Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Silk Fibroin Promotes the Regeneration of Pancreatic ß-Cells in the C57BL/KsJ-Leprdb/db Mouse.

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic ß-cell, we investigated the effects of hydrolyzed SF on the pancreatic ß-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic ß-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic ß-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Optimal high-density lipoprotein cholesterol level for decreasing benign prostatic hyperplasia in men not taking statin medication: A historical cohort study.

BACKGROUND: We evaluated the optimal high-density lipoprotein cholesterol level for benign prostatic hyperplasia (BPH) prevention in men not taking statin medication using a large historical cohort. METHODS: We initially selected 130 454 men who underwent health checkups in 2009 from the National Health Information Database of the National Health Insurance Service. After excluding 36 854 men with BPH in 2009, and 45 061 men for statin use, 48 539 men were ultimately included in the analysis. A Kaplan-Meier analysis and multivariable Cox regression analysis was performed to assess the optimal high-density lipoprotein cholesterol level for preventing BPH. RESULTS: High-density lipoprotein cholesterol levels were less than 40 mg/dL in 7431 (15.3%) men, 40 to 49 in 15 861 (32.7%), 50 to 59 in 15 328 (27.5%), and greater than or equal to 60 in 11 919 (24.6%). The overall cumulative incidence of BPH was 4.4%, 8.7%, 13.0%, and 17.8% at the 1-, 2-, 3-, and 4-year follow-up periods, respectively. In multivariable analysis, high-density lipoprotein greater than or equal to 60 mg/dL were significantly associated with a decreased incidence of BPH, as were age, residence, income, body mass index, diabetes, hypertension, triglyceride, and increased annual clinic visits, especially in men in their 40s. CONCLUSION: Elevated serum high-density lipoprotein cholesterol levels were negatively associated with BPH incidence. In addition, maintaining high-density lipoprotein greater than or equal to 60 mg/dL was associated with a decreased BPH incidence compared with high-density lipoprotein less than 40 mg/dL, especially in men in their 40s.

A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu.

A novel autosomal recessive mutant was produced using N-ethyl-N-nitrosourea mutagenesis. The characteristics of the mutant mice included progressive irreversible hair loss within a month of birth, wrinkled skin, and long curved nails. Linkage analysis revealed that the causative gene is linked to D14Mit193 on chromosome 14. Sequence analysis of the complete cDNA of the candidate gene, hairless (Hr), identified a homozygous G-to-T transition at nucleotide 3572, leading to the substitution of glycine by tryptophan, designated Gly960Trp. This missense mutation occurs in the vicinity of repression domain 3 of the hairless protein (HR). This allele was named Hr(m1Enu). The relative amounts of Hr mRNA and HR protein determined by real-time PCR and Western blot analyses, respectively, were slightly elevated in the mutant mice. Quantitative real-time PCR analysis revealed the increased expression of Kc1 and Vdr in the mutant mice, whereas the expression of Nrs1 and Krtap16-6 was decreased. These results suggest that the Gly960Trp substitution in HR protein in Hr(m1Enu) mice may alter the function of HR as a transcriptional corepressor.