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This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress.

Vaginal reconstruction using the posterior vaginal wall is required following radical cystectomy in women with resection of the uterus, adnexa, and anterior vaginal wall. Roll closure and clamshell closure are two widely known techniques. Of these, clamshell closure is recommended because roll closure has a high likelihood of breakdown or a resultant canal that is too narrow for sexual intercourse. In clamshell closure, however, folding the posterior vaginal wall anteriorly can be difficult. Therefore, we devised Mercedes-Benz closure, in which the vaginal wall is sutured from three directions to form a Mercedes-Benz shape, for anastomosis without tension on the vaginal wall. The present study was performed to investigate the efficacy of this alternative surgical technique for vaginal reconstruction.Twenty-six patients who underwent vaginal reconstruction following robot-assisted radical cystectomy were divided into two groups: 15 underwent clamshell closure and 11 underwent Mercedes-Benz closure. The patients' characteristics and surgical outcomes were compared between the two groups.There were no significant differences in clinical characteristics, including age, body mass index, and prior abdominal surgery between the two groups. The median vaginal reconstruction time tended to be longer in the Mercedes-Benz closure group than in the clamshell closure group (35.0 vs. 27.0 min, p = 0.102). No complications associated with vaginal reconstruction were identified.The surgical outcomes were comparable between Mercedes-Benz closure and clamshell closure. If vaginal reconstruction with clamshell closure is difficult, Mercedes-Benz closure is a valuable alternative technique.

PDF file - 1.2MB, (A) FACS profiles of KMRC-1 (p53 wildtype) cells that were treated with siDDX31 or siEGFP. Cells were harvested with supernatant, stained with propidium iodide and analyzed by flow cytometry at 96 h after transfection. (B) Effects of DDX31 knockdown on cell growth and p53 and/or p21 expression in p53 mutant cell. Quantitative RT-PCR showing the suppression of endogenous DDX31 expression by DDX31 siRNA oligonucleotides (left). MTT assay showed a slight decrease in the cell numbers upon DDX31 knockdown in KMRC-20 (right ).(C) Effects of DDX31 knockdown on p53 and p21 protein levels in KMRC-20

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PDF file - 1.5MB, (A) Effects of siRNA-mediated NPM1 knockdown on DDX31 localization in the RCC cell line, Caki-1. NPM1 knockdown did not affect DDX31 nucleolar localization. (B) Effects of DDX31 knockdown on Nucleolin localization. Nucleolin localization was not affected by the presence or the absence of DDX31. Scale bar shows 50 mum

PDF file - 1MB, Effects of DDX31 knockdown on p53 and p21 expression at the mRNA and protein levels. The cells were harvested and examined by quantitative RT-PCR at 48h (A) and 72h after transfection (B). (C) western blot analysis with the indicated antibodies at 72h after transfection

PDF file - 1.7MB, S1 (A) western blot analysis of DDX31 transfected HEK293 cells (left panel) and endogenous DDX31 in Caki-1 cells (right panel) using purified anti-DDX31 polyclonal antibody. (B)NPM1 protein expression in RCC and HK-2 cells. (C) NPM1 expression in clinical RCC cases by quantitative RT-PCR. (D) immunohistochemical analysis of NPM1 in ccRCC tissue sections. Representative images of ccRCC tissue (776T) and normal kidney tissue (776N). Scale bar shows 50 mum

PDF file - 1.6MB, (A) Effects of doxorubicin-induced cellular stress. NPM1 translocated to the nucleoplasm or cytoplasm in DDX31-depleted RCC cells, but not in siEGFP-transfected cells even under doxorubicin treatment. �iB) NPM1 translocated to nucleoplasm in HK-2 cells under doxorubicin treatment. Scale bar shows 50 mum

The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.

Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment. J. Med. Invest. 69 : 127-134, February, 2022.

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

Objectives : To evaluate whether virtual partial nephrectomy images could help surgeons identify vascular and collecting system around tumors during actual surgery. Materialsmethods : We retrospectively analyzed 36 patients who underwent robot-assisted partial nephrectomy (RAPN) between 2016 and 2017. Virtual partial nephrectomy images were created from preoperative CT images using computer software, and then analyzed. For analysis, blood vessels and collecting system portions within a 5-mm-thick safety margin around the tumor were examined. During analysis, we predicted whether targeted vasculature around the tumor would require clipping or suturing during surgery, and also whether the collecting system would require opening during resection. Surgical outcomes for virtual partial nephrectomy analyses and actual RAPNs were compared and analyzed for sensitivity and specificity. Results : In 36 cases, 119 arteries and 100 veins were targeted on virtual partial nephrectomy images. Arterial suturing or clipping for hemostasis showed a sensitivity and specificity of 83.3% and 84.5%, respectively. For veins, the sensitivity and specificity were 39.1% and 92.2%, respectively. Collecting system opening prediction sensitivity was 85.7%, and specificity was 65.2%. Conclusion : Virtual partial nephrectomy imaging is useful for RAPN planning, particularly regarding arteries and the collecting system. It is hoped that techniques for visualizing veins will improve. J. Med. Invest. 69 : 237-243, August, 2022.

The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p p p

To compare the postoperative outcomes of robot-assisted partial nephrectomy when only the inner layer is sutured (single-layer technique with soft coagulation) with those when sutures are placed in the inner and outer layers (double-layer technique) in patients with and without complex renal tumors.This retrospective three-institution study included 371 patients with renal tumors who underwent robot-assisted partial nephrectomy with a double-layer technique or a single-layer technique with soft coagulation. Tumors that were cT1b, completely embedded, located in the renal portal, or had a RENAL score of ≥10 were considered complex. Relevant data were collected from hospital records. Propensity score matching was performed to minimize selection bias.Propensity score matching created 83 patient pairs with non-complex tumors and 32 with complex tumors. Regardless of tumor complexity, there was no significant difference in operation time, console time, warm ischemia time, positive surgical margin rate, or length of hospital stay between the double-layer and single-layer groups. Although Clavien-Dindo grade I-II urinomas not requiring intervention were significantly more common in the single-layer group regardless of tumor complexity, there was no significant between-group difference in the rate of decline in renal function or grade III-IV complications.Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity.

We describe two cases of locally advanced rectal cancer (LARC) treated with robot-assisted total pelvic exenteration (Ra-TPE) and intracorporeal ileal conduit (ICIC). The first case was in a 71-year-old man with LARC (RbP, T4bN2bM0, cStage IIIc). He was started on bevacizumab+S-1/oxaliplatin therapy in July 2019. In April 2020, he developed Fournier's gangrene due to subcutaneous penetration of rectal cancer. Emergency drainage and colostomy were performed simultaneously, and a percutaneous vesical fistula was created. In May 2020, Ra-TPE and ICIC were performed. Histopathological analysis revealed moderately differentiated tubular adenocarcinoma (ypT3N0, RM0). At postoperative 9 months, thoracoscopic right upper lobectomy was performed for a right metastatic lung tumor. At present, ie, at postoperative 12 months, the patient has been free of recurrence and metastasis, with a carcinoembryonic antigen (CEA) level of 1.4 ng/ml and carcinoma antigen (CA) 19-9 level of 11 U/ml. The second case was in a 61-year-old man with fistula-associated anal cancer (PRb, T4N3M1b, cStage IVb). In April 2019, he was started on FOLFOXIRI+cetuximab therapy. In August 2020, Ra-TPE, ICIC, and transperineal total mesenteric excision were performed. Histopathological analysis revealed adenocarcinoma (ypT4N0, RM0). At postoperative 11 months, thoracoscopic left lower lobectomy was performed for a left metastatic lung tumor. At present, ie, at postoperative 12 months, the patient remains free of recurrence and metastasis, with a CEA level of 7.3 ng/ml and CA19-9 level of 12 U/ml. Ra-TPE, which allows transperineal removal of a specimen, can be performed as a minimally invasive surgery in combination with ICIC.

Introduction Granulocyte colony-stimulating factor-producing nonhematopoietic malignancies have poor clinical outcomes. Case presentation A 62-year-old woman complaining of fever and left lower quadrant pain was referred to our hospital. A left retroperitoneal tumor was suspected on computed tomography, and laboratory data showed leukocytosis and markedly elevated granulocyte colony-stimulating factor. She underwent left nephroureterectomy, partial colectomy, and psoas muscle resection. The histological examination showed a granulocyte colony-stimulating factor-producing retroperitoneal leiomyosarcoma. Three months after the operation, she developed lung and liver metastases and received the chemotherapy, including doxorubicin and ifosfamide. Eight months after the operation, these lesions had progressed, and a new bone metastasis appeared. Twelve months after the operation, she received pazopanib and radiation for bone metastases. However, the metastases progressed, and she died 17 months after the operation. Conclusion Since granulocyte colony-stimulating factor-producing retroperitoneal leiomyosarcoma had a very poor prognosis irrespective of intensive treatment including wide resection, effective systemic therapy should be required.

Background: Creation of an arteriovenous fistula (AVF) as vascular access is a basic operation that should be learned by all surgeons involved in renal failure treatment. AVF creation is often challenging for inexperienced young surgeons because it requires comprehensive surgical techniques. For such young surgeons, we introduced cadaveric surgical training (CST) for AVF creation using fresh-frozen cadavers (FFCs). This study was performed to identify the differences in AVF surgical techniques between FFCs and living bodies and to examine the impact of CST on young surgeons. Methods: Twelve CST sessions were performed for AVF creation at the Clinical Anatomy Education and Research Center of Tokushima University Hospital from March 2021 to June 2022. Seven young surgeons (1st- and 2nd-year) performed the operation, and two surgeons (10th- and 11th-year) supervised it. We conducted an anonymous questionnaire survey using a 5-point Likert scale to examine the impact of CST on young surgeons. Results: Twelve CST sessions were performed on nine FFCs. All training sessions allowed completion of AVF creation with a median operative time of 78.5 min. Although veins and arteries were more difficult to identify than in a living body, other surgical operations could be performed in the same way as in a living body. All the respondents stated that it was good for them to experience CST. In addition, 86% of surgeons responded that CST improved their surgical techniques, and 71% of surgeons responded that they were less anxious about AVF creation. Conclusions: CST for AVF creation is useful for surgical education because it enables learning of surgical techniques that are almost equivalent to those in living bodies. In addition, this study suggested that CST not only contributes to the improvement of surgical skills of young surgeons but also promotes the reduction of anxiety and stress about AVF creation.

Purpose : To evaluate the efficacy of the direct grasping technique using pean forceps under fluoroscopic guidance for ureteral stent replacement in women. Methods : Between April 2018 and September 2020, 28 female patients underwent ureteral stent replacements at our facility, and 184 stent replacement procedures were performed. A total of 127 stents were replaced using pean forceps under fluoroscopic guidance (pean forceps group), and 57 stents were replaced using the cystoscope (cystoscopy group). Clinical characteristics and surgical outcomes were compared between the groups. Results : All stents were successfully replaced. There was a statistically significant difference in the procedure time between the two groups (median [interquartile range], pean forceps group : 10.8 [8.2-13.9] minutes vs. cystoscopy group : 15.8 [11.1-20.9] minutes, P

We report a case of papillary renal cell carcinoma that responded well to the combination of ipilimumab and nivolumab. The patient was a 68-year-old male who was being followed up for a small left renal mass without treatment. Two years later, computed tomography (CT) showed enlarged cervical and para-aortic lymph nodes, and lymph node biopsy suggested metastases of the cancer. After resection of the renal tumor, we performed pararenal aortic lymph node biopsy, and we diagnosed the case as papillary renal cell carcinoma type 1 with lymph node metastasis. The combination of ipilimumab and nivolumab each metastatic site showed regression on CT. Since immune-related adverse events occurred during the therapy nivolumab was discontinued, but partial response of the metastases was maintained.

Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported.A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia.When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient's condition. J. Med. Invest. 69 : 148-151, February, 2022.

To identify and raise awareness of the radiation exposure of urologists due to X-ray fluoroscopic procedures in daily practice.This was a single-center, cohort study of 30 consecutive patients who underwent periodic percutaneous or transurethral replacements of urinary tract catheters. A total of 55 replacements every 3 months with cases aligned were performed by a single urologist. The urologist's radiation exposure and the incident dose to patients per case were measured with thermoluminescent dosimeters. In the latter 3-month period, the pulse fluoroscopy condition was changed from 15 to 7.5 pulses per second, and collimation was added to the field of view.In the analysis of all patients, the use of a modified pulse rate and collimation did not affect the fluoroscopy time, but it did significantly reduce the air kerma and dose area product; in addition, with respect to the medical exposure dose during percutaneous catheter replacement, fluoroscopy time was longer, but air kerma and dose area product showed significant decreases. As with decreases in medical exposure of patients, the equivalent dose for eye lenses of the urologist decreased from 1.2 mSv in the first 3-month period to 0.2 mSv in the second 3-month period. Similarly, the exposure dose for the extremities also decreased significantly, from 33.9 mSv to 8.1 mSv.Urologists are exposed to non-negligible amounts of radiation due to fluoroscopy. Appropriate management such as modified pulse fluoroscopy condition and precautions are required.

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.

While robot-assisted radical cystoprostatectomy (RARC) for locally advanced prostate cancer (LAPC) may sometimes prove to be excessive treatment, it can significantly reduce the risk of positive surgical margins and lower urinary tract obstruction in some cases. Here, we report a case of LAPC treated with RARC in a patient with right hydronephrosis due to bladder infiltration and left hypoplastic kidney. A 71-year-old man presented with frequent urination in August 2019. Prostate-specific antigen (PSA) level was 8.633 ng/ml, and magnetic resonance imaging led to the suspicion that the prostate cancer extended beyond the prostate capsule without distant metastasis. Prostatic biopsy revealed Gleason score 10 (5＋5) adenocarcinoma in 8 out of 8 specimens. We diagnosed left hypoplastic kidney and LAPC with right hydronephrosis due to bladder infiltration. We performed percutaneous right nephrostomy and started neoadjuvant hormone therapy. RARC and intracorporeal ileal conduit were performed in March 2020. The prostate was adherent to the anterior surface of the rectum and was difficult to remove. At present, five months after the surgery, the patient remains free of recurrence and metastasis with PSA level ＜0.003 ng/ml. RARC for LAPC with bladder infiltration can be an effective therapeutic strategy in some cases.

We report a case of desmoid tumor that was initially diagnosed as metastasis from renal cell carcinoma. A follow-up computed tomographic (CT) scan after nephrectomy for renal cell carcinoma in a 64-year-old man revealed a right retroperitoneal tumor 3.5 cm in diameter. Though the CT density of the tumor was similar to that of muscles, we first suspected metastasis from renal cell carcinoma or other cancer because the tumor growth was relatively fast. We resected the tumor. The pathological diagnosis was desmoid type fibromatosis. We also review six cases of desmoid tumors after nephrectomy for renal cell carcinoma reported in Japan. Careful followup is required for the patients with desmoid tumors because of frequent recurrence.

We report a case of bladder diverticulum presumably caused by lower urinary tract dysfunction due to pelvic organ prolapse (POP) simultaneously treated with transurethral coagulation (TUC) of the bladder diverticulum and laparoscopic sacrocolpopexy (LSC). A literature search showed this is the first report of bladder diverticulum and POP surgically treated at the same time. A 71-year-old woman was referred to our hospital for the treatment of cystocele. She had both storage and voiding symptoms. She had a POPQ stage III cystocele and stage I uterine prolapse. Ultrasonography and computed tomographic scan showed a large volume of residual urine along with a bladder diverticulum. Since urodynamic studies revealed a low compliance bladder and obstruction, we opined that the lower urinary tract symptoms were induced by the cystocele. TUC of the bladder diverticulum and LSC were performed at the same time. After the operation, clean intermittent catheterization (CIC) was needed once a day for one month. Gradually, residual urine decreased and CIC became unnecessary. The bladder diverticulum disappeared, and there has been no recurrence of POP.

The p53 and EGFR pathways are frequently altered in bladder cancer, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle-invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31-bound mutp53/SP1 enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin in advanced MIBC, leading to EGFR–Akt signaling activation. High expression of both cytoplasmic DDX31 and p53 proteins correlated with poor prognosis in patients with MIBC, and blocking the DDX31/NCL interaction resulted in downregulation of EGFR/Akt signaling, eliciting an in vivo antitumor effect against bladder cancer. These findings reveal that DDX31 cooperates with mutp53 and EGFR to promote progression of MIBC, and inhibition of DDX31/NCL formation may lead to potential treatment strategies for advanced MIBC. Significance: DDX31 cooperates with mutp53 and EGFR to promote progression of muscle invasive bladder cancer. Cancer Res; 78(9); 2233–47. ©2018 AACR.

The development of the human gonads is tightly regulated by the correct sequential expression of many genes and hormonal activity. Disturbance of this regulation does not only prevent proper development of the gonads, but it also contributes to the development of testicular germ cell tumors. Recent genetic studies, especially genome-wide association studies, have made great progress in understanding genetic susceptibility. Although there is strong evidence of inherited risks, many environmental factors also contribute to the development of testicular germ cell tumors. Histopathological studies have shown that most testicular germ cell tumors arise from germ cell neoplasia in situ, which is thought to be arrested and transformed primordial germ cells. Seminoma has features identical to germ cell neoplasia in situ or primordial germ cells, whereas non-seminoma shows varied differentiation. Seminomas and embryonic cell carcinomas have the feature of pluripotency, which is thought to be the cause of histological heterogeneity and mixed pathology in testicular germ cell tumors. Testicular germ cell tumors show high sensitivity to chemotherapies, but 20-30% of patients show resistance to standard chemotherapy. In the present review, the current knowledge of the epidemiological and genomic factors for the development of testicular germ cell tumors is reviewed, and the mechanisms of resistance to chemotherapies are briefly mentioned.

Background: We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. Materials and Methods: Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. Results: In cases with prostate volume more than 30 cm3, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. Conclusion: Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.

Background: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. Materials and Methods: We examined tumor cell invasion and migration using the xCELLigence system. Control LNCaP and galectin-3-expressing LNCaP (LNCaP-Gal-3) cells were cultured with androgen-depleted medium with 5% charcoal-stripped serum. Cells were treated for 24 h with or without dihydrotestosterone alone or combined with MDV3100 and bicalutamide; gene profile was then analyzed by microarray analysis and mRNA expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated tumor growth using spheroids and xenograft tumor growth in a mouse model. Results: In vitro, LNCaP-Gal-3 cells promoted both cell migration and invasion in an androgen-independent manner compared to control LNCaP cells. Galectin-3 also enhanced anchorage-independent growth and xenograft tumor growth even after castration. Importantly, galectin-3 greatly enhanced transcriptional activity of the androgen receptor (AR), especially on treatment with dihydrotestosterone. In microarray and qRT-PCR analyses, galectin-3 increased the expression of several AR-target genes, such as kallikrein-related peptidase 3 (KLK3), and transmembrane protease, serine 2 (TMPRSS2). These AR-target genes were not fully suppressed by anti-androgen drugs such as bicalutamide or MDV3100. Galectin-3 significantly inhibited the effect induced by anti-androgen drugs MDV3100 and bicalutamide, suggesting that galectin-3 may be involved in resistance to anti-androgen drug through enhancement of transcriptional activity of AR and expression of AR-related genes. Conclusion: These results suggest that galectin-3 is a potential target molecule for future treatment of anti-androgen drug-resistant prostate cancer.