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1.
J Family Med Prim Care ; 10(1): 567-571, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34017792

RESUMO

Wernicke's encephalopathy (WE) is an acute neurological condition characterized by the triad of ophthalmoparesis with nystagmus, ataxia, and global confusion. WE is a life-threatening illness caused by thiamine deficiency, primarily affecting the peripheral and central nervous systems. Thiamine deficiency is predominantly associated with chronic alcoholism, but various other causes have also been reported, including severe malnutrition, prolonged parenteral nutrition, malignancies, immunodeficiency syndromes, liver disease, hyperthyroidism and severe anorexia nervosa, and hyperemesis gravidarum. We, hereby, report a unique case of WE induced by hyperemesis gravidarum that presented in mid-trimester of pregnancy in a rather extremely unusual way with focal seizures and secondary generalization but fortunately ended up with a good feto-maternal outcome.

2.
J Cytol ; 37(2): 87-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606496

RESUMO

BACKGROUND: Being a minimally invasive diagnostic technique, Fine-Needle Aspiration Cytology (FNAC) has become the first-line test and corresponding aspirated material has become the target specimen for diagnosis and ancillary tests in lung carcinoma. Although the role of Cell Blocks (CBs) in diagnosis and in ancillary testing is well recognized in literature, limited attention has been paid to specimen procurement and triage in the preparation of CBs. In the present scenario, CBs are not consistently optimal because of its low cellularity. AIMS: This study is aimed to describe an improvised technique of specimen acquisition and cell block preparation in CT-guided FNACs of lung carcinoma cases in a resource-constrained center and to assess its efficacy for optimal representation of cellularity, morphology, and architecture. MATERIALS AND METHODS: Total 85 lung carcinoma cases undergoing CT-guided FNAC in our center from February 2017 to January 2018 were included in this study. 4 to 5 direct smears and subsequent CBs were made from material obtained by single pass. Cellularity of smears and corresponding cell blocks were assessed and categorized according to a scoring system (score 1 to 3 for number of cells <50, 50-100, >100, respectively). Preserved architecture and morphology were also assessed in smears and CBs. RESULTS: The evaluated samples showed a cellularity score 3 in 65.4%CBs and score 2 in 24.7% CBs. Overall, 90.1% cell blocks had acceptable cellularity. Cell morphology was preserved in all CBs of acceptable cellularity, except for two adenocarcinoma, one squamous cell carcinoma, and one small cell carcinoma blocks. Cellular architecture was also preserved in all CBs of acceptable cellularity. CONCLUSIONS: This simple improvised technique of CB preparation optimized its cellularity, morphology, and architectural preservation, even after adequate cellular FNA smears.

3.
Front Biosci (Landmark Ed) ; 24(3): 435-450, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468665

RESUMO

In cerebral tissues, due to continuous and high metabolic demand, energy is produced exclusively by mitochondrial oxidative phosphorylation (OXPHOS). Obstruction of blood flow leads to cerebral ischemia, hypoxia and decreased cellular ATP production. The reactive oxygen species (ROS) generated as by-product of OXPHOS alter many intracellular signaling pathways and result in damaged cellular components. Under such hypoxic conditions, a key factor known as hypoxia inducible factor 1 (HIF1) is stabilized and activated and such activation induces expression of a defined set of target genes which are required for cell survival and angiogenesis. Reperfusion that follows such ischemia alters signaling pathways which are involved in cellular fate. Here, we will review the role of ROS, HIF-1 alpha and other signaling network in mitochondrial dysfunction and cell fate determination in ischemia-reperfusion models in the brain. We will also address both current and future therapeutic strategies for clinical significance that are being developed for treatment of cerebral ischemia.


Assuntos
Isquemia Encefálica/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Mitocôndrias/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia
4.
Indian J Tuberc ; 64(2): 136-140, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28410697

RESUMO

Tuberculosis is a major health problem in the developing world. One-third of children infected with Mycobacterium tuberculosis have extra pulmonary involvement. Skeletal tuberculosis occurs in 1-6% of them with vertebra being the commonest site. Pure tubercular osteomyelitis without joint involvement occurs in only 2-3% cases of osteoarticular tuberculosis. Common sites are femur, tibia, and fibula. Disseminated skeletal involvement is very rare in children (7%) and calvarial osteomyelitis is even rarer (1%). Here, we report a unique case of disseminated skeletal TB. A 7-year-old tribal girl with no evidence of immunodeficiency presented with multiple lytic lesions involving skull, sternum, and hip bone surprisingly sparing the joints and appendicular skeleton. There was no pulmonary involvement either. FNAC from all three swellings showed presence of acid-fast bacillus. Bone biopsy followed by culture in BACTEC further confirmed the diagnosis. There was complete resolution of the swellings after one year of anti-tubercular drug therapy.


Assuntos
Osteomielite/diagnóstico por imagem , Osteomielite/microbiologia , Tuberculose/complicações , Tuberculose/diagnóstico por imagem , Criança , Feminino , Osso Frontal , Humanos , Órbita , Esterno , Tomografia Computadorizada por Raios X
5.
Dalton Trans ; 46(17): 5670-5679, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28181614

RESUMO

4-Nitrobenzoic acid, 3-nitrobenzoic acid and 4'-nitro[1,1'-biphenyl]-4-carboxylic acid react with the multiply bonded paramagnetic dirhenium(iii,ii) complex Re2(µ-O2CCH3)Cl4(µ-Ph2PCH2PPh2)2 (1) in refluxing ethanol to afford the paramagnetic substitution products of the type Re2(µ-L)Cl4(µ-Ph2PCH2PPh2)2, where L represents the nitrobenzoate ligands [L = 4-nitrobenzoate, 2; 3-nitrobenzoate, 3; 4'-nitro[1,1'-biphenyl]-4-carboxylate, 4]. These are the first examples of paramagnetic dirhenium complexes containing nitrobenzoate ligands. The spectral (UV-vis, IR, and EPR) and electrochemical properties of the complexes are described. The identity of 4 has been established by single-crystal X-ray structure determination (Re-Re distance of 2.2967(4) Å). The electronic structures of the complexes were scrutinized by density functional theory (DFT) calculations. X-band EPR spectral measurements along with the DFT analysis show that the unpaired electron resides in the metal-metal δ* antibonding orbital. The complexes were also screened in vitro for their antiproliferative properties against the human breast cancer cell line MCF-7 by the MTT assay. Flow cytometry analysis showed that the complexes arrested the sub-G0/G1 phase.


Assuntos
Complexos de Coordenação/química , Magnetismo , Nitrobenzoatos/química , Rênio/química , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Ligantes , Células MCF-7 , Microscopia Confocal , Conformação Molecular , Teoria Quântica , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
6.
Indian J Med Res ; 143(6): 739-747, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27748298

RESUMO

BACKGROUND & OBJECTIVES: Insulin resistance (IR) is a major confounding factor in polycystic ovarian syndrome (PCOS) irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. METHODS: Polymorphism study was performed by restriction fragment length polymorphism (RFLP) analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women. Serum testosterone, BMI and HOMA-IR (homeostatic model of assessment-insulin resistance) were analyzed by standard techniques. A realistic cut-off value for the HOMA-IR was obtained through receiver operating characteristic (ROC) curve for exploring any possible link between IR and T/C polymorphism in the case group. RESULTS: Significant increases in serum testosterone and HOMA-IR values were observed among the case group (P<0.001) without any significant elevation in BMI and FBG compared to controls. Cut-off value for IR in the PCOS patients was 1.40 against a maximum sensitivity of 0.83 and a minimum false positivity of 0.13. The analysis revealed an inconclusive link between the C/T polymorphic distribution and insulin resistant case subjects. INTERPRETATION & CONCLUSIONS: The results showed that CYP17A1 gene was not conclusively linked to either IR or its associated increased androgen secretion in non-obese women with PCOS. We propose that an increased sensitivity of insulin on the ovarian cells may be the predominant reason for the clinical effects and symptoms of androgen excess observed in non-obese PCOS patients in our region.


Assuntos
Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Glicemia , Índice de Massa Corporal , Estudos Transversais , Feminino , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Insulina/sangue , Insulina/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Polimorfismo de Nucleotídeo Único/genética , Gravidez
7.
Nanomedicine ; 12(7): 1973-1985, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27133192

RESUMO

Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women, associated with poor prognosis. Standard chemotherapy targets all dividing cells, resulting in dose-limiting toxicities. In this study, we demonstrated a strategy of encapsulating a hydrophobic synthetic compound, nifetepimine, having anticancer properties, in poly (lactic-co-glycolic acid) nanoparticles to increase selectivity of drug to cancerous cells with minimum toxicity towards normal cells. Nanoencapsulated nifetepimine (30-100nm) having loading and encapsulation efficiency of 7.45% and 75% respectively, was successfully internalized inside TNBC cells upon sustained release resulting in apoptosis. An in vivo bio-distribution study indicated that nanonifetepimine selectively accumulated into breast tumor sites of mice, primarily due to prolonged blood circulation time and binding of nifetepimine to epidermal growth factor receptor that remains overexpressed in most of the TNBC tumors. Moreover, we observed significant reduction in breast tumor volume with improved survival implying high tumor targetability of nanonifetepimine.


Assuntos
Antineoplásicos/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Mama , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Nanopartículas , Pirimidinonas/farmacologia , Distribuição Tecidual
8.
Cell Signal ; 28(6): 675-87, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27012497

RESUMO

Protein kinase CK2α is frequently upregulated in different cancers. Alteration of CK2α expression and its activity is sufficient to induce dramatic changes in cell fate. It has been established that CK2α induces oncogenesis through modulation of both AKT and PML. CK2α has been found to be overexpressed in breast cancer. In contrary, statistical reports have shown low level of PML. However, the regulation of CK2α gene expression is not fully understood. In the current study, we found that CK2α and activated AKT positively correlate with ERα, whereas PML follows an inverse correlation in human breast cancer tissues. Modulation of ERα signalling leads to recruitment of activated ERα on the ERE sites of CK2α promoter, resulting in CK2α transactivation. Furthermore, the DMBA induced tumours in rat showed elevated level of active CK2α. Consequently it mediates enhancement of AKT activity and PML degradation, resulting in increased cellular proliferation, migration and metastasis. Syngeneic ERα overexpressing stable mouse 4T1 cells produce larger primary tumours and metastatic lung nodules in mice, corroborating our in vitro findings. Hence, our study provides a novel route of ERα dependent CK2α mediated oncogenesis that causes upregulation and consequent AKT activation along with degradation of tumour suppressor PML.


Assuntos
Neoplasias da Mama/genética , Carcinogênese , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinógenos , Caseína Quinase II/genética , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Neoplasias Pulmonares/secundário , Células MCF-7 , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/enzimologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas , Proteína da Leucemia Promielocítica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Ativação Transcricional
9.
Front Biosci (Landmark Ed) ; 21(2): 225-50, 2016 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-26709771

RESUMO

DEAD box protein family of RNA helicases are vital players of RNA metabolism, and constitute the largest family of RNA helicases. Members of this family share nine conserved motifs including an Asp-Glu-Ala-Asp motif, giving this family its characteristic name as DEAD box RNA helicases. These conserved motifs confer RNA binding and RNA unwinding properties. Besides functioning in RNA metabolism, emerging evidences suggests several DEAD box RNA helicases to possess potential roles in regulating gene expression by acting as a transcriptional co-activator. Many of them are deregulated in cancers, and are implicated in possessing oncogenic potential. On the contrary, each of them also possesses tumor suppressive property in a context dependent manner. In this review, we discuss the mechanistic insights of gene regulation by DEAD box RNA helicases, and their significance in cancers.


Assuntos
RNA Helicases DEAD-box/metabolismo , Carcinogênese , RNA Helicases DEAD-box/química , Regulação da Expressão Gênica , Conformação Proteica
10.
Biomed Res Int ; 2015: 320941, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25866775

RESUMO

Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier.


Assuntos
Antineoplásicos , Barreira Hematoencefálica , Neoplasias Encefálicas , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Transporte Biológico Ativo/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Humanos
11.
Mol Ther ; 23(2): 255-69, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25327178

RESUMO

PTEN mutation is a frequent feature across a plethora of human cancers, the hot-spot being its C-terminus (PTEN-CT) regulatory domain resulting in a much diminished protein expression. In this study, the presence of C-terminus mutations was confirmed through sequencing of different human tumor samples. The kinase CKII-mediated phosphorylation of PTEN at these sites makes it a loopy structure competing with the E3 ligases for binding to its lipid anchoring C2 domain. Accordingly, it was found that PTEN-CT expressing stable cell lines could inhibit tumorigenesis in syngenic breast tumor models. Therefore, we designed a novel exosome-mediated delivery of the intrinsic PTEN domain, PTEN-CT into different cancer cells and observed reduced proliferation, migration, and colony forming ability. The delivery of exosome containing PTEN-CT to breast tumor mice model was found to result in significant regression in tumor size with the tumor sections showing increased apoptosis. Here, we also report for the first time an active PTEN when its C2 domain is bound by PTEN-CT, probably rendering its anti-tumorigenic activities through the protein phosphatase activity. Therefore, therapeutic interventions that focus on PTEN E3 ligase inhibition through exosome-mediated PTEN-CT delivery can be a probable route in treating cancers with low PTEN expression.


Assuntos
Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Exossomos/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Domínios e Motivos de Interação entre Proteínas , Animais , Linhagem Celular , Proliferação de Células , Expressão Gênica , Humanos , Camundongos , Mutação , Neoplasias/genética , Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/química , Domínios e Motivos de Interação entre Proteínas/genética , Proteólise , Especificidade por Substrato , Ubiquitina-Proteína Ligases/metabolismo
12.
Trop Gastroenterol ; 35(2): 79-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25470869

RESUMO

BACKGROUND AND AIM: The internal diameter of the portal vein varies with age and anthropometric parameters. The caliber of the normal portal vein in adults has been extensively studied but little is known about portal vein dimensions in the growing child. This study was conducted to establish standards of portal vein diameter by ultrasonography in healthy Indian children based on age, gender and anthropometric parameters. METHODS: Total 306 healthy children between the age of < 1 month and 12 years, visiting our outpatient departmentor accompanying their siblings were enrolled in the study. The children were distributed into ten age-groups. Each group was further divided in two sub-groups based on gender. Anthropometric parameters including weight, height and chest circumference were measured.Portal vein diameter was assessed by ultrasonography. RESULTS: The portal vein diameter increases with age, height, weight and chestcircumference. But the values are similar in boys and girls. Multiple logistic regression (adjusted R- square: 0.922) revealed age (p = 0.002), height/length (p < 0.0001), weight (p = 0.011), and chest circumference (p < 0.0001), as independent determinants of portal vein diameter. However, height/length emerged as the most consistent determinant (coefficient of regression: 1.536; p < 0.001; 95% confidence interval: 0.066-0.092). CONCLUSION: Our results provide a normal range of portal vein diameter according to age, gender and anthropometric parameters. We conclude that portal vein diameter strongly correlates with age and anthropometric variables like height, weight and chestcircumference,with height being the strongest determinant.


Assuntos
Veia Porta/anatomia & histologia , Distribuição por Idade , Antropometria , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Veia Porta/diagnóstico por imagem , Valores de Referência , Distribuição por Sexo , Ultrassonografia
13.
Breast Cancer Res ; 16(6): 496, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25499975

RESUMO

INTRODUCTION: Nuclear accumulation of ß-catenin is important for cancer development and it is found to overlap with p68 (DDX5) immunoreactivity in most breast cancers, as indicated by both clinical investigations and studies in cell lines. In this study, we aim to investigate the regulation of p68 gene expression through ß-catenin/transcription factor 4 (TCF4) signaling in breast cancer. METHODS: Formalin-fixed paraffin-embedded sections derived from normal human breast and breast cancer samples were used for immunohistochemical analysis. Protein and mRNA expressions were determined by immunoblotting and quantitative RT-PCR respectively. Promoter activity of p68 was checked using luciferase assay. Occupancy of several factors on the p68 promoter was evaluated using chromatin immunoprecipitation. Finally, a syngeneic mouse model of breast cancer was used to assess physiological significance. RESULTS: We demonstrated that ß-catenin can directly induce transcription of p68 promoter or indirectly through regulation of c-Myc in both human and mouse breast cancer cells. Moreover, by chromatin immunoprecipitation assay, we have found that both ß-catenin and TCF4 occupy the endogenous p68 promoter, which is further enhanced by Wnt signaling. Furthermore, we have also established a positive feedback regulation for the expression of TCF4 by p68. To the best of our knowledge, this is the first report on ß-catenin/TCF4-mediated p68 gene regulation, which plays an important role in epithelial to mesenchymal transition, as shown in vitro in breast cancer cell lines and in vivo in an animal breast tumour model. CONCLUSIONS: Our findings indicate that Wnt/ß-catenin signaling plays an important role in breast cancer progression through p68 upregulation.


Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , RNA Helicases DEAD-box/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Adenocarcinoma/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , RNA Helicases DEAD-box/metabolismo , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Células HEK293 , Humanos , Células MCF-7 , Camundongos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição 4 , Ativação Transcricional
14.
Biomed Res Int ; 2014: 435197, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25121098

RESUMO

The process of cell death has important physiological implications. At the organism level it is mostly involved in maintenance of tissue homeostasis. At the cellular level, the strategies of cell death may be categorized as either suicide or sabotage. The mere fact that many of these processes are programmed and that these are often deregulated in pathological conditions is seed to thought. The various players that are involved in these pathways are highly regulated. One of the modes of regulation is via post-translational modifications such as ubiquitination and deubiquitination. In this review, we have first dealt with the different modes and pathways involved in cell death and then we have focused on the regulation of several proteins in these signaling cascades by the different deubiquitinating enzymes, in the perspective of cancer. The study of deubiquitinases is currently in a rather nascent stage with limited knowledge both in vitro and in vivo, but the emerging roles of the deubiquitinases in various processes and their specificity have implicated them as potential targets from the therapeutic point of view. This review throws light on another aspect of cancer therapeutics by targeting the deubiquitinating enzymes.


Assuntos
Neoplasias/enzimologia , Neoplasias/patologia , Proteases Específicas de Ubiquitina/metabolismo , Morte Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Transdução de Sinais/efeitos dos fármacos
15.
Cell Signal ; 26(8): 1725-34, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24726840

RESUMO

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation in cancer cells have not been clearly evaluated. In our findings, correlation studies on the expression of CK2 and Stat3 Ser-727 phosphorylation levels in human glioma patient samples as well as rat orthotopic tumor model show a degree of negative correlation. Moreover, brain tumor cell lines were treated with various pharmacological inhibitors to inactivate the CK2 pathway. Here, increased Stat3 Ser-727 phosphorylation upon CK2 inhibition was observed. Overexpression of CK2 (α, α' or ß subunits) by transient transfection resulted in decreased Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residue was conversely phosphorylated in similar situations. Interestingly, we found PP2A, a protein phosphatase, to be a mediator in the negative regulation of Stat3 Ser-727 phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of Stat3 affects the transcriptional activity of its downstream targets like SOCS3, bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A mutant showed increased survival, proliferation and invasion which are characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A mutant cell line formed more aggressive tumors when compared to the Stat3 WT expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727 phosphorylation enhances tumorigenicity which may be regulated in part by CK2-PP2A pathway.


Assuntos
Caseína Quinase II/metabolismo , Proteína Fosfatase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Serina/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Caseína Quinase II/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transformação Celular Neoplásica , Ciclina D1/genética , Ciclina D1/metabolismo , Glioma/metabolismo , Glioma/patologia , Células HEK293 , Humanos , Ácido Okadáico/farmacologia , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 2/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Transplante Heterólogo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
16.
Heart Views ; 13(3): 91-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23181176

RESUMO

OBJECTIVES: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic renal failure (CRF). This study attempts to identify the factors responsible for atherosclerosis in CRF patients using carotid artery intima media thickness (CAIMT) as a surrogate marker of atherosclerosis. MATERIALS AND METHODS: CAIMT was measured by high-resolution B-mode ultrasonography in 100 CRF patients and 50 age- and sex-matched healthy controls. Data were analyzed by software SPSS (17(th) version) for Windows. RESULTS: CRF patients had a significantly higher CAIMT (1026.83 ± 17.19 micron, mean ± SE, P < 0.001) than age- and sex-matched healthy controls (722.46 ± 7.61 micron). There was inverse correlation between CAIMT and glomerular filtration rate (GFR) (P < 0.001) independent of traditional risk factors. There was also significant positive correlation between CAIMT and traditional risk factors of atherosclerosis. Ischemic heart disease (IHD) also showed positive correlation with CAIMT (P = 0.007) and inverse correlation with GFR (P = 0.005). CONCLUSIONS: There is high prevalence of atherosclerosis in CRF patients. CAIMT can be used to detect and predict future incidence of IHD in CRF patients.

17.
J Pept Sci ; 18(12): 720-30, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23109400

RESUMO

Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of >96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Feminino , Glioma/metabolismo , Transplante de Neoplasias , Octreotida/síntese química , Octreotida/metabolismo , Octreotida/farmacocinética , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/metabolismo , Compostos de Organotecnécio/farmacocinética , Ligação Proteica , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Ratos Sprague-Dawley , Receptores de Somatostatina/metabolismo , Distribuição Tecidual
18.
J Cardiovasc Dis Res ; 3(2): 128-31, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22629031

RESUMO

BACKGROUND: Carotid artery intima media is a surrogate marker of atherosclerosis and related with ethnicity, age, sex, traditional and non-traditional risk factors. Black ethnicity is related to greater mean and maximum carotid artery intima media thickness when compared to South Asians. Our study was done to find out the mean carotid artery intima media thickness (CAIMT) of normal healthy people of India and Bangladesh, and the relationship of non-modifiable risk factors such as age and sex with CAIMT. MATERIALS AND METHODS: In this observational study, CAIMT of 93 people were examined by B-mode ultrasonography. All subjects underwent a careful interview and clinical, radiological, biochemical examination. Data was analyzed by software statistical package for social sciences (SPSS) (17(th) version for window). RESULTS: In our study, the mean CAIMT of healthy subjects including all age group was (754.94 ± 11.96 micron.). Mean CAIMT was higher in age group of 61-80 years (908.75 ± 39.02 micron) than age group of 20-40 years (713.62 ± 16.59 micron) and 41-60 years (745.55 ± 13.05 micron). CAIMT was positively correlated with age (P value <0.001) and sex (P value=0.001). CONCLUSION: An aggregated analysis based on this study in different age groups of healthy people may be useful for assessing carotid artery abnormalities as an aid to defining abnormalities and predicting risk of atherosclerosis in individual healthy people living in India and Bangladesh.

19.
N Am J Med Sci ; 4(2): 77-80, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22408752

RESUMO

BACKGROUND: In patients with chronic renal failure (CRF), carotid artery intima media thickness (CAIMT) is increased when the patients are on hemodialysis. Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis. AIMS: This study was done to find out the relationship between carotid artery intima media thickness and hemodialysis in chronic renal failure patients independent of classical risk factors and also the relationship between CAIMT of hemodialyzed patients and nonhemodialyzed CRF patients. MATERIALS AND METHODS: In this observational study, CAIMT of 78 CRF patients was examined by B-mode ultrasonography. Glomerular filtration rate (GFR) was calculated by using the "Modification of Diet in Renal Disease" formula. CRF patients, who had been on regular hemodialysis treatment (treated thrice weekly) for at least 6 months, were identified as hemodialyzed patients. Data were analyzed by software Statistical package for the social Sciences (SPSS) (17(th) version). RESULTS: There was significant positive correlation between CAIMT and hemodialysis (P=0.045) independent of traditional risk factors. Hemodialyzed patients had higher mean CAIMT (1136.30±21.21 µm, P<0.001) than mean CAIMT of age and sex matched nondialyzed patients (959.30±23.01 µm). CONCLUSION: Hemodialysis is an independent risk factor for atherosclerosis in CRF patents. Hemodialyzed patients have significantly higher CAIMT than nondialyzed CRF patients.

20.
Indian Pediatr ; 48(4): 321-3, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21532102

RESUMO

Umbilical myiasis is rare in newborns. We are reporting two cases of umbilical myiasis from rural West Bengal (India) that were infected by larval forms of blow fly (Chrysomya megacephala). One of them subsequently developed septicemia while the other one was clinically well.


Assuntos
Dípteros , Doenças do Recém-Nascido/parasitologia , Miíase/diagnóstico , Cordão Umbilical/parasitologia , Animais , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/patologia , Larva , Masculino , Miíase/tratamento farmacológico , Miíase/parasitologia , Miíase/patologia , Cordão Umbilical/patologia
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