Activation of CWI pathway through high hydrostatic pressure, enhancing glycerol efflux via the aquaglyceroporin Fps1 in Saccharomyces cerevisiae.

The fungal cell wall is the initial barrier for the fungi against diverse external stresses, such as osmolarity changes, harmful drugs, and mechanical injuries. This study explores the roles of osmoregulation and the cell-wall integrity (CWI) pathway in response to high hydrostatic pressure in the yeast Saccharomyces cerevisiae. We demonstrate the roles of the transmembrane mechanosensor Wsc1 and aquaglyceroporin Fps1 in a general mechanism to maintain cell growth under high-pressure regimes. The promotion of water influx into cells at 25 MPa, as evident by an increase in cell volume and a loss of the plasma membrane eisosome structure, activates the CWI pathway through the function of Wsc1. Phosphorylation of Slt2, the downstream mitogen-activated protein kinase, was increased at 25 MPa. Glycerol efflux increases via Fps1 phosphorylation, which is initiated by downstream components of the CWI pathway, and contributes to the reduction in intracellular osmolarity under high pressure. The elucidation of the mechanisms underlying adaptation to high pressure through the well-established CWI pathway could potentially translate to mammalian cells and provide novel insights into cellular mechanosensation.

Impact of Previous, Simultaneous or Subsequent Bladder Cancer on Prognosis after Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.

PURPOSE: We investigated the impact of previous, simultaneous or subsequent bladder cancer on the clinical outcomes of upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively collected data on 2,668 patients who underwent radical nephroureterectomy of nonmetastatic upper urinary tract urothelial carcinoma in 1995 to 2009. We evaluated the impact of bladder cancer on overall mortality and the factors predictive of subsequent bladder cancer. RESULTS: A total of 631 patients (23.7%) had previous or simultaneous bladder cancer. Patients with previous or simultaneous bladder cancer had significantly shorter overall survival than patients without previous or simultaneous bladder cancer (HR 1.29, 95% CI 1.09-1.53, p=0.0026). Of the 2,037 patients without previous or simultaneous bladder cancer 683 (33.5%) subsequently had bladder cancer after radical nephroureterectomy. Of patients with pT0-2 disease those with subsequent bladder cancer had significantly shorter overall survival than patients without subsequent bladder cancer (HR 1.81, 95% CI 1.23-2.67, p=0.0025). In patients with pT3-4 disease subsequent bladder cancer was not associated with worse overall survival. On multivariable analyses independent predictors of subsequent bladder cancer were gender, preoperative urine cytology and clinical node status in the preoperative setting, and gender, adjuvant chemotherapy and pathological node status in the postoperative setting. CONCLUSIONS: Bladder cancer was significantly associated with worse clinical outcomes after radical nephroureterectomy of upper urinary tract urothelial carcinoma. Preventing subsequent bladder cancer in patients with pT0-2 upper urinary tract urothelial carcinoma may lead to better prognosis in those who undergo radical nephroureterectomy.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

Role of lymph node dissection during radical nephroureterectomy for upper urinary tract urothelial cancer: multi-institutional large retrospective study JCOG1110A.

PURPOSE: To evaluate the impact of lymph node dissection (LND) on clinical outcome during radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). METHODS: We, the Urologic Oncology Study Group of the Japan Clinical Oncology Group (JCOG), retrospectively collected data from patients with non-metastatic UTUC who underwent RNU in 30 centers in 1995-2009. Ineligible patients and patients with previous and/or synchronous bladder cancer were excluded, and the remaining 2037 patients were analyzed. We compared overall and cancer-specific mortality between patients who underwent LND (LND group) and those without LND (no-LND group). RESULTS: Among 2037 patients, LND was performed in 1046 (51.4%) patients, and 223 (10.9%) patients had pathological node-positive (pN+) disease. All-cause mortality was observed in 503 patients (24.7%) during follow-up (median 45.8 months), including 363 patients (17.8%) who died of UTUC. Patients with pN+ disease showed significantly shorter overall survival (OS) compared with pN0 patients, and the estimated 5-year OS for pN+ patients was 30%. Older age, ≥cT3, and clinical node-positive disease were found as preoperative predictors for pN+ disease by multivariate analysis. In the comparison of OS and cancer-specific mortality between LND and no-LND groups, there was no significant improvement by LND in multivariate analysis. The median number of lymph nodes removed was six (IQR 3-11). There was no significant association between the number of lymph nodes removed and OS. CONCLUSIONS: The present study indicates that there is no therapeutic benefit of LND during RNU for UTUC, although pathologically positive LN status can predict poor prognosis.