We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons.
We report the isolation and characterization of four compounds from a cytotoxic fraction F-17, isolated from the DCM extract of C. odorata by bioactivity guided fractionation.
Purpose: To quantify aerosol and droplets generated during noncontact tonometry (NCT) and assess the spread distance of the same. Methodology: This was an experimental study on healthy human volunteers (n=8 eyes). In an experimental setup, NCT was performed on eyes (n=8) of human volunteers under normal settings, with a single and 2 drops of lubricant. High-speed shadowgraphy, frontal lighting technique, and fluorescein analysis were used to detect the possible generation of any droplets and aerosols. Mathematical computation of the spread of the droplets was then performed. Results: In a natural setting, there was no droplet or aerosol production. Minimal splatter along with droplet ejection was observed when 1 drop of lubricant was used before NCT. When 2 drops of lubricant were instilled, a significant amount of fluid ejection in the form of a sheet that broke up into multiple droplets was observed. Some of these droplets traversed back to the tonometer. Droplets ranging from 100 to 500 µm in diameter were measured. Conclusions: There was no droplet generation during NCT performed in a natural setting. However, NCT should be avoided in conditions with high-tear volume (natural or artificial) as it would lead to droplet spread and tactile contamination.
Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma.
Purpose/Objective(s) Premature discontinuation of radiation therapy (RT) is a significant challenge portending inferior outcomes, particularly with curative intent RT. This study measures the impact of the COVID-19 pandemic compared to prior treatment terminations (TTs) from a multi-institutional health system in the New York Metropolitan area. Materials/Methods TT data was collected from the internal quality assurance records of a multicenter radiation oncology department for the September 2019-February 2020 pre-pandemic interval (BP) and the March 2020-August 2020 post-pandemic interval (AP). We measured aggregate and monthly CT simulations (CT sims), TTs, and terminations with zero fractions of radiation given (0Fx), the latter stratified by palliative vs. curative intent (0Fx-P vs. 0Fx-C). AP TTs attributed to COVID-19 anxiety were also obtained. The data were analyzed as aggregate ratios with monthly weighting of TTs/CT sims, 0Fx/CT sims, and 0Fx/TTs. Ratio statistics were employed and 95% confidence intervals generated. 0Fx-P and 0Fx-C were tested for association with BP and AP by chi-square analysis. Results For BP and AP respectively: TTs/CT sims were 8.1% (95% CI 5.2%-11.0%) and 11.2% (95% CI 9.2%-13.3%); 0Fx/CT sims were 1.4% (95% CI 0.16%-2.70%) and 2.5% (95% CI 1.49%-3.6%); 0Fx/TTs were 15.8% (95% CI 6.35%-25.21%) and 22% (95% CI 16.0%-27.9%). The association of 0Fx-P and 0Fx-C with BP and AP yielded chi-square = 0.43, P = 0.51. TTs attributed to COVID-19 anxiety comprised 3.9% of TTs in AP. Conclusion The endpoints for TTs in the BP and AP periods in our study cohort were suggestive of a COVID impact on patients discontinuing radiation therapy, but without statistical significance. Given the subtleties of TT dynamics and uncertainties such as the count of COVID-19 anxiety-related terminations, along with a relatively small sample size, it is reasonable to infer that this review was underpowered. Moreover, direct statistical attribution of TTs to COVID understates knock-on effects, e.g., the case of a 0Fx TT that would have occurred regardless of COVID but under the stress of the pandemic exacerbates the harm of the waste of resources. At the patient care level, understanding how COVID affects TT patterns may enable interventions that facilitate completion of care as intended by the treating physician. At the health system level, such understanding may elucidate a plausible mechanism of COVID's cascading downstream influence on oncologic outcomes. Nevertheless, it will require a multi-institutional cohort to quantitatively discern the impact of the pandemic on TT dynamics.
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