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Sample records for renal epithelial tumors

  1. Immunoprofiles of Adult Renal Epithelial Tumors: Immunohistochemistry Is Still Essential for Diagnosis of Renal Tumors (A Comprehensive Update

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    Ayhan Ozcan

    2015-09-01

    Full Text Available Renal cell carcinoma (RCC is the third most common cancer of the genitourinary tract and accounts for approximately 2-3% of all cancer deaths. The recent classification of renal tumors, The International Society of Urological Pathology (ISUP Vancouver Classification of Renal Neoplasia, has been proposed new distinct epithelial tumors and provisional new entities. Although most renal tumors are morphologically diagnosed, they need to use a panel of immunomarkers due to their overlapping morphologic features in some cases such as benign mimickers and newly emerged tumor types. Overlapping morphologic features are especially complicated in small biopsies and in distinguishing metastatic RCCs from other tumors. Immunohistochemistry is still more useful in renal tumors than non-renal tumors. A wide panel has been performed in the differential diagnosis of renal tumors. If immunohistochemical results are conflict or unconvincing, a diagnosis of unclassified RCC is appropriate. For accurate diagnosis of RCC, it should be careful in performing immunohistochemistry on needle biopsy due to variable expressions of immunomarkers originated from heterogeneity in RCCs. Morphology is still gold standard, but immunohistochemistry should be kept in mind as a useful and supportive diagnostic tool upon morphological features of renal tumors as always. [J Interdiscipl Histopathol 2015; 3(3.000: 81-101

  2. Renal mixed epithelial and stromal tumor: case report

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    Karla Lais Pêgas

    2015-02-01

    Full Text Available Mixed epithelial and stromal tumor (MEST represents a recently described biphasic kidney neoplasm, which predominantly affects perimenopausal females. The authors report the case of a young male patient with a MEST exhibiting positivity for estrogen and progesterone receptors. Computed tomography/magnetic resonance imaging (CT/MRI showed an expansive lesion affecting the right kidney. Grossly, a solid-cystic tumor was identified, which measured 5.7 × 3.5 × 2.4 cm. On microscopic examination, a biphasic tumor constituted by stromal and epithelial elements, without significant atypias, was identified. The stromal element was composed of spindle cells revealing positive immunoexpression for actin, desmin, vimentin, and estrogen receptors. The epithelial component exhibited a predominantly tubular pattern showing positive immunoreaction for cytokeratins. The diagnosis of MEST was then established.

  3. [Mixed epithelial and stromal tumor growing with polypoid pattern in the renal pelvis].

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    Yamasaki, Toshinari; Yagihashi, Yuusuke; Iwamura, Hiroshi; Shirahase, Toshiaki; Hashimura, Takayuki; Katsura, Yoshitaka

    2004-01-01

    A 68-year-old woman was found incidentally to have right hydronephrosis and a renal pelvic mass by abdominal ultrasonography. Radiographic examinations revealed a heterogeneous renal pelvic tumor, and right nephroureterectomy was performed. The tumor was well circumscribed yellow-whitish solid mass with scattered cysts. Histologically, the tumor was composed of both mesenchymal and epithelial components. The mesenchymal elements consisted of fibroblasts and smooth muscle cells, and the epithelial elements of cystic and tubular structures lined by cuboidal epithelium. Atypia and mitoses were not identified. The patient was free of recurrence 42 months postoperatively. Mixed epithelial and stromal tumor of the kidney is a recently recognized neoplasm that occurs almost exclusively in perimenopausal woman. Similar tumors have been reported previously under various names, including adult mesoblastic nephroma and cystic hamartoma of the renal pelvis. Histogenesis of the tumor is still controversial.

  4. CYTOGENETIC ANALYSIS OF EPITHELIAL RENAL-CELL TUMORS - RELATIONSHIP WITH A NEW HISTOPATHOLOGICAL CLASSIFICATION

    NARCIS (Netherlands)

    VANDENBERG, E; VANDERHOUT, AH; OOSTERHUIS, JW; STORKEL, S; DIJKHUIZEN, T; ZWEERS, HMM; MENSINK, HJA; BUYS, CHCM; DEJONG, B; Dam, A.

    1993-01-01

    Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and

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

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    Tepeler, Abdulkadir; Erdem, Mehmet Remzi; Kurt, Omer; Topaktas, Ramazan; Kilicaslan, Isin; Armağan, Abdullah; Önol, Şinasi Yavuz

    2011-01-01

    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. PMID:22110514

  6. 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...

  7. Renal primitive neuroectodermal tumors.

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    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  8. Renal neuroendocrine tumors

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    Brian R Lane

    2009-01-01

    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  9. Renal Tumor Biopsy Technique

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xue-Song Li; Li-Qun Zhou

    2016-01-01

    Objective:To review hot issues and future direction of renal tumor biopsy (RTB) technique.Data Sources:The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015.Study Selection:We included all the relevant articles on RTB technique in English,with no limitation of study design.Results:Computed tomography and ultrasound were usually used for guiding RTB with respective advantages.Core biopsy is more preferred over fine needle aspiration because of superior accuracy.A minimum of two good-quality cores for a single renal tumor is generally accepted.The use of coaxial guide is recommended.For biopsy location,sampling different regions including central and peripheral biopsies are recommended.Conclusion:In spite of some limitations,RTB technique is relatively mature to help optimize the treatment of renal tumors.

  10. Calcifying epithelial odontogenic tumor (Pindborg tumor)

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    Singh, Neeraj; Sahai, Sharad; Singh, Sourav; Singh, Smita

    2011-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare entity and represents less than 1% of all odontogenic tumors. Dr. J J Pindborg (1958) first described four cases of this unusual lesion; subsequently Shafer et al coined the term Pindborg tumor. This lesion is a locally aggressive benign odontogenic neoplasm arising from epithelial tissue. It occurs most commonly in 4th-5th-6th decade of life and bears no gender predilection. A case of CEOT in a 50-year-old male arising in the left body region is described. PMID:22639521

  11. Malignant renal tumors in children

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    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  12. 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.

  13. The nuclear factor κB family member RelB facilitates apoptosis of renal epithelial cells caused by cisplatin/tumor necrosis factor α synergy by suppressing an epithelial to mesenchymal transition-like phenotypic switch.

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    Benedetti, Giulia; Fokkelman, Michiel; Yan, Kuan; Fredriksson, Lisa; Herpers, Bram; Meerman, John; van de Water, Bob; de Graauw, Marjo

    2013-07-01

    Cis-diamminedichloroplatinum(II) (cisplatin)-induced renal proximal tubular apoptosis is known to be preceded by actin cytoskeleton reorganization, in conjunction with disruption of cell-matrix and cell-cell adhesion. In the present study, we show that the proinflammatory cytokine tumor necrosis factor α (TNF-α) aggravated these cisplatin-induced F-actin and cell adhesion changes, which was associated with enhanced cisplatin-induced apoptosis of immortalized proximal tubular epithelial cells. TNF-α-induced RelB expression and lentiviral small hairpin RNA (shRNA)-mediated knockdown of RelB, but not other nuclear factor κB members, abrogated the synergistic apoptosis observed with cisplatin/TNF-α treatment to the level of cisplatin-induced apoptosis. This protective effect was associated with increased stress fiber formation, cell-matrix, and cell-cell adhesion in the shRNARelB (shRelB) cells during cisplatin/TNF-α treatment, mimicking an epithelial-to-mesenchymal phenotypic switch. Indeed, gene array analysis revealed that knockdown of RelB was associated with upregulation of several actin regulatory genes, including Snai2 and the Rho GTPase proteins Rhophilin and Rho guanine nucleotide exchange factor 3 (ARHGEF3). Pharmacological inhibition of Rho kinase signaling re-established the synergistic apoptosis induced by combined cisplatin/TNF-α treatment of shRelB cells. In conclusion, our study shows for the first time that RelB is required for the cisplatin/TNF-α-induced cytoskeletal reorganization and apoptosis in renal cells by controlling a Rho kinase-dependent signaling network.

  14. Primary renal primitive neuroectodermal tumor.

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    Goel, V; Talwar, V; Dodagoudar, C; Singh, S; Sharma, A; Patnaik, N

    2015-01-01

    Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  15. Ossifying renal tumor of infancy.

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    Schelling, Johannes; Schröder, Annette; Stein, Raimund; Rösch, Wolfgang H

    2007-06-01

    A renal ossifying tumor of infancy is a rare event with few cases having been published, and the etiology has not yet been established. We report on two new cases of this unusual neoplasm. A 2-year-old boy presented with intermittent painless gross hematuria. After several diagnostic procedures, an open pyelolithotomy was performed and the histological diagnosis of renal tumor of infancy was finally made. The history of the second case is very similar. An 8-week-old infant presented with gross hematuria. As in the first case, an open pyelolithotomy was performed and a tumor entirely covered with blood clots was found in the renal pelvis and completely removed. A histological diagnosis of renal ossifying tumor of infancy was made. Using the literature available, the histological criteria and biological behavior are discussed, together with the diagnostic and therapeutic algorithm for this tumor. In infants with gross hematuria and a calcified (non-)invasive mass in the pelvi-calceal system, renal ossifying tumor should be considered in the differential diagnosis. MRI or CT scan offers a good diagnostic guide.

  16. Contemporary treatment of renal tumors

    DEFF Research Database (Denmark)

    Nisen, Harry; Järvinen, Petrus; Fovaeus, Magnus

    2017-01-01

    questions on renal tumor management and surgical education was designed and sent to 91 institutions performing renal tumor surgery in 2015. The response rate was 68% (62 hospitals), including 28 academic, 25 central and nine district hospitals. Hospital volume was defined as low (LVH: ...% thermoablations. For RN and PN, the percentages of open, laparoscopic and robotic approaches were 47%, 40%, 13% and 47%, 20%, 33%, respectively. The mean complication rate (Clavien–Dindo 3–5) was 4.9%, and 30 day mortality (TDM) was 0.5%. The median length of hospital stay was 4 days. Training with a simulator...

  17. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

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    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  18. Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy

    OpenAIRE

    M.F.B. Andersen; Norus, T.P.

    2016-01-01

    Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed.

  19. Palliative embolization of renal tumors

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    Jaganjac Suad

    2015-01-01

    Full Text Available Background/Aim. Palliative embolization of renal tumors is the method of choice in the treatment of advanced inoperable renal cell carcinoma in patients with hematuria and pain. Patients with small tumors in the remaining solitary kidney who refuse surgery are suitable for this type of therapy as well as patients with centrally located inoperable tumors. The prerequisite for successful capillary embolization is the closure of the main arte-rial trunk with metal spirals. Methods. In the period from 2000 to 2010 we conducted 42 palliative embolizations. The average age of the patients was 75 years, including 26 men and 16 women. In 8 of the patients the intervention was repeated and in one with severe AV shunts embolization was performed 4 times. Embolization was performed with alcohol, Ivalon 150-250 μm and with metal coils. Results. No serious complications were observed during and after the intervention. Fourteen patient were still alive then and among the deceased patients the average survival time was 13.5 ± 10.8 months with the range of 1 to 56 months. The minimal survival time was 1 month with a maxi-mum survival time of 56 months. Conclusion. Our results are consistent with data in the literature. Survival in patients without metastases was longer than in those with metastases, as con-firmed by the 14 of the patients from the study. An additional therapeutic safety in the treatment of small cancers is provided with a combination therapy of embolization and radiofrequency thermoablation.

  20. Epithelial-Mesenchymal Transition in tumor microenvironment

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    Jing Yingying

    2011-08-01

    Full Text Available Abstract The epithelial to mesenchymal transition (EMT plays crucial roles in the formation of the body plan and also in the tumor invasion process. In addition, EMT also causes disruption of cell-cell adherence, loss of apico-basal polarity, matrix remodeling, increased motility and invasiveness in promoting tumor metastasis. The tumor microenvironment plays an important role in facilitating cancer metastasis and may induce the occurrence of EMT in tumor cells. A large number of inflammatory cells infiltrating the tumor site, as well as hypoxia existing in a large area of tumor, in addition many stem cells present in tumor microenvironment, such as cancer stem cells (CSCs, mesenchymal stem cells (MSCs, all of these may be the inducers of EMT in tumor cells. The signaling pathways involved in EMT are various, including TGF-β, NF-κB, Wnt, Notch, and others. In this review, we discuss the current knowledge about the role of the tumor microenvironment in EMT and the related signaling pathways as well as the interaction between them.

  1. Dock180 expression in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Huhua Ling; Zhenwei Yao

    2012-01-01

    Objective: The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer.Methods: Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases.Results: Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor (P < 0.01).In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade.Conclusion: Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.

  2. A mixed epithelial and stromal tumor of the kidney in a ringtail lemur (Lemur catta).

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    Muller, S; Oevermann, A; Wenker, C; Altermatt, H J; Robert, N

    2007-03-01

    Primary renal tumors are rare neoplasms in nonhuman primates. This report describes a mixed epithelial and stromal tumor of the kidney (MESTK) in a 14.5-year-old female ringtail lemur. The well-demarcated, solid, and cystic mass was located in the pelvis of the left kidney and consisted histologically of both epithelial and mesenchymal components. The mesenchymal cells were arranged in fascicles around cysts lined by a well-differentiated epithelium. Neither the mesenchymal nor the epithelial parts showed significant nuclear atypia or mitotic figures. To our knowledge, only 1 similar case, classified as adenoleiomyofibromatous hamartoma, has been reported in a ringtail lemur. In humans this tumor affects predominantly perimenopausal women and can express estrogen and progesterone receptors. However, neither estrogen nor progesterone receptors could be identified by immunohistochemistry in the tumor of the present ringtail lemur. Therefore, a hormonal mechanism could not be demonstrated in this case.

  3. Renal Primitive Neuroectodermal Tumor: A Case Report.

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    Yang, Cheng; Xu, Hanjiang; Zhou, Jun; Hao, Zongyao; Wang, Jianzhong; Lin, Changmin; Zhang, Li; Zhu, Xia; Liang, Chaozhao

    2015-12-01

    Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor and typically arises from bone or soft tissue in adolescents and young adults. Renal PNET is extraordinarily rare and exhibits highly aggressive biological behavior with poor prognosis.We present here a new case of renal PNET in a 31-year-old female. The patients were referred to our hospital because of left flank pain with nausea and vomiting for 1 week. A computed tomography scan revealed a 14.7 × 12.7 cm well-defined, unevenly mass lesion with both solid and cystic components and the tumor was not enhanced uniformly.A preoperative diagnosis of cystic renal cell carcinoma and urinary tract infection was made. The patient undergone anti-inflammatory therapy followed by a left radical nephrectomy. Taken with morphological pattern and immunohistochemical markers, a diagnosis of renal PNET was made. Two cycles of combined chemotherapy were executed. At the 14-month follow-up, no evidence of metastasis or recurrence was indicated.This case reminds clinicians that for adolescents and young adults with a suspicious renal mass, a diagnosis of renal PNET should be always considered. An initial surgery followed by radiotherapy and chemotherapy is suggested for the therapeutic management.

  4. [Renal cholesteatoma: keratin accumulation tumor].

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    González Castillo, P; Mora, M J; Mañas, A; Extramiana, J; Manzarbeitia, F; Pérez, M J; Paniagua, P; Pamplona, M

    1992-01-01

    Presentation of 6 cases of renal cholesteatoma in 4 male and 2 female patients ranging between 30 and 67 years of age. The most consistent clinical data was a history of relapsing nephritic colic of long-evolution. The average time to diagnose was 19 years. In 50% cases an association to malignant neoplastic pathology was found. The clinical diagnosis was based on the urography and the histopathological examination of the material passed with the urine. Renal exeresis was performed in 5 cases. One was treated in a conservative fashion. Also the etiology causes, diagnostic procedure and other therapeutic possibilities were reviewed.

  5. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

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    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.

  6. Angiomotin promotes renal epithelial and carcinoma cell proliferation by retaining the nuclear YAP.

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    Lv, Meng; Li, Shuting; Luo, Changqin; Zhang, Xiaoman; Shen, Yanwei; Sui, Yan Xia; Wang, Fan; Wang, Xin; Yang, Jiao; Liu, Peijun; Yang, Jin

    2016-03-15

    Renal cell carcinoma (RCC) is one of the common tumors in the urinary system without effective therapies. Angiomotin (Amot) can interact with Yes-associated protein (YAP) to either stimulate or inhibit YAP activity, playing a potential role in cell proliferation. However, the role of Amot in regulating the proliferation of renal epithelial and RCC cells is unknown. Here, we show that Amot is expressed predominantly in the nucleus of RCC cells and tissues, and in the cytoplasm and nucleus of renal epithelial cells and paracancerous tissues. Furthermore, Amot silencing inhibited proliferation of HK-2 and 786-O cells while Amot upregulation promoted proliferation of ACHN cells. Interestingly, the location of Amot and YAP in RCC clinical samples and cells was similar. Amot interacted with YAP in HK-2 and 786-O cells, particularly in the nucleus. Moreover, Amot silencing mitigated the levels of nuclear YAP in HK-2 and 786-O cells and reduced YAP-related CTGF and Cyr61 expression in 786-O cells. Amot upregulation slightly increased the nuclear YAP and YAP-related gene expression in ACHN cells. Finally, enhanced YAP expression restored proliferation of Amot-silencing 786-O cells. Together, these data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation.

  7. Primary renal carcinoid tumor: A radiologic review

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    Leslie Lamb, MD, Msc, Bsc

    2014-01-01

    Full Text Available Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney.

  8. Control the invasive growth of gastrointestinal epithelial tumor

    Institute of Scientific and Technical Information of China (English)

    Wang Cunyu

    2014-01-01

    Invasive growth of epithelial tumor is a very complex process. Therefore,clarifying the molecular mechanisms of the invasive growth of tumor cells will help us find new targets for cancer therapy,and suppress tumor growth and development more effectively.

  9. Mandibular brown tumor in renal osteodystrophy

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    Park, Jin Woo; Choi, Bo Ram; Huh, Kyung Hoe; Yi, Won Jin; Choi, Soon Chul [Department of Oral and Maxillofacial Radiology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Gang, In Tae [Department of Oral and Maxillofacial Surgery, Kangnam Sacred Heart Hospital, Hallym Medical Center, Seoul (Korea, Republic of)

    2008-12-15

    Brown tumor is a histologically benign lesion that is a serious complication of renal osteodystrophy because it may result in severe deformity and discomfort. We report a case of brown tumor, which occurred in a 35-year-old woman with chronic renal failure, who had been treated with hemodialysis for 14 years. The lesion was found on the lingual side of the mandible. Standard panoramic radiograph showed generally decreased bone mineral density, loss of lamina dura, and thin cortical plates. Computed tomography (CT) revealed multilocular expansible lesions with heterogeneous attenuation in the anterior mandible, as well as generalized trabecular alteration with homogeneous sclerosis, and thinning or obliteration of cortical plates. Excision of the mandibular lesion and curettage of the affected bone were performed.

  10. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    OpenAIRE

    Mujeeburahiman Thottathil; Ashish Verma; Nischith D′souza; Altaf Khan

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too.

  11. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

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    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  12. Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro.

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    Zhou, Xiangjun; Yao, Qisheng; Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo; Shan, Guang

    2017-03-01

    Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)-1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells

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    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis. PMID:27936102

  14. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.

    Science.gov (United States)

    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito; Kihara, Akio

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.

  15. Renal tumor and trauma: a pitfall for conversative management

    Directory of Open Access Journals (Sweden)

    Simone de Campos Vieira Abib

    2011-08-01

    Full Text Available PURPOSE: Conservative management has been largely used for renal trauma. Although this approach is safe and highly recommended, it can hide a pre-existing unknown condition, such as tumors or urinary malformations. A high index of suspicion is needed for early recognition of these conditions. We present four cases treated at the Pediatric Oncology Institute - Federal University of São Paulo, which have been initially treated conservatively for renal trauma. MATERIALS AND METHODS: We reviewed all 218 renal cases of renal tumors treated at our institution in a 22-year period, searching for associated trauma events. RESULTS: Four cases of renal tumors were initially treated conservatively for blunt renal trauma of low energy mechanism. Patients' ages ranged from 7 to 12 years old. Two patients had no previous symptoms, one patient had hematuria and another had an abdominal mass. Computerized Axial Tomography (CT of the abdomen revealed disparate magnitude of the renal bleeding to the low energy mechanism of trauma. All patients underwent surgical treatment. Kidney specimens showed Wilms tumor in three cases and renal carcinoma in one. CONCLUSIONS: The association between renal tumors and trauma should be suspected when renal trauma hemorrhage on abdominal CT scan does not match the low energy mechanism of blunt abdominal trauma. The key for a successful diagnosis of renal tumor or congenital malformations is the high index of suspicion for these conditions.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Thymic Epithelial Tumor with Heart Metastasis in a Horse

    Directory of Open Access Journals (Sweden)

    Farshid Shahriar

    2010-01-01

    Full Text Available Thymic malignancy is rare in horses. Thymic epithelial tumor was diagnosed in an 18-year-old mare with invasion and metastasis to the pericardium and heart. At necropsy, the cranial thoracic cavity was obliterated by a large mass located in the thymic region and the right atrium was also expanded and effaced by a similar mass. Histologically, the neoplasm was composed of sheets of spindle cells with intraparenchymal Hassall's corpuscles and formation of pseudorosettes around blood vessels compatible with type A thymic epithelial tumor according to World Health Organization classification. The neoplastic cells were diffusely immunoreactive for cytokeratin and negative for vimentin, S100, neuron specific enolase, glial fibrillar acidic protein, chromogranin A, synaptophysin, CD3 and CD79a markers. To the authors' knowledge, cardiac invasion and distinct histological pattern of pseudorosette formation have not been described in equine thymic epithelial tumors previously.

  18. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

    Science.gov (United States)

    Chen, Jun-Feng; Wu, Qi-Shun; Xie, Yu-Xian; Si, Bo-Lin; Yang, Ping-Ping; Wang, Wen-Yan; Hua, Qin; He, Qing

    2017-10-01

    Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria. © FASEB.

  19. Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Chen; Chung-Wei Wu; Wen-Chen Wang; Li-Min Lin; Yuk-Kwan Chen

    2013-01-01

    We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

  20. The use of immunohistochemical expression of SF-1 and EMA in distinguishing adrenocortical tumors from renal neoplasms.

    Science.gov (United States)

    Enriquez, Miriam L; Lal, Priti; Ziober, Amy; Wang, Liping; Tomaszewski, John E; Bing, Zhanyong

    2012-03-01

    Steroidogenic factor -1 (SF-1) is an orphan member of the nuclear hormone receptor superfamily, and is considered to play an important role in the differentiation of steroidogenic tissues. In this study, we compared the immunohistochemical stains of SF-1 and epithelial membrane antigen (EMA) in non-neoplastic adrenal tissue, and adrenal and renal tumors using tissue microarrays (TMAs). The adrenal tissue array included 19 cases of normal adrenal cortex, 22 cases of adrenal adenoma, and 20 cases of adrenal cortical carcinoma. The renal tissue array included 20 cases of each of the following types of renal cell carcinoma: clear cell, papillary, and chromophobe. In addition, 20 cases of renal oncocytoma were also included in the study. SF-1 showed positive staining in all cases (100%) of normal adrenal cortex and adrenal cortical adenoma, and in 18 (90%) cases of adrenocortical carcinoma. In renal tumors, SF-1 showed negative stains in all of oncocytoma, papillary, and chromophobe renal cell carcinoma. Only 3 out of 20 cases of clear cell renal cell carcinoma showed weak positivity in approximately 10% of tumor cells. EMA stained positively in 85%, 95%, 100%, and 95% of clear cell, papillary, chromophobe renal cell carcinomas, and oncocytomas, respectively. EMA was completely negative in the adrenal TMAs. In conclusion, SF-1 and EMA may be helpful in the differentiation of adrenal tumors from renal tumors in difficult cases.

  1. H-ras-transformed NRK-52E renal epithelial cells have altered growth, morphology, and cytoskeletal structure that correlates with renal cell carcinoma in vivo.

    Science.gov (United States)

    Best, C J; Tanzer, L R; Phelps, P C; Merriman, R L; Boder, G G; Trump, B F; Elliget, K A

    1999-04-01

    We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2, and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1 cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma, including mixed populations of sarcomatoid, granular, and clear cells. H/6.1 cells consistently showed more extensive alterations of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo, and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton.

  2. Mammary Tumor Development: Stromal-Epithelial Interactions in Oncogenesis.

    Science.gov (United States)

    1996-09-01

    to EGF (2). It is encoded by malignant fibroma virus (MV), which produces malignant tumors of fibroblasts. Epithelial proliferation overlies fibrosarco...expression of an epidermal growth factor related gene in Shope fibroma virus. Virol., 179:926-930, 1990. 3. Strayer, DS, Cabirac, GF, Sell, S, Leibowitz, JL...Malignant rabbit fibroma virus: Observa- tions on the cultural and histopathologic characteristics of a new virally-induced rabbit tumor. JNCI, 71:91

  3. Isolation, growth, and characterization of human renal epithelial cells using traditional and 3D methods.

    Science.gov (United States)

    Gildea, John J; McGrath, Helen E; Van Sciver, Robert E; Wang, Dora Bigler; Felder, Robin A

    2013-01-01

    The kidney is a highly heterogeneous organ that is responsible for fluid and electrolyte balance. Much interest is focused on determining the function of specific renal epithelial cells in humans, which can only be accomplished through the isolation and growth of nephron segment-specific epithelial cells. However, human renal epithelial cells are notoriously difficult to maintain in culture. This chapter describes the isolation, growth, immortalization, and characterization of the human renal proximal tubule cell. In addition, we describe new paradigms in 3D cell culture which allow the cells to maintain more in vivo-like morphology and function.

  4. Clinical utility of concurrent single-nucleotide polymorphism microarray on fresh tissue as a supplementary test in the diagnosis of renal epithelial neoplasms.

    Science.gov (United States)

    Hamilton, Heidi H; McDermott, Annie; Smith, M Timothy; Savage, Stephen J; Wolff, Daynna J

    2015-11-01

    The histologic and immunohistochemical variability of renal epithelial tumors makes classification difficult; with significant clinical implications, efforts to make the proper diagnoses are necessary. Single-nucleotide polymorphism (SNP) microarray analysis has been proposed as a supplementary study for the classification of renal epithelial neoplasms; however, its practical use in the routine clinical setting has not been explored. Surgical pathology cases that were classified histologically as renal epithelial tumor subtypes and had concurrent SNP microarray were retrospectively reviewed to correlate tumor morphology and SNP microarray results. Of the 99 cases reviewed, 88 (89%) had concordant histologic and microarray results. Four (4%) cases were unclassifiable by microarray due to uncharacteristic chromosomal abnormalities. Seven (7%) of the 99 cases had discordant microarray and histologic diagnoses, and following review of the histology, the diagnoses in two of these cases were subsequently changed. For most cases, concurrent SNP microarray confirmed the histologic diagnosis. However, discrepant microarray results prompted review of morphology and further ancillary studies, resulting in amendment of the final diagnosis in 29% of discrepant cases. SNP microarray analysis can be used to assist with the diagnosis of renal epithelial tumors, particularly those with atypical morphologic features. Copyright© by the American Society for Clinical Pathology.

  5. Calcifying epithelial odontogenic tumor (Pindborg tumor without calcification: A rare entity

    Directory of Open Access Journals (Sweden)

    Seema Kaushal

    2012-01-01

    Full Text Available The calcifying epithelial odontogenic tumor is a rare benign odontogenic tumor that was first described by Pindborg in 1955. It accounts for less than 1% of all odontogenic neoplasms. The tumor is characterized histologically by the presence of polygonal epithelial cells, calcification, and eosinophilic deposits resembling amyloid. Noncalcifying Pindborg tumor is very rare and only three cases have been documented in the English language literature so far. We present an additional case of noncalcifying Pindborg tumor and review the previously reported cases. Because noncalcifying Pindborg tumor is believed to be an aggressive variant, a definitive resection of the tumor with tumor-free surgical margins and long-term follow-up is recommended.

  6. Calcifying epithelial odontogenic tumor (Pindborg tumor) without calcification: A rare entity.

    Science.gov (United States)

    Kaushal, Seema; Mathur, Sandeep R; Vijay, Maneesh; Rustagi, Ankur

    2012-01-01

    The calcifying epithelial odontogenic tumor is a rare benign odontogenic tumor that was first described by Pindborg in 1955. It accounts for less than 1% of all odontogenic neoplasms. The tumor is characterized histologically by the presence of polygonal epithelial cells, calcification, and eosinophilic deposits resembling amyloid. Noncalcifying Pindborg tumor is very rare and only three cases have been documented in the English language literature so far. We present an additional case of noncalcifying Pindborg tumor and review the previously reported cases. Because noncalcifying Pindborg tumor is believed to be an aggressive variant, a definitive resection of the tumor with tumor-free surgical margins and long-term follow-up is recommended.

  7. Expression of Beta-Catenin and APC Protein in Ovarian Epithelial Tumor and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expression of beta-catenin, APC protein and its implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and APC protein in 48 cases of ovarian epithelial tumor. Results: The abnormal expression rates of beta-catenin in ovarian malignant and borderline epithelial tumors were higher than that in benign epithelial tumors. The expression of APC protein in benign epithelial tumors was significantly greater than that in malignant epithelial tumors. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors. Conclusion: Beta-catenin and APC protein have important effect on pathogenesis and development of ovarian epithelial tumors.

  8. Characterizing the interactions of organic nanoparticles with renal epithelial cells in vivo.

    Science.gov (United States)

    Nair, Anil V; Keliher, Edmund J; Core, Amanda B; Brown, Dennis; Weissleder, Ralph

    2015-01-01

    Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA-approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose- and time-dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in a dose-dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased, but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function, but changes in endocytosis-mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available.

  9. Carcinoid tumor with bilateral renal involvement in a child.

    Science.gov (United States)

    Warrier, Raj P; Varma, Aditi Vian; Chauhan, Aman; Ward, Ken; Craver, Randal

    2011-12-01

    Carcinoid tumors are uncommon in children. Kidneys are rarely involved as they do not possess neuro-endocrine cells. Work up of painless hematuria after abdominal trauma in a 10-year-old boy revealed primary carcinoid tumors with metastasis to both kidneys. We were unable to find any previous reports of renal involvement by carcinoid tumor in children.

  10. Primary renal primitive neuroectodermal tumor: A rare presentation

    Directory of Open Access Journals (Sweden)

    V Goel

    2015-01-01

    Full Text Available Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  11. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    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

  12. Gonadal vein tumor thrombosis due to renal cell carcinoma.

    Science.gov (United States)

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei

    2015-01-01

    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.

  13. 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.

  14. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study

    OpenAIRE

    2015-01-01

    Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC) profile of estrogen receptors (ER), progesterone receptors (PR), Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue ar...

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

    DEFF Research Database (Denmark)

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

    status: 1.2 (95%CI 1.0;1.3). Mean tumor size: 27 mm (95%CI 26;29). Mean follow-up time: 24 months (95%CI 20;27). A total of 16 patients (13%) were previously diagnosed with renal cancer and the majority of these patients had previously undergone nephrectomy. PADUA-score was found to be low or moderate......Background: Renal cryoablation is a valid treatment option for localized pT1a renal tumors and has been the modality of choice at Aarhus University Hospital since 2005. Anatomical tumor classification systems such as PADUA and RENAL scores were initially introduced as tools to evaluate complication...... 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...

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

    DEFF Research Database (Denmark)

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

    status: 1.2 (95%CI 1.0;1.3). Mean tumor size: 27 mm (95%CI 26;29). Mean follow-up time: 24 months (95%CI 20;27). A total of 16 patients (13%) were previously diagnosed with renal cancer and the majority of these patients had previously undergone nephrectomy. PADUA-score was found to be low or moderate......Background: Renal cryoablation is a valid treatment option for localized pT1a renal tumors and has been the modality of choice at Aarhus University Hospital since 2005. Anatomical tumor classification systems such as PADUA and RENAL scores were initially introduced as tools to evaluate complication...... 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...

  17. Radiographic study on oral malignant tumors of epithelial tissue origin

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seung Don; Kim, Jae Duck [Dept. of Oral Radiology, College of Dentistry, Chosun University, Kwangju (Korea, Republic of)

    1993-02-15

    The author analyzed the clinical and radiographic findings of 109 malignant tumors of epithelial origin occurred in the jaws of the patients visited the infirmaries of Dentistry, Chosun University and several university in Korea during 1978 to 1988. The observed results were as follows: 1. It appeared that 93% of the total 397 cases diagnosed as oral malignant tumors were squamous cell carcinomas. 2. The incidence ratios between nodular type and ulcer type were 4 to 1 in maxilla and 3 to 1 mandible. 3. In nearly 50% of all patients complained of pain due to impingement of tumor mass or ulcer. 4. Most of carcinomas of maxila eventually invaded into maxillary sinus and palate. 5. Characteristic features on the radiographs were the lesion with ill-defined border, the direct destruction of the alveolar bone and anatomical landmark without displacement of the involved teeth and the gray shadow of the tumor mass in the lesion.

  18. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Pooja S Naik

    2015-01-01

    Full Text Available Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC profile of estrogen receptors (ER, progesterone receptors (PR, Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue array was employed for cases subjected for IHC. The primary antibodies used were ER, PR, p53, and Ki-67. A correlation was attempted between histopathological and IHC findings. Results were subjected to statistical analysis. Software program "the primer of biostatistics 5.0" was used for calculation of interrelationships between the analyzed ER, PR, p53, and Ki-67 expression and histological factors by Pearson′s Chi-square test. The results were considered to be significant when the P < 0.05. Results: There were 110 cases of surface epithelial ovarian tumors (SEOT encountered over the period of 4 years. The expression of ER was more in malignant tumors (13/16, 81.25% than borderline (9/12, 75% and benign (20/82, 24.39%. As compared to ER, the expression of PR was more in benign (51/82, 62.19% than borderline (8/12, 66.67% and malignant tumors (9/16, 56.25%. The expression of PR was more in benign tumors than borderline and malignant tumors. However, this was not statistically significant (Chi-square = 0.335 with 2 degrees of freedom; P = 0.846. The expression of p53 was less in benign (5/82, 6.1% than borderline (9/12, 75% and malignant tumors (13/16, 81.25%. The expression of Ki-67 was more in malignant (4/82, 4.88% than borderline (10/12, 83.33% and benign tumors (15/16, 93.75%. In all the above cases, the difference was statistically significant (P < 0.05. There was statistically significant difference in the expression of ER, PR, p53, and Ki-67 in the patients with

  19. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  20. Expressions of Beta-catenin,E-cadherin and MMP-7 in Ovarian Epithelial Tumors

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2008-01-01

    Objective:To investigate the expressions of Beta-catenin,E-cadherin and MMP-7 and their implications in ovarian epithelial tumor.Methods:lmmunohistochemicai staining with SP method was conducted to identify the expressions of Beta-catenin,E-cadherin and MMP-7 in ovarian epithelial tumor in 66 cases.Results:The abnormal expression rate of Beta-catenin in malignant ovarian epithelial tumor was higher than those in borderline and benign epithelial tumors(P<0.05).The positive rates of E-cadherin in benign and borderline ovarian epithelial tumors were significantly greater than that in malignant epithelial tumor.The expression rates of MMP-7 in malignant and borderline ovarian epithelial tumors were higher than that in benign epithelial tumor(P<0.05).Conclusion:The abnormal expressions of Beta-catenin,E-cadherin and MMP-7 might be used to indicate the malignance transform of ovarian epithelial tumors,but they have no significant correlation with peritoneal dropsy invasion,caul invasion and appendant invasion in ovarian epithelial tumor.

  1. Calcifying epithelial odontogenic tumor: a clinico-radio-pathological dilemma.

    Science.gov (United States)

    Hada, M S; Sable, M; Kane, S V; Pai, Prathamesh S; Juvekar, S L

    2014-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasm of mandible in adults. The presentation of this entity is varied and often confused with a variety of mucosal and jaw lesions and clinical, radiological, and pathological feature of CEOT often-mimic malignancy. The objective of this report is to highlight the clinical features and radiological findings which should arouse suspicion of a benign lesion and importance of providing adequate clinical information to the pathologist to attain accurate diagnosis.We discussed two cases with tumors located in the maxilla. Both presented as expansile lesions with one biopsy proven squamous cell carcinoma. Both were pursued with clinico-radiological suspicion of benign lesions and confirmed with pathological correlation of histology and immunohistochemistry as CEOT. Therefore a High index of suspicion and clinico-radiological information are the key feature for diagnosis of this rare tumor.

  2. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

    Directory of Open Access Journals (Sweden)

    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  3. Cell cycle regulatory factors in juxta-tumoral renal parenchyma.

    Science.gov (United States)

    Petruşcă, Daniela Nicoleta; Petrescu, Amelia; Vrabie, Camelia; Niculescu, L; Jinga, V; Diaconu, Carmen; Braşoveanu, Lorelei

    2005-01-01

    The aim of this study was to evaluate regulatory cell cycle factors in juxta-tumoral renal parenchyma in order to obtain information regarding early primary changes occurred in normal renal cells. Specimens of juxta-tumoral renal parenchyma were harvested from the tumoral kidney in 10 patients with no history of treatment before surgery. The expression of p53, Bcl-2, Rb and PCNA was studied by immunohistochemical methods in paraffin-embedded tissues. The apoptotic status was evaluated by flow-cytometry analysis following propidium iodide incorporation. The p53 protein expression was recognized in most of the cases (80%) with different intensities. High intensity apoptotic process detected in juxta-tumoral parenchyma seemed to be p53 dependent and well correlated with the low Bcl-2 expression. 70% of cases were Rb positive. In this type of tissue Rb has only an anti-proliferative and anti-tumoral role. PCNA was present in half of the cases being low expressed due to the tissue regenerating mechanism. Our data suggest that the high intensity of programmed cell death in this type of tissue is supported by the status of cell regulatory factors that control this process. Previous studies have demonstrated that healthy renal tissue has neither apoptosis nor mitotic activity. Juxta-tumoral renal tissue is also displaying normal morphology and DNA content (diploidy) but the microenvironmental status induced by the tumor presence prompts cells to choose death rather than malignant transformation. Further studies are necessary to emphasize if these results have a clinical relevance for the outcome of therapeutical approaches in renal carcinomas.

  4. Adherence of uropathogenic Escherichia coli to human primary epithelial cells of renal pelvis

    Institute of Scientific and Technical Information of China (English)

    CHAO GU; JIN YING CHEN; MIN HOU; JING DONG HE; JI WU CHANG

    2006-01-01

    Human primary epithelial cells of renal pelvis was established to investigate the adherence of uropathogenic Escherichia coli (UPEC) to this cell line, in which the primary cell culture was performed by using cultivation of the normal epithelium of renal pelvis in keratinocyte serum free medium (K-SFM)with epidermal growth factor (EGF) and bovine pituitary extract (BPE). Both UPEC132 obtained from urine specimen of patients with pyelonephritis and the pilus-free representative strain E. coli K-12p678-54 were used to study the adherence of these strains on human primary epithelial cells of renal pelvis.The UPEC adherence was performed with observation on the morphological changes of the adhered cells,while the adhesion rates and indices were calculated in different times of experiment. In addition, the virulence genes hly and cnf1 of UPEC132 were detected by multiplex PCR assay. In this study, the human primary epithelial cells of renal pelvis was found to exhibit the character of the transitional epithelial cells. Compared with the control group, the adhesion rates and indices began to increase from 15 min of the experiment time and reached its peak in 120 min. The adhesion rate and index of UPEC132 to human primary epithelial cells of renal pelvis were 74.4% and 34.0 respectively. Many microscopic changes in the primary cells adhered with UPEC132 could be detected, such as rounding or irregularity in shape,unevenness in staining and the cytoplasmic and nuclear changes. It suggests that human primary epithelial cells of renal pelvis can be used for the experiment on UPEC adhesion, thus providing a basis for the further study on the pathogenesis of UPEC.

  5. Renal primitive neuroectodermal tumor: does age at diagnosis impact outcomes?

    Directory of Open Access Journals (Sweden)

    Mahkameh Zare

    2012-01-01

    Full Text Available Primitive n euroectodermal tumor (PNET of the kidney is a rare and highly malignant neoplasm. The median age for renal PNET is 27 years but it can be seen also in a wide age range between 3 and 78 years. We performed a Medline search for the term renal PNET and identified 79 cases up till December of 2010. We report here a new case of renal PNET and a literature review for published data for evaluation of clinicopathological prognostic factors, with an emphasis on prognosis in two groups of adults and children-adolescents: 18 years of age or under and over 18 years.

  6. Interactions of virulent and avirulent leptospires with primary cultures of renal epithelial cells

    DEFF Research Database (Denmark)

    Ballard, S A; Williamson, M; Adler, B

    1986-01-01

    A primary culture system for the cells of mouse renal-tubular epithelium was established and used to observe the adhesion of leptospires. Virulent strains of serovars copenhageni and ballum attached themselves to epithelial cells within 3 h of infection whereas an avirulent variant of serovar...... copenhageni did not adhere to epithelial cells at all within the experimental period of 24 h. The saprophytic Leptospira biflexa serovar patoc became attached non-specifically to inert glass surfaces as well as to the cells. The adhesion of leptospires to epithelial cells was not inhibited by homologous...

  7. 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.

  8. Hepatitis B virus X protein promotes renal epithelial-mesenchymal transition in human renal proximal tubule epithelial cells through the activation of NF-κB.

    Science.gov (United States)

    Li, Mei; Hu, Liping; Zhu, Fengxin; Zhou, Zhangmei; Tian, Jianwei; Ai, Jun

    2016-08-01

    Hepatitis B virus (HBV)-associated glomerulo-nephritis is the most common extra-hepatic disorder occurring with hepatitis B virus infection. In the present study, we hypothesized that HBV X protein (HBx) may play a critical role in renal interstitial fibrosis, as HBx has been shown to induce epithelial-mesenchymal transition (EMT) in renal cells. For this purpose, we successfully transfected HBx plasmid into human renal proximal tubule epithelial cells (HK-2 cells). We found that transfection with HBx plasmid significantly downregulated E-cadherin expression and upregulated α-smooth muscle actin, collagen I and fibronectin expression in a time- and concentration-dependent manner (at the lower concentrations and earlier time points). HBx also increased nuclear factor-κB (NF-κB) phosphorylation in a time- and concentration-dependent manner (again at the lower concentrations and earlier time points); however, it did not alter the phosphorylation of Smad2, Smad3, p38, phosphoinositide 3-kinase (PI3K) or extracellular signal-regulated kinase (ERK). Thus, the findings of this study demonstrate that HBx promotes EMT in renal HK-2 cells, and the potential underlying mechanisms may involve the activation of the NF-κB signaling pathway.

  9. 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 .

  10. Molecular markers and clinical behavior of uterine carcinosarcomas : focus on the epithelial tumor component

    NARCIS (Netherlands)

    de Jonge, Renske A; Nijman, Hans W.; Wijbrandi, Tera F.; Reyners, Anna K. L.; Boezen, H. Marike; Hollema, Harry

    2011-01-01

    Carcinosarcomas (malignant mixed Mullerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component and are considered as metaplastic endometrial carcinomas. This study evaluated molecular characteristics and clini

  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. HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.

    Science.gov (United States)

    Ross, Michael J; Fan, Cheng; Ross, Michael D; Chu, Te-Huatearina; Shi, Yueyue; Kaufman, Lewis; Zhang, Weijia; Klotman, Mary E; Klotman, Paul E

    2006-05-01

    HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-1 infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.

  13. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  14. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  15. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells.

    Science.gov (United States)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury.

  16. Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Jason Bennett

    2016-04-01

    Full Text Available Epithelial-mesenchymal transition (EMT, a process which describes the trans-differentiation of epithelial cells into motile mesenchymal cells, is pivotal in stem cell behavior, development and wound healing, as well as contributing to disease processes including fibrosis and cancer progression. Maintenance immunosuppression with calcineurin inhibitors (CNIs has become routine management for renal transplant patient, but unfortunately the nephrotoxicity of these drugs has been well documented. HK-2 cells were exposed to Tacrolimus (FK506 and EMT markers were assessed by RT PCR and western blot. FK506 effects on TGF-β mRNA were assessed by RT PCR and TGF-β secretion was measured by ELISA. The impact of increased TGF-β secretion on Smad signaling pathways was investigated. The impact of inhibition of TGF-β signaling on EMT processes was assessed by scratch-wound assay. The results presented in this study suggest that FK506 initiates EMT processes in the HK-2 cell line, with altered expression of epithelial and myofibroblast markers evident. Additionally, the study demonstrates that FK506 activation of the TGF-β/ SMAD pathways is an essential step in the EMT process. Overall the results demonstrate that EMT is heavily involved in renal fibrosis associated with CNI nephrotoxicity.

  17. Pathology of epithelial tumors & carcinoma in situ of bladder.

    Science.gov (United States)

    Mostofi, F K; Sesterhenn, I A

    1984-01-01

    We have reviewed the World Health Organization International Histological Classification of Tumors of Urinary Bladder. The classification recognizes papilloma as a distinct entity, which, although histologically benign, has a definite increased risk of progression to carcinoma. The classification further characterizes carcinomas of bladder in terms of certain features which have considerable influence on treatment, recurrence and prognosis. These are: the patterns of growth, the histology of the tumor, the grade, the pathological stage, the mode and location of spread, and the status of the remaining mucosa. We have called attention to the need for proper recognition of nonpapillary, noninvasive superficial mucosal lesions which have hitherto been dismissed as atypia and dysplasia. We have demonstrated that these lesions present a high risk for development of invasive carcinoma and recommended that the term "intraepithelial neoplasia" be employed and graded one to three to eliminate the use of terms atypia, dysplasia and CIS. We have emphasized the need for development of technics to demonstrate invasive and metastatic potential of epithelial tumors of bladder.

  18. Renal Cell Carcinoma Mimicking Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-01-01

    Full Text Available There are a variety of causes of adrenal pseudotumors on computerized tomography (CT scan, including upper-pole renal mass, gastric diverticulum, prominent splenic lobulation, pancreatic mass, hepatic mass, and periadrenal varices. We present a case of a large subhepatic mass that discrimination of its origin from neighborhood organs was difficult preoperatively. Our patient was a 58 years old man, that three months after an unsuccessful operation in another center for a pseudoadrenal mass underwent a very difficult subcapsular tumorectomy in our center.

  19. Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT in Renal and Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Anusha H. Tennakoon

    2015-12-01

    Full Text Available Epithelial to mesenchymal transition (EMT, particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis, the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs, as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data.

  20. Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

    Science.gov (United States)

    Tennakoon, Anusha H.; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-01-01

    Epithelial to mesenchymal transition (EMT), particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis), the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs), as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data. PMID:26729181

  1. Renal inflammatory myofibroblastic tumor - a new case report.

    Science.gov (United States)

    Petrescu, Amelia; Berdan, Gabriela; Hulea, Ionela; Gaitanidis, Raluca; Ambert, V; Jinga, V; Popescu, M; Andrei, F; Niculescu, L

    2007-01-01

    Renal inflammatory pseudotumor is uncommon, benign tumor that has been classified into separate group but there is a risk that this lesion could be misdiagnosed. The aim of this work is to report a new case of 57-years-old man presented in our hospital with hematuria, minimal grade fever and right flank pain. Magnetic resonance imaging (MRI) and sonography revealed a tumor of the right mediorenal parenchyma, 2.5 cm in diameter. The patient underwent right nephroureterectomy under the diagnosis of renal cell carcinoma. Macroscopically examination carried out on the removed kidney showed a 2/2/1.5 cm yellowish, gelatinous, well circumscribed, mediorenal and pericaliceal mass. Fragments of the tumor were fixed in 10% formaldehyde, included in paraffin, and the sections were stained with HE, VG and immunohistochemically with vimentin (VIM), MNF116, SyN, smooth muscle actin (ACT), desmin, CD68, S100, HMB45, and CD117. The histological examination revealed a compact spindle cell proliferation, a hypocellular fibrous area in an edematous myxoid background infiltrated by small lymphocytes, histiocytes, some plasma cells and small bone area. The spindle cells were diffuse positive for VIM, ACT, CD68 and negative for desmin, MNF116, SyN, S100, HMB45, and CD117. The pathologic diagnosis was renal inflammatory pseudotumor, raising the problem of differential diagnosis, as the clinical and imagistic aspects are similar to those of a renal carcinoma and the problem in establishing a preoperative correct diagnosis.

  2. Role of Stat3 Signaling in Control of EMT of Tubular Epithelial Cells During Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jingsong Liu

    2017-08-01

    Full Text Available Background/Aims: Transforming growth factor β 1 (TGFβ1 plays a critical role in the epithelial-to-mesenchymal transition (EMT of renal tubular epithelial cells (TECs during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. Methods: Expression of TGFβ1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFβ1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. Results: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFβ1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. Conclusion: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.

  3. Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

    Science.gov (United States)

    Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

    2016-11-18

    Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10(8) renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. A rare renal pelvis tumor: Mucinous cystadenocarcinoma

    Directory of Open Access Journals (Sweden)

    Gül Türkcü

    2015-03-01

    Full Text Available Urothelial carcinomas are the most common neoplasms in the renal pelvis. However mucinous cystadenocarcinomas (MCA are very rare in this localization. Although some theories are attributed on the patogenesis of MCA, its exact etiology is not known. Herein, we present histopathological characteristic of a case with MCA. Multiple cystic lesions and millimetric calculi with ectasia of the left kidney were detected by abdominal ultrasound and magnetic resonance imaging. Left simple nephrectomy was performed because of a pre-diagnosis of atrophic pyonephrotic kidney. The sections of the nephrectomized kidney revealed, multilocular mucinous cysts and histopathological appearance of MCA. We aimed to present this rare case mimicking atrophic cystic kidney with clinical, radiological findings, and histopathological characteristics in the lights of literature.J Clin Exp Invest 2015; 6(1: 78-80

  5. Current Concepts and Occurrence of Epithelial Odontogenic Tumors: I. Ameloblastoma and Adenomatoid Odontogenic Tumor

    Science.gov (United States)

    Kim, Yeon Sook

    2013-01-01

    Ameloblastomas and adenomatoid odontogenic tumors (AOTs) are common epithelial tumors of odontogenic origin. Ameloblastomas are clinico-pathologically classified into solid/multicystic, unicystic, desmoplastic, and peripheral types, and also divided into follicular, plexiform, acanthomatous, granular types, etc., based on their histological features. Craniopharyngiomas, derived from the remnants of Rathke's pouch or a misplaced enamel organ, are also comparable to the odontogenic tumors. The malignant transformation of ameloblastomas results in the formation of ameloblastic carcinomas and malignant ameloblastomas depending on cytological dysplasia and metastasis, respectively. AOTs are classified into follicular, extrafollicular, and peripheral types. Ameloblastomas are common, have an aggressive behavior and recurrent course, and are rarely metastatic, while AOTs are hamartomatous benign lesions derived from the complex system of the dental lamina or its remnants. With advances in the elucidation of molecular signaling mechanisms in cells, the cytodifferentiation of epithelial tumor cells in ameloblastomas and AOTs can be identified using different biomarkers. Therefore, it is suggested that comprehensive pathological observation including molecular genetic information can provide a more reliable differential diagnosis for the propagation and prognosis of ameloblastomas and AOTs. This study aimed to review the current concepts of ameloblastomas and AOTs and to discuss their clinico-pathological features relevant to tumorigenesis and prognosis. PMID:23837011

  6. A rare case of TFE-related pigmented renal tumor with overlapping features between melanotic Xp11 translocation renal cancer and Xp11 renal cell carcinoma with melanotic features.

    Science.gov (United States)

    Cardili, Leonardo; Wrublevsky Pereira, Gregório; Viana, Cristiano Ribeiro

    2017-02-16

    In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3-related pigmented renal tumor showing unusual immunoexpression of cytokeratins (AE1/AE3) and renal cell carcinoma markers (RCC, CD10). Cathepsin-K and Vimentin were diffusely positive whereas melanocytic markers (HMB-45 and Melan-A) displayed weak and patchy expression. We found no labelling for PAX-8, muscle markers (desmin, smooth muscle actin, muscle-specific actin and caldesmon) and S-100. TFE3 fusion was confirmed by break-apart fluorescence in situ hybridization (FISH). This case corroborates previous evidence for overlap in the TFE3-associated cancer family and illustrates that it may not be possible to set a clear cutoff between epithelial (XRCCM) and mesenchymal (MXTRC) subgroups.

  7. Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury

    Institute of Scientific and Technical Information of China (English)

    冯娟

    2013-01-01

    Objective To explore the mechanism of protecting cells from hypoxia/reoxygenation(H/R) injury by constructing specific small interference RNA(siRNA) to inhibit NALP3 expression in rat renal tubular epithelial

  8. Renal Function Recovery after Nephrectomy or Nephron-Sparing Surgery in Children with Unilateral Renal Tumor.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Cozzi, Francesco

    2017-02-01

    Introduction Children with unilateral renal tumor (URT) and preoperative renal dysfunction (PRD) may benefit from nephron-sparing surgery (NSS). To test this hypothesis, we studied the outcome of baseline renal function after nephrectomy or NSS among children with URT. Materials and Methods Retrospective records review of children with URT who underwent nephrectomy (25 children) or NSS (11 children) at our institution. We analyzed the estimated glomerular filtration rate (eGFR) changes over time among patients, stratified by both preoperative renal function (with or without PRD) and surgical extent (NSS vs. nephrectomy). The primary end point was evaluation of compensatory recovery of preoperative eGFR after surgery. Only children older than 2 years at surgery were included in the study. Renal dysfunction was defined as an eGFR  100 mL/min/1.73 m(2), respectively, achieved or maintained two-kidney eGFR values (T-KEV) (p = 0.01). After NSS, four adolescent patients with PRD and seven without PRD achieved or maintained T-KEV. Conclusion The majority of children with URT and low baseline eGFR present with an impaired renal function recovery after nephrectomy and may benefit from NSS. Collaborative studies are needed to support present findings. Georg Thieme Verlag KG Stuttgart · New York.

  9. Investigation of cadmium toxicity on renal epithelial cells using nuclear microprobe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Khodja, Hicham E-mail: khodja@drecam.cea.fr; Avoscan, Laure; Carriere, Marie; Carrot, Francine; Gouget, Barbara

    2003-09-01

    Cadmium is a highly toxic metal that causes well-known severe renal damages. Its toxicity is frequently investigated in vitro using numerous epithelial models. The accumulation and transport of cadmium in cultured renal epithelial cells has been studied by means of nuclear microscopy (micro-PIXE coupled with micro-RBS) for cell monolayer analyses, and by ICP-MS for culture medium analyses. Cell viability, measured by biochemical tests, was used as toxicity indicator. Dependence on cadmium concentration (1-100 {mu}M) and exposure time (1-24 h) was found. Micro-PIXE reveals a strong anti-correlation of intra-cellular cadmium concentration with zinc concentration, a biological metal, suggesting substitution mechanism of both metals.

  10. 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

    Objective: The diagnostic accuracy of in-bench core biopsies (CBs) from renal masses, and the interobserver and intraobserver variability in pathological subtyping of renal tumors were assessed. Methods: We performed two CBs in 62 consecutive renal masses suspected for renal cell carcinoma (RCC...

  11. Endothelial protein C receptor in renal tubular epithelial cells and ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... placenta, heart, liver and lung endothelial cell. However, there ... The effects of some reagents (high glucose, tumor necrosis factor–α and interleukin-1β) were measured by .... functional domains, including N terminal signal peptide ..... endothelial cell protein C receptor (EPCR) 23bp insert in patients with.

  12. Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

    Science.gov (United States)

    Shapiro, Mark; Korst, Robert J

    2014-01-14

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

  13. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    NARCIS (Netherlands)

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypoth

  14. The Impact of Ethnicity-Dependent Differences in Breast Epithelial Hierarchy on Tumor Incidence and Characteristics

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0707 TITLE: The Impact of Ethnicity-Dependent Differences in Breast Epithelial Hierarchy on Tumor Incidence and...3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE The Impact of Ethnicity-Dependent Differences in Breast Epithelial Hierarchy on...Accomplishments: Specific Aim 1: To demonstrate that differences in normal breast epithelial hierarchy between African American and Caucasian

  15. Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells.

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    Damien Maggiorani

    Full Text Available Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2 were subjected to FSS (0.5 Pa for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1, Par polarity complex (Pard6, adherens junctions (E-Cadherin, β-Catenin and the primary cilium (α-acetylated Tubulin were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and β-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E-cadherin and β-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium.

  16. Interaction between submicron COD crystals and renal epithelial cells

    Directory of Open Access Journals (Sweden)

    Peng H

    2012-08-01

    Full Text Available Hua Peng1,2 Jian-Ming Ouyang1,2 Xiu-Qiong Yao1, Ru-E Yang11Department of Chemistry, Jinan University, 2Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou, ChinaObjectives: This study aims to investigate the adhesion characteristics between submicron calcium oxalate dihydrate (COD with a size of 150 ± 50 nm and African green monkey kidney epithelial cells (Vero cells before and after damage, and to discuss the mechanism of kidney stone formation.Methods: Vero cells were oxidatively injured by hydrogen peroxide to establish a model of injured cells. Scanning electron microscopy was used to observe Vero–COD adhesion. Inductively coupled plasma emission spectrometry was used to quantitatively measure the amount of adhered COD microcrystals. Nanoparticle size analyzer and laser scanning confocal microscopy were performed to measure the change in the zeta potential on the Vero cell surface and the change in osteopontin expression during the adhesion process, respectively. The level of cell injury was evaluated by measuring the changes in malonaldehyde content, and cell viability during the adhesion process.Results: The adhesion capacity of Vero cells in the injury group to COD microcrystals was obviously stronger than that of Vero cells in the control group. After adhesion to COD, cell viability dropped, both malonaldehyde content and cell surface zeta potential increased, and the fluorescence intensity of osteopontin decreased because the osteopontin molecules were successfully covered by COD. Submicron COD further damaged the cells during the adhesion process, especially for Vero cells in the control group, leading to an elevated amount of attached microcrystals.Conclusion: Submicron COD can further damage injured Vero cells during the adhesion process. The amount of attached microcrystals is proportional to the degree of cell damage. The increased amount of microcrystals that adhered to the injured epithelial

  17. Tumor-infiltrating Cytotoxic T Lymphocytes as Independent Prognostic Factor in Epithelial Ovarian Cancer With Wilms Tumor Protein 1 Overexpression

    NARCIS (Netherlands)

    Vermeij, Renee; de Bock, Geertruida H.; Leffers, Ninke; ten Hoor, Klaske A.; Schulze, Ute; Hollema, Harry; van der Burg, Sjoerd H.; van der Zee, Ate G. J.; Daemen, Toos; Nijman, Hans W.

    2011-01-01

    Immune response characterization at the primary tumor site enables the design of therapeutic vaccination strategies with higher efficacy in epithelial ovarian cancer (EOC). In this study, we related Wilms tumor protein 1 (WT1) overexpression, a well-established immunotherapeutic target, to clinicopa

  18. 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

    The diagnostic problems in the subtyping of renal tumors were evaluated by a panel of five pathologists studying a set of selected tumors. Five pathologists independently assessed a single hematoxylin-and-eosin (HE)-stained slide from 28 selected renal tumors. After this independent assessment...

  19. Distinct mesenchymal alterations in N-cadherin and E-cadherin positive primary renal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Christof Keller

    Full Text Available BACKGROUND: Renal tubular epithelial cells of proximal and distal origin differ markedly in their physiological functions. Therefore, we hypothesized that they also differ in their capacity to undergo epithelial to mesenchymal alterations. RESULTS: We used cultures of freshly isolated primary human tubular cells. To distinguish cells of different tubular origin we took advantage of the fact that human proximal epithelial cells uniquely express N-cadherin instead of E-cadherin as major cell-cell adhesion molecule. To provoke mesenchymal alteration we treated these cocultures with TGF-β for up to 6 days. Within this time period, the morphology of distal tubular cells was barely altered. In contrast to tubular cell lines, E-cadherin was not down-regulated by TGF-β, even though TGF-β signal transduction was initiated as demonstrated by nuclear localization of Smad2/3. Analysis of transcription factors and miRNAs possibly involved in E-cadherin regulation revealed high levels of miRNAs of the miR200-family, which may contribute to the stability of E-cadherin expression in human distal tubular epithelial cells. By contrast, proximal tubular epithelial cells altered their phenotype when treated with TGF-β. They became elongated and formed three-dimensional structures. Rho-kinases were identified as modulators of TGF-β-induced morphological alterations. Non-specific inhibition of Rho-kinases resulted in stabilization of the epithelial phenotype, while partial effects were observed upon downregulation of Rho-kinase isoforms ROCK1 and ROCK2. The distinct reactivity of proximal and distal cells was retained when the cells were cultured as polarized cells. CONCLUSIONS: Interference with Rho-kinase signaling provides a target to counteract TGF-β-mediated mesenchymal alterations of epithelial cells, particularly in proximal tubular epithelial cells. Furthermore, primary distal tubular cells differed from cell lines by their high phenotypic stability

  20. Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.

    Science.gov (United States)

    Ramkumar, Nirupama; Stuart, Deborah; Mironova, Elena; Bugay, Vladislav; Wang, Shuping; Abraham, Nikita; Ichihara, Atsuhiro; Stockand, James D; Kohan, Donald E

    2016-07-01

    The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 mo of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+) excretion and investigated the signaling mechanisms by which PRR regulates Na(+) balance. No detectable differences in BP were observed between control and PRR KO mice fed normal- or low-Na(+) diets. However, compared with controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+) balance with normal- and low-Na(+) intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+) retention following angiotensin II (ANG II) infusion. Furthermore, PRR KO mice had significantly lower epithelial Na(+) channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT1, ERK1/2, or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+) wasting and reduces the hypertensive response to ANG II.

  1. Investigation of recurrent deletion loci specific to conventional renal cell carcinoma by comparative allelotyping in major epithelial carcinomas

    Directory of Open Access Journals (Sweden)

    Rashmi R Bhat (Singh

    2012-01-01

    Full Text Available Objective: Loss of heterozygosity (LOH studies were undertaken to investigate the consistently deleted loci/? tumor suppressor gene loci (TSG on 3p in conventional renal cell carcinoma (cRCC. Materials and Methods: LOH studies were performed by polymerase chain reaction (PCR using 15 micro satellite markers mapped in region 3p12-p26 on 40 paired cRCC tumors and normal kidney at Stages I-IV. Simultaneously, fluorescent in-situ hybridization (FISH studies were performed to investigate the allelic deletion of fragile histidine triad (FHIT. Results: Our studies revealed three affected regions; 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 with differential frequencies in Group I (Stage I and II and Group II (Stage III and IV. Incidence for D3S1234 (FHIT locus and D3S2454 (3p13 was 75% and 83% in Group I and II, respectively. Comparative allelotyping in epithelial malignancies like lung, bladder, and breast tumors revealed LOH (frequency 14−20% only in breast tumors for D3S2406, D3S1766 (distal to FHIT, and D3S1560 (distal to VHL, Von-Hippal Lindau. FISH using FHIT gene probe revealed deletions in cRCC (88%, breast (30%, and lung tumors (10% with no deletions in bladder tumors and leukemias, signifying the importance of FHIT in the pathogenesis of tumors of epithelial origin. Conclusion: Our findings suggested FHIT deletion as an early and VHL deletion as an early and/or late event in cRCC. Additionally, studies also disclosed the recurrent deletions of flanking loci to FHIT and VHL in cRCC. The dilemma of interstitial or continuous deletion on 3p needs to be resolved by implementation of latest sensitive molecular techniques that would further help to narrow down search for TSG loci specific to cRCC, other than VHL and FHIT.

  2. Clear cell renal cell tumors: Not all that is "clear" is cancer.

    Science.gov (United States)

    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy.

  3. Chronic kidney disease in children with unilateral renal tumor.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Schiavetti, Amalia; Cozzi, Francesco

    2012-05-01

    In patients who have undergone nephrectomy lower stage chronic kidney disease may develop, which is an independent risk factor for cardiovascular disease and overall mortality. We investigated whether the prevalence of lower stage chronic kidney disease is related to the amount of renal parenchyma excised in children with unilateral renal tumor. A total of 15 patients treated with nephrectomy and 10 treated with nephron sparing surgery were enrolled at a single academic center. The Kidney Disease Outcomes Quality Initiative guidelines were used to classify patients by chronic kidney disease stage based on estimated glomerular filtration rate values. The Modification of Diet in Renal Disease study equation and Schwartz equation were used in patients older and younger than 17 years, respectively. At a mean followup of more than 12 years 8 patients who had undergone nephrectomy and 1 treated with bilateral nephron sparing surgery presented with stage II chronic kidney disease (estimated glomerular filtration rate 60 to 89 ml/min/1.73 m(2)). Sequential measurements from diagnosis to 12 to 17 years postoperatively showed that stage II chronic kidney disease in patients who had undergone nephrectomy manifested as a negligible postoperative increase in mean ± SD estimated glomerular filtration rate (75.7 ± 25.5 vs 79.4 ± 3.9 ml/min/1.73 m(2), p = 0.6). Five of the 8 patients presented with stage II chronic kidney disease even before nephrectomy. The other 7 patients who had undergone nephrectomy and those treated with nephron sparing surgery presented with a significant postoperative increase in mean ± SD estimated glomerular filtration rate (81.1 ± 24 vs 102.3 ± 3 ml/min/1.73 m(2), p = 0.02, and 88.7 ± 2 vs 107.4 ± 14 ml/min/1.73 m(2), p = 0.005, respectively). A subset of children with unilateral renal tumor presents before and/or after nephrectomy, and not after nephron sparing surgery, with stage II chronic kidney disease, probably due to a reduced renal

  4. Lin28 sustains early renal progenitors and induces Wilms tumor.

    Science.gov (United States)

    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

    2014-05-01

    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.

  5. Mixed epithelial and stromal tumor of the kidney (MEST) simulating an upper tract TCC.

    Science.gov (United States)

    Sountoulides, Petros; Koptsis, Michail; Metaxa, Linda; Theodosiou, Alexandros; Kikidakis, Dimitrios; Filintatzi, Chrysa; Paschalidis, Konstantinos

    2012-02-01

    We present a rare and interesting case of a mixed epithelial and stromal tumour (MEST) of the kidney. The case is unique as it involves a male patient with no history of hormonal therapy presenting with a filling defect in the renal collecting system and positive urine cytology. The patient was diagnosed with transitional cell carcinoma of the renal pelvis and subjected to nephroureterectomy, which revealed a solid tumour arising from the lower calyces and extending into the renal pelvis and upper ureter. Pathology revealed a MEST. The patient was disease-free at the 6-month follow-up.

  6. Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells.

    Science.gov (United States)

    Song, Jingyuan; Chen, Xiao; Bai, Jin; Liu, Qinghua; Li, Hui; Xie, Jianwan; Jing, Hui; Zheng, Junnian

    2016-08-01

    Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray. The function of DDR1 was then evaluated in vitro using collagen I and DDR1 small interfering RNA (siRNA) to regulate the expression of DDR1 in OS-RC-2 and ACHN renal cancer cells (RCC). DDR1 expression correlated with increased RCC cell migration, invasion, and angiogenesis. Further study revealed that high expression of DDR1 can result in epithelial to mesenchymal transition (EMT) activation. Western blot assay showed that the N-cadherin protein and vimentin were induced while E-cadherin was reduced after DDR1 over expression. Our results suggest that DDR1 is both a prognostic marker for RCCC and a potential functional target for therapy.

  7. Mixed epithelial-stromal tumor (MEST) of seminal vesicle: a proposal for unified nomenclature.

    Science.gov (United States)

    Reikie, Brian A; Yilmaz, Asli; Medlicott, Shaun; Trpkov, Kiril

    2015-03-01

    In contrast to the common tumors of the prostate, seminal vesicle demonstrates low potential for neoplastic proliferation. Of the rare primary seminal vesicle tumors, adenocarcinoma is the most common, but there are also rare seminal vesicle neoplasms which demonstrate epithelial and stromal components. These neoplasms have been described in the literature under various names, including "epithelial-stromal tumor," "cystic epithelial-stromal tumor," "cystadenoma," "cystomyoma," "mesenchymoma," "Müllerian adenosarcoma-like tumor," "phyllodes tumor," and "cystosarcoma phyllodes." The spectrum of reported mixed epithelial-stromal tumors (MEST) of seminal vesicle encompasses low, intermediate and high-grade tumors, but the precise distinction and nomenclature for these tumors remain unsettled. We propose a common nomenclature for these tumors, based on the review of published cases and 2 index cases from our practice, which represent the low-grade category. The first patient was 46 years old and presented with seminal vesicle neoplasm detected on routine rectal examination. The neoplasm measured 4 cm in greatest dimension, and completely replaced the left seminal vesicle. The tumor was circumscribed and consisted of multiple cysts separated by spindle-cell stroma. The second patient was a 60-year-old man, who had an incidental seminal vesicle neoplasm, which was discovered when he underwent a radical prostatectomy for a prostatic adenocarcinoma, (Gleason score 3+4, stage 3a). Both neoplasms contained hypercellular stroma, which was composed of uniform spindle cells, arranged in fascicles and interspersed between the glands. Both tumors lacked worrisome morphology, such as infiltrative borders, cell atypia, increased mitotic activity, hemorrhage, and necrosis. The stromal cells were reactive for estrogen and progesterone receptors, and desmin. The cysts and dilated glands were lined by epithelial cells, which were positive for cytokeratin 7 and were negative for

  8. Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification

    Directory of Open Access Journals (Sweden)

    Nicastri A.L.

    2002-01-01

    Full Text Available The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP was evaluated by rhodamine fluorescence. Renal cells (MDCK were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss. Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000. Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism.

  9. Histopathological evaluation of surgically treated adult renal tumors: Report from a tertiary care center in India

    Directory of Open Access Journals (Sweden)

    B Datta

    2016-01-01

    Full Text Available Background: This retrospective study was performed in a tertiary care center from India analyzing the histopathological reports and the clinical data of the adult patients admitted in this institute with a diagnosis of renal tumors and had undergone nephrectomy for the disease. Objective: The objective of this study is to determine the relative frequencies of different renal tumors in adults (above the age of 16 years and to analyze the histopathological characters of the tumors. Materials and Methods: In this retrospective study, we have analyzed the histopathology reports along with the demographic and clinical data of the adult patients who had undergone nephrectomy for renal tumors in our institute from January 2005 to December 2011. Results: A total 113 adult patients underwent tumor nephrectomy during the last 7 years in our institute. Mean age of the patients was 54.5 years (range 16-69 years. Male:Female ratio was 1.9:1. Out of 131 cases of adult renal tumors, 91.6% cases were malignant and 8.45 cases were benign tumors. Among the malignant tumors, renal cell carcinoma was the most common type. There were 2 cases of renal primitive neuroectodermal tumors and one case of renal myofibroblastoma in our series. Conclusion: The spectrum of adult renal tumors in this series is consistent with the other series of cases reported by different authors. Only few cases of the renal tumors were diagnosed incidentally among our patients which is just opposite to the rate of renal tumors diagnosed incidentally in the developed countries. Myofibroblastoma, a benign kidney tumor diagnosed in our series is probably the first reported case in the world.

  10. The tumor microenvironment: An irreplaceable element of tumor budding and epithelial-mesenchymal transition-mediated cancer metastasis.

    Science.gov (United States)

    Li, Hui; Xu, Fangying; Li, Si; Zhong, Anjing; Meng, Xianwen; Lai, Maode

    2016-07-03

    Tumor budding occurs at the invasive front of cancer; the tumor cells involved have metastatic and stemness features, indicating a poor prognosis. Tumor budding is partly responsible for cancer metastasis, and its initiation is based on the epithelial-mesenchymal transition (EMT) process. The EMT process involves the conversion of epithelial cells into migratory and invasive cells, and is a profound event in tumorigenesis. The EMT, associated with the formation of cancer stem cells (CSCs) and resistance to therapy, results from a combination of gene mutation, epigenetic regulation, and microenvironmental control. Tumor budding can be taken to represent the EMT in vivo. The EMT process is under the influence of the tumor microenvironment as well as tumor cells themselves. Here, we demonstrate that the tumor microenvironment dominates EMT development and impacts cancer metastasis, as well as promotes CSC formation and mediates drug resistance. In this review, we mainly discuss components of the microenvironment, such as the extracellular matrix (ECM), inflammatory cytokines, metabolic products, and hypoxia, that are involved in and impact on the acquisition of tumor-cell motility and dissemination, the EMT, metastatic tumor-cell formation, tumor budding and CSCs, and cancer metastasis, including subsequent chemo-resistance. From our point of view, the tumor microenvironment now constitutes a promising target for cancer therapy.

  11. Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts in the tumor microenvironment

    DEFF Research Database (Denmark)

    De Neergaard, Michala; Kim, Jiyoung; Villadsen, René

    2010-01-01

    Tumor cells can activate stroma, yet the implication of this activation in terms of reciprocal induction of gene expression in tumor cells is poorly understood. Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene originally isolated from heterotypic recombinant cultures of hu...

  12. Proximal tubule epithelial cell specific ablation of the spermidine/spermine N1-acetyltransferase gene reduces the severity of renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Kamyar Zahedi

    Full Text Available BACKGROUND: Expression and activity of spermidine/spermine N1-acetyltransferase (SSAT increases in kidneys subjected to ischemia/reperfusion (I/R injury, while its ablation reduces the severity of such injuries. These results suggest that increased SSAT levels contribute to organ injury; however, the role of SSAT specifically expressed in proximal tubule epithelial cells, which are the primary targets of I/R injury, in the mediation of renal damage remains unresolved. METHODS: Severity of I/R injury in wt and renal proximal tubule specific SSAT-ko mice (PT-SSAT-Cko subjected to bilateral renal I/R injury was assessed using cellular and molecular biological approaches. RESULTS: Severity of the loss of kidney function and tubular damage are reduced in PT-SSAT-Cko- compared to wt-mice after I/R injury. In addition, animals treated with MDL72527, an inhibitor of polyamine oxidases, had less severe renal damage than their vehicle treated counter-parts. The renal expression of HMGB 1 and Toll like receptors (TLR 2 and 4 were also reduced in PT-SSAT-Cko- compared to wt mice after I/R injury. Furthermore, infiltration of neutrophils, as well as expression of tumor necrosis factor-α (TNF-α, monocyte chemoattractant protein-1 (MCP-1 and interleukin-6 (IL-6 transcripts were lower in the kidneys of PT-SSAT-Cko compared to wt mice after I/R injury. Finally, the activation of caspase3 was more pronounced in the wt compared to PT-SSAT-Cko animals. CONCLUSIONS: Enhanced SSAT expression by proximal tubule epithelial cells leads to tubular damage, and its deficiency reduces the severity of renal I/R injury through reduction of cellular damage and modulation of the innate immune response.

  13. Large calcifying epithelial odontogenic tumor with extension into the maxillary sinus: a case report.

    Science.gov (United States)

    da Rosa, Marize Raquel Diniz; de Oliveira, James Maxwell Souza; Dias-Ribeiro, Eduardo; Ferreira-Rocha, Julierme; de Barros, Iolanda Maria Cariry Carvalho Lacet; Lopes, Patricia de Medeiros Loureiro

    2011-01-01

    Calcifying epithelial odontogenic tumor (CEOT) is a rare, locally invasive neoplasm characterized by the presence of amyloid material that can become calcified. It often is found in the posterior region of the mandible. Such tumors in the maxilla and those that invade the maxillary sinus are extremely rare. This article presents the sixth reported clinical case of a CEOT that invaded the maxillary sinus and extended to the interior of the nasal cavity. The tumor had grown toward the sinus roof, but there was no association with an impacted tooth. Histopathologically, the tumor was composed of plates of polyhedral epithelial cells with highly eosinoplilic cytoplasm, nuclear polymorphism, clear-cell contours, and intercellular bridges in fibrous conjunctive tissue. Amorphous eosinophilic material and diverse calcifications permeated the epithelial cells.

  14. Effects of uric acid on mitochondrial oxidative damage and apoptosis in human renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    张涛

    2014-01-01

    Objective To observe the effects of uric acid(UA)on mitochondrial oxidative damage and apoptosis in renal tubular epithelial cells(HK-2),and investigate the possible mechanism.Methods HK-2 cells were exposed to UA(480μmol/L,720μmol/L)for different time(0 h,24 h,48 h)in vitro.The mitochondrial ROS production was detected by Mito SOX staining.The mitochondrial membrane potential was measured by JC-1 staining.The expressions of prohibitin and AIF were examined by Western blotting and immunofluorescence cytochemistry.

  15. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells. Henning F. Bjerregaard, Roskilde University, Department of Science, Systems and Models , 4000 Roskilde, Denmark. HFB@ RUC.DK Reactive oxygen species (ROS) like, hydrogen...... to G-protein stimulation of phospholipase C and release of inositol -3 phosphate. Cd (0.4 mM) treatment of A6 cells enhanced the ROS production after one minutes incubation. The production rate was constant for at least 10 to 20 min. Experiments showed that the Cd induced increase in ROS production...

  16. Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells

    Directory of Open Access Journals (Sweden)

    Florian Kopp

    2014-12-01

    Full Text Available Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC–specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition.

  17. Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells.

    Science.gov (United States)

    Kopp, Florian; Hermawan, Adam; Oak, Prajakta Shirish; Ulaganathan, Vijay Kumar; Herrmann, Annika; Elnikhely, Nefertiti; Thakur, Chitra; Xiao, Zhiguang; Knyazev, Pjotr; Ataseven, Beyhan; Savai, Rajkumar; Wagner, Ernst; Roidl, Andreas

    2014-12-01

    Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC)-specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition.

  18. Early Alterations in Ovarian Surface Epithelial Cells and Induction of Ovarian Epithelial Tumors Triggered by Loss of FSH Receptor

    Directory of Open Access Journals (Sweden)

    Xinlei Chen

    2007-06-01

    Full Text Available Little is known about the behavior of the ovarian surface epithelium (OSE, which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and plateletderived growth factor receptors α and β in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

  19. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case.

    Science.gov (United States)

    Badrashetty, Dinesh; Rangaswamy, Shruthi; Belgode, Niranjan

    2013-09-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  20. Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation

    DEFF Research Database (Denmark)

    Eichenlaub, Teresa; Cohen, Stephen M; Herranz, Héctor

    2016-01-01

    Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechan......Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging....... The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells...... of the Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms...

  1. Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Jian Fei; Ying Chen; Bing Zhao; Zhi-Tao Yang; Lu Wang; Hui-Qiu Sheng

    2016-01-01

    Background:The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases,but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown.The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).Methods:A Sprague-Dawley rat HS model was established in vivo in this study.The expression level and location of DC-SIGN were observed in kidneys.Also,the degree of histological damage,the concentrations of tumor necrosis factor-α and interleukin-6 in the renal tissues,and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group),with or without VitC treatment before resuscitation,were evaluated.Results:HS induced DC-SIGN expression in rat tubular epithelial cells.The proinflammatory cytokine concentration,histological damage scores,and functional injury of kidneys had increased.All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.Conclusions:The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN,and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly.The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

  2. Composite renal cell carcinoma with clear cell renal cell carcinomatous and carcinoid tumoral elements: a first case report.

    Science.gov (United States)

    Bressenot, A; Delaunay, C; Gauchotte, G; Oliver, A; Boudrant, G; Montagne, K

    2010-02-01

    Renal endocrine tumours are extremely rare, and carcinoid tumoral elements in renal cell carcinoma have never been reported. This is the first report of a composite renal cell carcinoma containing a clear cell renal cell carcinoma associated with carcinoid tumoral elements, in a patient with synchronous metastatic disease. In the absence of specific radiological and clinical manifestations, typical morphological features as well as an immunostaining profile of neuroendocrine differentiation were identified by microscopy. Secondary nodal and liver localisations were characterised by carcinoid elements only. Despite antiangiogenic therapy, liver metastasis progressed, suggesting that adjuvant therapy cannot be based on the presence of the clear cell renal cell carcinoma component. In this context, extensive tissue sampling is recommended to reveal the endocrine component that is the most aggressive element of such a composite carcinoma.

  3. Ossifying renal tumor of infancy: findings at ultrasound, CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hwan; Choi, Young Hun; Kim, Woo Sun; Cheon, Jung-Eun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Moon, Kyung Chul [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of)

    2014-05-15

    A 4-month-old boy presented with persistent gross hematuria. At ultrasonography, a 3.5-cm echogenic mass with posterior shadowing and tumor vascularity was detected within the right renal pelvis. Precontrast CT showed a slightly hyperattenuating mass in the renal pelvis. At MRI the mass was heterogeneously hypointense on T2-weighted images and isointense on T1-weighted images. Contrast-enhanced CT and MRI both revealed peripheral enhancement of the mass. A histological diagnosis of ossifying renal tumor of infancy was made after open pyelostomy and tumor enucleation. We suggest that ossifying renal tumor of infancy should be considered when a mass with posterior acoustic shadowing and tumor vascularity on US, hyperattenuation on precontrast CT and hypointensity on T2-weighted MRI is seen within the renal pelvis of an infant with hematuria. (orig.)

  4. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer

    OpenAIRE

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-01-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormal...

  5. Expression of Wnt-1,beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; HU Zhuo-ying

    2008-01-01

    Objective:To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods:Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1,beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results:The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell(P<0.05).The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell(P<0.05).A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor(P<0.05).A significant difierence of expressions of Beta-catenin and C-myc was found between serous and mutinous tumors (P<0.05). Conclusion:The abnormal expression of Wnt-1,beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.

  6. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    Science.gov (United States)

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

  7. Akt2 is involved in loss of epithelial cells and renal fibrosis following unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Aiping Lan

    Full Text Available Obstructive nephropathy is an aggressive form of chronic kidney disease (CKD, which is characterized by an epithelial-to-mesenchymal transition (EMT and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we investigated the contribution of Akt2 to experimental renal EMT and fibrosis using the well-established model of unilateral ureteral obstruction (UUO. We found that Akt2 and phosphor (p-Akt protein levels were increased in the obstructed kidneys. UUO induced activation of transforming growth factor-β1 (TGF-β1 signaling. Importantly, knockout of Akt2 suppressed UUO-induced EMT, kidney fibrosis, increased GSK3β activity, and decreased expression of Snail and β-catenin. Inhibition of GSK3β with LiCl (the inhibitor of GSK3β increased the expression of Snail and β-catenin in cultured kidney epithelial cells. Our findings suggest that Akt2 partially contributes to interstitial fibrosis following UUO and that inhibition of this signaling pathway may provide a novel approach of prevent progression of renal fibrosis.

  8. The Effect of Connective Tissue Growth Factor on Human Renal Tubular Epithelial Cell Transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    张春; 朱忠华; 邓安国

    2004-01-01

    To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of α-smooth muscle actin (α-SMA) were assessed by indirect immuno-fluorescence, and the percentage of α-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of α-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of α-SMA were markedly stronger than that in negative controls. The percentages of α-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9 %, 65.5 % vs 2.4 %, P<0.01) . α-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).

  9. Benign phyllodes tumor with tubular adenoma-like epithelial component in FNAC: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Kishori M Panda

    2016-01-01

    Full Text Available Benign phyllodes tumor (BPT is a biphasic neoplasm composed of bland stromal and epithelial elements. Cytologic diagnostic criteria of BPT, though documented in the literature, diagnostic pitfalls in fine-needle aspiration cytology (FNAC may occur due to sampling error, high cellularity, ductal hyperplasia, paucity of stromal component, and occasional dissociation of epithelial cells. Here, we describe a case of BPT diagnosed by histology in a 19-year-old female, where FNAC features were inconclusive due to paucity of stromal component, predominance of tubular adenoma-like epithelial component, and due to the presence of other overlapping features with fibroadenoma.

  10. Benign phyllodes tumor with tubular adenoma-like epithelial component in FNAC: A diagnostic pitfall

    Science.gov (United States)

    Panda, Kishori M

    2016-01-01

    Benign phyllodes tumor (BPT) is a biphasic neoplasm composed of bland stromal and epithelial elements. Cytologic diagnostic criteria of BPT, though documented in the literature, diagnostic pitfalls in fine-needle aspiration cytology (FNAC) may occur due to sampling error, high cellularity, ductal hyperplasia, paucity of stromal component, and occasional dissociation of epithelial cells. Here, we describe a case of BPT diagnosed by histology in a 19-year-old female, where FNAC features were inconclusive due to paucity of stromal component, predominance of tubular adenoma-like epithelial component, and due to the presence of other overlapping features with fibroadenoma. PMID:28028339

  11. Effects of Helicobacter pylori infection on gastric epithelial cell kinetics in patients with chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    Selim Aydemir; Binnaz Handan Ozdemir; Gurden Gur; Ibrahim Dogan; Ugur Yilmaz; Sedat Boyacioglu

    2005-01-01

    AIM: To evaluate the effects of Helicobacter pylori infection on gastric epithelial cell kinetics in patients with chronic renal failure (CRF).METHODS: Forty-four patients were enrolled in this study and divided into four groups with respect to their Helicobacter pylori (H pylori) and CRF status. Groups were labeled as follows: 1a: normal renal function, H pylori negative (n = 12), 1b: normal renal function,H pylori positive (n = 11), 2a: CRF, H pylori negative (n = 10), 2b: CRF, H pylori positive (n = 11). Upper gastrointestinal endoscopy was done in all the patients involved in the study. During endoscopical investigation,antral biopsy specimens were taken from each patient.In order to evaluate the cell apoptosis and proliferation in gastric epithelial cells, Bax and proliferating cell nuclear antigen (PCNA) labeling indexes (LI) were assessed with immunohistochemical staining method.RESULTS: For groups 1a, 1b, 2a, and 2b, mean Bax LI was identified as 34.4±13.7, 44.1±16.5, 46.3±20.5,60.7±13.8, respectively and mean PCNA LI was identified as 36.2±17.2, 53.6±25.6, 59.5±25.6, 67.2±22,respectively. When the one-way ANOVA test was applied,statistically significant differences were detected between the groups for both Bax LI (P = 0.004 <0.01) and PCNA LI (P = 0.009 <0.01). When groups were compared further in terms of Bax LI and PCNA LI with Tukey's HSD test for multiple pairwise comparisons, statistically significant difference was observed only between groups 1a and 2b (P = 0.006 <0.01).CONCLUSION: In gastric epithelial cells, expression of both the pre-apoptotic protein Bax and the proliferation marker PCNA increase with H pylori infection. This increase is more evident in patients with uremia. These findings suggest that uremia accelerates apoptosis and proliferation in gastric epithelial cells.

  12. Urinary Proteolytic Activation of Renal Epithelial Na+ Channels in Chronic Heart Failure.

    Science.gov (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P

    2016-01-01

    One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06, and plasmin 3.57 versus sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch clamp was conducted in cultured renal collecting duct M-1 cells to record Na(+) currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na(+) inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ≈2-folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid, which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na(+) retention commonly observed in CHF.

  13. The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells.

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H

    2011-06-24

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis.

  14. The Small GTPase Cdc42 Is Necessary for Primary Ciliogenesis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H.

    2011-01-01

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. PMID:21543338

  15. Chronic fluid flow is an environmental modifier of renal epithelial function.

    Science.gov (United States)

    Resnick, Andrew

    2011-01-01

    Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is been known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca(++), which can then result in a variety of activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5(th) decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because ADPKD is a slowly progressing disease, I asked how fluid flow may act, via the primary cilium, to alter epithelial physiology during the course of cell turnover. I performed an experiment to determine under what conditions fluid flow can result in a change of function of renal epithelial tissue. A wildtype epithelial cell line derived the cortical collecting duct of a heterozygous offspring of the Immortomouse (Charles River Laboratory) was selected as our model system. Gentle orbital shaking was used to induce physiologically relevant fluid flow, and periodic measurements of the transepithelial Sodium current were performed. At the conclusion of the experiment, mechanosensitive proteins of interest were visualized by immunostaining. I found that fluid flow, in itself, modifies the transepithelial sodium current, cell proliferation, and the actin cytoskeleton. These results significantly impact the understanding of both the mechanosensation function of primary cilia as well as the understanding of ADPKD disease progression.

  16. Chronic fluid flow is an environmental modifier of renal epithelial function.

    Directory of Open Access Journals (Sweden)

    Andrew Resnick

    Full Text Available Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is been known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca(++, which can then result in a variety of activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease (ADPKD is a progressive disease, typically appearing in the 5(th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because ADPKD is a slowly progressing disease, I asked how fluid flow may act, via the primary cilium, to alter epithelial physiology during the course of cell turnover. I performed an experiment to determine under what conditions fluid flow can result in a change of function of renal epithelial tissue. A wildtype epithelial cell line derived the cortical collecting duct of a heterozygous offspring of the Immortomouse (Charles River Laboratory was selected as our model system. Gentle orbital shaking was used to induce physiologically relevant fluid flow, and periodic measurements of the transepithelial Sodium current were performed. At the conclusion of the experiment, mechanosensitive proteins of interest were visualized by immunostaining. I found that fluid flow, in itself, modifies the transepithelial sodium current, cell proliferation, and the actin cytoskeleton. These results significantly impact the understanding of both the mechanosensation function of primary cilia as well as the understanding of ADPKD disease progression.

  17. Pentraxin 3 Activates JNK Signaling and Regulates the Epithelial-To-Mesenchymal Transition in Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Tung-Wei Hung

    2016-12-01

    Full Text Available Background/Aims: Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3 is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2 cells and a rat unilateral ureteral obstruction (UUO model of renal fibrosis. Methods: Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3 on HK-2 cells. Cell proliferation (MTT assay and in vitro cell migration were measured. The levels of PTX3, p-JNK, and EMT markers were measured using immunohistochemistry, RT-PCR, and western blotting in UUO rats and HK-2 cells. Results: HK-2 cells treated with Rh PTX3 did not affect cell viability, but significantly increased cell migration. Moreover, Rh-PTX3 increased the expression of snail, slug, N-cadherin, and vimentin, decreased the expression of E-cadherin, and increased the phosphorylation of JNK. SP600126 (a specific JNK inhibitor enhanced the effects of Rh-PTX3. Rats with UUO exhibited time-dependent increased levels of PTX3, p-JNK, and vimentin, and decreased expression of E-cadherin. Conclusions: Our results suggest that PTX3 induces cell migration via upregulation of EMT in a JNK-dependent mechanism, and highlight the role of PTX3 in the pathogenesis renal fibrosis.

  18. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Science.gov (United States)

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  19. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  20. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

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

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    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.

  2. Bilateral synchronous occurrence of three different histological types of renal tumor: a case report

    Directory of Open Access Journals (Sweden)

    Radopoulos Demetrios

    2009-04-01

    Full Text Available Abstract Introduction Renal cell carcinomas account for 85% of all renal neoplasms. With the introduction of modern imaging modalities, there has been an increased diagnosis of renal tumors. Recent studies have shown that partial nephrectomy can be as safe as radical nephrectomy for smaller renal tumors. Renal cell carcinomas are usually unilateral, however, they can be bilateral in 2% to 4% of sporadic cases and considerably more common in familial cases. Case presentation In this case report, we describe an unusual case of two bilateral synchronous chromophobe renal cell carcinomas accompanied by an oncocytoma and an angiomyolipoma, that were all treated by open partial nephrectomy. Conclusions To the best of our knowledge, this is the first case report on the synchronous occurrence of bilateral chromophobe renal cell carcinomas associated with an oncocytoma and an angiomyolipoma.

  3. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

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    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  4. Experimental study on the pathogenesis of epithelial tumors (VI report)

    OpenAIRE

    Fujiki, Hirota; Ichikawa, Koichi; Yamagiwa, Katsusaburo; Maruyama, Koshichiro; Lee, Kunsei; Fukuda,Tamotsu; Kinoshita, Riojun; Kashiwagi, Masatoshi; Ogawa, Juntaro

    2014-01-01

    The concept of cancer and inflammation has a long history. Virchow's irritation theory based on human cancer engendered the essential role of inflammation in carcinogenesis. Drs. Yamagiwa and Ichikawa first published a comprehensive paper entitled “Experimental study on the pathogenesis of epithelial tumors” (I report) in 1915 in German, and went on to publish five more reports (1915–1924) under the same title. They succeeded in demonstrating that inflammation is an important carcinogenic fac...

  5. Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model.

    Science.gov (United States)

    Chen, Liang; Yang, Sixing; Liao, Wenbiao; Xiong, Yunhe

    2015-06-01

    Renal cell carcinoma (RCC) microenvironment plays critical roles in antitumor immune response. Resveratrol exhibits a direct antitumor effect in various tumor models. However, the immunomodulatory effect of resveratrol on RCC microenvironment is unknown. In this study, we found that administration of low dose of resveratrol inhibits Renca tumor growth and its inhibition effect depends on CD8(+) T cells. Moreover, the proportion of regulatory T cells is decreased, while the proportion of myeloid-derived suppressor cells does not alter after resveratrol treatment. More importantly, massive amount of activated CD8(+) T cells accumulates in tumor microenvironment in the resveratrol-treated group and shows increased cytotoxicity, as indicated by a higher expression of Fas ligand. We also found that resveratrol switches the expression of T-helper (Th) 2 cytokines such as interleukin (IL)-6 and IL-10 to Th 1 cytokines with dominance of interferon (IFN)-γ, which increases the expression of Fas in Renca cells. Furthermore, we found resveratrol down-regulates angiogenesis along with decreased level of vascular endothelial growth factor in tumor microenvironment. Our results strongly suggest that resveratrol might be used for RCC immunotherapy through modulating tumor microenvironment.

  6. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.

    Science.gov (United States)

    Nagai, Junya; Takano, Mikihisa

    2014-08-15

    Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways.

  7. Effect of hepatitis B virus X gene on apoptosis and immune molecules of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    王轩

    2013-01-01

    Objective To investigate the effect of hepatitis B virus X(HBX)gene on apoptosis and immune moleculesof human proximal renal tubular epithelial cell line(HK-2).Methods The eukaryotic vector pcDNA3.1-myc-HBX containing HBX gene was transiently transfected into

  8. Renal cell carcinoma with vena caval tumor thrombus extending into the right atrium

    Institute of Scientific and Technical Information of China (English)

    JIANG Hai; ZHANG Zhi-gen; CHEN Zhao-dian; SHI Shi-fang; CAI Song-liang; WANG Shuo

    2006-01-01

    @@ The incidence of the inferior vena cava (IVC)tumor thrombus is reported to be 4%-10% in patients with renal cell carcinoma (RCC). Tumor thrombus may extend through to the right atrium.Management of patients with level Ⅲ/Ⅳ tumor thrombus is usually difficult. We report two cases of level Ⅳ thrombus in our hospital in 2002 and 2004.

  9. Review of the touch preparation cytology of spindle epithelial tumor with thymus-like differentiation

    Science.gov (United States)

    Yi, Kijong; Rehman, Abdul; Jang, Se Min; Paik, Seung Sam

    2016-01-01

    We experienced a case of spindle epithelial tumor with thymus-like differentiation (SETTLE) with touch preparation cytology performed during the intraoperative frozen section diagnosis in a 22-year-old woman. The tumor was partially encapsulated by fibrous capsule. It was a highly cellular biphasic tumor characterized by fasciculated spindle cells with streaming pattern and tubulopapillary epithelial component. The tumor cells were positive for cytokeratin, vimentin, c-kit, epithelial membrane antigen (EMA), and thyroid transcription factor-1 (TTF-1). However, the tumor cells were negative for thyroglobulin, calcitonin, CD99, S-100 protein, CD34, smooth muscle actin, HBME-1, and galectin-3. The reviewed touch smears showed tight clusters with high cellularity. Most cellular clusters showed papillary configuration. However, some clusters showed spindle cells with streaming pattern. The spindle tumor cells showed elongated and cigar-shaped nuclei. Although the incidence is very rare, SETLLE should be included in the differential diagnosis when a spindle cell neoplasm is encountered in touch preparation cytology in young patients with a thyroid mass. PMID:27011438

  10. CLINICAL VALUE OF SERUM TUMOR SUPPLIED GROUP OF FACTOR IN DIAGNOSIS OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    程琪辉; 张喜平; 曾小澜

    2003-01-01

    Objective: To evaluate the clinical value of serum tumor supplied group of factor (TSGF) in diagnosis of epithelial ovarian cancer. Methods: The serum TSGF was tested in 69 patients with epithelial ovarian cancer, 28 patients with benign ovarian lesion and 61 healthy women. The serum levels of vascular endothelial growth factor (VEGF) and CA125 were determined in patients with epithelial ovarian cancer and in those with benign ovarian lesion. The correlations of TSGF with VEGF and CA125 were investigated. Results: The serum level of TSGF in patients with epithelial ovarian cancer was obviously higher than in patients with benign ovarian lesion and in healthy women (P0.05). The serum level of TSGF and VEGF and CA125 in patients with epithelial ovarian cancer showed positive correlation (P<0.01, P<0.05, respectively). Conclusion: There is no marked difference in diagnostic value among TSGF, VEGF and CA125. TSGF has a certain value in diagnosis of epithelial ovarian cancer, and is helpful to distinguish epithelial ovarian cancer from benign ovarian lesion.

  11. Detection of Laminin in Serum and Ascites from Patients with Epithelial Ovarian Tumor

    Institute of Scientific and Technical Information of China (English)

    初永丽; 杨元先; 林美华; 王泽华

    2002-01-01

    The change in serum laminin (LN) level and its clinical significance in epithelial ovarian tumor were investigated. The LN levels in serum and ascites samples from 69 patients with epithelial ovarian tumor and 42 cases as control group before and after operation were analyzed by radioimmunoassay. The results showed that the serum LN levels in the patients with malignant tumors (157. 85 ± 14.37 ng/ml) were significantly higher than that in the control group (125.14 47.03ng/ml) and in the patients with benign tumors (128. 36±8. 75 ng/ml)(both P<0. 01) before operation. The serum LN levels in the malignant group were decreased significantly after operation as compared with those before operation (P<0. 05). The serum LN levels in low-differentiated tumors was higher than those in moderate-differentiated tumors and high-differentiated tumors (P<0. 05). The LN levels in ascites (172.94±15.26 ng/ml) was significantly higher than in serum (161.34±6.59ng/ml) (P<0. 05) in malignant tumors. The serum LN levels in the patients with lymph node metastasis (165.41± 19.91 ng/ml) was obviously higher than those without lymph node metastasis (152.35±10. 34 ng/ml)(P<0. 05). It was concluded that LN levels in serum and acistes were remarkably increased in malignant epithelial ovarian tumors, suggesting that LN might be one of important diameters reflecting tumor biological characteristics.

  12. Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy.

    Directory of Open Access Journals (Sweden)

    Ching-Yuang Lin

    Full Text Available Maternal hyperglycemia can inhibit morphogenesis of ureteric bud branching, Glial cell line-derived neurotrophilic factor (GDNF is a key regulator of the initiation of ureteric branching. Early growth response gene-1 (EGR-1 is an immediate early gene. Preliminary study found EGR-1 persistently expressed with GDNF in hyperglycemic environment. To evaluate the potential relationship of hyperglycemia-GDNF-EGR-1 pathway, in vitro human renal proximal tubular epithelial (HRPTE cells as target and in vivo streptozotocin-induced mice model were used. Our in vivo microarray, real time-PCR and confocal morphological observation confirmed apoptosis in hyperglycemia-induced fetal nephropathy via activation of the GDNF/MAPK/EGR-1 pathway at E12-E15. Detachment between ureteric branch and metanephrons, coupled with decreasing number and collapse of nephrons on Day 1 newborn mice indicate hyperglycemic environment suppress ureteric bud to invade metanephric rudiment. In vitro evidence proved that high glucose suppressed HRPTE cell migration and enhanced GDNF-EGR-1 pathway, inducing HRPTE cell apoptosis. Knockdown of EGR-1 by siRNA negated hyperglycemic suppressed GDNF-induced HRPTE cells. EGR-1 siRNA also reduced GDNF/EGR-1-induced cRaf/MEK/ERK phosphorylation by 80%. Our findings reveal a novel mechanism of GDNF/MAPK/EGR-1 activation playing a critical role in HRPTE cell migration, apoptosis and fetal hyperglycemic nephropathy.

  13. Renal Collecting Duct Cancer: a Report of 2 Cases

    Institute of Scientific and Technical Information of China (English)

    Shiying Zhou

    2005-01-01

    @@ Renal collecting duct cancer is a rare malignant tumor, which accounts for 1% to 2% of epithelial kidney tumors,[1] Its pathological appearance has been easily misdiagnosed as a mammilliform renal cell carcinoma or as other tumors. The malignancy of renal collecting duct cancer is high, with early metastasis and poor prognosis. The clinical data for 2 cases of the tumor are discussed in this report, including reports on the histopathology and the changes in immunohistochemistry.

  14. Leiomyosarcoma presenting as a spontaneously ruptured renal tumor-case report

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    Ather M

    2002-11-01

    Full Text Available Abstract Background Ruptured renal neoplasms can be a catastrophic clinical presentation. Angiomyolipoma is the commonest renal tumor which presents in this fashion. Renal sarcomas are rare renal neoplasms. Renal leiomyosarcomas are the most common histological subtype of renal sarcomas, accounting for approximately 50–60% of the reported cases. These tumors are usually peripherally located and appear to arise from either the renal capsule or smooth muscle tissue in the renal pelvic wall. Case presentation A 70 years old male, with hypertension and ischemic disease, developed acute left flank pain. The general physician evaluated this using ultrasound, which showed a solid left renal mass. Two weeks later, he presented in the emergency room in a state of shock with a palpable flank mass. CT scan of the abdomen showed a large heterogeneous mass lesion in the left perinephric space with minimal post contrast enhancement. Per-operatively, large retroperitoneal hematoma was found within Gerota's fascia along with spleen plastered to the upper limit of hematoma. Nephrectomy and splenectomy were performed. Postoperative course was uneventful and patient was discharged on the 10th post-operative day. Histopathological evaluation of the specimen showed high-grade leiomyosarcoma Conclusions Spontaneous rupture of renal neoplasm is a rare clinical presentation. Angiomyolipoma is the commonest cause of spontaneous rupture of the kidney. Presentation of a leimyosarcoma as a ruptured renal neoplasm has not been previously reported in the English literature.

  15. Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo.

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    Lakshmipathi Khandrika

    Full Text Available Oxalate is a metabolic end product excreted by the kidney. Mild increases in urinary oxalate are most commonly associated with Nephrolithiasis. Chronically high levels of urinary oxalate, as seen in patients with primary hyperoxaluria, are driving factor for recurrent renal stones, and ultimately lead to renal failure, calcification of soft tissue and premature death. In previous studies others and we have demonstrated that high levels of oxalate promote injury of renal epithelial cells. However, methods to monitor oxalate induced renal injury are limited. In the present study we evaluated changes in expression of Kidney Injury Molecule-1 (KIM-1 in response to oxalate in human renal cells (HK2 cells in culture and in renal tissue and urine samples in hyperoxaluric animals which mimic in vitro and in vivo models of hyper-oxaluria. Results presented, herein demonstrate that oxalate exposure resulted in increased expression of KIM-1 m RNA as well as protein in HK2 cells. These effects were rapid and concentration dependent. Using in vivo models of hyperoxaluria we observed elevated expression of KIM-1 in renal tissues of hyperoxaluric rats as compared to normal controls. The increase in KIM-1 was both at protein and mRNA level, suggesting transcriptional activation of KIM-1 in response to oxalate exposure. Interestingly, in addition to increased KIM-1 expression, we observed increased levels of the ectodomain of KIM-1 in urine collected from hyperoxaluric rats. To the best of our knowledge our studies are the first direct demonstration of regulation of KIM-1 in response to oxalate exposure in renal epithelial cells in vitro and in vivo. Our results suggest that detection of KIM-1 over-expression and measurement of the ectodomain of KIM-1 in urine may hold promise as a marker to monitor oxalate nephrotoxicity in hyperoxaluria.

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

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    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.

  17. Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.

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    Calpurnia Jayakumar

    Full Text Available BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.

  18. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project

    DEFF Research Database (Denmark)

    Kondo, Kazuya; Van Schil, Paul; Detterbeck, Frank C

    2014-01-01

    Stage classification is an important underpinning of management of patients with cancer, and rests on a combination of three components: T for tumor extent, N for nodal involvement, and M for more distant metastases. This article details an initiative to develop proposals for the first official...

  19. Prohibitin is associated with antioxidative protection in hypoxia/reoxygenation-induced renal tubular epithelial cell injury

    Science.gov (United States)

    Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Huang, Wei-Fang; Drummen, Gregor P. C.

    2013-11-01

    Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735 each P < 0.01), but positively correlated with superoxide dismutase, glutathione and mitochondrial membrane potential (r = 0.807, 0.815, 0.739; each P < 0.01). We postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

  20. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case

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    Dinesh Badrashetty

    2013-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT is a rare benign tumor of the jaws. Pindborg′s tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  1. Case of radiation cancer associated with spinocellular carcinoma and basal cell epithelial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oohara, K.; Ootsuka, F. (Tokyo Univ. (Japan). Faculty of Medicine); Mizoguchi, M.

    1980-12-01

    The patient was a 66 year-old male who had received radiotherapy for psoriasis vulgaris in frontal plane for 10 years since the age of 19. This radiotherapy was carried out once a week for 5 to 6 weeks and stopped for following 5 to 6 weeks. The source and the dose were unknown. Multiple superficial basal cell epithelial tumor occurred 32 to 33 years after that in the region over which radiation had been given. Moreover, 37 years after that, spinocellular carcinoma occurred in the same region. Spinocellular carcinoma in this case increased rapidly and reached the depth of frontal plane. Atypic of cancer cells was marked, and various findings were observed. Characteristics of these tumor cells were mixture of spindle cells and cells with vacuoles. Partially, findings common to basal cell epithelial tumor were coexisted, and senile keratosis was also discovered.

  2. Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up

    Directory of Open Access Journals (Sweden)

    Nisa Azizun

    2010-10-01

    Full Text Available Spindle epithelial tumor with thymus-like differentiation (SETTLE is a rare malignant thyroid tumor showing thymic or related branchial pouch differentiation. The tumors are composed predominantly of spindle cells along with focal epithelial component and ductular formations. SETTLE occurs in young patients, with indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively.

  3. Sox9 expression in canine epithelial skin tumors

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    E. Fantinato

    2015-07-01

    Full Text Available Sox9 is a master regulatory gene involved in developmental processes, stem cells maintenance and tumorigenesis. This gene is expressed in healthy skin but even in several skin neoplasms, where its expression patterns often resembles those of the developing hair follicle. In this study, samples from eleven different types of canine skin neoplasms (squamous papilloma, squamous cell carcinoma, infundibular keratinizing acanthoma, inferior tricholemmoma, isthmic tricholemmoma, trichoblastoma, trichoepitelioma, malignant trichoepitelioma, pilomatricoma, subungual keratoacanthoma, subungual squamous cell carcinoma were immunohistochemically stained and evaluated for Sox9 with the aim to correlate tumor phenotype with molecular characteristics that may help to better define tumor development, contribute to its diagnosis and clinical management. Keratoacanthoma excluded, all the skin neoplasms examined showed a variable positivity to Sox9, especially in the basal layers, but with major intensity in neoplasms developing from the bulge region of the hair follicle, as trichoblastoma. According to our results, Sox9 could be employed as a stem cell marker to better assess the role of stem cells in canine epidermal and follicular tumors.

  4. Enhanced propagation of adult human renal epithelial progenitor cells to improve cell sourcing for tissue-engineered therapeutic devices for renal diseases.

    Science.gov (United States)

    Westover, Angela J; Buffington, Deborah A; Humes, H D

    2012-08-01

    Renal cell therapy employing cells derived from adult renal epithelial cell (REC) progenitors promises to reduce the morbidity of patients with renal insufficiency due to acute renal failure and end stage renal disease. To this end, tissue engineered devices addressing the neglected biologic component of renal replacement therapy are being developed. Because human donor tissue is limited, novel enhanced progenitor cell propagation (EP) techniques have been developed and applied to adult human kidney transplant discards from six donors. Changes include more efficient digestion and the amplification of progenitors prior to terminal epithelial differentiation promoted by contact inhibition and the addition of retinoic acid. Differentiated morphology in EP populations was demonstrated by the ability to form polarized epithelium with tight junctions, apical central cilia and expression of brush border membrane enzymes. Evaluation of lipopolysaccharide stimulated interleukin-8 secretion and γ-glutamyl transpeptisade activity in EP derived cells was used to confirm therapeutic equivalence to REC obtained using published techniques, which have previously shown efficacy in large animal models and clinical trials. Yield exceeded 10(16) cells/gram cortex from the only kidney obtained due to an anatomical defect, while the average yield from diseased kidneys ranged from 1.1 × 10(9) to 8.8 × 10(11) cells/gram cortex, representing an increase of more than 10 doublings over standard methods. Application of the EP protocol to REC expansion has solved the problem of cell sourcing as the limiting factor to the manufacture of cell based therapies targeting renal diseases and may provide a method for autologous device fabrication from core kidney biopsies. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

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    Bernhard Moser

    Full Text Available Recently, a role of the receptor for advanced glycation endproducts (RAGE in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1 play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (pB3>thymic carcinoma (p<0.001. Conversely, HMGB1 cytoplasmic staining intensities were as follows: A and AB (none, B1 (strong, B2 (moderate, B3 and thymic carcinoma (weak; (p<0.001. Fetal thymic tissue showed a distinct expression of RAGE and HMGB1 in subcapsular cortical epithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay: serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008; and in invasive tumors (p = 0.008. Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003, HMGB1 was only elevated in malignancies (p = 0.036. Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.

  6. Laminin, a noncollagenous component of epithelial basement membranes synthesized by a rat yolk sac tumor

    DEFF Research Database (Denmark)

    Wewer, U; Albrechtsen, R; Ruoslahti, E

    1981-01-01

    Laminin, a glycoprotein antigenically similar or identical to a component of epithelial basement membranes, was identified as a major component of the abundant extracellular matrix synthesized by an experimentally induced rat yolk sac tumor. Immunocytochemical staining revealed laminin in cultured...... polypeptides with molecular weights of approximately 200,000 and 400,000. These comigrated with the polypeptides of mouse laminin isolated previously. The yolk sac tumor tissue grown in vivo contained laminin in the tumor cells and in the extracellular material as evidenced by immunofluorescence...... and in their basement membranes suggesting, but not proving, that both types of cells have ability to synthesize laminin. Production of laminin and the presence of laminin-containing basement membrane material may be important for the biological behavior of the yolk sac tumor. This tumor will also be a useful source...

  7. Laparoscopic partial nephrectomy for T1a renal tumors is safe and feasible

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; GAO Zhen-li; LIN Chun-hua; WU Ji-tao; WANG Lin; WANG Jian-ming; SUN De-kang; WANG Ke; YU Qing-xia

    2011-01-01

    Background Some patients with exophytic renal masses less than 4 cm and suboptimal renal function, or a solitary kidney and bilateral renal tumors are considered for laparoscopic partial nephrectomy (LPN), which is feasible for early-stage renal tumors, although it is still considered technically difficult and time consuming. Shortening the time of the operation and renal warm ischemia are required urgently. In this study, we report our initial experiences of LPN,especially with some improved surgical techniques. Methods Between July 2005 and October 2009, 74 patients with T1a renal tumor were treated by LPN, 39 using transperitoneal approach and 35 using retroperitoneal approach. In all cases, the tumor was removed with a margin of 0.5 cm. We compared glomerular filtration rate (GFR) preoperatively and postoperatively, and renal warm ischemia time between traditional ligature and Hem-o-lok methods. Results All operations were completed successfully, and there was no conversion to open surgery. Mean operation time was 76 minutes (range, 68-120), mean time of renal warm ischemia was 23 minutes (range, 15-32), and mean blood loss was 65 ml (range, 40-300). No hemorrhage or urine leak was observed in two cases with the collecting system sewn. Thirteen cases used Hem-o-lok to clamp the suture instead of traditional ligature, and mean time of renal warm ischemia was (16.5±2.3) minutes (range, 12-18). Mean postoperative hospital stay was 6.3 days (range, 5-12).Sixty-seven cases had renal clear cell carcinoma, six papillary renal cell carcinoma, and one renal collecting duct carcinoma. All the tumor margin specimens were negative. The mean follow-up was 30.6 months (range, 3-51), and no recurrence or metastasis was observed. Conclusions LPN for pT1 stage renal tumor was safe and feasible. Hem-o-lok instead of traditional ligature to clamp the suture when sewing the renal wound could shorten the warm ischemia time.

  8. [Tumor of upper urinary tract in renal polycystic disease].

    Science.gov (United States)

    Rabii, Redouane; el Mejjad, Amine; Fekak, Hamid; Querfani, Baderdine; Joual, Abdenbi; el Mrini, Mohamed

    2003-09-01

    Upper urinary tract tumours are exceptional in the context of renal polycystic disease. The authors report the case of Mrs B. F., 56 years old, who presented with left loin pain associated with haematuria. Clinical examination was normal and ultrasound examination revealed bilateral renal polycystic disease with a mass in the left renal sinus. CT urography showed a tumour arising from the renal pelvis suggestive of an upper urinary tract tumour. The laboratory assessment revealed normal renal function and normal urine cytology. Treatment consisted of radical nephroureterectomy with resection of a bladder cuff. Histological examination revealed a urothelial tumour of the renal pelvis with negative surgical margins. In the light of this case, the authors discuss the diagnostic difficulties and specificities, the treatment and the outcome of this unusual clinical association.

  9. CD133 Expression in Normal Skin and in Epithelial Cutaneous Tumors

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    S. H. Nam-Cha

    2013-01-01

    Full Text Available Background. Expression of human CD133 (human prominin-1 in cancer cells has been postulated to be a marker of stemness and is considered as a putative marker of cancer stem cells (CSCs. We designed a study to describe the expression pattern of CD133 in normal skin and in epithelial cutaneous neoplasms. Methods. The CD133 immunohistochemical expression of forty-three eccrine and apocrine tumors was compared to that observed in other epithelial tumors of the skin. In addition, flow cytometry was used to detect the CD133 expression of four epithelial skin neoplasms, including one porocarcinoma. Results. CD133 immunoreactivity at the apical or at the apicolateral surface of cells forming glandular structures was observed. Cells from solid areas of benign or malignant tumors were not stained. The porocarcinoma derived culture cells showed a 22% of CD133 positive cells using flow cytometry, while squamous cell carcinoma cultures contained less than 0.1%. Conclusions. These observations indicate that CD133 is a specific marker of glandular differentiation that could be included in the diagnostic panel of cutaneous tumors with possible eccrine or apocrine differentiation. However, the use of CD133 expression as a marker of CSCs should be interpreted with caution in experiments of skin.

  10. Left adrenal tumor extending into the renal vein: surgical management with ipsilateral kidney preservation.

    Science.gov (United States)

    Doerfler, Arnaud; Vaudreuil, Lionel; Le Gal, Sophie; Lebreton, Gil; Tillou, Xavier

    2015-08-04

    If single adrenal metastasis surgery is well admitted, no recommendation exists about the management of a renal vein tumor thrombus, even though the actual consensual attitude consists in a nephrectomy associated to an adrenalectomy. We report, here, the case of a 74-year-old man with a suspected adrenal metastasis of a lung carcinoma associated with a left adrenal and renal vein tumor thrombus treated by adrenalectomy and renal vein thrombectomy and ipsilateral kidney sparing. The postoperative computed tomography scan showed no thrombus in the left renal vein. Doppler ultrasound performed 1 month after adrenalectomy proved a good left renal vein flux. At 36 months of follow-up, the patient is alive without signs of recurrence. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2015.

  11. [Conservative surgical treatment of renal carcinoma. Personal experience with 29 surgical excisions of tumors].

    Science.gov (United States)

    Villani, U; Pastorello, M

    1991-03-01

    From 1980 to 1988, elective conservative surgery (tumorectomy by enucleo-resection) was performed for renal cell carcinoma at stage I in 29 patients. An accurate preoperative renal investigation was carried out to identify the exact extension of the tumor and to study all the parenchimal situation, through IVP, ultrasound, CT scanning and, particularly, conventional selective angiography. The operative technique employed was: lymphadenectomy, peri-pararenal fat extirpation, in situ tumor enucleation by circular incision of the renal capsule and blunt dissection of the renal parenchyma with 2 cm safety margin to the tumor; multiple biopsies in the "bed" of resection for histopathologic peroperative evaluation; careful examination of the pseudocapsule and surrounding renal tissue; hemostasis. Follow-up was 10-113 months (mean 40,34 months). 2 of 29 patients died for progression of disease (at 52nd and 16yh month from surgery, 2/29 died for non-neoplastic reasons; 25/29 pts are living without local recurrences or distant metastases. In the same period (1980-1988), radical nephrectomy was performed for renal tumors at stage I in 34 patients. In an average observation period of 49,67 months, 2/34 patients died for progression of disease; 3/34 pts died for non-neoplastic reasons. 1/34 patient is living with pulmonar metastases and 28/34 are living without evidence of cancer. From this study we have got the conclusion that elective renal-sparing excision of the tumor (with macro-micro examination of the abscission surfaces) should be considered as a curative treatment in the case of low stage single tumors smaller than 7 cm, peripherally located in renal cortex, with unbroken pseudocapsule.

  12. The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells.

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    Liu, Huiying; Zhang, Xiaofeng; Li, Jun; Sun, Bin; Qian, Haihua; Yin, Zhengfeng

    2015-02-01

    Movement of tumor cells from a primary tumor to a nonadjacent or distant site is a contiguous and complex process. Among the multiple natural cellular programs that promote initiation and progression of tumor metastasis, epithelial-mesenchymal transition (EMT) may play a key role in the ultimate generation of a metastatic foci. Acquisition of the EMT phenotype by tumor cells not only increases their migration and invasion potentials, thereby facilitating their ability to infiltrate blood vessels and to produce circulating tumor cells (CTCs), but also promotes survival of CTCs in the bloodstream and their ability to extravasate out of the circulatory system and invade proximal tissues. In organs distal to the primary tumor, the phenotypic switching mechanism of mesenchymal-epithelial transition (MET) enables CTCs to grow and colonize, enhancing the likelihood of establishing metastasis. In addition, CTCs that have undergone EMT attain increased resistance to chemotherapy and targeted therapy. CTCs with the EMT phenotype have become recognized as an active source of metastases, and targeting EMT/MET processes during the individual steps of tumor metastasis represents a promising new approach for alleviating cancer metastasis and recurrence. In this article, we focus on the biological and clinical importance of EMT and/or MET in CTCs during the individual steps of tumor metastasis, summarizing the recent findings of the regulatory roles played by EMT and/or MET in the generation, survival, and recolonization of CTCs and discussing the EMT-targeting strategies developed for tumor diagnosis as well as their potential for management of metastatic malignant diseases.

  13. Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.

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    Prabhat Bastola

    Full Text Available Von Hippel-Lindau tumor suppressor (VHL is lost in the majority of clear cell renal cell carcinomas (ccRCC. Folliculin (FLCN is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD, a disorder characterized by renal cancer of multiple histological types including clear cell carcinoma, cutaneous fibrofolliculoma, and pneumothorax. Here we explored whether there is connection between VHL and FLCN in clear cell renal carcinoma cell lines and tumors. We demonstrate that VHL regulates expression of FLCN at the mRNA and protein levels in RCC cell lines, and that FLCN protein expression is decreased in human ccRCC tumors with VHL loss, as compared with matched normal kidney tissue. Knockdown of FLCN results in increased formation of tumors by RCC cells with wild-type VHL in orthotopic xenografts in nude mice, an indication that FLCN plays a role in the tumor-suppressing activity of VHL. Interestingly, FLCN, similarly to VHL, is necessary for the activity of LC3C-mediated autophagic program that we have previously characterized as contributing to the tumor suppressing activity of VHL. The results show the existence of functional crosstalk between two major tumor suppressors in renal cancer, VHL and FLCN, converging on regulation of autophagy.

  14. Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability.

    Science.gov (United States)

    Pattabiraman, Diwakar R; Bierie, Brian; Kober, Katharina Isabelle; Thiru, Prathapan; Krall, Jordan A; Zill, Christina; Reinhardt, Ferenc; Tam, Wai Leong; Weinberg, Robert A

    2016-03-04

    The epithelial-to-mesenchymal transition enables carcinoma cells to acquire malignancy-associated traits and the properties of tumor-initiating cells (TICs). TICs have emerged in recent years as important targets for cancer therapy, owing to their ability to drive clinical relapse and enable metastasis. Here, we propose a strategy to eliminate mesenchymal TICs by inducing their conversion to more epithelial counterparts that have lost tumor-initiating ability. We report that increases in intracellular levels of the second messenger, adenosine 3',5'-monophosphate, and the subsequent activation of protein kinase A (PKA) induce a mesenchymal-to-epithelial transition (MET) in mesenchymal human mammary epithelial cells. PKA activation triggers epigenetic reprogramming of TICs by the histone demethylase PHF2, which promotes their differentiation and loss of tumor-initiating ability. This study provides proof-of-principle for inducing an MET as differentiation therapy for TICs and uncovers a role for PKA in enforcing and maintaining the epithelial state.

  15. Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

  16. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    Science.gov (United States)

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  17. Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.

    Science.gov (United States)

    Buijs, Nikki; Vermeulen, Mechteld A R; Weeda, Viola B; Bading, James R; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2015-01-01

    Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

  18. Mitochondrial DNA sequence variants in epithelial ovarian tumor subtypes and stages

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    Aikhionbare Felix O

    2007-01-01

    Full Text Available Abstract Background A majority of primary ovarian neoplasms arise from cell surface epithelium of the ovaries. Although old age and a positive family history are associated risk factors, the etiology of the epithelial ovarian tumors is not completely understood. Additionally, knowledge of factors involved in the histogenesis of the various subtypes of this tumor as well as those factors that promote progression to advanced stages of ovarian malignancy are largely unknown. Current evidence suggests that mitochondrial alterations involved in cellular signaling pathways may be associated with tumorigenesis. Methods In this study, we determined the presence of polymorphisms and other sequence variants of mitochondrial DNA (mtDNA in 102 epithelial ovarian tumors including 10 matched normal tissues that paired with some of the tumors. High-resolution restriction endonucleases and PCR-based sequencing were used to assess the mtDNA variants spanning 3.3 kb fragment that comprised the D-Loop and 12S rRNA-tRNAphe, tRNAval, tRNAser, tRNAasp, tRNAlys, ATPase 6, ATPase 8, cytochrome oxidase I and II genes. Results Three hundred and fifty-two (352 mtDNA sequence variants were identified, of which 238 of 352 (68% have not been previously reported. There were relatively high frequencies of three mutations in the 12S rRNA gene at np 772, 773, and 780 in stage IIIC endometrioid tumors, two of which are novel (773delT and 780delC, and occurred with a frequency of 100% (7/7. Furthermore, two mutations were observed in serous tumors only at np 1657 in stage IV (10/10, and at np 8221delA in benign cystadenomas (3/3 and borderline tumors (4/4. A high frequency, 81% (13/16 of TC insertion at np 310 was found only in early stages of serous subtype (benign cystadenomas, 3/3; borderline tumors, 4/4; stage I tumors, 2/5 and matched normal tissues 4/4. Conclusion Our findings indicate that certain mtDNA mutations can reliably distinguish the different histologic subtypes of

  19. A novel sorbitol transport mechanism in cultured renal papillary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Siebens, A.W.; Spring, K.R. (National Heart, Lung, and Blood Institute, Bethesda, MD (USA))

    1989-12-01

    The renal papillary epithelial cell line, GRB-PAP1, accumulates sorbitol when grown in a hypertonic (500 mosmol/kgH2O) bathing medium. When the cells are returned to a 300 mosmol/kgH2O medium, they lose their sorbitol rapidly to the bath. Sorbitol movement across the membranes of these cells was investigated by studying the uptake of radioactive sorbitol and related compounds. Sorbitol uptake increased 71-fold when cells grown in 500 mosmol/kgH2O medium were exposed to a 300 mosmol/kgH2O test solution. The magnitude of the permeability increase was proportional to the size of the change in the osmolality of the bathing medium and not the absolute osmolality. Sorbitol uptake was a linear function of medium sorbitol concentration with no sign of saturation at sorbitol concentrations up to 315 mM. Although the permeability of other polyols was increased when the osmolality was reduced, competition between sorbitol and related sugars and polyols could not be demonstrated. Both the increased sorbitol uptake after a decrease in medium osmolality and the decrease to control permeability after return to the original osmolality were complete within 30 s. A wide variety of transport inhibitors and ion substitutions failed to alter the magnitude of the sorbitol permeability increase. The most effective inhibitor was quinidine, 1 mM reducing sorbitol uptake by 73%. The sorbitol permeability increase could also be blocked by reducing the temperature to 0 degrees C. Nonspecific uptake of sorbitol, such as endocytosis, was shown to be of only minor significance. The large increase in sorbitol permeability and subsequent sorbitol efflux enables these cells to withstand large decreases in osmolality without excessive swelling and consequent damage. A similar compensatory mechanism may operate in vivo in the renal papilla during the onset of diuresis.

  20. Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

    Science.gov (United States)

    Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

    2017-08-01

    Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Biocompatibility, uptake and endocytosis pathways of polystyrene nanoparticles in primary human renal epithelial cells.

    Science.gov (United States)

    Monti, Daria Maria; Guarnieri, Daniela; Napolitano, Giuliana; Piccoli, Renata; Netti, Paolo; Fusco, Sabato; Arciello, Angela

    2015-01-10

    Recent years have witnessed an unprecedented growth in the number of applications—such as drug delivery, nutraceuticals and production of improved biocompatible materials—in the areas of nanoscience and nanotechnology. Engineered nanoparticles (NPs) are an important tool for the development of quite a few of these applications. Despite intense research activity, mechanisms regulating the uptake of NPs into cells are not completely defined, being the phenomenon dramatically influenced by physico-chemical properties of NPs and cell-specific differences. Since the cellular uptake of NPs is a prerequisite for their use in nanomedicine, the definition of their internalization pathway is crucial. For this reason, we used 44 nm polystyrene NPs as a model to analyze the uptake and endocytosis pathways in primary human renal cortical epithelial (HRCE) cells, which play a key role in the clearance of drugs. NPs were found not to affect the viability and cell cycle progression of HRCE cells. Distinct internalization pathways were analyzed by the use of drugs known to inhibit specific endocytosis routes. Analyses, performed by confocal microscopy in combination with quantitative spectrofluorimetric assays, indicated that NPs enter HRCE cells through multiple mechanisms, either energy-dependent (endocytosis) or energy-independent.

  2. Pediatric epithelial salivary gland tumors: spectrum of histologies and cytogenetics at a children's hospital.

    Science.gov (United States)

    Craver, Randall D; Fonseca, Paula; Carr, Ronald

    2010-01-01

    There are conflicting reports regarding the relative frequency of benign and malignant epithelial salivary gland tumors in children. There are only a few reports of the cytogenetic abnormalities in the pleomorphic adenomas (PA) that arise in children, and even less information regarding the pleomorphic adenoma gene 1 (PLAG1) and high motility group A2 (HMGA2 ) histochemical staining in PAs, or their correlation with histologic types (stromal vs epithelial predominance). A retrospective 14 year review of epithelial salivary gland tumors encountered at a children's hospital identified 13 tumors: 12 PAs and 1 acinic cell carcinoma (ACC). No mucoepidermoid carcinomas were identified. Tumors arose in the parotid (7) and other sites (2 submandibular, 4 minor). Ten PAs in our cohort had cytogenetic studies. Four were normal, 5 involved 8q12, and 1 involved 12q13. Immunohistochemistry identified an additional 2 PAs with PLAG1 staining, and 5 additional PAs with HMGA2 staining. One tumor with ins(18;8)(q21.1;q12q22.2) had no PLAG1 staining, but stained with HMGA2. This ins(18;8) may not have involved the PLAG1 gene. There was no demonstrable correlation of 8q12/PLAG1 staining or 12q13/HMGA2 staining with histologic type. Thus we found abnormalities in either 8q12/PLAG1 staining or 12q13/HMGA2 staining in all PAs. The HMGA2 staining in 50% of PAs suggests that it may be more frequently involved in PAs than previously thought based on cytogenetic studies, at least in children.

  3. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells.

    Science.gov (United States)

    Liang, Jie; Chen, Fuxue; Gu, Fu; Liu, Xin; Li, Feng; Du, Dongshu

    2017-04-01

    The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca(2+) intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca(2+) intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca(2+) concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

  4. A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock.

    Science.gov (United States)

    Westover, Angela J; Buffington, Deborah A; Johnston, Kimberly A; Smith, Peter L; Pino, Christopher J; Humes, H David

    2017-03-01

    Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery. To address these limitations, the bioartificial renal epithelial cell system (BRECS) was developed. The BRECS contains human renal tubule epithelial cells derived from adult progenitor cells using enhanced propagation techniques. Cells were seeded onto trabeculated disks of niobium-coated carbon, held within cryopreservable, perfusable, injection-moulded polycarbonate housing. The study objective was to evaluate the BRECS in a porcine model of SS to establish conservation of efficacy after necessary cell sourcing and design modifications; a pre-clinical requirement to move back into clinical trials. SS was incited by peritoneal injection of E. coli simultaneous to insertion of BRECS (n=10) or control (n=15), into the ultrafiltrate biofeedback component of an extracorporeal circuit. Comparable to RAD, prolonged survival of the BRECS cohort was conveyed through stabilization of cardiac output and vascular leak. In conclusion, the demonstration of conserved efficacy with BRECS therapy in a porcine SS model represents a crucial step toward returning renal cell therapy to the clinical setting, initially targeting ICU patients with acute kidney injury requiring continuous renal replacement therapy. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  5. THE ADVISABILITY AND SAFETY OF TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY FOR RENAL PARENCHYMAL TUMORS

    Directory of Open Access Journals (Sweden)

    V. B. Matvee

    2014-01-01

    Full Text Available Objective: to assess the advisability and safety of transperitoneal laparoscopic nephrectomy for renal parenchymal tumors.Subjects and methods. The investigation enrolled 163 patents with clinically localized renal parenchymal tumors that had been resected through laparoscopic (n = 81 (49.7 % and open (n = 82 (50.3 % accesses. The groups of patients operated on via laparoscopic and laparotomic accesses were matched for demographic characteristics, somatic status, baseline renal function, and nephrometric signs of tumor nodules, except the involved side (7 patients in the laparoscopic group had bilateral renal tumors. Renal resection was carried out in all the patients; a contralateral kidney tumor was also removed in 7 patients with a bilateral lesion (nephrectomy and kidney resection were done in 3 and 4 patients, respectively. Histological examination verified benign tumors in 15 (9.2 % cases, renal cell carcinoma in 148 (90.8 %, including all bilateral renal tumors [рТ1а (n = 135 (91.2 % cases; рТ1b (n = 4 (2.7 %; рТ3а (n = 9 (6.1 %]; according to the pT category, the distribution of patients in the laparoscopic and open resection groups was even (p = 0.586. No additional treatment was performed in any case. The median follow-up was 48.2 ± 11.8 months.Results. The use of the laparoscopic access significantly increased the frequency of intraoperative complications (6.1 and 16.0 %; p = 0.037, but failed to affect that of postoperative complications (13.0 and 18.3 %, respectively; p = 0.291 versus the open access. Laparoscopic versus conventional techniques did not cause any reduction in 5-year overall, specific, and relapse-free survival rates (93.3, 100.0, 80.0 % and 97.1, 100.0, 98.5 %, respectively; р > 0.05 for all. The rate of acute renal dysfunction and its distribution by the RIFLE classes, the rate and level of a decrease in glomerular filtration rate in the late postoperative period did not depend on the surgical access (p

  6. THE ADVISABILITY AND SAFETY OF TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY FOR RENAL PARENCHYMAL TUMORS

    Directory of Open Access Journals (Sweden)

    V. B. Matvee

    2014-07-01

    Full Text Available Objective: to assess the advisability and safety of transperitoneal laparoscopic nephrectomy for renal parenchymal tumors.Subjects and methods. The investigation enrolled 163 patents with clinically localized renal parenchymal tumors that had been resected through laparoscopic (n = 81 (49.7 % and open (n = 82 (50.3 % accesses. The groups of patients operated on via laparoscopic and laparotomic accesses were matched for demographic characteristics, somatic status, baseline renal function, and nephrometric signs of tumor nodules, except the involved side (7 patients in the laparoscopic group had bilateral renal tumors. Renal resection was carried out in all the patients; a contralateral kidney tumor was also removed in 7 patients with a bilateral lesion (nephrectomy and kidney resection were done in 3 and 4 patients, respectively. Histological examination verified benign tumors in 15 (9.2 % cases, renal cell carcinoma in 148 (90.8 %, including all bilateral renal tumors [рТ1а (n = 135 (91.2 % cases; рТ1b (n = 4 (2.7 %; рТ3а (n = 9 (6.1 %]; according to the pT category, the distribution of patients in the laparoscopic and open resection groups was even (p = 0.586. No additional treatment was performed in any case. The median follow-up was 48.2 ± 11.8 months.Results. The use of the laparoscopic access significantly increased the frequency of intraoperative complications (6.1 and 16.0 %; p = 0.037, but failed to affect that of postoperative complications (13.0 and 18.3 %, respectively; p = 0.291 versus the open access. Laparoscopic versus conventional techniques did not cause any reduction in 5-year overall, specific, and relapse-free survival rates (93.3, 100.0, 80.0 % and 97.1, 100.0, 98.5 %, respectively; р > 0.05 for all. The rate of acute renal dysfunction and its distribution by the RIFLE classes, the rate and level of a decrease in glomerular filtration rate in the late postoperative period did not depend on the surgical access (p

  7. Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible?

    Science.gov (United States)

    Kloboves-Prevodnik, Veronika; Jazbec, Janez; Us-Krasovec, Marija; Lamovec, Janez

    2002-05-01

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor of the thyroid gland which occurs predominantly in children, adolescents, and young adults. It usually presents as a painless neck or thyroid mass and only exceptionally as a diffusely enlarged thyroid gland, without metastatic disease at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine-needle aspiration biopsy (FNAB) was performed 8 mo after the first admission. Cytological examination of smears showed unusual morphological features. FNAB smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and groups. Three main cell types were observed: spindle, epithelioid, and epithelial. These cells were uniform, cytologically bland, with few mitotic figures. The distinction between these cells was not always unequivocal. In the background of the smears abundant red extracellular material in the form of fine, dust-like granules and irregular patches were present. It was also observed in some aggregates and groups of tumor cells. Spindle and epithelioid cells were immunocytochemically diffusely pan-cytokeratin-positive. In the differential diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse thyromegaly the correct diagnosis may be delayed because clinically and ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should be used preoperatively. It can provide specific cytological diagnosis based on morphological features and certain immunocytochemical characteristics of the tumor.

  8. Prostatic adenocarcinoma (PCa metastasizing to renal cell carcinoma (RCC with periureteral tumor deposit: A case of tumor-to-tumor metastasis (TTM

    Directory of Open Access Journals (Sweden)

    Jenissa Amor Dionisio Arceño, MD

    2017-06-01

    Full Text Available Renal cell carcinoma (RCC and prostatic adenocarcinoma (PCa, occurring as a double primary is uncommon, but well documented. However, metastatic PCa in a RCC is quite rare. We report a case of an 81-year old male chemical engineer with history of hematuria and prostatomegaly suspicious for carcinoma, who underwent left radical nephrectomy for a renal mass. Histopathology revealed RCC that harbored an undiagnosed PCa. Periureteral tumor deposit likewise showed combined metastasis of RCC and PCa.

  9. Role of tumor-associated macrophages in renal cell carcinoma pathogenesis

    Directory of Open Access Journals (Sweden)

    O. V. Kovaleva

    2017-01-01

    Full Text Available The role of tumor stroma in malignant tumor pathogenesis cannot be disputed. Macrophages are one of the crucial elements of tumor stroma. Tumor-associated macrophages (TAMs are type 2-activated macrophages (M2. They were first described in 1992. They carry CD206, CD163, FXIIIa, βIG-H3, stabilin 1, YKL-39, SI-CLP, tenascin С, LOX-1, fibronectin, MARCO, interleukin 1 receptor antagonist (IL-1RA and other markers. Unlike proinflammatory macrophages (M1, М2 display high anti-inflammatory activity and are responsible for inflammation reaction suppression and tissue recovery in inflamed area. TAMs significantly contribute to tumor progression by stimulating cell proliferation, angiogenesis, and suppression of antitumor immune response. Identification of macrophages in renal tumors involves a limited number of markers, which doesn’t allow making a conclusive answer about their function. However, a correlation between TAMs content and a negative disease prognosis can be considered proven. Studies of M1 and M2 using different markers have shown that renal tumors contain high levels of TAMs with mixed M1/M2 phenotype. TAMs in renal tumors are highly proangiogenic and immunosuppressive. TAMs density can be used as a prognostic marker, but development of an effective treatment strategy aimed at inhibition of TAMs antitumor activity requires systemic research involving a wide panel of M1 and M2 macrophage markers. 

  10. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer.

    Science.gov (United States)

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-12-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormalities arising in the setting of known renal cell carcinoma, particularly late in the course of disease. This is frequently associated with internal jugular vein thrombi, which should be evaluated with an abnormal thyroid. Thyroglobulin levels are usually normal in such patients.

  11. Preventing acute renal failure is crucial during acute tumor lysis syndrome

    Directory of Open Access Journals (Sweden)

    Darmon Michael

    2007-01-01

    Full Text Available Tumour Lysis syndrome (TLS is characterized by the massive destruction of tumoral cells and the release in the extracellular space of their content. While TLS may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms and cause hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Moreover, TLS may lead to an acute renal failure (ARF. In addition to the hospital mortality induced by the acute renal failure itself, development of an ARF may preclude optimal cancer treatment. Therefore, prevention of the acute renal failure during acute tumor lysis syndrome is mandatory. The objective of this review is to describe pathophysiological mechanisms leading to acute tumor lysis syndrome, clinical and biological consequences of this syndrome and to provide up-to-date guidelines to ensure prevention and prompt management of this syndrome.

  12. Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor.

    Science.gov (United States)

    Heikinheimo, K; Kurppa, K J; Laiho, A; Peltonen, S; Berdal, A; Bouattour, A; Ruhin, B; Catón, J; Thesleff, I; Leivo, I; Morgan, P R

    2015-01-01

    The aim of the study was to characterize the molecular relationship between ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide expression analysis. Total RNA from 27 fresh tumor samples of 15 solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was hybridized on Affymetrix whole genome arrays. Hierarchical clustering separated ameloblastomas and KCOTs into 2 distinct groups. The gene set enrichment analysis based on 303 dental genes showed a similar separation of ameloblastomas and KCOTs. Early dental epithelial markers PITX2, MSX2, DLX2, RUNX1, and ISL1 were differentially overexpressed in ameloblastoma, indicating its dental identity. Also, PTHLH, a hormone involved in tooth eruption and invasive growth, was one of the most differentially upregulated genes in ameloblastoma. The most differentially overexpressed genes in KCOT were squamous epithelial differentiation markers SPRR1A, KRTDAP, and KRT4, as well as DSG1, a component of desmosomal cell-cell junctions. Additonally, the epithelial stem cell marker SOX2 was significantly upregulated in KCOT when compared with ameloblastoma. Taken together, the gene expression profile of ameloblastoma reflects differentiation from dental lamina toward the cap/bell stage of tooth development, as indicated by dental epithelium-specific transcription factors. In contrast, gene expression of KCOT indicates differentiation toward keratinocytes. © International & American Associations for Dental Research 2014.

  13. Renal tubular epithelial-mesenchymal transition in kidney fibrosis%肾小管上皮间充质转化与肾脏纤维化

    Institute of Scientific and Technical Information of China (English)

    王来亮; 罗群

    2014-01-01

    Epithelial-mesenchymal transition ( EMT) , a process by which differentiated epithelial cells under-go a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury.However, the degree to which renal tubular epithelial EMT contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent.Renal tubular EMT is an adap-tive response of epithelial cells to a hostile or changing microenvironment and is regulated by many factors.Several intrace-llular signal transduction pathways such as transforming growth factor-β( TGF-β)/Smad and Wnt/β-catenin signaling are essential in controlling the process of renal tubular epithelial EMT which are potential targets of antifibrotic therapy present-ly.This review highlights the current understanding of renal tubular epithelial EMT and its underlying mechanisms to stimu-late further discussion on its role in the pathogenesis of renal interstitial fibrosis.

  14. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  15. Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

    OpenAIRE

    Brenner, Walburgis; Färber, Gloria; Jan G. Hengstler; Herget, Thomas; Thüroff, Joachim W.; Wiesner, Christoph

    2003-01-01

    Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was ex...

  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. Diagnostic Value of Processing Cytologic Aspirates of Renal Tumors in Agar Cell (Tissue) Blocks

    DEFF Research Database (Denmark)

    Smedts, F.; Schrik, M.; Horn, T.;

    2010-01-01

    Objective To adapt a method enabling utilization of most of the harvest from a fine needle aspirate in an effort to improve diagnostic accuracy in the assessment of a renal tumor in a single histologic slide. Study Design In a series of 43 renal tumors, 2 fine needle aspirations were performed, 4...... smears were prepared after each aspiration for conventional cytology and the remaining aspirate was processed for the improved agar microbiopsy (AM) method. Conventional cytology slides, AM slides and surgical specimens were diagnosed separately, after which the diagnoses were compared...

  18. The Tumor-Associated Marker, PVRL4 (Nectin-4, Is the Epithelial Receptor for Morbilliviruses

    Directory of Open Access Journals (Sweden)

    Sebastien Delpeut

    2014-06-01

    Full Text Available PVRL4 (nectin-4 was recently identified as the epithelial receptor for members of the Morbillivirus genus, including measles virus, canine distemper virus and peste des petits ruminants virus. Here, we describe the role of PVRL4 in morbillivirus pathogenesis and its promising use in cancer therapies. This discovery establishes a new paradigm for the spread of virus from lymphocytes to airway epithelial cells and its subsequent release into the environment. Measles virus vaccine strains have emerged as a promising oncolytic platform for cancer therapy in the last ten years. Given that PVRL4 is a well-known tumor-associated marker for several adenocarcinoma (lung, breast and ovary, the measles virus could potentially be used to specifically target, infect and destroy cancers expressing PVRL4.

  19. 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.

  20. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II {approx} IV or WHO tumor type B2 {approx} C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; {rho} = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; {rho} = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; {rho} = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; {rho} = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated.

  1. Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

    Institute of Scientific and Technical Information of China (English)

    FU Xiao-yan; DING Ming-xing; ZHANG Ning; LIN Xing-qiu; LI Ji-cheng

    2007-01-01

    Objective: To explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods: In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. Results: VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors (P<0.05 or P<0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively (P<0.05 or P<0.01). VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors (P<0.05). VEGFR-3 positive vessels was significantly correlated with MVD(P<0.01). Conclusion: VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.

  2. Unusual Renal Tumors — Report of Four Cases

    African Journals Online (AJOL)

    A 56 years old male patient presented with history of pain in his right lumbar ... His renal and liver function tests were also normal. Serum cal- .... M protein concentration, if present (9). ... Soft tissue plasmacytoma can be classified into 3 clinical.

  3. The Effect of Tumor Histopathology on Renal Function After Radical Nephrectomy

    Directory of Open Access Journals (Sweden)

    Eymen Gazel

    2016-01-01

    Full Text Available Aim: Patients with renal cell carcinoma (RCC have increase risk for chronic kidney disease (CKD. In our study, it was aimed to find the relationship between tumor related histopathologic properties and post-op renal functions of patients who underwent radical nephrectomy due to renal tumor. Material and Method: The data of 130 patients, who underwent radical nephrectomy, was retrospectively examined.The patient groups were classified among themselves as those with a post-operative e-GFR of below (group1 and above(group2 60mL/min/1.73m² and those with a post-operative e-GFR of or below (groupA and above(groupB 30mL/min/1.73m². Results: In terms of tumoral properties of Group A and Group B, there was not a statistically significant difference between tumor types (p=0,263, tumor T stages (p=1,0, Fuhrman grades (p=0,12, capsular invasions (p=1,0, renal vein invasions (p=1,0, lymph node involvements (p=1,0, distant metastases presences (p=0,639 of two groups. In terms of tumoral properties of Group 1 and Group 2, there was not a statistically significant difference between tumor types (p=0,283, tumor T stages (p=0,096, Fuhrman grades (p=0,27, capsular invasions (p=0,345, renal vein invasions (p=0,183, lymph node involvements (p=0,718, distant metastases presences (p=1,0 of two groups. Discussion: There is need for comprehensive studies in order to find whether tumor histopathology is one of the parameters that affect renal functions after radical nephrectomy.It should be remembered that knowing the parameters that affect renal function of this patient group, which has an already increased CKD risk, will allow us to follow them up more closely and this will directly affect the survival of patients

  4. Radiological classification of renal angiomyolipomas based on 127 tumors

    Directory of Open Access Journals (Sweden)

    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

  5. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer.

    Science.gov (United States)

    Swisher, Elizabeth M; Wollan, Melissa; Mahtani, Sarita M; Willner, Julia B; Garcia, Rochelle; Goff, Barbara A; King, Mary-Claire

    2005-09-01

    Free tumor DNA in body fluids may be an important biomarker. We tested whether tumor-specific mutated p53 DNA can be detected in blood and peritoneal fluid from women with epithelial ovarian cancer. Sequencing of tumor DNA identified somatic p53 mutations. Free DNA from matched blood or peritoneal fluid was evaluated for the tumor-specific p53 mutation using a ligase detection reaction. Sixty-nine of 137 tumors (50%) had p53 mutations. Plasma or serum from 21 (30%) of the 69 informative cases contained the tumor-specific p53 mutation. Circulating tumor was an independent predictor of decreased survival in multivariate analysis (P=.02). We detected tumor DNA in peritoneal fluid in 28 of 30 (93%) cases, including all 6 cases with negative cytology. One third of women with ovarian cancer have circulating tumor DNA and an associated reduced survival. Free tumor DNA can be detected in the majority of peritoneal fluid samples.

  6. Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst-forming epithelial cells.

    Science.gov (United States)

    Buchholz, Bjoern; Faria, Diana; Schley, Gunnar; Schreiber, Rainer; Eckardt, Kai-Uwe; Kunzelmann, Karl

    2014-05-01

    Polycystic kidney diseases are characterized by multiple bilateral renal cysts that gradually enlarge and lead to a decline in renal function. Cyst enlargement is driven by transepithelial chloride secretion, stimulated by enhanced levels of cyclic adenosine monophosphate, which activates apical cystic fibrosis transmembrane conductance regulator chloride channels. However, chloride secretion by calcium-dependent chloride channels, activated through stimulation of purinergic receptors, also has a major impact. To identify the molecular basis of calcium-dependent chloride secretion in cyst expansion, we determined the role of anoctamin 1 and 6, two recently discovered calcium-activated chloride channels both of which are expressed in epithelial cells. We found that anoctamin 1, which plays a role in epithelial fluid secretion and proliferation, is strongly expressed in principal-like MDCK cells (PLCs) forming cysts within a collagen matrix, in an embryonic kidney cyst model, and in human autosomal dominant polycystic kidney disease tissue. Knockdown of anoctamin 1 but not anoctamin 6 strongly diminished the calcium-dependent chloride secretion of PLCs. Moreover, two inhibitors of anoctamin ion channels, tannic acid and a more selective inhibitor of anoctamin 1, significantly inhibited PLC cyst growth and cyst enlargement in an embryonic kidney cyst model. Knockdown of ANO1 by morpholino analogs also attenuated embryonic cyst growth. Thus, calcium-activated chloride secretion by anoctamin 1 appears to be a crucial component of renal cyst growth.

  7. Candidate Tumor-Suppressor Gene DLEC1 Is Frequently Downregulated by Promoter Hypermethylation and Histone Hypoacetylation in Human Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2006-04-01

    Full Text Available Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Deleted in Lung and Esophageal Cancer 1 (DLEC1 on 3p22.3 is a candidate tumor suppressor in lung, esophageal, and renal cancers. The potential involvement of DLEC1 in epithelial ovarian cancer remains unknown. In the present study, DLEC1 downregulation was found in ovarian cancer cell lines and primary ovarian tumors. Focus-expressed DLEC1 in two ovarian cancer cell lines resulted in 41% to 52% inhibition of colony formation. No chromosomal loss of chromosome 3p22.3 in any ovarian cancer cell line or tissue was found. Promoter hypermethylation of DLEC1 was detected in ovarian cancer cell lines with reduced DLEC1 transcripts, whereas methylation was not detected in normal ovarian epithelium and DLEC1-expressing ovarian cancer cell lines. Treatment with demethylating agent enhanced DLEC1 expression in 90% (9 of 10 of ovarian cancer cell lines. DLEC1 promoter methylation was examined in 13 high-grade ovarian tumor tissues with DLEC1 downregulation, in which 54% of the tumors showed DLEC1 methylation. In addition, 80% of ovarian cancer cell lines significantly upregulated DLEC1 transcripts after histone deacetylase inhibitor treatment. Therefore, our results suggested that DLEC1 suppressed the growth of ovarian cancer cells and that its downregulation was closely associated with promoter hypermethylation and histone hypoacetylation.

  8. Tumor antigens and markers in renal cell carcinoma.

    NARCIS (Netherlands)

    Mulders, P.F.A.; Bleumer, I.; Oosterwijk, E.

    2003-01-01

    Tumor markers are mainly used to diagnose specific malignancies. The methods commonly involve immunohistochemistry and cytogenetics, including FISH and RT-PCR. In RCC, the investigated tumor markers (summarized in Table 1) show additional prognostic value over classical prognostic factors such as st

  9. Tumor antigens and markers in renal cell carcinoma.

    NARCIS (Netherlands)

    Mulders, P.F.A.; Bleumer, I.; Oosterwijk, E.

    2003-01-01

    Tumor markers are mainly used to diagnose specific malignancies. The methods commonly involve immunohistochemistry and cytogenetics, including FISH and RT-PCR. In RCC, the investigated tumor markers (summarized in Table 1) show additional prognostic value over classical prognostic factors such as

  10. Tumor suppressor roles of CENP-E and Nsl1 in Drosophila epithelial tissues.

    Science.gov (United States)

    Clemente-Ruiz, Marta; Muzzopappa, Mariana; Milán, Marco

    2014-01-01

    Depletion of spindle assembly checkpoint (SAC) genes in Drosophila epithelial tissues leads to JNK-dependent programmed cell death and additional blockade of the apoptotic program drives tumorigenesis. A recent report proposes that chromosomal instability (CIN) is not the driving force in the tumorigenic response of the SAC-deficient tissue, and that checkpoint proteins exert a SAC-independent tumor suppressor role. This notion is based on observations that the depletion of CENP-E levels or prevention of Bub3 from binding to the kinetochore in Drosophila tissues unable to activate the apoptotic program induces CIN but does not cause hyperproliferation. Here we re-examined this proposal. In contrast to the previous report, we observed that depletion of CENP-E or Nsl1-the latter mediating kinetochore targeting of Bub3-in epithelial tissues unable to activate the apoptotic program induces significant levels of aneuploidy and drives tumor-like growth. The induction of the JNK transcriptional targets Wingless, a mitogenic molecule, and MMP1, a matrix metaloproteinase 1 involved in basement membrane degradation was also observed in these tumors. An identical response of the tissue was previously detected upon depletion of several SAC genes or genes involved in spindle assembly, chromatin condensation, and cytokinesis, all of which have been described to cause CIN. All together, these results reinforce the role of CIN in driving tumorigenesis in Drosophila epithelial tissues and question the proposed SAC-independent roles of checkpoint proteins in suppressing tumorigenesis. Differences in aneuploidy rates might explain the discrepancy between the previous report and our results.

  11. Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue.

    Science.gov (United States)

    Bratsun, D A; Merkuriev, D V; Zakharov, A P; Pismen, L M

    2016-01-01

    We propose a multiscale chemo-mechanical model of cancer tumor development in epithelial tissue. The model is based on the transformation of normal cells into a cancerous state triggered by a local failure of spatial synchronization of the circadian rhythm. The model includes mechanical interactions and a chemical signal exchange between neighboring cells, as well as a division of cells and intercalation that allows for modification of the respective parameters following transformation into the cancerous state. The numerical simulations reproduce different dephasing patterns--spiral waves and quasistationary clustering, with the latter being conducive to cancer formation. Modification of mechanical properties reproduces a distinct behavior of invasive and localized carcinoma.

  12. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    : Nationwide register-based case-control study. SETTING: Denmark during 1982-2011. POPULATION: Cases were all Danish women diagnosed with epithelial ovarian cancer (n = 13 241) or borderline ovarian tumor (n = 3605) in the study period. Age-matched female population controls were randomly selected by risk set......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...

  13. Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

    Directory of Open Access Journals (Sweden)

    Yonneau Laurent

    2010-12-01

    Full Text Available Abstract Background Germline mutations in the folliculin (FLCN gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS, a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. Methods BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. Results Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. Conclusions Our results support a genetic distinction between BHDS-associated tumors and other renal

  14. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  15. What meralgia paresthetica can hide: renal tumor as an infrequent cause.

    Science.gov (United States)

    Ramírez Huaranga, Marco Aurelio; Ariza Hernández, Andrés; Ramos Rodríguez, Claudia Carolina; González García, Jesús

    2013-01-01

    Meralgia paresthetica is a mononeuropathy of the femoral cutaneous nerve with characteristic findings, usually secondary to injury or compression, being most common in the inguinal area. Exceptional cases associated with compressions caused by abdominal or pelvic tumors have been published, so it is always advisable to extend the study with imaging tests. We present a case associated with a renal tumor. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience.

    Science.gov (United States)

    Alguersuari, A; Mateos, A; Falcó, J; Criado, E; Fortuño, J R; Guitart, J

    2016-01-01

    To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. RFA is efficacious and safe, with results comparable to those reported in the literature. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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)

  18. Rare Renal Incidentaloma in Pregnancy: An Unusual Primitive Neuroectodermal Tumor Presentation

    OpenAIRE

    2015-01-01

    Peripheral Primitive Neuroectodermal Tumors (PNETs) are rare lesions that arise from outside the central nervous system and normally do not affect the genitourinary system. Primary renal presentations are extremely rare but given their aggressive behavior and characteristic cytomorphologic and genetic features should be considered well-defined distinct clinical entities in order to distinguish them from other primary tumors featuring round cells in the kidney. We report one case of PNET invol...

  19. Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

    Science.gov (United States)

    Kuroda, N; Furuya, M; Nagashima, Y; Gotohda, H; Kawakami, F; Moritani, S; Ota, S; Hora, M; Michal, M; Hes, O; Nakatani, Y

    2014-06-01

    Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

  20. Photothermal Ablation of in Situ Renal Tumor by PEG-IR780-C13 Micelles and Near-Infrared Irradiation.

    Science.gov (United States)

    Qiu, Xuefeng; Xu, Linfeng; Zhang, Yanting; Yuan, Ahu; Wang, Kaikai; Zhao, Xiaozhi; Wu, Jinhui; Guo, Hongqian; Hu, Yiqiao

    2016-03-07

    PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.

  1. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

    Science.gov (United States)

    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  2. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice.

    Science.gov (United States)

    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  3. Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

    2013-11-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

  4. Heterogeneity of keratin expression in epithelial tumor cells of adenolymphoma in paraffin sections.

    Science.gov (United States)

    Orito, T; Shinohara, H; Okada, Y; Mori, M

    1989-06-01

    Immunohistochemical expressions of keratin polypeptides detected by monoclonal antibodies were described in tumor cells of adenolymphoma, and the possibility of intercalated duct and ductal basal cells in the salivary glands being the progenitors was discussed. Basal cells in the tumor showed positive staining for keratin nos. 8, 13, 16, 18 and 19 detecting for monoclonal keratin antibodies (PKK 1, K 4.62, K 8.12, K 8.13), columnar tumor cells displayed strongly positive reactions with RPN 1164 and K4.62 suggesting keratin nos. 8 and 19. Great heterogeneity of distribution for keratin polypeptides was displayed by epithelial cells of adenolymphoma. Intercalated duct cells of normal salivary glands reacted with RPN 1164, RPN 1165, K 4.62 and K 8.13 monoclonal antibodies, which indicates the presence of keratins 8 and 19; and ductal basal cells reacted with PKK 1, K 4.62 and K 8.12, suggesting nos. 8, 13, 16, 18 and 19 keratins. Distribution of involucrin was variable in tumor epithelium of adenolymphoma, and was negative in the normal gland. The immunohistochemical distribution of keratin types between basal tumor cells of adenolymphoma and ductal basal cells of the normal salivary gland was compared.

  5. Diagnostically Challenging Epithelial Odontogenic Tumors: A Selective Review of 7 Jawbone Lesions

    Science.gov (United States)

    Mishima, Kenji; Saito, Ichiro; Kusama, Kaoru

    2009-01-01

    Considerable variation in the clinicopathologic presentation of epithelial odontogenic tumors can sometimes be confusing and increase the chance of misdiagnosis. Seven diagnostically challenging jawbone lesions are described. There were 2 cases of mistaken identity in our ameloblastoma file. One unicystic type, initially diagnosed and treated as a lateral periodontal cyst, showed destructive recurrence 6 years postoperatively. The other globulomaxillary lesion was managed under the erroneous diagnosis of adenomatoid odontogenic tumor and recurred 4 times over an 11-year period. This tumor was found in retrospect to be consistent with an adenoid ameloblastoma with dentinoid. The diagnosis of cystic squamous odontogenic tumor (SOT) occurring as a radicular lesion of an impacted lower third molar was one of exclusion. Of two unsuspected keratocystic odontogenic tumors, one depicted deceptive features of pericoronitis, while the other case has long been in our files with the diagnosis of globulomaxillary SOT. Two cases of primary intraosseous squamous cell carcinoma appeared benign clinically and exhibited unexpected findings; an impacted third molar began to erupt in association with the growth of carcinoma and another periradicular carcinoma showed dentinoid formation. Cases selectively reviewed in this article present challenging problems which require clinical and radiographic correlation to avoid potential diagnostic pitfalls. PMID:20596984

  6. Multifocal Renal Cell Carcinoma: Clinicopathologic Features and Outcomes for Tumors ≤4 cm

    Directory of Open Access Journals (Sweden)

    Paul L. Crispen

    2008-01-01

    Full Text Available A significant increase in the incidental detection of small renal tumors has been observed with the routine use of cross-sectional abdominal imaging. However, the proportion of small renal tumors associated with multifocal RCC has yet to be established. Here then, we report our experience with the treatment of multifocal RCC in which the primary tumor was ≤4 cm. In our series of 1113 RCC patients, 5.4% (60/1113 had multifocal disease at the time of nephrectomy. Discordant histology was present in 17% (10/60 of patients with multifocal RCC. Nephron sparing surgery was utilized more frequently in patients with solitary tumors. Overall, cancer-specific, and distant metastasis-free survival appeared to be similar between multifocal and solitary tumors. These findings are consistent with previous series which evaluated multifocal RCC with tumors >4 cm. With the known incidence of multifocality RCC, careful inspection of the entire renal unit should be performed when performing nephron sparing surgery.

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

    Directory of Open Access Journals (Sweden)

    Yabuki T

    2003-08-01

    Full Text Available 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.

  8. Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

    Science.gov (United States)

    Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

    2016-05-01

    Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture

  9. Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells.

    Science.gov (United States)

    Castellano, Giuseppe; Cafiero, Cesira; Divella, Chiara; Sallustio, Fabio; Gigante, Margherita; Pontrelli, Paola; De Palma, Giuseppe; Rossini, Michele; Grandaliano, Giuseppe; Gesualdo, Loreto

    2015-03-22

    Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the gene expression profile of renal tubular epithelial cells, stimulated with interferon-alpha. We validated microarray results through real-time polymerase chain reaction, flow cytometry on renal tubular epithelial cells, and through immunohistochemical analysis and confocal microscopy on renal biopsies. Type I interferons signature was characterized by MXA-specific staining in renal tubular epithelial cells; in addition, in situ hybridization showed that renal tubular epithelial cells were the major producers of interferon-alpha, indicating a potential autocrine effect. Whole-genome expression profile showed interferon-alpha induced up-regulation of genes involved in innate immunity, protein ubiquitination and switching to immunoproteasome. In accordance with the in vitro data, class IV lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. Our data indicate that type I interferons might have a pathogenic role in lupus nephritis characterized by an autocrine effect of interferon-alpha on renal tubular epithelial cells. Therefore we hypothesize that inhibition of type I interferons might represent a therapeutic target to prevent tubulo-interstitial damage in patients with lupus nephritis.

  10. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Anne-Pierre Morel

    Full Text Available The epithelial-mesenchymal transition (EMT is an embryonic transdifferentiation process consisting of conversion of polarized epithelial cells to motile mesenchymal ones. EMT-inducing transcription factors are aberrantly expressed in multiple tumor types and are known to favor the metastatic dissemination process. Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins can prevent cells from undergoing oncogene-induced senescence and apoptosis by abolishing both p53- and RB-dependent pathways. Here we show that they also downregulate PP2A phosphatase activity and efficiently cooperate with an oncogenic version of H-RAS in malignant transformation of human mammary epithelial cells. Thus, by down-regulating crucial tumor suppressor functions, EMT inducers make cells particularly prone to malignant conversion. Importantly, by analyzing transformed cells generated in vitro and by characterizing novel transgenic mouse models, we further demonstrate that cooperation between an EMT inducer and an active form of RAS is sufficient to trigger transformation of mammary epithelial cells into malignant cells exhibiting all the characteristic features of claudin-low tumors, including low expression of tight and adherens junction genes, EMT traits, and stem cell-like characteristics. Claudin-low tumors are believed to be the most primitive breast malignancies, having arisen through transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this prevailing view, we propose that these aggressive tumors arise from cells committed to luminal differentiation, through a process driven by EMT inducers and combining malignant transformation and transdifferentiation.

  11. 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.

  12. HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells

    NARCIS (Netherlands)

    Nishizawa, Satoshi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Takahashi, Akari; Tamura, Yasuaki; Mori, Takashi; Kanaseki, Takayuki; Kamiguchi, Kenjiro; Asanuma, Hiroko; Morita, Rena; Sokolovskaya, Alice; Matsuzaki, Junichi; Yamada, Ren; Fujii, Reona; Kampinga, Harm H.; Kondo, Toru; Hasegawa, Tadashi; Hara, Isao; Sato, Noriyuki

    2012-01-01

    Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB

  13. 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.

  14. Infratentorial brain metastases of pediatric non-epithelial malignant tumors: three case reports.

    Science.gov (United States)

    Osawa, Shin-ichiro; Kumabe, Toshihiro; Saito, Ryuta; Sonoda, Yukihiko; Niizuma, Hidetaka; Watanabe, Mika; Tominaga, Teiji

    2011-04-01

    Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

  15. Radiofrequency Ablation of Renal Tumors: Four-Year Follow-Up Results in 47 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soo Dong; Yoon, Seong Guk; Sung, Gyung Tak [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2012-09-15

    To retrospectively evaluate the intermediate results of radiofrequency ablation (RFA) of small renal masses (SRMs). Percutaneous or laparoscopic RFA was performed on 48 renal tumors in 47 patients. The follow-up studies included a physical examination, chest radiography, creatinine level, and contrast-enhanced CT or MRI. To confirm the pathologic criteria of complete ablation, 35 patients underwent a follow-up biopsy. Recurrence was defined as contrast enhancement on imaging studies after 3 months, lesion growth at subsequent imaging, or viable cancer cells on follow-up biopsy. Technical success was achieved in 43 (89.6%) of 48 renal tumors. The mean tumor size was 2.3 cm and the mean follow-up period was 49.6 months. Repeated RFA was necessary in 5 tumors due to incomplete ablation. The overall complication rate was 35.8%, of which 96.2% were mild complications. Serum creatinine levels at 12 months after RFA did not differ from those before RFA (1.28 vs. 1.36 mg/dL). Four patients were found to have recurrence at various follow-up intervals, and distant metastasis was not found in any cases. RFA appears to be a useful treatment for selected patients with SRMs. Our 4-year follow-up results disclose an excellent therapeutic outcome with RFA, while achieving effective local tumor control.

  16. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.

    Science.gov (United States)

    Ahad, Amjid; Ahsan, Haseeb; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2015-10-05

    Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.

  17. Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.

    Science.gov (United States)

    Muhanna, Nidal; Mepham, Adam; Mohamadi, Reza M; Chan, Harley; Khan, Tahsin; Akens, Margarete; Besant, Justin D; Irish, Jonathan; Kelley, Shana O

    2015-10-01

    Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Advances of MicroRNAs in Translational Medicine and Immunotherapy of Renal Tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin-en

    2016-01-01

    microRNA (miRNA) is an important molecular component for cells under normal and pathological status, and plays an important role in oncobiology, including the improvement of tumor growth, invasion, angiogenesis and immunoescape by inhibiting the expression of gene miRNAs. Translational medicine can accelerate the industrialization process of transforming scientific research into engineering application, and its application in medicine may lead to the fast shortening of distance between basic research and clinical practice. According to the study of miRNAs in translational medicine, it is discovered that the pathological subtypes of relative diseases can be identiifed and patients’ survival time and prognosis can be predicted through the expression proifles of miRNAs in tumors. The invasive examinations can be reduced to realize the diagnosis of tumors by detecting tumor-associated miRNA biomarkers, and miRNAs can be used for clinical treatment of tumors. Renal cell carcinoma (RCC) is a common tumor in urinary system, and application of some specific miRNAs as a biomarker for the complementary diagnosis and treatment as well as evaluation of prognosis has become a hot topic in modern medicine. This study mainly analyzed and summarized the latest development in miRNAs and tumor studies, hoping to provide a theoretical basis for the diagnosis and prognosis of renal cancer.

  20. Epithelial-Mesenchymal Transition Is a Critical Step in Tumorgenesis of Pancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fendrich, Volker, E-mail: fendrich@med.uni-marburg.de; Maschuw, Katja; Waldmann, Jens [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Buchholz, Malte [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Rehm, Johannes [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Gress, Thomas M. [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Bartsch, Detlef K. [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); König, Alexander [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany)

    2012-03-08

    The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.

  1. Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer.

    Science.gov (United States)

    Mercier, Pierre-Luc; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Ghani, Karim; Têtu, Bernard; Bairati, Isabelle; Bachvarov, Dimcho

    2011-10-01

    In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest was DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5'-non-coding DNA region (located at nt -1158 to -850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the contrary, DOK1 was found to be strongly overexpressed in serous EOC tumors as compared to normal tissue and importantly, DOK1 overexpression significantly correlated with improved progression-free survival (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC cells and consecutive functional analyses pointed toward association of DOK1 expression with increased EOC cell migration and proliferation, and better sensitivity to cisplatin treatment. Gene expression profiling and consecutive network and pathway analyses were also confirmative for DOK1 association with EOC cell migration and proliferation. These analyses were also indicative for DOK1 protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some tumor suppressor factors and its suppression of pro-metastasis genes. Taken together, our findings are suggestive for a possible tumor suppressor role of DOK1 in EOC; however its implication in enhanced EOC cell migration and proliferation restrain us to conclude that DOK1 represents a true TSG in EOC. Further studies are needed to more completely elucidate the functional implications of DOK1 and other members of the DOK gene family in ovarian

  2. Epithelial-Mesenchymal Transition Is a Critical Step in Tumorgenesis of Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Alexander König

    2012-03-01

    Full Text Available The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT, a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.

  3. Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers.

    Science.gov (United States)

    Chopra, Sameer; Liu, Jie; Alemozaffar, Mehrdad; Nichols, Peter W; Aron, Manju; Weisenberger, Daniel J; Collings, Clayton K; Syan, Sumeet; Hu, Brian; Desai, Mihir; Aron, Monish; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning; Siegmund, Kimberly D

    2017-01-17

    The clinical management of small renal masses (SRMs) is challenging since the current methods for distinguishing between benign masses and malignant renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false negative rates increase the risk of cancer progression and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures. We built a predictive classification model for kidney tumors using 697 DNA methylation profiles from six different subgroups: clear cell, papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal kidney tissues. Furthermore, the DNA methylation-dependent classifier has been validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs). In general, the results were highly reproducible (89%, n=70) in predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent-normals (n=102) were correctly classified as normal, while 92% of tumors (n=71) were correctly classified malignant and 86% of benign (n=29) were correctly classified benign by this classification model. Overall, this study provides molecular-based support for using routine needle biopsies to determine tumor classification of SRMs and support the clinical decision-making.

  4. Disparate effects of roscovitine on renal tubular epithelial cell apoptosis and senescence: implications for autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Park, Jin-Young; Park, See-Hyoung; Weiss, Robert H

    2009-01-01

    Control of apoptosis in autosomal dominant polycystic kidney disease (ADPKD) and in at least some cancers is likely regulated by the endogenous cyclin kinase inhibitor p21, levels of this protein being decreased in ADPKD and increased in many malignancies. The cyclin kinase inhibitor roscovitine has shown efficacy in treatment of murine PKD. We asked how a single agent can be efficacious in both PKD and cancer. Renal tubular epithelial cells were incubated at diverse roscovitine concentrations; apoptosis and senescence were measured. Subsequently, levels of pro- and antiapoptotic proteins were evaluated. Renal tubular epithelial cells exposed to 'low' concentrations of roscovitine showed minimal apoptosis in association with markedly increased levels of the antiapoptotic protein p21, and these cells became senescent. Conversely, cells exposed to 'high' levels of roscovitine became apoptotic. The mechanism of antiapoptosis and senescence with 'low'-dose roscovitine involves augmentation of the antiapoptotic proteins. Data in this study provide a mechanistic explanation of how roscovitine is effective in PKD, and suggest that further study of this agent should focus on assessment of dose response. Furthermore, our discovery of senescence induced by a PKD effective drug suggests a new area of therapeutic investigation in this disease. (c) 2008 S. Karger AG, Basel.

  5. Cellular distribution of uranium after acute exposure of renal epithelial cells: SEM, TEM and nuclear microscopy analysis

    Science.gov (United States)

    Carrière, Marie; Gouget, Barbara; Gallien, Jean-Paul; Avoscan, Laure; Gobin, Renée; Verbavatz, Jean-Marc; Khodja, Hicham

    2005-04-01

    The major health effect of uranium exposure has been reported to be chemical kidney toxicity, functional and histological damages being mainly observed in proximal tubule cells. Uranium enters the proximal tubule as uranyl-bicarbonate or uranyl-citrate complexes. The aim of our research is to investigate the mechanisms of uranium toxicity, intracellular accumulation and repartition after acute intoxication of rat renal proximal tubule epithelial cells, as a function of its chemical form. Microscopic observations of renal epithelial cells after acute exposure to uranyl-bicarbonate showing the presence of intracellular precipitates as thin needles of uranyl-phosphate localized in cell lysosomes have been published. However the initial site of precipitates formation has not been identified yet: they could either be formed outside the cells before internalization, or directly inside the cells. Uranium solubility as a function and initial concentration was specified by ICP-MS analysis of culture media. In parallel, uranium uptake and distribution in cell monolayers exposed to U-bicarbonate was investigated by nuclear microprobe analyses. Finally, the presence of uranium precipitates was tested out by scanning electron microscopic observations (SEM), while extracellular and/or intracellular precipitates were observed on thin sections of cells by transmission electron microscopy (TEM).

  6. The epithelial sodium channel γ-subunit gene and blood pressure: family based association, renal gene expression, and physiological analyses.

    Science.gov (United States)

    Büsst, Cara J; Bloomer, Lisa D S; Scurrah, Katrina J; Ellis, Justine A; Barnes, Timothy A; Charchar, Fadi J; Braund, Peter; Hopkins, Paul N; Samani, Nilesh J; Hunt, Steven C; Tomaszewski, Maciej; Harrap, Stephen B

    2011-12-01

    Variants in the gene encoding the γ-subunit of the epithelial sodium channel (SCNN1G) are associated with both Mendelian and quantitative effects on blood pressure. Here, in 4 cohorts of 1611 white European families composed of a total of 8199 individuals, we undertook staged testing of candidate single-nucleotide polymorphisms for SCNN1G (supplemented with imputation based on data from the 1000 Genomes Project) followed by a meta-analysis in all of the families of the strongest candidate. We also examined relationships between the genotypes and relevant intermediate renal phenotypes, as well as expression of SCNN1G in human kidneys. We found that an intronic single-nucleotide polymorphism of SCNN1G (rs13331086) was significantly associated with age-, sex-, and body mass index-adjusted blood pressure in each of the 4 populations (Ppressure and 0.52-mm Hg increase in diastolic blood pressure (SE=0.33, P=0.002 for systolic blood pressure; SE=0.21, P=0.011 for diastolic blood pressure). The same allele was also associated with higher 12-hour overnight urinary potassium excretion (P=0.04), consistent with increased epithelial sodium channel activity. Renal samples from hypertensive subjects showed a nonsignificant (P=0.07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination.

  7. Cellular distribution of uranium after acute exposure of renal epithelial cells: SEM, TEM and nuclear microscopy analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carriere, Marie [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: carriere@drecam.cea.fr; Gouget, Barbara [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gallien, Jean-Paul [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Avoscan, Laure [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gobin, Renee [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Verbavatz, Jean-Marc [Laboratoire d' imagerie cellulaire et moleculaire, DBJC/SBFM/LTMD, CEA/Saclay, 91191 Gif sur Yvette (France); Khodja, Hicham [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)

    2005-04-01

    The major health effect of uranium exposure has been reported to be chemical kidney toxicity, functional and histological damages being mainly observed in proximal tubule cells. Uranium enters the proximal tubule as uranyl-bicarbonate or uranyl-citrate complexes. The aim of our research is to investigate the mechanisms of uranium toxicity, intracellular accumulation and repartition after acute intoxication of rat renal proximal tubule epithelial cells, as a function of its chemical form. Microscopic observations of renal epithelial cells after acute exposure to uranyl-bicarbonate showing the presence of intracellular precipitates as thin needles of uranyl-phosphate localized in cell lysosomes have been published. However the initial site of precipitates formation has not been identified yet: they could either be formed outside the cells before internalization, or directly inside the cells. Uranium solubility as a function and initial concentration was specified by ICP-MS analysis of culture media. In parallel, uranium uptake and distribution in cell monolayers exposed to U-bicarbonate was investigated by nuclear microprobe analyses. Finally, the presence of uranium precipitates was tested out by scanning electron microscopic observations (SEM), while extracellular and/or intracellular precipitates were observed on thin sections of cells by transmission electron microscopy (TEM)

  8. Evaluation of whether serum tumor markers in patients with epithelial ovarian carcinoma change following chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-ping; XU Qi-ying; WANG Jian-liu; WANG Shi-jun; ZHAO Yan; WEI Li-hui

    2012-01-01

    Background Phenotypic and genotypic heterogeneity is a known feature of many cancers.Whether serum tumor marker kinds vary and change following chemotherapy is still unclear.The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy,and the potential clinical significance in patients with epithelial ovarian carcinoma (EOC) or primary serous peritoneal carcinoma (PSPC).Methods Samples were collected before surgery,during chemotherapy and during follow-up for enzyme-linked immunosorbent assay (ELISA)-based evaluation of serum CA-125,CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy.In total,72 patients were examined,including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.Results In 35 de novo patients,20% (7/35) demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma (57.1%,4/7) showed resistance to chemotherapy.In the 37 recurrent patients,51.4% (19/37) had changed serum tumor markers,of whom 57.9% (11/19) presented with serous carcinoma.There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers.However,for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group.In the 17 patients with secondary recurrence,37.5% (6/17) had changed tumor marker levels.The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.Conclusions Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence,indicating that in addition to the markers that are abnormal before surgery,those markers

  9. 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.

  10. Robotic nephron-sparing surgery for renal tumors: Current status.

    Science.gov (United States)

    Azhar, Raed A; Gill, Inderbir S; Aron, Monish

    2014-07-01

    There have been a number of advances in robotic partial nephrectomy (RPN) for renal masses. We reviewed these advances with emphasis on the evolution of technique and outcomes as well as the expanding indications for RPN. Literature in the English language was reviewed using the National Library of Medicine database. Relevant articles were extracted, and their citations were utilized to broaden our search. The identified articles were reviewed and summarized with a focus on novel developments. RPN is an evolving procedure and is an emerging viable alternative to laparoscopic partial nephrectomy and open partial nephrectomy with favorable outcomes. The contemporary techniques used for RPN demonstrate excellent perioperative outcomes. The short-term oncologic outcomes are comparable to those of laparoscopic and open surgical approaches. Further studies are needed to assess long-term oncologic control.

  11. Histotype differentiation of hypo-echoic renal tumors on CEUS: usefulness of enhancement homogeneity and intensity.

    Science.gov (United States)

    Lu, Qing; Xue, Li-yun; Huang, Bei-jian; Wang, Wen-ping; Li, Cui-xian

    2015-08-01

    The purpose of this study is to evaluate qualitative and quantitative analysis of contrast-enhanced ultrasound (CEUS) in differential diagnoses of hypo-echoic renal tumor histotypes. Our study cohort comprised 103 clear cell renal cell carcinomas (ccRCCs), 24 papillary renal cell carcinomas (pRCCs), 28 chromophobe renal cell carcinomas (cRCCs), and 34 angiomyolipomas (AMLs), hypo-echoic on ultrasound, and imaged between January 2011 and December 2013. Enhancement homogeneity and tumor-to-cortex intensity ratio (TOC ratio) were retrospectively analyzed. Overall, heterogeneous enhancement was more common in ccRCCs than AMLs, pRCCs, and cRCCs. TOC ratio showed the trend ccRCC > AML > pRCC = cRCC. Similar trends were seen in tumors 107.5% to differentiate ccRCC from other histotypes, the sensitivity, specificity, positive and negative predictive values were 93.1%, 74.5%, 84.8%, and 87.5%, respectively. Tumors >4 cm exhibited considerable overlap in enhancement homogeneity among different histotypes. TOC ratios were similar between homo- and heterogeneously enhancing tumors for ccRCCs and for pRCCs and cRCCs, but higher in homogeneously enhancing than heterogeneously enhancing AMLs. In homo- and heterogeneously enhancing tumors, TOC ratios followed the trends ccRCCs > AMLs > pRCCs = cRCCs and ccRCCs > AMLs = pRCCs = cRCCs, respectively. With TOC ratio >105.81% and >72.37% to differentiate homo- and heterogeneously enhancing ccRCCs from other histotypes in tumors >4 cm with same enhancement homogeneity, the sensitivity, specificity, positive and negative predictive values were 70.0%, 85.7%, 70.0%, 85.7%, and 91.7%, 94.4%, 95.7%, 89.5%, respectively. CEUS homogeneity and TOC ratio are helpful in differential diagnosis of hypo-echoic renal tumor histotypes. Diameter and enhancement homogeneity should be considered when deciding the diagnostic TOC ratio cutoff.

  12. Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

    2014-06-01

    In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

  13. 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.)

  14. Resultado de la timectomía en los tumores epiteliales Result of thymectomy in epithelial tumors

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Martín González

    2013-03-01

    Full Text Available Introducción: el timoma describe las neoplasias que no presentan atipia manifiesta del componente epitelial, cuando se exhibe claramente atipia citológica se le conoce como carcinoma tímico, y la cirugía es el tratamiento de elección. Nuestro objetivo es evaluar la eficacia de la timectomía en los enfermos con tumores epiteliales del timo (timoma, carcinoma tímico. Métodos: se estudiaron 26 enfermos entre enero 2007 a enero 2012 que, con este diagnóstico, fueron operados en nuestro centro. Resultados: la miastenia gravis estuvo presente en 16 (61,5 % pacientes, de ellos en el posoperatorio se extubaron 11 (68,7 % después de 12 horas. La esternotomía total fue el abordaje principal 13 (50 %, cuando la lesión era superior a los 7 centímetros fue más probable la ampliación a un hemitórax. Cuando se necesitó resección de pulmón, pericardio o ambos, el tiempo quirúrgico fue superior a los 120 minutos. Se complicaron 7 (29,6 %, de ellos 5 (71,4 % de causa respiratoria. En 19 (73,9 % los tumores se clasificaron como estadio I de Masaoka y en 6 (23,1 % hubo carcinoma tímico.Tuvimos 1 fallecido (3,8 %. Todos los miasténicos tuvieron remisión completa o farmacológica, en 2 hubo recidiva local y en ninguno fallecimiento durante el seguimiento. Conclusiones: la timectomía transesternal es el tratamiento de elección, y se necesita ampliar a un hemitórax cuando la lesión es más de 7 cm con resección de pericardio, pulmón o ambos. En este caso, se obtendrán resultados favorables en los miasténicos y en el control del tumor durante el seguimiento.Introduction: Thymomea describes the neoplasias that do not present evident atypia of the epithelial component; the clear cytological atypia indicated thymic carcinoma and surgery is the treatment of choice. The objective of this paper was to evaluate the efficacy of thymectomy aimed at patients with epithelial tumors in the thymus (thymoma, thymic carcinoma. Methods: Twenty six

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

    Energy Technology Data Exchange (ETDEWEB)

    Meloni, Maria Franca, E-mail: meloni.mariafranca@gmail.com [Department of Radiology, Ospedale Valduce, Como (Italy); Smolock, Amanda [Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Cantisani, Vito; Bezzi, Mario; D' Ambrosio, Ferdinando [Department of Radiology, Oncology and Anatomo-Pathology “Sapienza” University of Rome, Rome (Italy); Proiti, Maria [Department of Internal Medicine, Vittorio-Emanuele University Hospital, Catania (Italy); Lee, Fred [Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Aiani, Luca [Department of Radiology, Ospedale Valduce, Como (Italy); Calliada, Fabrizio [Department of Radiology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia (Italy); Ferraioli, Giovanna [Ultrasound Unit, Infectious Diseases Department, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia (Italy)

    2015-09-15

    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.

  16. Autophagy regulates keratin 8 homeostasis in mammary epithelial cells and in breast tumors

    Science.gov (United States)

    Kongara, Sameera; Kravchuk, Olga; Teplova, Irina; Lozy, Fred; Schulte, Jennifer; Moore, Dirk; Barnard, Nicola; Neumann, Carola A.; White, Eileen; Karantza, Vassiliki

    2010-01-01

    Autophagy is activated in response to cellular stressors and mediates lysosomal degradation and recycling of cytoplasmic material and organelles as a temporary cell survival mechanism. Defective autophagy is implicated in human pathology, as disruption of protein and organelle homeostasis enables disease-promoting mechanisms such as toxic protein aggregation, oxidative stress, genomic damage and inflammation. We previously showed that autophagy-defective immortalized mouse mammary epithelial cells (iMMECs) are susceptible to metabolic stress, DNA damage and genomic instability. We now report that autophagy deficiency was associated with ER and oxidative stress, and deregulation of p62-mediated keratin homeostasis in mammary cells and allograft tumors and in mammary tissues from genetically engineered mice. In human breast tumors, high phospho(Ser73)-K8 levels inversely correlated with Beclin 1 expression. Thus, autophagy preserves cellular fitness by limiting ER and oxidative stress, a function potentially important in autophagy-mediated suppression of mammary tumorigenesis. Furthermore, autophagy regulates keratin homeostasis in the mammary gland via a p62-dependent mechanism. High phospho(Ser73)-K8 expression may be a marker of autophagy functional status in breast tumors and, as such, could have therapeutic implications for breast cancer patients. PMID:20530580

  17. Tumor progression, metastasis, and modulators of epithelial-mesenchymal transition in endometrioid endometrial carcinoma: an update.

    Science.gov (United States)

    Makker, Annu; Goel, Madhu Mati

    2016-02-01

    Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis - the most fatal consequence of endometrial carcinogenesis.

  18. Lysosomal Changes in Renal Proximal Tubular Epithelial Cells of Male Sprague Dawley Rats Following Decalin Exposure

    Science.gov (United States)

    1990-01-01

    decalin-treated animal. Note large, pale, rcd-staining lysosome (-). An exfoliated epithelial cell can iu- seen in the tubular lumen containing large...photomicrograph contains an exfoliated epithelial cell (-) with enlarged, intact lysosomes. The tubule on the left half of the photomicrograph contains an...metabolism of proteins. In: Cytology , GH Bourne and JF Danielli (eds). Academ- The Kidney: Physiology and Pathophysiology, DW ic Press, NY, pp. 251-300. - ~- i :- d .L n .- 2

  19. Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity.

    Science.gov (United States)

    Moghadasali, Reza; Mutsaers, Henricus A M; Azarnia, Mahnaz; Aghdami, Nasser; Baharvand, Hossein; Torensma, Ruurd; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2013-07-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0-3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500-3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity. Copyright © 2012 Elsevier GmbH. All rights reserved.

  20. 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

  1. [The expression of MKP-1 and p-ERK(1/2) in primary ovarian epithelial tumor tissues].

    Science.gov (United States)

    Zhou, Jian Wei; Gan, Ning Yue; Zhang, Wei Jiang

    2009-06-01

    To investigate the expression of mitogen activated protein kinase phosphatase-1 (MKP-1) and phosphorylation extracellular signal-regulated kinases (p-ERK(1/2)) in primary ovarian epithelial tumor tissues, and provide experiment's foundation on the new treatment in ovarian cancer. Expression of MKP-1 and p-ERK(1/2) in tissues from 64 patients with primary ovarian epithelial tumor, 35 patients with ovarian epithelial bordline tumor, 32 patients with ovarian epithelial benign tumor and 26 normal ovarian tissues was detected by immunohistochemistry. Western-blot was also used for detecting the expression of MKP-1 and p-ERK(1/2) protein in these tissues. Immunohistochemistry and Western-blot assay showed that the expression of MKP-1 was gradually decreased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were significant differences among them (P ERK(1/2) was gradually increased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were also significant differences among them (P ERK(1/2) expression level in the carcinoma tissues of stage III/IV patients was significantly higher than that of stage I/II patients. Expression of MKP-1 and p-ERK(1/2) in same ovarian carcinoma tissues detected by immunohistochemistry and Western-blot assay showed significant negative correlation (r = -0.90, P ERKs may play a role in the development of ovarian carcinoma. The abnormal expression of MKP-1 and p-ERK(1/2) probably assists in promoting the development and progression of ovarian carcinoma.

  2. The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development

    Science.gov (United States)

    2015-09-01

    prognosis triple negative (ER-, PR-, and HER2-) invasive carcinomas with high frequencies of metaplastic and medullary differentiation(23-25). To...Clinically, the majority of CL tumors are poor prognosis triple - negative (ER, PR, and HER2) invasive carcinomas with high frequencies of metaplastic and...AWARD NUMBER: W81XWH-13-1-0282 TITLE: The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor

  3. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients.

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Naso, Giuseppe; Vincenzi, Bruno; Petracca, Arianna; Nicolazzo, Chiara; Palazzo, Antonella; Saltarelli, Rosa; Spremberg, Franco; Cortesi, Enrico; Gazzaniga, Paola

    2011-11-01

    Currently used methods to detect and enumerate circulating tumor cells (CTCs) rely on the expression of the epithelial cell adhesion molecule (EpCAM) and cytokeratins. This selection may exclude cells that have undergone intrinsic modifications of their phenotype, as epithelial-mesenchymal transition (EMT). Aim of the study was to investigate the expression of EMT and stemness markers in CTCs from breast cancer patients in all stages of disease. 92 female breast cancer patients were enrolled. CTCs were isolated by CELLection Dynabeads coated with the monoclonal antibody toward EpCam. Samples found positive for CTCs presence (CD45-/CK+) were evaluated for the expression of ER alpha, HER2, ALDH1, vimentin, and fibronectin. Samples negative for CTCs presence (CD45-/CK-) were also evaluated for the expression of vimentin and fibronectin, used as markers of EMT. CTCs were found in 66% of patients. The distribution of CTCs presence according to stage and grade of disease was found statistically significant. The expression of ALDH1 on CTCs was found to correlate to stage of disease and to the expression of vimentin and fibronectin. In 34% of patients, we detected cells with negative CK/CD45 expression but positive expression of vimentin and fibronectin. There is an urgent need for optimizing CTCs detection methods through the inclusion of EMT markers. The detection of cells in mesenchymal transition, retaining EMT and stemness features, may contribute to discover additional therapeutic targets useful to eradicate micrometastatic disease in breast cancer.

  4. Multiparameter analysis of human epithelial tumor cell lines by laser scanning cytometry.

    Science.gov (United States)

    Pollice, A A; Smith, C A; Brown, K; Farkas, D L; Silverman, J F; Shackney, S E

    2000-12-15

    Laser scanning cytometry (LSC) is a relatively new slide-based technology developed for commercial use by CompuCyte (Cambridge, MA) for performing multiple fluorescence measurements on individual cells. Because techniques developed for performing four or more measurements on individual lymphoid cells based on light scatter as a triggering parameter for cell identification are not suitable for the identification of fixed epithelial tumor cells, an alternative approach is required for the analysis of such cells by LSC. Methods for sample preparation, event triggering, and the performance of multiple LSC measurements on disaggregated fixed human cells were developed using normal lymphocytes and two human breast cancer cell lines, JC-1939 and MCF-7, as test populations. Optimal conditions for individual cell identification by LSC were found to depend on several factors, including deposited cell density (cells per unit area), the dynamic range of probe fluorescence intensities, and intracellular distribution of the fluorescent probe. Sparsely deposited cells exhibited the least cell overlap and the brightest immunofluorescent staining. Major advantages of using DNA probes over a cytoplasmic immunofluorescent protein marker such as tubulin for event triggering are that the former exhibit greater fluorescence intensity within a relatively sharply demarcated nuclear region. The DNA-binding dye LDS-751 was found to be suboptimal for quantitative DNA measurements but useful as a triggering measurement that permits the performance of simultaneous fluorescein isothiocyanate-, phycoerythrin-, and indodicarbocyanine-based measurements on each cell. A major potential advantage of LSC over flow cytometry is the high yields of analyzable cells by LSC, permitting the performance of multiple panels of multicolor measurements on each tumor. In conclusion, we have developed and optimized a technique for performing multiple fluorescence measurements on fixed epithelial cells by LSC

  5. 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

  6. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, A.L.; Kjaer, S.K.; Christensen, I.J.;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  7. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Kjaer, Susanne Krüger; Christensen, Ib J;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology....

  8. Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Krastan B. Blagoev

    2013-02-01

    Full Text Available Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents.

  9. 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

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient's individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations...... therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... 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...

  10. 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.

  11. A Survey of Mesenchyme-related Tumors of the Rat Kidney in the National Toxicology Program Archives, with Particular Reference to Renal Mesenchymal Tumor.

    Science.gov (United States)

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J

    2016-08-01

    In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165 cases of mesenchyme-related tumors and nephroblastomas of the rat kidney were reexamined from the National Toxicology Program (NTP) Archives. This survey demonstrated that renal mesenchymal tumor (RMT) was the most common spontaneous nonepithelial tumor in the rat kidney, also occurring more frequently in the NTP studies than nephroblastoma. Renal sarcoma was a distinct but very rare tumor entity, representing a malignant, monomorphous population of densely crowded, fibroblast-like cells, in which, unlike RMT, preexisting tubules did not persist. Nephroblastoma was characterized by early death of affected animals, suggesting an embryonal origin for this tumor type. Male and female rats were equally disposed to developing RMT, but most of the cases of nephroblastoma occurred in female rats and liposarcoma occurred mostly in male rats. This survey confirmed discrete histopathological and biological differences between the mesenchyme-related renal tumor types and between RMT and nephroblastoma. Statistical analysis also demonstrated a lack of any relationship of these renal tumor types to test article administration in the NTP data bank.

  12. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    Science.gov (United States)

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  13. RENAL TUMOR QUANTIFICATION AND CLASSIFICATION IN TRIPLE-PHASE CONTRAST-ENHANCED ABDOMINAL CT

    Science.gov (United States)

    Gautam, Rabindra; Peterson, James; Yao, Jianhua; Linehan, W. Marston; Summers, Ronald M.

    2009-01-01

    It is estimated that a quarter of a million people in the USA are living with kidney cancer. In clinical practice, the response to treatment is monitored by manual measurements of tumor size, which are time consuming and show high intra- and inter-operator variability. We propose a computer-assisted radiology tool to assess renal tumors in contrast-enhanced CT for the management of tumor diagnoses and treatments. The algorithm employs anisotropic diffusion, a combination of fast-marching and geodesic level-sets, and a novel statistical refinement step to adapt to the shape of the lesions. It also quantifies the 3D size, volume and enhancement of the lesion and allows serial management of tumors. The comparison between manual and semi-automated quantifications shows disparity within the limits of inter-observer variability. The automated tumor classification shows great separation between cysts, von Hippel-Lindau syndrome (VHL) lesions and hereditary papillary renal carcinomas (HPRC) (p < 0.004). PMID:20383290

  14. 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.

  15. 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.

  16. Interleukin-13 promotes expression of Alix to compromise renal tubular epithelial barrier function.

    Science.gov (United States)

    Xu, Chen; Sun, Guangdong; Yang, Jie; Sun, Qianmei; Tong, Zhaohui

    2015-05-01

    The epithelial barrier dysfunction plays a critical role in a number of kidney diseases. The mechanism is unclear. Alix is a protein involving in protein degradation in epithelial cells. This study aims to investigate that interleukin (IL)-13 inhibits Alix to compromise the kidney epithelial barrier function. In this study, the murine collecting duct cell line (M-1) was cultured in Transwell inserts to investigate the significance of Alix in compromising the epithelial barrier functions. T cell (Teff cells) proliferation assay was employed to assess the antigenicity of ovalbumin (OVA) that was transported across the M-1 monolayer barrier. The results showed that M-1 cells express Alix. Exposure to interleukin (IL)-13 markedly decreased the expression of Alix in M-1 cells, which compromised the M-1 monolayer barrier functions by showing the increases in the permeability to OVA. Over-expression of Alix abolished the IL-13-induced M-1 monolayer barrier dysfunction. Knockdown of Alix significantly increased M-1 monolayer permeability. The OVA collected from the Transwell basal chambers induced the OVA-specific T cell proliferation. We conclude that IL-13 compromises M-1 epithelial barrier functions via inhibiting Alix expression.

  17. Serum level of proximal renal tubular epithelial cell-binding immunoglobulin G in patients with lupus nephritis.

    Science.gov (United States)

    Yap, D Y H; Yung, S; Zhang, Q; Tang, C; Chan, T M

    2016-01-01

    In vitro data showed that immunoglobulin G (IgG) from lupus nephritis (LN) patients could bind to proximal renal tubular epithelial cells (PTEC), but the clinical relevance of such binding remained unclear. Binding of IgG and subclasses to PTEC was measured by cellular ELISA (expressed as OD index) in 189 serial serum samples from 23 Class III/IV ± V LN patients who had repeated renal flares (48 during renal flares, 141 during low level disease activity (LLDA)), and compared with 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals. Total IgG PTEC-binding index was 0.34 ± 0.16, 0.29 ± 0.16, 0.62 ± 0.27 and 0.83 ± 0.38 in healthy controls, NLGD, LN patients during LLDA, and LN patients during nephritic flare, respectively (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). PTEC-binding index for IgG1 was 0.09 ± 0.05, 0.16 ± 0.12, 0.44 ± 0.34 and 0.71 ± 0.46 for the corresponding groups (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). Sixteen of 48 episodes (33.3%) of nephritic flare showed persistent PTEC-binding IgG seropositivity for more than 9.4 ± 3.1 months, despite clinical response to immunosuppressive treatment. Total IgG and IgG1 PTEC-binding correlated with anti-dsDNA level (r = 0.34 and 0.52, respectively, p < 0.001 for both), and inversely with C3 level (r = -0.26 and -0.50, respectively, p = 0.002 and<0.001). Sensitivity/specificity of PTEC-binding index in detecting renal flares was 45.8%/80.1% for total IgG (ROC AUC 0.630, p = 0.007) and 87.5%/35.5% for IgG1 (ROC AUC 0.615, p = 0.018). IgG1 PTEC-binding index correlated with tubulo-interstitial inflammation score in renal biopsy from corresponding patients. Our data suggested that total IgG and IgG1 PTEC-binding index in serum of LN patients correlate with serological activity, and in combination could predict renal flares. The correlation between IgG1

  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. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF gene.

    Directory of Open Access Journals (Sweden)

    Jenny Leitz

    2014-03-01

    Full Text Available The expression of the human papillomavirus (HPV E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  20. Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-01-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic. PMID:24604027

  1. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF) gene.

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-03-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  2. Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.

    Directory of Open Access Journals (Sweden)

    Maoyong Fu

    Full Text Available Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2, a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

  3. Short Term Clinical Outcome after Laparoscopic Cryoablation of the Renal Tumor < or = 3.5 cm.

    Science.gov (United States)

    Polascik, T J; Nosnik, I; Mayes, J M; Mouraviev, V

    2007-12-01

    Between September 2000 and September 2006, 26 patients underwent primary laparoscopic cryosurgical procedures (28) for an organ-confined renal tumor(s). In one case, cryosurgery was done sequentially on both kidneys. All patients had been carefully selected based on the following criteria: tumor size < or = 3.5 cm, the absence of local and systemic spread on cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI), and the ability to tolerate general anesthesia. A pure laparoscopic approach was employed using third generation cryotechnology (Galil Medical Inc., Plymouth Meeting, USA). Patients were followed by serial CT or MRI scan, creatinine level, and physical examination at least every six months after cryotherapy. The mean patient age was 64 years (range: 44-79) and the mean follow-up was 20.9 +/- 17.2 months. The median tumor size was 2.0 cm (range: 1-3.5 cm). Only one patient required a blood transfusion and one patient developed a transient ileus. The median length of stay was 2.0 days (range: 0-9 days). The median change in creatinine was 0.1 mg/dl (range:-0.4 to 1.8). No patient was converted to open surgery. No evidence of recurrence or progression was found in all patients, and overall survival rate was 100%. Laparoscopic renal cryoablation of the small renal tumor is a safe procedure with minimal complications. Although there were no recurrences with short term follow-up, further long term study is needed to verify its efficacy.

  4. Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells.

    Science.gov (United States)

    Pasqualon, Tobias; Lue, Hongqi; Groening, Sabine; Pruessmeyer, Jessica; Jahr, Holger; Denecke, Bernd; Bernhagen, Jürgen; Ludwig, Andreas

    2016-04-01

    Surface expressed proteoglycans mediate the binding of cytokines and chemokines to the cell surface and promote migration of various tumor cell types including epithelial tumor cells. We here demonstrate that binding of the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) to epithelial lung and breast tumor cell lines A549 and MDA-MB231 is sensitive to enzymatic digestion of heparan sulphate chains and competitive inhibition with heparin. Moreover, MIF interaction with heparin was confirmed by chromatography and a structural comparison indicated a possible heparin binding site. These results suggested that proteoglycans carrying heparan sulphate chains are involved in MIF binding. Using shRNA-mediated gene silencing, we identified syndecan-1 as the predominant proteoglycan required for the interaction with MIF. MIF binding was decreased by induction of proteolytic shedding of syndecan-1, which could be prevented by inhibition of the metalloproteinases involved in this process. Finally, MIF induced the chemotactic migration of A549 cells, wound closure and invasion into matrigel without affecting cell proliferation. These MIF-induced responses were abrogated by heparin or by silencing of syndecan-1. Thus, our study indicates that syndecan-1 on epithelial tumor cells promotes MIF binding and MIF-mediated cell migration. This may represent a relevant mechanism through which MIF enhances tumor cell motility and metastasis.

  5. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    Science.gov (United States)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  6. Molecules involved in epithelial-mesenchymal transition and epithelial-stromal interaction in phyllodes tumors: implications for histologic grade and prognosis.

    Science.gov (United States)

    Kwon, Ji Eun; Jung, Woo-Hee; Koo, Ja Seung

    2012-06-01

    The aim of this study was to investigate the expression of molecules associated with epithelial-mesenchymal transition (EMT) and epithelial-stromal interactions (ESI) and to evaluate their roles in phyllodes tumors (PTs). Tissue microarrays (TMAs) were constructed from 207 PT specimens (157 benign, 34 borderline and 16 malignant). The presence of EMT-related markers including N-cadherin, Twist, TGF-beta, HMGA2, S100A4 and Ezrin as well as ESI-related molecules such as SDF1 and CXCR4 among the TMAs was assessed immunohistochemically. Immunohistochemical results were analyzed in terms of clinicopathologic parameters. For higher grade PTs, expressions of Twist (p EMT-associated molecules, and CXCR4, an ESI-associated molecule, were increased in the stromal component of advanced grade PTs. Further, high expression of Twist in the stromal component was correlated with poorer prognoses.

  7. Assessment of the ITMIG Statement on the WHO Histological Classification and of the Eighth TNM Staging of Thymic Epithelial Tumors of a Series of 188 Thymic Epithelial Tumors.

    Science.gov (United States)

    Meurgey, Alexandra; Girard, Nicolas; Merveilleux du Vignaux, Claire; Maury, Jean-Michel; Tronc, François; Thivolet-Bejui, Françoise; Chalabreysse, Lara

    2017-07-08

    Thymic epithelial tumors (TETs) are rare intrathoracic malignancies that are categorized histologically according to the WHO classification, which was recently updated in 2015 on the basis of a consensus statement of the International Thymic Malignancy Interest Group (ITMIG); at the same time, the standard Masaoka-Koga staging system is scheduled to be replaced by the eighth edition of the TNM staging classification by the American Joint Committee on Cancer/Union for International Cancer Control consortium. Our objectives were to analyze the feasibility of assessing ITMIG consensus major and minor morphological and immunohistochemical criteria and the eighth edition of the TNM staging classification in a routine practice setting. This is a single-center study conducted at the Louis-Pradel Hospital of Lyon University, one of the largest centers for TETs in France. Overall, a large surgical series of 188 TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed. There were 89 men (49%) and 92 women (51%); 57 patients (31%) presented with myasthenia gravis at time of diagnosis. According to the WHO classification, there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1 thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20 thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100% of type A, AB, B1, and B2 thymomas. After restaging according to the eighth edition of the TNM staging classification, there were 127 stage I (84%), three stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three stage IVb (2%) thymomas. Significant correlation between histological type and stage at diagnosis was maintained after restaging according the TNM classification. Comprehensive analysis of our well-characterized surgical series of 188 TETs indicates the feasibility and the diagnostic value of the ITMIG consensus statement on WHO histological classification and highlights the

  8. EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells.

    Science.gov (United States)

    Elberg, Gerard; Elberg, Dorit; Lewis, Teresa V; Guruswamy, Suresh; Chen, Lijuan; Logan, Charlotte J; Chan, Michael D; Turman, Martin A

    2007-11-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E2 (PGE2) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE2 directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE2 effect has not been characterized. Our goal is to define the PGE2 receptor subtype involved in ADPKD. We used a three-dimensional cell-culture system of human epithelial cells from normal and ADPKD kidneys in primary cultures to demonstrate that PGE2 induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP2 receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE2-selective analogs further demonstrates that EP2 mediates cAMP formation and cystogenesis. Functional evidence for a role of EP2 receptor in mediating cAMP signaling was also provided by inhibiting EP2 receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE2 produced in cyst fluid binds to adjacent EP2 receptors located on the apical side of cysts and stimulates EP2 receptor expression. PGE2 binding to EP2 receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP2 receptor in mediating the PGE2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease.

  9. AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

    Science.gov (United States)

    2014-02-21

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Renal Cell Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  10. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma.

    Science.gov (United States)

    Younes, E; Haas, G P; Dezso, B; Ali, E; Maughan, R L; Kukuruga, M A; Montecillo, E; Pontes, J E; Hillman, G G

    1995-10-15

    We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.

  11. Silencing megalin and cubilin genes inhibits myeloma light chain endocytosis and ameliorates toxicity in human renal proximal tubule epithelial cells.

    Science.gov (United States)

    Li, Min; Balamuthusamy, Saravanan; Simon, Eric E; Batuman, Vecihi

    2008-07-01

    Using target-specific short interfering (si) RNAs, we silenced the tandem endocytic receptors megalin and cubilin genes in cultured human renal proximal tubule epithelial cells. Transfection by siRNA resulted in up to 90% suppression of both megalin and cubilin protein and mRNA expression. In HK-2 cells exposed to kappa-light chain for up to 24 h, light chain endocytosis was reduced in either megalin- or cubilin-silenced cells markedly but incompletely. Simultaneous silencing of both the cubilin and megalin genes, however, resulted in near-complete inhibition of light chain endocytosis, as determined by measuring kappa-light chain protein concentration in cell cytoplasm and by flow cytometry using FITC-labeled kappa-light chain. In these cells, light chain-induced cytokine responses (interleukin-6 and monocyte chemoattractant protein-1) and epithelial-to-mesenchymal transition as well as the associated cellular and morphological alterations were also markedly suppressed. The results demonstrate that light chain endocytosis is predominantly mediated by the megalin-cubilin tandem endocytic receptor and identify endocytosis as a key step in light chain cytotoxicity. Blocking light chain endocytosis prevents its nephrotoxic effects on human kidney proximal tubule cells.

  12. 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

    2017-07-21

    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.Modern Pathology advance online publication, 21

  13. Tumor cell marker PVRL4 (nectin 4 is an epithelial cell receptor for measles virus.

    Directory of Open Access Journals (Sweden)

    Ryan S Noyce

    2011-08-01

    Full Text Available Vaccine and laboratory adapted strains of measles virus can use CD46 as a receptor to infect many human cell lines. However, wild type isolates of measles virus cannot use CD46, and they infect activated lymphocytes, dendritic cells, and macrophages via the receptor CD150/SLAM. Wild type virus can also infect epithelial cells of the respiratory tract through an unidentified receptor. We demonstrate that wild type measles virus infects primary airway epithelial cells grown in fetal calf serum and many adenocarcinoma cell lines of the lung, breast, and colon. Transfection of non-infectable adenocarcinoma cell lines with an expression vector encoding CD150/SLAM rendered them susceptible to measles virus, indicating that they were virus replication competent, but lacked a receptor for virus attachment and entry. Microarray analysis of susceptible versus non-susceptible cell lines was performed, and comparison of membrane protein gene transcripts produced a list of 11 candidate receptors. Of these, only the human tumor cell marker PVRL4 (Nectin 4 rendered cells amenable to measles virus infections. Flow cytometry confirmed that PVRL4 is highly expressed on the surfaces of susceptible lung, breast, and colon adenocarcinoma cell lines. Measles virus preferentially infected adenocarcinoma cell lines from the apical surface, although basolateral infection was observed with reduced kinetics. Confocal immune fluorescence microscopy and surface biotinylation experiments revealed that PVRL4 was expressed on both the apical and basolateral surfaces of these cell lines. Antibodies and siRNA directed against PVRL4 were able to block measles virus infections in MCF7 and NCI-H358 cancer cells. A virus binding assay indicated that PVRL4 was a bona fide receptor that supported virus attachment to the host cell. Several strains of measles virus were also shown to use PVRL4 as a receptor. Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a

  14. Double Primary Tumors-Renal Cell Carcinoma and Duodenal Mucinous Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Dejan Vuckovic

    2012-12-01

    Full Text Available A 59-year old patient was admited to the Gastroenterology Clinic with the signs of gastrointestinal bleeding. Computerized tomography (CT and a barium-meal radiography revealed a circumferential nodular wall narrowing and incomplete stricture at the D2 part of the duodenum. CT also showed a poorly demarcated mass in the upper and lower poles of the left kidney. During the operation, the whole kidney together with the tumor was removed and also a part of the duodenum. Morphological features of both tumors were typical and distinctive enough to set the diagnosis of two independent primary tumors. The possibility of one being the metastasis of the other was excluded. The diagnosis of double primary malignant neoplasms - renal cell carcinoma and duodenal mucinous adenocarcinoma was made.

  15. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney ston

  16. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

    Science.gov (United States)

    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

  17. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney ston

  18. Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Yi-Ying Wu; Hwei-Fang Tsai; We-Cheng Lin; Ai-Hsiang Chou; Hui-Ting Chen; Jyh-Chin Yang; Ping-I Hsu; Ping-Ning Hsu

    2004-01-01

    AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori(H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL onthe surface of infiltrating T-cells in Hpylori-infected gastric mucosa.METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylorialone. Interestingly,the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vsTRAIL and H pylori: 0.51±0.06 vs 2.29±0.27,P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.CONCLUSION: H pylori can sensitize human gastric epithelial ceils and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.

  19. GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression.

    Science.gov (United States)

    Xiao, Yun; Liu, Jishi; Peng, Yu; Xiong, Xuan; Huang, Ling; Yang, Huixiang; Zhang, Jian; Tao, Lijian

    2016-01-01

    Tubular epithelial-mesenchymal transition (EMT) has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF). The production of reactive oxygen species (ROS) plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3) in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO). Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

  20. Effects of Escherichia Coli Subtilase Cytotoxin and Shiga Toxin 2 on Primary Cultures of Human Renal Tubular Epithelial Cells

    Science.gov (United States)

    Márquez, Laura B.; Velázquez, Natalia; Repetto, Horacio A.; Paton, Adrienne W.; Paton, James C.; Ibarra, Cristina; Silberstein, Claudia

    2014-01-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2. PMID:24466317

  1. Effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on primary cultures of human renal tubular epithelial cells.

    Directory of Open Access Journals (Sweden)

    Laura B Márquez

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC cause post-diarrhea Hemolytic Uremic Syndrome (HUS, which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC and compare its effects with those produced by Shiga toxin type 2 (Stx2, in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.

  2. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma.

    Science.gov (United States)

    Bousquet, Guilhem; El Bouchtaoui, Morad; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-08-07

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities.We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.

  3. Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma.

    Science.gov (United States)

    Ning, Hao; Shao, Qian-Qian; Ding, Ke-Jia; Gao, De-Xuan; Lu, Qing-le; Cao, Qing-Wei; Niu, Zhi-Hong; Fu, Qiang; Zhang, Chun-Huan; Qu, Xun; Lü, Jia-Ju

    2012-06-01

    Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P Tregs was higher than that of peripheral blood Tregs in patients with RCC (P Tregs was shown to significantly correlate with the pathological stage (P Tregs and VEGF protein expression (r = 0.51, P Tregs and MVD score (r = 0.39, P Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

  4. Absence of loss of heterozygosity of BRCA1 in a renal tumor from a BRCA1 germline mutation carrier

    OpenAIRE

    Alanee, Shaheen; Shah, Sohela; Murali, Rajmohan; Rau-Murthy, Rohini; Kasmintan A Schrader; Offit, Kenneth

    2013-01-01

    BRCA1 functions as a tumor suppressor gene and germline and somatic mutations in this gene have been shown to be associated with many types of cancer. We report the first tumor study of renal cell carcinoma in a carrier of the deleterious BRCA1 mutation-c.68_69delAG.

  5. Hnf-1β transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair.

    Directory of Open Access Journals (Sweden)

    Stanislas Faguer

    Full Text Available Epithelial repair following acute kidney injury (AKI requires epithelial-mesenchyme-epithelial cycling associated with transient re-expression of genes normally expressed during kidney development as well as activation of growth factors and cytokine-induced signaling. In normal kidney, the Hnf-1β transcription factor drives nephrogenesis, tubulogenesis and epithelial homeostasis through the regulation of epithelial planar cell polarity and expression of developmental or tubular segment-specific genes. In a mouse model of ischemic AKI induced by a 2-hours hemorrhagic shock, we show that expression of this factor is tightly regulated in the early phase of renal repair with a biphasic expression profile (early down-regulation followed by transient over-expression. These changes are associated to tubular epithelial differentiation as assessed by KSP-cadherin and megalin-cubilin endocytic complex expression analysis. In addition, early decrease in Hnf1b expression is associated with the transient over-expression of one of its main target genes, the suppressor of cytokine signaling Socs3, which has been shown essential for renal repair. In vitro, hypoxia induced early up-regulation of Hnf-1β from 1 to 24 hours, independently of the hypoxia-inducible factor Hif-1α. When prolonged, hypoxia induced Hnf-1β down-regulation while normoxia led to Hnf-1β normalization. Last, Hnf-1β down-regulation using RNA interference in HK-2 cells led to phenotype switch from an epithelial to a mesenchyme state. Taken together, we showed that Hnf-1β may drive recovery from ischemic AKI by regulating both the expression of genes important for homeostasis control during organ repair and the state of epithelial cell differentiation.

  6. Perfusion-CT monitoring of cryo-ablated renal cells tumors

    Directory of Open Access Journals (Sweden)

    Vespasiani Giuseppe

    2009-10-01

    Full Text Available Abstract Background No single and thoroughly validated imaging method in monitoring of cryoablated renal cell carcinoma (RCC is available. The purpose of our study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (pCT in evaluating the hemodynamic response of RCC. Methods 15 patients (14 male, 1 female; age range, 43-81 years; mean age, 62 years with cryoablated RCC via a transperitoneal approach, underwent to pCT 6-8 months after cryo-therapy. pCT was performed for 65 seconds after intravenous injection of contrast medium (80 mL, 370 mg iodine per millilitre, 4 mL/sec. Perfusion parameters (Time/Density curve; Blood flow, BF; Blood Volume, BV; Mean Transit Time, MTT; Permeability-Surface Area Product, PS were sampled in the cryoablated tumor area and in ipsilateral renal cortex using deconvolution-based method. A tumor was considered to be not responsive to treatment by CT evidence of pathological contrast enhancement in the cryoablated area or renal mass persistence compared with the preoperative CT control. Written informed consent was obtained from all participants before the study. Results After cryotherapy, successfully ablated tumor (n = 13 showed decrease in BV (5,39 +/- 1,28 mL/100 g, BF (69,92 +/- 20,12 mL/100 g/min and PS (16,66 +/- 5,67 mL/100 g/min value and increased value of MTT (25,35 +/- 4,3 sec compared with those of normal renal cortex (BV: 117,86 +/- 31,87 mL/100 g/min; BF: 392,39 +/- 117,32 mL/100 g/min; MTT: 18,02 +/- 3,6 sec; PS: 81,68 +/- 22,75 mL/100 g/min. In one patient, assessment of perfusion parameters was not feasible for breathing artifacts. One tumor showed poor response to treatment by the evidence of nodular contrast enhancement in the region encompassing the original lesion. Two typical enhancement patterns were obtained comparing the Time-Density curves of responsive and not responsive ablated tumors. Conclusion Perfusion CT seems to be a feasible and promising technique in

  7. Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.

    Science.gov (United States)

    Dardour, Leila; Verleyen, Pieter; Lesage, Karl; Holvoet, Maureen; Devriendt, Koen

    2016-10-01

    Smith-Magenis syndrome (SMS) is a contiguous-gene disorder most commonly caused by a deletion of chromosome 17p11.2. We report a 57 year-old man with SMS who presents bilateral renal tumors. This is most likely related to haploinsufficiency of FLCN gene, located in the deleted region, and a known tumor suppressor gene. Haploinsufficiency of FLCN causes Birt-Hogg-Dubé syndrome (BHDS), characterized by pulmonary cysts, renal and skin tumors. The present observation suggests that the follow-up of patients with SMS should also focus on possible manifestations of BHDS.

  8. 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.

  9. The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma.

    Science.gov (United States)

    Hu, Susie L; Chang, Anthony; Perazella, Mark A; Okusa, Mark D; Jaimes, Edgar A; Weiss, Robert H

    2016-08-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel-Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist's tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist's tumor.

  10. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  11. 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.

  12. Chemo-mechanical modeling of tumor growth in elastic epithelial tissue

    Energy Technology Data Exchange (ETDEWEB)

    Bratsun, Dmitry A., E-mail: bratsun@pspu.ru [Department of Applied Physics, Perm National Research Polytechnical University, Perm, 614990 (Russian Federation); Zakharov, Andrey P. [Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); Theoretical Physics Department, Perm State Humanitarian Pedagogical University, Perm, 614990 (Russian Federation); Pismen, Len [Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, 32000 Israel (Israel)

    2016-08-02

    We propose a multiscale chemo-mechanical model of the cancer tumor development in the epithelial tissue. The epithelium is represented by an elastic 2D array of polygonal cells with its own gene regulation dynamics. The model allows the simulation of the evolution of multiple cells interacting via the chemical signaling or mechanically induced strain. The algorithm includes the division and intercalation of cells as well as the transformation of normal cells into a cancerous state triggered by a local failure of the spatial synchronization of the cellular rhythms driven by transcription/translation processes. Both deterministic and stochastic descriptions of the system are given for chemical signaling. The transformation of cells means the modification of their respective parameters responsible for chemo-mechanical interactions. The simulations reproduce a distinct behavior of invasive and localized carcinoma. Generally, the model is designed in such a way that it can be readily modified to take account of any newly understood gene regulation processes and feedback mechanisms affecting chemo-mechanical properties of cells.

  13. Chemo-mechanical modeling of tumor growth in elastic epithelial tissue

    Science.gov (United States)

    Bratsun, Dmitry A.; Zakharov, Andrey P.; Pismen, Len

    2016-08-01

    We propose a multiscale chemo-mechanical model of the cancer tumor development in the epithelial tissue. The epithelium is represented by an elastic 2D array of polygonal cells with its own gene regulation dynamics. The model allows the simulation of the evolution of multiple cells interacting via the chemical signaling or mechanically induced strain. The algorithm includes the division and intercalation of cells as well as the transformation of normal cells into a cancerous state triggered by a local failure of the spatial synchronization of the cellular rhythms driven by transcription/translation processes. Both deterministic and stochastic descriptions of the system are given for chemical signaling. The transformation of cells means the modification of their respective parameters responsible for chemo-mechanical interactions. The simulations reproduce a distinct behavior of invasive and localized carcinoma. Generally, the model is designed in such a way that it can be readily modified to take account of any newly understood gene regulation processes and feedback mechanisms affecting chemo-mechanical properties of cells.

  14. Characterization and staging of renal tumors: significance of MRI diagnostics; Charakterisierung und Staging von Nierentumoren: Bedeutung der MRT-Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Kalinka, A.; Gerlach, A.; Arlart, I.P.; Guenes, N.; Hauser, T.K.; Wuerstlin, S. [Inst. fuer Diagnostische und Interventionelle Radiologie, Katharinenhospital Stuttgart (Germany); Bosse, A. [Inst. fuer Pathologie, Katharinenhospital Stuttgart (Germany)

    2006-03-15

    Purpose: Retrospective evaluation of MRI in the diagnosis of renal masses and determination of the correlation of MRI with histology or follow-up. Materials and methods: 46 consecutive patients (13 female, 33 male, mean age 64.7 yrs) with suspected renal tumors were examined with a 1.5T MR scanner using a standardized protocol (TSE T2fs, 2DGRE T1, dynam. ce3DGRE T1fs, ce2DGRE T1fs, ce3DGRE urogram). Results: 142 renal lesions were found with diameters of <2 cm up to 14 x 18 cm. A primary classification as solid and cystic lesions was performed according to MRI criteria. In 29 cases we found lesions bilaterally, in 17 patients only in one kidney, and in four cases we found multifocal renal tumors unilaterally (n=3) or bilaterally (n=1). In 22 patients with renal tumors, cystic lesions could be seen as well. In 19 cases these were uncomplicated cysts, and in 3 cases these were complicated cysts. 35/43 lesions were histologically proven solid vascularized tumors (29 renal cell carcinomas, 6 urothelial carcinomas), five additional masses with tumor signs in MRI appeared to be progressive during follow-up thus suggesting malignancy, and one case was a multifocal bilateral renal tumor. 3/43 lesions were initially reported as being suspected of malignancy but were proven during follow-up or histologically to be benign. Tumor thrombus was depicted in MRI in the renal vein in 5 cases, stretching into the IVC in 4 cases and proven histologically in 4 and 3 cases, respectively. Of these solid masses, 99 cystic lesions could be differentiated clearly in MRI (88 simple cysts, 11 complicated cysts) that remained unchanged during follow-up (6-65 months) or were proven to be cysts histologically. In 17 cases these cysts were bilateral, in 19 cases unilateral, and 33 kidneys showed multicystic changes. In characterizing renal masses, MRI showed a positive predictive value of 93% for the diagnosis of a malignant tumor. The T-stage of histologically proven renal cell carcinomas using

  15. Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-09-16

    Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Diseases; Breast Diseases; Renal Neoplasm; Solid Tumors

  16. Study of microsatellite instability in epithelial ovarian tumors%上皮性卵巢癌中微卫星不稳定的研究

    Institute of Scientific and Technical Information of China (English)

    卢媛; 刘惜时; 王跃祥; 宋后燕; Nanbert ZHONG

    2006-01-01

    Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were collected. Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel by fluorescence-labeled polymerase chain reaction. Results: Of 90 epithelial ovarian tumors analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30 demonstrated a low level of microsatellite instability (MSI-L), and the remaining 42 exhibited microsatellite stability (MSS). Frequency of microsatellite instability (MSI) at loci BAT-25 was higher than that at any other loci. No correlation was found between MSI level and patient age, tumor type, tumor differentiation (P>0.05). But the microsatellite instability-high phenotype correlates with clinical stage.It tended to occur more frequently in early-stage tumors (P=0.03). Conclusion: The frequent MSI in epithelial ovarian tumors suggests that it is an early event to involve in the development of epithelial ovarian tumors.

  17. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-α

    Institute of Scientific and Technical Information of China (English)

    Jae Sung Ko; Hye Ran Yang; Ju Young Chang; Jeong Kee Seo

    2007-01-01

    AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α(TNF-α) on intestinal epithelial cells.METHODS: Caco-2 cells were incubated with TNF-α alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 (IL-8) secretion by intestinal epithelial cells was measured using an ELISA.Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase (ERK), anti-phospho-ERK and anti-IκB-α.RESULTS: A TNF-α-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF-α-induced IL-8 secretion was reduced by L. plantarum.L. plantarum inhibited the activation of ERK and the degradation of IκB-α in TNF-α-treated Caco-2 cells.CONCLUSION: Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-α is inhibited by L. plantarum.Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway.

  18. Successful Treatment of Extra-Renal Noncerebral Rhabdoid Tumors with VIDE.

    Science.gov (United States)

    Yasui, Naoko; Yoshida, Akihiko; Kobayashi, Eisuke; Nakatani, Fumihiko; Kawamoto, Hiroshi

    2016-02-01

    Extra-renal noncerebral rhabdoid tumors (ERRTs) are highly aggressive and often lethal. An optimal chemotherapy regimen for ERRT remains undetermined. We report on three pediatric patients successfully treated with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE). Two of our patients who had metastatic or refractory disease have survived more than 2 years, one disease free without myeloablative megatherapy. The treatment with high-dose alkylator therapy is reported to have a beneficial effect on survival. A VIDE regimen containing high-dose ifosfamide is feasible and appears to prolong the survival of patients with ERRT. This regimen may be a promising option for ERRT treatment without myeloablative megatherapy.

  19. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ilson Sepúlveda

    2013-08-01

    Full Text Available We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

  20. Renal Tumor

    Directory of Open Access Journals (Sweden)

    Yarisdey Corrales Hernández

    2016-02-01

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  1. Cushing syndrome as presenting symptom of calcifying nested stromal-epithelial tumor of the liver in an adolescent boy: a case report.

    Science.gov (United States)

    Weeda, V B; de Reuver, Ph R; Bras, H; Zsíros, J; Lamers, W H; Aronson, D C

    2016-06-16

    Ectopic adrenocorticotropic hormone-producing primary liver tumors are rare, especially in children. We report the case of an adolescent boy of mixed Dutch and Moroccan descent with an adrenocorticotropic hormone-producing calcifying nested stromal-epithelial tumor with long-term follow-up. Thus far, only two such cases have been reported. A 16-year-old boy of mixed Dutch and Moroccan descent presented with Cushing syndrome and a palpable abdominal mass. A calcifying nested stromal-epithelial tumor was diagnosed. Postoperatively, his plasma adrenocorticotropic hormone concentration normalized. He remains in complete remission 13 years after tumor resection. Calcifying nested stromal-epithelial tumor should be in the differential diagnosis of liver tumors, especially if associated with Cushing syndrome as significant morbidity and mortality may be associated. Literature on the topics involved is comprehensively reviewed.

  2. Postoperative radiotherapy of patients with thymic epithelial tumors (TET). A retrospective analysis of outcome and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Haefner, Matthias Felix; Roeder, Falk; Sterzing, Florian; Krug, David; Koerber, Stefan A.; Debus, Juergen [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (dkfz), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Kappes, Jutta [University of Heidelberg, Department of Pneumology, Thoraxklinik Heidelberg, Heidelberg (Germany); Hoffmann, Hans [University of Heidelberg, Department of Thoracic Surgery, Thoraxklinik Heidelberg, Heidelberg (Germany); Slynko, Alla [German Cancer Research Center (dkfz), Biostatistics, Heidelberg (Germany); Bischof, Marc [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); SLK-Kliniken Heilbronn, Department of Radiation Oncology, Heilbronn (Germany)

    2014-08-26

    The purpose of this study was to evaluate postoperative radiotherapy regarding outcome and toxicity in patients with thymic epithelial tumors (TET) after surgery. We retrospectively analyzed medical records of 41 patients with TET treated with postoperative radiotherapy at our institution between 1995 and 2012. The impact of prognostic factors (e.g., Masaoka stage, histological subtype) was investigated and radiation-related toxicity was assessed. Median age was 59.8 years and median follow-up was 61 months. In 24.4 %, TETs were associated with paraneoplastic syndromes. The 5-year overall survival (OS) was 89.5 % and the 5-year disease-free survival (DFS) was 88.9 %. Masaoka stage had a significant impact on OS (p = 0.007). Locally limited stages I + II had a 5-year OS of 100 % compared to 80 % for stage III and 66.7 % for stage IV. The 5-year DFS was excellent with 100 % for both WHO groups A/AB/B1 and B2, respectively, and significantly (p = 0.005) differed from B3/C-staged patients with a 5-year DFS of 63.6 %. Resection status, paraneoplastic association, radiation dose, or tumor size did not influence survival. There were no high-grade acute or late side effects caused by radiotherapy. Masaoka stage has a significant impact on OS as WHO type has on DFS in patients with TETs after surgery and adjuvant irradiation. Postoperative radiotherapy with doses around 50 Gy is safe and not likely to cause high-grade toxicity. Further prospective trials are necessary to separate patient subgroups that benefit from radiotherapy from those that do not. (orig.) [German] Die vorliegende Studie hatte zum Ziel, die postoperative Radiotherapie von Patienten nach Resektion einer Thymusneoplasie epithelialen Ursprungs (Thymom, Thymuskarzinom, ''thymic epithelial tumors'', TET) hinsichtlich prognostischer Relevanz und Nebenwirkungsprofil zu beurteilen. Wir analysierten retrospektiv die medizinischen Krankenakten von 41 Patienten mit TET, die zwischen 1995 und

  3. A new translocation between chromosomes 6 and 9 helps to establish diagnosis of renal oncocytoma.

    Science.gov (United States)

    Hudacko, Rachel; May, Michael; Aviv, Hana

    2011-08-01

    Renal oncocytomas are benign epithelial tumors of the kidney. Histologically, they resemble certain malignant renal tumors, such as chromophobe renal cell carcinoma and the eosinophilic or granular form of clear cell renal carcinoma. It is, therefore, important to be able to differentiate among these tumors. Cytogenetic analysis is an important adjunct to the diagnosis of renal tumors, as the various subtypes have specific acquired chromosome abnormalities. Oncocytomas present either with loss of chromosome 1 and a sex chromosome, or with recurring translocations involving chromosome 11. We describe 2 patients with renal oncocytoma and a new translocation between chromosomes 6 and 9. The tumors in both patients were histologically virtually identical. The t(6;9)(p21;p23) may be a new translocation associated with renal oncocytomas.

  4. Role of epithelial mesenchymal transition (EMT in pancreatic ductal adenocarcinoma (PDAC: is tumor budding the missing link?

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-09-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is <5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of epithelial-mesenchymal transition (EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.

  5. 肾小管上皮细胞损伤的研究进展%Progress in research of renal tubular epithelial cell injury

    Institute of Scientific and Technical Information of China (English)

    彭单单

    2013-01-01

    肾小管上皮细胞(RTEC)是肾小管间质的主要细胞,具有旺盛的代谢活性和潜在的增殖能力,并能分泌多种细胞因子.RTEC损伤,不仅是引起急性肾衰竭的直接原因,而且是导致慢性肾衰竭、贫血、肾性骨病等不可逆的终末期肾病的主要原因和共同病理过程.防治RTEC损伤对于减缓或逆转肾间质纤维化进展具有重要意义.%Renal tubular epithelial cell (RTEC) is the major cell type in renal tubulointerstitium. It has strong metabolic activity and proliferative potency. It secretes a variety of cytokines. RTEC injury is not only the direct cause of acute renal failure, but also the main reason of renal interstitial fibrosis (RIF) and the common pathological process of irreversible end-stage renal diseases such as chronic renal failure, anemia and renal osteodystrophy. Prevention and treatment of RTEC injury is of great significance in slowing down and reversing the progress of RIF.

  6. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  7. Double-echo gradient chemical shift MR imaging fails to differentiate minimal fat renal angiomyolipomas from other homogeneous solid renal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ferré, R., E-mail: kn638@yahoo.fr [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Cornelis, F. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Verkarre, V. [Department of Pathology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Eiss, D.; Correas, J.M. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Grenier, N. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Hélénon, O. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France)

    2015-03-15

    Highlights: •Diagnosis of AMLs with minimal fat (mfAMLs) is still challenging with MRI. •Drop of signal on opposed-phase MR imaging is not specific of mfAMLs. •Double-echo gradient-echo sequences cannot accurately differentiate renal mfAMLs from other renal tumors. -- Abstract: Objectives: The purpose of this retrospective study was to evaluate the diagnostic performance of double-echo gradient chemical shift (GRE) magnetic resonance (MR) imaging for the differentiation of angiomyolipomas with minimal fat (mfAML) from other homogeneous solid renal tumors. Methods: Between 2005 and 2010 in two institutions, all histologically proven homogenous solid renal tumors imaged with computed tomography and MR imaging, including GRE sequences, have been retrospectively selected. A total of 118 patients (mean age: 61 years; range: 20–87) with 119 tumors were included. Two readers measured independently the signal intensity (SI) on GRE images and calculated SI index (SII) and tumor-to-spleen ratio (TSR) on in-phase and opposed-phase images. Intra- and interreader agreement was obtained. Cut-off values were derived from the receiver operating characteristic (ROC) curve analysis. Results: Twelve mfAMLs in 11 patients were identified (mean size: 2.8 cm; range: 1.2–3.5), and 107 non-AML tumors (3.2 cm; 1–7.8) in 107 patients. The intraobserver reproducibility of SII and TSR was excellent with an intraclass correlation coefficient equal to 0.99 [0.98–0.99]. The coefficient of correlation between the readers was 0.99. The mean values of TSR for mfAMLs and non-mfAMLs were −7.0 ± 22.8 versus −8.2 ± 21.2 for reader 1 and −6.7 ± 22.8 versus −8.4 ± 20.9 for reader 2 respectively. No significant difference was noticed between the two groups for SII (p = 0.98) and TSR (p = 0.86). Only 1 out of 12 mfAMLs and 11 of 107 non-AML tumors presented with a TSR inferior to −30% (p = 0.83). Conclusion: In a routine practice, GRE sequences cannot be a confident tool to

  8. [Renal tumors: The International Society of Urologic Pathology (ISUP) 2012 consensus conference recommendations].

    Science.gov (United States)

    Rioux-Leclercq, Nathalie; Ferran, Algaba; Mahul, Amin; Argani, Pedram; Billis, Athanase; Bonsib, Stephen; Cheng, Liang; Cheville, John; Eble, John; Egevad, Lars; Epstein, Jonathan; Grignon, David; Hes, Ondrej; Humphrey, Peter; Magi-Galluzzi, Cristina; Martignoni, Guido; McKenney, Jesse; Merino, Maria; Moch, Holger; Montironi, Rodolfo; Netto, George; Reuter, Viktor; Samaratunga, Hemamali; Shen, Steven; Srigley, John; Tamboli, Pheroze; Tan, Puay Hoon; Tickoo, Satish; Trpkov, Kiril; Zhou, Ming; Delahunt, Brett; Comperat, Eva

    2014-12-01

    During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells.

    Science.gov (United States)

    Brown, Dennis; Bouley, Richard; Păunescu, Teodor G; Breton, Sylvie; Lu, Hua A J

    2012-05-15

    Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes.

  10. Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Mele, Ermelinda; Cozzi, Francesco

    2013-09-01

    Mild-to-moderate renal function loss may be an independent risk factor for cardiovascular disease and overall mortality. As in adults with renal carcinoma nephrectomy is associated with an high risk for moderate renal function loss, we aimed to assess the renal function adaptation over a long period of time in children with unilateral renal tumor (URT). Seventy-two children who underwent surgery for URT were enrolled in this study. Glomerular filtration rate was estimated (eGFR) with the Modification of Diet in Renal Study or the Schwartz equation, as appropriate for the age. Twelve patients treated by nephron-sparing surgery (Group A) and 42 treated by nephrectomy (Group B) had an age between 2 and 30 years; 18 patients treated by nephrectomy had an age between 33 and 51 years (Group C). At cross-sectional follow-up 8% patients of Group A, 42% of Group B and 78% of Group C presented a mild-to-moderate renal function. The longitudinal data stratified by post-operative intervals showed that patients of Group C presented a significant progressive decrease in mean ± standard deviation eGFR (88.1 ± 22.6 during the third decade after surgery vs. 66.6 ± 15.6 ml/min/1.73 m(2) during the fifth decade after surgery; P = 0.02). The longitudinal data stratified by age showed that patients with an age between 45 and 54 years presented a mean eGFR significantly lower than that expected for the physiological renal function decline with aging (P = 0.001). Aging is associated with a mild-to-moderate renal function loss in many adult patients following nephrectomy during childhood for URT. Copyright © 2013 Wiley Periodicals, Inc.

  11. Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Lining Jia

    Full Text Available This study was to investigate whether sorafenib can inhibit the progression of renal fibrosis and to study the possible mechanisms of this effect.Eight-week-old rats were subjected to unilateral ureteral obstruction (UUO and were intragastrically administered sorafenib, while control and sham groups were administered vehicle for 14 or 21 days. NRK-52E cells were treated with TGF-β1 and sorafenib for 24 or 48 hours. HE and Masson staining were used to visualize fibrosis of the renal tissue in each group. The expression of α-SMA and E-cadherin in kidney tissue and NRK-52E cells were performed using immunohistochemistry and immunofluorescence. The apoptosis rate of NRK-52E cells was determined by flow cytometry analysis. The protein levels of Smad3 and p-Smad3 in kidney tissue and NRK-52E cells were detected by western blot analysis.HE staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration in the sorafenib-treated-UUO groups were significantly decreased compared with the vehicle-treated-UUO group (p<0.05. Masson staining showed that the area of fibrosis was significantly decreased in the sorafenib-treated-UUO groups compared with vehicle-treated-UUO group (p<0.01. The size of the kidney did not significantly increase; the cortex of the kidney was thicker and had a richer blood supply in the middle-dose sorafenib group compared with the vehicle-treated-UUO group (p<0.05. Compared with the vehicle-treated-UUO and TGF-β-stimulated NRK-52E groups, the expression of a-SMA and E-cadherin decreased and increased, respectively, in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (p<0.05. The apoptotic rate of NRK-52E cells treated with sorafenib decreased for 24 hours in a dose-dependent manner (p<0.05. Compared with the vehicle-treated UUO and TGF-β-stimulated NRK-52E groups, the ratio of p-Smad3 to Smad3 decreased in the sorafenib-treated groups (p<0.05.Our results suggest that

  12. 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.

  13. Correlation between Dynamic Spiral-CT Enhancement Parameters and Tumor Angiogenesis in Renal Cell Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jinhong Wang; Weixia Chen; Xiuhui Zhang; Pengqiu Min; Rongbo Liu; Hengxuan Yang

    2005-01-01

    OBJECTIVE To prospectively investigate the correlation between the enhancement parameters of a dynamic-CT (D-CT) scan for renal cell carcinomas (RCC) and the carcinoma tissue microvessel density (MVD) in renal cell carcinomas (RCC).METHODS Twenty-four cases of renal cell carcinoma verifyied by histopathology were scanned via dynamic-CT, followed by a whole kidney scan. Enhancement parameters were derived as follows .The slope of the contrast media uptake curve (S), area under the curve(AR), the density difference before and after tissue enhancement (△HU) and tissue blood ratio (TBR) were calculated for all lesions. Time-density curve types were ranked from the lowest to the highest of the slope of the contrast media uptake curve (S) as type A, B and C. Pathologic slides corresponding to the CT imagings were subjected to CD34 monoclonal antibodies, then were evaluated with an image analyzer to count hot spots of MVD. By using the Spearman rank correlation tests, statistical analysis was performed to determine the strength of the relationship between enhancement parameters and MVD determinations.RESULTS The carcinoma tissue MVD showed a direct correlation with the enhancement parameters of D-CT (r=0.54, r=0.62, r=0.55, r=0.64, r=0.44,P< 0.05). Moreover the S, △HU, TBR and type curves all demonstrated a strong correlation with the MVD. By analyzing the various enhancement parameters of the time-density curves, the relationship between the enhancement CT parameters corresponding to the tumor's MVD was identified.CONCLUSION A dynamic spiral-CT scan may be a helpful method as a measurement of tumor angiogenesis in vivo in RCC.

  14. Tumor necrosis factor inhibitors block apoptosis of human epithelial cells of the salivary glands.

    Science.gov (United States)

    Sisto, Margherita; D'Amore, Massimo; Caprio, Simone; Mitolo, Vincenzo; Scagliusi, Pasquale; Lisi, Sabrina

    2009-08-01

    Inhibition of tumor necrosis factor-alpha (TNF-alpha) in organ-specific autoimmune disease is proving efficacious for a large number of patients. A wide array of biological agents has been designed to inhibit TNF-alpha, such as adalimumab (fully humanized) and etanercept (soluble TNF-alpha receptor fusion constructs p75 subunit). Recently, we suggested that anti-Ro and anti-La autoantibodies (Abs) isolated from patients with Sjögren's syndrome, an autoimmune rheumatic disease, are able to trigger cell death through extrinsic apoptotic mechanisms in human salivary gland epithelial cells (SGEC). We analyzed if primary human SGEC cultures, established from biopsy of labial minor salivary glands, are able to produce TNF-alpha, an inductor of the extrinsic apoptotic pathway, when treated with anti-Ro autoantibodies. A comparative study was performed to test the efficacy of adalimumab and etanercept to block TNF-alpha-mediated apoptosis. ELISA assay and RT-PCR were employed to visualize TNF-alpha production, and apoptosis was evaluated by DNA ladder and flow cytometry. We found that cell treatment with anti-Ro autoantibodies determines TNF-alpha production that reaches a maximum at 16 h and is decreased (P < 0.05) at 24 and 48 h. Adalimumab seems to be more efficacious than etanercept in blocking TNF-alpha-mediated apoptosis. The YOPRO-1 (+) and propidium iodide (-) method revealed 60% of apoptotic cells after 24 h of incubation with anti-Ro compared with 15% of apoptotic cells treated with anti-Ro plus adalimumab and 25% of apoptotic cells treated with anti-Ro plus etanercept. The antiapoptotic effect of adalimumab and etanercept was supported by inhibition of DNA laddering induced by anti-Ro Abs. These data validate the therapeutic efficacy of the anti-TNF reagents in the treatment of autoimmune disorders.

  15. RET receptor expression in thyroid follicular epithelial cell-derived tumors.

    Science.gov (United States)

    Bunone, G; Uggeri, M; Mondellini, P; Pierotti, M A; Bongarzone, I

    2000-06-01

    The RET proto-oncogene encodes a receptor tyrosine kinase for transforming growth factor-beta-related neurotrophic factors, which include GDNF and neurturin. The expression of RET proto-oncogene was detected in several tissues, such as spleen, thymus, lymph nodes, salivary gland, and spinal cord, and in several neural crest-derived cell lines. RET expression in the thyroid gland was reported to be restricted to neural crest-derived C cells. The presence of RET mRNA or protein has not yet been reported in thyroid follicular cells. We previously demonstrated the expression of oncogenic rearranged versions of RET in papillary thyroid carcinomas: tumors derived from thyroid follicular cells. To assess the expression of the normal RET proto-oncogene in follicular cells, we analyzed its expression in a panel of neoplasias originating from thyroid follicular epithelial cells: papillary carcinomas and both follicular adenomas and carcinomas. We also demonstrated the presence of RET normal transcripts in two follicular thyroid carcinoma lymph node metastases. Moreover, we found the presence of the RET/ELE1 transcript, the reciprocal complementary form of the oncogenic fusion transcript ELE1/RET, in a papillary thyroid carcinoma specimen expressing the RET/PTC3 oncogene, thus demonstrating that the RET promoter is active in those cells after rearrangement. Finally, we show that in a papillary carcinoma-derived cell line expressing the proto-RET receptor and the related GFRalpha2 co-receptor, GDNF treatment induced RET tyrosine phosphorylation and subsequent signal transduction pathway, indicating that RET could be active in thyroid follicular cells.

  16. ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC.

    Science.gov (United States)

    Griffin, Nicolas I; Sharma, Gayatri; Zhao, Xiangshan; Mirza, Sameer; Srivastava, Shashank; Dave, Bhavana J; Aleskandarany, Mohammed; Rakha, Emad; Mohibi, Shakur; Band, Hamid; Band, Vimla

    2016-11-16

    We have established the critical role of ADA3 as a coactivator of estrogen receptor (ER), as well as its role in cell cycle progression. Furthermore, we showed that ADA3 is predominantly nuclear in mammary epithelium, and in ER+, but is cytoplasmic in ER- breast cancers, the latter correlating with poor survival. However, the role of nuclear ADA3 in human mammary epithelial cells (hMECs), and in ER+ breast cancer cells, as well as the importance of ADA3 expression in relation to patient prognosis and survival in ER+ breast cancer have remained uncharacterized. We overexpressed ADA3 in hMECs or in ER+ breast cancer cells and assessed the effect on cell proliferation. The expression of ADA3 was analyzed then correlated with the expression of various prognostic markers, as well as survival of breast cancer patients. Overexpression of ADA3 in ER- hMECs as well as in ER+ breast cancer cell lines enhanced cell proliferation. These cells showed increased cyclin B and c-MYC, decreased p27 and increased SKP2 levels. This was accompanied by increased mRNA levels of early response genes c-FOS, EGR1, and c-MYC. Analysis of breast cancer tissue specimens showed a significant correlation of ADA3 nuclear expression with c-MYC expression. Furthermore, nuclear ADA3 and c-MYC expression together showed significant correlation with tumor grade, mitosis, pleomorphism, NPI, ER/PR status, Ki67 and p27 expression. Importantly, within ER+ cases, expression of nuclear ADA3 and c-MYC also significantly correlated with Ki67 and p27 expression. Univariate Kaplan Meier analysis of four groups in the whole, as well as the ER+ patients showed that c-MYC and ADA3 combinatorial phenotypes showed significantly different breast cancer specific survival with c-MYC-high and ADA3-Low subgroup had the worst outcome. Using multivariate analyses within the whole cohort and the ER+ subgroups, the significant association of ADA3 and c-MYC expression with patients' outcome was independent of tumor grade

  17. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ) in normal mammary epithelial cells and breast tumors.

    Science.gov (United States)

    Smart, Chanel E; Askarian Amiri, Marjan E; Wronski, Ania; Dinger, Marcel E; Crawford, Joanna; Ovchinnikov, Dmitry A; Vargas, Ana Cristina; Reid, Lynne; Simpson, Peter T; Song, Sarah; Wiesner, Christiane; French, Juliet D; Dave, Richa K; da Silva, Leonard; Purdon, Amy; Andrew, Megan; Mattick, John S; Lakhani, Sunil R; Brown, Melissa A; Kellie, Stuart

    2012-01-01

    The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.

  18. Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Fernandez Hervé

    2009-10-01

    Full Text Available Abstract Background Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC, currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ, an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation. Results GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P P Conclusion The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.

  19. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    Science.gov (United States)

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.

  20. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications

    Science.gov (United States)

    Janik, S.; Schiefer, A. I.; Bekos, C.; Hacker, P.; Haider, T.; Moser, J.; Klepetko, W.; Müllauer, L.; Ankersmit, H. J.; Moser, B.

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  1. Promotion on Nucleation and Aggregation of Calcium Oxalate Crystals by Injured African Green Monkey Renal Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    张燊; 彭花; 姚秀琼; 苏泽轩; 欧阳健明

    2012-01-01

    The purpose of this work was to detect the properties of African green monkey renal epithelial cells (Vero) after oxidative injury and to study the mediation of the injured Vero on aggregation and formation of calcium oxalate crystals. This injury model was induced by 0.15 mmol/L H2O2 according to the pretest evaluation. The results suggested that H2O2 could injure Vero significantly and decrease cell viability in a time-dependent manner for exposure time of 0.5--2 h. After cell injury, the indexes connected with oxidative injury changed. The malondialdehyde (MDA) content and osteopontin (OPN) expression increased, while superoxide dismutase (SOD) level decreased. It resulted in the increase of both the amount of CaOxa crystals and the degree of crystal aggregation on the injured cells. This work indicated that injured cells promoted the formation of calcium oxalate monohydrate (COM) crystals, thus increased the risk of formation of urinary stone.

  2. Physiological Functions and Regulation of the Na+/H+ Exchanger [NHE1] in Renal Tubule Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Patricia G Vallés

    2015-08-01

    Full Text Available The sodium-hydrogen exchanger isoform-1 [NHE1] is a ubiquitously expressed plasma membrane protein that plays a central role in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Outside of this important physiological function, the NHE1 cytosolic tail domain acts as a molecular scaffold regulating cell survival and actin cytoskeleton organization through NHE1-dependent signaling proteins. NHE1 plays main roles in response to physiological stress conditions which in addition to cell shrinkage and acidification, include hypoxia and mechanical stimuli, such as cell stretch. NHE1-mediated modulation of programmed cell death results from the exchanger-mediated changes in pHi, cell volume, and/or [Na+]I; and, it has recently become known that regulation of cellular signaling pathways are involved as well. This review focuses on NHE1 functions and regulations. We describe evidence showing how these structural actions integrate with ion translocation in regulating renal tubule epithelial cell survival.

  3. Epinephrine Evokes Renalase Secretion via a-Adrenoceptor/NF-κB Pathways in Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2014-08-01

    Full Text Available Background/Aims: Renalase is a recently discovered, kidney-specific monoamine oxidase that metabolizes circulating catecholamines. These findings present new insights into hypertension and chronic kidney diseases. Previous data demonstrated that renalase was mainly secreted from proximal tubules which could be evoked by catecholamines. The purpose of this study is to investigate whether renalase expression is induced by epinephrine via a-adrenoceptor/NFκB pathways. Methods: HK2 cells were utilized to explore renalase expression in response to epinephrine in vitro. Phentolamine, an a-adrenoceptor antagonist, and Tosyl Phenylalanyl Chloromethyl Ketone (TPCK were used to block a-adrenoceptor and to knock down the transcription factor NFκB, respectively. Renalase expression was analyzed using Western blot and quantitative PCR. Results: Both protein and mRNA levels of renalase in HK2 cells increased in response to epinephrine (PConclusion: Epinephrine evokes renalase secretion via a-adrenoceptor/NF-κB pathways in renal proximal tubular epithelial cells.

  4. Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip.

    Science.gov (United States)

    Li, Encheng; Xu, Zhiyun; Liu, Fen; Wang, Huiling; Wen, Jiabin; Shao, Shujuan; Zhang, Lichuan; Wang, Lei; Liu, Chong; Lu, Jianxin; Wang, Wenxin; Gao, Zhancheng; Wang, Qi

    2014-08-01

    Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear. In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE. Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways. The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.

  5. [Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)].

    Science.gov (United States)

    Kristiansen, G; Delahunt, B; Srigley, J R; Lüders, C; Lunkenheimer, J-M; Gevensleben, H; Thiesler, T; Montironi, R; Egevad, L

    2015-05-01

    The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

  6. 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.

  7. Natural history of untreated renal cell carcinoma with venous tumor thrombus.

    Science.gov (United States)

    Reese, Adam C; Whitson, Jared M; Meng, Maxwell V

    2013-10-01

    The natural history of untreated renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is poorly characterized. We aimed to describe the natural history of this disease, and to identify prognostic factors associated with disease-specific survival. We identified patients in the Surveillance, Epidemiology, and End Results (SEER) database with untreated renal cell carcinoma and venous tumor thrombi. Disease-specific median and 1-year survival rates were determined, and disease-free survival curves were plotted using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to identify factors associated with disease-specific and overall survival in this patient group. Of 2,265 patients with RCC and VTT, 390 (17%) underwent no treatment; 278 (71%) patients died during follow-up; of these, 243 deaths (87%) were due to RCC. Median and 1-year disease-specific survival for this group was 5 months and 29%, respectively. On multivariable analysis, the extent of tumor thrombus (HR 1.7 for T3c vs. T3b, 95% CI 1.0-2.7) and the presence of metastases (HR 3.1 for M+ vs. M0, 95% CI 1.7-5.5) were most strongly associated with disease-specific mortality. Prognosis is poor for the majority of untreated patients with RCC and VTT. Supradiaphragmatic thrombi and distant metastases are adverse prognostic factors in this patient group. This information is important when counseling patients as to the risk and benefits of surgical vs. nonoperative management of RCC and VTT. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Tumor perfusion assessed by dynamic contrast-enhanced MRI correlates to the grading of renal cell carcinoma: Initial results

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    Palmowski, Moritz, E-mail: mpalmowski@ukaachen.d [Department of Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen (Germany); Department of Diagnostic Radiology, Medical Faculty, RWTH Aachen University, Aachen (Germany); Schifferdecker, Isabel [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany); Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany); Zwick, Stefan [Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany); Macher-Goeppinger, Stephan [Institute of Pathology, Heidelberg University, Heidelberg (Germany); Laue, Hendrik [MeVis Research, Center for Medical Image Computing, Bremen (Germany); Haferkamp, Axel [Department of Urology, Heidelberg University (Germany); Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany); Kiessling, Fabian [Department of Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen (Germany); Hallscheidt, Peter [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany)

    2010-06-15

    In this study, we investigated whether assessment of the tumor perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) enables to estimate the morphologic grading of renal cell carcinomas. A total of 21 patients with suspected renal cell cancer were examined using a Gadobutrol-enhanced, dynamic saturation-recovery, turbo-fast, low-angle shot sequence. Tumor perfusion and the tissue-blood ratio within the entire tumor and the most highly vascularized part of the tumor were calculated according to the model of Miles. Immediately after examination, patients underwent surgery, and the results from imaging were compared with the morphological analysis of the histologic grading. Fourteen patients had G2 tumors, and seven patients had G3 tumors. Significantly higher perfusion values (p < 0.05) were obtained in G3 tumors than in G2 tumors when the entire tumor area was considered (1.59 {+-} 0.44 (ml/g/min) vs. 1.08 {+-} 0.38 (ml/g/min)) or its most highly vascularized part (2.14 {+-} 0.89 (ml/g/min) vs. 1.40 {+-} 0.49 (ml/g/min)). By contrast, the tissue-blood ratios did not differ significantly between the two groups. In conclusion, unlike tissue-blood ratio, surrogate parameters of the tumor perfusion determined by DCE MRI seem to allow an estimation of the grading of renal cell carcinoma. However, further studies with high case numbers and including patients with G1 tumors are required to evaluate the full potential and clinical impact.

  9. Activation of SUR2B/Kir6.1-type KATP channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage

    Institute of Scientific and Technical Information of China (English)

    Ying ZHAO; Hai WANG

    2012-01-01

    Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure.Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (KATP) in the endothelium.It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium,glomerular mesangium,and the endothelium and the smooth muscle of blood vessels.Herein,we hypothesized that activating renal KATP channels with iptakalim might have directly neroprotective effects.In this study,glomerular endothelial,mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h.0.25 μl/ml OA could cause cellular damage of glomerular endothelium and mesangium,while 1.25μl/ml OA could lead to the injury of three types of renal cells.It was observed that pretreatment with iptakalim at concentrations of 0.1,1,10 or 100 μmol/L prevented cellular damage of glomerular endothelium and tubular epithelium,whereas iptakalim from 1 to 100 μmol/L prevented the injury of mesangial cells.Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner,significantly antagonized by glibenclamide,a KATP blocker.Iptakalim played a protective role in the main cell types of kidney,which was consistent with natakalim,a highly selective SUR2B/Kir6.1 channel opener.Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels,suggesting a new strategy for renal injury by its endothelial and renal cell protection.

  10. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management.

    Science.gov (United States)

    Vollherbst, Dominik; Bertheau, Robert; Kauczor, Hans-Ulrich; Radeleff, Boris Alexis; Pereira, Philippe L; Sommer, Christof-Matthias

    2017-03-01

    Background Radiofrequency ablation (RFA) is an established treatment for small renal tumors. The objective of this review is to systematically assess the type, frequency, risk factors and management of treatment failure after image-guided percutaneous RFA of renal tumors. Method 10 studies (967 patients, 1033 tumors) with a mean/median follow-up of ≥ 30 months were systematically identified and analyzed. Results and Conclusion Image-guided percutaneous RFA of localized renal tumors is very effective. The most common type of treatment failure is residual unablated tumor (5.9 %), followed by local tumor progression (4.7 %). De novo tumors in the kidneys occur in 1.3 % of cases and extra-renal metastases in 2.0 %. Local tumor progression, de novo tumors in the kidneys and extra-renal metastases occur predominantly later than 12 months after initial RFA. Tumor size > 3 cm and central tumor location are the major risk factors for treatment failure. In the case of treatment failure, repeated RFA shows high success rates (86.3 % for residual unablated tumors and 87.5 % for local tumor progression). Key Points: · Treatment failure can be subdivided into residual unablated tumor and local tumor progression.. · Residual unablated tumor occurs in 5.9 % of cases.. · Local tumor progression occurs in 4.7 % of cases.. · Tumor size and location are the major risk factors for treatment failure.. · Repeated RFA is effective and commonly used for management.. Citation Format · Vollherbst D, Bertheau R, Kauczor H et al. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management. Fortschr Röntgenstr 2017; 189: 219 - 227.

  11. Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Carmen Y S Chu

    Full Text Available Mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1 can cause distal renal tubular acidosis (dRTA, a disease often due to mis-trafficking of the mutant protein. In this study, we investigated whether trafficking of a Golgi-retained dRTA mutant, G701D kAE1, or two dRTA mutants retained in the endoplasmic reticulum, C479W and R589H kAE1, could be functionally rescued to the plasma membrane of Madin-Darby Canine Kidney (MDCK cells. Treatments with DMSO, glycerol, the corrector VX-809, or low temperature incubations restored the basolateral trafficking of G701D kAE1 mutant. These treatments had no significant rescuing effect on trafficking of the mis-folded C479W or R589H kAE1 mutants. DMSO was the only treatment that partially restored G701D kAE1 function in the plasma membrane of MDCK cells. Our experiments show that trafficking of intracellularly retained dRTA kAE1 mutants can be partially restored, and that one chemical treatment rescued both trafficking and function of a dRTA mutant. These studies provide an opportunity to develop alternative therapeutic solutions for dRTA patients.

  12. Craniofacial brown tumor as a result of secondary hyperparathyroidism in chronic renal disease patient: A rare entity

    Science.gov (United States)

    Verma, Pradhuman; Verma, Kanika Gupta; Verma, Dinesh; Patwardhan, Nitin

    2014-01-01

    Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to primary or secondary hyperparathyroidism resulting in a local destructive phenomenon. The differential diagnosis based on histological examination is only presumptive. Clinical, radiological and laboratory data are necessary for definitive diagnosis. Here, we report a very rare case of brown tumor involving maxilla and mandible, which is the result of secondary hyperparathyroidism in 30-year-old female patient with chronic renal disease. PMID:25328310

  13. Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development.

    Science.gov (United States)

    Giammanco, Antonina; Blanc, Valerie; Montenegro, Grace; Klos, Coen; Xie, Yan; Kennedy, Susan; Luo, Jianyang; Chang, Sung-Hee; Hla, Timothy; Nalbantoglu, Ilke; Dharmarajan, Sekhar; Davidson, Nicholas O

    2014-09-15

    HuR is a ubiquitous nucleocytoplasmic RNA-binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur (IKO) mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of Apc(min/+) mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a three-fold decrease in tumor burden characterized by reduced proliferation, increased apoptosis, and decreased expression of transcripts encoding antiapoptotic HuR target RNAs. Similarly, Hur(IKO) mice subjected to an inflammatory colon carcinogenesis protocol [azoxymethane and dextran sodium sulfate (AOM-DSS) administration] exhibited a two-fold decrease in tumor burden. Hur(IKO) mice showed no change in ileal Asbt expression, fecal bile acid excretion, or enterohepatic pool size that might explain the phenotype. Moreover, none of the HuR targets identified in Apc(min/+)Hur(IKO) were altered in AOM-DSS-treated Hur(IKO) mice, the latter of which exhibited increased apoptosis of colonic epithelial cells, where elevation of a unique set of HuR-targeted proapoptotic factors was documented. Taken together, our results promote the concept of epithelial HuR as a contextual modifier of proapoptotic gene expression in intestinal cancers, acting independently of bile acid metabolism to promote cancer. In the small intestine, epithelial HuR promotes expression of prosurvival transcripts that support Wnt-dependent tumorigenesis, whereas in the large intestine epithelial HuR indirectly downregulates certain proapoptotic RNAs to attenuate colitis-associated cancer. Cancer Res; 74(18); 5322-35. ©2014 AACR.

  14. Cushing syndrome as presenting symptom of calcifying nested stromal-epithelial tumor of the liver in an adolescent boy: a case report

    NARCIS (Netherlands)

    Weeda, V.B.; Reuver, P.R.; Bras, H.; Zsiros, J.; Lamers, W.H.; Aronson, D.C.

    2016-01-01

    BACKGROUND: Ectopic adrenocorticotropic hormone-producing primary liver tumors are rare, especially in children. We report the case of an adolescent boy of mixed Dutch and Moroccan descent with an adrenocorticotropic hormone-producing calcifying nested stromal-epithelial tumor with long-term

  15. [Radical nephrectomy and thrombectomy in patients with renal cell cancer complicated by tumoral thrombosis of the renal vein and vena cava inferior].

    Science.gov (United States)

    Rusyn, V I; Korsak, V V; Rusyn, A V; Boĭko, S O

    2013-01-01

    Surgical treatment was conducted in 81 patients, suffering renocellular cancer (RCC), complicated by a renal vein and vena cava inferior thrombosis. According to the Mayo clinic classification, the level of a tumoral thrombus spread was established: the 0 level--in 37 patients, the level I--in 19, the level II--in 17, the level III --in 6, and the level IV--in 2. There were substantiated the optimal surgical accesses and technique of radical nephrectomy and thrombectomy for RCC, complicated by a renal vein and vena cava inferior thrombosis. It is recommended to apply transabdominal accesses: the extended median laparotomic, bilateral subcostal of a "Chevron" or "Mercedes" type. There was shown, that the access choice depends on the level of the tumoral thrombus localization.

  16. Does a venous tumor thrombus exclude renal transitional cell carcinoma? Implications for neo-adjuvant treatment strategies.

    Science.gov (United States)

    Huber, Johannes; Teber, Dogu; Hatiboglu, Gencay; Popeneciu, Valentin; Jakobi, Hildegard; Hallscheidt, Peter; Pahernik, Sascha; Hohenfellner, Markus

    2014-02-01

    A venous tumor thrombus (VTT) is well-known in renal cell carcinoma, but we experienced a series of five patients with VTT due to renal transitional cell carcinoma (TCC). Our study aimed to determine the incidence and clinical relevance of this entity. From our prospectively-maintained tumor database, we identified 102 patients with renal TCC according to postoperative histology and analyzed the incidence of VTT in renal TCC from 1990 to 2010. Five out of 102 patients with TCC (5%) had a VTT. None of these five patients experienced gross haematuria and we presumed correct diagnosis preoperatively in one out of five patients. Univariate analysis revealed that TNM stage and resection status were inferior in the VTT group. All five patients from the VTT group died from their disease, with a median survival of 8.9 months. With regard to all diagnosed VTT, the effective incidence of vena cava involvement in RCC was 48-fold higher than in renal TCC. A VTT is very suggestive of renal cell carcinoma. However, before neo-adjuvant treatment, the diagnosis should be assured whenever there is doubt.

  17. Berberine reverses epithelial-to-mesenchymal transition and inhibits metastasis and tumor-induced angiogenesis in human cervical cancer cells.

    Science.gov (United States)

    Chu, Shu-Chen; Yu, Cheng-Chia; Hsu, Li-Sung; Chen, Kuo-Shuen; Su, Mei-Yu; Chen, Pei-Ni

    2014-12-01

    Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-β1-induced EMT and caused upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and snail-1. Selective snail-1 inhibition by snail-1-specific small interfering RNA also showed increased E-cadherin expression in SiHa cells. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Importantly, an in vivo BALB/c nude mice xenograft model and tail vein injection model showed that berberine treatment reduced tumor growth and lung metastasis by oral gavage, respectively. Taken together, these findings suggested that berberine could reduce metastasis and angiogenesis of cervical cancer cells, thereby constituting an adjuvant treatment of metastasis control.

  18. 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.

  19. Presentación sincrónica de cáncer colorrectal y tumor renal

    OpenAIRE

    JENSEN B,CHRISTIAN; RIFFO R,RODRIGO; MARTINEZ R,NICOLÁS; VALENZUELA V,ANTONIA

    2007-01-01

    Introducción: La presencia simultánea de dos cánceres primarios en el organismo es un evento de baja frecuencia. La presentación sincrónica de cáncer colorectal y renal es un ejemplo de esto, con una prevalencia entre el 0,33-0,5% de tumores renales en pacientes portadores de cáncer colorrectal. Objetivos: Determinar la frecuencia de presentación simultánea de cáncer colorectal y tumor renal en nuestro medio, y analizar el manejo de esta doble patología desde el punto de vista quirúrgico. Mat...

  20. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  1. 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.

  2. P16 and p53 expression in (pre)malignant epidermal tumors of renal transplant recipients and immunocompetent individuals.

    NARCIS (Netherlands)

    Blokx, W.A.M.; Jong, E.M.G.J. de; Wilde, P.C.M. de; Bulten, J.; Link, M.M.G.M.; Ruiter, D.J.; Kerkhof, P.C.M. van de

    2003-01-01

    Ultraviolet (UV) radiation is a prevailing factor implicated in the etiology of keratinocytic intraepidermal neoplasia (KIN) and squamous cell carcinomas (SCCs), as evidenced by the high frequency of UV-related mutations in the p53 and p16 tumor suppressor genes. In renal transplant recipients (RTRs

  3. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    OpenAIRE

    Néstor Moisés Tineo Araque; Helen Daniela Uzcátegui Camacaro; Henrry Ramírez; Humberto Ruz

    2010-01-01

    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...

  4. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    OpenAIRE

    Néstor Moisés Tineo Araque; Helen Daniela Uzcátegui Camacaro; Henrry Ramírez; 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...

  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. Paraneoplastic Erythropoietin Secreting Tumor of Renal Origin:A Forgotten Endocrine Hormone

    Institute of Scientific and Technical Information of China (English)

    Yaseen Ali; Amila M. Parekh; Rahul K. Rao; Taseen Ali; Jordan Garvey

    2015-01-01

    Paraneoplastic syndromes are a group of disorders associated by the presence of cancer in the human body, but are not caused by the cancer or its metastatic potential. These syndromes are usually the result of cell mediators. For instance, the interleukins and cytokines secreted by the body’s defense system combat with neoplastic cells that inadvertently bind to cell speciifc receptors in the endocrine system due to similar structural morphology and produce undesired side effects. In this article, we presented an interesting case of a 44-year-old male veteran who came to our free clinic for his chronic constipation unmitigated by over the counter laxatives and sought other provider care in the past few months. During our brief clinic visit, his history and examination revealed that he had also been suffering from mild abdominal pain, decrease in appetite, inconvenient reddish plethoric facial appearance and lethargy. A careful review of the history, physical and laboratory examination revealed erythrocytosis and mild hypercalcemia. Meanwhile, a renal mass biopsy was proven to be erythropoietin secreting renal cell tumor. Subsequently, the patient underwent resection and was followed to complete resolution of his symptoms.

  7. Everolimus in the treatment of renal cell carcinoma and neuroendocrine tumors.

    Science.gov (United States)

    Chan, Hiu-yan; Grossman, Ashley B; Bukowski, Ronald M

    2010-08-01

    Renal cell carcinoma (RCC) and neuroendocrine tumors (NET) are uncommon malignancies, highly resistant to chemotherapy, that have emerged as attractive platforms for evaluating novel targeted regimens. Everolimus is an oral rapamycin derivative within the mammalian target of rapamycin class of agents. Preclinical series have shown that everolimus exhibits anticancer effects in RCC and NET cell lines. A phase 3 placebo-controlled study in advanced clear-cell RCC, known as RECORD-1 (for "REnal Cell cancer treatment with Oral RAD001 given Daily"), documented that everolimus stabilizes tumor progression, prolongs progression-free survival and has acceptable tolerability in patients previously treated with the multikinase inhibitors sunitinib and/or sorafenib. Everolimus has been granted regulatory approval for use in sunitinib-pretreated and/or sorafenib-pretreated advanced RCC and incorporated into clinical practice guidelines, and the RECORD-1 safety data are being used to develop recommendations for managing clinically important adverse events in everolimus-treated patients. Ongoing clinical trials are evaluating everolimus as earlier RCC therapy (first-line for advanced disease and as neoadjuvant therapy), in non-clear-cell tumors, and in combination with various other approved or investigational targeted therapies for RCC. Regarding advanced NET, recently published phase 2 data support the ability of everolimus to improve disease control in patients with advanced NET as monotherapy or in combination with somatostatin analogue therapy, octreotide long-acting release (LAR). Forthcoming data from phase 3 placebo-controlled trials of everolimus, one focused on monotherapy for pancreatic NET and the other on combination use with octreotide LAR for patients with advanced NET and a history of carcinoid syndrome, will provide insight into its future place in NET therapy. The results of a number of ongoing phase 3 evaluations of everolimus will determine its broader

  8. 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.

  9. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis.

    Science.gov (United States)

    Delahunt, Brett; McKenney, Jesse K; Lohse, Christine M; Leibovich, Bradley C; Thompson, Robert Houston; Boorjian, Stephen A; Cheville, John C

    2013-03-01

    Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.

  10. Utility of anteroposterior diameter ratio of tumor and abdomen for laparoscopic approach for radical nephrectomy in large renal masses.

    Science.gov (United States)

    Yadav, Priyank; Srivastava, Devarshi; Arakere, Sachin; Gupta, Shashikant; Aga, Pallavi; Mandhani, Anil

    2017-08-07

    Laparoscopic radical nephrectomy (LRN) is now increasingly done for tumors larger than 10 cm. Despite selection of favorable cases, LRN may not be successful due to lack of adequate working space with large tumors. We describe a new feature on Contrast Enhanced Computed Tomography (CECT) abdomen to predict feasibility of LRN for large renal masses between 10 and 15 cm. From January 2005 to December 2015, renal tumors between 10 and 15 cm were selected retrospectively for LRN. Patients with retroperitoneal lymphadenopathy, Inferior vena cava (IVC) thrombus and involvement of adjacent organs were excluded. Anteroposterior (AP) diameter ratio of renal tumor and abdomen (APROTA) was calculated by dividing the maximum AP diameter of tumor along with normal renal parenchyma, by the AP diameter of abdomen on CECT. The patients were stratified into two groups: Group A (successful LRN) and Group B (conversion to open surgery) and outcomes were compared. The reasons for conversion were also noted. Of 29 patients, 16 (55.2%) had successful LRN (Group A), while 13 (44.8%) had conversion to open surgery (group B). The median tumor size in Group A was 11.3 ± 1.8 cm and in Group B was 13.6 ± 1.26 cm. Eleven of 13 patients had conversion due to large tumor size causing failure to progress. Two conversions were due to bleeding and injury to the colon each. There was a significant difference in the APROTA in group A and B [0.43 ± 0.09 in group A and 0.64 ± 0.14 in group B (p = 0.0001)]. Patients with APROTA of more than 0.65 are unlikely to have successful outcome with LRN.

  11. Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways.

    Directory of Open Access Journals (Sweden)

    Shu-Fen Liu

    Full Text Available Renal interstitial fibrosis is characterized by increased extracellular matrix (ECM synthesis. Epithelial-mesenchymal transition (EMT in kidneys is driven by regulated expression of fibrogenic cytokines such as transforming growth factor-beta (TGF-β. Yam, or Dioscorea alata (DA is an important herb in Chinese medicine widely used for the treatment of clinical diabetes mellitus. However, the fibrosis regulatory effect of DA is unclear. Thus, we examined TGF-β signaling mechanisms against EMT in rat fibroblast cells (NRK-49F. The characterization of DA water-extracts used various methods; after inducing cellular fibrosis in NRK-49F cells by treatment with β-hydroxybutyrate (β-HB (10 mM, we used Western blotting to examine the protein expression in the TGF-β-related signal protein type I and type II TGF-β receptors, Smads2 and Smad3 (Smad2/3, pSmad2 and Smad3 (pSmad2/3, Smads4, Smads7, and EMT markers. These markers included E-cadherin, alpha-smooth muscle actin (α-SMA, and matrix metalloproteinase-2 (MMP-2. Bioactive TGF-β and fibronectin levels in the culture media were determined using ELISA. Expressions of fibronectin and Snail transcription factor, an EMT-regulatory transcription factor, were assessed by immunofluorescence staining. DA extract dose-dependently (50-200 µg/mL suppressed β-HB-induced expression of fibronectin in NRK-49F cells concomitantly with the inhibition of Smad2/3, pSmad2/3, and Smad4. By contrast, Smad7 expression was significantly increased. DA extract caused a decrease in α-SMA (α-smooth muscle actin and MMP-2 levels, and an increase in E-cadherin expression. We propose that DA extract might act as a novel fibrosis antagonist, which acts partly by down regulating the TGF-β/smad signaling pathway and modulating EMT expression.

  12. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

    Science.gov (United States)

    Rinaldo, Christine Hanssen; Gosert, Rainer; Bernhoff, Eva; Finstad, Solrun; Hirsch, Hans H

    2010-11-01

    Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC(90)) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC(90)s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells in vitro.

  13. Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.

    LENUS (Irish Health Repository)

    Irnaten, Mustapha

    2009-08-01

    The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the nature of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (<5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis.

  14. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    C.E. Henry

    2017-06-01

    Full Text Available OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178. Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

  15. Imatinib Spares cKit-Expressing Prostate Neuroendocrine Tumors, whereas Kills Seminal Vesicle Epithelial-Stromal Tumors by Targeting PDGFR-β.

    Science.gov (United States)

    Jachetti, Elena; Rigoni, Alice; Bongiovanni, Lucia; Arioli, Ivano; Botti, Laura; Parenza, Mariella; Cancila, Valeria; Chiodoni, Claudia; Festinese, Fabrizio; Bellone, Matteo; Tardanico, Regina; Tripodo, Claudio; Colombo, Mario P

    2017-02-01

    Prostate cancer is a leading cause of cancer-related death in males worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favors prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of imatinib in TRAMP mice. Imatinib-treated TRAMP mice experience a partial benefit against prostate adenocarcinoma, because of inhibition of supportive MCs. However, they show an unexpected outgrowth of prostate NE tumors, likely because of defective signaling pathway downstream of cKit receptor. Also unexpected but very effective was the inhibition of epithelial-stromal tumors of the seminal vesicles achieved by imatinib treatment. These tumors normally arise in the seminal vesicles of TRAMP mice, independently of the degree of prostatic glandular lesions, and resemble phyllodes tumors found in human prostate and seminal vesicles, and in breast. In both mice and in patients, these tumors are negative for cKit but express PDGFR-β, another tyrosine kinase receptor specifically inhibited by imatinib. Our results imply a possible detrimental effect of imatinib in prostate cancer patients but suggest a promising therapeutic application of imatinib in the treatment of recurrent or metastatic phyllodes tumors. Mol Cancer Ther; 16(2); 365-75. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    Science.gov (United States)

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  17. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    Directory of Open Access Journals (Sweden)

    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  18. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  19. Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Iribe, Yasuhiro; Kuroda, Naoto; Nagashima, Yoji; Yao, Masahiro; Tanaka, Reiko; Gotoda, Hiroko; Kawakami, Fumi; Imamura, Yoshiaki; Nakamura, Yasushi; Ando, Midori; Araki, Akinobu; Matsushima, Jun; Nakatani, Yukio; Furuya, Mitsuko

    2015-03-01

    Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA-IX, Ksp-cadherin, CD82 and CK7.

  20. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    Directory of Open Access Journals (Sweden)

    Nestor Moisés Tineo Araque

    2011-02-01

    Full Text Available 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 enfermedad actual en febrero de 2010 caracterizado por autodetección de masa a nivel de hemiabdomen derecho. Se realizó nefrectomía derecha tomando en cuenta lo descrito en la literatura actual. El informe histológico definitivo reportó Sarcoma de Ewing extra esquelético. Esta es una patología quirúrgica poco frecuente, lo cual incentiva a su presentación y a la revisión de la literatura. Palabras Clave: tumor neuroectodérmico primitivo, diagnóstico, ultrasonido.

  1. Immunohistochemical expression of WNT5A and MMPs in odontogenic epithelial tumors and cysts.

    Science.gov (United States)

    Guimarães, Douglas Magno; Antunes, Daniella Moraes; Saturno, Juvani Lago; Massuda, Fabiola; Paiva, Katiúcia Batista da Silva; Nunes, Fabio Daumas

    2015-10-01

    The aim of this study was compare the expression of WNT5A and MMP2, 7 and 20, in frequent benign odontogenic tumors and odontogenic cysts, since these lesions have a different biological behavior. Eighty-one paraffin-embedded specimens of odontogenic tumors, including ameloblastoma and keratocystic odontogenic tumor, and thirty-two odontogenic cysts were used for immunohistochemical analysis. The expression of WNT5A in odontogenic tumors and inflammatory cyst was higher than in developmental odontogenic cyst. There was no statistical difference (p<0.05) in the expression of WNT5A when comparing the analyzed tumors. The expression of MMP7 was lower in RC with a statistical difference when compared with all tumors and cysts. Statistical differences also occurred when comparing glandular odontogenic cyst (GOC) to keratocyst odontogenic tumor (KOT) and calcifying cystic odontogenic tumor (CCOT). MMP20 expression was higher in ameloblastoma when compared to adenomatoid odontogenic tumor (AOT), DC and GOC. The expression of MMP20 was lower in CCOT when compared to all tumors and cysts. The expression of WNT5A in a group of odontogenic lesions suggests the participation of a non-canonical WNT signaling pathway in the progression and maintenance of these lesions. These molecules are possibly involved in the biological differences between odontogenic tumors and cysts. Considering previous studies, WNT5A may help promote the calcification seen in AOT, CCOT and CEOT by activating MMP7. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. Siva1 suppresses epithelial-mesenchymal transition and metastasis of tumor cells by inhibiting stathmin and stabilizing microtubules.

    Science.gov (United States)

    Li, Nan; Jiang, Peng; Du, Wenjing; Wu, Zhengsheng; Li, Cong; Qiao, Mengran; Yang, Xiaolu; Wu, Mian

    2011-08-02

    Epithelial-mesenchymal transition (EMT) enables epithelial cells to acquire motility and invasiveness that are characteristic of mesenchymal cells. It plays an important role in development and tumor cell metastasis. However, the mechanisms of EMT and their dysfunction in cancer cells are still not well understood. Here we report that Siva1 interacts with stathmin, a microtubule destabilizer. Siva1 inhibits stathmin's activity directly as well as indirectly through Ca(2+)/calmodulin-dependent protein kinase II-mediated phosphorylation of stathmin at Ser16. Via the inhibition of stathmin, Siva1 enhances the formation of microtubules and impedes focal adhesion assembly, cell migration, and EMT. Low levels of Siva1 and Ser16-phosphorylated stathmin correlate with high metastatic states of human breast cancer cells. In mouse models, knockdown of Siva1 promotes cancer dissemination, whereas overexpression of Siva1 inhibits it. These results suggest that microtubule dynamics are critical for EMT. Furthermore, they reveal an important role for Siva1 in suppressing cell migration and EMT and indicate that down-regulation of Siva1 may contribute to tumor cell metastasis.

  3. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.

    Science.gov (United States)

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J; Hayashi, Shim-Mo

    2007-04-01

    Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.

  4. 肾癌患者循环肿瘤细胞的研究进展%Advances in the Detection of Circulating Tumor Cells in Patients with Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    陈业刚

    2011-01-01

    Renal cell carcinoma is one of the most common renal malignancies in adults. Almost 1/3 of renal cell carcinomas are metastatic when diagnosed. Hcmatogenous disscmimtion is a significant pathway for tumor metastasis. Dissemination of tumor cells into the peripheral blood is the premise for tumor metastasis. Recent publications have reported that the presence of circulafing tumor cells (CTCs) correlates to lymph node status and presence of synchronous metastases from renal cell carcinoma. Detection of circulating tumor cells in the peripheral blood is a significant and independent prognostic factor for renal cell carcinoma. The study of circulating tumor cells will contribute to the discovery of the mechanism of tumor metastasis, provide guidance for tumor therapy, determine therapeutic efficacy and patient prognosis. Because of the small number of CTCs in the peripheral blood and lack of tumor specific markers, the application of CTCs is limited m clinical work. With the improvement ofthe TRAIL method, the development of new techniques and related research on tumor-specific markers, the sensitivity and specificity of CTC detection have been greatly enhanced. Methods to detect circulating tumor cells using tumor-specific markers include Magnetic Cell Sorting, isolation by size of epithelial tumor cells, Density Gradient Centrifugation, immunocytochemistry, Reverse Transcription Polymerase Chain Reaction, Flow Cytometry Assay, Laser Scanning Cytometry, and the CellSearch System. In this article, the progress of circulating tumor cell application in renal cell carcinoma patients is reviewed.%肾癌是成人肾脏最常见的恶性肿瘤,近1/3的肾细胞癌患者在诊断原发肿瘤时已有转移灶,血行播散是肾癌转移的重要途径,肿瘤细胞进入外周血是肿瘤远处转移的前提.近年研究表明,肾癌CTCs与淋巴结转移和肿瘤浸润有明显的相关性,外周血CTC,的检测可成为判断肿瘤预后的重要指标,CTCs的检测有

  5. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

    Science.gov (United States)

    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome.

    Science.gov (United States)

    Cornejo, Kristine M; Dong, Fei; Zhou, Amy G; Wu, Chin-Lee; Young, Robert H; Braaten, Kristina; Sadow, Peter M; Nielsen, G P; Oliva, Esther

    2015-10-01

    Histologic prognostic parameters in papillary renal cell carcinoma (PRCC) are unclear. The aims were to review the clinicopathological features of PRCC, including Fuhrman grade and International Society of Urological Pathology (ISUP) nucleolar grade, and to identify parameters that may be independent prognostic indicators. PRCCs in patients treated by nephrectomy were retrieved from the pathology files from 1984 to 2010. Parameters studied included tumor multifocality, size, PRCC type (1 or 2), Fuhrman grade, ISUP nucleolar grade, presence of necrosis, lymphovascular invasion, and stage at presentation. Cancer-specific survival (CSS) and overall survival (OS) were used as prognostic measures. Of 154 PRCCs, 112 (73%) were type 1, and 42 (27%), type 2. A total of 125 patients were male, and 29, female, with ages from 26 to 86 (mean, 62.7) years. Fuhrman grade was 1 in 8 (5%), 2 in 95 (62%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. ISUP nucleolar grade was 1 in 47 (31%), 2 in 56 (36%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. Mean follow-up interval was 73.9 months (0.13-222 months). ISUP nucleolar grade was a significant predictor of both CSS and OS in univariate (CSS, P = .001; OS, P = .004) and multivariate (CSS, P = .04; OS, P = .008) analyses, whereas Fuhrman grade was only predictive of CSS in univariate (P = .001) and multivariate (P = .04) analyses. Only ISUP nucleolar grade and lymphovascular invasion were independently prognostic for CSS and OS in univariate and multivariate analyses. Therefore, the ISUP nucleolar grade appears to be superior in predicting survival in patients with PRCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy.

    Science.gov (United States)

    Chua, Terence C; Chong, Chanel H; Liauw, Winston; Zhao, Jing; Morris, David L

    2012-08-01

    The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment.

  8. [Presurgical treatment of axitinib reduced operation risk by downsizing the vena cava tumor thrombus in advanced renal cell carcinomas: two case reports].

    Science.gov (United States)

    Hamada, Akihiro; Yamasaki, Toshinari; Negoro, Hiromitsu; Kobayashi, Takashi; Terada, Naoki; Sugino, Yoshio; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Yoshimura, Koji; Ogawa, Osamu

    2014-12-01

    In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus, surgical resection of both tumor and thrombus contributes to the improvement of patient's prognosis, but the risk of perioperative complication is still high. We experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor reduction effect without any severe adverse event. We could remove both tumor and thrombus without perioperative complications. In these two cases, downsizing of IVC thrombus enabled us to reduce the extent of the surgery.

  9. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  10. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor.

    NARCIS (Netherlands)

    Niekerk, C.C.; Vooijs, G.P.; Bulten, J.; Dijck, J.A.A.M. van; Verbeek, A.L.M.

    2007-01-01

    Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based st

  11. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor.

    NARCIS (Netherlands)

    Niekerk, C.C.; Vooijs, G.P.; Bulten, J.; Dijck, J.A.A.M. van; Verbeek, A.L.M.

    2007-01-01

    Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based

  12. Dexamethasone Inhibits Tumor Necrosis Factor-α-stimulated Gastric Epithelial Cell Migration

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    Jiing-Chyuan Luo

    2009-10-01

    Conclusion: TNF-α plays a regulatory role in rat gastric epithelial cell migration and dexamethasone inhibited TNF-α-stimulated cell migration, which was associated with a decrease in COX-2 expression and PGE2 formation. [J Chin Med Assoc 2009;72(10:509–514

  13. Smad mediated regulation of inhibitor of DNA binding 2 and its role in phenotypic maintenance of human renal proximal tubule epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mangalakumar Veerasamy

    Full Text Available The basic-Helix-Loop-Helix family (bHLH of transcriptional factors plays a major role in regulating cellular proliferation, differentiation and phenotype maintenance. The downregulation of one of the members of bHLH family protein, inhibitor of DNA binding 2 (Id2 has been shown to induce de-differentiation of epithelial cells. Opposing regulators of epithelial/mesenchymal phenotype in renal proximal tubule epithelial cells (PTEC, TGFβ1 and BMP7 also have counter-regulatory effects in models of renal fibrosis. We investigated the regulation of Id2 by these growth factors in human PTECs and its implication in the expression of markers of epithelial versus myofibroblastic phenotype. Cellular Id2 levels were reduced by TGFβ1 treatment; this was prevented by co-incubation with BMP7. BMP7 alone increased cellular levels of Id2. TGFβ1 and BMP7 regulated Id2 through Smad2/3 and Smad1/5 dependent mechanisms respectively. TGFβ1 mediated Id2 suppression was essential for α-SMA induction in PTECs. Although Id2 over-expression prevented α-SMA induction, it did not prevent E-cadherin loss under the influence of TGFβ1. This suggests that the loss of gate keeper function of E-cadherin alone may not necessarily result in complete EMT and further transcriptional re-programming is essential to attain mesenchymal phenotype. Although BMP7 abolished TGFβ1 mediated α-SMA expression by restoring Id2 levels, the loss of Id2 was not sufficient to induce α-SMA expression even in the context of reduced E-cadherin expression. Hence, a reduction in Id2 is critical for TGFβ1-induced α-SMA expression in this model of human PTECs but is not sufficient in it self to induce α-SMA even in the context of reduced E-cadherin.

  14. Linking of mPGES-1 and iNOS activates stem-like phenotype in EGFR-driven epithelial tumor cells.

    Science.gov (United States)

    Terzuoli, Erika; Finetti, Federica; Costanza, Filomena; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2017-03-01

    Inflammatory prostaglandin E-2 (PGE-2) favors cancer progression in epithelial tumors characterized by persistent oncogene input. However, its effects on tumor cell stemness are poorly understood at molecular level. Here we describe two epithelial tumor cells A431 and A459, originating from human lung and skin tumors, in which epithelial growth factor (EGF) induces sequential up-regulation of mPGES-1 and iNOS enzymes, producing an inflammatory intracellular milieu. We demonstrated that concerted action of EGF, mPGES-1 and iNOS causes sharp changes in cell phenotype demonstrated by acquisition of stem-cell features and activation of the epithelial-mesenchymal transition (EMT). When primed with EGF, epithelial tumor cells transfected with mPGES-1 or iNOS to ensure steady enzyme levels display major stem-like and EMT markers, such as reduction in E-cadherin with a concomitant rise in vimentin, ALDH-1, CD133 and ALDH activity. Tumorsphere studies with these cells show increased sphere number and size, enhanced migratory and clonogenic capacity and sharp changes in EMT markers, indicating activation of this process. The concerted action of the enzymes forms a well-orchestrated cascade where expression of iNOS depends on overexpression of mPGES-1. Indeed, we show that through its downstream effectors (PGE-2, PKA, PI3K/Akt), mPGES-1 recruits non-canonical transcription factors, thus facilitating iNOS production. In conclusion, we propose that the initial event leading to tumor stem-cell activation may be a leveraged intrinsic mechanism in which all players are either inherent constituents (EGF) or highly inducible proteins (mPGES-1, iNOS) of tumor cells. We suggest that incipient tumor aggressiveness may be moderated by reducing pivotal input of mPGES-1.

  15. Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

    Science.gov (United States)

    Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

    2016-11-01

    Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

  16. Fulminant Buddchiari syndrome caused by renal primitive neuroectodermal tumor with inferior vena cava thrombus extending to atrium.

    Science.gov (United States)

    Mete, Uttam K; Singh, Dig Vijay; Bhattacharya, Anish; Kakkar, Nandita

    2015-01-01

    Primitive neuroectodermal tumors (PNET) of the kidney are rare, the diagnosis usually being made at histopathology. A young female presented with a massive right renal mass with features of hepatic dysfunction. Computed tomography scan of the abdomen revealed a large tumor of right kidney with tumor thrombus extending from inferior vena cava (IVC) to right atrium with features suggesting Buddchiari syndrome (BCS). Needle biopsy of mass showed a round cell neoplasm and positive staining for neuron specific enolase and minimum inhibitory concentration-2 on immunohistochemistry. She was managed with neo-adjuvant chemotherapy, surgery and adjuvant chemotherapy. To the best of our knowledge this is the first case of renal PNET with inferior IVC tumor thrombus extending to right atrium with BCS. We suggest that renal PNET should be kept in mind as a differential diagnosis in young adults presenting with a large kidney mass extending to IVC that shows evidence of necrosis on imaging, which may be associated with BCS as in index case.

  17. Expression of pRb and p16INK4 in human thymic epithelial tumors in relation to the presence of human polyomavirus 7

    OpenAIRE

    Keijzers, Marlies; Rensspiess, Dorit; Pujari, Sreedhar; Abdul-Hamid, Myrurgia A.; Hochstenbag, Monique; Dingemans, Anne-Marie; Kurz, Anna Kordelia; Haugg, Anke; Maessen, Jos G; Baets, Marc H. De; zur Hausen, Axel

    2015-01-01

    Background We have recently reported the presence of the Human polyomavirus 7 (HPyV7) in human thymic epithelial tumors as assessed by diverse molecular techniques. Here we report on the co-expression of p16, retinoblastoma protein (pRb) and phosphorylated retinoblastoma protein (phospho-Rb) in human thymic epithelial tumors in relation to HPyV7. Methods PRB, phospho-RB and p16 expression was assessed by immuno-histochemistry in 37 thymomas and 2 thymic carcinomas. 17 thymomas (46 %) and 1 th...

  18. Spontaneous transformation of murine oviductal epithelial cells: A model system to investigate the onset of fallopian-derived tumors

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    MIchael P. Endsley

    2015-07-01

    Full Text Available High-grade serous carcinoma (HGSC is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described. Apart from a subpopulation of genetically predisposed women, most women develop ovarian cancer spontaneously, which is associated with aging and lifetime ovulations. A murine oviductal cell line (MOELOW was developed and continuously passaged in culture to mimic cellular aging (MOEHIGH. The MOEHIGH cellular model exhibited a loss of acetylated tubulin consistent with an outgrowth of secretory epithelial cells in culture. MOEHIGH cells proliferated significantly faster than MOELOW, and the MOEHIGH cells produced more 2D foci and 3D soft agar colonies as compared to MOELOW. MOEHIGH were xenografted into athymic female nude mice both in the subcutaneous and the intraperiteonal compartments. Only the subcutaneous grafts formed tumors that were negative for cytokeratin, but positive for oviductal markers such as oviductal glycoprotein 1 and Pax8. These tumors were considered to be poorly differentiated carcinoma. The differential molecular profiles between MOEHIGH and MOELOW were determined using RNA-Seq and confirmed by protein expression to uncover pathways important in transformation, like the p53 pathway, the FOXM1 pathway, WNT signaling, and splicing. MOEHIGH had enhanced protein expression of c-myc, Cyclin E, p53 and FOXM1 with reduced expression of p21. MOEHIGH were also less sensitive to cisplatin and DMBA, which induce lesions typically repaired by base-excision repair. A model of spontaneous tumorogenesis was generated starting with normal oviductal cells. Their transition to cancer involved alterations in pathways associated with high-grade serous cancer in humans.

  19. Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T-cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages

    Science.gov (United States)

    2013-12-01

    Figure   10   that   demonstrate   ring   enhancement   around   the   viable   circumference   of   the   tumor.   When...in head and neck cancer. Taken together, it is logical to build on this experience by developing the use of TiN-4+ T-cell immunotherapy for the

  20. Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma.

    Science.gov (United States)

    Demirović, Alma; Džombeta, Tihana; Tomas, Davor; Spajić, Borislav; Pavić, Ivana; Hudolin, Tvrtko; Milošević, Milan; Cupić, Hrvoje; Krušlin, Božo

    2010-10-15

    The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

  1. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Vascular Changes Induced by Sunitinib in Papillary Renal Cell Carcinoma Xenograft Tumors

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    Gilda G. Hillman

    2009-09-01

    Full Text Available To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI. A dosage of 10 mg/kg per day caused mild changes in Gd uptake and clearance kinetics in kidney tumors. A dosage of 40 mg/kg per day induced increased vascular tumor permeability with Gd retention, probably resulting from the destruction of tumor vasculature, and also caused vascular alterations of normal vessels. However, sunitinib at 20 mg/kg per day caused increased tumor perfusion and decreased vascular permeability associated with thinning and regularization of tumor vessels while mildly affecting normal vessels as confirmed by histologic diagnosis. Alterations in tumor vasculature resulted in a significant inhibition of KCI-18 RCC tumor growth at sunitinib dosages of 20 and 40 mg/kg per day. Sunitinib also exerted a direct cytotoxic effect in KCI-18 cells in vitro. KCI-18 cells and tumors expressed vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β molecular targets of sunitinib that were modulated by the drug treatment. These data suggest that a sunitinib dosage of 20 mg/kg per day, which inhibits RCC tumor growth and regularizes tumor vessels with milder effects on normal vessels, could be used to improve blood flow for combination with chemotherapy. These studies emphasize the clinical potential of DCE-MRI in selecting the dose and schedule of antiangiogenic compounds.

  2. Differences in Renal Tumor Size Measurements for Computed Tomography Versus Magnetic Resonance Imaging: Implications for Patients on Active Surveillance.

    Science.gov (United States)

    Khan, Irtaza; Beksac, Alp Tuna; Paulucci, David J; Abaza, Ronney; Eun, Daniel D; Bhandari, Akshay; Badani, Ketan K

    2017-08-11

    To evaluate and compare the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in predicting the final pathologic tumor size of partial nephrectomy specimens. We analyzed a multi-institutional database of 807 patients who underwent robotic partial nephrectomy for a cT1a renal mass from 2006 to 2016. Patients who had a solitary tumor with complete data on the baseline imaging modality and the tumor size (baseline and pathologic) (n = 349) were included for analysis. Baseline tumor size evaluated by both imaging modalities, in addition to the difference between the measurements and final pathologic tumor size (cm) measurements, was compared between patients who received a baseline CT (n = 276, 79.1%) and those who received an MRI (n = 73, 20.9%). There were no statistically significant differences between any baseline characteristics and receipt of a CT versus MRI. In multivariable analysis adjusting for confounders, there was no significant difference in the baseline tumor size between patients receiving an MRI and those receiving a CT (2.3 versus 2.6 cm; β = -0.13; 95% confidence interval [CI] = -0.33 to 0.07; P = .208). Tumor size on imaging was smaller from final pathology by 0.43 cm on average (P = .002). Measurement error for the measured baseline versus actual pathologic tumor size did not significantly differ for patients receiving an MRI versus those receiving a CT (0.38 versus 0.44 cm; β = -0.06; 95% CI = -0.16 to 0.04; P = .232). Baseline renal tumor size measurements were not significantly different for CT scan and MRI. Choice of imaging modality can be based on doctor and patient preference, including cost and exposure to radiation.

  3. In Vivo Tagging of Lung Epithelial Cells to Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2014-10-01

    derived lung cells, only the epithelium will be tagged by this method. Prior to using these animals for our studies, we will ensure that lineage labeled...1 AWARD NUMBER: W81XWH-13-1-0184 TITLE: In Vivo Tagging of Lung Epithelial Cells To Define...REPORT TYPE Annual 3. DATES COVERED 15Sep2013-14Sep2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER In Vivo Tagging of Lung

  4. Survival Outcomes and Tumor IMP3 Expression in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma

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    Srinivas K. Tantravahi

    2015-01-01

    Full Text Available Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC is associated with poor survival. No data is available from randomized trials on the efficacy of vascular endothelial growth factor (VEGF and mammalian target of rapamycin (mTOR inhibitors in SmRCC. We identified SmRCC patients from a single institutional database. To identify predictive and prognostic biomarkers, immunohistochemistry (IHC analysis was performed on the tumor samples for downstream targets of VEGF and mTOR pathways. Survival outcomes were stratified by IHC analysis, extent of sarcomatoid component, Memorial Sloan-Kettering Cancer Center (MSKCC, and Heng risk criteria. Twenty-seven patients with SmRCC were included. First line therapy included targeted therapy (n=19, immunotherapy (n=4, cytotoxic chemotherapy (n=1, and no treatment (n=3. Median OS was 8.2 months (95% CI 3.8–14.2 months. Median survival in months, based on MSKCC and Heng risk groups, was favorable 89.3 versus 84.5, intermediate 9.5 versus 12.7, and poor 3.9 versus 5.1. None of the IHC markers predicted outcomes of treatment with VEGF or mTOR inhibitors. Only tumor IMP3 expression was associated with inferior OS, although not statistically significant (IMP3 negative 14.2 versus IMP3 positive 4.9 months; HR 0.46, 95% CI 0.16–1.21; P=0.12. The study was limited by small sample size.

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

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    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.

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

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    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

  7. A simple multicolor flow cytometry protocol for detection and molecular characterization of circulating tumor cells in epithelial cancers.

    Science.gov (United States)

    Hristozova, Tsvetana; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

    2012-06-01

    Circulating tumor cells (CTCs) might not only serve as prognostic marker but could also be useful for monitoring treatment efficacy. A multicolor flow cytometry protocol for their detection and molecular characterization in peripheral blood was developed which consisted of erythrocyte lysis followed by staining of cells with fluorochrome-labeled antibodies against CD45 and the epithelial markers EpCam and cytokeratin 7/8. For reducing the number of events acquired by flow cytometry, an electronic threshold for the fluorescent signals from the epithelial markers was applied. After establishment of the protocol by using spiking experiments, its suitability to determine the absolute number of CTCs as well as their expression of epidermal growth factor receptor (EGFR) and its phosphorylated form (phospho-EGFR) in blood samples from patients with squamous cell carcinoma of the head and neck (SCCHN) was validated. Spiking experiments demonstrated an excellent recovery (mean 85%) and a linear performance (R(2) = 0.98) of the protocol. Sensitivity and specificity were comparable to our former protocol using immunomagnetic CTC pre-enrichment. The analysis of 33 SCCHN patient samples revealed the presence of CTCs in 33.3% of cases with a mean ± SD of 1.5 ± 0.5 CTCs per 3.75 ml blood. EGFR was expressed in 100% and phospho-EGFR in 36.4% of the CTC+ cases. We have established a simple and sensitive multicolor flow cytometry protocol for detection of CTCs in patients with epithelial cancers including SCCHN which will allow their detailed molecular characterization.

  8. An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells.

    Science.gov (United States)

    Vanachayangkul, P; Byer, K; Khan, S; Butterweck, V

    2010-07-01

    Teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") have been traditionally used in Egypt as a remedy to treat kidney stones. It was the aim of our study to evaluate the effect of a Khella extract (KE) as well as the two major constituents khellin and visnagin on renal epithelial injury using LLC-PK1 and Madin-Darby-canine kidney (MDCK) cells. Both cell lines provide suitable model systems to study cellular processes that are possibly involved in the development of a renal stone. LLC-PK1 and MDCK cell lines were exposed to 300 microM oxalate (Ox) or 133 microg/cm(2) calcium oxalate monohydrate (COM) in presence or absence of 10, 50, 100 or 200 microg/mL KE. To evaluate cell damage, cell viability was assessed by determining the release of lactate dehydrogenase (LDH). KE (e.g. 100 microg/ml) significantly decreased LDH release from LLC-PK1 (Ox: 8.46+0.76%; Ox + 100 microg/ml KE: 5.41+0.94%, p<0.001) as well as MDCK cells (Ox: 30.9+6.58%; Ox+100 microg/ml KE: 17.5+2.50%, p<0.001), which indicated a prevention of cell damage. Similar effects for KE were observed in both cell lines when COM crystals were added. In LLC-PK1 cells khellin and visnagin both decreased the % LDH release significantly in cells that were pretreated with Ox or COM crystals. However, khellin and visnagin exhibited different responses in MDCK cells. Whereas khellin slightly reduced the % LDH release after exposure of the cells to Ox and COM crystals, visnagin significantly decreased % LDH release only after COM crystal exposure. Overall both compounds were more active in LLC-PK1 than in MDCK cells. In summary, exposure of renal epithelial cells to Ox or COM crystals was associated with a significant release of LDH indicating cell injury. Our data demonstrate that KE as well as khellin and visnagin could prevent renal epithelial cell damage caused by Ox and COM and could therefore play a potential role in the prevention of stone formation associated with hyperoxaluria.

  9. 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.

  10. Robotic partial nephrectomy for renal tumors larger than 4 cm: a systematic review and meta-analysis.

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    Liangkuan Bi

    Full Text Available BACKGROUND: With the establishment of minimally invasive surgery in society, the robot has been increasingly widely used in the urologic field, including in partial nephrectomy. This study aimed to comprehensively summarize the currently available evidence on the feasibility and safety of robotic partial nephrectomy for renal tumors of >4 cm. METHOD AND FINDINGS: An electronic database search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed. This systematic review and meta-analysis was based on all relevant studies that assessed robotic partial nephrectomy for renal tumors of >4 cm. Five studies were included. The meta-analysis involved 3 studies from 11 institutions including 154 patients, while the narrative review involved the remaining 2 studies from 5 institutions including 64 patients. In the meta-analysis, the mean ischemic time, operation time, and console time was 28, 319, and 189 minutes, respectively. The estimated blood loss and length of stay was 317 ml and 3.8 days, respectively. The rates of conversion, positive margins, intraoperative complications, postoperative complications, hilar clamping, and collecting system repair were 7.0%, 3.5%, 7.0%, 9.8%, 93.9%, and 47.5%, respectively. The narrative review showed results similar to those of the meta-analysis. CONCLUSIONS: Robotic partial nephrectomy is feasible and safe for renal tumors of >4 cm with an acceptable warm ischemic time, positive margin rate, conversion rate, complication rate, operation time, estimated blood loss, and length of stay.

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

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    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.

  12. Correlation between coagulation function, tumor stage and metastasis in patients with renal cell carcinoma: a retrospective study

    Institute of Scientific and Technical Information of China (English)

    XIAO Bo; MA Lu-lin; ZHANG Shu-dong; XIAO Chun-lei; LU Jian; HONG Kai; LIAO Hong-yi

    2011-01-01

    Background The coagulation function in carcinoma patients is abnormal, but in renal cell carcinoma the extent and relationships of coagulation function remain unclear. This study retrospectively investigated the relationships between coagulation function, clinical stage and metastasis in patients with renal cell carcinoma.Methods A total of 350 consecutive patients admitted to our Urology Department from 2004 to 2010 were diagnosed with renal cell carcinoma by histolopathologic examination and were included in this study. A total of 231 cases of renal benign tumors were considered as the control group. Fibrinogen, prothrombin time, activated partial thromboplastin time and international normalized ratio were evaluated in all subjects. Tumor size, clinical stage, lymph node metastasis, and distant metastasis were evaluated using radiologic imaging, intraoperative findings, and histological studies.Results The preoperative plasma fibrinogen levels of patients with renal cell carcinoma ((383.9±146.7) mg/dl) were significantly higher than those of the control group ((316.7±62.0) mg/dl) (P <0.01). We divided the renal cell carcinoma group into stages la, lb, Ⅱ, Ⅲ, and Ⅳ. The fibrinogen values were (315.6±64.6) mg/dl, (358.3±91.1) mg/dl, (465.6±164.7)mg/dl, (500.0±202.1) mg/dl, and (585.8±179.7) mg/dl, respectively. There were no significant differences in fibrinogen values between stage la and control groups. However, results of other stages showed significant differences when compared to control group values (P <0.01). Using the cutoff value of 440 mg/dl, which defines hyperfibrinogenemia,plasma fibrinogen levels had a positive predictive value of 39.8% and a negative predictive value of 93.3% for predicting distant metastasis, with a sensitivity of 64.7% and specificity of 83.3%.Concluslons Preoperative plasma fibrinogen levels are elevated in patients with renal cell carcinoma with distant metastasis or lymph node metastasis. Potential metastasis is

  13. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

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    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  14. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Science.gov (United States)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Bhadja, Poonam; Yao, Xiu-Qiong; Ouyang, Jian-Ming

    2016-01-01

    Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H2O2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H2O2-injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone

  15. Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

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    Graffe Carolina C

    2010-10-01

    Full Text Available Abstract Background Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. Methods The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2, the beta-fraction of the epithelial sodium channel (u-ENaCbeta, cyclic-AMP (u-cAMP, prostaglandin E2 (u-PGE2. Free water clearance (CH2O, fractional excretion of sodium (FENa, and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. Results Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. Conclusion During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system Trial Registration Clinical Trials Identifier: NCT00281762

  16. Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

    Science.gov (United States)

    2016-04-14

    Childhood Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Clear Cell Sarcoma of the Kidney; Papillary Renal Cell Carcinoma; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Renal Wilms Tumor; Stage II Renal Cell Cancer; Stage II Renal Wilms Tumor; Stage III Renal Cell Cancer; Stage III Renal Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Renal Wilms Tumor

  17. Chronic epithelial NF-kappaB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation

    NARCIS (Netherlands)

    Shaked, H.; Hofseth, L.J.; Chumanevich, A.; Chumanevich, A.A.; Wang, J.; Wang, Y.; Taniguchi, K.; Guma, M.; Shenouda, S.; Clevers, H.; Harris, C.C.; Karin, M.

    2012-01-01

    The role of NF-kappaB activation in tumor initiation has not been thoroughly investigated. We generated Ikkbeta(EE)(IEC) transgenic mice expressing constitutively active IkappaB kinase beta (IKKbeta) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation,

  18. Chronic epithelial NF-kappaB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation

    NARCIS (Netherlands)

    Shaked, H.; Hofseth, L.J.; Chumanevich, A.; Chumanevich, A.A.; Wang, J.; Wang, Y.; Taniguchi, K.; Guma, M.; Shenouda, S.; Clevers, H.; Harris, C.C.; Karin, M.

    2012-01-01

    The role of NF-kappaB activation in tumor initiation has not been thoroughly investigated. We generated Ikkbeta(EE)(IEC) transgenic mice expressing constitutively active IkappaB kinase beta (IKKbeta) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation, Ikkbeta(

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

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    Kiersten Marie Miles

    Full Text Available BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

  20. Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients.

    Science.gov (United States)

    Kar, Rajarshi; Chawla, Diwesh; Gupta, Bindiya; Mehndiratta, Mohit; Wadhwa, Neelam; Agarwal, Rachna

    2017-08-16

    Ovarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol. Complete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media. Primary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages. This study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

  1. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human adamantinomatous craniopharyngioma cells and promotes tumor cell migration

    Science.gov (United States)

    Zhou, Jie; Zhang, Chao; Pan, Jun; Chen, Ligang; Qi, Song-Tao

    2017-01-01

    Total resection of adamantinomatous craniopharyngioma (ACP) is complex and often leads to postoperative recurrence. This is due to the tendency of the tumor to invade the surrounding brain tissue and the generation of a local inflammatory state between the tumor cells and parenchyma. While there is evidence to suggest that interleukin-6 (IL-6) induces craniopharyngioma (CP)-associated inflammation, particularly in ACP, the role of IL-6 in the progression of ACP remains unclear. The results of the present study demonstrated that CP inflammation was associated with pathological classification, extent of surgery, degree of calcification and postoperative hypothalamic status scale. Cytokine antibody arrays were conducted to measure the expression of IL-6 and other inflammatory factors in tumor tissues in response to various levels of inflammatory exposure. IL-6, IL-6 receptor (IL-6R) and glycoprotein 130 expression was detected by immunohistochemistry. In addition, an ELISA was performed to quantify the levels of soluble IL-6R (sIL-6R) in the cystic fluid and supernatants of ACP cells and tumor-associated fibroblasts. These measurements demonstrated that ACP cells produce IL-6 and its associated proteins. In addition, the results revealed that while the viability of ACP cells was not affected, the migration of ACP cells was promoted by IL-6 treatment in a concentration-dependent manner. Conversely, treatment with an IL-6-blocking monoclonal antibody significantly decreased the migration of ACP cells. In addition, IL-6 treatment increased the expression of vimentin and decreased the expression of E-cadherin in a dose-dependent manner. The findings of the present study demonstrate that IL-6 may promote migration in vitro via the classic- and trans-signaling pathways by inducing epithelial-mesenchymal transition in ACP cell cultures. PMID:28487953

  2. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables

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    Mary T Sylvia

    2012-01-01

    Full Text Available Background: This study aims to evaluate the expression of estrogen receptor alpha (ER α, progesterone receptor A (PRA, Her-2-neu, p53, and Ki-67 in epithelial ovarian tumors and their correlation with various clinicopathologic variables. Materials and Methods: This study included 60 consecutive cases of epithelial ovarian tumors. Sections of 4 μm were taken from paraffin embedded tissue blocks for immunohistochemistry (IHC. Statistical analysis was done using Chi square test, ANOVA. Results: ER α had lower expression in benign (29% and PRA higher expression in malignant (63.6% tumors. ERα, PRA had higher expression in serous (72.72%, 57.14%, postmenopausal (81.8%, 71.42%, advanced stage (63.63%, 52.38%, grade 3 (45.45%, 38.09%, and tumors with ascites (90.90%, 85.7%. Her-2-neu, p53 were negative in benign and higher in malignant (21%, 57.6%, serous (71.42%, 57.89%, grade 3 (57.14%, 31.57%, and tumors with ascites (85.7%, 84.21%. Ki-67 had a significant higher expression in malignant (48.6± 26.76, serous (55.43± 27.85, and grade 3 tumors (68 ± 22. CA-125 levels were significantly higher in malignant, serous, advanced stage, grade 3 and ER α, Her-2-neu and p53 positive tumors. Conclusion: ERα, PRA expression in tumors with adverse prognostic factors support the mitogenic role of estrogen and estrogenic regulation of PR. Her-2-neu and p53 expression only in malignant tumors suggest their carcinogenic role and aid in the differentiation of borderline and malignant tumors. Higher Ki-67 in tumors with adverse prognostic factors would help in prognostication and differentiation. Lack of co-expression of markers proves the extreme heterogeneity of ovarian tumors. These markers may aid in differentiation and prognostication of ovarian tumors.

  3. Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data

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    Baudis Michael

    2007-12-01

    Full Text Available Abstract Background Chromosomal abnormalities have been associated with most human malignancies, with gains and losses on some genomic regions associated with particular entities. Methods Of the 15429 cases collected for the Progenetix molecular-cytogenetic database, 5918 malignant epithelial neoplasias analyzed by chromosomal Comparative Genomic Hybridization (CGH were selected for further evaluation. For the 22 clinico-pathological entities with more than 50 cases, summary profiles for genomic imbalances were generated from case specific data and analyzed. Results With large variation in overall genomic instability, recurring genomic gains and losses were prominent. Most entities showed frequent gains involving 8q2, while gains on 20q, 1q, 3q, 5p, 7q and 17q were frequent in different entities. Loss "hot spots" included 3p, 4q, 13q, 17p and 18q among others. Related average imbalance patterns were found for clinically distinct entities, e.g. hepatocellular carcinomas (ca. and ductal breast ca., as well as for histologically related entities (squamous cell ca. of different sites. Conclusion Although considerable case-by-case variation of genomic profiles can be found by CGH in epithelial malignancies, a limited set of variously combined chromosomal imbalances may be typical for carcinogenesis. Focus on the respective regions should aid in target gene detection and pathway deduction.

  4. Imaging findings of common benign renal tumors in the era of small renal masses: Differential diagnosis from small renal cell carcinoma: Current status and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sung Min; Cho, Jeong Yeon [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-02-15

    The prevalence of small renal masses (SRM) has risen, paralleling the increased usage of cross-sectional imaging. A large proportion of these SRMs are not malignant, and do not require invasive treatment such as nephrectomy. Therefore, differentation between early renal cell carcinoma (RCC) and benign SRM is critical to achieve proper management. This article reviews the radiological features of benign SRMs, with focus on two of the most common benign entities, angiomyolipoma and oncocytoma, in terms of their common imaging findings and differential features from RCC. Furthermore, the role of percutaneous biopsy is discussed as imaging is yet imperfect, therefore necessitating biopsy in certain circumstances to confirm the benignity of SRMs.

  5. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

    2015-01-01

    BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

  6. Aberrant promoter methylation and gene expression of H-cadherin gene is associated with tumor progression and recurrence in epithelial ovarian carcinoma

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    Rahul Bhagat

    2014-01-01

    Full Text Available Background: Loss of expression of cadherins by promoter hypermethylation has been described in many epithelial cancers, and it may play a role in tumor cell invasion and metastasis. Previously, we reported that E-cadherin gene is frequently methylated in epithelial ovarian cancer. Aim: The aim of this study was to compare the promoter hypermethylation of H-cadherin gene in ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Materials and Methods: We examined the promoter methylation of the H-cadherin gene in 134 epithelial ovarian carcinomas (EOC, 23 low malignant potential (LMP tumors, 26 benign cystadenomas and 15 normal ovarian tissues. Methylation was investigated by methylation specific polymerase chain reaction (MSP and the results confirmed by bisulfite DNA sequencing. Relative gene expression of H-cadherin was done using quantitative reverse transcriptase PCR on 51 EOC cases, 9 LMP tumors, 7 benign cystadenomas with 5 normal ovarian tissues. Results: Aberrant methylation of H-cadherin was present in 20 of 134 (15% carcinoma cases, 2 of 23 (09% LMP tumors and 1 of 26 (4% benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of H-cadherin was significantly down-regulated in EOC and LMP tumors than the corresponding normal tissues, whereas the expression level was normal in benign cystadenomas. A significant correlation of H-cadherin promoter methylation was observed with reduced gene expression in EOC. The prevalence of H-cadherin methylation was associated significantly with stage, histopathological grade, and menopausal status of the patient. H-cadherin methylation also had significant association with recurrence and differentiation of tumor. Conclusion: Our findings suggest an association between H-cadherin methylation, tumor progression and recurrence in EOC.

  7. 肌酐代谢产物对肾小管上皮细胞凋亡的影响%Effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    胡白瑛

    2013-01-01

    目的 研究肌酐产物是否能促进肾小管上皮细胞凋亡.方法 原代培养人肾小管上皮细胞,将肌酐产物与肾小管上皮细胞共同培养,对肾小管上皮细胞进行形态学观察;抽提DNA进行琼脂糖电泳观察有无梯形条带.结果 肾小管上皮细胞在肌酐产物作用下逐渐变小、变圆、固缩,最后漂浮死亡,但胞膜始终完整;肌酐产物导致肾小管上皮细胞凋亡,琼脂糖凝胶中有DNA梯形条带,加入谷胱甘肽(GSH)未见DNA梯形条带.结论 肌酐产物促进肾小管上皮细胞凋亡,GSH可阻断之.%Objective To study the effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells. Methods Renal tubular epithelia were cultured in vitro. The metabolites of creatinine and renal tubular epithelial cells were incubated together. The morphological change of renal tubular epithelial cells was observed. Gel electrophoresis of DNA extracted from that to observe bands of apoptotsis. Results Affected by metabolites of creatinine, renal tubular epithelial cells showed characters of apoptosis (smaller, round, pyknosis and death), but the cell membrane was always integral. Agarose gel electrophoresis revealed the appearance of DNA ladder, which disappeared with the addition of GSH. Conclusion The metabolites of creatinine can induce the apoptosis of renal tubular epithelial cells, which could be reversed by GSH.

  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. Kidney volume correlates with tumor diameter in renal cell carcinoma and is associated with histological poor prognostic features.

    Science.gov (United States)

    Hayes, Brian D; Finn, Stephen P

    2014-02-01

    We aimed to correlate kidney volume (KV) in renal cell carcinoma nephrectomy specimens with tumor diameter (TD), macroscopic growth pattern, and histological features associated with poor prognosis. Histopathology reports, macroscopic specimen photographs, and selected glass slides were retrospectively reviewed. KV was approximated to the volume of an ellipsoid. A total of 273 specimens were identified with median KV 245 cm(3). Kidneys larger than this contained larger tumors (7.5 vs 4.5 cm). KV was significantly greater in tumors of high grade, involving perinephric fat, exhibiting venous invasion, and involving renal sinus. There was a robust linear correlation between KV and TD (r = 0.602) and a weaker correlation between kidney diameter (KD) and TD (r = 0.53). In pT1 tumors, KV (r = 0.40) also correlated better with TD than did KD (r = 0.27). By multiple regression analysis, both TD and venous invasion independently predicted both KD (R (2) = 38.27%) and KV (R (2) = 51.97%). KV and KD correlate well with TD and histopathological features of aggressiveness, although KD correlates better overall and in the pT1 subset.

  10. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition

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    Masola Valentina

    2012-10-01

    Full Text Available Abstract Background Epithelial-mesenchymal transition of tubular cells is a widely recognized mechanism that sustains interstitial fibrosis in diabetic nephropathy (DN. The signaling of FGF-2, a growth factor involved in this mechanism, is regulated by glycosaminoglycans. Heparanase-1, an endoglycosidase that cleaves heparan sulfate, is implicated in the pathogenesis of diabetic nephropathy and is necessary to FGF-2 for the induction of tubular cells transition. Well known Heparanase-1 inhibitors are heparin(s and sulodexide, a low-molecular weight heparin – dermatan sulphate blend, which is effective in the treatment of DN. Methods We have investigated the inhibition by sulodexide and its components of Heparanase-1 by an ELISA assay. We have analyzed its effect on the epithelial-mesenchymal transition of tubular cells by real time gene expression analysis, zymography and migration assay. Results Results show that sulodexide is an effective heparanase-1 inhibitor, exclusively in virtue to the heparin component, with an IC50 of 5 μg/ml. In FGF-2 treated tubular cells, sulodexide also prevents the over-expression of the mesenchymal markers αSMA, vimentin and fibronectin and the motility increase, i.e. the epithelial-mesenchymal transition of tubular cells. Moreover, sulodexide prevents FGF-2 induced heparanase-1 and MMP9 increase switching off the autocrine loop that FGF-2 activates to support its signal. Conclusions The findings highlight the capacity of sulodexide to inhibit heparanase-1 and to control tubular fibrosis triggered by epithelial-mesenchymal transition. In conclusion, these sulodexide activities support the value of this agent in controlling the progression of nephropathy to renal failure.

  11. Differing von Hippel Lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma

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    Susan A.J. Vaziri

    2012-05-01

    Full Text Available In sporadic clear cell renal cell carcinoma (CCRCC, the von Hippel Lindau (VHL gene is inactivated by mutation or methylation in the majority of primary (P tumors. Due to differing effects of wild-type (WT and mutant (MT VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization (CGH analysis studies have reported genetic differences between paired P and metastatic (M tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s in patients with CCRCC. Using paraffin embedded specimens, genomic DNA from microdissected samples (>80% tumor of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GeneBank Accession No. AF010238. Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40% patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.

  12. YThe BigH3 Tumor Suppressor Gene in Radiation-Induced Malignant Transformation of Human Bronchial Epithelial Cells

    Science.gov (United States)

    Zhao, Y.; Shao, G.; Piao, C.; Hei, T.

    Carcinogenesis is a multi-stage process with sequences of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer Previous studies from this laboratory have identified a 7 fold down- regulation of the novel tumor suppressor Big-h3 among radiation induced tumorigenic BEP2D cells Furthermore ectopic re-expression of this gene suppresses tumorigenic phenotype and promotes the sensitivity of these tumor cells to etoposide-induced apoptosis To extend these studies using a genomically more stable bronchial cell line we ectopically expresses the catalytic subunit of telomerase hTERT in primary human small airway epithelial SAE cells and generated several clonal cell lines that have been continuously in culture for more than 250 population doublings and are considered immortal Comparably-treated control SAE cells infected with only the viral vector senesced after less than 10 population doublings The immortalized clones demonstrated anchorage dependent growth and are non-tumorigenic in nude mice These cells show no alteration in the p53 gene but a decrease in p16 expression Exponentially growing SAEh cells were exposed to graded doses of 1 GeV nucleon of 56 Fe ions accelerated at the Brookhaven National Laboratory Irradiated cells underwent gradual phenotypic alterations after extensive in vitro cultivation Transformed cells developed through a series of successive steps before becoming anchorage independent in semisolid medium These findings indicate

  13. CONVERGENCE OF P53 AND TGFβ SIGNALING ON ACTIVATING EXPRESSION OF THE TUMOR SUPPRESSOR GENE MASPIN IN MAMMARY EPITHELIAL CELLS

    Science.gov (United States)

    Wang, Shizhen Emily; Narasanna, Archana; Whitell, Corbin W.; Wu, Frederick Y.; Friedman, David B.; Arteaga, Carlos L.

    2014-01-01

    Using two-dimensional difference gel electrophoresis, we identified the tumor suppressor gene maspin as a TGFβ target gene in human mammary epithelial cells. TGFβ upregulates maspin expression both at the RNA and protein levels. This upregulation required Smad2/3 function and intact p53 binding elements in the maspin promoter. DNA affinity immunoblot and chromatin immunoprecipitation (ChIP) revealed the presence of both Smads and p53 at the maspin promoter in TGFβ-treated cells, suggesting that both transcription factors cooperate to induce maspin transcription. TGFβ did not activate maspin-luciferase reporter in p53-mutant MDA-MB-231 breast cancer cells, which exhibit methylation of the endogenous maspin promoter. Expression of ectopic p53, however, restored ligand-induced association of Smad2/3 with a transfected maspin promoter. Stable transfection of maspin inhibited basal and TGFβ-stimulated MDA-MB-231 cell motility. Finally, knockdown of endogenous maspin in p53 wild-type MCF10A/HER2 cells enhanced basal and TGFβ-stimulated motility. Taken together, these data support cooperation between the p53 and TGFβ tumor suppressor pathways in the induction of maspin expression, thus leading to inhibition of cell migration. PMID:17204482

  14. The Serum CA-125 Concentration Data Assists in Evaluating CT Imaging Information When Used to Differentiate Borderline Ovarian Tumor from Malignant Epithelial Ovarian Tumors

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    Shin, Ji Eun; Choi, Hyuck Jae; Kim, Mi Hyun; Cho, Kyoung Sik [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2011-08-15

    We wanted to evaluate the diagnostic value of serum CA-125 concentration, when used in combination with the preoperative contrast-enhanced CT results, to differentiate borderline ovarian tumors (BOTs) from stage I malignant epithelial ovarian tumors (MEOTs). Ninety-eight masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced computed tomography (CT) and surgical staging were evaluated retrospectively and independently by two radiologists. The preoperative serum CA-125 concentration was measured in all patients. The utility of analyzing serum CA-125 concentration in combination with the CT results was evaluated by receiver operating characteristic (ROC) curve analysis. An irregular tumor surface and lymphadenopathy were predictive of a MEOT. ROC analysis showed that the combination of CT data and the serum CA-125 level resulted in a higher diagnostic performance than did using the CT alone for differentiating BOTs from MEOTs. The areas under the curves (AUCs) without and with the use of the serum CA-125 level data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68-0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and 0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). The serum CA-125 concentration is of additional diagnostic value when used in conjunction with the CT imaging results for differentiating BOTs from MEOTs.

  15. Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    YU Xiaofang; XU Xialian; YE Zhibin

    2007-01-01

    In patients with chronic renal failure,whether they have had hemodialysis or not,the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with norrnal kidney function.The detection of tumor markers is extensively used for the diagnosis of corresponding tumors.It has been recently shown that some tumor markers are higher in patients with chronic kidney disease(END)than in the normal population.The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA,CA199,CA125,AFP,CA153,CA724,CYFRA21-1,NSE,SCC-Ag,PSA,and fPSA.The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study.The 232 non-dialysis patients were divided into three groups according to their Ccr.In group 1,Ccr was≤25 mL/min.In group 2,Ccr was between 25 and 50 mL/min.In group 3,Ccr was≥50 mL/min.The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups.Nine tumor markers in 37 uremic patients were tested.For comparison.37 non-dialysis patients with similar Ccr of the same age and gender served as controls.There existed significant difierences in serum levels of CEA,CA199,CYFRA21.1,NSE,and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr.There were no significant differences among the three groups in the serum concentrations of CA125,AFP,CA153,CA724,PSA and fPSA.The serum levels of CA125 and NSE were significantly higher(P<0.01)in hemodialysis patients than in the nondialysis control patients.In patients with chronic renal failure,who were or were not on hemodialysis,the specificity of serum CEA,CA199,CYFRA21-1,NSE,CA125 and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP,CA153,CA724,PSA and fPSA were as valuable as they were in

  16. 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.

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    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.

  17. The Impact of Epithelial-Stromal Interactions on Human Breast Tumor Heterogeneity

    Science.gov (United States)

    2015-10-01

    Mitochondria   organelle   transplantation:  introduction  of  normal  epithelial  mitochondria  into human cancer cells inhibits proliferation and...patients  with  similar   gene  expression  profiles  that  cluster  closely  together.    However,  due  to  the  complexity of the gene expression...chemotherapeutic  agents  and  that  uptake  of  functional  mitochondria   by  cancer  cells  increases  drug  sensitivity  [15].    In addition, mitochondrial

  18. CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor

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    Jiunn-Min Shieh

    2014-10-01

    Full Text Available Background/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lung carcinoma epithelial cells. Methods: CXCL1 expression was determined by ELISA and RT-PCR. TNF-α signaling was examined by western blotting. Monocyte migration was assayed by a Transwell migration system. Results: TNF-α stimulated CXCL1 release and mRNA expression, and this release was inhibited by inhibitors of JNK, p38 MAPK, PI-3K/Akt and AP-1 transcription factor. TNF-α treatment was followed by JNK, p38 MAPK and PI3K/Akt activation. However, only the JNK inhibitor could reduce the CXCL1 mRNA level, suggesting that JNK is required mainly for CXCL1 mRNA synthesis, whereas p38 MAPK and PI-3K/Akt might be responsible for CXCL1 secretion. Dexamethasone (dex and TGF-β reduced CXCL1 secretion, with dex upregulating the expression of MAP kinase phosphatase-1 and TGF-β causing smad2/3 activation and nuclear translocation. A functional analysis showed that the released CXCL1 enhanced monocyte migration and could be abolished by a CXCL1 neutralizing antibody and CXCR antagonist. Conclusion: We demonstrate that TNF-α induces CXCL1 expression through the JNK, p38 MAPK and PI-3K/Akt signaling pathways in human pulmonary epithelial cells.

  19. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

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    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  20. Chronic epithelial NF-κB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation

    OpenAIRE

    Shaked, Helena; Hofseth, Lorne J.; Chumanevich, Alena; Chumanevich, Alexander A.; Wang, Jin; Wang, Yinsheng; Taniguchi, Koji; Guma, Monica; Shenouda, Steve; Clevers, Hans; Curtis C Harris; Karin, Michael

    2012-01-01

    The role of NF-κB activation in tumor initiation has not been thoroughly investigated. We generated Ikkβ(EE)IEC transgenic mice expressing constitutively active IκB kinase β (IKKβ) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation, Ikkβ(EE)IEC mice developed intestinal tumors after a long latency. However, when crossed to mice with IEC-specific allelic deletion of the adenomatous polyposis coli (Apc) tumor suppressor locus, Ikkβ(EE)IEC mice exhibited m...

  1. Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice

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    Xin-Xin Pang

    2016-07-01

    Full Text Available Background/Aims: Urotensin II (UII and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN. The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress and Epithelial-mesenchymal transition (EMT in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1, fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

  2. Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

    Science.gov (United States)

    Tilki, Derya; Hu, Brian; Nguyen, Hao G; Dall'Era, Marc A; Bertini, Roberto; Carballido, Joaquín A; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C; Koppie, Theresa M; Linares, Estefania; Lorentz, C Adam; Mandel, Philipp; Martinez-Salamanca, Juan I; Master, Viraj A; Matloob, Rayan; McKiernan, James M; Mlynarczyk, Carrie M; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S; Ramaswamy, Krishna; Rodriguez Faba, Oscar; Russo, Paul; Shariat, Shahrokh F; Spahn, Martin; Terrone, Carlo; Thieu, William; Vergho, Daniel; Wallen, Eric M; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A; Evans, Christopher P

    2015-02-01

    Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Skin-to-tumor Distance Predicts Treatment Failure of T1A Renal Cell Carcinoma Following Percutaneous Cryoablation.

    Science.gov (United States)

    Vernez, Simone L; Okhunov, Zhamshid; Kaler, Kamaljot; Youssef, Ramy F; Dutta, Rahul; Palvanov, Arkadiy; Shah, Paras; Osann, Kathryn; Siegel, David N; Lobko, Igor; Kavoussi, Louis; Clayman, Ralph V; Landman, Jaime

    2017-06-23

    To determine the impact of skin-to-tumor (STT) distance on the risk for treatment failure following percutaneous cryoablation (PCA). We retrospectively reviewed patients who underwent PCA with documented T1a recurrent renal cell carcinoma (RCC) at 2 academic centers between 2005 and 2015. Patient demographics, tumor characteristics, and perioperative and postoperative course variables were collected. Additionally, we measured the STT distance by averaging the distance from the skin to the center of the tumor at 0°, 45°, and 90° on preoperative computed tomography imaging. We identified 86 patients with documented T1a RCC. The mean age at the time of surgery was 69 years (range: 37-91 years), and the mean tumor size was 2.7 cm (range: 1.0-4.0 cm). With a mean follow-up of 24 months (range: 3-63 months), 11 (12.8%) treatment failures occurred. Patients with treatment failure had significantly higher mean STT distance than those without: 11.0 cm (range: 6.3-20.1 cm) compared to 8.4 cm (range: 4.4-15.2 cm), respectively (P = .002). STT distance was an independent predictor of treatment failure (odds ratio: 1.32, 95% confidence interval: 1.04-1.69, P = .029). STT distance greater than 10 cm had a fourfold increased risk of tumor treatment failure (odds ratio: 4.43, 95% confidence interval: 1.19-16.39, P = .018). Tumor size, R.E.N.A.L. Nephrometry score, and number of cryoprobes placed were not associated with treatment failure. STT, an easily measured preoperative variable, may inform the risk of RCC treatment failure following PCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment

    NARCIS (Netherlands)

    Oosting, Sjoukje F; Brouwers, Adrienne H; van Es, Suzanne C; Nagengast, Wouter B; Oude Munnink, Thijs H; Lub-de Hooge, Marjolijn N; Hollema, Harry; de Jong, Johan R; de Jong, Igle J; de Haas, Sanne; Scherer, Stefan J; Sluiter, Wim J; Dierckx, Rudi A; Bongaerts, Alfons H H; Gietema, Jourik A; de Vries, Elisabeth G E

    2015-01-01

    UNLABELLED: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before

  5. 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment

    NARCIS (Netherlands)

    Oosting, Sjoukje F; Brouwers, Adrienne H; van Es, Suzanne C; Nagengast, Wouter B; Oude Munnink, Thijs H; Lub-de Hooge, Marjolijn N; Hollema, Harry; de Jong, Johan R; de Jong, Igle J; de Haas, Sanne; Scherer, Stefan J; Sluiter, Wim J.; Dierckx, Rudi A; Bongaerts, Alfons H H; Gietema, Jourik A; de Vries, Elisabeth G E

    UNLABELLED: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before

  6. A benign salivary gland tumor of minor salivary gland mimicking an epithelial malignancy

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    Vandana Reddy

    2015-01-01

    Full Text Available Pleomorphic adenoma (PA is the most common benign tumor of major or minor salivary glands. Microscopically, PA exhibits a great diversity of morphological aspects. Here, we present an unusual case of PA with extensive squamous metaplasia and keratin-filled cysts in the left retromolar region of a 50-year-old edentulous person whose microscopic finding may represent a diagnostic dilemma for pathologists.

  7. IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer

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    Mosig Rebecca A

    2012-01-01

    Full Text Available Abstract Background We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach. Methods RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis. Results Insulin-like growth factor binding protein (IGFBP-4 was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases, IGFBP-4 levels were significantly increased (p -5. IGFBP-4 levels were ~3× greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816. In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients. Conclusions This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients. Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4

  8. Selective arterial embolization of symptomatic and asymptomatic renal angiomyolipomas: a retrospective study of safety, outcomes and tumor size reduction

    Science.gov (United States)

    Bardin, Florian; Chevallier, Olivier; Bertaut, Aurélie; Delorme, Emmanuel; Moulin, Morgan; Pottecher, Pierre; Di Marco, Lucy; Gehin, Sophie; Mourey, Eric; Cormier, Luc; Mousson, Christiane; Midulla, Marco

    2017-01-01

    Background Angiomyolipoma (AML) is the most common renal benign tumor. Treatment should be considered for symptomatic patients or for those at risk for complications, especially retroperitoneal bleeding which is correlated to tumor size, grade of the angiogenic component and to the presence of tuberous sclerosis complex (TSC). This study reports our single-center experience with the use of selective arterial embolization (SAE) in the management of symptomatic and asymptomatic renal AMLs. Methods In this retrospective mono-centric study, all demographic and imaging data, medical records, angiographic features, outpatient charts and follow-up visits of patients who underwent prophylactic or emergency SAE for AMLs between January 2005 and July 2016 were reviewed. Tumor size and treatment outcomes were assessed at baseline and after the procedure during follow-up. Computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography was used to evaluate AML shrinkage. Renal function was measured pre- and post-procedure. Results Twenty-three patients (18 females, 5 males; median age, 45 years; range, 19–85 years) who underwent SAE either to treat bleeding AML (n=6) or as a prophylactic treatment (n=17) were included. Overall, 34 AMLs were embolized. TSC status was confirmed for 6 patients. Immediate technical success rate was 96% and 4 patients benefitted from an additional procedure. Major complications occurred in 3 patients and minor post-embolization syndrome (PES) in 14 patients. The mean AML size reduction rate was 26.2% after a mean follow-up was 20.5 months (range, 0.5–56 months), and only non-TSC status was significantly associated with better shrinkage of tumor (P=0.022). Intralesional aneurysms were significantly more frequent in patients with hemorrhagic presentation (P=0.008). There was no change in mean creatinine level after SAE. Conclusions SAE is a safe and effective technique to manage renal AMLs as a preventive treatment as well as in

  9. 卵巢上皮性肿瘤中PIEN和Survivin的表达及意义%Expression and significance of SUrvivin and PIEN in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    丁月红

    2011-01-01

    Objective To investigate the expression and significance of Survivin and PIEN in epithelial ovarian tumors.Methods Immunohistochemical detection of PTEN and Survivin in 52 cases of epithelial ovarian cancer, 20 cases of benign ovarian epithelial tumors and 18 normal ovarian tissue in rats.Results In normal ovarian tissues Survivin protein expression in non- benign epithelial ovarian tumors and epithelial ovarian cancer in the Survivin protein expression rates were 26.32% ( 5/19 ), 66.67% (30/45), epithelial ovarian cancer in the Survivin protein expression was significantly higher than that of normal ovarian and benign epithelial ovarian tumor group, the difference was significant ( P < 0.05 ); PTEN protein in normal ovarian tissue, benign epithelial ovarian tumors and epithelial ovarian carcinoma were 100.0% (18/18), 95.0% (20/19), 38.5% (20/52).PTEN protein in normal ovarian tissues and benign epithelial ovarian expression of swelling was higher than that of epithelial ovarian cancer (all P < 0.01 ).Conclusions PTEN expression was decreased and increased expression of Survivin and related to the occurrence of epithelial ovarian cancer, the detection of ovarian cancer patients Survivin and PIEN expression for the evaluation of malignancy, and prognosis has important clinical value.%目的 探讨卵巢上皮性肿瘤中PIEN和Survivin的表达及意义.方法 采用免疫组织化学法检测PTEN和survivin在52例卵巢上皮性癌、20例卵巢良性上皮性肿瘤和18例正常卵巢组织标本中的表达.结果 正常卵巢组织中无Survivin蛋白表达,良性上皮性卵巢肿瘤和卵巢上皮性癌中Survivin蛋白表达率分别为26.32%(5/19)、66.67%(30/45),卵巢上皮性癌中Survivin蛋白阳性表达率明显高于正常卵巢及良性上皮性卵巢肿瘤组,差异有显著性(P<0.05);PTEN蛋白在正常卵巢组织、卵巢良性上皮性肿瘤和卵巢上皮性癌中的表达率分别为100.0%(18/18)、95.0%(20/19)、38

  10. Knockdown of Collagen Triple Helix Repeat Containing-1 Inhibits the Proliferation and Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Jin, Xue-Fei; Li, Hai; Zong, Shi; Li, Hong-Yan

    2016-10-27

    Collagen triple helix repeat containing-1 (CTHRC1), a secreted glycoprotein, is frequently upregulated in human cancers. However, the functional role of CTHRC1 in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to explore the role of CTHRC1 in RCC. Our results demonstrated that CTHRC1 was upregulated in RCC tissues and cell lines. Knockdown of CTHRC1 significantly inhibits the proliferation in RCCs. Furthermore, knockdown of CTHRC1 significantly inhibited the epithelial-to-mesenchymal transition (EMT) process in RCCs, as well as suppressed RCC cell migration and invasion. Mechanistically, knockdown of CTHRC1 inhibited the expression of β-catenin, c-Myc, and cyclin D1 in RCC cells. In conclusion, the results of the present study indicated that CTHRC1 downregulation inhibited proliferation, migration, EMT, and β-catenin expression in RCC cells. Therefore, CTHRC1 may be a potential therapeutic target for the treatment of RCC.

  11. THE ROLE OF CHRONIC POLYPOID RHINOSINUSITIS IN OCCURRENCE OF MALIGNANT EPITHELIAL TUMORS OF THE PARANASAL SINUSES AND THE NASAL CAVITY

    Directory of Open Access Journals (Sweden)

    M. Yu. Vereshchagin

    2014-01-01

    Full Text Available Growth of occurrence of malignant epithelial tumors of the nasal cavity (NC and the paranasal sinuses (PNS is noted. Absolute majority of patients come for treatment with the III and the IV stage of the disease. No trend for decreasing of the untreatedness parameter is observed. Increasing of the efficiency of treatment of patients with cancer depends on timely diagnostics. The main reason of late diagnostics is insufficient oncological alertness of doctors in polyclinics. The issues of therapy tactics at the stage of pre-tumor diseases of the NC and the PNS remain unsolved, while background process that precede development of cancer are morphologically revealed with 56.7 % of patients. One of the most frequently occurred background development processes of the NC and the PNS cancer is chronic polypoid rhinosinusitis (CPR. The degree of occurrence of CPR is high, and the annual growth of its incidence by 2 to 4 % has been observed for the previous 10 years. There are only certain works that view CPR as a pre-cancer disease.The objective of the study is improvement of results of early diagnostics of cancer and optimization of the surgical tactics with pre-cancer diseases of the upper jaw and the PNS.Materials and methods. Retrospective and prospective clinical and morphological analysis of data of 58 patients with benign polypous changes (BPC and of 182 patients with malignant epithelial tumors (MET  of the NC and the PNS treated at the Arkhangelsk Regional Clinical Oncology Dispensary from 1980 to 2010 has been performed.Results and discussion The maximum number of patients in both groups is at the age category from 40 to 59 years. Besides, the average age of patients with the BPC was lower than that of the patients with the MET (45.6 ± 2.3 and 54.0 ± 1.5 years old, respectively.Patients of working age prevailed both in the group with the BPC and the group with the MET of the NC and the PNS (19.0 / 81.0 % and 39.6 / 62.1 %, respectively

  12. In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2015-12-01

    determine the tumor cell of origin [KrasG12D L/-/ /Sftpc- creER or KrasG12D L/-/ / p53 L/L /Sftpc-creER], or the contribution of alveolar type II cells in...cancer have advanced disease at the time of presentation, a finding that may be consistent with early spread. Even when lung cancer is diagnosed and...identify early stage patients at high risk of recurrence or metastatic disease as well as to develop more effective therapies for NSCLC. 7 The studies

  13. The Impact of Epithelial Stromal Interactions on Human Breast Tumor Heterogeneity

    Science.gov (United States)

    2016-12-01

    Massachusetts  General  Hospital  or  the  Dana‐Farber  Cancer  Institute.    These  on‐site  sessions included  shadowing  doctors meeting with their patients...2009‐19.    9.   Cheung KJ,  Ewald AJ. A  collective  route  to metastasis:  Seeding  by  tumor  cell  clusters.  Science  2016;352:167‐9.    10

  14. The role of metabolic tumor volume and total lesion glycolysis on {sup 18}F-FDG PET/CT in the prognosis of epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won; Cho, Arthur; Lee, Jae-Hoon; Yun, Mijin; Lee, Jong Doo; Kang, Won Jun [Yonsei University College of Medicine, Department of Nuclear Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul (Korea, Republic of); Kim, Young Tae [Yonsei University College of Medicine, Department of Obstetrics and Gynecology, 134 Shinchon-dong, Seodaemoon-gu, Seoul (Korea, Republic of)

    2014-10-15

    This study assessed the prognostic value of pre-operative 2-[{sup 18}F] fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer. A total of 175 patients with epithelial ovarian cancer who underwent {sup 18} F-FDG PET/CT and subsequent cytoreductive surgery were retrospectively enrolled. Maximum standardized uptake value (SUVmax) on {sup 18}F-FDG PET/CT was measured for all patients. Because nine patients showed low tumor-to-background uptake ratios, MTV and TLG were measured in 166 patients. Univariate and multivariate analyses were performed to evaluate the prognostic significance of SUVmax, MTV, TLG, and clinicopathological factors for disease progression-free survival. Disease progressed in 78 (44.6 %) of the 175 patients, and the 2-year disease progression-free survival rate was 57.5 %. Univariate analysis showed that tumor stage, histopathological type, presence of regional lymph node metastasis, residual tumor after cytoreductive surgery, pre-operative serum carbohydrate antigen 125 (CA125) level, SUVmax, MTV, and TLG were significant prognostic factors (p < 0.05). Among these variables, tumor stage (p = 0.0006) and TLG (p = 0.008) independently correlated with disease progression-free survival on multivariate analysis. The disease progression rate was only 2.3 % in stage I-II patients with low TLG (≤100.0), compared to 80.0 % in stage III-IV patients with high TLG (>100.0). Along with tumor stage, TLG is an independent prognostic factor for disease progression after cytoreductive surgery in patients with epithelial ovarian cancer. By combining tumor stage and TLG, one can further stratify the risk of disease progression for patients undergoing cytoreductive surgery. (orig.)

  15. Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease

    Science.gov (United States)

    Lococo, Filippo; Bajocchi, Gianluigi; Caruso, Andrea; Valli, Riccardo; Ricchetti, Tommaso; Sgarbi, Giorgio; Salvarani, Carlo

    2016-01-01

    Abstract Background: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. Methods: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). Results: The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. Conclusion: Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history. PMID:27603335

  16. Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors.

    Science.gov (United States)

    Gazzaniga, Paola; Naso, Giuseppe; Gradilone, Angela; Cortesi, Enrico; Gandini, Orietta; Gianni, Walter; Fabbri, Maria Agnese; Vincenzi, Bruno; di Silverio, Franco; Frati, Luigi; Aglianò, Anna Maria; Cristofanilli, Massimo

    2010-05-15

    The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.

  17. Investigation of Renal Cell Carcinoma by Contrast-Enhanced Ultrasound- Predictive Value of Time Intensity Curve Analysis in Establishing Local Tumor Invasion and Stage: A Pilot Study.

    Science.gov (United States)

    Tamas-Szora, Attila; Socaciu, Mihai; Crișan, Nicolae; Dobrotă, Florentin; Prunduș, Paul; Bungărdean, Cătălina; Buruian, Mircea; Coman, Ioan; Opincariu, Iulian; Badea, Radu

    2015-07-01

    Contrast-enhanced ultrasound (CEUS) allows for real-time examination of signal intensity changes in a region of interest (ROI) and quantification of contrast agent kinetics. This study assessed the predictive ability of time-intensity curve (TIC) parameters for local tumor invasion and T stage of renal cell carcinoma (RCC). Renal tumors in 41 patients were examined by CEUS. Thirty-two met the inclusion criteria, with a total of 33 tumors (27 clear cell, 4 chromophobe, and 2 papillary type I). Nineteen (57.6%) tumors were included in group A (stages pT1 and pT2) and 14 (42.4%) in group B (stage pT3). ROIs were established as: whole tumor (TuW); tumor area with the highest signal intensity (TuMAX) and renal cortex (Ref). The TIC param­eters for each ROI were calculated as below: peak signal intensity, time to peak (TTP), rise time (RT), and mean transit time (MTT). They were analyzed as a whole value for each ROI and as a ratio between the different ROIs. There were significant differences between the tumors invading and not invading the renal sinus fat for TTP (TuW/Ref) [0.98 (0.67-1.25) vs. 1.18 (1.08-1.3), P 0.91. TIC parameters were predictors of locally noninvasive and invasive RCC.

  18. Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury.

    Science.gov (United States)

    Jang, Hee-Seong; Han, Sang Jun; Kim, Jee In; Lee, Sanggyu; Lipschutz, Joshua H; Park, Kwon Moo

    2013-12-01

    Extracellular signal-regulated kinase (ERK) signals play important roles in cell death and survival. However, the role of ERK in the repair process after injury remains to be defined in the kidney. Here, we investigated the role of ERK in proliferation and differentiation of tubular epithelial cells, and proliferation of interstitial cells following ischemia/reperfusion (I/R) injury in the mouse kidney. Mice were subjected to 30min of renal ischemia. Some mice were administered with U0126, a specific upstream inhibitor of ERK, daily during the recovery phase, beginning at 1day after ischemia until sacrifice. I/R caused severe tubular cell damage and functional loss in the kidney. Nine days after ischemia, the kidney was restored functionally with a partial restoration of damaged tubules and expansion of fibrotic lesions. ERK was activated by I/R and the activated ERK was sustained for 9days. U0126 inhibited the proliferation, basolateral relocalization of Na,K-ATPase and lengthening of primary cilia in tubular epithelial cells, whereas it enhanced the proliferation of interstitial cells and accumulation of extracellular matrix. Furthermore, U0126 elevated the expression of cell cycle arrest-related proteins, p21 and phospholylated-chk2 in the post-ischemic kidney. U0126 mitigated the post-I/R increase of Sec10 which is a crucial component of exocyst complex and an important factor in ciliogenesis and tubulogenesis. U0126 also enhanced the expression of fibrosis-related proteins, TGF-β1 and phosphorylated NF-κB after ischemia. Our findings demonstrate that activation of ERK is required for both the restoration of damaged tubular epithelial cells and the inhibition of fibrosis progression following injury.

  19. Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients.

    Science.gov (United States)

    Kuthi, Levente; Jenei, Alex; Hajdu, Adrienn; Németh, István; Varga, Zoltán; Bajory, Zoltán; Pajor, László; Iványi, Béla

    2017-07-01

    The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a two-tiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the four-tiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.

  20. Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells.

    Science.gov (United States)

    Wang, Tao; He, Qian; Xiao, Liang; Wang, Qianqian; Zhang, Bo; Wang, Beilei; Liu, Guoyan; Zheng, Jiemin; Yu, Bentong; Zhang, Liming

    2013-11-01

    Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E