Histopathology of castration-resistant prostate cancer confirms changes in bone metastasis during radium-223 treatment: A case report.

Radium-223 is used for treating castration-resistant prostate cancer with bone metastases. Here, we report the case of a 76-year-old man diagnosed with castration-resistant prostate cancer with bone metastases who was started on radium-223. Although the patient ultimately died from causes unrelated to the treatment before starting the third treatment course, we observed that radium-223 was more effective in areas closer to the bone cortex than in deeper tumor regions. Through histopathological analysis, we provide important mechanistic insights on the therapeutic effect of radium-223 in human prostate cancer bone metastases.

Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study.

BACKGROUND: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. METHODS: We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. RESULTS: Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum ß-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL. CONCLUSION: Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Caveolin-1 regulates hormone resistance through lipid synthesis, creating novel therapeutic opportunities for castration-resistant prostate cancer.

Caveolin-1 (Cav-1) is overexpressed in aggressive and metastatic prostate cancer (PCa) and induces PCa cell proliferation. Androgens mediate lipid synthesis through acetyl-CoA carboxylase-1 (ACC1) and fatty acid synthase (FASN). We investigated the Cav-1-mediated lipid synthesis in the development of castration resistance, and identified novel therapeutic opportunities. Using the PBCre+;Ptenloxp/loxp;PBCav-1+ mouse model we found that Cav-1 induction increased cancer incidence and growth, and ACC1-FASN expression in intact and castrated mice. We demonstrated that Cav-1 regulated ACC1 and FASN expression in an AR-independent way and increased palmitate synthesis using western blot analysis, qRT-PCR and mass spectrometry in vitro. By using FASN siRNA and C-75, we found that FASN inhibition was more effective in Cav-1-overexpressing cells. This inhibition was abrogated by ACC1si RNA, revealing the role of malonyl-CoA, an ACC1 product, as a mediator of cytotoxicity. Cav-1 was associated with ACC1 in human tumors and ACC1, FASN, and Cav-1 expression were increased in metastatic PCa compared to primary tumors and normal prostate epithelium. Palmitoleate and oleate levels were higher in BMA from patients with metastatic PCa who responded poorly to abiraterone acetate. Our findings suggest that Cav-1 promotes hormone resistance through the upregulation of ACC1-FASN and lipid synthesis under androgen deprivation, suggesting that FASN inhibition could be used to treat PCa that demonstrates Cav-1 overexpression.

[Investigation of changes in sexual and ejaculatory functions after holmium laser enucleation of the prostate (HoLEP)].

Changes in sexual function and ejaculatory function in patients who had undergone holmium laser enucleation of the prostate (HoLEP) were investigated using questionnaires. In this study, 77 patients on whom HoLEP was performed at our department from July 2010 to December 2010 were included. Of the 77 patients, the number of patients who could achieve an erection increased from 36 (46.8%) preoperatively to 52 (67.5%) postoperatively after HoLEP. Although postoperative ejaculatory dysfunction was found in 38 (73%) of 52 patients, 47 (90%) experienced orgasms, regardless of ejaculation, which is a high rate. With respect to ejaculatory satisfaction, patients who experienced an ejaculation had significantly higher satisfaction levels than those who did not. These results suggest that changes in postoperative ejaculatory function might affect satisfaction levels of ejaculation.

Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer.

Androgen deprivation is the standard treatment for advanced prostate cancer (PCa), but most patients ultimately develop resistance and tumor recurrence. We found that MYB is transcriptionally activated by androgen deprivation therapy or genetic silencing of the androgen receptor (AR). MYB silencing inhibited PCa growth in culture and xenografts in mice. Microarray data revealed that c-Myb and AR shared a subset of target genes that encode DNA damage response (DDR) proteins, suggesting that c-Myb may supplant AR as the dominant regulator of their common DDR target genes in AR inhibition-resistant or AR-negative PCa. Gene signatures including AR, MYB, and their common DDR-associated target genes positively correlated with metastasis, castration resistance, tumor recurrence, and decreased survival in PCa patients. In culture and in xenograft-bearing mice, a combination strategy involving the knockdown of MYB, BRCA1, or TOPBP1 or the abrogation of cell cycle checkpoint arrest with AZD7762, an inhibitor of the checkpoint kinase Chk1, increased the cytotoxicity of the poly[adenosine 5'-diphosphate (ADP)-ribose] polymerase (PARP) inhibitor olaparib in PCa cells. Our results reveal new mechanism-based therapeutic approaches for PCa by targeting PARP and the DDR pathway involving c-Myb, TopBP1, ataxia telangiectasia mutated- and Rad3-related (ATR), and Chk1.

[Three case reports of metastatic germ cell tumors in the lumbar vertebra during first-line chemotherapy].

We report three patients with germ cell tumors whose diagnosis was confirmed in the progress of the first-line chemotherapy regimen as metastatic cancer in the lumbar vertebra. Two of the 3 cases were mixed-type nonseminoma, and the other case was an extragonadal tumor. After the first-line chemotherapy regimen, the patients underwent salvage chemotherapy using Paclitaxel either with or without irradiation. We confirmed the efficacy that the bone metastasis had completely been resolved and the lymph node metastasis was significantly reduced after the completion of all treatments.

Varicocele complicating spontaneous arteriovenous fistula.

We describe herein a rare case of a varicocele complicating spontaneous arteriovenous fistula. A 40-year-old man was referred to our hospital in November 2006, complaining of a non-tender mass in the left scrotum at the age of 15 and thereafter. On examination, his left scrotum revealed a large varicocele, but no manifest superficial thrill was noted. Scrotal ultrasonograpy revealed approximately 7 cm large varicocele. Computed tomography angiography revealed the existence of an arteriovenous fistula between the left testicular artery and the veins of the left pampiniform plexus. We laparoscopically carried out internal spermatic vessels ligation under the diagnosis of a varicocele complicating a spontaneous arteriovenous fistula. The postoperative course was uneventful. At 18 months postoperatively, the varicocele and fistula had not recurred.