Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.

Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF's impact on mitochondrial function persists, even in cells lacking septins. Furthermore, the impaired mitochondrial function leads to the degradation of HIF-1α, facilitated by increased cellular oxygen. FCF also induces AMPK activation, suppresses Erk1/2 phosphorylation, and reduces the expression of HER2, ß-catenin, and PD-L1. Endometrial cancer is characterized by metabolic disorders such as diabetes and aberrant HER2/Ras-Erk1/2/ß-catenin signaling. Thus, FCF may hold promise as a potential therapeutic in endometrial cancer.

A Systematic Review of Breast Implant-Associated Squamous Cell Carcinoma.

Breast augmentation is considered safe, but rare cases of breast implant-associated squamous cell carcinoma (BIA-SCC) have been reported. This study aimed to systematically review published cases of BIA-SCC, providing valuable clinical data. The review included 14 articles and 18 cases of BIA-SCC. An increasing trend in reported BIA-SCC cases was observed, with four cases in the 1990s and 14 cases since 2010. The mean age of affected patients was 56 years, and symptoms typically appeared around 21 years after breast augmentation. Silicone implants used in cosmetic procedures were most commonly associated with BIA-SCC. Implant removal was necessary in all cases, and some patients required a mastectomy. Treatment approaches varied, with the selective use of chemotherapy and/or radiotherapy. The estimated 6-month mortality rate was 11.1%, while the 12-month mortality rate was 23.8%. The estimated 6-month mortality rate should be cautiously interpreted due to the limited sample size. It appears lower than the rate reported by the American Society of Plastic Surgeons, without clear reasons for this discrepancy. This study highlights the importance of enhanced monitoring and information sharing to improve detection and management of BIA-SCC. Healthcare providers should maintain vigilance during the long-term follow-up of breast augmentation patients.

Time to treatment initiation and outcomes in high-grade glioma patients in rehabilitation: a retrospective cohort study.

Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods: A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

Clinical Efficacy of Tumor Treating Fields for Newly Diagnosed Glioblastoma.

BACKGROUND/AIM: Whether adding tumor treating fields (TTF) to the Stupp protocol increases survival for glioblastoma (GBM) patients in routine clinical care remains unknown. PATIENTS AND METHODS: We retrospectively identified adult patients with newly diagnosed GBM (n=104) treated with the Stupp protocol or TTF at our Institution. RESULTS: Thirty-six percent (37/104) of patients received TTF in conjunction with the Stupp protocol and these patients had increased 6-month (p=0.006) and 1-year (p=0.170), but not 2-year survival rates compared to the 67-patients who received Stupp alone. The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (p=0.010). However, we did not observe any improvement in overall survival (OS) with a Cox model. CONCLUSION: While adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect was mild and may be largely due to selection bias.

Immune checkpoint inhibitors in older adults with melanoma or cutaneous malignancies: The Wilmot Cancer Institute experience.

OBJECTIVES: The purpose of this study was to explore the associations between age and frailty with immune-related adverse events (irAEs) among patients with cutaneous malignancies receiving immune checkpoint inhibitor (ICI) therapy. METHODS: A retrospective review of all patients receiving ipilimumab, nivolumab, or pembrolizumab for treatment of cutaneous malignancies at the Wilmot Cancer Institute between 1 Jan 2011 and 3 Apr 2017. RESULTS: A total of 120 patients (age <70 N = 68, age ≥70 N = 52; range, 26-93) were identified. 44.1%[95%CI:32-57%] of patients age <70 and 31.4%[95%CI:19-46%] of patients age ≥70 experienced ≥1 irAE on 1st line ICI therapy (P = 0.158). A total of 3 adults died of irAEs (2 age ≥70; 1 age <70). Patients ≥70 were more frequently treated with anti-PD-1 monotherapy than dual checkpoint blockade or ipilimumab (P < 0.01) in the first line setting. Among patients on first line anti-PD-1 monotherapy for cutaneous melanoma, 21 were age <70 and 20 were age ≥70, with similar observed rates of irAEs (52.4%[95%CI 29.8-74.3] and 63.2%[95%CI 38.4-83.7]). Indirect frailty markers in patients age ≥70 such as having fallen in the prior six months, ECOG PS ≥2 or Charlson comorbidity scores ≥11 experienced similar rates of response and toxicity. Among 9 patients with a PS = 3, 8 died, 6 due to progressive disease. No deaths due to irAEs occurred in this frail subgroup. CONCLUSION: Anti-PD-1 monotherapy for older adults with cutaneous malignancies have similar response and irAE rates when compared to those of younger patients. Deaths from disease progression were more frequent than those from toxicity in both age subgroups.

Weight-related self-efficacy in relation to maternal body weight from early pregnancy to 2 years post-partum.

Excessive gestational weight gain may lead to long-term increases in maternal body weight and associated health risks. The purpose of this study was to examine the relationship between maternal body weight and weight-related self-efficacy from early pregnancy to 2 years post-partum. Women with live, singleton term infants from a population-based cohort study were included (n = 595). Healthy eating self-efficacy and weight control self-efficacy were assessed prenatally and at 1 year and 2 years post-partum. Body weight was measured at early pregnancy, before delivery, and 6 weeks, 1 year and 2 years post-partum. Behavioural (smoking, breastfeeding) and sociodemographic (age, education, marital status, income) covariates were assessed by medical record review and baseline questionnaires. Multi-level linear regression models were used to examine the longitudinal associations of self-efficacy measures with body weight. Approximately half of the sample (57%) returned to early pregnancy weight at some point by 2 years post-partum, and 9% became overweight or obese at 2 years post-partum. Body weight over time was inversely related to healthy eating (ß = -0.57, P = 0.02) and weight control (ß = -0.99, P < 0.001) self-efficacy in the model controlling for both self-efficacy measures as well as time and behavioural and sociodemographic covariates. Weight-related self-efficacy may be an important target for interventions to reduce excessive gestational weight gain and post-partum weight gain.

Maternal weight change between 1 and 2 years postpartum: the importance of 1 year weight retention.

Pregnancy weight gain may lead to long-term increases in maternal BMI for some women. The objective of this study was to examine maternal body weight change 1y-2y postpartum, and to compare classifications of 2y weight retention with and without accounting for 1y-2y weight gain. Early pregnancy body weight (EPW, first trimester) was measured or imputed, and follow-up measures obtained before delivery, 1 year postpartum (1y) and 2 years postpartum (2y) in an observational cohort study of women seeking prenatal care in several counties in upstate New York (n = 413). Baseline height was measured; demographic and behavioral data were obtained from questionnaires and medical records. Associations of 1y-2y weight change (kg) and 1y-2y weight gain (≥2.25 kg) with anthropometric, socioeconomic, and behavioral variables were evaluated using linear and logistic regressions. While mean ± SE 1y-2y weight change was 0.009 ± 4.6 kg, 1y-2y weight gain (≥2.25 kg) was common (n = 108, 26%). Odds of weight gain 1y-2y were higher for overweight (OR(adj) = 2.63, CI(95%) = 1.43-4.82) and obese (OR(adj) = 2.93, CI(95%) = 1.62-5.27) women than for women with BMI <25. Two year weight retention (2y-EPW ≥2.25 kg) was misclassified in 38% (n = 37) of women when 1y-2y weight gain was ignored. One year weight retention (1YWR) (1y-EPW) was negatively related to 1y-2y weight change (ß(adj) ± SE = -0.28 ± 0.04, P < 0.001) and weight gain (≥2.25 kg) (OR(adj) = 0.91, CI(95%) = 0.87-0.95). Relations between 1y weight retention and 1y-2y weight change were attenuated for women with higher early pregnancy BMI. Weight change 1y-2y was predicted primarily by an inverse relation with 1y weight retention. The high frequency of weight gain has important implications for classification of postpartum weight retention.

Maternal weight gain during pregnancy and child weight at age 3 years.

OBJECTIVES: To determine the importance of pregnancy weight gain as a predictor of overweight (Body Mass Index [BMI] >85th percentile) in offspring at age 3 years and if its influence varies by maternal BMI. METHODS: Chi-square and logistic regression analyses were conducted on a sample of 208 mother-child pairs from an earlier observational cohort study on postpartum weight retention. RESULTS: In the final reduced regression model, maternal early pregnancy BMI was positively and significantly associated with overweight in offspring, as were birth weight above the sample median of 3,600 g and maternal smoking during pregnancy (P < or = 0.01). In addition, a significant interaction was found between maternal BMI and gestational weight gain (P = 0.03). The risk of offspring overweight that is associated with 5 excess pounds of net pregnancy weight gain increases with maternal BMI. CONCLUSIONS: Excess pregnancy weight gain is associated with increased risk of child overweight at age 3 years and its impact is greater among high and obese BMI women than it is in normal BMI women. Reducing maternal BMI in the preconception period in overweight women and preventing excessive weight gain in pregnancy for all women appear to be appropriate strategies to address the childhood obesity epidemic.

Modifiable behavioral factors in a biopsychosocial model predict inadequate and excessive gestational weight gain.

OBJECTIVE: The research addresses two questions: Are potentially modifiable psychosocial and behavioral factors related to gestational weight gain? Do the same factors relate to both excessive and insufficient weight gain? DESIGN: Prospective cohort study that followed women from early pregnancy until two years postpartum. Data were collected through mailed questionnaires and an audit of the medical record. Subjects/setting The sample included 622 healthy adult women who gave birth to live singleton infants. Subjects were recruited from all women who registered for prenatal care in a hospital and primary care clinic system serving a 10-county area of Upstate New York. Statistical analyses performed Multiple linear and logistic regression with adjustment for timing of measurements and length of gestation were performed. RESULTS: Only 38% of women gained an amount of weight in pregnancy that was within the range recommended by the Institute of Medicine. Valid and easily implemented measures of change in food intake and physical activity from prepregnancy and cigarette smoking during pregnancy were each significantly (P<.05) and independently related to gestational weight gain. Along with other variables in a biopsychosocial regression model, these variables accounted for 27% of the variance in gestational weight gain and were also significantly related to risk of inadequate and excessive gain. APPLICATIONS/CONCLUSIONS: The findings facilitate the design of more effective nutrition interventions to promote appropriate gestational weight gain and the long-term health of women and their infants.