In Vitro Inhibition of Colorectal Cancer Gene Targets by Withania somnifera L. Methanolic Extracts: A Focus on Specific Genome Regulation.

An approach that shows promise for quickening the evolution of innovative anticancer drugs is the assessment of natural biomass sources. Our study sought to assess the effect of W. somnifera L. (WS) methanolic root and stem extracts on the expression of five targeted genes (cyclooxygenase-2, caspase-9, 5-Lipoxygenase, B-cell lymphoma-extra-large, and B-cell lymphoma 2) in colon cancer cell lines (Caco-2 cell lines). Plant extracts were prepared for bioassay by dissolving them in dimethyl sulfoxide. Caco-2 cell lines were exposed to various concentrations of plant extracts, followed by RNA extraction for analysis. By explicitly relating phytoconstituents of WS to the dose-dependent overexpression of caspase-9 genes and the inhibition of cyclooxygenase-2, 5-Lipoxygenase, B-cell lymphoma-extra-large, and B-cell lymphoma 2 genes, our novel findings characterize WS as a promising natural inhibitor of colorectal cancer (CRC) growth. Nonetheless, we recommend additional in vitro research to verify the current findings. With significant clinical benefits hypothesized, we offer WS methanolic root and stem extracts as potential organic antagonists for colorectal carcinogenesis and suggest further in vivo and clinical investigations, following successful in vitro trials. We recommend more investigation into the specific phytoconstituents in WS that contribute to the regulatory mechanisms that inhibit the growth of colon cancer cells.

Current clinical practices of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of affected patients' prognoses. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with favorable long-term outcomes in carefully selected patients with peritoneal metastases (PM). We aim to summarize the current results about the initial malignancies and their peritoneal spreads. The current literature has been scrutinized, and studies between 2016 and 2022 were included wherein long-term, progression-free (PFS), and overall survival (OS) data were considered relevant information. Medline, Embase, and Google Scholar have been the main sources. Hereby, we cover all the primer malignancies: gastric, ovarian, and colorectal cancers with peritoneal metastases (PM), malignant peritoneal mesothelioma, and pseudomyxoma peritonei. Examining the advances in the current peer-reviewed literature about the indications of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), target groups, risk factors, and other influencing elements, we intend to provide a complex state-of-the-art report, establishing the relevant aspects of that emerging treatment method.

Pancreatic SABR using peritumoral fiducials, triggered imaging and breath-hold.

Background: We aim to present our linear accelerator-based workflow for pancreatic stereotactic ablative radiotherapy (SABR) in order to address the following issues: intrafractional organ motion management, Cone Beam CT (CBCT) image quality, residual errors with dosimetric consequences, treatment time, and clinical results. Methods: Between 2016 and 2021, 14 patients with locally advanced pancreatic cancer were treated with induction chemotherapy and SABR using volumetric modulated arc therapy (VMAT). Internal target volume (ITV) concept (5), phase-gated (4), or breath hold (5) techniques were used. Treatment was verified by CBCT before and after irradiation, while tumor motion was monitored and controlled by kV triggered imaging and beam hold using peritumoral surgical clips. Beam interruptions and treatment time were recorded. The CBCT image quality was scored and supplemented by an agreement analysis (Krippendorff's-α) of breath-hold CBCT images to determine the position of OARs relative to the planning risk volumes (PRV). Residual errors and their dosimetry impact were also calculated. Progression free (PFS) and overall survival (OS) were assessed by the Kaplan-Meier analysis with acute and late toxicity reporting (CTCAEv4). Results: On average, beams were interrupted once (range: 0-3) per treatment session on triggered imaging. The total median treatment time was 16.7 ± 10.8 min, significantly less for breath-hold vs. phase-gated sessions (18.8 ± 6.2 vs. 26.5 ± 13.4, p < 0.001). The best image quality was achieved by breath hold CBCT. The Krippendorff's-α test showed a strong agreement among five radiation therapists (mean K-α value: 0.8 (97.5%). The mean residual errors were <0.2 cm in each direction resulting in an average difference of <2% in dosimetry for OAR and target volume. Two patients received offline adaptation. The median OS/PFS after induction chemotherapy and SABR was 20/12 months and 15/8 months. No Gr. ≥2 acute/late RT-related toxicity was noted. Conclusion: Linear accelerator based pancreatic SABR with the combination of CBCT and triggered imaging + beam hold is feasible. Peritumoral fiducials improve utility while breath-hold CBCT provides the best image quality at a reasonable treatment time with offline adaptation possibilities. In well-selected cases, it can be an effective alternative in clinics where CBCT/MRI-guided online adaptive workflow is not available.