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1.
Blood Cell Ther ; 6(4): 124-128, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38149023

RESUMO

Introduction: While there are data about return to work after hematopoietic cell transplantation (HCT) in survivors from resource-rich regions, similar data from resource-challenged settings are scarce. This study assessed the incidence of and factors affecting return to work/school (RTW) among HCT survivors in India. Methods: This single-center cross-sectional study was conducted at the long-term follow-up (LTFU) clinic of a large-volume HCT center during 2022-2023. HCT survivors surviving beyond four months were included after obtaining informed consent. Patients' sociodemographic, disease, HCT, and work details were recorded. The factors affecting RTW were evaluated using univariate (ANOVA) and logistic regression analyses. Results: A total of 126 HCT survivors participated in the study. Of these, 34 (27%) did not RTW, 47 (37%) returned to part-time work, and 45 (36%) returned to full-time work at a median of more than three years post-HCT. The three groups did not significantly differ in age, sex, or marital status. The univariate analysis revealed that education, pre-HCT job status, income, and conditioning intensity were significantly associated with RTW. Logistic regression analysis revealed that survivors with a higher (taxable) income were more likely to RTW than those with a lower (non-taxable) income (OR 3.5; CI 1.2-10.2, p=0.01). Survivors with a desk job were more likely to RTW than those who were unemployed/retired or students (OR 4.5; CI 1.1-18.0, p=0.03). Conclusion: Socioeconomic factors, like pre-HCT job status and income, were significantly associated with post-HCT RTW. Therefore, there is a need to integrate multidisciplinary RTW programs for HCT survivors in India.

2.
Haemophilia ; 29(2): 591-599, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36571800

RESUMO

INTRODUCTION: Inherited Factor VII (FVII) deficiency is commonest among the rare bleeding disorders. A small number of patients present in infancy with severe bleeding, and many may remain asymptomatic but detected before surgery/invasive procedures. Genetic testing may be helpful in predictive testing/prenatal diagnosis in severe cases. AIM: Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency. METHODS: Retro-prospectively, 35 cases with prolonged prothrombin time and FVII activity (FVII:C) <50 IU/dl were subjected to targeted resequencing. After in-silico analysis, variant/s were validated by Sanger sequencing in index cases and family members. Haplotype analysis was done for F7 polymorphisms. RESULTS: Severe FVII deficiency was found in 50% of patients (FVII:C ≤1 IU/dl), and 42.9% were asymptomatic. Clinical severity assessment revealed 17% severe, 17% moderate and 22.9% patients with mild bleeds. FVII levels ranged from .3 to 38 IU/dl. Molecular analysis revealed variants in 30/35 cases, of which 17 were homozygous, 10 were compound heterozygous and 3 were heterozygous. Twelve genetic variants were identified, one promoter variant c.-30A>C; seven missense (c.215C>G, c.244T>C, c.253G>C, c.904G>A, c.961C>T, c.1109G>T, c.1211G>A), two deletions (c.21delG, c.868_870delATC), and one each of nonsense c.634C>T and splice-site variant c.316+1G>A. Recurrent variants c.1109G>T and c.215C>G were found in 17 and 8 cases, 12 of the former cases were homozygous. They had the same haplotype, indicating the founder effect in North Indians. CONCLUSION: This is the largest cohort of FVII genotyping from India, confirming heterogeneity in terms of clinical manifestations, FVII activity and zygosity of the variants with a limited genotypic phenotypic correlation.


Assuntos
Transtornos da Coagulação Sanguínea , Deficiência do Fator VII , Humanos , Efeito Fundador , Mutação , Deficiência do Fator VII/diagnóstico , Deficiência do Fator VII/genética , Fator VII/genética , Hemorragia
3.
ACS Omega ; 7(41): 36092-36107, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278104

RESUMO

Cancer mortality is increasing at an alarming rate across the globe. Albeit, many therapeutics are available commercially, they are not effective and have no cure up to today. Moreover, the knowledge gap in cancer therapy persists, representing a potential blind spot for the innovation of effective anticancer therapeutics. This review presents an update on current advancements in nanopeptide therapeutics. Herein, a detailed exploration of peptide-functionalized nanoparticles for the development of nanotherapeutics was carried out. Different approaches that include self-assembly nanostructures, solid phase peptide synthesis, ligand exchange, chemical reduction, and conjugation methods for assembling peptides for functionalizing nanodrugs are also highlighted. An outlook on biomedical applications is also reviewed. Additionally, a comprehensive discussion on targeted cancer cell therapy and mechanism of action are provided. The present review reflects the functional novelty of nanodrugs to improve stability, accessibility, bioavailability, and specificity toward cancerous cells. Finally, it summarizes the current challenges and future perspectives on the formulation of these nanodrugs.

4.
Cancer Treat Res Commun ; 32: 100610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35878518

RESUMO

The diagnosis and treatment of cancer can be an extremely stressful experience for the patient. COVID-19 pandemic has further created an environment of stress and anxiety amongst cancer patients. A cross-sectional study was conducted from March 2020 to May 2020 using google forms to assess the knowledge, distress level, practices, and attitude toward the COVID-19 pandemic in cancer patients. It was observed that the females and elderly patients (> 55 years) were more knowledgeable about the COVID-19 pandemic. Also, females were more prone to emotional stress compared to males. While the younger age group (18-35 years) had a more hard time in dealing with family-related issues compared to other age groups. Therefore, the younger age group (18-35 years) and female gender being more prone to distress, warrant more attention from health care staff and caretakers. Moreover, the study highlights the need for mental and general health screening and intervention to balance the oncological care and COVID-19 situation.


Assuntos
COVID-19 , Neoplasias , Angústia Psicológica , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Neoplasias/epidemiologia , Pandemias , Adulto Jovem
5.
Sci Rep ; 12(1): 9341, 2022 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-35662279

RESUMO

The adverse effects of maternal prenatal stress (PS) on child's neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.


Assuntos
Ferritinas , Feto , Biomarcadores , Estudos de Coortes , Feminino , Sangue Fetal/metabolismo , Feto/metabolismo , Homeostase , Humanos , Recém-Nascido , Ferro/metabolismo , Masculino , Gravidez , Estudos Prospectivos
6.
Open Forum Infect Dis ; 9(3): ofac017, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35169589

RESUMO

Coccidioidomycosis is the second most common endemic fungal infection in the United States. Prior descriptions of coccidioidal peritonitis include only single cases. We describe 17 new cases previously unreported from healthcare institutions in California. The majority of cases presented with nonspecific abdominal complaints. PubMed and Google Scholar were searched for additional case series and only single case reports and reviews of single cases were found. The diagnosis was confirmed by culture or histopathology and/or serology in each patient. All patients were treated with anti-fungal therapy. This case series demonstrates that coccidioidal peritonitis may be asymptomatic or present with only subtle abdominal symptoms. In a minority of our patients, the diagnosis was established incidentally during surgery. Based on this series, the overall outcome of coccidioidal peritonitis is favorable with long-term triazole treatment. The term cure is not usually used in disseminated coccidioidal disease because of the risk of late relapse.

8.
J Oral Maxillofac Pathol ; 25(2): 272-278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703121

RESUMO

CONTEXT: Odontogenic cysts are among the most common lesions to affect the oral and maxillofacial region. Cysts are capable of causing significant bony disfigurement, tooth displacement and pathological fractures. Several surgical approaches exist for the management of larger cysts of the jaws. These include enucleation, marsupialization and decompression. AIMS: 1. Analysis of histopathologic findings in odontogenic cysts before and after decompression2. Analysis of Ki-67 expression in odontogenic jaw cysts before and after decompression. SETTINGS AND DESIGN: Decompression technique was used for the treatment of 10 cases of odontogenic cysts in the study. Incisional biopsies of cystic lining (pretreatment) and corresponding excisional biopsies (posttreatment) were received for histopathologic and immunohistochemical examination. SUBJECTS AND METHODS: Hematoxylin and eosin stain was used for histopathologic findings, and Ki-67 was used for immunohistochemical findings using antibody Ki-67 in fresh tissue samples. RESULTS: Overall, radicular cysts, dentigerous cysts, and sialo-odontogenic cyst contained fewer Ki-67 + cells than odontogenic keratocysts. The average scores were found to be 2.2 and 1 for before and after decompression, respectively. A statistically significant difference was observed between the two groups. The two-tailed P value was found to be <0.0001. The confidence interval was found to be 95%. CONCLUSIONS: The proliferative activity evaluated by Ki-67 marker was greater in predecompression epithelial lining compared to postdecompression. Our study infers that proliferative rate of the cystic epithelial lining is significantly diminished after decompression.

9.
Curr Drug Metab ; 21(11): 885-901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33032505

RESUMO

BACKGROUND: Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. OBJECTIVES: In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. METHODS: 243 papers were reviewed and included in this review. RESULTS: Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. CONCLUSION: Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.


Assuntos
Lipídeos , Veículos Farmacêuticos , Tensoativos , Animais , Humanos , Lipídeos/classificação , Lipídeos/farmacologia , Veículos Farmacêuticos/classificação , Veículos Farmacêuticos/farmacologia , Tensoativos/classificação , Tensoativos/farmacologia
10.
J Investig Med High Impact Case Rep ; 8: 2324709620966855, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33054423

RESUMO

Vasculitis is an inflammatory process involving blood vessels of various sizes, including the small vessels in the kidneys to the large vessels, such as the aorta. This inflammatory condition is usually autoimmune in nature and is associated with involvement of many locations, such as the sinuses, lungs, kidneys, and even the heart. Specifically, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that may initially hide as asthma, allergic rhinitis, and/or sinusitis. However, it is known to become a lethal disease once progressed to include cardiovascular manifestations. It is important to remember EGPA as a differential for any patient with a history of asthma, allergic rhinitis, and/or sinusitis who also presents with cardiovascular complaints and eosinophilia. Treatment recommendations focus on immunosuppression in such cases. In this article, we discuss the case of a 62-year-old male, with a known history of asthma, who presented to the emergency department with concern for his chest pain and right-sided weakness. He was later diagnosed with EGPA with eosinophilic myocarditis. Diagnosis and treatment are described.


Assuntos
Síndrome de Churg-Strauss/complicações , Miocardite/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miocardite/tratamento farmacológico , População Branca
11.
Int J Biol Macromol ; 164: 2569-2582, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800950

RESUMO

Several pathological disorders have known linkages with the misfolding and abnormal oligomerization of peptides and proteins and their accumulation into numerous aggregates. One such peptide is human islet amyloid polypeptide (hIAPP) responsible for amyloid aggregation in type 2 diabetes. This aggregation can be altered by osmolytes, which are natural agents that can alter the environment surrounding of hIAPP. Here, we implemented several replica-exchange molecular dynamics (REMD) simulations to examine the effects of the denaturing osmolyte urea and the protective osmolyte trimethylamine N-oxide (TMAO) on amyloid aggregation and on the conformational ensemble of the hIAPP peptide. We analyzed specific modulations in hIAPP peptide and observed a state shift in the conformational population of hIAPP. Our results confirmed that urea restricted the peptide aggregation and led to the formation of unfolded conformations, whereas TMAO promoted folding and a compact state of the hIAPP peptide.


Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Metilaminas/química , Agregados Proteicos , Dobramento de Proteína , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Estrutura Secundária de Proteína
12.
Antioxidants (Basel) ; 9(2)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093300

RESUMO

: Cassia fistula L. is a highly admirable traditional medicinal plant used for the treatment of various diseases and disorders. The present study was performed to divulge the antioxidant, antiproliferative, and apoptosis-inducing efficacy of fractions from C. fistula leaves. The hexane (CaLH fraction), chloroform (CaLC fraction), ethyl acetate (CaLE fraction), n-butanol (CaLB fraction), and aqueous (CaLA fraction) were sequentially fractionated from 80% methanolic (CaLM extract) of C. fistula leaves. The CaLE fraction was fractionated using column chromatography to yield a pure compound, which was characterized as Epiafzelechin (CFL1) based on 1H, 13C, and DEPT135 NMR. Among these fractions, CaLE and isolated CFL1 fractions exhibited an effective antioxidant potential in Ferric ion reducing power, (2,2'-azino-bis (3-ethylbenzothiazoline -6-sulfonic acid)) cation radical scavenging, and nitric oxide radical scavenging assays. Epiafzelechin was investigated for its antiproliferative effects against MG-63 (osteosarcoma), IMR-32 (neuroblastoma), and PC-3 (prostate adenocarcinoma), and was found to inhibit cell proliferation with a GI50 value of 8.73, 9.15, and 11.8 µM respectively. MG-63 cells underwent apoptotic cell death on treatment with Epiafzelechin as the cells showed the formation of apoptotic bodies, enhanced reactive oxygen species (ROS) generation, mitochondrial membrane depolarization along with an increase in early apoptotic cell population analyzed using Annexin V-FITC/PI double staining assay. Cells showed cell cycle arrest at the G0/G1 phase accompanied by a downregulation in the expression levels of p-Akt (Protein kinase B), p-GSK-3ß (Glycogen synthase kinase-3 beta), and Bcl-xl (B-cell lymphoma-extra large) proteins. RT-PCR (Real time-polymerase chain reaction) analysis revealed downregulation in the gene expression level of ß-catenin and CDK2 (cyclin-dependent kinases-2) while it upregulated the expression level of caspase-8 and p53 genes in MG-63 cells.

13.
RSC Adv ; 10(43): 25929-25946, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35518630

RESUMO

Aberrant misfolding and amyloid aggregation, which result in amyloid fibrils, are frequent and critical pathological incidents in various neurodegenerative disorders. Multiple drugs or inhibitors have been investigated to avert amyloid aggregation in individual peptides, exhibiting sequence-dependent inhibition mechanisms. Establishing or inventing inhibitors capable of preventing amyloid aggregation in a wide variety of amyloid peptides is quite a daunting task. Bleomycin (BLM), a complex glycopeptide, has been widely used as an antibiotic and antitumor drug due to its ability to inhibit DNA metabolism, and as an antineoplastic, especially for solid tumors. In this study, we investigated the dual inhibitory effects of BLM on Aß aggregation, associated with Alzheimer's disease and hIAPP, which is linked to type 2 diabetes, using both computational and experimental techniques. Combined results from drug repurposing and replica exchange molecular dynamics simulations demonstrate that BLM binds to the ß-sheet region considered a hotspot for amyloid fibrils of Aß and hIAPP. BLM was also found to be involved in ß-sheet destabilization and, ultimately, in its reduction. Further, experimental validation through in vitro amyloid aggregation assays was obtained wherein the fibrillar load was decreased for the BLM-treated Aß and hIAPP peptides in comparison to controls. For the first time, this study shows that BLM is a dual inhibitor of Aß and hIAPP amyloid aggregation. In the future, the conformational optimization and processing of BLM may help develop various efficient sequence-dependent inhibitors against amyloid aggregation in various amyloid peptides.

14.
J Oral Maxillofac Pathol ; 23(2): 267-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516234

RESUMO

CD44 is a group of protein molecules which perform a variety of functions. Their wide range of functions are mainly based on their multiple variations in their molecular structure. Furthermore, they are distributed in various tissues of the human body. They have a unique property of cell adhesion, which can lead to interaction between two different cells or a cell and its pericellular matrix. CD44 as a cell surface adhesive molecule helps in aggregation and migration of tumor cells. CD44 plays an important role in cancer of bladder, liver, lungs, pancreas, etc. Expression profile of CD44 has been seen in the epithelia of the lip, tongue, gingiva, hard palate, floor of the mouth, buccal mucosa and pharynx. The relationship between the expression of CD44 v6 and regional lymph node metastasis has been studied immunohistochemically. The expression of CD44 v6 was apparently downregulated in oral squamous cell carcinoma, but not in normal oral mucosa. Carcinomas expressing lower levels of CD44 v6 exhibited more frequent regional lymph node metastasis. No significant relation was found between the expression of CD44 v6 in primary and metastatic lesions. Still, the precise function of CD44 in the metastatic process and the degree of involvement in human malignancies is yet to be established.

15.
Indian J Anaesth ; 62(11): 887-891, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30532326

RESUMO

BACKGROUND AND AIMS: Atrial fibrillation (AF) is a common postoperative complication after cardiac surgery due to multifactorial causes. The aim of this study was to evaluate the incidence and risk factors of postoperative atrial fibrillation (POAF) after cardiac surgery under cardiopulmonary bypass (CPB). METHODS: A total of 150 adult patients undergoing coronary artery bypass graft (CABG) surgery and valvular surgeries were included. They were evaluated with respect to preoperative risk factors [age, use of ß-blockers, left ventricular ejection fraction (LVEF), previous myocardial infarction (MI) and diabetes], intraoperative factors (CABG or valvular surgery, duration of CPB and aortic cross clamp time) and postoperative factors (duration of inotropic support and ventilatory support). Outcome measure was POAF after cardiac surgery under CPB. Postoperative intensive care unit and hospital stay and mortality were also studied. RESULTS: Of the patients who developed POAF, 50% were less than 60 years, 50.6% were diabetics, 50.7% had prior MI,19.7% had LVEF <40%, 82.6%were not on ß-blockers, 66.7% had aortic cross clamp time >60 min and 60% had surgery with CPB time >100 min. About 38.8% underwent CABG and 43.1%underwent valvular surgery. There was a positive association with LVEF <40%, prior MI, post-bypass inotropic support greater than 10 min and ventilatory support more than 24 h with the development of POAF. CONCLUSION: The incidence of POAF after cardiac surgery was 40.7%. Preoperative LVEF <0.4, prior MI, CPB time >100 minand extended ventilation for >24 h were significantly associated with POAF.

16.
J Org Chem ; 83(20): 12702-12710, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30211555

RESUMO

Here, a facile and efficient protocol for the synthesis of 3-hydroxyquinolin-8-yl propanoates via Rh(III)-catalyzed C(8)-H activation of 2-substituted quinolines has been developed. The reaction proceeds via C(8)-H activation, functionalization with acrylates, followed by intramolecular migration of the oxygen atom from quinoline N-oxides to the acrylate moiety. In this approach, N-oxide plays a dual role of a traceless directing group as well as a source of an oxygen atom for hydroxylation. This catalytic method involves simultaneous formation of new C-C and C-O bonds and is applicable only for C2-substituted quinolines. A catalytically competent five-membered rhodacycle has been characterized, thus revealing a key intermediate in the catalytic cycle. In silico docking studies against Falcipan-2 have revealed that 3a, 3b, 3g, and 3m have better scores. In vitro evaluation of selected compounds against CQ-sensitive pf3D7 and CQ-resistant pfINDO strains provided evidence that 3d (IC50 13.3 µM) and 3g (IC50 9.5 µM) had good promise against Plasmodium falciparum in the in vitro culture. Compound 3g was found to be the most potent on the basis of both in vitro antiplasmodial activity [IC50 9.5 µM ( Pf3D7) and 11.9 µM ( PfINDO), resistance index 1.25] and in silico studies.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Quinolinas/síntese química , Quinolinas/farmacologia , Ródio/química , Catálise , Óxidos N-Cíclicos/química , Cisteína Endopeptidases/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Simulação de Acoplamento Molecular , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Ligação Proteica , Relação Estrutura-Atividade
17.
Oncotarget ; 8(34): 57246-57264, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915668

RESUMO

The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

18.
Anticancer Agents Med Chem ; 16(11): 1445-1454, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27087163

RESUMO

PURPOSE: Phenobarbital is a commonly employed antidepressant and anti-epileptic drug. The cancer promoting activity of this genotoxic xenobiotic is often ignored. It is responsible for oxidative stress leading to modulation in xenobiotic and antioxidative enzymes. Glucosinolates and more specifically their hydrolytic products are known for their antioxidative and anticancer activities. The present study involves the analysis of hepatoprotective effect of erucin (isolated from Eruca sativa (Mill.) Thell.) against phenobarbital mediated hepatic damage in male wistar rats. METHODS: The liver homogenate was analyzed for oxidative stress (superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione reductase and lactate dehydrogenase), other oxidative parameters (thiobarbituric acid reactive species, conjugated dienes and lipid hydroperoxide), phase I enzymes (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P420, cytochrome P450 and cytochrome b5), phase II enzymes (γ-glutamyl transpeptidase, DT-diaphorase and glutathione-S-transferase), serum parameters (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin) and certain histological parameters. RESULTS: Erucin accorded protection from phenobarbital induced hepatic damage by normalizing antioxidative enzymes, other oxidative parameters, phase I, II, and serum parameters. CONCLUSIONS: Erucin, an analogue of sulforaphane has the potential to act as an anticancer agent by regulating various biochemical parameters.


Assuntos
Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenobarbital/farmacologia , Sulfetos/farmacologia , Tiocianatos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Brassicaceae/química , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Estrutura Molecular , Fenobarbital/química , Ratos , Ratos Wistar , Sulfetos/química , Sulfetos/isolamento & purificação , Tiocianatos/química , Tiocianatos/isolamento & purificação
19.
Life Sci ; 139: 145-52, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26334567

RESUMO

Colorectal cancer (CRC) is the third leading cause of death in both men and women in North America. Despite chemotherapeutic efforts, CRC is associated with a high degree of morbidity and mortality. Thus, to develop effective treatment strategies for CRC, one needs knowledge of the pathogenesis of cancer development and cancer resistance. It is suggested that colonic tumors or cell lines harbor truncated adenomatous polyposis coli (APC) without DNA repair inhibitory (DRI)-domain. It is also thought that the product of the APC gene can modulate base excision repair (BER) pathway through an interaction with DNA polymerase ß (Pol-ß) and flap endonuclease 1 (Fen-1) to mediate CRC cell apoptosis. The proposed therapy with temozolomide (TMZ) exploits this particular pathway; however, a high percentage of colorectal tumors continue to develop resistance to chemotherapy due to mismatch repair (MMR)-deficiency. In the present communication, we have comprehensively reviewed a critical issue that has not been addressed previously: a novel mechanism by which APC-induced blockage of single nucleotide (SN)- and long-patch (LP)-BER play role in DNA-alkylation damage-induced colorectal carcinogenesis.


Assuntos
Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Colo/patologia , Reparo do DNA , Reto/patologia , Polipose Adenomatosa do Colo/tratamento farmacológico , Polipose Adenomatosa do Colo/metabolismo , Proteína da Polipose Adenomatosa do Colo/análise , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , DNA Polimerase beta/análise , DNA Polimerase beta/metabolismo , Reparo do DNA/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Endonucleases Flap/análise , Endonucleases Flap/metabolismo , Humanos , Modelos Moleculares , Terapia de Alvo Molecular , Mutação , Reto/efeitos dos fármacos , Reto/metabolismo , Temozolomida
20.
J Cytol ; 31(3): 161-4, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25538387

RESUMO

BACKGROUND: Fine-needle aspiration cytology (FNAC) has been used as a diagnostic tool in evaluating suspected lesions. It shows a high diagnostic accuracy for diagnosing salivary gland lesions. AIM: The aim of this study was to highlight FNAC as an effective diagnostic tool in the presumptive diagnosis of ameloblastoma. MATERIALS AND METHODS: A total of 12 cases of ameloblastoma sampled by FNAC retrieved from the archives of the Oral Pathology Department were retrospectively studied. The smears were alcohol-fixed and stained with hematoxylin and eosin. All the 12 cases of FNAC had subsequent corresponding surgical incisional biopsy or excision specimens. RESULTS: Cytologically, seven cases were diagnosed as benign odontogenic tumor more in favor of ameloblastoma. All the 12 fine-needle aspiration cases were given a histopathologic work-up and diagnosed as ameloblastomas. Of these, the seven cytologically diagnosed benign odontogenic lesions were also confirmed to be ameloblastoma by both incisional biopsy as well as surgical excision. CONCLUSION: It was deduced from the above results that FNAC helps potentially in diagnosing ameloblastoma.

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