Inhibitory effects of medium-chain fatty acids on the proliferation of human breast cancer cells via suppression of Akt/mTOR pathway and modulating the Bcl-2 family protein.

Medium-chain fatty acids (MCFAs) have 6-12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis-inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT-qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase-3, and the downregulation of antiapoptotic protein (Bcl-2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling-related proteins were observed in lauric acid-treated ER-positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.

Repurposing EORTC QLQ-H&N43 and NCCN Distress Thermometer and Problem List: Adaptation and Validation in Kannada.

To translate, validate and test the reliability of Kannada version of "EORTC QLQ-H&N43" and "NCCN Distress Thermometer and Problem list" version 2.2022. The English version of "EORTC QLQ H&N43" and "NCCN Distress thermometer and Problem List" version 2.2022 tools were translated into Kannada language according to standard guideline. The translated version was validated by EORTC and by using content validity index (CVI). Further, the reliability of validated tools was established via test-retest and internal consistency method whereas construct was determined via spearman rank correlation. The Cronbach alpha value > 0.7 and correlation coefficients (ρ) < 0.05 was considered as significant. The Kannada version of "EORTC QLQ-H&N43" was validated by EORTC as well as by experts whereas  NCCN distress tool was validated only by experts with average CVI score of 1 and 0.97 respectively. Out of total 80 patients, 50% were head and neck cancer (HNC) patients and 50% belonged to other cancer types. Kannada version of EORTC QLQ-H&N43 and NCCN distress tool was found to be reliable among HNC and general cancer patients respectively with the Cronbach alpha value between 0.819-1 and 0.71-1 for all the domains. Further, only 7.72% of EORTC QLQ-H&N43 and 13.33% of NCCN distress tool construct were significantly correlated with construct of EORTC QLQ-C30 (p < 0.05). The Kannada version of QoL and distress instrument was found to be valid and reliable to use among HNC and/ general cancer patients respectively. Thus, this method of translation, validation and reliability testing can be used as a novel practice in healthcare. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04366-0.

Prognostic significance of tetraspanin CD9 and oncogenic epidermal growth factor receptor in tongue squamous cell carcinoma survival.

The most prevalent locations for head and neck cancer is the tongue. The surviving patients who are receiving therapy have considerably compromised speech, taste, chewing, and swallowing. CD9 is a cell surface protein that has contradictory role in cancer progression. The objective of the study is to analyze the Cluster of Differentiation 9(CD9), Epidermal Growth Factor Receptor (EGFR) and Phosphorylated Akt (p-Akt) expression in tongue cancer specimens and its clinical significance.50 tongue cancer sections were used to analyze the expression of CD9,EGFR and p-Akt by immunohistochemistry. Data regarding the histological grade of the tumor, age, sex, and habits were recorded, and relation with CD9,EGFR and p-Akt expression was assessed. Data were expressed as mean ± SEM. Categorical data was analyzed by Chi-square test. Student t-test was used to check the significance of data between two groups.A significant increase in the CD9,EGFR and p-Akt expression (1.8 ± 0.11, 2.06 ± 0.18 and 2.3 ± 0.15 respectively) was seen in the tongue cancer specimens. CD9 and p-Akt expression had a significant association with the histological grade (p < 0.004 and p < 0.006 respectively). CD9 expression was higher in patients with the combination of addiction/habit compared to patients with single addictions(1.08 ± 0.11 and 0.75 ± 0.47). Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.

Medium-Chain Fatty Acids and Breast Cancer Risk by Receptor and Pathological Subtypes.

Introduction: Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where they are immediately utilized for energy. We aimed to determine the medium-chain fatty acid levels in women with and without breast cancer. Materials and Methods: A total of 200 women (100 breast cancer subjects and 100 control subjects) were recruited for the study as per the inclusion and exclusion criteria. Blood samples were collected for biochemical estimations. Fatty acid methyl esters were isolated, and medium-chain fatty acid levels in plasma were analyzed using gas chromatography (GC-FID). Statistical analysis was performed using SPSS 20.0 software; p ≤ 0.05 was considered statistically significant. Results: The fatty acid analysis revealed a significant decrease in the levels of caprylic acid (C:8) and lauric acid (C:12) and a significant increase in the level of capric acid (C:10) in the breast cancer subjects when compared to the control group. The level of caproic acid (C:6) was not significantly increased in the breast cancer subjects. In particular, the HER2- and ER-positive breast cancer subjects showed a decrease in their caprylic acid and lauric acid levels compared to other receptors. Conclusions: The results of the current study imply that lower levels of caprylic and lauric acid may be associated with a higher risk of breast cancer. The relevance of medium-chain fatty acids for preventive and therapeutic interventions will be amplified by further research on the possibility that alteration in a patient's medium-chain fatty acid composition may mechanistically contribute to disease progression or breast cancer risk.

Comprehensive Review of Hepatocellular Carcinoma in India: Current Challenges and Future Directions.

There is not much information on hepatocellular carcinoma (HCC) in India. Here, we review the existing data, available treatment choices, and future directions in HCC management. An extensive search was conducted through PubMed and MEDLINE for studies published between January 2000 and June 2022 on the epidemiology of HCC in India using the following key words: atezolizumab, BCLC staging, hepatocellular carcinoma, immune checkpoint inhibitors, immunotherapy, and programmed cell death ligand-1, with the filters humans and English language. The most frequent risk factors for the development of HCC in India include nonalcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infection, liver cirrhosis, and alcohol intake. On the basis of new findings, the Barcelona Clinic Liver Cancer (BCLC) Staging Criteria need to be revised. As most cases in India are discovered at a later stage, curative treatments such as surgical resection, ablation, or liver transplantation may not be an option. Clinical trials are underway for a number of immune checkpoint drugs that target cytotoxic T-cell lymphocyte-4 and programmed cell death-1/programmed cell death-ligand 1. In India, phase III trials of atezolizumab in combination with other drugs are underway for the treatment of various malignancies. Renin angiotensin system inhibitors, antivirals, primary hepatocyte transplantation, and bioartificial liver devices are among the future options for the management of HCC. In developing countries like India, HCC is often diagnosed at an advanced stage because of a delay in routine testing or screening. Therefore, developing effective treatment regimens for such stages is critical. Immunotherapy is a promising treatment option that has the potential to increase overall response and survival rate.