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1.
Article in English | MEDLINE | ID: mdl-38629770

ABSTRACT

Introduction: To evaluate by using 3D renal volumetric assessment and compare renal parenchymal preservation between patient who underwent open partial nephrectomy (OPN) and robot assisted laparoscopic partial nephrectomy (RALPN). Methods: We retrospectively reviewed the records of the patients to evaluate the effect of OPN (23 patients) or RALPN (19 patients) partial nephrectomy on renal parenchymal preservation. The CT or MRI were examined using 3D-Slicer image processing software. The tumor volume and preoperative and postoperative non-tumor bearing parenchymal volumes were evaluated with the segmentation. The preoperative and postoperative parenchymal volumes, serum creatinine levels, and estimated glomerular filtration rates (eGFRs) were compared between the surgical techniques. Results: The data of 42 patients were included in the final analysis. The patient and tumor characteristics were similar between the two groups. Postoperative renal parenchymal volumetric changes were seen similar between groups. Although the serum creatinine levels and eGFRs did not change postoperatively in the RALPN group (P = .145 and P = .085, respectively), creatinine increased while eGFR decreased in the OPN group (P = .003 and P = .002, respectively). Conclusions: Our analysis showed that RALPN could be considered similar to OPN in terms of parenchymal volume preservation, but the rate of parenchymal volume preservation was not associated with the change in functional parameters. These results should be supported by further research.

2.
Cancer Biol Med ; 2021 Mar 12.
Article in English | MEDLINE | ID: mdl-33710813

ABSTRACT

OBJECTIVE: Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear. METHODS: The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas. RESULTS: HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/ß-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas. CONCLUSIONS: The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.

3.
Cancer Med ; 10(2): 605-614, 2021 01.
Article in English | MEDLINE | ID: mdl-33280246

ABSTRACT

OBJECTIVE: Based on the eighth TNM staging system, T3a renal cell carcinoma (RCC) is identified as an anatomical extrarenal invasion and does not consider the size of the tumor; however, it may not fully predict the prognosis of the patient. The objective of this study was to evaluate the prognostic value of tumor size effects on prognosis in T3a RCC and propose an alternative tumor stage system combined with T1-2. METHODS: Data relating to T1-3aN0M0 RCC (n = 49586) were obtained from the Surveillance, Epidemiology, and End Results database (2004-2015). Survival analyses were conducted by Cox regression and Fine and Gray regression. Harrell's concordance index (c-index) was used to assess the discriminatory ability of the prognostic factors. RESULTS: A 1-cm increase in T3a RCC resulted in an 8% increase in all-cause mortality (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.06-1.10, p < 0.001) and 14% increase in the risk of RCC-specific mortality (sub-distribution HR [sHR]: 1.14; 95% CI: 1.11-1.16, p < 0.001). T3a tumor size stratified by the cutoff of 4 cm and 7 cm showed a better prediction of RCC-special survival (c-index: 0.644), compared with a cutoff just by 4 cm (c-index: 0.571) or by 7 cm (c-index: 0.602). Compared with T1b tumors, T3a RCC ≤4 cm showed no differences in terms of all-cause mortality (HR: 0.93; 95% CI: 0.79-1.09; p = 0.37) and mortality caused by RCC (sHR: 0.91; 95% CI: 0.70-1.19; p = 0.50). Last, the alternative T-staging system (T1a, a combination of T1b and T3a [≤4 cm], T2a, T2b, T3a [4-7 cm], and T3a [>7] cm) demonstrated good RCC-special survival predictive accuracy (c-index: 0.729), which was higher than that shown by the current eighth edition T-staging system (c-index: 0.720). CONCLUSION: Tumor size should be taken into consideration for T3aN0M0 RCC rather than based on anatomical features alone.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Databases, Factual , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Neoplasm Staging/standards , Nephrectomy/mortality , Aged , Aged, 80 and over , Carcinoma, Renal Cell/surgery , Female , Follow-Up Studies , Humans , Kidney Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Survival Rate
4.
West Indian med. j ; 69(5): 309-314, 2021. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1515678

ABSTRACT

ABSTRACT Objective: Developing anti-cancer drugs from natural products is receiving increasing interest worldwide due to limitations and side effects of anti-cancer drugs. The purpose of this study was to explore the anti-proliferative or cytopathic potential of natural compounds derived from plant sources as alternatives of synthetic compounds on human embryonic kidney carcinoma (HEK) cell line. Methods: In this study, aqueous and methanolic extracts were obtained from various plants, viz, Thapsia garganica, Citrus sinesis, Citrus limon and Vinca rosea. Extracts were serially diluted into 96-well microtitre plates and were screened for anti-proliferative potential against the HEK cell line via the neutral red dye uptake assay. Results: The findings revealed that methanolic extracts of T. garganica leaf and V. rosea leaf were the most effective as anti-proliferative or cytotoxic against the HEK cell line, with IC50 at 32-fold dilution of the extract. Conclusion: The extracts of T. garganic and V, rosea have been used as anti-proliferative drugs but after trial in experimental animals for being not toxic.

5.
Rep Pract Oncol Radiother ; 25(5): 808-819, 2020.
Article in English | MEDLINE | ID: mdl-32884453

ABSTRACT

miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as 'oncomiR-1', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.

6.
Chinese Journal of Urology ; (12): 57-58, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-869592

ABSTRACT

This paper reports two cases of mixed epithelial and stromal tumor of the kidney in elderly women.Both cases underwent radical nephrectomy and were confirmed by pathology.The patients were followed up for 10 months and 18 months respectively,without recurrence or metastasis.The purpose of this study was to further understand the disease by describing its clinical data and imaging manifestations.

7.
Chinese Journal of Urology ; (12): 57-58, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-798864

ABSTRACT

This paper reports two cases of mixed epithelial and stromal tumor of the kidney in elderly women. Both cases underwent radical nephrectomy and were confirmed by pathology. The patients were followed up for 10 months and 18 months respectively, without recurrence or metastasis. The purpose of this study was to further understand the disease by describing its clinical data and imaging manifestations.

8.
Environ Toxicol ; 34(11): 1208-1220, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31298468

ABSTRACT

Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti-inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2-methyl-5-isopropyl-1,4-benzoquinone (thymoquinone) on human renal carcinoma cell lines 786-O and 786-O-SI3 and transitional carcinoma cell line BFTC-909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase-3 activation and restored the decreased cell viability of 786-O-SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786-O-SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct-4 in 786-O-SI3 cells. The tumor-bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786-O-SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786-O-SI3 and BFTC-909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.


Subject(s)
Apoptosis/drug effects , Benzoquinones/pharmacology , Cell Proliferation/drug effects , Reactive Oxygen Species/metabolism , Animals , Autophagy/drug effects , Benzoquinones/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Survival/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred BALB C , Neoplastic Stem Cells/cytology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism
9.
Mol Carcinog ; 58(2): 279-292, 2019 02.
Article in English | MEDLINE | ID: mdl-30334578

ABSTRACT

This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR-194-5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si-MALAT1, pcDNA-MALAT1, miR-194-5p mimic, miR-194-5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK-8 assay, colony formation assay, and flow cytometry. Dual-luciferase reporter gene assay was implemented to validate the targeted relationships between MALAT1 and miR-194-5p, as well as between miR-194-5p and ACVR2B. The results showed that highly expressed MALAT1, ACVR2B, and lowly expressed miR-194-5p were associated with larger tumor size (≥4 cm), advanced TNM stage and poor prognosis of KIRC patients, when, respectively, compared with lowly expressed MALAT1, ACVR2B, and highly expressed miR-194-5p (P < 0.05). Transfection of pcDNA-MALAT1, miR-194-5p inhibitor, and pcDNA-ACVR2B conferred the KIRC cells with promoted viability and proliferation, as well as reduced apoptosis (P < 0.05). Treatment of rats with pcDNA-MALAT1, miR-194-5p inhibitor, or pcDNA-ACVR2B also contributed to larger tumor size growing in them (P < 0.05). Moreover, MALAT1 could directly target miR-194-5p to suppress its expression, and ACVR2B was the targeted molecule of miR-194-5p (P < 0.05). Finally, ACVR2B could reverse the effects exerted by miR-194-5p on viability, proliferation, and apoptosis of KIRC cells (P < 0.05). In conclusion, LncRNA MALAT1/miR-194-5p/ACVR2B signaling was regarded as a candidate pathway for modulating KIRC progression.


Subject(s)
Activin Receptors, Type II/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Activin Receptors, Type II/metabolism , Animals , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Survival , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Neoplasm Transplantation , Rats , Signal Transduction
10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-744364

ABSTRACT

Objective To explore the clinical curative effect of using different blocking methods to renal artery in laparoscopic nephron sparing surgery.Methods A total of 118 cases admitted in the Affiliated Heji Hospital of Changzhi Medical College who reserved the nephron routine after laparoscopic surgery of renal tumor surgery were selected.According to different methods of renal artery block,the patients were divided into the whole block group (61 cases) and selective blocking group (57 cases).The clinical curative effects of the two groups were compared.Results The differences of age,sex,suffering from kidney area and excising were not statistically significant between the two groups(all P > 0.05).The blocking time,operation time and intraoperative blood loss,drainage at postoperative 1 day in the whole block group were (22.58 ± 4.62) min,(138.75 ± 21.76) min,(108.47 ± 75.39) mL and (137.36 ±18.34) mL,respectively,which in the selective block group were (28.61 ± 4.59) min,(103.26 ± 18.64) min,(132.58 ± 68.43) mL and (163.15 ± 15.87) mL,respectively,the differences were significant between the two groups (t =5.356,-8.247,7.463,10.358,all P < 0.01).The postoperative hospital stay [(8.36 ± 2.19) d vs.(7.78 ±2.35)d] had no statistically significant difference between the two groups(P >0.05).There were no statistically significant differences in preoperative creatinine level and glomerular filtration rate between the two groups (all P >0.05).After operation,the creatinine and glomerular filtration rate in the whole block group were (106.38 ±32.76) μmol/L,(33.53 ± 6.14) % statistically,which in the selective block group were (95.26 ± 25.49) μmol/L,(38.27 ± 5.29)% statistically,the differences were statistically significant between the two groups (t =-2.154,4.572,all P < 0.05).Conclusion Renal artery block has shorter operation time,larger haemorrhage amount,increased postoperative creatinine,reduced glomerular filtration rate,for a small single kidney surgery,using selective renal artery block as far as possible,it has less intraoperative bleeding,and postoperative effect is better.

11.
J Cancer Res Ther ; 14(4): 795-798, 2018.
Article in English | MEDLINE | ID: mdl-29970655

ABSTRACT

OBJECTIVE: This study was aimed to investigate the characteristics of multi-slice spiral computed tomography (CT) image in kidney cancer patients and its clinical value in staging diagnosis of kidney cancer. MATERIALS AND METHODS: This study included 57 patients who were confirmed as kidney cancer through postoperative pathological examination; they were diagnosed within February 2014 and December 2016 in our hospital. The data obtained from multi-slice spiral CT plain scan and contrast-enhanced CT of these patients was retrospectively analyzed. Moreover, we determined the characteristics of multi-slice spiral CT image for kidney cancer and analyzed their consistency with pathological staging. RESULTS: CT plain scan showed that kidney lumps were mostly found in the prominent renal contour or renal parenchyma, and they were round-like or round in shape. Among the 57 included patients, the tumors of 43 cases showed regular edges, and 14 showed irregular edges. Among the 14 cases, 10 patients had tumors with lobulated edges and 5 with spinous tumor edge. Among all the 57 patients, CT plain scan showed there were 5 cases with slightly higher density, 24 cases with mixed density, 28 cases with equal density or slightly lower density. The range of tumor diameter was 2.1-12.6 cm; the tumor diameter was smaller than 3 cm in 11 cases, 3-7 cm in 34 cases, and larger than 7 cm in 12 cases. In terms of contrast enhancement, the arterial phase was obviously enhanced in 31 cases, moderately and irregularly enhanced in 18 cases, and slightly enhanced in 8 cases. Moreover, the renal parenchymal scan showed a rapid decline in the enhancement and a further decline in the enhancement of renal pelvic tumor; the three stages of enhancement could be expressed in terms of fast forwardness and fast backwardness. A total of 33, 4, 9, and 11 cases were classified as postoperative pathological Stage I, II, III, and IV, respectively; 35, 5, 7, and 10 cases were classified as CT scan Stage I, II, III, and IV, respectively; and 34, 5, 8, and 10 cases were classified as contrast-enhanced CT scan Stage I, II, III, and IV, respectively. No significant difference was observed in the frequency of CT scan, the enhanced stage and pathological stage (P > 0.05). CONCLUSION: CT image of kidney cancer revealed the morphological and enhanced features of this tumor. The consistency between CT stage and pathological stage was high; thus, this method can be applied as a forecasting method for pathological staging.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/diagnosis , Tomography, Spiral Computed , Adult , Aged , Female , Humans , Image Enhancement , Male , Middle Aged , Neoplasm Staging , Tomography, Spiral Computed/methods , Tumor Burden
12.
Biochem Biophys Res Commun ; 501(4): 913-919, 2018 07 02.
Article in English | MEDLINE | ID: mdl-29772238

ABSTRACT

Transforming growth factor-ß1 (TGF-ß1) plays a crucial role in the signaling network that controls cellular invasion and motility capability during tumor development. To investigate whether fascin1 plays a crucial role in TGF-ß1-facilitated invasion and migration of kidney cancer cells (KCC), real-time PCR and western blotting were used to test the fascin1 expression after TGF-ß1 treatment (10 ng/ml) in 769-P and OSRC cells. Fascin1 was silenced using the small interfering RNA (siRNA) technique. Cytoskeleton staining was used to test the change of Cytoskeleton. Cell migration and invasion changes were measured by wound-healing and Transwell assay. The results indicate that mRNA and protein levels of fascin1 were dramatically increased after treatment with 10 ng/ml TGF-ß1 in 769-P and OSRC cells. TGF-ß1 promoted the occurrence of EMT (Epithelial-Mesenchymal Transition) and the invasive and migratory capabilities of the two cell lines after treatment with 10 ng/ml TGF-ß1. In addition, fascin1 siRNA dramatically attenuated the invasiveness and migration induced by TGF-ß1. Furthermore, we identified that specific inhibitors of ERK and JNK signaling pathways, FR180204 and SP600125, can suppress TGF-ß1-induced fascin1 expression. In conclusion, these results reveal that fascin1 is an important mediator of TGF-ß1-induced invasion and migration of KCC through ERK and JNK signal pathways.


Subject(s)
Carrier Proteins/genetics , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , MAP Kinase Signaling System/drug effects , Microfilament Proteins/genetics , Transforming Growth Factor beta1/pharmacology , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Epithelial-Mesenchymal Transition/drug effects , Gene Knockdown Techniques , Humans , Kidney Neoplasms/enzymology , Microfilament Proteins/metabolism , Neoplasm Invasiveness , RNA, Small Interfering/metabolism
13.
Mol Cell Oncol ; 5(2): e1271494, 2018.
Article in English | MEDLINE | ID: mdl-29487893

ABSTRACT

Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression. Downregulation of UBASH3B prevents SAC satisfaction leading to inhibition of chromosome segregation, mitotic arrest, and cell death. In contrast, increased cellular levels of UBASH3B trigger premature and uncontrolled chromosome segregation. Interestingly, elevated levels of UBASH3B were found in aggressive tumors. Therefore, we raised the question whether the oncogenic potential of UBASH3B is linked to its role in chromosome segregation. Here we show that in cancer cells expressing high levels of UBASH3B and SAC proteins, downregulation of UBASH3B, can further potentiate SAC response inducing mitotic arrest and cell death. Moreover, data mining approaches identified a correlation between mRNA levels of UBASH3B and SAC components in a set of primary patient tumors including kidney and liver carcinomas. Thus, inhibition of UBASH3B may offer an attractive therapeutic perspective for cancers.

14.
Endocr Relat Cancer ; 24(9): C9-C19, 2017 09.
Article in English | MEDLINE | ID: mdl-28667082

ABSTRACT

Two recent independent studies published in Nature show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α). This commentary published in Endocrine-Related Cancer is based on the recognition of similar molecular drivers in ccRCC and the endocrine neoplasias pheochromocytomas and paragangliomas (PPGLs), ultimately leading to stabilization of HIFs. HIF-stabilizing mutations have been detected in the von Hippel-Lindau (VHL) gene, as well as in other genes, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH) and transcription elongation factor B subunit 1 (TCEB1), as well as the gene that encodes HIF2α itself: EPAS1HIF2α Importantly, the recent discovery of EPAS1 mutations in PPGLs and the results of comprehensive in vitro and in vivo studies revealing their oncogenic roles characterized a hitherto unknown direct mechanism of HIF2α activation in human cancer. The now available therapeutic opportunity to successfully inhibit HIF2α pharmacologically with PT2385 and PT2399 will certainly spearhead a series of investigations in several types of cancers, including patients with SDHB-related metastatic PPGL for whom limited therapeutic options are currently available. Future studies will determine the efficacy of these promising drugs against the hotspot EPAS1 mutations affecting HIF2α amino acids 529-532 (in PPGLs) and amino acids 533-540 (in erythrocytosis type 4), as well as against HIF2α protein activated by VHL, SDHx and FH mutations in PPGL-derived chromatin cells.


Subject(s)
Adrenal Gland Neoplasms/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Paraganglioma/drug therapy , Pheochromocytoma/drug therapy , Adrenal Gland Neoplasms/genetics , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use , Paraganglioma/genetics , Pheochromocytoma/genetics
15.
Exp Ther Med ; 13(5): 2473-2479, 2017 May.
Article in English | MEDLINE | ID: mdl-28565866

ABSTRACT

Kidney cancer is among the most important causes of cancer-associated mortality worldwide. The present study aimed to evaluate protein kinase C α (PKCα) expression in kidney cancer tissues and cell lines, and its significance in apoptosis and migration. Expression of PKCα was analyzed using quantitative polymerase chain reaction and western blotting. In addition, the inhibitor of PKCα (calphostin C and GO6976) was used to treat kidney cancer cells. The ACHN cell line was generated with PKCα-small-interfering RNA (siRNA) and a stable expression of PKCα, in order to facilitate the analysis of apoptosis and migration of PKCα during knockdown and inactivation. Flow cytometry was used to determine the rates of apoptosis. Immunohistochemical staining was used to identify the localization of PKCα in renal clear cell carcinoma and normal sections. PKCα expression in normal tissues was found to be greater than in cancerous tissues. Furthermore, apoptosis was not promoted with PKCα inhibitors or PKCα-siRNA treatment, and a decrease of the migration ability was observed following transfection with PKCα-dominant negative. The results indicated that inhibition of PKCα might not contribute to apoptosis progression in kidney carcinoma.

16.
Kidney Cancer ; 1(2): 133-141, 2017 Nov 27.
Article in English | MEDLINE | ID: mdl-30334015

ABSTRACT

BACKGROUND: Checkpoint inhibitors (CPI) have now been established as standard agents in the management of patients with metastatic renal cell carcinoma (mRCC). Given the unique toxicity profiles of CPIs, a detailed understanding of their incidence rate and characteristics is critical. OBJECTIVE: To perform a systematic review for the analysis of the incidence rate and characteristics of toxicities in mRCC patients treated with CPIs in published clinical trials. METHODS: A systematic search of EMBASE (Ovid) and MEDLINE (Ovid) was conducted as per PRISMA guidelines to identify prospective clinical trials of checkpoint inhibitors in mRCC. The search method involved querying for the terms renal cell carcinoma or kidney carcinoma with any of the following: programmed cell death 1, PD-1, programmed cell death ligand 1, PD-L1, cytotoxic T-lymphocyte antigen 4, CTLA-4, immunotherapy, checkpoint inhibitor, anti-PD-1, or anti-PD-L1. Only prospective clinical trials were included. RESULTS: The systematic review yielded 9,722 records through the MEDLINE (Ovid) and EMBASE (Ovid) databases. Ultimately, five prospective clinical trials with 722 patients were selected for inclusion. The rates of any grade adverse event (AE) and grade (G) 3-4 AEs were 79.9% and 20.9%, respectively. Regarding immune-related AEs (irAEs), the most common system affected by any grade irAE was the skin (30.89%) and the most common grade 3-4 irAE was related to the hepatic system (8.23%). Rates of AEs were similar across the CPI monotherapy clinical trials. CONCLUSIONS: The rates of AEs in mRCC patients treated with CPI is similar to rates in other cancers. AEs in mRCC are fairly consistent among monotherapy trials with PD-1 and PD-L1 inhibitors and as one would expect higher when CTLA-4 and PD-1 inhibitors are offered in combination.

17.
Clinical Medicine of China ; (12): 90-92, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-469510

ABSTRACT

Objective To investigate the clinical features and prognosis of the patients with renal cell carcinoma and venous tumor thrombus.Methods Fifty-six patients with renal cell carcinoma and venous tumor thrombus were selected as our subjects,who underwent radical nephrectomy and thrombectomy in the Second Hospital of Tianjin Medical University from June 2002 to May 2014.There were 28 patients with stage Ⅰ tumor thrombus,l5with stage Ⅱtumor thrombus,9 with stage Ⅲ tumor thrombus and 4 with stage Ⅳtumor thrombus.All patients underwent renal tumor resection and embolectomy,and were follow-up.Results Of all the patients,46 were male and 10 were female with a mean age of 61.7(age ranging from 42 to 83).Twenty-four were presented on the left kidney and 32 were right.The clinical features were as follows:The tumor size was 2.5 to 14 cm in diameter(mean:6.2 cm),there were 21 cases with low back pain,18 cases with hematuria,lcases with abdominal.Pathological results showed that 39 with clear cell carcinoma,9 with papillary cell carcinoma,3 with chromophobe cell carcinoma,1 with low-differentiated cell carcinoma and 1 with undifferentiated cell carcinoma,3 with sarcomatoid differentiation.Forty-three patients were followed up,and the median follow up period was 20.4 months (2-90 months).The median survival time for the patients was 47 months and the 5 year overall survival was 45.2%.The survival time of the patients with early tumor thrombus(below hepaticvein) was (55.3 ± 4.9) month,significantly longer than that of the patients with advanced tumor thrombus (above hepaticvein) ((24.8 ± 5.3) months,P =0.047).Conclusion Patients with renal cell carcinoma and venous tumor thrombus are characterized with high malignancy and poor prognosis.Surgical operations are effective therapies for the patients.Long term outcome of the early tumor thrombus patients is significantly better than that of the advanced tumor.

18.
Cancer Lett ; 354(2): 455-66, 2014 Nov 28.
Article in English | MEDLINE | ID: mdl-25149066

ABSTRACT

Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, ß-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application.


Subject(s)
MicroRNAs/metabolism , Neural Cell Adhesion Molecule L1/biosynthesis , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Carcinoma/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Disease-Free Survival , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , MicroRNAs/genetics , Neural Cell Adhesion Molecule L1/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism
19.
Cancer ; 120(10): 1565-71, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24523042

ABSTRACT

BACKGROUND: The delivery of urologic oncology care is susceptible to regional variation. In the current study, the authors sought to define patterns of care for patients undergoing genitourinary cancer surgery to identify underserved areas for urologic cancer care in Washington State. METHODS: The authors accessed the Washington State Comprehensive Hospital Abstract Reporting System from 2003 through 2007. They identified patients undergoing radical prostatectomy, radical cystectomy (RC), partial nephrectomy (PN), radical nephrectomy, and transurethral resection of the prostate (TURP). TURP was included for comparison as a reference procedure indicative of access to urologic care. Hospital service areas (HSAs) are where the majority of local patients are hospitalized; hospital referral regions (HRR) are where most patients receive tertiary care. The authors created multivariate hierarchical logistic regression models to examine patient and HSA characteristics associated with the receipt of urologic oncology care out of the HRR for each procedure. RESULTS: Greater than one-half of patients went out of their HRR in 7 HSAs (11%) for radical prostatectomy, 3 HSAs (5%) for radical nephrectomy, 10 HSAs (15%) for PN, and 14 HSAs (22%) for RC. No HSAs had high export rates for TURP. Few patient factors were found to be associated with surgical care out of the HRR. High-export HSAs for PN and RC exhibited lower socioeconomic characteristics than low-export HSAs, adjusting for HSA population, race, and HSA procedure rates for PN and RC. CONCLUSIONS: Patients living in areas with lower socioeconomic status have a greater need to travel for complex urologic surgery. Consideration of geographic delineation in the delivery of urologic oncology care may aid in regional quality improvement initiatives.


Subject(s)
Catchment Area, Health/statistics & numerical data , Cystectomy/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Medically Underserved Area , Nephrectomy/statistics & numerical data , Prostatectomy/statistics & numerical data , Urologic Neoplasms/epidemiology , Urologic Neoplasms/surgery , Adult , Aged , Cystectomy/economics , Female , Health Maintenance Organizations , Humans , Insurance, Health , Logistic Models , Male , Medicare , Middle Aged , Multivariate Analysis , Nephrectomy/economics , Odds Ratio , Prostatectomy/economics , Referral and Consultation/statistics & numerical data , Transurethral Resection of Prostate/statistics & numerical data , United States , Urologic Surgical Procedures/statistics & numerical data , Washington/epidemiology
20.
Oncol Lett ; 7(3): 621-626, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24520285

ABSTRACT

The matrix metalloproteinase (MMP) family has been shown to play a critical role in tissue remodeling and tumor infiltration. Their activity is normally strictly controlled by tissue inhibitors of metalloproteinases (TIMPs). However, TIMPs act indirectly through modulation of protease activity or directly through cell surface receptors to direct cell fate. These molecules have been proposed as markers of malignant cancer. Previous studies on MMP and TIMP expression in kidney carcinoma have been limited and have reported variable observations. The current study measured the content of MMP-2 and -9 and TIMP-1 and -2 in the sera and urine of patients with kidney carcinoma by enzyme-linked immunosorbent assay. Of these patients, 16 exhibited clear cell renal cell carcinoma (ccRCC) and 4 exhibited oncocytoma. Sera and urine samples of 53 healthy subjects were used as controls. In the sera of the control group, MMP-2 and TIMP-2 were detectable in all samples, while MMP-9 and TIMP-1 were below the sensitivity of the assay. In the pathological specimens, the mean serum values of MMP-2 and TIMP-1 and -2 were similar in the ccRCC and oncocytoma patients, whereas the value for MMP-9 was 2-fold higher in the ccRCC patients compared with the oncocytoma patients. With regard to the urine specimens, all four molecules were undetectable in the normal healthy samples and in a few pathological samples. The mean values for MMP-2 and -9 and TIMP-2 in the positive urine specimens were similar in the ccRCC and oncocytoma patients, whereas the mean value of TIMP-1 was higher in the ccRCC patients compared with that of the oncocytoma patients. The mean urinary levels of the four molecules were less than those of the sera. Statistical analysis of the data did not reveal any correlation between the tumor grades and expression levels of the molecules examined.

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