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2.
Gene ; 711: 143952, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31265880

RESUMO

Ets-1 is one of the crucial member of transcription factor family which share a unique DNA binding domain. It is predominantly expressed in various tumor subtypes and has shown its association in the regulation of various important genes which include ECM-degrading proteases. Our study aimed to understand the mechanism(s) in the pathogenesis of breast carcinogenesis by Ets-1 transcription factor and its downstream target gene MMP-9. Role of Ets-1 in MCF-7 and MDA-MB-231 breast cancer cells was studied by RNA-interference in combination with pull down and ChIP assays to identify the regulation of MMP-9 in these cell lines. Our results showed that transfection of Ets-1 siRNA in breast cancer cell lines resulted in downregulation of Ets-1 and MMP-9. Ets-1 knock down also showed reduced cell invasion and altered expression of EMT markers. Moreover, we could also predict that MMP-9 gene promoter harbors a binding site for Ets-1 transcription factor may be responsible in direct transactivation of Ets-1 along with EMT markers. Phenotypic changes and molecular alterations that may result in increased aggressiveness/invasiveness and metastatic nature of cancerous cells may lead to changes in EMT markers. Therefore, these findings may suggest a plausible role of Ets-1 dependent regulation of MMP-9 gene and may have a significant impact on breast carcinogenesis.


Assuntos
Neoplasias da Mama/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteína Proto-Oncogênica c-ets-1/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Invasividade Neoplásica , Regiões Promotoras Genéticas , Proteína Proto-Oncogênica c-ets-1/genética
3.
J Cell Biochem ; 120(9): 14213-14225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31037763

RESUMO

Cancer is a disease that claims millions of lives each year across the world. Despite advancement in technologies and therapeutics for treating the disease, these modes are often found to turn ineffective during the course of treatment. The resistance against drugs in cancer patients stems from multiple factors, which constitute genetic heterogeneity like gene mutations, tumor microenvironment, exosomes, miRNAs, high rate of drug efflux from cells, and so on. This review attempts to collate all such known and reported factors that influence cancer drug resistance and may help researchers with information that might be useful in developing better therapeutics in near future to enable better management of several cancers across the world.

4.
J Cell Biochem ; 120(9): 14552-14561, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31016780

RESUMO

Breast cancer is a highly aggressive disease contributing to high mortality rate among females across the globe owing to wide geographical variations, change in lifestyle along with rapid tumor growth, drug resistance, and high metastasis rate. To understand the molecular and genetic basis of breast cancer progression; we studied the role of E26 transformation-specific-1 (Ets-1) transcription factor which is implicated to have a role in carcinogenesis like invasion, metastasis, angiogenesis, etc. Our findings revealed an overexpression of Ets-1 gene in 75 breast cancer tumors as compared with their normal adjacent tissues. The findings significantly established a co-relation between Ets-1 expression in breast cancer tissue with hormonal receptor profiles and ductal-lobular histological subtypes in Indian population. In addition, a differential expression pattern of Ets-1 was observed between high, moderate, and low grades of breast cancer patients. The present study demonstrates a crucial role of Ets-1 transcription factor which may serve as a potential biomarker for breast carcinogenesis.

5.
Gulf J Oncolog ; 1(29): 72-75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30956198

RESUMO

Human papilloma virus (HPV) associated cancers represents a special subgroup of cancers which are potential targets of screening strategy to reduce the burden of HPV-associated cancers. The viruses have different molecular pathways which ultimately lead to the immortalization of cells. The unique pathobiology and detailed discovery of molecular signaling pathways have paved the new dimensions and advancements in both early detection and development of newer treatment strategy in terms sensitivity towards radiotherapy in HPVinduced cancers versus others. Their clinical behavior suggests good prognosis when compared to Non-HPV positive group cancers. The better prognosis between HPV positive and Non-HPV positive cancer demands a timely diagnosis of HPV status to stratify high risk cases to promote personalized management.


Assuntos
Neoplasias/patologia , Papillomaviridae/patogenicidade , Feminino , Humanos , Prognóstico
7.
Mutat Res ; 778: 61-71, 2018 Oct - Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30454684

RESUMO

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.

8.
BMJ Case Rep ; 20182018 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-30249738

RESUMO

A 35-year-old man presented with a history of cough, haemoptysis, weight loss for 2 months along with ulceroproliferative lesions on the chin and the scalp. On evaluation he was found to have non-seminomatous germ cell tumour, stage 3 c, poor risk with Eastern Cooperative Oncology Group Performance Status of 4. The skin lesions were proven to be metastasis by fine-needle aspiration cytology. He showed significant improvement with a 3-day protocol of abbreviated etoposide and cisplatin chemotherapy and is planned for 4 cycles of VIP. This case describes an uncommon presentation of germ cell tumour in the form of skin metastasis with excellent response to chemotherapy.

10.
Mol Carcinog ; 57(11): 1664-1671, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30035346

RESUMO

Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non-malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low-Dose Radiation (LDR)-primed and M1-retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer-related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR-primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down-modulating HIF-1 in irradiated tumors in the course of polarization of irradiated tumor-associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine-1-phosphate/VEGF-induced angiogenic signaling in tumor-derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor-derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer-directed immunotherapy in particular.

11.
Intractable Rare Dis Res ; 6(3): 230-233, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28944149

RESUMO

A young adult man with 4-years history of lepromatous leprosy (received irregularly multidrug therapy) presented with two and half years history of symptoms suggestive of chronic erythema nodosum leprosum (ENL), initially responded to steroids and thalidomide, but later on failed. During the last 2-months, he developed fever, vomiting, and subsequently altered sensorium. On evaluation, he had hepatosplenomegaly, hyponatremia, hyperferritinemia, hemophagocytosis in bone marrow aspiration, lobular panniculitis in skin biopsy, and multiple parenchymal nodules in chest imaging. Hence diagnosis of ENL with hemophagocytic lymphohistiocytic (HLH) syndrome was established and treatment with dexamethasone (10 mg/m2) started. During hospitalization, he developed sinus bradycardia, QT prolongations, recurrent ventricular tachycardia, and moderate systolic dysfunction. The cardiac complications recovered using a temporary pacemaker and were presumed to be due to micronodular cardiac deposition of ENL. This case iterates that ENL can present with varied presentations like asymptomatic lung nodules and storming cardiac complications. More importantly leprosy, ENL, and HLH are a continuum of manifestations of the same agent-host interactions.

12.
Urol Ann ; 9(1): 96-98, 2017 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28216942

RESUMO

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.

13.
Front Oncol ; 7: 326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29376027

RESUMO

Breast cancer (BC) is the most common cancer diagnosed in women and the second most common cancer overall, ranking as the fifth cause of death from cancer. The chronicity of the disease produces long-term physiological and psychological manifestations, which adversely affect the quality of life of the individual. The primary treatment while managing cancer presents with various debilitating side effects. With the recent advances in treatment techniques that have improved the survival rate, patients suffer from continuing posttreatment complications. Patients seem to cope well with the stress of treatment of BC and sustain a normal life; however, the deterioration in physical well-being makes the patient functionally inefficient. Exercise has been proven to be an effective, safe, and feasible tool in combating the adverse effects of treatment, prevents complications and decreases the risk of BC-specific mortality. This review briefly presents an overview of the burden of the disease and its management strategies. Owing to the heterogeneity of the population and the multitude of therapies they receive, the response of each patient to treatment is different and so is the magnitude of adverse effects. The review discusses the late sequelae following treatment and evidence supporting the role of physical activity in their management. In conclusion, there is a need for personalized physical activity plans to be developed to suit the individual and their circumstances.

14.
J Clin Diagn Res ; 9(8): JA01, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26435968
15.
J Clin Diagn Res ; 8(7): FD09-10, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25177572

RESUMO

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.

17.
J Cytol ; 29(1): 66-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22438623

RESUMO

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.

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