Saroj Gupta Cancer Centre & Research Institute

Traumatic brain injury (TBI) causes neuroinflammation and can generate long-term pathological consequences, including motor and visual impairments, cognitive deficits, and depression. In our previous study, we found that Fat1+-transgenic mice with higher endogenous n-3 polyunsaturated fatty acids (n-3 PUFA) were protected from post-TBI behavioral deficits and exhibited reduced levels of TBI-induced microglial activation, inflammatory factors, and sphingolipid ceramide, a lipid mediator of inflammation and cell death. This study’s objective was to evaluate if feeding n-3 PUFA (EPA and docosahexaenoic acid, DHA 2:1) could restrict the elevation of ceramide in brain tissue and prevent TBI-mediated sensory-motor and behavioral deficits. Wildtype C57/BL6 mice were gavage pre-fed with PUFA (EPA: DHA = 2:1) at 500 mg/kg body weight/week for 2 weeks before and 4 weeks after exposure to left side focal cranial air-blast (50 psi) TBI or sham-blast (0-psi). Saline-gavaged mice served as controls. Following blast injury, various motor, visual, and behavioral tests were conducted, and brain tissues were collected for histological and biochemical assays. Lipidomics analysis confirmed a significant elevation of EPA in the plasma and brain tissue of PUFA-fed mice. TBI-Blast brain tissues were found to have elevated ceramide levels in control mice but not in PUFA-fed mice. Moreover, PUFA-fed mice demonstrated protection against motor impairment, photoreceptor dysfunction, depression, oculomotor nerve degeneration, and microglia activation in the optic tract. Our results demonstrate that EPA-mediated suppression of ceramide biosynthesis and neuroinflammatory factors in PUFA-fed mice is associated with significant protection against the visual, motor, and emotional deficits caused by TBI.

Introduction Epithelial ovarian cancer (EOC) is one of the leading causes of mortality among women worldwide. The present study aimed to estimate the frequency of various histopathological types, clinical and surgico-pathological factors, and spectrum of lymph node (LN) metastasis in early and advanced EOC.Material and Methods Women with EOCs who underwent cytoreductive surgery (CRS) between January 2019 and May 2022 were included. The distribution of Clinico-demographic parameters, histological type, stage, and LN metastasis were analyzed.Results A total of 101 women with EOCs underwent CRS, out of which 5 (4.95%) with coexistent endometrial cancer were excluded (N = 96). Fifty women (52%) underwent primary CRS and 46 (48%) women underwent interval CRS. The mean age of the women was 48.42 ± 11.6 years. Initial serum cancer antigen 125 (CA 125) level was elevated (>35 U/mL) in 88 (91.67%) women and normal in 8 (8.33%) women. Complete cytoreduction was achieved in 75 (78.12%) cases. High-grade serous carcinoma was the most common histology (66/96, 68.75%), followed by mucinous carcinoma (15/96, 15.63%), endometrioid carcinoma (6/96, 6.25%), low-grade serous carcinoma (4/96, 4.17%), and carcinosarcoma (2/96, 2.08%). The majority of women, 69 (71.88%), were in stages III and IV at presentation. Most serous carcinomas were diagnosed at stage III (71.22%) or IV (13.64%). In contrast, the majority of endometrioid, mucinous, and clear cell carcinomas were diagnosed at stages I and II. Seventy-five women (78.13%) with EOC underwent pelvic and/or para-aortic lymphadenectomy, out of which 23 (30.67%) were histologically positive. Three out of 23 patients (13%) with early-stage disease showed positive LNs.Conclusion Serous carcinoma ovary is the most common histological subtype, presenting mostly in the advanced stage. A significant number of affected women were younger at presentation and diagnosis was made a decade earlier than the western population. A systematic pelvic and para-aortic lymphadenectomy in apparently early-stage (pelvic confined) ovarian cancer could detect additional LNs in 13% of women, especially in high-grade tumors and serous histology, suggesting the role of systematic lymphadenectomy for accurate staging in apparently early-stage ovarian cancer.

The KRAS mutation stands out as one of the most influential oncogenic mutations, which directly regulates the hallmark features of cancer and interacts with other cancer-causing driver mutations. However, there remains a lack of precise information on their cooccurrence with mutated variants of KRAS and any correlations between KRAS and other driver mutations. To enquire about this issue, we delved into cBioPortal, TCGA, UALCAN, and Uniport studies. We aimed to unravel the complexity of KRAS and its relationships with other driver mutations. We noticed that G12D and G12V are the prevalent mutated variants of KRAS and coexist with the TP53 mutation in PAAD and CRAD, while G12C and G12V coexist with LUAD. We also noticed similar observations in the case of PIK3CA and APC mutations in CRAD. At the transcript level, a positive correlation exists between KRAS and PIK3CA and between APC and KRAS in CRAD. The existence of the co-mutation of KRAS and other driver mutations could influence the signaling pathway in the neoplastic transformation. Moreover, it has immense prognostic and predictive implications, which could help in better therapeutic management to treat cancer.

Abstract Background: Mobile screening units (MSUs) offer an effective approach to increasing access to cancer screening and reducing geographical and financial barriers. This study reports the outcomes of MSUs in cervical, breast, and oral cancer screening. Methodology: The MSU was integrated into a bus with three compartments, with designated areas for registration, cervical cancer screening, oral visual examination (OVE), and mammography. Between May 2023 and August 2024, 178 community camps were held in Kolkata and nearby districts. A total of 6205 women underwent cervical, breast, and oral cancer screening. Women aged 30–60 years were screened for cervical cancer by high-risk human papillomavirus (hrHPV) DNA test while breast cancer screening was conducted using clinical breast examination. Any abnormal findings on examination were referred for mammography. Results: HrHPV positivity was detected in 323 (5.3%) women by Cobas assay. Following this, 218 women were referred for colposcopy and treatment. Following clinical breast examination, 316 women were referred for mammography. In addition, 28 women with suspicious breast lesions were referred to the Chittaranjan National Cancer Institute for further management. Abnormal OVE was diagnosed in 18 women who were advised to quit tobacco. Conclusion: MSUs serve as a valuable tool for expanding access to cancer screening in resource-limited settings and reduce the global burden of preventable cancers as well as meet cancer screening targets.

BackgroundTraumatic brain injury (TBI) causes neuroinflammation and can lead to long-term neurological dysfunction, even in cases of mild TBI (mTBI). Despite the substantial burden of this disease, the management of TBI is precluded by an incomplete understanding of its cellular mechanisms. Sphingolipids (SPL) and their metabolites have emerged as key orchestrators of biological processes related to tissue injury, neuroinflammation, and inflammation resolution. No study so far has investigated comprehensive sphingolipid profile changes immediately following TBI in animal models or human cases. In this study, sphingolipid metabolite composition was examined during the acute phases in brain tissue and plasma of mice following mTBI.MethodsWildtype mice were exposed to air-blast-mediated mTBI, with blast exposure set at 50-psi on the left cranium and 0-psi designated as Sham. Sphingolipid profile was analyzed in brain tissue and plasma during the acute phases of 1, 3, and 7 days post-TBI via liquid-chromatography-mass spectrometry. Simultaneously, gene expression of sphingolipid metabolic markers within brain tissue was analyzed using quantitative reverse transcription-polymerase chain reaction. Significance (P-values) was determined by non-parametric t-test (Mann–Whitney test) and by Tukey’s correction for multiple comparisons.ResultsIn post-TBI brain tissue, there was a significant elevation of 1) acid sphingomyelinase (aSMase) at 1- and 3-days, 2) neutral sphingomyelinase (nSMase) at 7-days, 3) ceramide-1-phosphate levels at 1 day, and 4) monohexosylceramide (MHC) and sphingosine at 7-days. Among individual species, the study found an increase in C18:0 and a decrease in C24:1 ceramides (Cer) at 1 day; an increase in C20:0 MHC at 3 days; decrease in MHC C18:0 and increase in MHC C24:1, sphingomyelins (SM) C18:0, and C24:0 at 7 days. Moreover, many sphingolipid metabolic genes were elevated at 1 day, followed by a reduction at 3 days and an absence at 7-days post-TBI. In post-TBI plasma, there was 1) a significant reduction in Cer and MHC C22:0, and an increase in MHC C16:0 at 1 day; 2) a very significant increase in long-chain Cer C24:1 accompanied by significant decreases in Cer C24:0 and C22:0 in MHC and SM at 3 days; and 3) a significant increase of C22:0 in all classes of SPL (Cer, MHC and SM) as well as a decrease in Cer C24:1, MHC C24:1 and MHC C24:0 at 7 days.ConclusionsAlterations in sphingolipid metabolite composition, particularly sphingomyelinases and short-chain ceramides, may contribute to the induction and regulation of neuroinflammatory events in the early stages of TBI, suggesting potential targets for novel diagnostic, prognostic, and therapeutic strategies in the future.

Sill et al.

Alzheimer's disease (AD) is one of the significant neurocognitive disorders, generally occurring among older population that progressively worsens with time initially showing symptoms of mild cognitive impairment (M C I). People suffering from AD usually lose their thinking skills and eventually fail to manage their daily routine tasks because of decline in successive memory functions. There exist well-documented evidences suggesting constant deterioration of communication among anatomical regions of the brain in individuals with Alzheimer's disease (AD) and mild cognitive impairment (M C I). Recent studies also exhibit the differences in topological properties of brain network between the individual patients suffering from AD and MC I compared to healthy controls (HC). In this work, we propose a novel hybrid model NeuroANATOP by employing both the anatomical and the topological properties of a brain network to capture the structural and/or topological changes occurring in networks during the progression from H C to MC I and H C to AD. Given a brain atlas, the Euclidean distance between two regions of interest (ROIs) in the brain is regarded as a measure of anatomical distance, quantifying an anatomical property. On the other hand, the topological similarity, quantifying a topological property, is defined by taking the cosine distance between nodes after embedding the whole real brain network into a d-dimensional vector space. Empirical results over real-brain network data suggest that the proposed hybridization successfully models the topological differences observed across the transition from HC to MCI and HC to AD.