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OBJECTIVE: To determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Affiliated university hospital. METHODS: We reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS). RESULTS: The 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05). CONCLUSION: Our study suggests that the HS-mGPS is useful as prognostic factor in HSCC.
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BACKGROUND: Recurrent tonsillitis is one of the most common otolaryngological disorders caused by cell-invading bacteria, such as Streptococcus pyogenes (S. pyogenes) and Haemophilus influenzae. The aim of this study was to investigate the effect of antibacterial agents against cell-invading bacteria. METHODS: The intracellular invasion of Detroit 562 cells by five strains of nontypeable Haemophilus influenzae (NTHi) and four strains of S. pyogenes was investigated. The antibacterial agents used were garenoxacin (GRNX), clarithromycin (CAM), amoxicillin (AMPC), cefditoren pivoxil (CDTR-PI), and levofloxacin (LVFX). RESULTS: Both NTHi and S. pyogenes fully invaded Detroit 562 cells in 6 h and were less sensitive to CAM. GRNX, CAM, and LVFX were effective against bacteria invading the cells, but AMPC and CDTR-PI were not effective. GRNX was the most effective. CONCLUSION: GRNX was the most effective agent against bacteria invading cells.
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Antibacterianos/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Amoxicilina/farmacologia , Cefalosporinas/farmacologia , Claritromicina/farmacologia , Fluoroquinolonas/farmacologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/crescimento & desenvolvimento , Humanos , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/crescimento & desenvolvimentoRESUMO
The Warburg effect is a well-known feature in cancer-specific metabolism. We previously reported on the role of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. In this study, we reveal that miR-145 decreases the Warburg effect by silencing KLF4 in BC cells. The expression levels of miR-145 were significantly lower in clinical BC samples and BC cell lines compared to those in normal tissues and HUC cells. Luciferase assay results showed that miR-145 directly bound to 3'UTR of KLF4, which was shown to be overexpressed in the clinical BC samples using Western blot analysis and immunohistochemistry. Remarkable growth inhibition and apoptosis were induced by the ectopic expression of miR-145 or by the gene silencing of KLF4 (siR-KLF4). Also, Warburg effect-related genes such as PTBP1/PKMs were regulated by the transfection of BC cells with miR-145 or siR-KLF4. These results thus indicate that the miR-145/KLF4/PTBP1/PKMs axis is one of the critical pathways that maintain the Warburg effect in BC carcinogenesis. MiR-145 perturbed the Warburg effect by suppressing the KLF4/PTBP1/PKMs pathway in BC cells, resulting in significant cell growth inhibition.
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Regulação para Baixo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Neoplasias da Bexiga Urinária/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-IdadeRESUMO
Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa.
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Tecido Adiposo/citologia , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Exossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Células Estromais/citologia , Proteína bcl-X/metabolismoRESUMO
BACKGROUND: We vigorously reviewed patients' operation record who had adhesion of the Denonvilliers' fascia and found out most of these patients had prostatic bleeding after prostatic gland biopsies. We examined the magnitude of prostatic bleeding and frequency after biopsies and the relationship with oncological outcomes. MATERIALS AND METHODS: A total of 285 patients were selected for the final analyses. Inclusion criteria were as follows: receiving MRI three weeks after biopsiesand laparoscopic radical prostatectomy within 300 days after biopsy. We divided the patients into two groups with (group A) or without (group B) prostatic bleeding. We examined the magnitude of prostatic bleeding after biopsies and the relationship with operation time (OT), positive surgical margin (PSM), biochemical recurrence (BCR) and other factors. Furthermore, we created a logistic-regression model to derive a propensity score for prostatic bleeding after biopsies, which included all patient and hospital characteristics as well as selected interaction terms, and we examined the relationship with PSM and BCR. RESULTS: In all patients, the OT in the group B was shorter than the group A (p < 0.001). Prostatic bleeding was associated with PSM (p=0.000) and BCR (p=0.036). In this propensity-matched cohort, 11 of 116 patients in the group B had PSM as compared with 36 of 116 patients from group A (match-adjusted odds ratio, 4.30; 95%CI confidence interval, 2.06 to 8.96; P=0.000). In addition, eight of 116 patients in group B encountered BCR, as compared with 18 of 116 patients in group A (match-adjusted odds ratio, 2.48; 95%CI, 1.03 to 5.96; P=0.042). Kaplan-Meier analysis in the propensity matching cohort showed a significant biochemical recurrence-free survival advantage for being free of prostate bleeding after biopsies. CONCLUSIONS: Our findings in the present cohort should help equip surgeons to pay attention to careful excision especially for those who experienced deferred prostatic bleeding.
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Biópsia/efeitos adversos , Laparoscopia/efeitos adversos , Recidiva Local de Neoplasia/diagnóstico , Hemorragia Pós-Operatória/etiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. MATERIALS AND METHODS: Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. RESULTS: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. CONCLUSIONS: This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.
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Compostos de Boro/farmacologia , Proliferação de Células/efeitos da radiação , Nêutrons/uso terapêutico , Neoplasias da Próstata/radioterapia , Animais , Apoptose/efeitos da radiação , Terapia por Captura de Nêutron de Boro/métodos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Humanos , Masculino , Camundongos , Camundongos Nus , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
PURPOSE: Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. METHODS: In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. RESULTS: Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. CONCLUSIONS: Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.
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We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, ß-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model.
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Administração Intravesical , MicroRNAs/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Camundongos , Camundongos Nus , MicroRNAs/administração & dosagem , Transplante de Neoplasias , Transdução de Sinais , Transfecção , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology, recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, still ranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity are needed. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamic diagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or 2nd-transurethelial resection (TUR). MATERIALS AND METHODS: The present study was performed from October 2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white light and blue light followed by the resection of tumors identified. Resections were performed from bladder mucosa areas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by random biopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivity and specificity. RESULTS: A total of 147 specimens extracted from 25 patients were included in the analysis. Some 45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55 specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was 52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5% (19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases. CONCLUSIONS: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.
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Carcinoma in Situ/diagnóstico , Luz , Neoplasias Musculares/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/uso terapêutico , Carcinoma in Situ/terapia , Terapia Combinada , Cistectomia/métodos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/terapia , Invasividade Neoplásica , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Bexiga Urinária/terapiaRESUMO
A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/cirurgia , Quimioterapia Adjuvante , Cistoscopia , Feminino , Humanos , Tegafur/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagem , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
OBJECTIVES: To assess whether bipolar transurethral resection of the prostate (B-TURP) using the TURis system has a similar level of efficacy and safety to that of the traditional monopolar transurethral resection of the prostate (M-TURP), and to evaluate the impact of the TURis system on postoperative urethral stricture rates over a 36-month follow-up period. PATIENTS AND METHODS: A total of 136 patients with benign prostatic obstruction were randomised to undergo either B-TURP using the TURis system or conventional M-TURP, and were regularly followed for 36 months after surgery. The primary endpoint was safety, which included the long-term complication rates of postoperative urethral stricture. The secondary endpoint was the follow-up measurement of efficacy. RESULTS: In peri-operative findings, no patient in either treatment group presented with transurethral resection syndrome, and the decline in levels of haemoglobin and hematocrit were similar. The mean operation time was significantly extended in the TURis treatment group compared with the M-TURP group (79.5 vs 68.6 min; P = 0.032) and postoperative clot retention was more likely to be seen after M-TURP (P = 0.044). Similar efficacy findings were maintained throughout 36 months, but a significant difference in postoperative urethral stricture rates between groups was detected (6.6% in M-TURP vs 19.0% in TURis; P = 0.022). After stratifying patients according to prostate volume, there was no significant difference between the two treatment groups with regard to urethral stricture rates in patients with a prostate volume ≤ 70 mL (3.8% in M-TURP vs 3.8% in TURis), but in the TURis group there was a significantly higher urethral stricture rate compared with the M-TURP group in patients with a prostate volume >70 mL (20% in TURis vs 2.2% in M-TURP; P = 0.012). Furthermore, the mean operation time for TURis was significantly longer than for M-TURP for the subgroup of patients with a prostate volume > 70 mL (99.6 vs 77.2 min; P = 0.011), but not for the subgroup of patients with a prostate volume ≤ 70 mL. CONCLUSION: The TURis system seems to be as efficacious and safe as conventional M-TURP except that there was a higher incidence of urethral stricture in patients with larger preoperative prostate volumes.
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Próstata/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Estreitamento Uretral/etiologia , Idoso , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Próstata/patologia , Hiperplasia Prostática/cirurgia , Resultado do Tratamento , Obstrução do Colo da Bexiga Urinária/cirurgiaRESUMO
PURPOSE: We investigated the effect of balloon occluded arterial infusion of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, along with concurrent radiation (referred to as the Osaka Medical College regimen) in patients with advanced bladder cancer. MATERIALS AND METHODS: A total of 329 patients (TisN0 16, T2N0 174, T3N0 77, T4N0 22 and TxN+ 40) were assigned to receive the Osaka Medical College regimen. Patients who did not achieve complete response underwent total cystectomy or secondary balloon occluded arterial infusion with an increased amount of cisplatin and/or gemcitabine. RESULTS: The Osaka Medical College regimen allowed 83.6% (276 of 329) of patients in total and 93.6% (250 of 267) of patients with organ confined disease (including T3b) to achieve complete response. Of the patients with a complete response 96% (240 of 250) survived with a functional bladder without evidence of recurrent disease within a mean followup of 159 weeks. Although lymph node involvement, especially N2 stage, was selected as a significant risk factor for treatment failure and survival, it was noteworthy that 61.9% of patients with N1 disease achieved complete response and that the 5-year overall survival rate was 72.2%. No patients had grade III or more severe toxicities. CONCLUSIONS: The Osaka Medical College regimen, a new bladder preservation strategy, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment because of disease stage, age or other factors, and for whom merely palliative therapy would otherwise seem the only option.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Oclusão com Balão , Diálise Renal , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Terapia Combinada , Cistectomia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , GencitabinaRESUMO
OBJECTIVE: To assess whether bipolar transurethral resection of the prostate using the TURis (Olympus, Tokyo, Japan) system demonstrates comparable efficacy and safety reporting 36 months of follow-up findings. METHODS: The trial was registered at University hospital Medical Information Network Clinical Trials Registry in Japan (trial number UMIN 000010801). Patients were randomly selected to undergo transurethral resection of the prostate using either the TURis or the conventional monopolar technique. Primary end points were safety according to operation time, decline of sodium and hemoglobin levels, clot retention, and catheterization time. Secondary end points were efficacy findings for patients after 36 months of follow-up. RESULTS: A total of 136 patients were enrolled. Mean operation times were significantly prolonged in the TURis group (68.4 and 79.5 minutes for monopolar and TURis groups, respectively; P = .048). No significant differences in the decline of hemoglobin, hematocrit, and perioperative transfusion rates between groups were seen, whereas clot retention (grade 2) after the treatment seemed to occur more often in the monopolar group (7 of 62 [12.3%] in monopolar group vs 1 of 63 [1/8%] in TURis group; P = .061). No case presented symptomatic transurethral resection syndrome in either groups. CONCLUSION: Continued efficacy at 36 months after the treatment could be confirmed for the first time in TURis system, which also seems to be preferable as they produced more clinically favorable outcomes. Nevertheless, the TURis system required significantly more resection time, which might not entirely be a panacea for the treatment of benign prostatic obstruction, especially for patients having larger prostatic volumes.
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Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Humanos , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-ß signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-ß signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.
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Tecido Adiposo/citologia , Apoptose , Proliferação de Células , Próstata/patologia , Neoplasias da Próstata/terapia , Células Estromais/transplante , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais , Células Estromais/citologia , Células Estromais/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Regulação para CimaRESUMO
We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom surgery after neoadjuvant chemotherapy would otherwise be necessary, and also facilitate potential cure in patients for whom, otherwise, merely palliative treatment would seem the only option.
Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Desoxicitidina/análogos & derivados , Metástase Linfática/radioterapia , Recidiva Local de Neoplasia/terapia , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Oclusão com Balão , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Dosagem Radioterapêutica , Diálise Renal/métodos , Neoplasias da Bexiga Urinária/patologia , GencitabinaRESUMO
PURPOSE: To investigate the treatment outcomes of a single-session high-intensity focused ultrasound (HIFU) using the Sonablate(®) for patients with localized prostate cancer. METHODS: Biochemical failure was defined according to the Stuttgart definition [a rise of 1.2 ng/ml or more above the nadir prostate-specific antigen (PSA)] and the Phoenix definition (a rise of 2 ng/ml or more above the nadir PSA). Disease-free survival rate was defined using the Phoenix criteria and positive follow-up biopsy. RESULTS: A total of 171 patients were identified. Fifty-two (30.4 %) patients were identified to be with D'Amico low risk, 47 (27.5 %) with intermediate risk, and 72 (42.1 %) with high risk. In the median follow-up time of 43 months, there was 44 (25.7 %) and 36 (21.1 %) patients experienced biochemical failure for Stuttgart and Phoenix definition with mean (±SD) time to failure of 17.8 ± 2.1 and 19.4 ± 2.3 months, respectively. A total of 44 (25.7 %) patients were diagnosed as disease failure. Cox multivariate analysis revealed PSA nadir level (PSA cutoff = 0.2 ng/ml; HR = 9.472, 95 % CI 4.527-19.820, p < 0.001) and D'amico risk groups [HR = 3.132 (95 % CI 1.251-6.389), p = 0.033] were the predictor for failure in single-session HIFU. CONCLUSIONS: Single-session HIFU treatment using the Sonablate(®) seems to be potentially curative approach. When treated carefully with neoadjuvant hormonal therapy or preoperative transurethral resection of the prostate, higher-risk disease might be able to choose this minimally invasive procedure as primary therapy.
Assuntos
Neoplasias da Próstata/cirurgia , Ultrassom Focalizado Transretal de Alta Intensidade , Idoso , Humanos , Masculino , Resultado do Tratamento , Ultrassom Focalizado Transretal de Alta Intensidade/métodosRESUMO
We have developed a novel bladder preservation therapy, balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, since more than 95% of free Pt was efficiently eliminated by hemodialysis, which enables short hospital stay. In this study, we investigated the efficiency of OMC regimen in patients aged over 70 years with muscle-invasive bladder cancer without metastasis. A total of 134 such patients were assigned to receive either the OMC regimen (n=89) or cystectomy (n=45). OMC regimen patients who failed to achieve CR underwent cystectomy, or secondary BOAI with gemcitabine (1,600 mg). The OMC regimen, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, yielded CR in >91% (81/89) of patients. More than 96% (78/81) of the CR patients survived without recurrence with intact bladder after a mean follow-up of 164 (range 16-818) weeks. The 5- and 10-year bladder intact survival rates were 87.2 and 69.8%, and overall survival rates were 88.4 and 70.7% (vs. 59.9 and 33.3% for cystectomy, p=0.0002), respectively, although the median age in the OMC regimen group was significantly greater than in the cystectomy group (median, range = 77, 70-98 vs. 74, 70-89; p=0.0003). No patients suffered grade II or more severe toxicities; the oldest patient, aged 91 years, successfully completed this therapy. In conclusion, the OMC regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.
Assuntos
Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia/radioterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Oclusão com Balão , Terapia Combinada , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Dosagem Radioterapêutica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/radioterapia , GencitabinaRESUMO
Erythropoietin (Epo) is a potent inducer of erythropoiesis that is mainly produced in the kidney. Epo is expressed not only in the normal kidney, but also in renal cell carcinomas (RCCs). The aim of the present study was to gain insights into the roles of Epo and its receptor (EpoR) in RCC cells. The study used two RCC cell lines, Caki-1 and SKRC44, in which Epo and EpoR are known to be highly expressed. The proliferation rate and expression level of hypoxia-inducible factor-1α (HIF-1α) were measured prior to and following Epo treatment and under normoxic and hypoxic conditions. To examine whether HIF-1α or Epo were involved in cellular proliferation during hypoxia, these proteins were knocked down using small interfering RNA (siRNA) in Caki-1 and SKRC44 cells. The results demonstrated that Epo enhanced the proliferation of the Caki-1 and SKRC44 cells. HIF-1α expression was increased upon the induction of hypoxia in the Caki-1 cells, but remained unaffected in the SKRC44 cells. The proliferation rate was increased under hypoxic conditions in the Caki-1 cells, but was decreased in the SKRC44 cells. Under hypoxic conditions, the proliferation of the Caki-1 cells was significantly reduced by the knock-down of HIF-1α or Epo, while the proliferation of the SKRC44 cells was significantly suppressed by the knock-down of Epo, but not HIF-1α. In conclusion, these data suggest that the induction of Epo may accelerate the proliferation of the RCC cell lines in either a HIF-1α-dependent or -independent manner.
RESUMO
We have developed a novel form of bladder preservation therapy [OMC (Osaka Medical College)-regimen] involving balloon-occluded-arterial-infusion (BOAI) of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation. We previously reported that the OMC-regimen elicited a complete response (CR) in >90% of patients with organ confined tumors, while LN(+), T4 tumors and a non-UC histological type were statistically significant risk factors for treatment failure and patient survival. In this study, we investigated the effects of the OMC-regimen in patients with organ confined urothelial cancer tumors and the outcomes were compared to those with total cystectomy. Three hundred and one patients were assigned to receive either the OMC-regimen (n=162) or total cystectomy (n=139). Patients in the OMC-regimen group who failed to achieve CR underwent cystectomy, or secondary BOAI with an increased amount of CDDP or gemcitabine (1600 mg). The OMC-regimen yielded 98.1% of clinical response; CR in 93.8% (152/162) of patients; PR in 4.3% (7/162). More than 96% of the CR patients (146/152) were alive with no evidence of recurrence after a mean follow-up of 166 (range 23-960) weeks. No patients suffered grade III toxicity; all patients successfully completed this therapy. The patient survival was significantly better compared to the cystectomy group; the overall 5-, 10- and 15-year survival rates were 87.3, 79.6 and 59.7%, respectively. Moreover, the 5-, 10- and 15-year bladder intact survival rates, the most important issue for bladder preservation therapy, were 85.7, 78.4 and 58.8%, respectively. In conclusion, the OMC-regimen is a useful bladder-preservation strategy, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.
Assuntos
Oclusão com Balão , Infusões Intra-Arteriais , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Terapia Combinada , Cistectomia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia , GencitabinaRESUMO
In this study, we investigated the novel bladder preservation therapy, the balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the 'Osaka Medical College (OMC)-regimen'] in patients >70 years of age with muscle-invasive bladder cancer. Eighty-three such patients were assigned to receive either the OMC-regimen (n=56) or cystectomy (n=27). The OMC-regimen patients who failed to achieve complete response (CR) underwent cystectomy, or secondary BOAI with gemcitabine (1600 mg). The OMC-regimen, which delivers an extremely high concentration of anti-cancer agent to the tumor site without systemic adverse effects, yielded CR in >90% (39/43) of patients with locally invasive tumors [70% (39/56) of all patients including those with T4 and N+ disease]. None of the CR patients showed recurrence after a mean follow-up of 162 (range, 35-683) weeks, and 2 patients died of unrelated causes. The 5- and 12-year overall survival rates were 92.7 and 69.5% (vs. 59.6 and 20.9% for cystectomy; P<0.0092), respectively, although the median age in the OMC-regimen group was significantly greater than that in the cystectomy group (median, 77; range, 70-98; vs. 74; 70-79; p<0.0001). No patients suffered grade III or more severe toxicities. The oldest patient, aged 98 years, successfully completed this therapy. The OMC-regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only for those for whom cystectomy has been indicated, but also for patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.