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1.
Hinyokika Kiyo ; 69(9): 249-254, 2023 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-37794675

RESUMO

We report three patients with T1 high-grade (HG) bladder cancer who suffered from distant metastasis during bladder preservation. The patients were a 48-year-old female (Case 1), a 75-year-old female (Case 2) and an 82-year-old male (Case 3) with the chief complaint of asymptomatic gross hematuria. The histopathological diagnoses of the initial transurethral resection of the bladder tumor (TURBT) and second TURBT were urothelial carcinoma, pT1, HG and no malignancy in all three patients. Bladder tumors of all patients revealed sessile growth pattern and no presence of carcinoma in situ. Case 2 and 3 did not receive BCG vesical instillation after the second TURBT. Lymph node metastases appeared in Case 1 and Case 2 and lung metastasis appeared in Case 3. Tumor budding (TB) was positive in Case 1 and Case 2. Variant histology (VH) of nested morphology was detected in Case 1 and VH of inverted morphology in Case 2 and Case 3. Twenty-four months after the initial TURBT, Case 1 died due to cancer progression after cisplatin-based chemotherapy and pembrolizumab therapy. Thirty-three and 11 months after the initial TURBT, Case 2 and Case 3 were alive without cancer progression after cisplatin-based chemotherapy and/or pembrolizumab therapy, respectively. The two patients with T1 HG bladder cancer with TB had lymphatic metastasis and the patient without TB had hematogenous metastasis. Nested morphology is reportedly categorized as high-risk disease and inverted morphology as low-risk disease. TB might be correlated with lymphatic metastasis in T1 HG bladder cancer, and TB should be considered in the management of T1 HG bladder cancer. In the case of VH, the guidelines should be followed during the treatment decision of T1 HG bladder cancer.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Bexiga Urinária , Cisplatino , Metástase Linfática , Recidiva Local de Neoplasia
2.
Mol Clin Oncol ; 18(1): 3, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36545210

RESUMO

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing.

3.
Int J Oncol ; 61(3)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35894141

RESUMO

Pyruvate dehydrogenase kinase 4 (PDK4) is an important regulator of energy metabolism. Previously, knockdown of PDK4 by specific small interfering RNAs (siRNAs) have been shown to suppress the expression of Κirsten rat sarcoma viral oncogene homolog (KRAS) and the growth of lung and colorectal cancer cells, indicating that PDK4 is an attractive target of cancer therapy by altering energy metabolism. The authors previously reported that a novel small molecule, cryptotanshinone (CPT), which inhibits PDK4 activity, suppresses the in vitro three­dimensional (3D)­spheroid formation and in vivo tumorigenesis of KRAS­activated human pancreatic and colorectal cancer cells. The present study investigated the molecular mechanism of CPT­induced tumor suppression via alteration of glutamine and lipid metabolism in human pancreatic and colon cancer cell lines with mutant and wild­type KRAS. The antitumor effect of CPT was more pronounced in the cancer cells containing mutant KRAS compared with those containing wild­type KRAS. CPT treatment decreased glutamine and lipid metabolism, affected redox regulation and increased reactive oxygen species (ROS) production in the pancreatic cancer cell line MIAPaCa­2 containing mutant KRAS. Suppression of activated KRAS by specific siRNAs decreased 3D­spheroid formation, the expression of acetyl­CoA carboxylase 1 and fatty acid synthase (FASN) and lipid synthesis. The suppression also reduced glutathione­SH/glutathione disulfide and increased the production of ROS. Knockdown of FASN suppressed lipid synthesis in MIAPaCa­2 cells, partially promoted ROS production and mildly suppressed 3D­spheroid formation. These results indicated that CPT reduced tumorigenesis by inhibiting lipid metabolism and promoting ROS production in a mutant KRAS­dependent manner. This PDK4 inhibitor could serve as a novel therapeutic drug for KRAS­driven intractable cancers via alteration of cell metabolism.


Assuntos
Neoplasias Colorretais , Neoplasias Pancreáticas , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/patologia , Glutamina/metabolismo , Humanos , Lipídeos , Lipogênese , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fenantrenos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Neoplasias Pancreáticas
4.
Asian J Endosc Surg ; 15(1): 172-175, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33890712

RESUMO

Fluorescence image-guided surgery has improved intraoperative identification of anatomic structures including visualization of vascular anatomy. Herein, indocyanine green (ICG) fluorescence imaging was applied to identify of a recurrent small tumor of renal cell carcinoma (RCC) during laparoscopic surgery. The patient underwent left laparoscopic radical nephrectomy via the retroperitoneal approach for RCC (clear cell carcinoma, pT1bN0M0) at the age of 39 years. A solitary retroperitoneal mass (14 mm in diameter) was identified in a computed tomography scan 6 years after surgery. We performed laparoscopic resection with the application of the ICG angiography, because RCC is recognized as one of the most hypervascular cancers. The tumor was clearly visualized by fluorescence. Histopathological diagnosis of the resected tumor was recurrent RCC (low grade, G1). The patient remained free of disease at 2 years after surgery. The ICG fluorescence imaging would be a useful method for identification of metastatic small lesions of RCC during laparoscopic surgery.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Neoplasias Retroperitoneais , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Verde de Indocianina , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia , Imagem Óptica , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia
5.
Prostate ; 81(15): 1172-1178, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34418129

RESUMO

BACKGROUND: In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. METHODS: A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. RESULTS: In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. CONCLUSIONS: Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Inquéritos Epidemiológicos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia
6.
Int J Oncol ; 59(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33982789

RESUMO

The phosphorylation of pyruvate dehydrogenase (PDH) by pyruvate dehydrogenase kinase (PDK) 4 inhibits its ability to induce a glycolytic shift. PDK4 expression is upregulated in various types of human cancer. Because PDK4 regulation is critical for metabolic changes in cancer cells, it is an attractive target for cancer therapy given its ability to shift glucose metabolism. It was previously shown that a novel PDK4 inhibitor, cryptotanshinone (CPT), suppressed the three­dimensional (3D)­spheroid formation of pancreatic and colorectal cancer cells. In the present study, the effects of CPT on the invasiveness of bladder cancer cells were investigated. CPT significantly suppressed the invasiveness and 3D­spheroid formation of T24 and J82 bladder cancer cells. CPT also suppressed the phosphorylation of PDH and ß­catenin, as well as the expression of N­cadherin, which are all critical for inducing epithelial­mesenchymal transition (EMT). The knockdown of ß­catenin or PDK4 using specific small interfering RNAs suppressed N­cadherin expression and invasiveness in T24 cells. An mTOR inhibitor also suppressed the phosphorylation of ß­catenin and N­cadherin expression. Furthermore, CPT injection significantly suppressed pancreatic tumor growth and peritoneal dissemination of highly metastatic SUIT­2 pancreatic cancer cells in a mouse orthotopic pancreatic cancer model, without evident toxicity. Moreover, immunohistochemistry analyses demonstrated decreased ß­catenin expression in CPT­treated pancreatic tumors compared with control tumors. Taken together, these results indicate that CPT reduced the invasiveness and metastasis of bladder cancer cells by suppressing EMT via the mTOR/ß­catenin/N­cadherin pathway.


Assuntos
Antineoplásicos/farmacologia , Fenantrenos/farmacologia , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
7.
In Vivo ; 35(2): 1141-1145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622912

RESUMO

BACKGROUND: This study evaluated the efficacy of a single instillation of pirarubicin with a short retention time for preventing intravesical recurrence of low-risk non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We analyzed 165 patients with low-risk non-muscle-invasive bladder cancer who underwent transurethral surgery. Single instillation of pirarubicin with 15-min retention time immediate after surgery was performed in 47 (28%) patients. The other patients (118, 72%) were treated without instillation therapy. The primary endpoint was recurrence-free survival. RESULTS: Median overall follow-up was 50 (range=6-134) months. Recurrence-free survival at 1 and 5 years was 91% and 72%, and 79% and 54% in the group treated with pirarubicin, and that treated with surgery alone, respectively (p=0.031). Cox's hazard analysis revealed lack of instillation and larger tumor size (>10 mm) as significant factors for risk of recurrence. No adverse events regarding intravesical chemotherapy were observed. CONCLUSION: Pirarubicin instillation with 15-min retention time can prevent intravesical recurrence of low-risk bladder tumors.


Assuntos
Neoplasias da Bexiga Urinária , Administração Intravesical , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia
8.
Mol Carcinog ; 58(10): 1726-1737, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31106493

RESUMO

Phosphorylation of pyruvate dehydrogenase by pyruvate dehydrogenase kinase 4 (PDK4) 4 inhibits its ability to induce a glycolytic shift. PDK4 expression is frequently upregulated in various cancer tissues, with its elevation being critical for the induction of the Warburg effect. PDK4 is an attractive target for cancer therapy given its effect on shifting glucose metabolism. Previous research has highlighted the necessity of identifying a potent compound to suppress PDK4 activity at the submicromolar concentrations. Here we identified natural diterpene quinones (KIS compounds) that inhibit PDK4 at low micromolar concentrations. KIS37 (cryptotanshinone) inhibited anchorage-independent growth in three-dimensional spheroid and soft agar colony formation assays of KRAS-activated human pancreatic (MIAPaCa-2 and Panc-1) and colorectal (DLD-1 and HCT116) cancer cell lines. KIS37 also suppressed KRAS protein expression in such cell lines. Furthermore, KIS37 suppressed phosphorylation of Rb protein and cyclin D1 protein expression via the PI3K-Akt-mTOR signaling pathway under nonadherent culture conditions and suppressed the expression of cancer stem cell markers CD44, EpCAM, and ALDH1A1 in MIAPaCa-2 cells. KIS37 also suppressed pancreatic cancer cell growth in both subcutaneous xenograft and orthotopic pancreatic tumor models in nude mice at 40 mg/kg (intraperitoneal dose) without any evident toxicity. Reduced ALDH1A1 expression was observed in KIS37-treated pancreatic tumors, suggesting that cancer cell stemness was also suppressed in the orthotopic tumor model. The aforementioned results indicate that KIS37 administration is a novel therapeutic strategy for targeting PDK4 in KRAS-activated intractable human pancreatic cancer.


Assuntos
Família Aldeído Desidrogenase 1/genética , Inibidores Enzimáticos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Retinal Desidrogenase/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Inibidores Enzimáticos/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/genética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int J Clin Oncol ; 23(5): 951-956, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29761307

RESUMO

BACKGROUND: To evaluate the effect of intravesical bacillus Calmette-Guerin (BCG) instillation therapy after second transurethral resection (TUR) on primary T1 bladder cancer. METHODS: The subjects were 180 patients diagnosed with T1 bladder cancer at our university and at affiliated hospitals between January 1990 and December 2015. Tumor residual rate, intravesical recurrence rate, and risk factors for intravesical recurrence were investigated. RESULTS: The median follow-up period was 26 (1-175) months. Of the 180 patients, 78 (43%) underwent a second TUR. Residual tumors were detected in 42 patients (53.8%), and no up-staging cases were observed. Within the whole group, 42 patients were treated with intravesical BCG therapy following a second TUR (group 1), 36 were treated with second TUR alone (group 2), 28 were treated with intravesical BCG therapy alone (group 3), and 74 were treated without second TUR or intravesical BCG therapy (group 4). The 1- and 5-year recurrence-free survival rates of the four groups were 80.7 and 59.7% (group 1), 69.0 and 26.3% (group 2), 76.3 and 56.6% (group 3), 64.6 and 48.6% (group 4), respectively. There was no significant difference between group 1 and group 3 (p = 0.401). Intravesical BCG therapy was the only factor preventing intravesical recurrence (p = 0.013). CONCLUSIONS: Intravesical BCG therapy alone showed a significant preventive effect with regard to intravesical recurrence. In our cohort, however, second TUR did not improve recurrence-free survival in those individuals who underwent BCG instillation.


Assuntos
Vacina BCG/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
10.
Int J Oncol ; 52(1): 231-240, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115414

RESUMO

The human cyclin D1 gene generates two major isoforms, cyclin D1a and cyclin D1b, by alternative splicing. Although cyclin D1b mRNA is hardly expressed in normal human tissues, it is detected in approximately 60% of human bladder cancer tissues and cell lines. In the present study, to assess the therapeutic ability of cyclin D1b siRNA, we investigated the anti-oncogenic effects of cyclin D1b siRNA on human bladder cancer cell lines, SBT31A and T24, which express cyclin D1b mRNA. Knockdown of cyclin D1b by specific siRNA significantly suppressed cell proliferation, in vitro cell invasiveness and three-dimensional (3D) spheroid formation in these cell lines. Cell cycle analyses revealed that cyclin D1b siRNA inhibited G1-S transition in T24 cells. The increase in the sub-G1 fraction, morphological aberrant nuclei with nuclear fragmentation and caspase-3 activity in SBA31A cells treated with cyclin D1b siRNA showed that cyclin D1b siRNA induced apoptosis. In T24 cells, knockdown of cyclin D1b suppressed the expression of the stem cell marker CD44. Knockdown of cyclin D1b or CD44 suppressed the invasiveness under 3D spheroid culture conditions and expression of N-cadherin. Tumor growth of SBT31A cells in nude mice was significantly inhibited by cyclin D1b siRNA. Taken together, these results indicate that knockdown of cyclin D1b suppresses the malignant phenotypes of human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and epithelial-mesenchymal transition. Applying cyclin D1b siRNA will be a novel therapy for cyclin D1b-expressing bladder cancers.


Assuntos
Ciclina D1/genética , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi/métodos , Neoplasias da Bexiga Urinária/terapia , Animais , Apoptose/genética , Testes de Carcinogenicidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Camundongos Transgênicos , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Distribuição Aleatória , Transfecção , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncol Lett ; 13(6): 4276-4284, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28599427

RESUMO

Periostin is an extracellular matrix protein involved in the regulation of intercellular adhesion. The present study investigated the in vivo tumor suppressor function of periostin in a mouse orthotopic model of bladder cancer. Retroviral vectors were used to transfect human bladder cancer UMUC-3 cell line with periostin. Bladders of nude mice that were transurethrally instilled with periostin-expressing UMUC-3 cells were revealed to weigh less compared with bladders instilled with vector control cells. In total, five (83.3%) of six vector control UMUC-3 bladder tumors exhibited histological evidence of muscle invasion. However, none of the five periostin-expressing UMUC-3 bladder tumors revealed muscle invasion. Thick edematous lesions were present in the submucosa of periostin-expressing UMUC-3 bladder tumors. The expression of periostin also suppressed in vitro cell invasiveness of UMUC-3 cells without affecting cellular proliferation. The level of phosphorylation of phosphoinositide-dependent kinase-1 (PDK1), protein kinase B (Akt) and S6 ribosomal protein, a downstream protein of mammalian target of rapamycin (mTOR) was decreased in periostin-expressing UMUC-3 cells compared with vector control cells. Treatment with 100 ng/ml recombinant human periostin protein also suppressed cell invasiveness and phosphorylation of PDK1, Akt and S6 in UMUC-3 cells, consistent with results using periostin-expressing UMUC-3 cells. Treatment with PDK1, Akt and mTOR inhibitors significantly suppressed UMUC-3 cell invasiveness. These results demonstrate that periostin suppresses in vivo and in vitro invasiveness of bladder cancer via the PDK1/Akt/mTOR signaling pathway. Periostin may be useful as a potent chemotherapeutic agent by suppressing bladder cancer invasiveness.

12.
Hinyokika Kiyo ; 62(10): 509-514, 2016 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-27919123

RESUMO

Percutaneous radiofrequency ablation (PRFA) has been applied as an option of minimally invasive treatment for small renal tumor. We retrospectively evaluated 5 patients with small renal tumor for whom PRFA was performed at our hospital. The average age was 69.6 years (range 45-86), average tumor diameter 20.0 mm (8-34), average preoperative glomerular filtration rate (eGFR) 66.8 ml/min/1.73m2 (42. 1-93.2), and follow-up period was 23.4 months (8-34). There were two minor complications (grade 1), including perirenal hematoma and pain at the probe insertion site in each patient. One patient had local recurrence 22 months after PRFA and the additional PRFA will be performed. PRFA could be a feasible, safe and effective therapy for small renal tumor.


Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter , Neoplasias Renais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Hinyokika Kiyo ; 62(11): 591-594, 2016 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-27919138

RESUMO

A 65-year-old man underwent radical cystectomy and cutaneous ureterostomy for bladder cancer. Because the patient had left complete duplex ureters,we modified the Toyoda method to construct the tubeless cutaneous ureterostomy with a unilateral stomal creation. The adhesive portion of both ureteral walls in duplex ureters was simultaneously cut approximately 5 mm from the distal end longitudinally,and the common sheath of the cut portion of the ureters was cut approximately 5 mm longitudinally in order to separate the two ureters. This procedure was repeated to make a"fish-mouth"aperture. Two opened ureteral walls were formed into the upper and lower plates of the Toyoda method stoma,respectively. To our knowledge,this is the first report of a surgical procedure of the tubeless cutaneous ureterostomy in complete duplex ureters.


Assuntos
Ureterostomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Humanos , Masculino , Ureterostomia/instrumentação
14.
Mol Carcinog ; 55(1): 52-63, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25620379

RESUMO

Previously, we showed that drs contributes to suppression of malignant tumor formation in drs-knockout (KO) mice. In this study, we demonstrate the regulation of glucose metabolism by drs using comparisons of drs-KO and wild-type (WT) mouse embryonic fibroblasts (MEFs). Extracellular acidification, lactate concentration, and glucose consumption in drs-KO cells were significantly greater than those in WT cells. Metabolomic analyses also confirmed enhanced glycolysis in drs-KO cells. Among glycolysis-regulating proteins, expression of lactate dehydrogenase (LDH)-B was upregulated at the post-transcriptional level in drs-KO cells and increased LDH-B expression, LDH activity, and acidification of culture medium in drs-KO cells were suppressed by retroviral rescue of drs, indicating that LDH-B plays a critical role for glycolysis regulation mediated by drs. In WT cells transformed by activated K-ras, expression of endogenous drs mRNA was markedly suppressed and LDH-B expression was increased. In human cancer cell lines with low drs expression, LDH-B expression was increased. Database analyses also showed the correlation between downregulation of drs and upregulation of LDH-B in human colorectal cancer and lung adenocarcinoma tissues. Furthermore, an LDH inhibitor suppressed anchorage-independent growth of human cancer cells and MEF cells transformed by activated K-ras. These results indicate that drs regulates glucose metabolism via LDH-B. Downregulating drs may contribute to the Warburg effect, which is closely associated with malignant progression of cancer cells.


Assuntos
Genes Supressores de Tumor , Glucose/metabolismo , L-Lactato Desidrogenase/metabolismo , Proteínas de Membrana/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Análise por Conglomerados , Feminino , Técnicas de Inativação de Genes , Humanos , Isoenzimas/metabolismo , Masculino , Metaboloma , Metabolômica/métodos , Camundongos , Camundongos Knockout , Neoplasias/genética , Neoplasias/metabolismo
15.
Oncol Lett ; 12(6): 4850-4856, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105192

RESUMO

A total of two major isoforms, cyclin D1a and cyclin D1b, are generated from the human cyclin D1 gene by alternative splicing. Cyclin D1b is scarcely expressed in normal tissues; however, it is expressed at a high frequency in certain types of cancerous tissue. The present authors previously constructed cyclin D1b transgenic (Tg) mice and identified rectal tumors, including adenocarcinoma and sessile serrated adenoma, in 62.5% of female Tg mice. In addition, the present authors indicated that cyclin D1b expression enhances phosphorylation of extracellular signal-regulated kinase (Erk) in these rectal tumors, and in mouse embryonic fibroblast (MEF) cells and human 293T cells. In the present study, it was initially demonstrated that cyclin D1b has the ability to enhance cell invasiveness by itself; it additionally increases cell invasiveness, anchorage-independent growth and tumorigenicity in cooperation with an activated K-ras oncogene in MEF cells. Phosphorylation of Akt was increased in cyclin D1b-expressing MEF cells and in the rectal tumor tissues of cyclin D1b Tg mice. Phosphorylation of Akt was also enhanced by transfection of cyclin D1b, but not cyclin D1a, in human 293T cells. Treatment with an Akt inhibitor suppressed phosphorylation of Erk in 293T cells expressing cyclin D1b and D1bTgRT cells established from rectal cancer of the cyclin D1b Tg mouse. Furthermore, the Akt inhibitor suppressed the invasiveness of D1bTgRT cells and the tumor growth of these cells in nude mice when the Akt inhibitor was injected into the tumors. These results indicate that cyclin D1b activates Erk through Akt, and that activation of Akt contributes to the tumorigenicity of the cyclin D1b Tg mice. Inhibitors targeting the phosphoinositide 3-kinase/Akt signaling pathway are thus expected to have therapeutic potential in a variety of human cancer types expressing cyclin D1b.

16.
Carcinogenesis ; 35(1): 227-36, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23975835

RESUMO

Human cyclin D1 generates two major isoforms via alternative splicing: cyclin D1a and cyclin D1b. Cyclin D1b is hardly expressed in normal tissues but is frequently expressed in certain types of cancer tissues. To clarify the oncogenic potential of cyclin D1b variant, we developed cyclin D1b transgenic (Tg) mice and analyzed their phenotypes. We detected rectal tumors in 63% (15/24) of the female Tg mice. All rectal tumors had the histological characteristics similar to human sessile serrated adenoma/polyps (SSA/Ps). Adenocarcinomas were also found in 53% (8/15) of the rectal tumors, suggesting that these adenocarcinomas originated from the SSA/P-like lesions. No rectal tumors were found in the ovariectomized female cyclin D1b Tg mice (0/10), indicating that ovarian hormones played a critical role in rectal carcinogenesis in these Tg mice. Both phosphorylation of Erk, without activating MEK, and expression of estrogen receptor ß were elevated in the rectal tumors of female cyclin D1b Tg mice compared with normal rectums of female wild-type mice. In addition, we established a cell line, D1bTgRT, derived from a rectal cancer of female Tg mouse. Small interfering RNA-induced cyclin D1b knockdown in this cell line suppressed Erk phosphorylation, anchorage-independent growth, cell invasiveness and tumorigenicity in nude mice. In humans, expression of cyclin D1b messenger RNA was detected in 17% (1/6) of colorectal cancer cell lines and 9.7% (3/31) of colorectal cancer tissues. Taken together, these results indicate that cyclin D1b expression contributes to the female- specific rectal carcinogenesis in mouse model.


Assuntos
Ciclina D1/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Retais/patologia , Animais , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Ovariectomia , Neoplasias Retais/genética , Neoplasias Retais/cirurgia
17.
Korean J Urol ; 54(5): 322-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23700498

RESUMO

PURPOSE: To evaluate (99m)Tc-mercaptoacetyltriglycine diuretic renograms for diagnosing stomal obstruction in tubeless cutaneous ureterostomy. MATERIALS AND METHODS: Cutaneous ureterostomy was performed in 29 patients (56 renal units) with a minimum follow-up period of 12 months. Stomal obstruction was evaluated with (99m)Tc-mercaptoacetyltriglycine diuretic renography 3 months after surgery. Regions of interest were drawn that completely encircled and snugly fit the kidney, renal pelvis, and ureter. The data analyses were performed with half-times to tracer clearance following furosemide (0.5 mg/kg) administration. RESULTS: The mean half-times to tracer clearance were 6.90±6.30, 5.25±4.29, and 8.75±7.63 minutes in the total, ipsilateral, and contralateral kidneys, respectively, in side relationships between the ureter and the stoma. There were significant differences between the ipsilateral and contralateral kidneys in the mean half-time to tracer clearance (p=0.038). Forty-eight renal units (85.7%) had a half-time to tracer clearance of less than 15 minutes, and all 48 renal units had no hydronephrosis. On the other hand, 5 renal units (8.9%) had a half-time to tracer clearance of more than 20 minutes, and these 5 renal units required the insertion of stent catheters or became atrophic. CONCLUSIONS: (99m)Tc-mercaptoacetyltriglycine diuretic renography was very useful for diagnosing stomal obstruction of tubeless cutaneous ureterostomy. The upper limit of the half-time to tracer clearance for unobstructed systems was 15 minutes, which allowed for the confident exclusion of stomal obstruction in tubeless cutaneous ureterostomy.

18.
Korean J Urol ; 54(3): 168-71, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23526413

RESUMO

PURPOSE: To investigate hydronephrosis after the establishment of tubeless cutaneous ureterostomy by using our definition of the tubeless condition and our indications for catheter insertion. MATERIALS AND METHODS: Twenty-eight (54 renal units) patients with both establishment of tubeless cutaneous ureterostomy 3 months after surgery and at least 12 months of follow-up were investigated in this study. The 4-grade system was used to evaluate the hydronephrosis. The definition of the tubeless condition in cutaneous ureterostomy was as follows: 1) the catheter stent is not placed in the renal pelvis through the stoma, 2) the grade of hydronephrosis is less than 3, and 3) the kidney is functioning. Indications for catheter insertion after the establishment of tubeless cutaneous ureterostomy were as follows: 1) difficulty in curing acute pyelonephritis by drug treatments, 2) flank pain due to hydronephrosis, or 3) increase in the grade of hydronephrosis. RESULTS: The follow-up period was 12 to 78 months (average, 40.5±22.1 months). After the establishment of tubeless cutaneous ureterostomy, 6 of 54 renal units (11.1%) were eligible for catheter insertion. The catheter insertion was performed in 4 renal units. Another 2 renal units were followed up without intervention, and they gradually became atrophic. The renal functions were preserved in the other 52 renal units. CONCLUSIONS: Our results suggest that our definition of the tubeless condition and our indications for catheter insertion would be useful for the evaluation and management of hydronephrosis after establishment of tubeless cutaneous ureterostomy.

19.
Hinyokika Kiyo ; 58(7): 341-4, 2012 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-22895130

RESUMO

A 69-year-old man underwent a radical cystectomy and cutaneous ureterostomy for carcinoma in situ of the urinary bladder. The ureteral stents were exchanged for cutaneous ureterostomy 35 days after the operation. The patient suffered from high fever with chills a few hours after the stent exchange, and was readmitted to our hospital. High fever was not improved by treatment with Ceftriaxone for 5 days. Five days after the stent exchange, computed tomography (CT) revealed a right psoas abscess. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the blood culture. Urine culture showed MRSA, Pseudomonas aeruginosa and Enterococcus faecium. Computed tomography-guided percutaneous catheter drainage and treatment consisting of vancomycin, minocycline and ciprofloxacin were performed for the psoas abscess. This treatment significantly reduced the size of the abscess and high fever was improved. The catheter was removed 22 days after the drainage. However, magnetic resonance imaging revealed a spondylitis at L4 and L5. Therefore, antibiotics treatment was continued for about 3 months. There has been no sign of recurrence of bladder cancer and psoas abscess at 23 months after the operation.


Assuntos
Abscesso do Psoas/etiologia , Stents , Ureter , Ureterostomia , Idoso , Carcinoma in Situ/cirurgia , Enterococcus faecium/isolamento & purificação , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/tratamento farmacológico , Abscesso do Psoas/microbiologia , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/cirurgia
20.
Hinyokika Kiyo ; 57(10): 535-8, 2011 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-22089149

RESUMO

To identify the incidence and risk factors for developing early postoperative paralytic ileus (POPI) after radical cystectomy and cutaneous ureterostomy with a unilateral and parallel stoma, we retrospectively reviewed 21 patients (mean age 73.0, 19 males and 2 females) with a minimum of 3 months of follow-up. POPI occurred in 4 patients (19.0%), who did not need surgical treatment and the insertion of a nasogastric tube. Age and past history of abdominal surgery influenced the occurrence of POPI. The patients with and without POPI had a mean age of 82.3±7.4 and 70.8±6.3 years old, respectively (p=0.0025), and 75.0% (3/4) and 11.8% (2/17) of the patients, respectively, had a past history of abdominal surgery (p= 0.0276). There were no significant differences between patients with and without POPI in any of the following factors examined : sex, body mass index, American Society of Anesthesiologists score, pT-category, neoadjuvant chemotherapy, preoperative serum levels of hemoglobin, creatinine, total protein, and albumin, operative time, blood loss, transfusion volume, stomal side, postoperative day of ambulation, and removal of epidural anesthesia tube. In conclusion, our results showed that increasing age and a past history of abdominal surgery were significantly associated with the occurrence of POPI after radical cystectomy and cutaneous ureterostomy.


Assuntos
Cistectomia , Pseudo-Obstrução Intestinal/etiologia , Ureterostomia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pseudo-Obstrução Intestinal/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de Risco , Ureterostomia/métodos , Neoplasias da Bexiga Urinária/cirurgia
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