Practical Consensus Guidelines for the Use of S-1 in GI Malignancies.

Purvish M ParikhS-1 (5-fluorouracil prodrug [tegafur] in combination with 5-chloro-2,4-dihydroxypyridine [CDHP] and potassium oxonate [OXO]) was first approved in 1999. In order to make it easy for community oncologists, we decided to put together this expert consensus guideline for its use in gastrointestinal (GI) malignancies. A total of 15 subject matter experts used modified Delphi method to discuss, analyze, and vote on key aspects regarding practical approach to use of S-1 in GI cancers, a process involving 6 months of work. The consensus guidelines specify how S-1 use can be optimized in patients with colorectal, gastric, and pancreatic tumors. The voting for the 17 key points resulted in a majority consensus for all the statements (approval ranging from 13/15 [87%] to 15/15 [100%]). S-1 is a combination of three drugs (tegafur, CDHP, and OXO) specifically designed to reduce toxicity and enhance efficacy; clinical data and meta-analysis confirm both factors; and it is recommended as standard of care for GI cancers. S-1 is approved and one of the standards of care for all lines of therapy in colorectal cancer and pancreatic cancers. S-1 with oxaliplatin is the standard of care for gastric cancers.

Multiple myeloma as a mandibular primary - Dilemma in diagnosing rare tumours of the mandible.

Multiple myeloma (MM) is a plasma cell malignancy, and its typical radiographic presentation includes punched-out radiolucency of the skull. It is a bourgeois description of myeloma and often holds good in most cases. However, the diagnosis can get tricky when a patient walks into the clinic with non-specific signs and symptoms. Many suspicions arise when we examine a well-defined mandibular swelling, but the real picture is revealed with thorough screening. This article presents a rare mandibular swelling diagnosed as MM, emphasizing important differential diagnoses for maxillofacial surgeons and pathologists.

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.

Evaluation of the cytogenetic profile in patients with acute leukaemia.

Acute leukaemia (AL) is a heterogeneous neoplastic disease that occurs by the growth of abnormal lymphoid and myeloid cells in the bone marrow and blood leading to acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). Conventional cytogenetics is a characteristic technique to hunch chromosomal abnormalities, it helps in the diagnosis and therapeutic approach of the disease by the molecular cytogenetics technique of fluorescence in situ hybridization (FISH). Chromosomal abnormalities in AL are performed by karyotyping to confirm specific chromosomal abnormalities using FISH. The descriptive study included 42 clinically diagnosed AL patients. Karyotyping analysis was performed using the standard Giemsa banding procedure. To confirm specific chromosomal abnormalities and all culture failure (CF) cases, FISH was done. Among 42 cases, 29 (69.4%) males and 13 (30.9%) females, AML comprised 22 (52.38%) cases, ALL 14 (33.33%) cases, and AL 6 (14.2%) cases. Normal karyotype was found in 18 (42.85%), abnormal karyotype in 16 (39.09%), and 8 (19.09%) were CF. Specific abnormalities of t(15;17), hyperdiploidy; t(3;3) with monosomy 7 in; del(9q22); del(2p); del(17p); del(Xq); 1~2 dmin; der(3); +11, +13 and composite karyotype. Hypodiploidy was strongly associated with AL, which signifies the loss of chromosomes causing potential risk. Composite karyotype, rare t(3;3) double minutes, +11,+13, del(9q), and del(Xq) were the novel findings reported in the South Canara region of Karnataka. Despite other molecular techniques, conventional cytogenetics remains the baseline in the diagnosis of malignancies.

Theranostic Potential of EFNB2 for Cetuximab Resistance in Head and Neck Cancer.

Only 13% of head and neck cancer (HNC) patients respond to cetuximab therapy despite its target (EGFR) is expressed in about 80-90% of HNC patients. However, this problem remained unresolved till date despite of numerous efforts. Thus, the current study aimed to establish hub genes involved in cetuximab resistance via series of bioinformatics approach. The GSE21483 dataset was analysed for differentially expressed genes (DEGs) using GEO2R and enrichment analysis was carried out using DAVID. STRING 11.5 and Cytoscape 3.7.2 were used for protein-protein interactions and hub genes respectively. The significant hub genes (p < 0.05) were validated using ULCAN and Human protein atlas. Validated genes were further queried for tumor infiltration using TIMER2.0. Out of total 307 DEGs, 38 hub genes were identified of which IL1A, EFNB2, SPRR1A, ROBO1 and SOCS3 were the significant hub genes associated with both mRNA expression and overall survival. IL1A, ROBO1, and SOCS3 were found to be downregulated whereas EFNB2 and SPRR1A were found to be upregulated in our study. However, using UALCAN, we found that high expression of IL1A, EFNB2, SOCS3 negatively affects overall survival whereas high expression of SPRR1A and ROBO1 positively affects overall survival. Protein level for EFNB2 and SPRR1A expression was significant in tumor HNC tissue as compared to normal HNC tissue. EFNB2 was found to be a key regulator of CTX resistance among HNC patients. Targeting EFNB2 and associated PPI circuits might improve the response rate to CTX. Thus, EFNB2 has potential to be theranostic marker for CTX resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03739-9.

Development of evidence-based indicators for the detection of drug-related problems among ovarian cancer patients.

Background: Antineoplastic drugs produce serious drug-related problems and their management is challenging. DRPs are critical, for saving on therapeutic costs, particularly in resource poor settings within low-middle-income countries such as India. Indicators are clues that helps to detect DRPs within the healthcare organization and minimize overall harm from medications. Indicators enable healthcare professionals to determine the future therapeutic course. And enable healthcare professionals to take a proactive stand, and stay informed and empowered to both prevent and manage DRPs. This study aims to develop evidence-based indicators for detecting potential drug-related problems in ovarian cancer patients. Patients and Methods: A retrospective study was conducted in the Department of Oncology of a tertiary care teaching hospital in South India. Based on literature search, we developed a list of indicators, which were validated by a Delphi panel of multidisciplinary healthcare professionals (16 members). Based on 2 years of ovarian cancer data, we performed a feasibility test retrospectively and classified the DRPs according to the Pharmaceutical Care Network Europe classification of DRPs version-9.1. Results: The feasibility test identified 130 out of 200 indicators. A total of 803 pDRPs were identified under four main categories: drug selection problem, drug use problem, adverse drug reaction and drug-drug interaction The most frequently observed were ADR 381 (47.45%), DDIs 354 (44.08%), and drug selection problems 62 (7.72%). Conclusion: Indicators developed by us effectively identified pDRPs in ovarian cancer patients, which can potentially help healthcare professionals in the early detection, timely management, and attenuating severity of DRPs. Identifying the pDDIs can potentially improve interdisciplinary involvement and task sharing, including enhanced pharmacists' participation within the healthcare team.

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.

Effect of Exercise Training on Functional Capacity Head and Neck Cancer Patients Receiving Various Anticancer Therapies: An Interventional Study.

BACKGROUND: Anticancer therapies causes decreased respiratory function, quality of life and functional capacity in head and neck cancer patients. Patients receiving these cancer therapies suffer from fatigue which causes decrease in functional capacity and quality of life. The objective of this present study was to determine and compare the effect of exercise training on fatigue, functional capacity and quality of life in head and neck cancer patients receiving various anticancer therapies. METHOD: A total of 45 subjects were included based on inclusion and exclusion criteria. 6-minute walk test, brief fatigue inventory (BFI) and functional assessment of cancer therapy- general (FACT-G) was used to measure the functional capacity, fatigue and quality of life respectively at baseline and post intervention. Participants received exercise intervention for six weeks (three days a week) for 40 min. Exercise intervention is delivered by a qualified physiotherapist from the Department of Physiotherapy. RESULTS: The result of this study shows that there was highly significant improvement in six-minute walk distance pre and post intervention in chemotherapy (33.75+21.55, p=0.000), radiation therapy (39.69+25.46, p=0.000) and chemoradiotherapy (32.06+16.49, p=0.000) within the group. Similarly, significant improvement was also seen in quality of life within the groups, chemotherapy (2.92+2.43, p=0.002), radiation therapy (6.06+3.13, p=0.000) and chemo radiotherapy (5.65+6.93, p=0.004). There was significant reduction in fatigue in chemotherapy (6.92+11.07, p=0.045), radiation   therapy (12.38+7.28, p=0.000)   and   chemo   radiotherapy (11.47+8.89, p=0.000). No significant improvement was noted between the groups for six- minute walk distance (p=0.784), quality of life (p= 0.058) and reduction in fatigue (p=0.065). CONCLUSION: This study concluded that exercise training is effective in improving functional capacity, quality of life and reducing fatigue in head and neck cancer patients receiving various anticancer therapies.

Identification of signature genes and drug candidates for primary plasma cell leukemia: An integrated system biology approach.

BACKGROUND: Plasma cell leukemia (PCL) is one of the rare cancer which is characterized by the uncontrolled proliferation of plasma cells in peripheral blood and bone marrow. The aggressive behavior of the disease and high mortality rate among PCL patients makes it a thirst area to be explored. METHODS: The dataset for PCL was obtained from the GEO database and was analyzed using GEO2R for differentially expressed genes. Further, the functional enrichment analysis was carried out for DEGs using DAVID. The protein-protein interactions (PPI) for DEGs were obtained using STRING 11.5 and were analyzed in Cytoscape 3.7.2. to obtain the key hub genes. These key hub genes were investigated for their interaction with suitable drug candidates using DGIdb, DrugMAP, and Schrodinger's version 2022-1. RESULTS: Out of the total of 104 DEGs, 39 genes were up-regulated whereas 65 genes were down-regulated. A total of 11 biological processes, 2 cellular components, and 5 molecular functions were enriched along with the 7 KEGG pathways for the DEGs. Further, a total of 11 hub genes were obtained from the PPI of DEGs of which TP53, MAPK1, SOCS1, MBD3, and YES1 were the key hub genes. Oxaliplatin, mitoxantrone, and ponatinib were found to have the highest binding affinity towards the p53, MAPK1, and YES1 proteins respectively. CONCLUSION: TP53, MAPK1, SOCS1, MBD3, and YES1 are the signature hub genes that might be responsible for the aggressive prognosis of PCL leading to poor survival rate. However, p53, MAPK1, and YES1 can be targeted with oxaliplatin, mitoxantrone, and ponatinib.

A diagnostic approach to detect cytogenetic heterogeneity and its prognostic significance in multiple myeloma.

Objective: Multiple myeloma (MM) is a hematological disorder involving the uncontrolled proliferation of clonal plasma cells and its accumulation in the bone marrow. This study analyzed the frequency, cytogenetic heterogeneity, and clinical characteristics of patients with MM. Methods: Bone marrow aspirates were obtained from 72 patients with MM and evaluated by conventional cytogenetics (CCs) and interphase fluorescence in situ hybridization (iFISH) techniques for a panel of probes, including immunoglobulin heavy chain (IgH)/CCND1, IgH/fibroblast growth factor receptor 3 (FGFR3), IgH/MAFB, 13q deletion, and deletion 17p. Results: CCs revealed abnormal karyotypes in 39% of the patients examined. The incidence of hypodiploidy was 28% (20/72) while that of hyperdiploidy was 10% (7/72). iFISH analysis revealed t(11;14) in 6% (4/72) and t(4;14) in 11% (8/72) of patients. Patients with hyperdiploidy and hypodiploidy were associated with several monosomies and trisomies. Kaplan-Meier analysis revealed a significant difference between positive and negative groups for t(4;14), trisomy 14, and monosomy 13; this was associated with a shorter survival time. Cox proportional analysis identified t(4;14) (P = 0.032), trisomy 14 (P = 0.004), and monosomy 13 (P = 0.009), as significant factors with hazard ratio of 0.187 [confidence interval (CI): 0.041-0.862], 0.109 [CI: 0.024-0.500] and 0.134 [CI: 0.030-0.600]. Conclusion: In addition to cytogenetic abnormalities, iFISH analysis revealed significant heterogeneity among patients with MM. Cytogenetic heterogeneity in patients with MM should be considered as a major prognostic marker contributing to the variability of the disease. Our findings suggest that these abnormalities are independent prognostic factors.

Evaluation of chemotherapy infusion and phlebitis among cancer patients: A prospective observational single-center study.

INTRODUCTION: Chemotherapy is an integral part of cancer management which is associated with phlebitis in around 70% of patients receiving intravenous chemotherapy infusion. Thus, we aimed to estimate the incidence, severity, and management of phlebitis associated with chemotherapy infusion among cancer patients. METHODS: A prospective study was conducted among 145 patients receiving intravenous chemotherapy for the duration of six months in the oncology department. The relevant data for phlebitis was obtained and assessed using Phlebitis Grading Scale and Visual Analogue Scale for the assessment of severity and pain due to phlebitis, respectively. RESULTS: Out of 145 patients, female (56.6%) patients predominated over male patients (43.5%) with a mean age of 53.5 ± 11.82 years. Phlebitis was encountered in 30.34% of patients among whom 22.8% (33) were females followed by 7.6% were males and the majority of patients (13.1%) were from the 46 to 60 years age group. Phlebitis was observed frequently among stage 2 (11%) and satge 4 (11%) patients. The highest incidence of phlebitis was seen among hypertensive (34.09%) and diabetic patients (27.27%) followed by those receiving chemotherapy through the 20-gauge intravenous cannula (22.8%) and 22-gauge (6.9%). Platinum compounds (56.8%) were commonly associated with phlebitis, followed by cyclophosphamide (20.5%). Heparin and benzyl nicotinate topical gel were used to treat phlebitis. CONCLUSION: Platinum and cyclophosphamide are commonly associated with phlebitis which can be managed by topical heparin plus benzyl nicotinate. Phlebitis shouldn't be ignored as it has a high incidence, affects the quality of life, and increases the treatment burden.

Healthcare Scheme to Overcome Financial Burden Associated with Chemoradiation Therapy in Head and Neck Cancer Patients: A Retrospective Single Centre Study.

Head and neck cancer (HNC) is third highest prevalent cancer among Indian which constitutes about 25-30% of all the cancer in India. Further, out-of-pocket expenditure (OOPE) covers around 67% of total healthcare expenditure and direct medical cost is key factor responsible for raised OOPE in India. Thus, we aimed to quantify total direct medical cost and OOPE associated with HNC management among HNC patients using "Ayushman Bharat Arogya Karnataka scheme" (ABArK scheme). A retrospective study was conducted for the duration of 6 months to collect the data related to total direct medical cost, coverage of "ABArK Scheme" and OOPE of past 2 years of HNC patients. The data of HNC patients above 18 years of age utilizing "ABArK scheme" were included in the study whereas data of patients utilizing other healthcare schemes and incomplete data on target schemes were excluded. A total of 196 patients (54.1%) utilized the "ABArK Scheme" out of 362 HNC patients treated in past 2 years. Among 196 patients, males (76.5%) were predominant over females (23.5%) with the mean age of 53.60 ± 11.58 years. We found that INR 17,370,279 as the total direct medical expenditure for the management of HNC patients of which around 87.465% was covered by "ABArK Scheme" minimizing the OOPE up to INR 3,297,970. Thus, Introduction and implementation of novel healthcare policies like "ABArK Scheme" can counteract financial burden of cancer management by significantly reducing OOPE which could be milestone achievement for the low-middle income countries like India.

Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance.

The comprehensive bioinformatics analysis of breast cancer exosomes revealed that HSP90AA1, CCT2, and ENO1 were novel hub genes in the giant protein-protein interaction network of 110 exosomal proteins. Exosomes and their cargo such as discrete proteins, nucleic acids, and lipids are having potential role in the pathophysiology of breast cancer (BC). This study showed that the identified hub genes were particularly abundant in GO and KEGG pathways relevant to the positive regulation of telomerase. In addition, these hub genes were found to be considerably overexpressed in breast adenocarcinoma patients compared to healthy controls, and further, this overexpression is linked to the poor prognosis in BC patients. Furthermore, the ROC analysis revealed that CCT2 gene has strong diagnostic and prognostic value for BC. Additionally, this in silico analysis found that the anticancer agents and HSP90 inhibitors such as ganetespib, retaspimycin, and tanespimycin would have considerable potential in the treatment of BC. Overall, this study findings imply that HSP90AA1, a molecular chaperon and CCT2, a chaperonin would serve as diagnostic and prognostic biomarkers, respectively, for BC. However, these findings need to be further confirmed by laboratory and clinical studies for validating their potential applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03422-w.

Identification of the SIRT1 gene's most harmful non-synonymous SNPs and their effects on functional and structural features-an in silico analysis.

Introduction: The sirtuin (Silent mating type information regulation 2 homolog)1(SIRT1) protein plays a vital role in many disorders such as diabetes, cancer, obesity, inflammation, and neurodegenerative and cardiovascular diseases. The objective of this in silico analysis of SIRT1's functional single nucleotide polymorphisms (SNPs) was to gain valuable insight into the harmful effects of non-synonymous SNPs (nsSNPs) on the protein. The objective of the study was to use bioinformatics methods to investigate the genetic variations and modifications that may have an impact on the SIRT1 gene's expression and function. Methods: nsSNPs of SIRT1 protein were collected from the dbSNP site, from its three (3) different protein accession IDs. These were then fed to various bioinformatic tools such as SIFT, Provean, and I- Mutant to find the most deleterious ones. Functional and structural effects were examined using the HOPE server and I-Tasser. Gene interactions were predicted by STRING software. The SIFT, Provean, and I-Mutant tools detected the most deleterious three nsSNPs (rs769519031, rs778184510, and rs199983221). Results: Out of 252 nsSNPs, SIFT analysis showed that 94 were deleterious, Provean listed 67 dangerous, and I-Mutant found 58 nsSNPs resulting in lowered stability of proteins. HOPE modelling of rs199983221 and rs769519031 suggested reduced hydrophobicity due to Ile 4Thr and Ile223Ser resulting in decreased hydrophobic interactions. In contrast, on modelling rs778184510, the mutant protein had a higher hydrophobicity than the wild type. Conclusions: Our study reports that three nsSNPs (D357A, I223S, I4T) are the most damaging mutations of the SIRT1 gene. Mutations may result in altered protein structure and functions. Such altered protein may be the basis for various disorders. Our findings may be a crucial guide in establishing the pathogenesis of various disorders.

Identification of key gene signatures and their characterization by expression correlation with drug sensitivity in smoking-associated oral squamous cell carcinoma.

AIMS: Oral squamous cell carcinoma (OSCC), a most frequent type of head-and-neck cancer, is becoming more common and posing a substantial health risk. Using a network biology strategy, this study intended to find and investigate critical genes associated with OSCC. MATERIALS AND METHODS: The extended protein-protein interaction networks for differentially expressed genes related to smoking and nonsmoking conditions of OSCC were constructed and visualized using Cytoscape software. The hub genes/proteins were determined based on degree and betweenness centrality measures and then evaluated and validated for expression using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and their relationship to the sensitivity of small molecules was discovered utilizing the Gene Set Cancer Analysis (GSCA) web server. RESULTS: A total of 596 differentially expressed genes were screened, and four genes, interleukin (IL)-6, JUN, tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGFA), were identified as hub proteins, and their expression and overall survival in head-and-neck cancers were further investigated using GEPIA2. TNF and VEGFA gene expressions were considerably greater in cancers when compared to normal samples, while JUN and IL-6 gene expressions were not statistically significant. Further, these hub proteins are found to have a substantial favorable correlation with overall survival of head-and-neck cancer patients. Finally, GSCA was used to predict gene-specific potential drugs that act on these molecules by combining mRNA expression and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal. CONCLUSIONS: The hub genes/proteins identified in this study could help researchers better understand the molecular processes involved in the progression and metastasis of oral cancer in smokers.

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.

Detection of clinically-relevant EGFR variations in de novo small cell lung carcinoma by droplet digital PCR.

Targeted therapy that utilizes tyrosine kinase inhibitors (TKIs), specific to epidermal growth factor receptors (EGFR) has changed the landscape of treatment of non-small cell lung cancer (NSCLC). The success or failure of this approach depends on presence of certain variations in the tyrosine kinase domain of EGFR gene. Generally, patients diagnosed with Small cell lung cancer (SCLC) are considered ineligible for TKI therapy owing to the absence of EGFR variations. . However, there is evidence of these variations being detected in SCLCs, both in de-novo and in transformed SCLCs (TKI-treated adenocarcinomas). Despite the presence of clinically-relevant EGFR variations in SCLCs, the response to TKIs has been inconsistent.  Liquid biopsy is a well-established approach in lung cancer management with proven diagnostic, prognostic and predictive applications. It relies on detection of circulating tumor-derived nucleic acids present in plasma of the patient. In this study, a liquid biopsy approach was utilized to screen 118 consecutive lung cancer patients for four clinically-relevant variations in EGFR gene, which included three activating/sensitizing variations (Ex18 G719S, Ex19del E746-A750 and Ex21 L858R) and one acquired/resistance (Ex20 T790M, de novo) variation by droplet digital PCR, the most advanced third generation PCR technique. As expected, clinically-relevant EGFR variations were found in majority of the non-small cell lung cancer cases. However, among the handful of small cell lung cancer samples screened, sensitizing variations (Ex18 G719S and Ex21 L858R) were seen in almost all of them. Interestingly, Ex20 T790M variation was not detected in any of the cases screened.  The results of our study indicate that EGFR variations are present in SCLCs and highly sensitive liquid biopsy techniques like ddPCR can be effectively utilized for this purpose of screening EGFR variations in such samples.

Correlation of preferentially expressed antigen of melanoma (PRAME) gene expression with clinical characteristics in acute leukemia patients.

BACKGROUND: Preferentially expressed antigen of melanoma (PRAME) gene is regularly overexpressed in acute leukemia (AL) and other malignant diseases which are recognized by human leucocyte antigen (HLA-24) located in the human chromosome of 22q11 coded by 509 amino acids. To rule out the PRAME gene expression in AL patients and its correlation with clinical characteristics in the Indian population set up by RT-qPCR. RESULTS: A total of 42 samples collected, 29 (69.4%) were males, and 13 (30.95%) were females, with a mean and standard deviation for age were 39.07 ± 22.22 years. Of which AML were of 22 (52.38%) cases, ALL were of 14 (33.33%) cases, and 6 (14.2%) cases which included other forms of leukemia. PRAME gene expression was highly expressed in thirty-three 27 (64.28%) AL patients compared to the least expression in healthy individuals. No significant difference between the different forms of AL (p=0.3203) was observed. Cytogenetic analysis of normal karyotype (NK), abnormal karyotype (Ab. K), and culture failure (CF) displayed statistical non-significance (p=0.5801). Among cytogenetic abnormalities obtained, no significant differences between the groups were observed (p=0.8507). Chloride, potassium, and absolute lymphocyte count (ALC) was found to be statistically significant with p=0.0038**, p=0.0358*, and p=0.0216*, respectively, between all other clinical characteristics. There was no correlation between the PRAME gene expression and clinical parameters. CONCLUSION: PRAME gene expression in AL patients was highly expressed, comparable to studies reported globally with significant cytogenetic results. PRAME gene could be used as a potential diagnostic marker for monitoring the malignancies and minimal residual disease in AL.