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PurposeThe prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion.MethodsThis retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).ResultsThe median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival.ConclusionCompared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

Urinary and fecal incontinence as well as skin pressure injury are common healthcare problems in nursing homes; however, the prevalence and related risk factors were not well understood in the Japanese special elderly nursing home settings. We surveyed the prevalence of urinary, fecal and double incontinence, and skin pressure injury among the elderly living in special elderly nursing homes in Japan. A nationwide cross-sectional epidemiological survey was conducted with a total of 4881 residents. The prevalence of urinary, fecal and double incontinence was 82.9%, 68.9% and 64.9%, respectively. Skin pressure injury was found in 283 residents (283/4881, 5.8%). Age, Care-Needs level, loss of voiding desire, and fecal incontinence were significant risk factors for urinary incontinence. Residential period, Care-Needs level, loss of voiding and defecation desires, and urinary incontinence were significant risk factors for fecal incontinence. Only male sex was a significant risk factor for skin pressure injury. Our study revealed continence status and the prevalence of pressure skin injury among older adult residents who receive end-of-life care in special elderly nursing homes in Japan. Further studies should be conducted to examine whether recovery of urinary and fecal sensations improves continence status.

Background This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. Methods This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. Results A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p  = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p  = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of <65 years were independent predictors for TB upgrading (vs. the SB result). Conclusions PI-RADS v2 category 4 and an age of <65 years were predictive factors of upgrading the Gleason score by MRI/US-fusion TB. Thus, MRI/US-fusion TB may be appropriate for patients with those characteristics. Trial registration This study was retrospectively registered at the University Hospital Medical Information Network ( UMINID000025911 ) in Jan 30, 2017.

The steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues. We determined SXR immunoreactivity using an anti‐SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range: 0–8) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed. Western blot analyses validated the specificity of the anti‐SXR antibody in 293T cells transfected with pcDNA–FLAG–SXR. Positive (IR score: ≥ 2) nuclear SXR staining was observed in 91% (71/78) of benign foci and 47% (50/106) of cancerous lesions. Immunoreactivity scores were significantly lower in the cancerous lesions than in the benign foci (P < 0.0001). Clinicopathological analyses showed that cancer‐specific survival in patients with high SXR IR scores (≥4) was significantly increased (P = 0.046). Combined data of present and previous studies showed that high IR scores for both the SXR and CYP3A4 correlated with significantly better cancer‐specific survival rates in multivariate regression analyses (hazard ratio: 2.15, 95% confidence interval: 1.25–3.55, P = 0.007). We showed differential SXR expression in human prostate tissues. The high expression of the SXR and CYP3A4 is a strong prognostic indicator of favorable outcomes in prostate cancer, and could be a therapeutic target. (Cancer Sci 2012; 103: 176–180)

(Cancer Sci 2010; 101: 646–651) Estrogen‐related receptor (ERR) is a nuclear receptor that modulates the estrogen‐signaling pathway. Here, we investigated the expression of both ERRβ and ERRγ in human prostate tissues. Using original rabbit polyclonal anti‐ERRβ and anti‐ERRγ antibodies, the expression of ERRβ and ERRγ was evaluated by immunohistochemical analysis of cancerous lesions (n = 107) and benign foci (n = 92), obtained by radical prostatectomy. Stained slides were evaluated for the proportion of immunoreactive cells and their staining intensity. Total immunoreactivity scores (IR scores; range, 0–8) were calculated as the sum of the proportion and intensity scores. The relationship between the clinicopathological characteristics of the patients and the expression of the three ERRs (ERRα, ERR β, and ERR γ) was evaluated. IR scores for ERRβ and ERRγ were significantly lower in cancerous lesions than that in benign foci (P < 0.0001, for both). Clinicopathological analyses revealed that the patients with low ERRγ IR scores (≤4) tended to show poor cancer‐specific survival (P = 0.07). Then, we used data from our previous study (Fujimura T., Int J Cancer, 2007; 120: 2325–30). Patients with a high IR score for ERRα and a low score for ERRγ showed significantly poorer cancer‐specific survival than those with a low IR score for ERRα and a high score for ERRγ (P = 0.0003). We demonstrated the differential expression of ERRβ and ERRγ in prostate tissue. The combined evaluation of the expression of ERRα and ERRγ could be a significant prognostic factor for prostate cancer.

Solitary fibrous tumor has been reported infrequently in the kidney. Malignant solitary fibrous tumor of the kidney is quite rare. Only 9 cases have been reported before. We report a case of malignant solitary fibrous tumor clinically diagnosed as renal cell carcinoma in a 63-year-old man. The patient underwent radical left nephrectomy. Grossly, the tumor which measured 4.5 × 4.0 × 3.0 cm was well circumscribed. Microscopically, the tumor was composed of spindle cells with frequent mitoses, monomorphic storiform patterns, and occasionally patternless architecture. Furthermore, the tumor showed increased cellularity and focally invaded out of the capsule to the surrounding fatty connective tissue and blood vessels. Immunohistochemical study revealed strong expressions of CD34, bcl-2 and vimentin, with no expressions of CD99, c-kit, S-100, smooth muscle actin and epithelial membrane antigen. The surgical line was free from the tumor and no metastasis was found in the left adrenal gland. Because of the increased cellularity, a high number of mitosis and invasion to the adipose tissue and blood vessels, the tumor was histopathologically recognized as malignant. As far as we know, this is the tenth case of renal malignant solitary fibrous tumor. Surgical resection is the first choice for primary solitary fibrous tumor. Histopathological characters and prognosis of malignant solitary fibrous tumor of the kidney are still unknown. Long-term follow-up is generally required for malignant solitary fibrous tumor in the kidney.

In response to proteasome dysfunction, mammalian cells upregulate proteasome gene expression by activating Nrf1. Nrf1 is an endoplasmic reticulum-resident transcription factor that is continually retrotranslocated and degraded by the proteasome. Upon proteasome inhibition, Nrf1 escapes degradation and is cleaved to become active. However, the processing enzyme for Nrf1 remains obscure. Here we show that the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is required to cleave and activate Nrf1. Deletion of DDI2 reduced the cleaved form of Nrf1 and increased the full-length cytosolic form of Nrf1, resulting in poor upregulation of proteasomes in response to proteasome inhibition. These defects were restored by adding back wild-type DDI2 but not protease-defective DDI2. Our results provide a clue for blocking compensatory proteasome synthesis to improve cancer therapies targeting proteasomes. The proteasome is a machine that destroys unnecessary or damaged proteins inside cells. This role of the proteasome is essential for cell survival, and so when the proteasome is inhibited, cells produce new proteasomes to compensate. Upon proteasome inhibition, a protein called Nrf1 is activated and executes this “bounce-back” response. Some cancer treatments aim to kill cancer cells by inhibiting proteasomes, but these treatments may be unsuccessful if the bounce-back response is not also prevented. Therefore, understanding how Nrf1 is activated is an important issue. Nrf1 is produced at a structure called the endoplasmic reticulum in cells and is continually destroyed by the proteasome. On the other hand, when proteasomes are inhibited, Nrf1 accumulates and is cleaved into an active form, which moves to the cell nucleus to start producing proteasomes. However, it was not known which molecule cleaves Nrf1. Koizumi et al. set out to discover this molecule by screening the genetic material of human cells, and identified a gene that encodes a protease (an enzyme that cleaves other proteins) called DDI2. The loss of DDI2 from cells prevented Nrf1 from being cleaved and entering the nucleus, resulting in low levels of proteasome production. Further experiments showed that a mutant form of DDI2 that lacked protease activity was unable to cleave Nrf1, confirming DDI2’s role in activating Nrf1. Deleting DDI2 from cells does not completely prevent the cleavage of Nrf1, and so some other cleaving enzyme might exist; the identity of this enzyme remains to be discovered. Future work is also needed to establish exactly how DDI2 cleaves Nrf1. This could help to develop a DDI2 inhibitor for cancer treatment that could be used in combination with existing proteasome inhibitors.

A bstract We consider the junction of multiple one-dimensional systems and study how conserved currents transport at the junction. To characterize the transport process, we introduce reflection/transmission coefficients by applying boundary conformal field theory. We compute the reflection/transmission coefficients for some examples to derive the closed formulas. The formulas demonstrate spin-flip transport, where the spin polarization is flipped at the junction.

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin‐6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma (ADC) and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell‐cell adhesion‐related proteins and drug metabolism‐associated proteins (aldo‐keto reductase [AKR] family proteins) were significantly increased in CLDN6‐overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell‐cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical ADC, possibly due to increased cell‐cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6‐targeting therapy, against cervical ADC. High claudin‐6 (CLDN6) expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor of cervical adenocarcinoma. Shotgun proteome analysis revealed that cell‐cell adhesion‐related proteins and drug metabolism‐associated proteins (aldo‐keto reductase [AKR] family proteins) were significantly increased in CLDN6‐overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell‐cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin.