A synthetic bioactive peptide of the C-terminal fragment of adhesion protein Fibulin7 attenuates the inflammatory functions of innate immune cells in LPS-induced systemic inflammation.

OBJECTIVE: Systemic inflammation is associated with improper localization of hyperactive neutrophils and monocytes in visceral organs. Previously, a C-terminal fragment of adhesion protein Fibulin7 (Fbln7-C) was shown to regulate innate immune functionality during inflammation. Recently, a shorter bioactive peptide of Fbln7-C, FC-10, via integrin binding was shown to reduce ocular angiogenesis. However, the role of FC-10 in regulating the neutrophils and monocyte functionality during systemic inflammatory conditions is unknown. The study sought to explore the role of FC-10 peptide on the functionality of innate immune cells during inflammation and endotoxemic mice. METHODS: Neutrophils and monocytes were isolated from healthy donors and septic patient clinical samples and Cell adhesion assay was performed using a UV spectrophotometer. Gene expression studies were performed using qPCR. Protein level expression was measured using ELISA and flow cytometry. ROS assay, and activation markers analysis in vitro, and in vivo were done using flow cytometry. TREATMENT: Cells were stimulated with LPS (100 ng/mL) and studied in the presence of peptides (10 µg, and 20 µg/mL) in vitro. In an in vivo study, mice were administered with LPS (36.8 mg/kg bw) and peptide (20 µg). RESULTS: This study demonstrates that human neutrophils and monocytes adhere to FC-10 via integrin ß1, inhibit spreading, ROS, surface activation markers (CD44, CD69), phosphorylated Src kinase, pro-inflammatory genes, and protein expression, compared to scrambled peptide in cells isolated from healthy donors and clinical sample. In line with the in vitro data, FC-10 (20 µg) administration significantly decreases innate cell infiltration at inflammatory sites, improves survival in endotoxemia animals & reduces the inflammatory properties of neutrophils and monocytes isolated from septic patients. CONCLUSION: FC-10 peptide can regulate neutrophils and monocyte functions and has potential to be used as an immunomodulatory therapeutic in inflammatory diseases.

Demographic and clinicopathological Profile of Gall Bladder Cancer Patients: Study from a tertiary care center of the Sub-Himalayan region in Indo-Gangetic Belt.

INTRODUCTION: Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients. MATERIALS AND METHODS: All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled. RESULTS: A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC. CONCLUSIONS: Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.

Impact of COVID-19 Pandemic on Oncology Practices During Nationwide Lockdown Period: A Single Centre Experience and the Way Forward.

BACKGROUND: The COVID-19 pandemic has posed a grave challenge to mankind as it doesn't appear to get controlled in the near future. Worldwide, health care centers are working more than their capacity with the scarcity of medical resources. Cancer patients are considered to be at higher risk of developing life-threatening complications from COVID-19 and at the same time treatment delays can lead to poorer oncological outcomes. Appropriate planning is therefore important to continue with cancer treatment services and simultaneously avoiding the risk of infection to the patients and healthcare staff and not allowing community transmission of viral infection. METHODS AND RESULTS: We modified our practice measures in cancer patients receiving systemic therapy. Tele-consultations and use of electronic means, providing the best supportive care at or near home, and involvement of local/ family physicians were widely practiced. We minimised in-patient admissions, however, day-care chemotherapies were continued to provide optimum oncology services. CONCLUSIONS: Modified oncological practice measures need to be implemented as the pandemic seems to stay for a longer time.

Navigating breast cancer brain metastasis: Risk factors, prognostic indicators, and treatment perspectives.

In this editorial, we comment on the article by Chen et al. We specifically focus on the risk factors, prognostic factors, and management of brain metastasis (BM) in breast cancer (BC). BC is the second most common cancer to have BM after lung cancer. Independent risk factors for BM in BC are: HER-2 positive BC, triple-negative BC, and germline BRCA mutation. Other factors associated with BM are lung metastasis, age less than 40 years, and African and American ancestry. Even though risk factors associated with BM in BC are elucidated, there is a lack of data on predictive models for BM in BC. Few studies have been made to formulate predictive models or nomograms to address this issue, where age, grade of tumor, HER-2 receptor status, and number of metastatic sites (1 vs > 1) were predictive of BM in metastatic BC. However, none have been used in clinical practice. National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms; routine screening for BM in BC is not recommended in the guidelines. BM decreases the quality of life and will have a significant psychological impact. Further studies are required for designing validated nomograms or predictive models for BM in BC; these models can be used in the future to develop treatment approaches to prevent BM, which improves the quality of life and overall survival.

Tumor infiltrating lymphocytes in gastric cancer: Unraveling complex interactions for precision medicine.

This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment. The role of tumor infiltrating lymphocytes (TILs) will also be discussed in detail, including the types, mechanism of action, and role. Gastric cancer (GC) often presents in the advanced stage and has various factors predicting the outcomes. The interplay of these factors and their correlation with the TILs is discussed. A literature review revealed high intra-tumoral TILs associated with higher grade, HER2-, and Helicobacter pylori negativity. Moreover, stromal (ST) TILs correlated with lower grade and lesser recurrence risk in GC. High TILs in ST and invasive border also correlated with mismatch repair deficiency status. Further characterization of the CD3+, CD8+, and other cells is also warranted. In the future, this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

Reply to A. Mathew et al.

Gender disparities in young-onset CRC highlight health care access barriers in LMICs & changing global incidence trends. Increased awareness is crucial. #JCOGO @JCOGO_ASCO.

Carcinoma en Cuirasse as the heralding sign of underlying HER-2 positive male breast cancer.

Carcinoma en cuirasse (CeC) is an uncommon presentation of metastatic cutaneous carcinoma, most often originating from breast carcinoma. We present a case study of a man in his 30s exhibiting progressive skin thickening over the left chest, alongside appetite and weight loss. On examination, the patient had painless skin induration and palpable, matted, hard, immobile and non-tender axillary, cervical and inguinal lymphadenopathy. Imaging revealed metabolically active left cervical, retro pectoral, inguinal and bilateral axillary lymph nodes with muscle involvement, likely neoplastic. Histopathology demonstrated metastatic carcinoma, morphologically originating from the breast. CeC most often presents after therapy, but our case reveals that it may be a presenting sign of an occult malignancy. CeC should be differentiated from non-oncological causes of skin thickening. Detailed history, physical examination and appropriate radiological investigations are essential. Although rare in young individuals, neoplastic aetiology should be considered if the history and physical examination suggest it.

Maxillary Diffuse Large B-Cell Lymphoma Enshrouded as Osteomyelitis: A Case Report.

Extranodal non-Hodgkin's lymphoma (NHL) afflicting the head and neck region is rare, accounting for only about 5%. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL affecting the oral cavity. Due to its variable clinical presentation and non-pathognomic course, it can be easily misdiagnosed with overlapping characteristics to common oral pathologies. In the present case, the authors report an unusual presentation of DLBCL and highlight the significant diagnostic challenge encountered by the clinician. In our case, osteonecrosis of the maxilla with soft tissue swelling misleads the diagnosis of chronic osteomyelitis. However, further, work-up was pursued, and the patient was managed successfully with chemotherapy and is currently disease-free for the past 1 year. An accurate clinico-radiological diagnosis with histopathological confirmation is emphasized to deliver a potentially curative treatment in a timely manner.

A novel ultra-performance liquid chromatography detection method development and validation for paclitaxel and its major metabolite in human plasma.

BACKGROUND: Paclitaxel is a promising anticancer drug for patients with ovarian, breast, lung, gastrointestinal, genitourinary, prostate, and head-and-neck cancers. Paclitaxel follows nonlinear pharmacokinetics. The major metabolite of paclitaxel is 6-alpha-hydroxy paclitaxel, mediated by CYP2C8, while metabolism to two of its minor metabolites, 3'-p-hydroxypaclitaxel and 6a, 3'- p-dihydroxypaclitaxel, is catalyzed by CYP3A4. Therapeutic drug monitoring of paclitaxel could be a promising approach to improve the efficacy and safety of paclitaxel correct personalized doses and improve the overall benefit-risk ratio. A novel and highly sensitive chromatographic method for the detection of paclitaxel and its metabolite has been proposed that allows quantification in human plasma with 100% accuracy in terms of recovery without significant intraday or interday variations. MATERIALS AND METHODS: The present study was planned following bioanalytical method validation guidance according to the U.S. Food and Drug Administration requirements. The validation of the analytical procedure was performed as per ICH Q2(R1) guidelines. It was done to assure the reliability of the results obtained for various parameters such as linearity, accuracy, precision, limit of detection (LOD), limit of quantification, robustness, stability, and system suitability. RESULTS: The specificity of the method was established by ensuring no interference with peak obtained from paclitaxel and 6-alpha-hydroxy paclitaxel. LOD was found to be 0.05 and 0.033 while the limit of quantitation was 0.14 and 0.099 for paclitaxel and 6-alpha-hydroxy paclitaxel, respectively. Median (±interquartile range) accuracy for paclitaxel and 6-alpha-hydroxy paclitaxel was found to be 102.73 (±13.581) and 100.87 (±7.573), respectively. CONCLUSION: This novel method of simultaneous detection of paclitaxel and its major metabolite 6-alpha-hydroxy paclitaxel demonstrated significant resolution and was sensitive enough for its quantification in human plasma.

Prevalence and impact of endocrine disorders in advanced metastatic cancer patients undergoing cancer-directed therapy: A prospective observational study.

BACKGROUND: Noncommunicable diseases (NCDs) contribute significantly to global morbidity and mortality, with cancer being one of the leading causes. In this prospective observational study, we aimed to investigate the prevalence and impact of endocrine disorders, specifically diabetes and thyroid dysfunction, in patients with advanced metastatic cancer undergoing cancer-directed therapy. METHODS: Over 15 months, we recruited 100 histologically proven advanced metastatic cancer patients from the Department of Medical Oncology Haematology, All India Institute of Medical Sciences, Rishikesh, and conducted institutional-based prospective observational study. All participants over 18 years of age, treatment-naive, and potential candidates for systemic chemotherapy with an expected clinical survival of at least 6 months were included in the study. Patients with prior therapy, secondary neoplasms, and those unable to complete 3 months of palliative chemotherapy were excluded. Patients were assessed for diabetes and thyroid function at presentation, after 3 and 6 months of cancer-directed standard therapy. These data were analyzed, processed, and presented as results. RESULTS: The mean age of participants was 50.45 years, with a near-equal distribution of males and females. At baseline, 10% of the study population had preexisting endocrine disorders (2% hypothyroidism, 8% diabetes). By the end of 6 months, the prevalence increased to 18%, with females being more affected. Notably, the prevalence of new-onset endocrine disorders during cancer-directed therapy was only 3% for diabetes and 4% for thyroid dysfunction. CONCLUSION: Analysis of sociodemographic and cancer-related characteristics showed no significant association with changes in diabetic and thyroid status at 3 and 6 months. However, substance use, particularly smoking, was associated with an increased risk of diabetes development (p < .05). Cancer type and treatment regimen did not show statistically significant correlations with endocrine dysfunction. IMPLICATIONS: Our study highlights the importance of considering endocrine disorders in advanced metastatic cancer patients undergoing therapy. The prevalence of diabetes and thyroid dysfunction increased during cancer-directed therapy, particularly in females. Careful monitoring and timely intervention are essential to improve the quality of life for these patients. Further research is warranted to explore the long-term effects of cancer-directed therapy on endocrine health and develop tailored management strategies for this vulnerable population.