Expression of stem cell markers as predictors of therapeutic response in metastatic prostate cancer patients.

BACKGROUND: Cancer stem cells (CSCs) have been implicated in prostate cancer (PCA) progression and therapeutic resistance. This study aimed to compare the expression levels of CSC CD (CD 44, CD 133, and CD 24) markers in treatment-naive patients with metastatic PCA before and after treatment. METHODS: The study included 60 treatment-naïve patients with metastatic PCA who received androgen deprivation therapy (ADT) alone (n = 30) and ADT plus chemotherapy (n = 30). The level of CD44, CD133, and CD24 were obtained by flow cytometric analysis before and after treatment. Baseline characteristics were also assessed, including age, pretreatment testosterone levels, and pretreatment prostate-specific antigen (PSA) levels. RESULTS: The baseline characteristics analysis showed no significant difference in pre-treatment testosterone levels between the ADT+ chemotherapy and ADT-alone groups. In the flow cytometric analysis, no significant difference was observed in pre-treatment CD44+ and CD133+ levels between the 2 treatment groups, although a trend towards higher pretreatment CD24- levels was observed in the ADT+ chemotherapy group. After treatment, significant reductions in testosterone and PSA levels were observed in both treatment arms. The ADT+ chemotherapy group showed a greater reduction in CD44+ and CD133+ levels compared to the ADT-alone group. Bioinformatic analysis using the UALCAN TCGA database also showed a similar trend of CD 44, CD 24, and CD 133 gene expression patterns. CONCLUSION: Combination therapy involving chemotherapy and ADT appears to have a greater impact on suppressing CSCs compared to ADT alone. These findings highlight the potential of targeting CSCs as a prognostic and predictive marker therapeutic strategy in metastatic PCA.

Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities.

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.

Short-Term Outcomes of Patients With Hyponatremia Presenting to the Emergency Department: An Observational Study.

BACKGROUND: Hyponatremia is the predominant electrolyte imbalance disorder in the emergency department. It can manifest with a diverse array of symptoms, ranging from non-specific and moderate to severe and even life-threatening. There is a scarcity of literature addressing the clinical characteristics and prognosis of patients with hyponatremia presenting to the emergency department in the western part of Rajasthan. The objective of this study was to investigate the impact of hyponatremia on the outcomes of patients presenting to the emergency department. METHODS: In this prospective, cross-sectional, observational study, 200 patients aged more than 18 years who presented to the emergency department with serum sodium < 135 mEq/l were included. The triage of patients was determined by their primary complaints. The primary outcome was to study the clinical profile of patients with hyponatremia presenting to the emergency department. The secondary outcomes were to examine the etiology, i.e., hypovolemic, euvolemic, or hypervolemic, and the outcome of patients on the 7th day (patient admitted to the ward or intensive care unit) and the 28th day (discharged or death) with hyponatremia presenting to the emergency department. The clinical status of the patients was noted by telephonic follow-up in case they were not admitted for this period. RESULTS: Out of 200 patients, 66 (33%) had hypovolemic, 96 (48%) had euvolemic, and 38 (19%) had hypervolemic hyponatremia. We observed that seizures (84.2%), confusion (56%), and coma (77.7%) were the most common clinical features of patients with severe hyponatremia in the emergency, which was statistically significant than mild and moderate hyponatremia (p = 0.03, 0.023, and 0.029, respectively). On the 7th day of hospitalization, out of 181 (90.5%) admissions in the ward, 116 (64.08%) had severe hyponatremia, and out of 19 (9.5%) ICU admissions, 13 (68.4%) had severe hyponatremia. Death was seen in five (2.5%) patients, one (20%) in moderate and four (80%) in severe hyponatremia cases. CONCLUSION: Most cases of hyponatremia in this study were euvolemic. Most patients experienced severe hyponatremia, and seizures, confusion, and coma were the most prevalent symptoms. These disorders must be recognized early to properly diagnose and treat hyponatremia and prevent its morbidity and death.

Explaining the Unexplained: Examining the Predictive Value of Semen Parameters, Sperm DNA Fragmentation and Metal Levels in Unexplained Infertility.

Background: There is ongoing research to find an optimum modality to predict male fertility potential. Aims: To compare the semen parameters, sperm DNA damage and seminal metal levels of Zinc, Lead and Aluminium among the male partners of couples with unexplained infertility and men with proven fertility. Settings and Design: Prospective case-control study at a tertiary level teaching hospital. Materials and Methods: One hundred male partners of couples with unexplained subfertility and 50 men with proven fertility were included in the study. Male partners of unexplained infertility couples and fertile men were compared for their semen parameters, sperm DNA Fragmentation Index (DFI) and seminal metal levels in semen. Statistical Analysis Used: Chi-square test, Student's t-test, sensitivity and specificity analysis, binomial logistic regression analysis. Results: Fertile men had statistically significantly higher mean progressive sperm motility than male partners of unexplained infertility (53.12 ± 9.89% vs. 44.81 ± 19.47%, P = 0.005). Semen volume and sperm concentration were comparable among the cases and control population. The mean sperm DFI was significantly lower among fertile men (10.83 ± 6.28 vs. 21.38 ± 10.28, P < 0.0001). Plotting the receiver-operating characteristic curve the threshold for discrimination was calculated to be 18% DFI. The sensitivity specificity and overall accuracy were 43%, 84% and 56.67%, respectively when the DFI cut-off was set at 18%. Zinc concentration in the semen had a strong positive correlation (Point Biserial correlation coefficient = 0.831) with fertility, whereas lead and aluminium had a moderate negative correlation. Conclusion: Conventional semen analysis had limited differentiating ability for unexplained infertility. The sperm DFI may be employed for explanatory purposes among couples with unexplained subfertility. A lower discriminatory threshold of DFI (18%) has better overall accuracy as opposed to a 30% cutpoint for unexplained subfertility. Among metals, Zinc was strongly correlated with fertility status.