    Directory of Open Access Journals (Sweden)

    Arvind P Ganpule

    2008-01-01

    Full Text Available Aims: To compare laparoscopic radical nephrectomy (LRN with open radical nephrectomy (ORN in T1-T3 renal lesions. Materials and Methods: The records of 65 patients who underwent LRN between January 2002 and December 2006 were entered prospectively in a database. The patients were compared with 56 patients who had undergone ORN between January 2000 and December 2005. The two groups were comparable in terms of age, body mass index (BMI and tumor size. LRN was compared with ORN in terms of operative room time, blood loss, complications , analgesic requirement, hospital stay and start of oral intake. The oncologic efficacy was evaluated in stages T1 and T2 in terms of cancer-free and overall survival. Results: The laparoscopy group had a significantly shorter hospital stay (5.72, range 3-23 days vs. 9.18, range 4-23 days, p value: < 0.0001, analgesia requirement (175.65, range 50-550 mg vs. 236, range 0-1100 mg of tramadol, p value: < 0.03, hemoglobin decline (1.55, range 0.1 to 4.4 mg/dl vs. 2.25, range 0.2 - 7 mg/dL, p value: < 0.001 and hematocrit drop (4.83, range 0.3 - 12.9 vs. 7.06 range 2 -18, p value: < 0.0001. The majority of specimens showed renal cell carcinoma. In the laparoscopy group, 29 tumors were T1 stage, 18 were T2, while eight were T3. In the open surgery group, 25 tumors were T1, 19 were T2 and 12 were T3. The cancer-free survival rate at 24 months for ORN and LRN in T1 lesions was 91.7% and 93.15% respectively and the patient survival rate was 100% in both groups. The cancer-free survival rate at 24 months for ORN and LRN in T2 lesions was 88.9% and 94.1%, respectively and the patient survival was 100% and 94%, respectively. After LRN, there was one instance of port site metastasis, local recurrence and distant metastasis. All recurrences were distant after ORN. Conclusion: Laparoscopic radical nephrectomy has advantages in terms of shorter hospitalization and a lower analgesia requirement. It is feasible and produces effective

  14. Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

    Directory of Open Access Journals (Sweden)

    Shioyama Yasukazu

    2010-04-01

    Full Text Available Abstract Background Single minimum incision endoscopic surgery (MIES involves the use of a flexible high-definition laparoscope to facilitate open surgery. We reviewed our method of radical nephrectomy for renal tumors, which is single MIES combined with preoperative virtual surgery employing three-dimensional CT images reconstructed by the volume rendering method (3D-CT images in order to safely and appropriately approach the renal hilar vessels. We also assessed the usefulness of 3D-CT images. Methods Radical nephrectomy was done by single MIES via the translumbar approach in 80 consecutive patients. We performed the initial 20 MIES nephrectomies without preoperative 3D-CT images and the subsequent 60 MIES nephrectomies with preoperative 3D-CT images for evaluation of the renal hilar vessels and the relation of each tumor to the surrounding structures. On the basis of the 3D information, preoperative virtual surgery was performed with a computer. Results Single MIES nephrectomy was successful in all patients. In the 60 patients who underwent 3D-CT, the number of renal arteries and veins corresponded exactly with the preoperative 3D-CT data (100% sensitivity and 100% specificity. These 60 nephrectomies were completed with a shorter operating time and smaller blood loss than the initial 20 nephrectomies. Conclusions Single MIES radical nephrectomy combined with 3D-CT and virtual surgery achieved a shorter operating time and less blood loss, possibly due to safer and easier handling of the renal hilar vessels.

  15. Clinical experience in humans with radiolabeled antibody for tumor detection

    International Nuclear Information System (INIS)

    Morrison, R.T.; Lyster, D.M.; Szasz, I.; Alcorn, L.N.; Huckell, V.F.; Rhodes, B.; Breslow, K.; Burchiel, S.

    1982-01-01

    I-131 and Tc-99m labeled polyclonal or monoclonal antibody and fragments of antibody, specific to human chorionic gonadotropin (hCG) or to a melanoma cell surface antigen (MCSA) were injected into proven cancer patients. Using standard homeostasis parameters, and scanning techniques, the safety and efficacy of each antibody was evaluated. Antibody fragments were expected to clear faster from the circulation allowing for earlier imaging and a better target-to-non-target ratio. The technetium label may perturb the antiboby's kinetics so that clearance is more rapid for both whole antibody and fragments. After a statistical evaluation of all parameters measured pre and post injection it was concluded that no acute toxicity reactions were present in any patient studied. Scan results were not acceptable for a tumor detecting procedure used in routine practice. Tumor upake was seen in less than 10% of scans

  16. Tumor trapping of 5-fluorouracil: In vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits

    International Nuclear Information System (INIS)

    Wolf, W.; Servis, K.L.; El-Tahtawy, A.; Singh, M.; Ray, M.; Shani, J.; Presant, C.A.; King, M.; Wiseman, C.; Blayney, D.; Albright, M.J.; Atkinson, D.; Ong, R.; Barker, P.B.; Ring, R. III

    1990-01-01

    The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19 F NMR spectroscopy. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism previously documented using 19 F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients)

  17. Synchrotron radiation XRF microprobe study of human bone tumor slice

    International Nuclear Information System (INIS)

    Huang Yuying; Zhao Limin; Wang Zhouguang; Shao Hanru; Li Guangcheng; Wu Yingrong; He Wei; Lu Jianxin; He Rongguo

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described. Using the bovine liver as the standard reference, the minimum detection limit (MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe. The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated. The experimental result relation to the clinical medicine was also discussed. (author)

  18. Identification of Molecular Tumor Markers in Renal Cell Carcinomas with TFE3 Protein Expression by RNA Sequencing

    Directory of Open Access Journals (Sweden)

    Dorothee Pflueger

    2013-11-01

    Full Text Available TFE3 translocation renal cell carcinoma (tRCC is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study,we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 translocation. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNAread-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2 point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs. The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription-PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P<.001 and 22 papillaryRCCs (P<.05-.07. Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2 and Contactin 3 (CNTN3 expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both.

  19. Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas

    International Nuclear Information System (INIS)

    Yao, Masahiro; Murakami, Takayuki; Shioi, Koichi; Mizuno, Nobuhiko; Ito, Hiroki; Kondo, Keiichi; Hasumi, Hisashi; Sano, Futoshi; Makiyama, Kazuhide; Nakaigawa, Noboru; Kishida, Takeshi; Nagashima, Yoji; Yamanaka, Shoji; Kubota, Yoshinobu

    2014-01-01

    High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs

  20. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

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    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  1. Telomere length modulation in human astroglial brain tumors.

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    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  2. The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages.

    Science.gov (United States)

    Bougherara, Houcine; Némati, Fariba; Nicolas, André; Massonnet, Gérald; Pugnière, Martine; Ngô, Charlotte; Le Frère-Belda, Marie-Aude; Leary, Alexandra; Alexandre, Jérôme; Meseure, Didier; Barret, Jean-Marc; Navarro-Teulon, Isabelle; Pèlegrin, André; Roman-Roman, Sergio; Prost, Jean-François; Donnadieu, Emmanuel; Decaudin, Didier

    2017-11-21

    Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker. We then provided evidence that the tumor stroma of OC is enriched in tumor-associated macrophages and that these cells are responsible for 3C23K-induced killing of tumor cells through ADCP and ADCC mechanisms. In addition, we showed that 3C23K reduced macrophages induced-T cells immunosuppression. Finally, we evaluated the therapeutic efficacy of 3C23K alone and in combination with a carboplatin-paclitaxel chemotherapy in a panel of OC Patient-Derived Xenografts. In those experiments, we showed that 3C23K significantly increased the proportion and the quality of chemotherapy-based in vivo responses. Altogether, our data support the potential interest of AMHRII targeting in human ovarian cancers and the evaluation of 3C23K in further clinical trials.

  3. Phase transitions in tumor growth: IV relationship between metabolic rate and fractal dimension of human tumor cells

    Science.gov (United States)

    Betancourt-Mar, J. A.; Llanos-Pérez, J. A.; Cocho, G.; Mansilla, R.; Martin, R. R.; Montero, S.; Nieto-Villar, J. M.

    2017-05-01

    By the use of thermodynamics formalism of irreversible processes, complex systems theory and systems biology, it is derived a relationship between the production of entropy per unit time, the fractal dimension and the tumor growth rate for human tumors cells. The thermodynamics framework developed demonstrates that, the dissipation function is a Landau potential and also the Lyapunov function of the dynamical behavior of tumor growth, which indicate the directional character, stability and robustness of the phenomenon. The entropy production rate may be used as a quantitative index of the metastatic potential of tumors. The current theoretical framework will hopefully provide a better understanding of cancer and contribute to improvements in cancer treatment.

  4. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

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    Ferrone Soldano

    2007-06-01

    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  5. Architecture of the human renal inner medulla and functional implications.

    Science.gov (United States)

    Wei, Guojun; Rosen, Seymour; Dantzler, William H; Pannabecker, Thomas L

    2015-10-01

    The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. Copyright © 2015 the American Physiological Society.

  6. Studies on structural features of human tumor necrosis factor

    International Nuclear Information System (INIS)

    Yin Chuanyuan; Guo Donglin; Xi Tao; Xu Xianxiu; Gu Qingchao

    1997-01-01

    The microstructure of human tumor necrosis factor alpha (TNF-α) and its mutant (TNF-b) has been investigated by utilizing positron annihilation lifetime spectroscopy, radioiodination of human TNF and L929 cells assay. The experimental results show that the long lifetime (Τ 2 ) and corresponding intensity (I 2 ) of lower ortho-positronium annihilation in TNF-α are longer and less than those in the TNF-b, respectively. It suggests that the TNF-b is smaller in free volume and higher in density than the TNF-α. The TNF-b may maintain a more favorable conformation for binding to TNF receptors, thus increasing its biological activity. It is then concluded that the increases in the cytotoxicity and in the density for the TNF-b result from the decreases in the free volume in the TNF-b

  7. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

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    Kohan Donald E

    2002-08-01

    Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

  8. Renal cell carcinoma in patient with crossed fused renal ectopia

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    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  9. Renal Hemangiopericytoma

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    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  10. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  11. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

    Science.gov (United States)

    Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

    2009-12-01

    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

  12. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

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    Liying Gu

    Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

  13. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-11-30

    Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

  14. Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

    Science.gov (United States)

    Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

    2016-08-22

    Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations.

  15. Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study

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    Ahlström MG

    2015-08-01

    Full Text Available Magnus Glindvad Ahlström,1 Bo Feldt-Rasmussen,2 Rebecca Legarth,1 Gitte Kronborg,3 Court Pedersen,4 Carsten Schade Larsen,5 Jan Gerstoft,1 Niels Obel1 1Department of Infectious Diseases, 2Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, 3Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 4Department of Infectious Diseases, Odense University Hospital, Odense, 5Department of Infectious Diseases, Aarhus University Hospital, Skejby, Aarhus, Denmark Introduction: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV, but its potential association with renal impairment remains to be established. Methods: We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1 overall renal function and risk of chronic kidney disease (CKD, 2 risk of any renal replacement therapy (aRRT, and 3 mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft–Gault equation (CG-CrCl, and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs for risk of CKD, aRRT, and mortality rate ratios (MRRs following aRRT. Results: From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7–1.7; adjusted IRR: 1.3, 95% CI: 0.9–1.8 or aRRT (adjusted IRR: 0.8, 95% CI: 0.4–1.7; adjusted IRR: 0.9, 95% CI: 0.5–1.7. Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3

  16. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  17. Role of presurgical targeted molecular therapy in renal cell carcinoma with an inferior vena cava tumor thrombus

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    Peng C

    2018-04-01

    Full Text Available Cheng Peng,1,* Liangyou Gu,1,* Lei Wang,2 Qingbo Huang,1 Baojun Wang,1 Gang Guo,1 Yang Fan,1 Yu Gao,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, People’s Republic of China; 2Department of Urology, Chinese PLA 534 Hospital, Luoyang, People’s Republic of China *These authors contributed equally to this work Purpose: The clinical benefit of targeted molecular therapy (TMT in renal cell carcinoma (RCC with an inferior vena cava (IVC tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy. Patients and methods: We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy. Results: The tumor thrombus levels before TMT were stage I in 1 patient (5.6%, II in 12 patients (66.7%, III in 4 patients (22.2%, and IV in 1 patient (5.6%. After a median of two treatment cycles (range: 1–3, the thrombus height decreased measurably in 11 patients (61.1% with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8% and was enlarged in two (11.1%. Downstaging of the thrombus level occurred in four patients (22.2%; the surgical strategy was modified in three patients (16.7% to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056. Conclusion: Our data suggest a limited influence of presurgical TMT

  18. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

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    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  19. Renal cortical and medullary blood flow responses to altered NO-availability in humans

    DEFF Research Database (Denmark)

    Damkjaer, Mads; Vafaee, Manoucher; Møller, Michael Lehd

    2010-01-01

    The objective was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned and regional renal blood flow determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed...... of one voxel were eliminated stepwise from the external surface of the VOI ('voxel peeling'), and the blood flow subsequently determined in each new, reduced VOI. Blood flow in the shrinking volumes of interest (VOIs) decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood...... flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ±0.17 ml·(g·min)(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ±0.18 ml·(g·min)(-1) (p...

  20. Isotope release cytotoxicity assay applicable to human tumors: the use of 111-indium

    Energy Technology Data Exchange (ETDEWEB)

    Frost, P; Wiltrout, R; Maciorowski, Z; Rose, N R

    1977-01-01

    We have demonstrated that human tumors can be labelled efficiently with the 111indium-oxine chelate. Subsequently, this isotope can be released by cytotoxic lymphoid cells. Both natural and induced cytotoxicity can be demonstrated utilizing this isotope release method. Because of the slow spontaneous release of 111indium and its efficient labelling of human tumor cells, this isotope release assay can be utilized in long-term cytotoxic assays in the study of human tumor immunology.

  1. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  2. Renal cortical and medullary blood flow responses to altered NO availability in humans.

    Science.gov (United States)

    Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L; Braad, Poul Erik; Petersen, Henrik; Høilund-Carlsen, Poul Flemming; Bie, Peter

    2010-12-01

    The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor N(ω)-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.

  3. Differential transfection efficiency rates of the GM-CSF gene into human renal cell carcinoma lines by lipofection.

    Science.gov (United States)

    Hernández, A; Zöller, K; Enczmann, J; Ebert, T; Schmitz-Draeger, B; Ackermann, R; Wernet, P

    1997-01-01

    One of the major questions in any gene therapy approach is the selection of the appropriate vector system. Here, the optimization of a gene transfer protocol for renal cell carcinoma using lipofection as a nonviral gene transduction system was evaluated. To select the promoter which gives the highest expression, different plasmids which are able to express Escherichia coli beta-galactosidase gene as a reporter gene under the control of different promoters were tested: human cytomegalovirus promoter (pCMVbeta), simian virus 40 promoter (pSVbeta), adenovirus promoter (ADbeta), and herpes simplex virus thymidine kinase promoter (TKbeta). The pCMVbeta revealed the highest expression of the beta-gal gene in the renal cell carcinoma (RCC) lines. Thus this CMV promoter was selected for the expression of the granulocyte-macrophage colony stimulator factor (GM-CSF) gene. Three different lipids (LipofectAmine, LipofectAce, and Lipofectin) were compared for their transduction efficiency, and the optimal conditions for quantitatively high lipofection rates were established. The consistently best results regarding gene expression as well as viability of the RCC lines were obtained when Lipofectin was used. Gene expression was monitored by a specific enzyme-linked immunosorbent assay and functionally validated by a cell proliferation test. The GM-CSF expression profile showed a peak at 48 hours after transfection and was still detectable after 5 days. Here the feasibility of efficient lipofection of the GM-CSF gene into RCC lines is demonstrated. Most importantly, considerable differences in the relative quantity of GM-CSF gene transfer into the different RCC lines was observed here. This may be of critical relevance for the design of any clinical gene transduction protocol in tumor cell vaccination attempts.

  4. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass

    International Nuclear Information System (INIS)

    Williams, L.E.; Bares, R.B.; Buell, U.; Fass, J.; Schumpelick, V.; Hauptmann, S.

    1993-01-01

    An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (ρ=-0.510), developed using surgical samples was of the form u=ab b and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was in iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. (orig.)

  5. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  6. miR-192, miR-194 and miR-215: a convergent microRNA network suppressing tumor progression in renal cell carcinoma.

    Science.gov (United States)

    Khella, H W Z; Bakhet, M; Allo, G; Jewett, M A S; Girgis, A H; Latif, A; Girgis, H; Von Both, I; Bjarnason, G A; Yousef, G M

    2013-10-01

    MicroRNAs (miRNAs) play a crucial role in tumor progression and metastasis. We, and others, recently identified a number of miRNAs that are dysregulated in metastatic renal cell carcinoma compared with primary renal cell carcinoma. Here, we investigated three miRNAs that are significantly downregulated in metastatic tumors: miR-192, miR-194 and miR-215. Gain-of-function analyses showed that restoration of their expression decreases cell migration and invasion in renal cell carcinoma cell line models, whereas knockdown of these miRNAs resulted in enhancing cellular migration and invasion abilities. We identified three targets of these miRNAs with potential role in tumor aggressiveness: murine double minute 2, thymidylate synthase, and Smad Interacting protein 1/zinc finger E-box binding homeobox 2. We observed a convergent effect (the same molecule can be targeted by all three miRNAs) and a divergent effect (the same miRNA can control multiple targets) for these miRNAs. We experimentally validated these miRNA-target interactions using three independent approaches. First, we observed that miRNA overexpression significantly reduces the mRNA and protein levels of their targets. In the second, we observed significant reduction of the luciferase signal of a vector containing the 3'UTR of the target upon miRNA overexpression. Finally, we show the presence of inverse correlation between miRNA changes and the expression levels of their targets in patient specimens. We also examined the prognostic significance of miR-215 in renal cell carcinoma. Lower expression of miR-215 is associated with significantly reduced disease-free survival time. These findings were validated on an independent data set from The Cancer Genome Atlas. These results can pave the way to the clinical use of miRNAs as prognostic markers and therapeutic targets.

  7. The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

    Science.gov (United States)

    Ju, Julia A.; Baek, Jin Hyen; Yalamanoglu, Ayla; Buehler, Paul W.; Gilkes, Daniele M.; Palmer, Andre F.

    2018-01-01

    A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage. PMID:29414985

  8. Management for Patients with De Novo or Recurrent Tumors in the Residual Kidney after Surgery for Nonfamilial Bilateral Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Noboru Hara

    2009-01-01

    Full Text Available The tumor de novo in the residual kidney after surgery for nonfamilial bilateral renal cell carcinoma (RCC is problematic. We reviewed 5 patients who experienced such a situation. Three patients had had metachronous bilateral RCC, treated with radical nephrectomy in one kidney and nephron-sparing surgery (NSS in the other. Two patients had had synchronous disease; one patient had received radical nephrectomy and NSS, and the other bilateral NSS. The 5 patients had another solid mass/de novo tumor in the residual kidney 16–88 (mean 46.8 months after surgery. For the tumor de novo in earlier years (1992–1999, one patient underwent surgery and hemodialysis, and the other selected a conservative observation. In recent years (2000–2007, one patient was conservatively observed; the remaining 2 received computerized-tomography-guided radiofrequency ablation, and the local tumors were well controlled postoperatively for 20 and 12 months with their renal function unimpaired. Ablative techniques can potentially strike a balance between oncological and nephrological outcomes in patients with sporadic multiple RCC, successful management of which was difficult previously.

  9. Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')/sub 2/ fragments

    Energy Technology Data Exchange (ETDEWEB)

    Herlyn, D.; Munz, D.L.; Herlyn, M.; Koprowski, H.; Powe, J.; Alavi, A.; Meinken, G.E.; Srivastava, S.C.

    1986-01-01

    Procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice compared to experimentally immunosuppressed mice due to the higher tumor viability. MAb localization in tumor tissue was greatly enhanced when F(ab')/sub 2/ fragments rather than intact antibody molecules were used. Although tumors could be visualized with /sup 131/I-, /sup 123/I-or /sup 111/In-labeled MAb fragments without background subtraction, tumor-to-background ratios of radioactivity were highest for /sup 131/I-labeled fragments. /sup 131/I-labeled F(ab')/sub 2/ fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by ..gamma..-scintigraphy. Some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')/sub 2/ fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone.

  10. Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Peng Fang; Wang Jin; Zou Yi; Bao Yong; Huang Wenlin; Chen Guangming; Luo Xianrong; Chen Ming

    2011-01-01

    Objective: To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods: Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results: Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. (authors)

  11. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

    Science.gov (United States)

    Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

    2016-10-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-x L , and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-x L overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

  12. A Novel Tumor Antigen and Foxp3 Dual Targeting Tumor Cell Vaccine Enhances the Immunotherapy in a Murine Model of Renal Cell Carcinoma

    Science.gov (United States)

    2015-12-01

    MDSCs facilitate tumor progression by impairing T-cell and natural killer (NK)–cell activation (9) and by modulating angiogenesis. Preclinical data...tasquinimod. Left, tumor growth curves by serial calipermeasurements. Right, tumor weights at the endpoint. B, mice were inoculated s.c. with B16...25 mg/kg) was given as daily i.v. injections on days 3 to 6. Left, tumor growth curves by serial caliper measurements. Right, end-of-treatment tumor

  13. PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

    Directory of Open Access Journals (Sweden)

    Geetanjali Arora

    Full Text Available BACKGROUND: Peptide receptor radionuclide therapy (PRRT, employed for treatment of neuroendocrine tumors (NETs is based on over-expression of Somatostatin Receptors (SSTRs on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177Lu-DOTATATE loaded PLGA nanoparticles (NPs were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS: DOTATATE was labeled with Lutetium-177 ((177Lu (labeling efficiency 98%; R(f∼0.8. Polyethylene Glycol (PEG coated (177Lu-DOTATATE-PLGA NPs (50:50 and 75:25 formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated and 303.8±67.2 and 494.3±71.8 nm (coated for PLGA(50:50 and PLGA(75:25 respectively. Encapsulation efficiency (EE and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25 were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated and 65.385±5.67% & 58.495±5.35% (coated. NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177Lu-DOTATATE and (177Lu-DOTATATE-NP (uncoated and PEG-coated by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177Lu-DOTATATE-NP. The high liver uptake with uncoated (177Lu-DOTATATE-NP (13.68±3.08% ID/g, reduced to 7.20±2.04%ID/g (p = 0.02 with PEG coating. CONCLUSION: PLGA NPs were easily formulated and modified for desired release properties. PLGA

  14. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.; Ledinko, N.; Smith, D.J.

    1986-01-01

    The biological activity of retinoids was assayed in an in vitro quantitative assay of human tumor cell invasion using human amnion basement membrane (BM). The effects measured were the inhibition of tumor cell migration through the BM and tumor cell degradative enzyme activity on 14 C-proline labeled collagenous and noncollagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested, the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.009 μg/mL, and of TC-106 cells at 0.07 μg/mL. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels over 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more potent than retinol palmitate. The model system will be useful for investigating antiinvasive activity of other retinoids as well as other compounds

  15. A new method using multiphoton imaging and morphometric analysis for differentiating chromophobe renal cell carcinoma and oncocytoma kidney tumors

    Science.gov (United States)

    Wu, Binlin; Mukherjee, Sushmita; Jain, Manu

    2016-03-01

    Distinguishing chromophobe renal cell carcinoma (chRCC) from oncocytoma on hematoxylin and eosin images may be difficult and require time-consuming ancillary procedures. Multiphoton microscopy (MPM), an optical imaging modality, was used to rapidly generate sub-cellular histological resolution images from formalin-fixed unstained tissue sections from chRCC and oncocytoma.Tissues were excited using 780nm wavelength and emission signals (including second harmonic generation and autofluorescence) were collected in different channels between 390 nm and 650 nm. Granular structure in the cell cytoplasm was observed in both chRCC and oncocytoma. Quantitative morphometric analysis was conducted to distinguish chRCC and oncocytoma. To perform the analysis, cytoplasm and granules in tumor cells were segmented from the images. Their area and fluorescence intensity were found in different channels. Multiple features were measured to quantify the morphological and fluorescence properties. Linear support vector machine (SVM) was used for classification. Re-substitution validation, cross validation and receiver operating characteristic (ROC) curve were implemented to evaluate the efficacy of the SVM classifier. A wrapper feature algorithm was used to select the optimal features which provided the best predictive performance in separating the two tissue types (classes). Statistical measures such as sensitivity, specificity, accuracy and area under curve (AUC) of ROC were calculated to evaluate the efficacy of the classification. Over 80% accuracy was achieved as the predictive performance. This method, if validated on a larger and more diverse sample set, may serve as an automated rapid diagnostic tool to differentiate between chRCC and oncocytoma. An advantage of such automated methods are that they are free from investigator bias and variability.

  16. An immunophenotypic comparison of metanephric metaplasia of Bowman capsular epithelium with metanephric adenoma, Wilms tumor, and renal development: a case report and review of the literature.

    Science.gov (United States)

    Fischer, Edgar G; Carney, J Aidan; Anderson, Scott R; Klatt, Edward C; Lager, Donna J

    2004-06-01

    Metanephric metaplasia of the parietal epithelium of the Bowman capsule is a rare pathologic finding of unknown pathogenesis that has occurred in patients with widespread malignant neoplasms of various types. We report this finding in a 25-year-old woman with partial expression of the Carney triad who died of a disseminated gastrointestinal stromal tumor, specifically a gastric stromal sarcoma. The metaplasia involved both kidneys diffusely. It originated in the parietal epithelium of the Bowman capsule, extended into the proximal tubules, and focally surrounded the glomeruli in a semicircular manner Immunohistochemical analysis revealed that the cells of metanephric metaplasia expressed the Wilms tumor gene product, bcl-2 protein, and CD57 and cytokeratin 7 and keratin AE1/AE3 focally, but not CD56. This immunophenotype parallels that of metanephric adenoma, Wilms tumor, and nephrogenic rests and overlaps with antigen expression in certain periods of renal development.

  17. Five-chlorodeoxycytidine, a tumor-selective enzyme-driven radiosensitizer, effectively controls five advanced human tumors in nude mice

    International Nuclear Information System (INIS)

    Greer, Sheldon; Alvarez, Marcy; Mas, Marisol; Wozniak, Chandra; Arnold, David; Knapinska, Anna; Norris, Christina; Burk, Ronald; Aller, Alex; Dauphinee, Michael

    2001-01-01

    Purpose: The study's goals were as follows: (1) to extend our past findings with rodent tumors to human tumors in nude mice, (2) to determine if the drug protocol could be simplified so that only CldC and one modulator, tetrahydrouridine (H 4 U), would be sufficient to obtain efficacy, (3) to determine the levels of deoxycytidine kinase and dCMP deaminase in human tumors, compared to adjacent normal tissue, and (4) to determine the effect of CldC on normal tissue radiation damage to the cervical spinal cord of nude mice. Methods and Materials: The five human tumors used were as follows: prostate tumors, PC-3 and H-1579; glioblastoma, SF-295; breast tumor, GI-101; and lung tumor, H-165. The duration of treatment was 3-5 weeks, with drugs administered on Days 1-4 and radiation on Days 3-5 of each week. The biomodulators of CldC were N-(Phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartyl transcarbamoylase, 5-fluorodeoxycytidine (FdC), resulting in tumor-directed inhibition of thymidylate synthetase, and H 4 U, an inhibitor of cytidine deaminase. The total dose of focused irradiation of the tumors was usually 45 Gy in 12 fractions. Results: Marked radiosensitization was obtained with CldC and the three modulators. The average days in tumor regrowth delay for X-ray compared to drugs plus X-ray, respectively, were: PC-3 prostate, 42-97; H-1579 prostate, 29-115; glioblastoma, 5-51; breast, 50-80; lung, 32-123. Comparative studies with PC-3 and H-1579 using CldC coadministered with H 4 U, showed that both PALA and FdC are dispensable, and the protocol can be simplified with equal and possibly heightened efficacy. For example, PC-3 with X-ray and (1) no drugs, (2) CldC plus the three modulators, (3) a high dose of CldC, and (4) escalating doses of CldC resulted in 0/10, 3/9, 5/10, and 6/9 cures, respectively. The tumor regrowth delay data followed a similar pattern. After treating mice only 1((1)/(2)) weeks with CldC + H 4 U, 92% of the PC-3 tumor cells were found

  18. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

    2004-10-15

    Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

  19. Why Do SGLT2 inhibitors inhibit only 30-50% of renal glucose reabsorption in humans?

    Science.gov (United States)

    Liu, Jiwen Jim; Lee, TaeWeon; DeFronzo, Ralph A

    2012-09-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30-50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible.

  20. Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

    Science.gov (United States)

    Liu, Jiwen (Jim); Lee, TaeWeon; DeFronzo, Ralph A.

    2012-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible. PMID:22923645

  1. Effects of supine, prone, and lateral positions on cardiovascular and renal variables in humans

    DEFF Research Database (Denmark)

    Pump, Bettina; Talleruphuus, Ulrik; Christensen, Niels Juel

    2002-01-01

    The hypothesis was tested that changing the direction of the transverse gravitational stress in horizontal humans modulates cardiovascular and renal variables. On different study days, 14 healthy males were placed for 6 h in either the horizontal supine or prone position following 3 h of being...... supine. Eight of the subjects were in addition investigated in the horizontal left lateral position. Compared with supine, the prone position slightly increased free water clearance (349 +/- 38 vs. 447 +/- 39 ml/6 h, P = 0.05) and urine output (1,387 +/- 55 vs. 1,533 +/- 52 ml/6 h, P = 0...

  2. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

    Science.gov (United States)

    Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

    2017-09-27

    The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xinsheng; Jiang, Fuquan; Song, Haitao; Li, Xu; Xian, Jiantao; Gu, Xinquan, E-mail: guxqprofessor@163.com

    2016-02-12

    Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.

  4. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  5. Expression of CD44 splice variants in human primary brain tumors

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  6. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  7. [Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients].

    Science.gov (United States)

    Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M

    2014-11-01

    The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  8. A Qualitative Assessment of Human Cadavers Embalmed by Thiel's Method Used in Laparoscopic Training for Renal Resection

    Science.gov (United States)

    Rai, Bhavan Prasad; Tang, Benjie; Eisma, Roos; Soames, Roger W.; Wen, Haitao; Nabi, Ghulam

    2012-01-01

    Human cadaveric tissue is the fundamental substrate for basic anatomic and surgical skills training. A qualitative assessment of the use of human cadavers preserved by Thiel's method for a British Association of Urological Surgeons--approved, advanced laparoscopic renal resection skills training course is described in the present study. Four…

  9. Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

    DEFF Research Database (Denmark)

    Salamon, Johannes; Hoffmann, Tatjana; Elies, Eva

    2014-01-01

    were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume...... had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls...

  10. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  11. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  12. Vaccination directed against the human endogenous retrovirus-K envelope protein inhibits tumor growth in a murine model system.

    Science.gov (United States)

    Kraus, Benjamin; Fischer, Katrin; Büchner, Sarah M; Wels, Winfried S; Löwer, Roswitha; Sliva, Katja; Schnierle, Barbara S

    2013-01-01

    Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all cells of an individual. They are normally transcriptionally silenced and transmitted only vertically. Enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed in tumor patients and HIV-infected individuals. As HERV-K is usually not expressed and immunological tolerance development is unlikely, it is an appropriate target for the development of immunotherapies. We generated a recombinant vaccinia virus (MVA-HKenv) expressing the HERV-K envelope glycoprotein (ENV), based on the modified vaccinia virus Ankara (MVA), and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) or the HERV-K ENV gene (RLZ-HKenv cells). Intravenous injection of RLZ-HKenv cells into syngenic BALB/c mice led to the formation of pulmonary metastases, which were detectable by X-gal staining. A single vaccination of tumor-bearing mice with MVA-HKenv drastically reduced the number of pulmonary RLZ-HKenv tumor nodules compared to vaccination with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the formation of RLZ-HKenv tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to metastasis. Protection from tumor formation correlated with enhanced HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for the first time that HERV-K ENV is a useful target for vaccine development and might offer new treatment opportunities for diverse types of cancer.

  13. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  14. Effects of alkylating carcinogens on human tumor cells in culture

    International Nuclear Information System (INIS)

    Goth-Goldstein, R.; Hughes, M.

    1987-01-01

    In Escherichia coli 3-methyladenine and 3-methylguanine have been identified as lethal lesions, since two types of alkylating agent-sensitive mutants were deficient in repair of either of these lesions. Similar alkylation-sensitive human cell lines exist. These are the tumor cell lines of the complex Mer - phenotype. All Mer - cells examined were hypersensitive to killing by MNNG and other alkylating agents, and failed to repair O 6 -methylguanine. The widely studied HeLa S3 cell line has the Mer + phenotype, but a Mer - variant (HeLa MR) has arisen. This offers the possibility to study Mer - and Mer + cells of otherwise similar genetic background. We are using these two variants to analyze the Mer - phenotype further. When HeLa S3 and HeLa MR were treated with a highly dose of MNNG, and the surviving population exposed to a second dose of MNNG 2-3 weeks later, HeLa S3 (Mer + ) cells were equally or even slightly more sensitive to a second exposure of MNNG, whereas the surviving HeLa MR (Mer - ) population was much more resistant to MNNG. 1 fig., 1 tab

  15. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  16. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  17. INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS

    Directory of Open Access Journals (Sweden)

    E. S. Umnyakova

    2016-01-01

    Full Text Available Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new

  18. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

    2008-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  19. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

    Directory of Open Access Journals (Sweden)

    David Fecher

    Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

  20. Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

    Science.gov (United States)

    Yuan, Zhi-xiang; Wu, Xiao-juan; Mo, Jingxin; Wang, Yan-li; Xu, Chao-qun; Lim, Lee Yong

    2015-08-01

    We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Tc-99m Hydroxymethylene Diphosphonate (HMDP) Renal Uptake as a Surrogate Marker of Postoperative Impairment of the Glomerular Filtration Rate in Renal Tumor Patients Following Nephron-Sparing Surgery.

    Science.gov (United States)

    Choi, Hongyoon; Lee, Won Woo; So, Young; Ha, Seunggyun; Byun, Seok-Soo; Kim, Sang Eun

    2014-12-01

    We investigated Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy findings in renal tumor patients from the perspective of postoperative renal dysfunction following nephron-sparing surgery (NSS). Forty-three renal tumor patients (M:F = 28:15, age 53.9 ± 12.5 years) who had undergone Tc-99m HMDP scintigraphy after NSS were enrolled. The patients were divided into HMDP(+) or HMDP(-) groups by visual assessment, and the asymmetric index (ASI) was calculated using a region-of-interest analysis. In 16 patients, the total and split glomerular filtration rate (GFR) was assessed using Tc-99m diethylenetriaminepentaacetic acid (DTPA) scintigraphy at baseline and at 3 and 6 months post-NSS. High Tc-99m HMDP uptake was observed in the operated kidneys, but this did not persist later than 7 days post-NSS. Split GFR of the operated kidneys at baseline (58.5 ± 9.3 ml/min) was significantly reduced at 6 months post-NSS (40.1 ± 5.9 ml/min, p Tc-99m HMDP. Declines in both total GFR (p = 0.010 and p = 0.002 for 3 and 6 months, respectively) and split GFR of the operated kidneys (p Tc-99m HMDP in the operated kidneys. The ASI was negatively correlated with %change in the split GFR of these operated kidneys at 6 months post-NSS (rho =-0.578, p = 0.0304). Tc-99m HMDP uptake within 1 week following NSS is a surrogate marker of GFR impairment over 6 months post-NSS.

  2. Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

    Science.gov (United States)

    Williams, Ross; Hudson, John M; Lloyd, Brendan A; Sureshkumar, Ahthavan R; Lueck, Gordon; Milot, Laurent; Atri, Mostafa; Bjarnason, Georg A; Burns, Peter N

    2011-08-01

    To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome. © RSNA, 2011.

  3. Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Esther, E-mail: esther.peters@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Department of Pharmacology and Toxicology, Radboud university medical center, PO Box 9101, Internal Mailbox 149, 6500 HB, Nijmegen (Netherlands); Ergin, Bülent, E-mail: b.ergin@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Kandil, Asli, E-mail: aslikandil@istanbul.edu.tr [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Gurel-Gurevin, Ebru, E-mail: egurelgurevin@gmail.com [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Elsas, Andrea van, E-mail: a.vanelsas@am-pharma.com [AM-Pharma, Rumpsterweg 6, 3981 AK, Bunnik (Netherlands); Masereeuw, Rosalinde, E-mail: r.masereeuw@uu.nl [Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, PO Box 80082, 3508 TB Utrecht (Netherlands); Pickkers, Peter, E-mail: peter.pickkers@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Ince, Can, E-mail: c.ince@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

    2016-12-15

    Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n = 18) were subjected to renal ischemia (30 min) and reperfusion (I/R), or sham-operated. In a second model, rats (n = 18) received a 30 min infusion of lipopolysaccharide (LPS; 2.5 mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000 U/kg) was administered intravenously (15 min before reperfusion, or 90 min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. - Highlights: • Human recombinant alkaline phosphatase (recAP) is a potential new therapy for sepsis-associated acute kidney injury (AKI). • RecAP can modulate renal oxygenation and hemodynamics immediately following I/R-induced AKI. • RecAP did not modulate endotoxemia-induced changes in systemic hemodynamics and renal oxygenation. • RecAP did exert a clear renal protective

  4. Leiomyosarcoma of the renal pelvis

    Directory of Open Access Journals (Sweden)

    Dhamne Sagar

    2009-10-01

    Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

  5. Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

    Directory of Open Access Journals (Sweden)

    Patricia Keiko Saito

    Full Text Available Pre-transplant sensitization to human leukocyte antigens (HLA is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA. The percentages of panel-reactive antibodies (PRA and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.. The PRA-positive group consisted of 182 (67.7% patients, and the PRA-negative group of 87 (32.3% patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1% were positive for class I and negative for class II, 39 (21.4% were negative for class I and positive for class II, and 81 (44.5% were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

  6. Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

    Science.gov (United States)

    Saito, Patricia Keiko; Yamakawa, Roger Haruki; Aparecida, Erica Pereira; da Silva Júnior, Waldir Verissimo; Borelli, Sueli Donizete

    2014-01-01

    Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples. PMID:24927116

  7. Activation analysis study on subcellular distribution of trace elements in human brain tumor

    International Nuclear Information System (INIS)

    Zheng Jian; Zhuan Guisun; Wang Yongji; Dong Mo; Zhang Fulin

    1992-01-01

    The concentrations of up to 11 elements in subcellular fractions of human brain (normal and malignant tumor) have been determined by a combination of gradient centrifugation and INAA methods. Samples of human brain were homogenized in a glass homogenizer tube, the homogenate was separated into nuclei, mitochondrial, myelin, synaptosome fractions, and these fractions were then analyzed using the INAA method. The discussions of elemental subcelleular distributions in human brain malignant tumor are presented in this paper. (author) 11 refs.; 2 figs.; 4 tabs

  8. Computed tomography on renal masses in dogs and cats

    International Nuclear Information System (INIS)

    Yamazoe, Kazuaki; Ohashi, Fumihito; Kadosawa, Tsuyoshi; Nishimura, Ryohei; Sasaki, Nobuo; Takeuchi, Akira.

    1994-01-01

    Computed tomography (CT) was performed on renal tumors (Wilms' tumor and renal cell carcinoma) and renal cysts in dogs and cats. CT images in renal tumors were well correlated with macroscopic findings, and contrast CT images were quite useful in differentiating tumoral regions from non-tumoral ones. On renal cysts, intravenous pyelography and ultrasonography were as effective as CT images in morphological diagnosis, but CT was considered to be superior for evaluating three-dimensional (3-D) relationships in complicated lesions. (author)

  9. Human embryo immune escape mechanisms rediscovered by the tumor.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Riccobon, Angela; Ridolfi, Ruggero

    2009-01-01

    Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of co-stimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.

  10. [Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].

    Science.gov (United States)

    Costes, V; Medioni, D; Durand, L; Sarran, N; Marguerite, G; Baldet, P

    1997-03-01

    We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.

  11. Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer-GEnetic- and tumor-related biomarkers for response and toxicity.

    Science.gov (United States)

    van der Zanden, Loes F M; Vermeulen, Sita H; Oskarsdottir, Arna; Maurits, Jake S F; Diekstra, Meta H M; Ambert, Valentin; Cambon-Thomsen, Anne; Castellano, Daniel; Fritsch, Achim; Garcia Donas, Jesus; Guarch Troyas, Rosa; Guchelaar, Henk-Jan; Hartmann, Arndt; Hulsbergen-van de Kaa, Christina; Jaehde, Ulrich; Junker, Kerstin; Martinez-Cardus, Anna; Masson, Gisli; Oosterwijk-Wakka, Jeannette; Radu, Marius T; Rafnar, Thorunn; Rodriguez-Antona, Cristina; Roessler, Max; Ruijtenbeek, Rob; Stefansson, Kari; Warren, Anne; Wessels, Lodewyk; Eisen, Tim; Kiemeney, Lambertus A L M; Oosterwijk, Egbert

    2017-08-01

    For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort. EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses. In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and

  12. Accessing key steps of human tumor progression in vivo by using an avian embryo model

    Science.gov (United States)

    Hagedorn, Martin; Javerzat, Sophie; Gilges, Delphine; Meyre, Aurélie; de Lafarge, Benjamin; Eichmann, Anne; Bikfalvi, Andreas

    2005-02-01

    Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening. angiogenesis | animal model alternatives | glioblastoma

  13. Noninvasive perfusion imaging of human brain tumors with EPISTAR

    Energy Technology Data Exchange (ETDEWEB)

    Gaa, J. [Department of Radiology, AN-234, MRI, Beth Israel Hospital, Boston, MA 02215 (United States); Warach, S. [Department of Radiology, AN-234, MRI, Beth Israel Hospital, Boston, MA 02215 (United States); Wen, P. [Department of Neurology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA (United States); Thangaraj, V. [Department of Radiology, AN-234, MRI, Beth Israel Hospital, Boston, MA 02215 (United States); Wielopolski, P. [Department of Radiology, AN-234, MRI, Beth Israel Hospital, Boston, MA 02215 (United States); Edelman, R.R. [Department of Radiology, AN-234, MRI, Beth Israel Hospital, Boston, MA 02215 (United States)

    1996-08-01

    A total of 17 patients with histologically proven diagnoses of low-grade astrocytoma (n = 4), high-grade astrocytoma (n = 8), lymphoma (n = 3), and meningioma (n = 2) were examined by using EPISTAR MR imaging. Meningiomas had the highest EPISTAR tumor/white matter contrast and low-grade astrocytomas and lymphomas the lowest. High-grade astrocytomas demonstrated elevated EPISTAR signal with marked regional heterogeneity. There was agreement between tumor vascularity by SPECT and EPISTAR in the five cases where both were done. Our results show that tumor vascularity can be assessed qualitatively by using EPISTAR without the need for contrast medium injection. (orig.). With 5 figs.

  14. Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

    Science.gov (United States)

    Droguett, M A; Oyarzún, M J; Alruiz, P; Jerez, V; Mezzano, S; Ardiles, L

    2005-10-01

    An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

  15. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  16. Low Dose Cadmium Inhibits Proliferation of Human Renal Mesangial Cells via Activation of the JNK Pathway

    Science.gov (United States)

    Chen, Xiaocui; Li, Jing; Cheng, Zuowang; Xu, Yinghua; Wang, Xia; Li, Xiaorui; Xu, Dongmei; Kapron, Carolyn M.; Liu, Ju

    2016-01-01

    Cadmium (Cd) is a heavy metal and environmental pollutant. The kidney is the principal target organ of Cd exposure. Previously, we found that low concentration of Cd damages the integrity of the glomerular filtration barrier. However, little is known about the effects of Cd on renal mesangial cells, which provide structural support for the glomerular capillary loops and regulate intraglomerular blood flow. In this study, human renal mesangial cells (HRMCs) were cultured in the presence of serum and treated with 4 μM Cd. We found that Cd activates the c-Jun N-terminal kinase (JNK) pathway, and increases the protein levels of c-Jun and c-Fos. Cd treatment also induces a decrease in proliferation and an increase in apoptosis of HRMCs, but only the decrease in HRMC proliferation was reversed by pretreatment with SP600125, an inhibitor of the JNK pathway. In addition, Cd does not change the expression of α-smooth muscle actin and platelet-derived growth factor receptor-β, the markers of mesangial cells, or the alignment of the filamentous actin (F-actin) cytoskeleton of HRMCs. Our data indicate that the JNK pathway mediates the inhibitory effects of Cd on HRMC proliferation. PMID:27739415

  17. Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.

    Science.gov (United States)

    Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie

    2018-02-06

    Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal

  18. Dying and regeneration of human tumor cells after heterotransplantation to athymic mice

    OpenAIRE

    Köpf-Maler, P.

    1986-01-01

    The histologic phenomena occurring immediately after heterotransplantation of two human colon adenocarcinomas to athymic mice have been studied. The tumors differed with respect to velocity of growth and passage age. Three phases were discernible in both cases. (1) During the first phase, most inoculated tumor cells died. (2) The second phase was characterized by removal of the necrotic tumor cells by immigrated inflammatory cells and by penetration of the conn...

  19. A Genomics-Based Classification of Human Lung Tumors

    NARCIS (Netherlands)

    Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Groen, Harry; Timens, Wim

    2013-01-01

    We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

  20. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    International Nuclear Information System (INIS)

    Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

    1995-01-01

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

  1. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.

    1987-01-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters

  2. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

    Directory of Open Access Journals (Sweden)

    Marie Courbebaisse

    Full Text Available BACKGROUND: The sodium-hydrogen exchanger regulatory factor 1 (NHERF1 binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule. METHODS: We compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production. RESULTS: We identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a. CONCLUSIONS: Our results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.

  3. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  4. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  5. Further characterization of the adhesive-tumor-cell culture system for measuring the radiosensitivity of human tumor primary cultures

    International Nuclear Information System (INIS)

    Brock, W.A.; Bock, S.P.; Williams, M.; Baker, F.L.

    1987-01-01

    This study extends the use of the adhesive-tumor-cell culture system to include: over 100 sensitivity measurements at 2.0 Gy; tumorgenicity determinations in nude mice; and flow cytometry of the cells grown in the system. The malignant nature of the growing cells was proved by injecting cells into nude mice. Tumors resulted in 60% of the cases and the histology of each xenograft was similar to that of the human tumor. Flow cytometry was used to obtain DNA histograms of the original cell suspension and of cultures during the two week culture period in order to obtain quantitative information about the growth of aneuploid versus diploid populations. The results thus far demonstrate that 95% of aneuploid populations yield aneuploid growth; of the first 20 cases studied, only one suspension with an aneuploid peak resulted in diploid growth. Of further interest was the observation that it is not unusual for a minor aneuploid population to become the predominate growth fraction after two weeks in culture. These results demonstrate that the adhesive-tumor-cell culture system supports the growth of malignant cells, that multiple cell populations exist in cell suspensions derived from solid tumors, and that differences exist between the radiosensitivity of cells at 2.0 Gy in different histology types

  6. Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China); Fan, Jie, E-mail: jief67@sina.com [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

  7. Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

    Science.gov (United States)

    Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2016-03-01

    Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix. © The Author(s) 2015.

  8. Improvement of Gynecological Screening of Female Renal Transplant Recipients by Self-Sampling for Human Papillomavirus Detection

    NARCIS (Netherlands)

    Hinten, F.; Hilbrands, L.B.; Meeuwis, K.A.P.; Bergen-Verkuyten, M.C. van; Slangen, B.F.; Rossum, M.M. van; Rahamat-Langendoen, J.C.; Massuger, L.F.A.G.; Hullu, J.A. de; Melchers, W.J.G.

    2017-01-01

    OBJECTIVES: Female renal transplant recipients (RTRs) have increased risk for developing human papillomavirus (HPV)-related (pre)malignancies of the lower genital tract. Annual cervical screening is advised for RTRs, but the participation rate is low. The aim of this study is to investigate whether

  9. Renal expression of Toll-like receptor 2 and 4 : Dynamics in human allograft injury and comparison to rodents

    NARCIS (Netherlands)

    Stribos, Elisabeth G. D.; van Werkhoven, Maaike B.; Poppelaars, Felix; van Goor, Harry; Olinga, Peter; van Son, Willem J.; Damman, Jeffrey; Seelen, Marcus

    Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated

  10. Renal expression of Toll-like receptor 2 and 4: dynamics in human allograft injury and comparison to rodents

    NARCIS (Netherlands)

    Stribos, Elisabeth G. D.; van Werkhoven, Maaike B.; Poppelaars, Felix; van Goor, Harry; Olinga, Peter; van Son, Willem J.; Damman, Jeffrey; Seelen, Marc A.

    2015-01-01

    Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated

  11. The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Hoeyer, Morten; Keller, Johnny; Nielsen, Ole Steen; Jensen, Oluf Myhre; Overgaard, Jens

    1996-01-01

    Purpose: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. Methods and Materials: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO 2 and the percentage of pO 2 values ≤ 5 mmHg and ≤ 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. Results: There was a significant correlation between the median pO 2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO 2 values ≤ 2.5 and ≤ 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. Conclusion: This report is the first to suggest

  12. Basic studies on the tumor imaging using antibodies to human alpha-fetoprotein

    International Nuclear Information System (INIS)

    Sakahara, Harumi; Endo, Keigo; Nakashima, Tetsuo; Ohta, Hitoya; Torizuka, Kanji

    1984-01-01

    Using polyclonal antibodies to human α-fetoprotein (AFP), the effect of iodination on the antibody activity and tumor accumulation of radioiodinated antibodies in tumor bearing nude mice were examined. Antibodies, obtained from horse antiserum and purified by affinity chromatography, were iodinated by the chloramine-T method and their antibody activity was evaluated using RIA and Scatchard plot analysis. When high concentrations of chloramine-T were used or more than 2.6 iodine atoms were incorporated per antibody molecule, the antigen binding capacity rather than the affinity constant was affected by the iodination. The antibody activity was completely destroyed at an iodine to antibody molar ratio of 15.4. Antibodies, however, which were iodinated under low concentrations of chloramine-T and contained less than 0.8 iodines per antibody molecule, showed almost full retention of their antibody activity. Nude mice transplanted with AFP producing human testicular tumor or AFP non-producing human urinary bladder tumor were administered intravenously with 131 I-labeled antibodies to human AFP. Scintigrams were taken at 1, 2, 4 and 7 days after the injection of labeled antibodies. At day 7, nude mice were sacrificed and organs and tumor were removed, weighed and counted. In nude mice bearing testicular tumor, tumor image became gradually clear with decreasing background activity and tumor to blood ratio, obtained, was 0.82 for testicular tumor compared to 0.42 for bladder tumor. These results indicated a specific in vivo localization of 131 I-labeled antihuman AFP antibodies in AFP producing tumor. (author)

  13. Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

    Science.gov (United States)

    Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

    2018-02-15

    Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.

    1988-01-01

    The effects measured were the inhibition of tumor cell migration through the basement membrane (BM) and tumor cell degradative enzyme activity on 3 H-proline labeled collagenous and non collagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.09 μg/ml, and TC-106 cells at 0.08 μg/ml. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels almost 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more than retinol palmitate. Furthermore, A549 cells treated with retinol acetate, under conditions whereby an anti-invasive state was induced,showed an increase in the number of cellular retinoic acid binding proteins (CRABP), a decrease in the activity of type IV collagenase and ectosialyltransferase, and no change in the activity of transglutaminase

  15. Renal myxoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Henrique C Souza

    2015-04-01

    Full Text Available Myxomas are rare tumors that can appear in many anatomical locations. There are only 14 cases of renal involvement documented in the literature. This article reports a case of renal myxoma in an elderly woman with recurrent cystitis. After five years of follow-up, the computed tomography (CT revealed a large solid tumor mass in the left kidney. Tumor resection was performed preserving the affected kidney with histopathological diagnosis of renal myxoma. The objective of this study is to report a rare case of renal myxoma, emphasizing the importance of the differential diagnosis from other benign and malignant mesenchymal tumors.

  16. Roles of F-box proteins in human digestive system tumors (Review).

    Science.gov (United States)

    Gong, Jian; Lv, Liang; Huo, Jirong

    2014-12-01

    F-box proteins (FBPs), the substrate-recognition subunit of E3 ubiquitin (Ub) ligase, are the important components of Ub proteasome system (UPS). FBPs are involved in multiple cellular processes through ubiquitylation and subsequent degradation of their target proteins. Many studies have described the roles of FBPs in human cancers. Digestive system tumors account for a large proportion of all the tumors, and their mortality is very high. This review summarizes for the first time the roles of FBPs in digestive system tumorige-nesis and tumor progression, aiming at finding new routes for the rational design of targeted anticancer therapies in digestive system tumors.

  17. Distribution of Arsenic, Manganese, and Selenium in the Human Brain in Chronic Renal Insufficiency, Parkinsons Disease and Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Larsen, N. A.; Pakkenberg, H.; Damsgaard, Else

    1981-01-01

    The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were...... determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis...

  18. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

    Science.gov (United States)

    Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

  19. Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody

    International Nuclear Information System (INIS)

    Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Furuuchi, Takayuki; Abe, Osahiko; Takami, Hiroshi.

    1988-01-01

    The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125 I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 ± 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125 I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125 I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy. (author)

  20. Study on therapy of 188Re labelled stannic sulfur suspension in nude mice bearing human colon tumor

    International Nuclear Information System (INIS)

    Li Huiyuan; Wu Yuanfang; Dong Mo

    2003-01-01

    The effect of therapy, tissue distribution and stability are studied in nude mice bearing human colon tumor after injections of 188 Re labelled stannic sulfur suspension. The tissues are observed with electric microscope. The results show that 188 Re labelled stannic sulfur suspension is stabilized in the tumor and its inhibitive effects on human colon tumor cells are obvious. 188 Re labelled stannic sulfur suspension is a potential radiopharmaceuticals for therapy of human tumor

  1. A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2014-01-01

    Full Text Available Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

  2. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  3. Serial study of the concentration of misonidazole in human tumors correlated with histologic structure

    International Nuclear Information System (INIS)

    Rich, T.A.; Dische, S.; Saunders, M.I.; Stratford, M.R.L.; Minchinton, A.

    1981-01-01

    Multiple biopsies were obtained from eight patients with malignant tumors during a course of fractionated radiotherapy. An analysis of the total 2-nitroimidazole concentration and a histological examination of the biopsy sample was done on material which appeared macroscopically similar. The parts of the tumor biopsies showing necrosis were found to contain much lower concentrations of nitroimidazole when compared with those found in the samples with well-vascularized and apparently viable tumor. During the course of irradiation changes in misonidazole concentrations were not found when similar histological material was examined. The low values of misonidazole in necrotic regions in human tumors may partly account for the wide variation of misonidazole concentrations reported in the literature (percent tumor/plasma, mean 62.9 +- 34.4 STD). The clinical significance of the microscopic distribution of misonidazole in tumors in unknown but further work in this area may aid in predicting the usefulness of future radiosensitizers

  4. Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

    International Nuclear Information System (INIS)

    Peterson, Sarah M; Concino, Michael F; Liaw, Lucy; Martini, Paolo GV; Iskenderian, Andrea; Cook, Lynette; Romashko, Alla; Tobin, Kristen; Jones, Michael; Norton, Angela; Gómez-Yafal, Alicia; Heartlein, Michael W

    2010-01-01

    Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular

  5. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

    1995-04-30

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

  6. Mutational profile of GNAQQ209 in human tumors.

    Directory of Open Access Journals (Sweden)

    Simona Lamba

    Full Text Available BACKGROUND: Frequent somatic mutations have recently been identified in the ras-like domain of the heterotrimeric G protein alpha-subunit (GNAQ in blue naevi 83%, malignant blue naevi (50% and ocular melanoma of the uvea (46%. The mutations exclusively affect codon 209 and result in GNAQ constitutive activation which, in turn, acts as a dominant oncogene. METHODOLOGY: To assess if the mutations are present in other tumor types we performed a systematic mutational profile of the GNAQ exon 5 in a panel of 922 neoplasms, including glioblastoma, gastrointestinal stromal tumors (GIST, acute myeloid leukemia (AML, blue naevi, skin melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, and thyroid carcinomas. PRINCIPAL FINDINGS: We detected the previously reported mutations in 6/13 (46% blue naevi. Changes affecting Q209 were not found in any of the other tumors. Our data indicate that the occurrence of GNAQ mutations display a unique pattern being present in a subset of melanocytic tumors but not in malignancies of glial, epithelial and stromal origin analyzed in this study.

  7. Molecular profiles of progesterone receptor loss in human breast tumors

    NARCIS (Netherlands)

    Creighton, Chad J.; Kent Osborne, C.; van de Vijver, Marc J.; Foekens, John A.; Klijn, Jan G.; Horlings, Hugo M.; Nuyten, Dimitry; Wang, Yixin; Zhang, Yi; Chamness, Gary C.; Hilsenbeck, Susan G.; Lee, Adrian V.; Schiff, Rachel

    2009-01-01

    Background Patient prognosis and response to endocrine therapy in breast cancer correlate with protein expression of both estrogen receptor (ER) and progesterone receptor (PR), with poorer outcome in patients with ER+/PR- compared to ER+/PR+ tumors. Methods To better understand the underlying

  8. Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.

    Science.gov (United States)

    Mei, Wenhan; Wang, Kemin; Huang, Jian; Zheng, Xinmin

    2016-01-01

    Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail. Although PTP1BΔE6 revealed no phosphatase activity compared with wild-type PTP1B and the PTP1BΔE5 mutant, its expression induced oncogenic transformation of rat fibroblasts without Src activation, indicating that it involved signaling pathways independent of Src. The transformed cells were tumourigenic in nude mice, suggesting that the PTP1BΔE6 affected other molecule(s) in the human tumors. These observations may provide a novel therapeutic target for colon and thyroid cancer.

  9. Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.

    Science.gov (United States)

    Shinohara, Mayuka; Sumino, Yasuhiro; Sato, Fuminori; Kiyono, Tohru; Hashimoto, Naohiro; Mimata, Hiromitsu

    2017-06-01

    To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored. Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner. Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence. © 2017 The Japanese Urological Association.

  10. Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

    Science.gov (United States)

    Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

    2017-04-01

    At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

  11. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  12. Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors.

    Directory of Open Access Journals (Sweden)

    Xinzhu Deng

    Full Text Available Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202, a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202 is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

  13. The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yu-Ling Lin

    2013-01-01

    Full Text Available Glioblastoma multiforme (GBM is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

  14. Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells

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    Peiying Yu

    2014-01-01

    Full Text Available NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5 gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT and hypertensive subjects (HT. We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6–14/group. Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA, effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (−45.1±3.2% vs. mock-siRNA, n=6–8 in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (−32.5±1.8% than HT (−14.8±1.8. In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.

  15. Renal clearance of /sup 99m/Tc-methylene-diphosphonate in human beings

    Energy Technology Data Exchange (ETDEWEB)

    Vattimo, A.

    1987-12-01

    The renal clearance of /sup 99m/Tc-MDP was measured in 13 patients who had bone scans and compared with the renal clearance of /sup 51/Cr-EDTA. No difference was found between the renal clearance of the two tracers, showing a close correlation (r = 0.98). These data suggest that the /sup 99m/Tc-MDP is excreted by the kidneys by glomerular filtration without tubular secretion.

  16. Renal clearance of 99mTc-methylene-diphosphonate in human beings

    International Nuclear Information System (INIS)

    Vattimo, A.

    1987-01-01

    The renal clearance of 99m Tc-MDP was measured in 13 patients who had bone scans and compared with the renal clearance of 51 Cr-EDTA. No difference was found between the renal clearance of the two tracers, showing a close correlation (r = 0.98). These data suggest that the 99m Tc-MDP is excreted by the kidneys by glomerular filtration without tubular secretion. (orig.) [de

  17. Serum levels of CA15-3, AFP, CA19-9 and CEA tumor markers in cancer care and treatment of patients with impaired renal function on hemodialysis.

    Science.gov (United States)

    Estakhri, Rasoul; Ghahramanzade, Ali; Vahedi, Amir; Nourazarian, Alireza

    2013-01-01

    Since renal failure causes decrease in tumor marker excretion, use of these markers in cancer care and treatment in patients with renal insufficiency or hemodialysis is controversial. The aim of this study was to investigate differences of serum levels of tumor markers CA15-3, AFP, CA19-9 and CEA in patients with impaired renal function. A total of 100 patients referred to the Tabriz Immam Reza and Amiralmomenin hospital from June 2010 to November 2011 were selected for study. Subjects were divided to 3 groups of healthy, dialysis and renal failure but non hemodialysis cases, the last category being re-grouped based on creatinine clearance. No significant relationship between different groups in serum levels of CEA (P=0.99) and CA19-9 (P=0.29) tumor markers was found. A significant correlation was observed between serum levels of AFP (PCEA (r=0.05, P=0.625). Creatinine clearance significantly correlated with AFP (Ptumor markers in patients with impaired renal function should be performed with special precautions.

  18. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    International Nuclear Information System (INIS)

    Hillman, Gilda G; Wang, Yu; Che, Mingxin; Raffoul, Julian J; Yudelev, Mark; Kucuk, Omer; Sarkar, Fazlul H

    2007-01-01

    We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more

  19. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  20. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction

    International Nuclear Information System (INIS)

    Noonan, K.E.; Beck, C.; Holzmayer, T.A.; Chin, J.E.; Roninson, I.B.; Wunder, J.S.; Andrulis, I.L.; Gazdar, A.F.; Willman, C.L.; Griffith, B.; Von Hoff, D.D.

    1990-01-01

    The resistance of tumor cells ot chemotheraprutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in bitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refactory tumors untreated with chemotherapeutic drugs. The authors have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clincal samples, based on the polymerase chain reaction. They have used this assay to measure MDR1 gene expression in MDR cell lines and >300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were ost common among tumor types known to be relatively responsive to chemotherapy

  1. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    International Nuclear Information System (INIS)

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-01-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well

  2. Anatomical study of the renal excretory system in pigs. A review of its characteristics as compared to its human counterpart.

    Science.gov (United States)

    Gómez, F A; Ballesteros, L E; Estupiñán, H Y

    2017-01-01

    Despite the importance of the pyelocalyceal system in the pig as an experimental model, there is little information about this particular anatomical subject. We determined the morphological characteristics of the renal excretory system in pigs. This descriptive cross-sectional study evaluated 130 pairs of kidneys of pigs destined to slaughter. The pyelocalyceal system was subjected to injection technique - corrosion by infusion of polyester resin (85% Palatal and 15% Styrene) and subsequent infusion in potassium hydroxide (KOH) for 10 days. The significance level used was p renal excretory system is characterised by the presence of type A major cranial and caudal calyxes seen in 34.3% of the kidneys (type A1 in 30% and type A2 in 4.3%). type B calyxes, corresponding to minor calyxes draining directly into the renal pelvis, were present in 65.7% of the specimens (type B1 59.2%; type B2 6.5% of the cases). The number of minor calyxes in the collector system was 7.9 ± 2.27 with statistically significant differences in side (p = 0.0047). The morphometric characteristics of the kidneys in this study are slightly smaller than reported in humans. Similarly, the incidence of type A renal excretory system distribution is highest in humans and lowest in pigs. Due to its few morphological differences, the pig kidney is an excellent model for teaching- -learning processes, for research purposes, and for training of urologic applications.

  3. Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

    International Nuclear Information System (INIS)

    Aiyer, R.A.; Aggarwal, B.B.

    1990-01-01

    High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

  4. Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma.

    Science.gov (United States)

    Leung, Janet Y; Kim, William Y

    2017-08-01

    Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell renal cell carcinoma (ccRCC). In this issue of Cancer Discovery , Gu and colleagues model these genetic events in mice and report that dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. Cancer Discov; 7(8); 802-4. ©2017 AACR See related article by Gu et al., p. 900 . ©2017 American Association for Cancer Research.

  5. Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery

    Directory of Open Access Journals (Sweden)

    Kocot Arkadius

    2012-06-01

    Full Text Available Abstract Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC and tumor thrombus involving inferior vena cava (IVC treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42% distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%, thoracoabdominal (14 patients/28% or midline abdominal approach (21 patients/42%, depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB was performed in 10 patients (20% with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10 even had a better outcome (overall survival at 5 years of 58.33% than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal

  6. SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Yan, D [William Beaumont Hospital, Royal Oak, MI (United States); Chen, S; Krauss, D; Chen, P [Beaumont Health System, Royal Oak, Michigan (United States); Wilson, G [Beaumont Health System, Royal Oak, MI (United States)

    2016-06-15

    Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function of pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.

  7. L-arginine does not prevent the renal effects of endothelin in humans

    NARCIS (Netherlands)

    Bijlsma, J. A.; Rabelink, A. J.; Kaasjager, K. A.; Koomans, H. A.

    1995-01-01

    The infusion of endothelin to obtain plasma levels as present in sodium-retaining conditions such as heart failure and hepatorenal syndrome has been shown to cause sodium retention and renal vasoconstriction. Whether these renal effects of endothelin could be modulated by the stimulation of nitric

  8. Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.

    Science.gov (United States)

    Lee, S Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W Marston; Bottaro, Donald P; Vasselli, James R

    2008-10-01

    Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knock-down cells had escaped shRNA suppression. EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen.

  9. Von Hippel-Lindau Tumor Suppressor Gene Loss in Renal Cell Carcinoma Promotes Oncogenic Epidermal Growth Factor Receptor Signaling via Akt-1 and MEK1

    Science.gov (United States)

    Lee, S. Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W. Marston; Bottaro, Donald P.; Vasselli, James R.

    2008-01-01

    Objectives Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-α (TGF-α), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Methods Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. Results RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knockdown cells had escaped shRNA suppression. Conclusions EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen. PMID:18243508

  10. Proliferation in human tumors and optimum radiotherapy fractionation

    International Nuclear Information System (INIS)

    Fowler, J.F.; Wisconsin Univ., Madison, WI; Lindstrom, M.J.

    1991-01-01

    Within the last ten years a number of radiotherapy results have been published which enable the effect of overall time on local control to be examined. In all 12 papers a loss of local control with prolongation is shown, although not all papers show a dependence on total dose. The loss of local control per week ranges from 6 to 25% with a median value of 15%. Development of shorter radiotherapy schedules, by one or two weeks, with allocation of rapidly proliferating tumors to the shorter schedules, is recommended. (author)

  11. Examination of human brain tumors in situ with image-localized H-1 MR spectroscopy

    International Nuclear Information System (INIS)

    Luyten, P.R.; Segebarth, C.; Baleriaux, D.; Den Hollander, J.A.

    1987-01-01

    Human brain tumors were examined in situ by combined imaging and H-1 MR spectroscopy at 1.5 T. Water-suppressed localized H-1 MR spectra obtained from the brains of normal volunteers show resonances from lactate, N-acetyl aspartate (NAA), creatine, and choline. Several patients suffering from different brain tumors were examined, showing spectral changes in the region of 0.5-1.5 ppm; spectral editing showed that these changes were not due to lactic acid, but to lipid signals. The NAA signal was decreased in the tumors as compared with normal brain. This study shows that H-1 MR spectroscopy can monitor submillimolar changes in chemical composition of human brain tumors in situ

  12. MODERATE CYTOTOXICITY OF PROANTHOCYANIDINS TO HUMAN TUMOR-CELL LINES

    NARCIS (Netherlands)

    KOLODZIEJ, H; HABERLAND, C; WOERDENBAG, HJ; KONINGS, AWT

    In the present study the cytotoxicity of 16 proanthocyanidins was evaluated in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values ranging from 18 to >200 mu m following continuous

  13. Vav promotes differentiation of human tumoral myeloid precursors

    International Nuclear Information System (INIS)

    Bertagnolo, Valeria; Brugnoli, Federica; Mischiati, Carlo; Sereni, Alessia; Bavelloni, Alberto; Carini, Cinzia; Capitani, Silvano

    2005-01-01

    Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders

  14. Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy

    International Nuclear Information System (INIS)

    Mangin, M.; Webb, A.C.; Dreyer, B.E.

    1988-01-01

    Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A) + RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage λgt10. The library was screened with a codon-preference oligonucleotide synthesized on the basis of a partial N-terminal amino acid sequence from a human tumor-derived peptide, and a 2.0 kilo-base cDNA was identified. The cDNA encodes a 177 amino acid protein consisting of a 36 amino acid leader sequence and a 141 amino acid mature peptide. The first 13 amino acids of the deduced sequence of the mature peptide display strong homology to human PTH, with complete divergence thereafter. RNA blot-hybridization analysis revealed multiple transcripts in mRNA from tumors associated with the humor syndrome and also in mRNA from normal human keratinocytes. Southern blot analysis of genomic DNA from humans and rodents revealed a simple pattern compatible with a single-copy gene. The gene has been mapped to chromosome 12

  15. Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

    Science.gov (United States)

    Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

    2013-10-01

    Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

  16. Characterization of TEM1/endosialin in human and murine brain tumors

    International Nuclear Information System (INIS)

    Carson-Walter, Eleanor B; Walter, Kevin A; Winans, Bethany N; Whiteman, Melissa C; Liu, Yang; Jarvela, Sally; Haapasalo, Hannu; Tyler, Betty M; Huso, David L; Johnson, Mahlon D

    2009-01-01

    TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models. In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice. TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts. TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1

  17. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  18. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... as a standard, e.g. in therapeutic experiments. The course of tumor growth is independent of the size of the transplant, and whether tumors are transplanted in the right or left or both flanks of the recipient mice. Furthermore, the growth does not vary in a systematic way with the number of passages in nude...

  19. 1H-NMR of human blood lipids in cases of malignant and benign tumors

    International Nuclear Information System (INIS)

    Yushmanov, V.E.; Kotrikadze, N.G.; Pershin, A.D.; Dzhishkariani, O.S.; Tsartsidze, M.A.; Lomsadze, B.A.; Sibel'dina, L.A.

    1989-01-01

    High resolution 1 H-NMR (360MH z ) combined with thin-layer chromatography was used to study profile and molecular structure changes of inverted micelles of human blood developing in patients with malignant and benign tumors of the breast and uterus. Alterations were demonstrated in relative intensities of some lipid NMR peaks in tumor, as compared to normal blood. Changes in blood - lipid levels, e.g. cholesterol, in tumor affect lipid structural and dynamical status thus elucidating NMR-regularities obtained

  20. Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex.

    Directory of Open Access Journals (Sweden)

    Ling Chen

    Full Text Available Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs along with their association with anatomy specific biominerals were obtained. Results illustrated that intratubular spherical aggregates primarily form at the proximal regions distant from the papillary tip while interstitial spherical and fibrillar aggregates are distally located near the papillary tip. Biominerals at the papillary tip were closely localized with 10 to 50 μm diameter vasa recta immunolocalized for CD31 inside the medullo-papillary complex. Abundant NCPs known to regulate bone mineralization were localized within nanoparticles, forming early pathologic mineralized regions of the complex. Based on the physical association between vascular and urothelial tubules, results from light and electron microscopy techniques suggested that these NCPs could be delivered from vasculature to prompt calcification of the interstitial regions or they might be synthesized from local vascular smooth muscle cells after transdifferentiation into osteoblast-like phenotypes. In addition, results provided insights into the plausible temporal events that link the anatomically specific intratubular mineral aggregates with the interstitial biomineralization processes within the functional unit of the kidney.

  1. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  2. Evaluation of tumor targeting with radiolabeled F(ab2 fragment of a humanized monoclonal antibody

    Directory of Open Access Journals (Sweden)

    "Babaei MH

    2002-08-01

    Full Text Available Humanized monoclonal antibody U36 and its F(ab'2 fragment, radio labeled with 125I, were tested for tumor localization in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma. Monoclonal antibody IgG or F(ab'2 fragment were injected in parallel and at days 1, 2 and 3, mice were dissected for determination of isotope biodistribution. IgG as well as F(ab'2 showed highly specific localization in tumor tissue. The mean tumor uptake (n=3 is expressed as the percentage of the injected dose per gram of tumor tissue (%ID/g. %ID/g of IgG was 11.7% at day 1 and decreased to 10.9% at day 3 whereas %ID/g of F(ab'2 was 2.9% at day 1 and decreased on following days. Tumor to blood ratios (T/B at day 1 were 0.86 for IgG and 1.32 for F(ab'2 and reached a maximum at day 3 with values of 4.41 and 1.84 respectively. These findings suggest that the superior tumor to non-tumor ratios in the day of 1 render the F(ab'2 fragment more qualified for specific targeting radioisotopes to tumor xenografts in this exprimental setting.

  3. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    Science.gov (United States)

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    OpenAIRE

    Kyoung-jin Min; Ju-Ock Nam; Taeg Kyu Kwon

    2017-01-01

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (...

  5. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  6. Comparação dos métodos de imagem no diagnóstico dos tumores renais e calcificações nestas neoplasias Comparison of imaging methods for diagnosis of renal tumors and their calcifications

    Directory of Open Access Journals (Sweden)

    Sergio Marrone Ribeiro

    2004-12-01

    Full Text Available OBJETIVO: Tentar estabelecer uma metodologia no diagnóstico e conduta dos pacientes com massas renais sólidas e complexas, comparando os custos e benefícios dos diferentes métodos de diagnóstico por imagem. Procuramos avançar no diagnóstico diferencial entre lesões benignas e malignas, particularmente através da investigação das calcificações tumorais. MÉTODOS: Realizamos um estudo prospectivo em 31 pacientes portadores de massas renais sólidas ou complexas, todos eles submetidos à ultra-sonografia abdominal (US, ultra-sonografia doppler da massa renal (US Dop, tomografia computadorizada (TC e ressonância magnética (RM. RESULTADOS: Encontramos 28 pacientes com massas malignas e três com massas benignas. Entre os 28 pacientes com lesões malignas, 17 mostraram calcificações pela TC; 16 deles calcificações do tipo central e um calcificação do tipo curvilinear periférica pura (casca de ovo. A urografia excretora (UGE mostrou uma taxa de detecção para calcificações significantemente menor que a US e a TC. Massas benignas e malignas apareceram como descrito na literatura, com o US, TC e RM mostrando alta sensibilidade e especificidade no diagnóstico dos tumores renais. A exceção foi na US Dop, onde nós obtivemos menor sensibilidade para a caracterização de fluxo tumoral maligno. CONCLUSÕES: Foi surpreendente verificar que a TC revelou calcificações centrais em 51,6% dos pacientes desta série, todas elas em lesões malignas, quando a literatura refere uma freqüência de calcificações entre 8% e 22% dos carcinomas de células renais, em estudos utilizando radiografias simples do abdômen e UGE. Este achado é de grande importância quando consideramos que estas calcificações ocorrem particularmente em neoplasias malignas. Como resultado da comparação dos diferentes métodos de diagnóstico por imagem, nós propomos uma metodologia para adequada investigação dos tumores renais.BACKGROUND: To establish the

  7. A new model with an anatomically accurate human renal collecting system for training in fluoroscopy-guided percutaneous nephrolithotomy access.

    Science.gov (United States)

    Turney, Benjamin W

    2014-03-01

    Obtaining renal access is one of the most important and complex steps in learning percutaneous nephrolithotomy (PCNL). Ideally, this skill should be practiced outside the operating room. There is a need for anatomically accurate and cheap models for simulated training. The objective was to develop a cost-effective, anatomically accurate, nonbiologic training model for simulated PCNL access under fluoroscopic guidance. Collecting systems from routine computed tomography urograms were extracted and reformatted using specialized software. These images were printed in a water-soluble plastic on a three-dimensional (3D) printer to create biomodels. These models were embedded in silicone and then the models were dissolved in water to leave a hollow collecting system within a silicone model. These PCNL models were filled with contrast medium and sealed. A layer of dense foam acted as a spacer to replicate the tissues between skin and kidney. 3D printed models of human collecting systems are a useful adjunct in planning PCNL access. The PCNL access training model is relatively low cost and reproduces the anatomy of the renal collecting system faithfully. A range of models reflecting the variety and complexity of human collecting systems can be reproduced. The fluoroscopic triangulation process needed to target the calix of choice can be practiced successfully in this model. This silicone PCNL training model accurately replicates the anatomic architecture and orientation of the human renal collecting system. It provides a safe, clean, and effective model for training in accurate fluoroscopy-guided PCNL access.

  8. Evaluation of human thyroid tumors by proton nuclear magnetic resonance

    International Nuclear Information System (INIS)

    deCertaines, J.; Herry, J.Y.; Lancien, G.; Benoist, L.; Bernard, A.M.; LeClech, G.

    1982-01-01

    Proton nuclear magnetic resonance (NMR) was used in a study of 40 patients with thyroid tumors following partial or total thyroidectomy. Three patient groups were considered: those with nodules showing increased uptake, those with solitary nodules with decreased uptake, and those with multinodular goiters. Spin-lattice and spin-spin relaxation times (T 1 and T 2 ) were measured on samples of nodular and extranodular tissue from each patient. Increased T 1 and T 2 were observed for benign cold nodules, an increase in T 1 alone for nodules with increased uptake, and a wide fluctuation in T 1 and T 2 for multinodular goiters. The four cancers in the series did not show a distinctive proton NMR pattern in comparison with the other nodular structures studied. The results point to the feasibility of applying NMR techniques to the detection of thyroid disease

  9. Is IGSF1 involved in human pituitary tumor formation?

    Science.gov (United States)

    Faucz, Fabio R; Horvath, Anelia D; Azevedo, Monalisa F; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R; Wit, Jan M; Bernard, Daniel J; Stratakis, Constantine A

    2015-02-01

    IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. © 2015 Society for Endocrinology.

  10. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  11. Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression.

    Science.gov (United States)

    Gacerez, Albert T; Hua, Casey K; Ackerman, Margaret E; Sentman, Charles L

    2018-05-01

    B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display. In this study, we validate the functionality of these human scFvs when formatted into chimeric antigen receptors. The data indicate that T cells expressing these B7H6-specific human scFvs as CARs induced potent anti-tumor activity in vitro and in vivo against tumors expressing high amounts of B7H6. Importantly, these human scFv-based CARs are sensitive to changes in B7H6 expression which may potentially spare non-tumor cells that express B7H6 and provides the foundation for future clinical development.

  12. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    Science.gov (United States)

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  13. Near-Infrared Optical Imaging of Integrin αvβ3 in Human Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2004-10-01

    Full Text Available In vivo optical imaging is potentially useful for evaluating the presence of tumor markers that are targets of molecular medicine. Here we report the synthesis and characterization of integrin αvβ3-targeted peptide cyclo(Lys–Arg–Gly–Asp–Phe [c(KRGDf] labeled with fluorescence dyes with wavelength spanning from the visible/near infrared (Cy5.5 to the true near infrared (IRDye800 for optical imaging. In vitro, the peptide–dye conjugates bound specifically to tumor cells expressing αvβ3. When administered intravenously into mice at a dose of 6 nmol/mouse, the conjugates accumulated in tumors expressing αvβ3. The tumor-to-background ratios for human KS1767 Kaposi's sarcoma in mice injected with Cy5.5–c(KRGDf and Cy5.5 were 5.5 and 1.5, respectively. Preinjection of c(KRGDf blocked the uptake of Cy5.5–c(KRGDf in tumors by 89%. In αvβ3-positive M21 and αvβ3-negative M21-L human melanoma, fluorescence intensity in the tumor of mice injected with IRDye800–c(KRGDf was 2.3 and 1.3 times that in normal tissue, respectively. Dynamic imaging revealed that Cy5.5–c(KRGDf was rapidly taken up by KS1767 tumor immediately after bolus injection. The rate of its uptake in the tumor was reduced by preinjection of c(KRGDf in an interval time-dependent manner. Our data suggest that near-infrared fluorescence imaging may be applied to the detection of tumors expressing integrin αvβ3 and to the assessment of the optimal biological dose and schedule of targeted therapies.

  14. Localization of indium-111 in human malignant tumor xenografts and control by chelators

    International Nuclear Information System (INIS)

    Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

    1999-01-01

    The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

  15. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  16. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    International Nuclear Information System (INIS)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-01-01

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics

  17. Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

    Science.gov (United States)

    Zhang, Xiao-Dong; Luo, Zhentao; Chen, Jie; Song, Shasha; Yuan, Xun; Shen, Xiu; Wang, Hao; Sun, Yuanming; Gao, Kai; Zhang, Lianfeng; Fan, Saijun; Leong, David Tai; Guo, Meili; Xie, Jianping

    2015-03-01

    Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29-43(SG)27-37 nanoclusters (protecting shell. The GSH-coated Au29-43(SG)27-37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29-43(SG)27-37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

  18. Selective changes in expression of HLA class I polymorphic determinants in human solid tumors

    International Nuclear Information System (INIS)

    Natali, P.G.; Nicotra, M.R.; Bigotti, A.; Venturo, I.; Giacomini, P.; Marcenaro, L.; Russo, C.

    1989-01-01

    Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. The authors have found that in HLA-A2-positive patients, HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B.C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance

  19. Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1989-01-01

    The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D 0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus. (author)

  20. Evaluation of Antiproliferative Potential of Cerium Oxide Nanoparticles on HeLa Human Cervical Tumor Cell

    Directory of Open Access Journals (Sweden)

    Zoriţa Diaconeasa

    2015-05-01

    Full Text Available Cerium oxide nanoparticles (CeO2 nanoparticles as nanomaterials have promising biomedical applications. In this paper, the cytotoxicity induced by CONPs human cervical tumor cells was investigated. Cerium oxide nanoparticles were synthesized using the precipitation method. The nanoparticles were found to inhibit the proliferation of HeLa human cervical tumor cells in a dose dependent manner but did not showed to be cytotoxic as analyzed by MTT assay. The administrated treatment decreased the HeLa cell viability cells from 100% to 65% at the dose of 100 μg/mL.

  1. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment...... of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha...... indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms...

  2. The renal metallothionein expression profile is altered in human lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Penkowa, Milena; Andersen, Claus Bøgelund

    2008-01-01

    of standard statistical methods. RESULTS: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median......INTRODUCTION: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT......-I+II expression profile is altered during lupus nephritis. METHODS: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means...

  3. Gradient field echo imaging and Gd-DTPA for the assessment of renal function in humans

    International Nuclear Information System (INIS)

    Von Schulthess, G.K.; Kikinis, R.; Durr, R.; Bino, M.; Jager, P.; Kubler, O.

    1986-01-01

    To evaluate renal parenchymal function, 1.5 T gradient field echo imaging using a sequence of repetitive 10-second scans was performed in apneic patients after injection of Gd-DTPA (0.1 mmol/kg body weight). During the 10-second pauses the patients were allowed to breathe. Angled coronal images (TR=40 msec, TE =20 msec, flip angle = 40 0 ) were obtained in four volunteers and four patients with hydronephrosis. Image quality was excellent, suggesting unprecedented spatial resolution for renal function studies. Initially, cortical perfusion was observed. Then the papilae became isointense; after 70 seconds they became hypointense; and finally the renal pelvic signal dropped. No papillary signal drop was seen in hydronephrosis, as confirmed by region-of-interest analysis. These results strongly suggest that in MR renal ''function'' studies with Gd-DTPA, T1 and T2 paramagnetic effects are operative

  4. Expression of human soluble tumor necrosis factor (TNF)-related ...

    African Journals Online (AJOL)

    DR NJ TONUKARI

    2011-06-06

    Jun 6, 2011 ... bio-technique in bacterial (Lin et al., 2007), yeast (Xu et al., 2003) ... biological activity, such as human somatotropin (hST) .... sion way with chloroplast transit peptide (Wang et al., .... chloroplast protein synthesis capacity by massive expression of a ... necrosis factor-related apoptosis-inducing ligand in vivo.

  5. Dynamic tumor modeling of the dose–response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial

    International Nuclear Information System (INIS)

    Stein, Andrew; Wang, Wenping; Carter, Alison A; Chiparus, Ovidiu; Hollaender, Norbert; Kim, Hyewon; Motzer, Robert J; Sarr, Celine

    2012-01-01

    The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose–response relationship of everolimus. The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% ± 98.3%, +22.4% ± 17.2%, and –15.7% ± 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time. In this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose–response relationship

  6. Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

    Science.gov (United States)

    Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

    2016-09-01

    To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

  7. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Zhenyu Qiu

    2014-08-01

    Full Text Available Objective This study aims to observe the function of umbilical cord-mesenchymal stem cells (UC-MSCs labelled with enhanced green fluorescent protein (eGFP in the repair of renal ischaemia-reperfusion (I/R injury, to determine the effects on inflammatory cascade in an established rat model and to explore possible pathogenesis. Materials and Methods Sixty rats were randomly divided into three groups: the sham-operated, I/R and UC-MSC treatment groups. All rats underwent right nephrectomy. Ischaemia was induced in the left kidney by occlusion of the renal artery and vein for 1hour, followed by reperfusion for 24 hours or 48 hours. Kidney samples were collected to observe morphological changes. Immunohistochemistry was performed to assess the expression of intercellular adhesion molecule 1 (ICAM-1 in the renal tissue sample, as well as the number of infiltrating polymorphonuclear neutrophils (PMNLs and UC-MSCs with positive eGFP. Results Renal histopathological damages and the expression of ICAM-1 and PMNL increased significantly in the I/R group compared with those in the sham-operated group, whereas the damages were less conspicuous in the UC-MSC treatment group. Conclusions Renal ICAM-1, which mediated PMNL infiltration and contributed to renal damage, was significantly up-regulated in the I/R group. UC-MSCs were identified to inhibit these pathological processes and protect the kidney from I/R injury.

  8. Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

    International Nuclear Information System (INIS)

    Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

    2010-01-01

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

  9. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1981-12-01

    Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

  10. Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma

    Science.gov (United States)

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

  11. Radiosensitivity of different human tumor cells lines grown as multicellular spheroids determined from growth curves and survival data

    International Nuclear Information System (INIS)

    Schwachoefer, J.H.C.; Crooijmans, R.P.; van Gasteren, J.J.; Hoogenhout, J.; Jerusalem, C.R.; Kal, H.B.; Theeuwes, A.G.

    1989-01-01

    Five human tumor cell lines were grown as multicellular tumor spheroids (MTS) to determine whether multicellular tumor spheroids derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences paralleled clinical behavior. Multicellular tumor spheroids of two neuroblastoma, one lung adenocarcinoma, one melanoma, and a squamous cell carcinoma of the oral tongue, were studied in terms of growth delay, calculated cell survival, and spheroid control dose50 (SCD50). Growth delay and cell survival analysis for the tumor cell lines showed sensitivities that correlated well with clinical behavior of the tumor types of origin. Similar to other studies on melanoma multicellular tumor spheroids our spheroid control dose50 results for the melanoma cell line deviated from the general pattern of sensitivity. This might be due to the location of surviving cells, which prohibits proliferation of surviving cells and hence growth of melanoma multicellular tumor spheroids. This study demonstrates that radiosensitivity of human tumor cell lines can be evaluated in terms of growth delay, calculated cell survival, and spheroid control dose50 when grown as multicellular tumor spheroids. The sensitivity established from these evaluations parallels clinical behavior, thus offering a unique tool for the in vitro analysis of human tumor radiosensitivity

  12. Human breast tumor imaging using 111In labeled monoclonal antibody: Anthymic mouse model

    International Nuclear Information System (INIS)

    Ban An Khaw; Massachusetts General Hospital, Boston; Bailes, J.S.; Schneider, S.L.; Lancaster, J.; Lasher, J.C.; McGuire, W.L.; Powers, J.; Strauss, H.W.

    1988-01-01

    The monoclonal antibody (MoAb) 323/A3, an IgG1, was raised against the human breast tumor cell line MCF-7 and recognized a 43 Kd membrane associated glycoprotein. Histochemical studies with the antibody detected 75% of metastatic lymph nodes, 59% of primary breast tumors, and showed some staining in 20% of benign breast lesions. For radionuclide imaging, the MoAb 323/A3 was labeled with both 125 I and 111 In, via covalently coupled diethylenetriaminepentaacetic acid (DTPA) by the mixed anhydride method. The antibody activity of the DTPA modified 323/A3 was assessed by an immunoassay using viable and fixed MCF-7 target cells. Male athymic nude mice bearing BT-20 human mammary tumors were injected with dual 125 I/ 111 In labeled DTPA 323/A3 via the tail veins. The animals were imaged with a gamma camera equipped with a pinhole collimator at 1-3 h, 1, 2, 3, 4 and 5 days after the tracer administration. On day 5 or 6, the animals were killed, and the biodistribution of the radiotracers was determined for the blood, thyroid, heart, lungs, liver, spleen, kidneys, gastro-intestinal tract and tumor. Target to blood ratio at 6 days for the 111 In tracer was 24:1 in the group with a mean tumor weight of 0.492 g, and 13:1 in another group with a mean tumor weight of 0.1906 g (day 5). However, the 125 I activity showed only 3.6:1 and 5.4:1 target to blood ratios in the corresponding groups. The larger tumors localized less 111 I tracer (27.13%±7.57% injected dose/g, Mean±SD) than the smaller tumors (52.75%±22.25% ID/g). Analysis of the gamma images showed that the maximum tracer concentration occurred in the tumors at about 2 to 3 days after intravenous tracer administration. The excellent tumor resolution observed with BT-20 tumors may be due to increased 43 Kd glycoprotein antigen density in this tumor cell line. (orig.)

  13. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

    DEFF Research Database (Denmark)

    von Deimling, A; Fimmers, R; Schmidt, M C

    2000-01-01

    Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors....

  14. In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine.

    Science.gov (United States)

    Dunphy, Mark P S; Harding, James J; Venneti, Sriram; Zhang, Hanwen; Burnazi, Eva M; Bromberg, Jacqueline; Omuro, Antonio M; Hsieh, James J; Mellinghoff, Ingo K; Staton, Kevin; Pressl, Christina; Beattie, Bradley J; Zanzonico, Pat B; Gerecitano, John F; Kelsen, David P; Weber, Wolfgang; Lyashchenko, Serge K; Kung, Hank F; Lewis, Jason S

    2018-05-01

    Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07).