Department of Biochemistry

Chemotherapy-induced neutropenia (CIN) and chemotherapy-induced alopecia (CIA) are significant toxicities affecting cancer patients. CIN is a potentially fatal complication of chemotherapy caused by myelosuppression and increased infection susceptibility, while CIA, although not fatal, severely affects treatment adherence and mental health. This study provides a comprehensive comparative analysis of CIN and CIA, focusing on patient, disease, treatment, and genetic risk factors. Key risk factors for CIN and CIA include age, poor performance status, body mass index (BMI), laboratory abnormalities, and pre-existing comorbidities. Both toxicities were significantly associated with breast cancer patients, although CIN patients were more likely to have hematological cancer, and CIA patients were more likely to have solid tumors. Notably, anthracyclines, alkylators, and taxanes frequently induce both toxicities, although their timelines and clinical implications differed. There was no clear overlap between genetic predispositions and toxicities beyond single-nucleotide polymorphisms (SNPs) in the ABCB1 gene. This is the first study to directly compare CIN and CIA, offering insights into personalized oncology care. Understanding the risk factors implicated in the development of CIN and CIA will enable physicians to manage patient outcomes.

Objectives: This study investigates the association between microsatellite instability (MSI) and the risk of occult lymph node metastases (LNMs) in patients with early-stage endometrial cancer (EC) who showed no evidence of nodal involvement on preoperative imaging. Methods: A retrospective multicenter cohort study was conducted, including 237 patients with EC who underwent primary staging surgery between January 2022 and October 2024. The patients were stratified into two groups based on MSI status. The primary outcome was the prevalence of occult LNMs. Statistical analyses included univariate and multivariate logistic regression models, adjusting for potential confounders such as tumor grading and lymphovascular space invasion (LVSI). The significance of the models was assessed using the maximum likelihood method and Bayesian Information Criterion (BIC). Measures to reduce bias included blinding the data analyst, standardization of histopathological evaluation, and exclusion of patients with genetic conditions predisposing to MSI. Results: The MSI group had a significantly higher incidence of occult LNMs compared to the MSS group (19% vs. 6.7%, p = 0.005). The multivariate analysis confirmed MSI as an independent risk factor for LNMs (OR = 1.105, 95% CI 1.016-1.202, p = 0.020). The sub-analysis showed that loss of MLH1/PMS2 or both MLH1/PMS2 and MSH2/MSH6 heterodimers further increased LNMs risk, independently from other risk factors. Conclusions: MSI is independently associated with a higher risk of occult LNMs in early-stage EC, suggesting a potential role for MSI profiling in refining lymph node staging strategies. Future prospective studies should assess the prognostic impact of this association and its implications for surgical decision-making.

Traditional 2D cell culture models present significant limitations in replicating the intricate architecture and microenvironment of in vivo solid tumors, which are essential for accurately studying cancer initiation, growth, progression, and metastasis. This underscores the need for the development of advanced preclinical models to accelerate research outcomes. Emerging 3D cell culture systems, particularly spheroid models, provide a more realistic representation of solid tumor properties by capturing the complex interactions occurring within the tumor microenvironment, including the extracellular matrix dynamics that influence cancer progression. Among solid tumors, breast cancer remains the most frequently diagnosed cancer among women globally and a leading cause of cancer-related mortality. Here we emphasize the value of breast cancer cell-derived spheroids in revealing differential molecular characteristics and understanding cancer cell properties during the early stages of invasion into adjacent tissues. Conclusively, this study underscores the urgent need to adopt 3D cell culture platforms, given their significant contributions to advanced cancer research and pharmaceutical targeting. This may well offer a transformative approach for preclinical studies and enhance our ability to test therapeutic efficiency in conditions that closely mimic the growth and progression of in vivo solid tumors.

Background: Pleural mesothelioma (PM) is a rare and highly aggressive cancer which arises from mesothelial layer and primarily linked to asbestos exposure, genetic predispositions, and specific mutations. Despite current treatment modalities, including chemotherapy, antiangiogenic therapy and more recently immunotherapy, the prognosis remains dismal, with a median survival time of 6–18 months. Objectives: The urgent need for novel therapeutic strategies has prompted research into molecular targets and precision medicine approaches. At present, many potential targets for therapeutic strategies have been identified, and emerging clinical trials are demonstrating certain clinical efficacy. Methods: This review examines advancements in understanding PM’s genetic and epigenetic landscape, signaling pathways, and promising therapeutic targets. Results: We also discuss the results of recent clinical trials and their potential implications for future treatment paradigms.

Background: Inflammation plays a crucial role in lung cancer recurrence after surgery. This study aims to investigate the relationship between lung cancer recurrence and perioperative inflammatory status, assessed in both blood and bronchoalveolar lavage (BAL) fluid. Methods: We conducted a retrospective cohort study analyzing clinical variables, blood cytokine levels, and BAL fluid from lung cancer patients who underwent surgery. Logistic regression models were employed to predict recurrence. Results: Among 93 patients, 41.9% experienced recurrence within ten years. The logistic regression model identified vital status, tumor stage, and type of surgery as significant predictors of recurrence. Postoperatively, pro-inflammatory cytokines were elevated, particularly in patients who experienced recurrence. Higher levels of TNF-α in BAL fluid and increased IL-6 in blood correlated with recurrence. Additionally, metalloproteinases in BAL fluid exhibited distinct associations: MMP-2 was identified as a risk factor, whereas MMP-9 appeared to have a protective role. A multivariate model integrating clinical variables and inflammatory biomarkers significantly improved predictive accuracy (p < 0.0001). Discussion: Combining inflammatory biomarkers with clinical variables enhances the prediction of lung cancer recurrence after surgery. Understanding the dynamics of these biomarkers may facilitate early detection and enable more personalized treatment strategies.

Background/Objectives: The Clavien–Dindo classification (CDC) grades the most severe post-operative complication and may not comprehensively reflect cumulative surgical morbidity. Our objective was to investigate the potential incremental role of the comprehensive complication index (CCI) over the CDC in defining the quality of robot-assisted radical cystectomy (RARC). Methods: Data were extracted from the Asian RARC Consortium database. Complications were classified using the CCI (CCI = 0, CCI < 75th and ≥75th percentile) and CDC. Adverse peri-operative outcomes such as length of stay >14 days (LOS > 14 days), estimated blood loss >350 mL (EBL > 350 mL), time to solid food intake >4 days (TFI > 4 days) and 30-day readmission rates were analyzed. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves for CCI and CDC were compared for the various adverse outcomes. Results: The peri-operative complication rate was 44.4%, comprising 11.6% with severe complications (CDC ≥ III). The mean CCI was 10.2 (±13.5) while median CCI was 0 (IQR 0–21). There were 7.6% of patients with >one perioperative complication. On adjusted analysis, CCI ≥ 75th percentile was significantly associated with greater LOS (>14 days) (OR 2.21, 95% CI 1.47–3.31, p < 0.001) compared to when CCI = 0. There were no significant differences in the AUC between CDC and CCI in predicting LOS > 14 days, TFI > 4 days, 30-day readmission or EBL > 350 mL. Conclusions: In our multi-institutional cohort, the CCI did not provide additional discrimination over CDC, and this is likely related to the limited number of complications that occurred per individual in the Asian RARC cohort. Hence, the perceived advantages of CCI over CDC are contextual.