Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38762689

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. PATIENTS AND METHODS: A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. RESULTS: The mean age of this study population was 55.47 ± 8.45 with range 28-87 years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50 years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50 years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. CONCLUSION: Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

2.
Indian J Pharmacol ; 54(5): 349-352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36537404

RESUMO

BACKGROUND: Imatinib mesylate is the cornerstone therapy in the management of chronic myeloid leukemia (CML). Monitoring of adverse drug reactions (ADRs) of imatinib in our patients is very important to ensure their safety. Aims and Objectives: The current study aims to monitor ADRs encountered in CML patients in the chronic phase with imatinib (400 mg/day). MATERIALS AND METHODS: This prospective, observational study was conducted from November 2011 to May 2015 on 310 patients presented to the Departments of Clinical Hematology and Pharmacology of SCB MCH, Cuttack, diagnosed with CML at chronic phase. Collected ADRs were entered in the ADR reporting form (PvPI) and were analyzed for causality and severity. RESULTS: Anemia was the most common hematological ADR, whereas hyperpigmentation and nausea were the most common nonhematological ADRs reported. Maximum ADRs were mild to moderate and required no change in the treatment course. CONCLUSION: The study revealed that imatinib mesylate, a well tolerated drug, has very few cases of severe ADRs in Indian patients at the chronic stable phase of CML.


Assuntos
Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/uso terapêutico , Antineoplásicos/efeitos adversos , Estudos Prospectivos , Pirimidinas/efeitos adversos , Piperazinas/efeitos adversos , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
3.
Cell Mol Life Sci ; 79(8): 414, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35816252

RESUMO

Helicobacter pylori-mediated gastric carcinogenesis involves upregulation of the E3 ubiquitin ligase Siah2 and its phosphorylation-mediated stabilization. This study elucidates a novel mechanism of oxidative stress regulation by phosphorylated Siah2 in H. pylori-infected gastric epithelial cancer cells (GECs). We identify that H. pylori-mediated Siah2 phosphorylation at the 6th serine residue (P-S6-Siah2) enhances proteasomal degradation of the 78-kDa glucose-regulated protein (GRP78) possessing antioxidant functions. S6 phosphorylation stabilizes Siah2 and P-S6-Siah2 potentiates H. pylori-mediated reactive oxygen species (ROS) generation. However, infected S6A phospho-null Siah2-expressing cells have decreased cellular GRP78 level as surprisingly these cells release GRP78 to a higher extent and accumulate significantly higher ROS than the wild type (WT) Siah2 construct-expressing cells. Ectopic expression of GRP78 prevents the loss of mitochondrial membrane potential and cellular ROS accumulation caused by H. pylori. H. pylori-induced mitochondrial damage and mitochondrial membrane potential loss are potentiated in Siah2-overexpressing cells but these effects are further enhanced in S6A-expressing cells. This study also confirms that while phosphorylation-mediated Siah2 stabilization optimally upregulates aggresome accumulation, it suppresses autophagosome formation, thus decreasing the dependency on the latter mechanism in regulating cellular protein abundance. Disruption of the phospho-Siah2-mediated aggresome formation impairs proliferation of infected GECs. Thus, Siah2 phosphorylation has diagnostic and therapeutic significance in H. pylori-mediated gastric cancer (GC).


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Chaperona BiP do Retículo Endoplasmático , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/fisiologia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
4.
J Cytol ; 38(3): 145-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703091

RESUMO

INTRODUCTION: Gallbladder cancer (GBC) is the most common malignancy, representing 80-95% of biliary tract cancers. Although ultrasonography-guided fine-needle aspiration cytology (USG-FNAC) has emerged as an effective diagnostic the tool for the precise diagnosis of gallbladder lesions, data on its diagnostic utility and cytomorphological categorization of gallbladder lesions are lacking. AIMS: To study the diagnostic utility of USG-FNAC in gallbladder lesions. MATERIALS AND METHODS: This study was the conducted prospectively on patients who came with clinical and radiological evidence of gallbladder space-occupying lesion and then advised to USG-FNAC over 2 years and 6 months from January 2018 to June 2020. RESULTS: A total of 314 cases were included. The mean age was 56 years, with a range of 17-88 years. Women predominated over men (Male:Female = 1:2.3). Primary adenocarcinoma of the gallbladder was most common. On cyto-histological correlation, the sensitivity, specificity, and diagnostic accuracy of USG-FNAC of gallbladder lesions were found to be 98.82, 87.23, and 96.3%, respectively. CONCLUSION: The USG-FNAC of gallbladder lesion was found to be an easy, quick, cost-effective, and presumptive diagnostic procedure. It should be opted as an initial preoperative diagnostic modality in high incidence areas to avoid inappropriate management with unnecessary morbidity and cost. Moreover, a close cytological examination of the architectural pattern and the cytomorphological features would help in the sub-typing and prognosticating the tumor.

5.
Indian J Gastroenterol ; 40(4): 420-444, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34219211

RESUMO

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.


Assuntos
Antibacterianos/uso terapêutico , Gastroenterologia/normas , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Consenso , Resistência Microbiana a Medicamentos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Terapia de Salvação , Sociedades Médicas , Neoplasias Gástricas/microbiologia , Falha de Tratamento , Resultado do Tratamento
6.
J Biomed Sci ; 28(1): 12, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536006

RESUMO

BACKGROUND: Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression. METHODS: H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay. RESULTS: Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine6 (Ser6) and threonine279 (Thr279). Phosphorylation of Siah2 was mediated by MRCKß, a Ser/Thr protein kinase. MRCKß was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKß could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKß and use of proteasomal inhibitor MG132 could rescue MRCKß from Siah2-mediated degradation. Ser6 and Thr279 phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells. CONCLUSIONS: Increased level of Ser6 and Thr279-phosphorylated-Siah2 and downregulated MRCKß were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKß-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.


Assuntos
Infecções por Helicobacter/genética , Helicobacter pylori/fisiologia , Miotonina Proteína Quinase/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligases/genética , Animais , Linhagem Celular , Infecções por Helicobacter/microbiologia , Helicobacter felis/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Miotonina Proteína Quinase/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/microbiologia , Ubiquitina-Proteína Ligases/metabolismo
7.
Biochem Biophys Res Commun ; 523(4): 916-923, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31959473

RESUMO

Stomach cancer is a difficult-to-treat disease. Lack of detection markers and limited understanding of the disease mechanisms contribute to the aggressive nature of stomach cancer cells (SCCs). Recently, an ATPase, ATAD2 has been found to be highly expressed in stomach cancer contributing to increased malignancy. However, nothing is known about the mechanism of ATAD2 upregulation and its involvement in stomach carcinogenesis. Since hypoxic microenvironment plays a crucial role in the progression of solid tumors like stomach cancer; we have examined the regulation and function of ATAD2 expression in hypoxic SCCs. ATAD2 is induced in hypoxia-treated SCCs. Stomach adenocarcinoma and metastatic tissues with high HIF1α level also show enhanced ATAD2 expression. In the absence of hypoxia-inducible factor HIF1α, ATAD2 protein level is found to be less indicating towards a potential correlation between them. We identify the presence of HIF1α-binding site (HBS) and HIF1α ancillary site (HAS) in the ATAD2 promoter. Using both in vitro and in vivo binding studies, we confirm that HIF1α binds with the ATAD2 promoter in hypoxic condition. ATAD2 upregulation promotes proliferation and migration of SCCs exposed to hypoxia. Thus, we identify ATAD2 as a hypoxia-responsive and HIF1α-regulated gene and elucidate that upregulated expression of ATAD2 enhances tumor-promoting functions in hypoxic SCCs. Therefore, we propose ATAD2 as a promising therapeutic target for stomach cancer.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regulação para Cima/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Ativação Transcricional/genética
8.
J Cancer Res Clin Oncol ; 146(1): 245-259, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31617074

RESUMO

PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors. CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκß pathway.


Assuntos
Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/irrigação sanguínea , Carcinoma Ductal de Mama/genética , Moléculas de Adesão Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
9.
Int J Biochem Cell Biol ; 103: 14-24, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30063986

RESUMO

Helicobacter pylori is the strongest known risk-factor for gastric cancer. However, its role in gastric cancer metastasis remains unclear. Previously we have reported that H. pylori promotes gastric cancer invasiveness by stabilizing the E3 ubiquitin ligase Siah2 which is mediated by Siah2 acetylation at Lys 139 (K139) residue. Here we identify that cell adhesion-related proteins testin (TES) and filamin-C (FLN-C) interact with Siah2 and get proteasomally degraded. The efficiency of TES and FLN-C degradation is significantly potentiated by K139-acetylated Siah2 (ac-K139 Siah2) in infected gastric cancer cells (GCCs). ac-Siah2-mediated downregulation of TES and FLN-C disrupts filopodia structures but promotes lamellipodia formation and enhances invasiveness and migration of infected GCCs. Since H. felis-infected mice as well as human gastric cancer biopsy samples also show high level of ac-K139 Siah2 and downregulated TES and FLN-C, we believe that acetylation of Siah2 is an important checkpoint that can be useful for therapeutic intervention.


Assuntos
Proteínas do Citoesqueleto/biossíntese , Regulação para Baixo , Filaminas/biossíntese , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Proteínas com Domínio LIM/biossíntese , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas , Ubiquitina-Proteína Ligases/metabolismo , Acetilação , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Invasividade Neoplásica , Proteínas de Ligação a RNA , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
10.
FASEB J ; 32(10): 5378-5389, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29688807

RESUMO

Gastric epithelial cells infected with Helicobacter pylori acquire highly invasive and metastatic characteristics. The seven in absentia homolog (Siah)2, an E3 ubiquitin ligase, is one of the major proteins that induces invasiveness of infected gastric epithelial cells. We find that p300-driven acetylation of Siah2 at lysine 139 residue stabilizes the molecule in infected cells, thereby substantially increasing its efficiency to degrade prolyl hydroxylase (PHD)3 in the gastric epithelium. This enhances the accumulation of an oncogenic transcription factor hypoxia-inducible factor 1α (Hif1α) in H. pylori-infected gastric cancer cells in normoxic condition and promotes invasiveness of infected cells. Increased acetylation of Siah2, Hif1α accumulation, and the absence of PHD3 in the infected human gastric metastatic cancer biopsy samples and in invasive murine gastric cancer tissues further confirm that the acetylated Siah2 (ac-Siah2)-Hif1α axis is crucial in promoting gastric cancer invasiveness. This study establishes the importance of a previously unrecognized function of ac-Siah2 in regulating invasiveness of H. pylori-infected gastric epithelial cells.-Kokate, S. B., Dixit, P., Das, L., Rath, S., Roy, A. D., Poirah, I., Chakraborty, D., Rout, N., Singh, S. P., Bhattacharyya, A. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.


Assuntos
Células Epiteliais , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteólise , Neoplasias Gástricas , Ubiquitina-Proteína Ligases/metabolismo , Acetilação , Linhagem Celular Tumoral , Estabilidade Enzimática , Células Epiteliais/enzimologia , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/enzimologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
11.
Indian J Cancer ; 55(3): 292-296, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30693897

RESUMO

BACKGROUND: : Malignant melanoma is a tumor of melanocytic origin. Although uncommon in India as compared with the west, its prevalence is increasing. OBJECTIVES: To document the pattern of clinicopathological features of malignant melanoma cases attending in a regional cancer center in eastern India. MATERIAL AND METHODS: The present study was a retrospective study of 182 cases diagnosed histopathologically as malignant melanoma during 2011-2016. RESULTS: Out of the total cases, 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous melanoma. The most common age group was sixth decade with a male predominance. Conventional melanotic melanomas were 176 (96.70%), and only 6 cases (3.30%) were amelanotic melanoma. Among noncutaneous melanomas, 6 were in anorectum, 2 in conjunctiva, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina. The acrallentigenous type was the most common variety, and the mixed epithelioid and spindle cell type was the most common histopathological pattern. Clark's level III was the most common level of invasion. CONCLUSION: The lower extremity is the most common site for melanoma, whereas extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB 45 can be used for definitive diagnosis.


Assuntos
Melanócitos/patologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Criança , Feminino , Humanos , Índia/epidemiologia , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto Jovem
12.
Indian J Med Paediatr Oncol ; 38(3): 391-393, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200700

RESUMO

Extrapulmonary tuberculosis (TB) coexistent with lymphomas in the same organ are rare. Here, we report a case of a 14-year-old male patient who had cauliflower-like ulcerated mass over cervical lymphadenopathy. He was diagnosed extrapulmonary TB. Unresponsiveness of anti tubercular treatment (anti-tubercular) treatment after 6 months, he was diagnosed as diffuse large B-cell lymphoma.

13.
J Obstet Gynaecol India ; 67(6): 432-441, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29162958

RESUMO

Background: Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. Methods: This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. Results: There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. Conclusion: This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

14.
Indian J Clin Biochem ; 32(3): 306-314, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28811690

RESUMO

Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5 % of NAFLD had normal serum transaminases, whereas 20.8 % of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.

15.
J Cytol ; 34(3): 156-158, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28701830

RESUMO

Histoplasmosis is a mycotic infection caused by dimorphic fungus, Histoplasma capsulatum. The organisms are usually found within the cells (macrophages). This organism mostly affects lungs in immunocompetent individuals and disseminated forms are seen in immunocompromised cases. Here, we describe a case of disseminated histoplasmosis in an immunocompetent, 35-year-old female with lymphadenopathy diagnosed by fine-needle aspiration cytology and cell block.

16.
Int J Biochem Cell Biol ; 82: 28-40, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27890795

RESUMO

Hypoxia enhances immortality and metastatic properties of solid tumors. Deregulation of histone acetylation has been associated with several metastatic cancers but its effect on hypoxic responses of cancer cells is not known. This study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A, an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter, mitochondrial apoptotic events. Noxa induction in normal immortalized gastric epithelial cells after CTK7A and hypoxia-exposure is remarkably less in comparison to similarly-treated GCCs. Moreover, hypoxia-exposed GCCs, which have acquired invasive properties, become apoptotic after CTK7A treatment to a significantly higher extent than normoxic cells. Thus, we show the potential of CTK7A in sensitizing hypoxic and metastatic GCCs to apoptosis induction.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/análogos & derivados , Proteína p300 Associada a E1A/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Hidrazinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Acetilação/efeitos dos fármacos , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Linhagem Celular Transformada , Linhagem Celular Tumoral , Cobalto/farmacologia , Curcumina/efeitos adversos , Curcumina/química , Curcumina/farmacologia , Proteína p300 Associada a E1A/metabolismo , Inibidores Enzimáticos/efeitos adversos , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrazinas/efeitos adversos , Hidrazinas/química , Peróxido de Hidrogênio/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Hipóxia Tumoral/efeitos dos fármacos
17.
Biochem J ; 473(11): 1629-40, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27048589

RESUMO

Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose.


Assuntos
Infecções por Helicobacter/metabolismo , Proteínas Nucleares/metabolismo , Proteína Proto-Oncogênica c-ets-2/metabolismo , Neoplasias Gástricas/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Técnicas In Vitro , Proteínas Nucleares/genética , Ligação Proteica , Proteína Proto-Oncogênica c-ets-2/genética , Neoplasias Gástricas/patologia , Proteína 1 Relacionada a Twist/genética , Ubiquitina-Proteína Ligases/genética
18.
Biochem Biophys Res Commun ; 471(1): 205-12, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26826385

RESUMO

Hypoxia promotes cancer progression, and metastasis. The major protein expressed in hypoxic solid cancer is hypoxia-inducible factor 1 (HIF1). We show that enhanced phosphorylation of a conventional protein kinase C isoform, PKCα, at threonine 638 (T(638)) by hypoxia-mimetic cobalt chloride induces HIF1α in nuclei of gastric epithelial cells (GECs). Moreover, phospho-T(638)-PKCα (P-PKCα) interacts with p300-HIF1α complex in the nuclei of hypoxic GECs and PKCα phosphorylation at T(638) enhances transcriptional activity of HIF1α. High P-PKCα expression in neoplastic gastric cancer biopsy samples as compared to nonneoplastic samples suggests that P-PKCα might act as an indicator of gastric cancer progression.


Assuntos
Núcleo Celular/metabolismo , Cobalto/administração & dosagem , Mucosa Gástrica/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína Quinase C-alfa/metabolismo , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Mucosa Gástrica/efeitos dos fármacos , Humanos , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia
19.
Indian J Pathol Microbiol ; 58(3): 389-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26275275

RESUMO

A 32-year-old lady came for a routine gynecological check up. Her cervical cytologic smear was reported as low grade squamous intraepithelial lesion. As a part of basic routine investigation, cervical punch biopsy was done. Astonishingly it revealed multiple rhabditiform larvae of Strongyloides stercoralis. These were curved thick with pointed end and a short buccal cavity. She did not have any history of immunosuppression including steroid therapy and was otherwise normal. Extensive review of the literature on parasites encountered in cervix yielded few case reports on strongyloides in cytologic smears, but failed to reveal any report till date on S. stercoralis found in histopathology section. Our case is probably the first in the world and the first reported from India to the best of our knowledge. We describe this case of strongyloidiasis of cervix with review of the literature on various parasites encountered in the cervix because of its rarity and also to keep this parasitic infestation as a differential diagnosis of cervical lesions.


Assuntos
Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Estrongiloidíase/patologia , Doenças do Colo do Útero/diagnóstico , Doenças do Colo do Útero/patologia , Adulto , Animais , Biópsia , Feminino , Histocitoquímica , Humanos , Índia , Microscopia , Estrongiloidíase/parasitologia , Doenças do Colo do Útero/parasitologia
20.
J Cytol ; 32(1): 71-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25948955

RESUMO

Presence of endometrial glands and stroma in places other than the uterus is called endometriosis. It can be pelvic or extra-pelvic. Abdominal scar endometriosis is an extra-pelvic endometriosis that can occur after surgery involving the uterus. Post-caesarean section, scar endometriosis is a rare event. The diagnosis is frequently made only after excision of disease tissue. We present a case of post-caesarean section abdominal scar endometriosis presenting as a tumor on the abdominal wall, which was diagnosed by fine needle aspiration cytology and confirmed by cell block preparation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...