Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia

Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM). The necroptotic (RIPK1) and the apoptotic (caspase-8/3) markers were downregulated by CM, whereas the inhibitory effects of chemotherapy on the autophagy marker Beclin-1 (BECN1) were reduced suggesting CM exerts cytoprotective effects. GCs upregulated the RIPK1 ubiquitinating factor BIRC3 (cIAP2), in GC-sensitive (CEM-C7-14) but not in resistant (CEM-C1-15) cells. In addition, CM selectively affected GR phosphorylation in a site and cell-specific manner. GR is recruited to RIPK1, BECN1 and BIRC3 promoters in the sensitive but not in the resistant cells with phosphorylated GR forms being generally less recruited in the presence of hormone. FACS analysis and caspase-8 assays demonstrated that CM promoted a pro-survival trend. High molecular weight proteins reacting with the RIPK1 antibody were modified upon incubation with the BIRC3 inhibitor AT406 in CEM-C7-14 cells suggesting that they represent ubiquitinated forms of RIPK1. Our data suggest that there is a correlation between microenvironment-induced ALL proliferation and altered response to chemotherapy

Rudimentary Meningocele of the Scalp: A Pitfall in the Diagnosis of Vascular Neoplasms

We present a case of sequestrated meningocele in a 1-year-old girl, who presented with a 1x1cm occipital swelling since birth. CT brain revealed the soft tissue swelling to be extracranial. She underwent surgical excision of the specimen and the excised mass was sent for histopathological examination. The specimen consisted of skin and subcutaneous tissue measuring 2 x 1 x 1 cm. The entire tissue was paraffin processed. Multiple sections studied from the lesion showed an ill circumscribed locally infiltrative dermal lesion. The lesion was composed of whorled proliferations of meningothelial cells enclosing pseudovascular spaces. Immunohistochemically the lesion was positive for EMA, Desmin, and negative for endothelial markers. The present case was documented as a rare case of a rudimentary meningocele

Excision of Mucocele Using Diode Laser in Lower Lip

Mucoceles are nonneoplastic cystic lesions of major and minor salivary glands which result from the accumulation of mucus. These lesions are most commonly seen in children. Though usually these lesions can be treated by local surgical excision, in our case, to avoid intraoperative surgical complications like bleeding and edema and to enable better healing, excision was done using a diode laser in the wavelength of 940 nm

Correlation between Immunohistochemical and Histomorphological Features of Ampullary Carcinomas: A Study on 72 Cases from a Tertiary Health Care Center

Tumors involving the ampulla could be arising primarily in the ampulla or extending from the adjacent. When a neoplasm is centered primarily in the ampulla with or without periampullary mucosal involvement, it is considered a primary ampullary carcinoma. These tumors generally have a better prognosis than duodenal and pancreaticobiliary neoplasms secondarily involving the ampulla. Distinguishing between the two primary types has prognostic implications, as the pancreaticobiliary-type ampullary carcinomas are said to have a poorer prognosis than the intestinal-type. Morphological analysis alone may not suffice in this context. The role of immunohistochemistry has therefore been explored by various groups of workers. The purpose of the present study was to determine the role of morphology and cytokeratin profile in accurate typing of ampullary carcinomas as intestinal and pancreaticobiliary

Adamantinoma-Like Ewing’s Family Tumor of the Sino Nasal Region: A Case Report and a Brief Review of Literature

Ewing's sarcoma family of tumors (EFTs) are malignant mesenchymal tumors with a predilection for bone and soft tissue. They are characterized by their monomorphic small blue round cell morphology. However rare morphologic variants of EFTs can also show overt epithelial differentiation in the form of squamoid differentiation along with strong cytokeratin expression. This particular subset of EFTs are known as adamantinoma-like EFTs which can be difficult to differentiate from epithelial head and neck malignancies. Here we report a case of sinonasal adamantinoma-like EFT in an 18-year-old male patient. The lesion differed from a typical EFT by means of overt squamoid differentiation which showed a basaloid appearance with peripheral palisading. The immunohistochemistry was positive for pan-cytokeratin, p40, p63, ERG, FLI1, and CK5/6. It was negative for actin, desmin, and WT-1. Initial diagnosis of a basaloid squamous cell carcinoma was made. Further molecular studies were also done due to the complex presentation of the tumor. EWSR testing with break-apart analysis confirmed EWSR1 and FLI1 rearrangements. Further confirmation was done with RT-PCR. The case was found to be positive for EWS-FLI-1 translocation. The revised immunohistochemistry panel showed CD99, ERG, FLI1, and synaptophysin positivity. The lesion was reclassified as an adamantinoma-like ES. Our case reinforces the fact that a subset of EFTs can show histomorphologic and immunohistochemical features of aberrant epithelial differentiation. These cases are difficult to differentiate from usual epithelial malignancies which occur in this region. This diagnostic pitfall can be avoided by the inclusion of CD99 and/or FLI1 in the immunohistochemical assessment of any round cell malignancy at any anatomic location. A strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements

Localized orbital amyloidosis – A varied presentation

Localized orbital amyloidosis is rare, usually slowly progressive and benign disorder. The most common signs and symptoms include visible periocular mass, ptosis, proptosis, globe displacement, ocular motility disturbances, recurrent periocular subcutaneous hemorrhages, and dry eyes. Herein, we report a case of localized recurrent orbital amyloidosis with strabismus, restricted eye movement, ptosis, and orbital mass as the presentation in a 60-year-old female and managed with debulking and strabismus surgery, resulting in a good cosmetic and functional outcome

The value of systematic pattern analysis in FNAC of breast lesions: 225 cases with cytohistological correlation

Background : Fine needle aspiration cytology (FNAC) has a high rating in the assessment of breast lesions. Various methods have been used to diagnose cytology of breast lesions. Aims : Present study was undertaken to evaluate the feasibility of application of systematic pattern analysis based on morphology in diagnosing breast aspirates. Materials and Methods : This is a retrospective study of FNAC of the breast done over a period of 4 years in a tertiary care centre. A total of 225 cases of breast lesions for which FNAC was done with histological follow-up were included in the study. Breast aspirates were provisionally diagnosed based on systematic pattern analysis. Aspirates were grouped into six categories based on predominant cellular pattern, and correlation between cytological and histological diagnosis was assessed. Results : Application of pattern analysis on FNAC of breast lesions in our study had a sensitivity of 94.5%, specificity of 98%, diagnostic accuracy of 97%, positive predictive value of 95.8%, and negative predictive value of 97.4%. Conclusions : Systematic pattern analysis based on morphology of FNAC smears was found to be highly reliable and could be easily reproducible in the assessment of breast masses

Association between Tumor Prognosis Marker Visfatin and Proinflammatory Cytokines in Hypertensive Patients

Visfatin has been reported as a risk factor and a potential diagnostic marker in cancer. It is an adipokine, secreted by visceral fat and associated with the pathogenesis of arterial hypertension. We investigated the circulatory levels of visfatin in hypertensive patients with hypertriglyceridemia, which are the risk factors for various cancers and its association with proinflammatory cytokines. A total of 81 (male/female: 33/48) subjects with or without hypertension were enrolled for this study. Group 1 was normotensive, Group 2 hypertensive, and Group 3 with hypertension with hypertriglyceridemia. Data on anthropometric and biochemical data were recorded. Plasma visfatin levels were measured using an ELISA kit. The plasma inflammatory cytokines were estimated using a multiplex bead-based assay. The results revealed that the hypertension with hypertriglyceridemia group has the highest levels of visfatin compared to the hypertension and control groups with a significant difference (p<0.001). Besides, circulatory visfatin showed the strongest possible correlation with proinflammatory cytokines among hypertensive patients with hypertriglyceridemia. We found a positive correlation between visfatin and diastolic blood pressure as well as high-density lipoproteins. In conclusion, the outcomes of the present study demonstrate that plasma visfatin levels were found to be elevated in hypertensive patients with hypertriglyceridemia and associated with proinflammatory cytokines. Since hypertension has been documented as the most common comorbidity observed in cancer patients, visfatin may be a novel potential therapeutic target for hypertension in cancer patients and survivors

A holistic review of the present and future drivers of the renewable energy mix in Maharashtra, State of India

Das, NK ORCiD: 0000-0002-3396-4194A strong energy mix of Renewable Energy Sources (RESs) is needed for sustainable development in the electricity sector. India stands as one of the fastest developing countries in terms of RES production. In this framework, the main objective of this review is to critically scrutinize the Maharashtra state energy landscape to discover the gaps, barriers, and challenges therein and to provide recommendations and suggestions for attaining the RES target by 2022. This work begins with a discussion about the RES trends in various developing countries. Subsequently, it scrutinizes the installed capacity of India, reporting that Maharashtra state holds a considerable stake in the Indian energy mix. A further examination of the state energy mix is carried out by comparing the current and future targets of the state action plan. It is found that the installed capacity of RESs accounts for about 22% of the state energy mix. Moreover, the current installed capacity trend is markedly different from the goals set out in the action plan of the state. Notably, the installed capacity of solar energy is four times less than the target for 2020. Importantly, meeting the targeted RES capacity for 2022 presents a great challenge to the state. Considering this, an analysis of the state’s strengths, barriers, and challenges is presented. Moreover, strong suggestions and recommendations are provided to clear the track to reach the desired destination. This can be useful for the government agencies, research community, private investors, policymakers, and stakeholders involved in building a sustainable energy system for the future.</jats:p