Assessing the Therapeutic Impacts of HAMLET and FOLFOX on BRAF-Mutated Colorectal Cancer: A Study of Cancer Cell Survival and Mitochondrial Dynamics In Vitro and Ex Vivo.

Background and Objectives: Colorectal cancer (CRC) is a major global health challenge. The BRAF V600E mutation, found in 8-12% of CRC patients, exacerbates this by conferring poor prognosis and resistance to therapy. Our study focuses on the efficacy of the HAMLET complex, a molecular substance derived from human breast milk, on CRC cell lines and ex vivo biopsies harboring this mutation, given its previously observed selective toxicity to cancer cells. Materials and Methods: we explored the effects of combining HAMLET with the FOLFOX chemotherapy regimen on CRC cell lines and ex vivo models. Key assessments included cell viability, apoptosis/necrosis induction, and mitochondrial function, aiming to understand the mutation-specific resistance or other cellular response mechanisms. Results: HAMLET and FOLFOX alone decreased viability in CRC explants, irrespective of the BRAF mutation status. Notably, their combination yielded a marked decrease in viability, particularly in the BRAF wild-type samples, suggesting a synergistic effect. While HAMLET showed a modest inhibitory effect on mitochondrial respiration across both mutant and wild-type samples, the response varied depending on the mutation status. Significant differences emerged in the responses of the HT-29 and WiDr cell lines to HAMLET, with WiDr cells showing greater resistance, pointing to factors beyond genetic mutations influencing drug responses. A slight synergy between HAMLET and FOLFOX was observed in WiDr cells, independent of the BRAF mutation. The bioenergetic analysis highlighted differences in mitochondrial respiration between HT-29 and WiDr cells, suggesting that bioenergetic profiles could be key in determining cellular responses to HAMLET. Conclusions: We highlight the potential of HAMLET and FOLFOX as a combined therapeutic approach in BRAF wild-type CRC, significantly reducing cancer cell viability. The varied responses in CRC cell lines, especially regarding bioenergetic and mitochondrial factors, emphasize the need for a comprehensive approach considering both genetic and metabolic aspects in CRC treatment strategies.

Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus short-course radiotherapy without adjuvant chemotherapy both with delayed surgery for stage II-III resectable rectal cancer: 5-Year survival data of a randomized controlled trial.

BACKGROUND AND OBJECTIVE: At present, there are common recommendations for treatment for stage II-III resectable rectal cancer patients: preoperative conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) in two treatment groups: preoperative SCRT and CRT both with delayed surgery plus adjuvant chemotherapy in CRT arm. MATERIALS AND METHODS: A total of 150 patients were randomly assigned to two groups: 75 to CRT (preoperative conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the 5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT (preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks; then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were included in statistical analysis. Primary end points were OS and DFS. RESULTS: Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13-3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups, respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004). CONCLUSIONS: The 5-year DFS and OS were significantly better in the CRT than the SCRT group. For ITT population, OS was also significantly better after CRT versus SCRT.

Colonic intussusception caused by colonic lipoma: a case report.

Intussusception is a pediatric condition that rarely presents in adults. Colonic lipomas 4 cm and more in diameter can cause colonic intussusception leading to emergency operation. Surgical resection of the involved segment must be the procedure of choice. We report a case of colonic intussusception caused by colonic lipoma in an adult. The patient underwent operation, and histopathological examination of the specimen confirmed the diagnosis of colonic submucosal lipoma.