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Gallbladder cancer (GBC) is one of the quiet prevalent and aggressive biliary tract malignant neoplasms distinguished by significant cellular heterogeneity, metastatic activity, and a poor prognosis, with varied frequency worldwide. Most cases are detected incidentally while routine screening imaging or pathological investigation of cholecystectomy tissues and usually present with advanced disease. The surgical resection is usually done in the initial clinical stage having limited spread. Despite the surgical therapy, the death rate is significant. Furthermore, the molecular mechanisms affecting the clinical course of inflammatory gallbladder to carcinogenesis remain poorly understood. There is an impending need for developing diagnostic biomarkers and targeted approaches for GBC. The newer molecular platform, such as next-generation sequencing (NGS), such as RNA-sequencing (RNAseq), single-cell sequencing, and microarray technology, has revolutionized the field of genomics, opened a new perspective in defining genetic and epigenetic characteristics identifying molecules as possible therapeutic targets. Therefore, in this review, we would analyze transcriptomic and epigenomics profiles of GBC using already published high-throughput sequencing-based studies published between 2010 and 2023. The review would also analyze the possible impact of the technological advancement on the patient management strategy and overall survival. This may also help identify target genes and pathways linked to GBC, which may help establish molecular biomarkers, for early GBC diagnosis, personalized therapy, and management. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is one of the quiet prevalent and aggressive biliary tract malignant neoplasms distinguished by significant cellular heterogeneity, metastatic activity, and a poor prognosis, with varied frequency worldwide. Most cases are detected incidentally while routine screening imaging or pathological investigation of cholecystectomy tissues and usually present with advanced disease. The surgical resection is usually done in the initial clinical stage having limited spread. Despite the surgical therapy, the death rate is significant. Furthermore, the molecular mechanisms affecting the clinical course of inflammatory gallbladder to carcinogenesis remain poorly understood. There is an impending need for developing diagnostic biomarkers and targeted approaches for GBC. The newer molecular platform, such as next-generation sequencing (NGS), such as RNA-sequencing (RNAseq), single-cell sequencing, and microarray technology, has revolutionized the field of genomics, opened a new perspective in defining genetic and epigenetic characteristics identifying molecules as possible therapeutic targets. Therefore, in this review, we would analyze transcriptomic and epigenomics profiles of GBC using already published high-throughput sequencing-based studies published between 2010 and 2023. The review would also analyze the possible impact of the technological advancement on the patient management strategy and overall survival. This may also help identify target genes and pathways linked to GBC, which may help establish molecular biomarkers, for early GBC diagnosis, personalized therapy, and management. [ABSTRACT FROM AUTHOR]

Introduction: The treatment approach for recently diagnosed advanced non-small cell lung cancer (NSCLC) with EGFR mutations primarily relies on confirming the tissue diagnosis as non-squamous NSCLC. This routine clinical practice of tissue diagnosis imposes several barriers and delays in turnaround time (TAT) for biomarker testing, significantly delaying the time to treatment. The objective of this study is to investigate the ‘plasma first’ approach for detection of EGFR mutation in advanced stage treatment naïve NSCLC patients. Methods: We prospectively collected blood samples of treatment naïve patients with clinical and radiological suspicion of advanced stage NSCLC prior to obtaining tissue biopsy. Plasma cfDNA was tested for EGFR mutation using two different methods. We compared the sensitivity and TAT of liquid biopsy with tissue biopsy. Results: In total, we analyzed plasma cell-free DNA (cfDNA) of 236 patients suspected of having advanced NSCLC for EGFR mutations. We observed a notably shorter turnaround time (TAT) of 3 days, which was significantly quicker compared to the 12-day TAT for tissue biopsy (p < 0.05). The ddPCR method had a sensitivity of 82.8%, which was higher than 66.34% sensitivity of ARMS-PCR. The current study also highlights that there is no significant difference in the clinical outcome of the patients whether treated based on liquid biopsy only or tissue biopsy (median progression-free survival of 11.56 vs. 11.9 months; p = 0.94). Conclusions: Utilizing a ‘plasma first’ strategy, given its shorter turnaround time, strong positive concordance and comparable outcomes to tissue biopsy, emerges as a highly specific and reliable method for detecting EGFR mutations in advanced-stage NSCLC. [ABSTRACT FROM AUTHOR]

Fibromatosis form a spectrum of clinicopathologic entities characterized by the infiltrative proliferation of fibroblasts that lack malignant cytologic features. The fibromatosis can be localized or infiltrative and multicentric and can involve internal tissues and organs as the mesentery, retroperitoneum, breast, and almost every organ and region of the body, including the bones, the meninges and the central nervous system. We report a case of 37-year-old male who presented with a right supraclavicular mass with superficial infiltrative type of fibromatosis and fine needle aspiration cytology (FNAC) was performed. We report this case because of limited literature of FNAC in fibromatosis and quick role of FNAC in the diagnosis of fibromatosis. [ABSTRACT FROM AUTHOR]

Introduction: Thrombopoietin (TPO) is a protein that is encoded by the TPO gene. It regulates the production of platelets. It is believed that plasma level of TPO is regulated by its binding to platelets and megakaryocytes. Material & Method: A prospective study was conducted comprising of 72 cases (32 female, 40 male) of gastrointestinal cancer, which were undergone surgery in the year 2016. It included cancer of esophagus, stomach, colon and anorectum. Three serial whole blood samples were taken from single patient, one preoperatively, 2nd & 3rd postoperatively on day 3 & day 5. Serum samples were stored at-80C. Samples were tested for TPO and PCT by ELISA Technique. Statistical analysis was done. Result: Day 3 after surgery, patients (n = 72) showed a significant thrombocytopaenia followed by a reactive thrombocytosis on Day 5. Platelet recovery was preceded by a significant rise in TPO (from 162.4 +/- 118.8 pg/ml at baseline to 355.3 +/- 304.4pg/ml at 72 h, P. [ABSTRACT FROM AUTHOR]

Introduction: Presence of megakaryocytes (MGK) in peripheral blood smear (PBS) is a rare condition. This may be seen in myelodysplastic syndrome. I am presenting a case of CML with lymphoid blast crisis showing MGK in PBS, probably first case report of this kind. Method: The case was picked for study while reporting peripheral blood film Short Clinical History: A sixty year old female presented with generalised weakness for four months, low grade fever for two months and history of weight loss for two months. Pallor, mild hepatosplenomegaly and left cervical lymphadenopathy were present. Hemogram showed Total leukocyte count 15 x 109 /L, Differential count; Blasts 85, Neutrophil 15, Hemoglobin 8.7 gm % and platelet count 170 x 109/L. Peripheral blood smear showed a well formed large megakaryocyte. Bone marrow aspirate smear examination showed 80% blasts in diluted marrow. Bone marrow biopsy showed hypercellular marrow with near total replacement by blasts CD34+ and CD3-, CD20- & CD138-. Flowcytometry revealed 51% blasts positive for CD19, CD34, CD10, HLA-DR, dim positive for cCD79a & TdT and negative for CD45, CD20, CD38, CD33, CD13, CD117, CD64, CD3, CD4, CD5, CD7, CD8 & MPO. Diagnosis of ALL was given. On frequent routine haemogram, the value of platelet count was noticed always higher side (> 200 x 109/L). This raised suspicion of any other associated disease. Result: Cytogenetic study revealed chromosome XY, t (9, 22). RTPCR showed P210 positive. Finally the diagnosis chronic myeloid leukemia with blast crisis was considered. Close differential is Ph+ ALL. Conclusion: (1). MGK in PBS may be a presentation of CML. (2). Blast crisis may be the first presentation of CML. (3). Flowcytometer may not be useful in diagnosis of CML with blast crisis. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. Methods: This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. Results: In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. Conclusions: The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC. [ABSTRACT FROM AUTHOR]

The article discusses the scientific contributions of Doctor A. P. J. Abdul Kalam and explores his views regarding the impact of science to the population.

Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. Data will be made available on request. [Display omitted] • Natural products destroy leukemia cells by inhibiting proliferation, inducing cell cycle arrest, and apoptosis. • Natural products might be used as a promising chemotherapeutic and chemopreventive agents. • Natural products played an essential role in drug development for therapeutic interventions especially in leukemia. • Natural products emerged as a viable option for treating leukemia due to their affordability, safety, and less side effects. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. Methods: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. Results: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. Conclusion: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration. [ABSTRACT FROM AUTHOR]

Chronic inflammation in the gallbladder leading to persistent epithelium damage promotes invasive cancer. The study aimed to assess the prognostic value of PDL1 and CA19-9 markers in cancer/inflammatory lesions of the gallbladder. A total of 29 cases (19 cancer and 10 inflammatory) were included. The PDL1 protein concentration level and mRNA expression were assessed in the tissues' lysates by ELISA and real-time PCR, respectively. PDL1 and CA19-9 concentration levels were compared and statistically related with clinico-pathological variables. The PDL1 protein level and its relative mRNA expression were correlated. Kaplan–Meir survival and Cox regression analyses were conducted for predicting prognosis. This study investigated the PDL1 and CA19-9 marker expression in both cancer and inflammatory cases of the gallbladder (p = 0.48 and p = 0.17 respectively). PDL1 protein expression was significantly associated with the hormonal profile of the cases (p = 0.04) at an optimum cut-off value of 13 pg/mL, while the CA19-9 marker expression was correlated with the status of liver metastasis (p = 0.0043) and size of the tumor (p = 0.004). A low PDL1 concentration was found when compared to the CA19-9 level among cancer cases (p = 0.12) and proportional in the inflammatory lesions (p = 0.63). A significant positive correlation was found between the PDL1 protein and its relative mRNA expressions in the inflammatory lesions (p = 0.029) when compared to cancer cases (p = 0.069). Our results showed that a protein-based assay for PDL1 expression would be more sensitive compared to RNA based assays for GBC risk stratifications. Overall survival was predicted with CA19-9 and PDL1 levels (p = 0.0074, p = 0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases. [ABSTRACT FROM AUTHOR]

Almost half of the patients with Langerhans cell histiocytosis (LCH) are refractory to primary induction chemotherapy or undergo reactivation. The ideal treatment modality for refractory/relapsed LCH is yet not evidenced. This review aimed to determine the efficacy and safety of vemurafenib (a BRAF pathway inhibitor) in LCH, particularly the refractory/relapsed cases. The literature search was conducted using PubMed, Embase, CENTRAL, and abstracts published in the SIOP meetings. Studies that described the outcome of patients of LCH being treated with vemurafenib, alone or in combination, were included. A total of 416 studies were screened, and after applying exclusion criteria, 22 studies (n = 107) were included in the final analysis. The first-line therapy was prednisolone plus vinblastine for most patients (n = 92, 86%), and vemurafenib was started upfront in 3 patients (3%). The median time to first clinical response with vemurafenib was one week. The median time to best response was 5.25 months. Out of 107 patients, 62 patients (58%) had ultimately no active disease (NAD) while 39 (36%) had active disease better (ADB), making the overall response rate (ORR) of 101/107, ie, 94.4% (CI 0.88; 0.98). The main adverse effects of vemurafenib were rash or photosensitivity (47%) and other cutaneous adverse events (15%). Vemurafenib is highly efficacious and safe in the treatment of refractory LCH; however, the timing of its commencement and duration of therapy is yet to be established. Larger prospective collaborative trials are needed to answer the appropriate treatment duration and effective maintenance therapy approach. [ABSTRACT FROM AUTHOR]

The persistent infection of high-risk Human papillomavirus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications.This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics. [ABSTRACT FROM AUTHOR]

The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 57-year-old male with synchronous metastatic pulmonary adenocarcinoma with small cell lymphoma discovered on a bone marrow examination. 18F-fluorodeoxyglucose positron emission tomography/computer tomography (F-FDG PET/CT) of his whole-body was performed. The article discusses adenocarcinoma of the lung metastatic to bone marrow that harbors B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Abstract Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients which is associated with a variegated patient outcome. Multiple molecular markers have been used to risk-stratify these patients. Estimation of expression of BAALC gene (Brain and Acute Leukemia, Cytoplasmic) mRNA level is one of the predictive markers which has been identified in multiple studies. In this study, we examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. We also utilized multi-omics databases to ascertain the association of BAALC gene expression with comprehensive molecular and clinicopathologic features in AML. BAALC overexpression was associated with CD34 positivity on leukemic blasts (p = 0.0026) and the absence of NPM1 gene mutation (p < 0.0001), presence of RUNX1 gene mutation (p < 0.001) and poor patient outcomes, particularly in NPM1 –wild type/FLT3-ITD negative adult CN-AML patients. Additionally, BAALC expression was associated with the alteration of methylation of its promoter. Further, pathway analysis revealed that BAALC expression is correlated with MYC targets and Ras signalling. We conclude that high BAALC expression associates with poor patient outcome in NPM1 –wild type/FLT3-ITD negative adult CN-AML patients. • CN-AML is the largest group of AML patients which is associated with a variegated patient outcome. • We examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. • Multi-omics data was used to determine the association of BAALC expression with clinical and molecular attributes in AML. • High BAALC expression was associated with poor patient outcome in NPM1 –wild type /FLT3-ITD negative adult CN-AML patients. • Associated distinct gene expression profiles can help in the identification of novel therapeutic agents in AML. [ABSTRACT FROM AUTHOR]

Isolated bone marrow metastasis of testicular tumor is very rare. Here, we report this case of a 21-year-old male who was admitted to our hospital with generalized body pain, which was severe and weakness for one month. He had a history of an operative intervention for the left testicular mass about 6 months ago which was diagnosed as mixed germ cell tumor on histopathological examination. The blood investigations showed anemia, low platelets, and elevated tumor markers. Bone marrow aspiration and biopsy examination showed metastatic deposits of mixed germ cell tumor. There were no foci of disease in any other part of the body. The patient was given chemotherapy, i.e. cisplatin, etoposide, and bleomycin. After completion of chemotherapy, there was drastic improvement in pain and weakness. A repeat examination of bone marrow done after 3 month was free of tumor. [ABSTRACT FROM AUTHOR]

Spread of squamous cell carcinoma (SCC) commonly occurs vialocal lymphatic channels. Owing to scanty lymphatic drainage and vascular supply, SCC arising from the glottis rarely metastasizes. A 39-year-old male, operated for SCC of the glottis, presented 13 months later with complaints of headache. Computed tomography revealed a single ring-enhancing lesion in the right temporo-parietal region of the brain, suggestive of brain abscess. However, histopathological examination of the excised brain lesion showed metastasis of moderately differentiated SCC. Here, we report a rarecase of distant hematogenous brain metastasis of SCC of the glottis. [ABSTRACT FROM AUTHOR]

• Prolong infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is due to its fast mutating ability. • In this scenario, the computational methods have immense potential to explore and discover the more specific inhibitor. • Molecular dynamics simulation and protein-protein interaction studies showed that mutant strains of SARS-CoV2 formed stable protein structures with altered binding affinities to host protein. • Hence, the present study provides the molecular evidence of this endless pandemic which would help in designing a more specific inhibitor. Remarkable infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is due to the rapid emergence of various strains which enable the virus to ruling the world. Over the course of SARS-CoV2 pandemic, the scientific communities worldwide are responding to newly emerging genetic variants. However, mechanism behind the persistent infection of these variants is still not known due to the paucity of study of these variants at molecular level. In this scenario, computational methods have immense utility in understanding the molecular and functional properties of different variants. The various mutants (MTs) of SpikeS1 receptor binding domain (RBD) of highly infectious SARS-CoV2 strains were manifested and elucidated the protein structure and binding strength using molecular dynamics (MD) simulation and protein-protein docking approaches. MD simulation study showed that all MTs exhibited stable structures with altered functional properties. Furthermore, the binding strength of different MTs along with WT (wildtype) was revealed that MTs showed differential binding affinities to host protein with high binding strength exhibited by V367F and V483A MTs. Hence, this study shed light on the molecular basis of infection caused by different variants of SARS-CoV2, which might play an important role in to cease the transmission and pathogenesis of virus and also implicate in rational designing of a specific drug. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer prevalence is a major challenge worldwide due to the lack of early diagnostics and treatment modalities. In this era of technological advancements, researchers are exploring several grey areas in breast cancer research, which may lead to the appropriate point of care, non-invasive and diagnostic aid for early breast cancer detection and management. Exosome-based research, an emerging area, endeavors to locate and elucidate the role of exosomes in breast cancer diagnostics, immune response and clinical outcomes. This review may provide insights on small extracellular vesicles research and their role in breast cancer. Future extensive studies on exosome biology in conjunction with cancer genetics shall undoubtedly open up new vistas in exosome-based diagnostics for early cancer detection and therapeutics. Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies. [ABSTRACT FROM AUTHOR]

The treatment of pediatric acute lymphoblastic leukemias (ALL) has seen remarkable advances recently. However, relapse occurs in approximately 20% of cases which necessitates identifying additional high risk parameters for treatment intensification. The aim of this study is to assess the prognostic significance of CD45 antigen expression in pediatric ALL. We studied 363 pediatric patients with B cell precursor-ALL (BCP-ALL) (n = 313) and T-ALL (n = 50). The ratio of median fluorescence intensity of CD45 expressed in leukemic blasts and normal lymphocytes was calculated. The 75th percentile was taken as cut-off to categorise patients into CD45 high and CD45 low groups. The 75th percentile was 0.141 in BCP-ALL and 0.548 in T-ALL. In BCP-ALL, there was a statistically significant association of age (≥10 years) (p = 0.027) and National Cancer Institute high risk group (p = 0.001) with high CD45 expression but not in T-ALL. Worse event-free survival (EFS) was seen with high CD45 expression in BCP-ALL (42.17% versus 60.83%, p = 0.0053). In T-ALL, there was no association between CD45 expression and EFS (CD45 high 40.40% versus low 67.35%, p = 0.414). The overall survival (OS) was 70% versus 60% (p = 0.38) in BCP-ALL and the OS was 82% versus 68% (p = 0.16) in T-ALL for CD45 low versus CD45 high groups, respectively. We conclude that high CD45 surface expression is associated with worse EFS in pediatric BCP-ALL. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the Chronic Neutrophilic leukemia (CNL) that is uncommon type of chronic myeloproliferative disorder (CMPD).

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of the newly diagnosed adult non-Hodgkin lymphomas, but rarely presents in leukaemic phase. Here in, we report a case of DLBCL presenting in leukaemic phase and masquerading as acute leukaemia. A 28-year-old woman presented to our outpatient department with complaints of fever for 1 week. Her peripheral blood smear showed 5% to 8% blasts. Bone marrow aspirate showed an infiltration by ~30% blasts. Flow cytometry and immunohistochemistry confirmed relapse of DLBCL. Also, patient's poor response to therapeutic regimen for DLBCL prompted to consider second differential diagnosis of acute leukaemia. This case is a learning case, as it emphasizes the combined role of diagnostic ancillary techniques along with clinical judgments for management. The case also makes us more vigilant towards the pathobiology of DLBCL and dynamics of personalized individual treatment response. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of the newly diagnosed adult non-Hodgkin lymphomas, but rarely presents in leukaemic phase. Here in, we report a case of DLBCL presenting in leukaemic phase and masquerading as acute leukaemia. A 28-year-old woman presented to our outpatient department with complaints of fever for 1 week. Her peripheral blood smear showed 5% to 8% blasts. Bone marrow aspirate showed an infiltration by ~30% blasts. Flow cytometry and immunohistochemistry confirmed relapse of DLBCL. Also, patient's poor response to therapeutic regimen for DLBCL prompted to consider second differential diagnosis of acute leukaemia. This case is a learning case, as it emphasizes the combined role of diagnostic ancillary techniques along with clinical judgments for management. The case also makes us more vigilant towards the pathobiology of DLBCL and dynamics of personalized individual treatment response. [ABSTRACT FROM AUTHOR]

Myeloid sarcomas (MS) are the extramedullary presentation of acute myeloid leukemias. At times, they are difficult to diagnose due to lack of any supportive findings in peripheral blood/bone marrow aspirate examination. The involvement of gastrointestinal tract (GIT) by myeloid sarcoma is rare phenomenon. This diagnostic challenge becomes more complex when it is added by vague clinical symptoms. Many times, they have been misdiagnosed as Non-Hodgkin's lymphoma, small round cell tumour or carcinoma. Here, we are reporting a case of myeloid sarcoma with no haematological abnormality which presented with the symptoms of bowel obstruction and a rare combination of inv. (16) and trisomy 22. The journey to reach the conclusive diagnosis in this case is interesting and sensitizes us to have high index of suspicion in a case, where there is paucity of clinical evidences. [ABSTRACT FROM AUTHOR]