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ABSTRACT: OBJECTIVES: To investigate the potential mechanism of development of resistance to tyrosine kinase inhibitor in renal cell carcinoma. METHODS: A primary culture of renal cell carcinoma cells (KMRM-S2) was established from an advanced renal cell carcinoma patient with cutaneous metastasis, who had not responded to sorafenib. A total of 84 human angiogenesis-related genes were compared between cutaneous metastasis and the primary tumor by real time polymerase chain reaction. Spectral karyotyping and cell proliferation assay were carried out to determine the biological features of the cells. RESULTS: Primary tumor was histopathologically diagnosed as high-grade clear cell carcinoma with sarcomatoid change and rhabdoid features. The cutaneous metastasis also consisted of sarcomatoid components. Expression levels of many angiogenesis-related genes in the cutaneous metastasis were relatively higher than those of primary tumor. Chromosomal analysis of the KMRM-S2 showed cytogenetic abnormalities with hypertriploidy and translocation. In vitro proliferation assay showed the relatively higher resistance of KMRM-S2 against sorafenib. CONCLUSIONS: The sarcomatoid change and rhabdoid features of renal cell carcinoma with cytogenetic hyperploidy might be associated with elevated expression of angiogenesis-related genes, which leads to resistance against tyrosine kinase inhibitor. The present study might contribute to discovering novel therapeutic targets for the treatment of patients with advanced renal cell carcinoma resistant to tyrosine kinase inhibitor.
International Journal of Urology 02/2013; · 1.75 Impact Factor
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ABSTRACT: PURPOSE: To understand the current clinical features of kidney cancers in patients with von Hippel-Lindau (VHL) disease in Japan. SUBJECT AND RESULT: We performed a nationwide epidemiological survey of patients with VHL disease using the epidemiology program for incurable disease by the Ministry of Health, Labour and Welfare. The content of the survey included age of onset of VHL disease, sex, residential area, treatment modalities, kidney function, ECOG performance status, and prognosis. Here, we report the results of kidney cancer. The incidence rate of kidney cancer in VHL disease in Japan is 50.3% (206/409). Males and females are equally affected. The mean age of onset is 37.8 + 0.92 years. The median age of onset is 35 years. The ages of onset are distributed between 15 and 75 years. The mostly affected age of onset is between 20 and 50 years. The incidence rate of patients with metastasis is 11.1% (23/206). The most common site for metastasis is the lung (60%, 14/23). Due to multiple numbers of tumors at initial diagnosis and the metachronous development of tumors, patients received treatment on multiple occasions (mean 1.6 times), including partial nephrectomy (46%), total nephrectomy (31%) or radiofrequency ablation (14%) up to 6 times. The multiple treatments resulted in deterioration of the kidney function, causing chronic dialyses in 7 cases (3%). The ECOG performance status was scored as more than 1 in 42% of patients. The ten-year survival rate in VHL patients with kidney cancer was 94%, which is relatively high compared with that survival rates in sporadic kidney cancers. CONCLUSION: The current study indicates that the age of onset of kidney cancers in VHL disease is relatively young, and kidney cancers have features of metachronous development. The clinical features of kidney cancer developed in VHL disease among Japanese population are very similar with those in European countries. Multiple treatments result in deterioration of the kidney function.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 05/2012; 103(3):552-6.
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Takashi Anchi,
Kenji Tamura,
Mutsuo Furihata,
Hirofumi Satake,
Hatsune Sakoda,
Chiaki Kawada,
Maiko Kamei,
Tsutomu Shimamoto,
Hideo Fukuhara,
Satoshi Fukata,
Shingo Ashida,
Takashi Karashima,
Ichiro Yamasaki,
Masaharu Yasuda, Masayuki Kamada,
Keiji Inoue,
Taro Shuin
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ABSTRACT: Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 exhibit rapid growth and are more likely to spread beyond the prostate. These cancer types demonstrate a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among these genes, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells. Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. By contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for cell proliferation and progression of high-grade PC and that it may be a novel molecular target for cancer drugs.
Oncology letters 02/2012; 3(2):264-268. · 0.11 Impact Factor
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Keiji Inoue,
Hideo Fukuhara,
Tsutomu Shimamoto, Masayuki Kamada,
Tatsuo Iiyama,
Mitsuhiko Miyamura,
Atsushi Kurabayashi,
Mutsuo Furihata,
Masanobu Tanimura,
Hironobu Watanabe,
Taro Shuin
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ABSTRACT: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer.
Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT.
The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events.
This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.
Cancer 07/2011; 118(4):1062-74. · 4.77 Impact Factor
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ABSTRACT: We report a case of granulocyte-colony stimulating factor (G-CSF)-producing squamous cell carcinoma of the renal pelvis. A 71‒year-old woman presented with gross hematuria and leucocytosis of 21,300/mm3 (neutrophil : 86%) in the peripheral blood, but with no focus of infection. Right renal pelvic mass was found at a nearby hospital and she was referred to our hospital for examination and treatment. We performed right nephroureterectomy for a right renal pelvic tumor. Hematoxylin-eosin staining revealed squamous cell carcinoma of the renal pelvis and tumor cells stained strongly positive for G-CSF. According to these histopathological findings, we diagnosed this case as G-CSF-producing squamous cell carcinoma of the renal pelvis. She is presently alive without any new recurrent lesions for 12 months.
Hinyokika kiyo. Acta urologica Japonica 09/2010; 56(9):505-8.
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ABSTRACT: The objective of this study was to optimize the least invasive technique of radiofrequency ablation (RFA) for the degenerated renal parenchyma and to develop a novel RFA system.
Tissue temperature and pathological degeneration were investigated at regular time intervals and distances from the RFA needle electrode in the renal parenchyma of the pig kidney. We also examined whether interruption of the renal artery or irrigation in the renal pelvis had an influence on the therapeutic effects.
Pathological investigations showed a core necrotic area surrounded by an ischemic layer around the needle electrode. Interestingly, interruption of the renal artery and irrigation in the renal pelvis markedly enhanced the degeneration of the parenchyma. Especially the electric conductivity of irrigation solutions in the renal pelvis influenced the therapeutic effect. In this novel system which retains the flow of electricity between the 2 electrodes and maintains the electric power at a constant wattage, a marked therapeutic effect was observed between the 2 electrodes rather than on their outsides, and this was not influenced by renal artery interruption and/or renal parenchyma cooling.
This novel RFA system may contribute to more effective and highly reproducible therapeutic results.
Pathobiology 01/2010; 77(2):64-77. · 1.18 Impact Factor
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ABSTRACT: We report a case of successful response of lung metastases of reccurent adult Wilms' tumor by multiagent chemotherapy. The patient was a 19-year-old woman who had undergone left radical nephrectomy and adjuvant chemotherapy (actinomycin D, vincristine) for stageadult Wilms' tumor when she was 16 years old. Coputed tomography (CT) revealed multiple lung metastases (right parietal pleura, left S10, right S10). We treated the patient with thoracoscopic partial resection of inferior lobe of lung. Then she received multiagent chemotherapy (vincristine, adriamycin, etoposide, cyclophosphamide). CT scan showed complete response of the lung metastases at 8 months.
Hinyokika kiyo. Acta urologica Japonica 11/2009; 55(11):699-702.
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Keiji Inoue,
Takahira Kuno,
Hideo Fukuhara,
Takuya Hamaguchi,
Satoshi Fukata,
Takashi Karashima, Masayuki Kamada,
Taro Shuin,
Naoki Sakakura,
Kotaro Kasahara,
Hironobu Watanabe,
Tetsuo Kozai,
Masaharu Yasuda,
Shinichi Kataoka,
Masanobu Tanimura,
Kurabayashi Atsushi,
Mutsuo Furihata
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ABSTRACT: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method.
TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001).
It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 11/2009; 100(7):661-70.
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Takashi Anchi,
Kenji Tamura,
Keiji Inoue,
Hirofumi Satake,
Shingo Ashida,
Hiroshi Nishikawa, Masayuki Kamada,
Masaharu Yasuda,
Shinichi Kataoka,
Hideki Nakajima,
Taro Shuin
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ABSTRACT: Fournier's gangrene is a rare disease of rapidly progressive necrotising fasciitis of the genital, perineal and perianal regions and leads to sepsis and death. We report 8 cases of Fournier's gangrene treated at our hospital and affiliated hospitals from 1997 to 2007. There were seven males and one female in the series, and the age range was 23-89 years (mean age 56.6 years). Four patients among them had diabetes mellitus. We rescued all patients by broad-spectrum antibacterial chemotherapy and debridement. Good management should be based on broad-spectrum antibacterial chemotherapy, debridement and intensive care.
Hinyokika kiyo. Acta urologica Japonica 09/2009; 55(9):545-9.
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ABSTRACT: The purpose of this study was to clarify the regulatory mechanism of protoporphyrin IX (PpIX) synthesis mediated by 5-aminolevulinic acid (ALA) in human urothelial carcinoma (UC), leading to improved accuracy in photodynamic diagnosis and therapy using ALA.
PpIX accumulation in cultured UC cells after incubation for 1-5 h with 0.5-5 mM ALA was analyzed by fluorescence analysis using fluorescence microscopy and flow cytometry technique.
PpIX fluorescence mediated by ALA was increased, and the intensity of PpIX fluorescence was time-dependently increased in UC cells compared to noncancerous cells. The distribution of endogenous PpIX fluorescence primarily coincided with mitochondria, and then increased at a specific perinuclear region in the cells during the time of incubation. The ALA-mediated PpIX synthesis in UC cells was suppressed by beta-alanine, an inhibitor of beta-transporters of cell membrane, and carbonylcyanide p-trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, the ALA-mediated PpIX accumulation was increased by deferoxamine, an iron chelator, manganese and nitric oxide, which is contributed to PpIX metabolism by inhibiting ferrochelatase activity, generated by a nitric oxide-generating reagent NOC-18. As observed above, ALA-mediated PpIX synthesis in human UC cells was regulated by the process of ALA uptake, ALA conversion to PpIX and metabolism of accumulated PpIX to heme.
This shows that the suppression of ferrochelatase increased PpIX accumulation in UC cells using small amount of ALA, thus leading to an improved clinical practicability of photodynamic diagnosis and therapy.
Pathobiology 01/2009; 76(6):303-14. · 1.18 Impact Factor
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ABSTRACT: To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method.
Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy.
Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect.
Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 08/2006; 97(5):719-29.
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ABSTRACT: We report 7 renal cell carcinomas in 4 patients treated by percutaneous image-guided radiofrequency ablation (RFA). The mean age of the patients was 59 years (male: 2, female: 2). All 4 were imperative cases. Two patients (5 tumor) had hereditary multiple renal cell carcinomas with von Hippel-Lindau (VHL) disease. The other two patients had sporadic renal cell carcinomas. RFA was performed guided by computed tomography under conscious sedation with local anesthetics. The mean size of the treated tumors was 4.5 (1.8-8.1) cm. Impedance-regulated RF energy from a generator at 94 (45-130) watts was applied at 11 (8-14) min intervals. The average procedure time was 91 (45-165) minutes. The maximum tissue temperature reached 82 (56-91) degrees C immediately after ablation. Three of the 7 lesions (42.9 %) were locally well controlled during the mean follow-up period of 6.3 (4-9) months. The two patients with VHL disease developed visceral metastasis after There were no major complications. Minor complications encountered included flank pain, nausea, perinephritic hematoma and fever. Although percutaneous image-guided RFA showed limited success in large or central renal tumors, the therapy against small exophytic renal tumors would be well tolerable and successful.
Hinyokika kiyo. Acta urologica Japonica 05/2006; 52(4):241-7.
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ABSTRACT: To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.
Cancer Genetics and Cytogenetics 06/2005; 159(1):84-8. · 1.39 Impact Factor
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ABSTRACT: To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors.
They evaluated intratumoral microvessel density (MVD) by immunohistochemical staining, assessed the expression of angiogenesis-related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 metastatic tumor specimens were resected from 24 patients.
The pathologic stage (P=0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P=0.000025) and the ratio of matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P <0.05). Relative to the primary tumors, the metastatic tumors also had high MVD, overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P <0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P=0.049 and P=0.001, respectively). Furthermore, the M/E ratio in metastatic tumor specimens resected from the lung and lymph node was an independent prognostic factor for metastasis (P=0.01823 and P=0.03950, respectively).
The current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC.
Cancer 04/2005; 103(5):931-42. · 4.77 Impact Factor
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ABSTRACT: We report our clinical findings on 12 tumors (11 patients) successfully resected by partial nephrectomy with a microwave tissue coagulator (MTC) without renal pedicle clamping, including laparoscopic operation in 4 patients. All patients presented with a renal tumor detected incidentally by ultrasonography or computed tomography. The mean size of renal tumor was 1.9 (range 0.8-3.4) cm. Pathological diagnosis was renal cell carcinoma in 9 tumors and hemorrhagic cyst in 3 tumors. Mean operative time was 249 minutes. Mean blood loss was 183 ml in cases with a laparoscopic operation, that was statistically less than 486 ml in cases with an open operation (p<0.05), and 376 ml in all cases. There was no significant change in the creatinine clearance of cases with laparoscopic operation, compared with that of cases with an open operation. There were no other serious complications postoperatively. These findings suggested that partial nephrectomy with the MTC can be safely and successfully carried out while sparing renal function. Moreover, partial nephrectomy with the MTC for a laparoscopic operation may provide these patients with more benefits.
Hinyokika kiyo. Acta urologica Japonica 11/2004; 50(11):763-6.
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ABSTRACT: Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that is associated with various tumors and cysts in the central nervous system (CNS) and visceral organs. Inactivation of the VHL tumor-suppressor protein and subsequent loss of function in the VHL, and Elongin BC (VBC) complex result in dysfunction in the ubiquitination of hypoxia-inducible factor (HIF), which is an important step in the development of angiogenic tumors. The most frequent disorders in VHL disease are hemangioblastoma in the CNS and retina, pheochromocytoma in the adrenal gland, renal cell carcinoma, and pancreatic neuroendocrine tumor. Here, we review recent ideas on the pathogenesis and clinical diagnosis and treatment of VHL disease. Progress in molecular diagnosis and molecular targeting therapy is expected for improvement in the diagnosis and treatment of this disease. The family's support for patients with VHL disease is important, being mutually helpful to overcome various social and psychological problems in the patients.
International Journal of Clinical Oncology 09/2004; 9(4):283-7. · 1.41 Impact Factor
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ABSTRACT: To identify new diagnostic markers for testicular germ cell tumors (TGCTs), including seminomas, as well as potential targets of new drugs for treating the disease, we compared gene-expression profiles of cancer cells from 13 seminomas with normal human testis using laser-capture microdissection and a cDNA microarray representing 23,040 genes. We identified 347 genes that were commonly up-regulated in seminoma cells. The functions of 227 were known to some extent; the remaining 120 included 55 ESTs. On the list were cyclin D2 (CCND2), prostate cancer over-expressed gene 1 (POV1), and junction plakoglobin (JUP), all of which were already known to be over-expressed in seminomas. On the other hand, our protocol selected 593 genes as being commonly down-regulated in seminoma cells. That list included 340 functionally characterized genes; the other 253 included 131 ESTs. To confirm the expression data, we performed semi-quantitative RT-PCR experiments with nine highly up-regulated genes, and the results supported those of our microarray analysis. The information provided here should prove useful for identifying genes whose products might serve as molecular targets for treatment of TGCTs.
International Journal of Oncology 01/2004; 23(6):1615-35. · 2.40 Impact Factor
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ABSTRACT: In this study, we examined nine cases of advanced Japanese prostate cancer by comparative genomic hybridization (CGH) to detect chromosomal imbalances across the entire genome and to identify several new regions likely to contain genes important to the development and progression of this disease. These cases had been previously examined for numerical chromosomal aberrations by fluorescence in situ hybridization (FISH). By CGH, the following regions were found to be over-represented (gains), with fluorescence ratio values higher than the threshold: 4p, 6p, 8q, 11q, 12q, 15q, 16p, 17q, 20, and 21 (>4 cases); underrepresentation (losses) involved: 1q, 4q, 5q, 6q, 13q, 14q, and 22 (>4 cases). The shortest regions of overlap (SRO) of gains were noted at 8q24.1 through q24.3, 12q23, and 17q23 through q24 (>5 cases). The SRO of losses were seen at 5q14 through q21, 6q16.1 through q21, 13q21.3 through q22, and 14q21 (>5 cases). Notably, the gain of chromosomes 8 and 12 by CGH was in agreement with the FISH data, suggesting that the gain of chromosomes 8 and 12 may play an important role in prostate carcinogenesis. The genes on the SRO regions were also discussed in relation to oncogenes and bone metastases.
Cancer Genetics and Cytogenetics 08/2002; 137(1):59-63. · 1.39 Impact Factor
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ABSTRACT: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT).
We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis.
We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively.
We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.
Clinical Cancer Research 07/2002; 8(6):1863-70. · 7.74 Impact Factor
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ABSTRACT: Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.
Acta Medica Okayama.
