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1.
Gut ; 73(7): 1124-1130, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38499339

RESUMEN

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.


Asunto(s)
Enfermedad Celíaca , Duodeno , Transglutaminasas , Humanos , Enfermedad Celíaca/patología , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Femenino , Masculino , Adulto , Estudios de Casos y Controles , Duodeno/patología , Adulto Joven , Transglutaminasas/inmunología , Inmunoglobulina A/sangre , Proteínas de Unión al GTP/inmunología , Atrofia , Dieta Sin Gluten , Mucosa Intestinal/patología , Proteína Glutamina Gamma Glutamiltransferasa 2 , Gastroscopía , Persona de Mediana Edad
2.
Immunol Cell Biol ; 102(3): 179-193, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38228572

RESUMEN

Cancer immunotherapy has been rejuvenated by the growing understanding of the immune system's role in tumor activity over the past two decades. During cancer initiation and progression, tumor cells employ various mechanisms that resemble peripheral immune tolerance to evade the antitumor responses of the immune system. Immune checkpoint molecules are the major mechanism of immune resistance that are exploited by tumor cells to inhibit T-cell activation and suppress immune responses. The targeting of immune checkpoint pathways has led to substantial improvements in survival rates in a number of solid cancers. However, a lack of understanding of the heterogeneity of the tumor microenvironment (TME) has resulted in inefficient therapy responses. A greater understanding of the TME is needed to identify patients likely to respond, and those that will have resistance to immune checkpoint inhibitors (ICIs). Advancement in spatial single-cell technologies has allowed deeper insight into the phenotypic and functional diversities of cells in the TME. In this review, we provide an overview of ICI biomarkers and highlight how high-dimensional spatially resolved, single-cell approaches provide deep molecular insights into the TME and allow for the discovery of biomarkers of clinical benefit.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Activación de Linfocitos , Microambiente Tumoral , Neoplasias/tratamiento farmacológico
3.
J Transl Med ; 22(1): 239, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439077

RESUMEN

The spatial localisation of immune cells within tumours are key to understand the intercellular communications that can dictate clinical outcomes. Here, we demonstrate an analysis pipeline for highly multiplexed CODEX data to phenotype and profile spatial features and interactions in NSCLC patients that subsequently received PD1 axis immunotherapy. We found that regulatory T cells (Tregs) are enriched in non-responding patients and this was consistent with their localization within stromal and peripheral tumour-margins. Proximity-based interactions between Tregs and both monocytes (p = 0.009) and CD8+ T cells (p = 0.009) were more frequently found in non-responding patients, while macrophages were more frequently located in proximity to HLADR+ tumour cells (p = 0.01) within responding patients. Cellular neighbourhoods analysis indicated that both macrophages (p = 0.003) and effector CD4+ T cells (p = 0.01) in mixed tumour neighbourhoods, as well as CD8+ T cells (p = 0.03) in HLADR+ tumour neighbourhoods were associated with favorable clinical response. Evaluation of the inferred regulatory functions between immune cells relative to the tumour suggested that macrophages exhibit an immunosuppressive phenotype against both CD4+ and CD8+ T cells, and that this association scores more highly in ICI refractory patients. These spatial patterns are associated with overall survival in addition to ICI response and may thus indicate features for the functional understanding of the tumour microenvironment.


Asunto(s)
Adenoma Pleomórfico , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Linfocitos T CD8-positivos , Neoplasias Pulmonares/terapia , Inmunoterapia , Microambiente Tumoral
4.
Inflammopharmacology ; 32(2): 927-944, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38252220

RESUMEN

BACKGROUND: Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). METHODS: This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. RESULTS: Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: - 2.52; - 3.61 to - 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: - 2.60; - 3.74 to - 1.46; p value < 0.01). DISCUSSION: This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. FUNDING: The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).


Asunto(s)
Encefalomielitis Autoinmune Experimental , Melatonina , Esclerosis Múltiple , Humanos , Ratones , Animales , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/complicaciones , Melatonina/farmacología , Roedores , Cuprizona , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Suplementos Dietéticos
5.
Curr Treat Options Oncol ; 24(10): 1451-1471, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37561382

RESUMEN

OPINION STATEMENT: Prostate cancer (PCa) is the second most diagnosed malignant neoplasm and is one of the leading causes of cancer-related death in men worldwide. Despite significant advances in screening and treatment of PCa, given the heterogeneity of this disease, optimal personalized therapeutic strategies remain limited. However, emerging predictive and prognostic biomarkers based on individual patient profiles in combination with computer-assisted diagnostics have the potential to guide precision medicine, where patients may benefit from therapeutic approaches optimally suited to their disease. Also, the integration of genotypic and phenotypic diagnostic methods is supporting better informed treatment decisions. Focusing on advanced PCa, this review discusses polygenic risk scores for screening of PCa and common genomic aberrations in androgen receptor (AR), PTEN-PI3K-AKT, and DNA damage response (DDR) pathways, considering clinical implications for diagnosis, prognosis, and treatment prediction. Furthermore, we evaluate liquid biopsy, protein biomarkers such as serum testosterone levels, SLFN11 expression, total alkaline phosphatase (tALP), neutrophil-to-lymphocyte ratio (NLR), tissue biopsy, and advanced imaging tools, summarizing current phenotypic biomarkers and envisaging more effective utilization of diagnostic and prognostic biomarkers in advanced PCa. We conclude that prognostic and treatment predictive biomarker discovery can improve the management of patients, especially in metastatic stages of advanced PCa. This will result in decreased mortality and enhanced quality of life and help design a personalized treatment regimen.

6.
Indian J Med Res ; 156(1): 64-69, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36510899

RESUMEN

Background & objectives: Transforming growth factor-beta (TGF-ß) signalling pathway has been reported to be involved in metastasis and at the same time has been considered compellingly an important mediator of epithelial-to-mesenchymal transition (EMT). Besides, EMT process is maintained by zinc-finger E-box-binding homeobox 1 (ZEB1) gene which is induced by TGF-ß pathway. TGF-ß has been shown to be associated with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) phenomenon, which is one of the prognostic biomarkers of colorectal cancer (CRC). This study was conducted to determine the link among ZEB1-induced TGF-ß, EMAST status and metastasis. Methods: The expression level of ZEB1 was evaluated using quantitative reverse transcription (qRT) real-time PCR in 122 formalin fixed paraffin-embedded tissues of CRC sample with known EMAST status and TGF-ß/Smad-dependent pathways. The association among ZEB1 expression, TGF-ß signalling pathway, EMAST status and metastatic behaviour was examined. Results: ZEB1 gene expression level was higher in tumour tissues as compared to normal samples (P<0.045). In addition, ZEB1 positive expression level was associated significantly with metastasis (P=0.05), EMAST+ status (P=0.052) and activated TGF-ß signalling pathway (P=0.002). Interpretation & conclusions: Our results validated significant association between activated TGF-ß signalling pathway and EMAST+ phenotype with higher expression of ZEB1 and higher level of metastasis.


Asunto(s)
Neoplasias Colorrectales , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Repeticiones de Microsatélite/genética , Metástasis de la Neoplasia , Factor de Crecimiento Transformador beta/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
7.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36293349

RESUMEN

The identification of expression quantitative trait loci (eQTL) is an important component in efforts to understand how genetic variants influence disease risk. MicroRNAs (miRNAs) are short noncoding RNA molecules capable of regulating the expression of several genes simultaneously. Recently, several novel isomers of miRNAs (isomiRs) that differ slightly in length and sequence composition compared to their canonical miRNAs have been reported. Here we present isomiR-eQTL, a user-friendly database designed to help researchers find single nucleotide polymorphisms (SNPs) that can impact miRNA (miR-eQTL) and isomiR expression (isomiR-eQTL) in 30 cancer types. The isomiR-eQTL includes a total of 152,671 miR-eQTLs and 2,390,805 isomiR-eQTLs at a false discovery rate (FDR) of 0.05. It also includes 65,733 miR-eQTLs overlapping known cancer-associated loci identified through genome-wide association studies (GWAS). To the best of our knowledge, this is the first study investigating the impact of SNPs on isomiR expression at the genome-wide level. This database may pave the way for researchers toward finding a model for personalised medicine in which miRNAs, isomiRs, and genotypes are utilised.


Asunto(s)
MicroARNs , Neoplasias , Humanos , Sitios de Carácter Cuantitativo , MicroARNs/genética , MicroARNs/metabolismo , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Neoplasias/genética , Isoformas de Proteínas/genética
8.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36293264

RESUMEN

Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms.


Asunto(s)
Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata , Masculino , Humanos , Isoformas de ARN , Estudio de Asociación del Genoma Completo/métodos , Sitios de Carácter Cuantitativo , Predisposición Genética a la Enfermedad , Neoplasias de la Próstata/genética , Isoformas de Proteínas/genética
9.
Cancer Metastasis Rev ; 38(3): 333-346, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31659564

RESUMEN

The prostate-specific antigen (PSA) blood test is the accepted biomarker of tumor recurrence. PSA levels in serum correlate with disease progression, though its diagnostic accuracy is questionable. As a result, significant progress has been made in developing modified PSA tests such as PSA velocity, PSA density, 4Kscore, PSA glycoprofiling, Prostate Health Index, and the STHLM3 test. PSA, a serine protease, is secreted from the epithelial cells of the prostate. PSA has been suggested as a molecular target for prostate cancer therapy due to the fact that it is not only active in prostate tissue but also has a pivotal role on prostate cancer signaling pathways including proliferation, invasion, metastasis, angiogenesis, apoptosis, immune response, and tumor microenvironment regulation. Here, we summarize the current standing of PSA in prostate cancer progression as well as its utility in prostate cancer therapeutic approaches with an emphasis on the role of PSA in the tumor microenvironment.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Animales , Humanos , Calicreínas/sangre , Masculino , Microambiente Tumoral
10.
Dermatol Ther ; 33(4): e13463, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32338408

RESUMEN

Lymphangioma circumscriptum is a benign lymphatic malformation that usually presents at birth or early childhood. Acquired oral lymphangioma has been reported secondary to radiation therapy and denture-induced trauma due to damage to previously normal lymphatics. To the best of our knowledge, this is the first report of acquired oral lymphangioma due to childhood tuberculous adenitis.


Asunto(s)
Linfangioma , Úlceras Bucales , Tuberculosis Ganglionar , Preescolar , Humanos , Recién Nacido , Linfangioma/diagnóstico , Linfangioma/etiología , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológico
11.
Int J Immunogenet ; 47(5): 430-434, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32090437

RESUMEN

Recent studies have shown participation of long non-coding RNAs (lncRNAs) in the pathogenesis of psoriasis. Several mechanisms might be involved in the dysregulation of expression of lncRNAs in patients with psoriasis, among them is the presence of single nucleotide polymorphisms (SNPs) which modulate expression or function of these transcripts. In the present work, we genotyped three SNPs (rs12826786, rs1899663 and rs4759314) of the HOX Transcript Antisense RNA (HOTAIR) in 286 patients with psoriasis and 300 control subjects. The rs12826786 was associated with risk of psoriasis in dominant model (TC + TT vs. CC: OR (95% CI) = 1.59 (0.1.14-2.22), adjusted p-value = .02). In the allelic model, T allele of this SNP significantly increased the risk of psoriasis compared with the C allele (OR (95% CI) = 1.35 (1.06-1.71), adjusted p-value = .04). Other SNPs were not associated with risk of psoriasis in any inheritance model. No significant difference was found in haplotype frequencies between cases and controls. The current work shows association between a genomic variant within HOTAIR and risk of psoriasis. The clinical significance of this finding should be assessed in future studies.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Psoriasis/genética , ARN Largo no Codificante/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Genotipo , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Psoriasis/epidemiología , Psoriasis/patología , Factores de Riesgo , Adulto Joven
12.
Rev Esp Enferm Dig ; 112(2): 101-108, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31880159

RESUMEN

INTRODUCTION: a routine small bowel biopsy (SBB) during the follow up of celiac disease (CD) is controversial. Little information is available regarding the histological changes during (gluten free diet (GFD) in the long term. OBJECTIVES: the aim of the study was to evaluate a novel criterion to compare duodenal histology in CD patients after six months and two years of gluten withdrawal. METHODS: this was a cross-sectional study of 200 patients with confirmed Marsh I-III who were under the six months (group A, n = 100) and 24 months (group B, n = 100) of a GFD. Nineteen patients were excluded due to an inadequate adherence to the GFD and another 23 patients were excluded as they were unwilling to undergo a re-endoscopy and did not comply with the necessary criteria. Endoscopy with a duodenal biopsy, serological assays and clinical evaluation were performed and compared with baseline data in the remaining 58 patients (20 patients in group A and 38 patients in group B). RESULTS: a significant complete histological recovery was found in 47.4% of patients in group B compared to 30% in group A (p = 0.026). A partial histological recovery was reported in seven (35%) and eleven (28.9%) patients in groups A and B, respectively. Any changes in mucosal histology after GFD was observed in 35% of patients in group A and 23.7% in group B. Serological assessment and endoscopic appearance normalized in 78.9% vs 75.0% in group B and 68.4% vs 65.0% in group A, respectively. However, this improvement did not reach statistical significance (p > 0.05). CONCLUSIONS: the results of this study show that histological recovery in patients with Marsh ≥ III is slow and does not correlate with symptomatic improvement. We suggest that the long-term effects of a GFD can play an important role in achieving histological improvement, especially in older patients.


Asunto(s)
Enfermedad Celíaca , Dieta Sin Gluten , Anciano , Biopsia , Estudios Transversales , Humanos , Mucosa Intestinal
13.
J Cell Physiol ; 234(4): 4768-4777, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30370522

RESUMEN

BACKGROUND: The clinical relevance and prognostic value of tumor-infiltrating lymphocytes (TILs) as an interplay between malignant cells and immune function has been known for decades. On contrary, this potential may be different by T lymphocytes subsets endowed with a different function. Colorectal cancer (CRC) is a heterogeneous disease with different suggested prognostic biomarkers. So, this study was conducted to examine the prognostic value of CD8+ TILs on the survival rate of CRC as an independent factor of oncogenetic tumor features. METHODS: With respect to this, 281 formalin-fixed, paraffin-embedded tissue samples of Iranian CRC patients were evaluated for clinical features including tumor location, tumor stage, differentiation grade, and mucinous characteristics. Then, using the standard immunohistochemical technique, tumor sections were examined, and CD8+ TILs were counted and identified in two regions of the tumor, including intratumoral (ITCIL TILs) and stromal (S TILs). The prognostic value of CD8+ TILs was determined by comparing with parameters, such as diagnostic age, tumor stage, adjuvant therapy, microsatellite instability (MSI) status, KRAS and BRAF mutations, family history, and survival. RESULTS: The presence of intratumoral tumor cell-infiltrating lymphocytes (ITCIL) CD8+ lymphocytes are significantly associated with differentiation (p = 0.004), tumor, node, and metastases (TNM) stage (p = 0.001), and MSI (p = 0.001). Meanwhile, based on the level of stromal infiltrating lymphocytes (SIL) infiltration, analysis of CRC patients was statistically associated with a location (p = 0.002), TNM stage (p < 0.001), metastasis (p < 0.001), and KRAS mutation (p = 0.031). Also, tumors with severe ITCIL CD8+ lymphocytes have a good prognosis compared with tumors with poor or moderate ITCIL CD8+ lymphocytes. CONCLUSIONS: These results suggest that intratumor cell-infiltrating CD8- T lymphocytes as an independent prognostic factor that have an antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of CRC.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Neoplasias Colorrectales/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Metástasis Linfática , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Factores de Tiempo
14.
Ecotoxicol Environ Saf ; 178: 168-177, 2019 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-31004929

RESUMEN

OBJECTIVES: Among the numerous agents, genetic factors and environmental elements such as pesticides have an important role in colorectal cancer (CRC) incidence. The present study aimed to investigate the probable-role of some organochlorine pesticides (OCPs) and organophosphorous pesticides (OPPs) in patients with CRC. METHODS: In this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4DDT and 4,4DDT) were measured by gas chromatography (GC) method. Serum levels of malondialdehyde (MDA), and total antioxidant capacity (TAC) as well as the enzyme activity of acetylcholinesterase (AChE) and arylesterase activity of Paraoxonase-1 (PON-1) were evaluated in all participants. The methylation specific PCR (MSP) assay was used for determining the methylation status of CpG island of p16 and MGMT genes in CRC patients. RESULTS: The mean serum levels of each OCPs were significantly higher in the patient group compared to the control group (P < 0.001). The AChE and arylesterase activity of PON-1 in the patient group were significantly lower than the control group (P < 0.001). The mean serum levels of MDA and TAC in the serum of the patient group were significantly higher than the control group (P < 0.001 and P < 0.002, respectively). The current findings demonstrated significantly hypermethylation of p16 promoter in CRC patients. CONCLUSION: Regarding the higher levels of OCPs in CRC patients, along with hypermethylation of the p16 promoter gene, diminishing in AChE and PON-1 activity and increasing in oxidative stress factors, the role of OCPs and OPPs in the CRC progression in the South-East of Iran may be assumed.


Asunto(s)
Neoplasias Colorrectales/sangre , Hidrocarburos Clorados/sangre , Compuestos Organofosforados/sangre , Plaguicidas/sangre , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Islas de CpG , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Genes p16 , Humanos , Irán , Masculino , Malondialdehído/análisis , Persona de Mediana Edad , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor/genética
15.
Indian J Clin Biochem ; 34(3): 347-351, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31391727

RESUMEN

MUC4 is aberrantly expressed in several carcinomas including breast, colon, ovarian, lung, prostate, stomach and pancreatic cancers. MUC4 can regulate cell apoptosis negatively and facilitate stomach tumorigenesis. In this research, we aimed to evaluate the possible association between rs2641726 (C > A) polymorphism of MUC4 and gastric cancer risk in the Iranian population. In this case-control study, we collected blood samples from 168 gastric cancer patients and 66 healthy subjects. Allele-specific primer polymerase chain reaction method was applied to genotype rs2641726 in the obtained DNA samples. This study demonstrated that rs2641726 C allele was significantly associated with the incidence of gastric cancer, odds ratio = 3.382, 95% confidence interval: 1.840-6.217 (P < 0.001). Furthermore, the distribution of this risk allele was highly enriched in the samples with stage III. In silico studies revealed that the C allele of rs2641726, located within MUC4 3'UTR, is potential to attenuate the interaction between miR-581 and MUC4 mRNA. This disturbing effect, which might result in higher expression of MUC4 oncoprotein, was proposed for the mechanism of action of the rs2641726 risk allele. rs2641726 C allele is significantly enriched in gastric cancer specimens. The attenuating effect of this allele on miR-581 and MUC4 interaction might be a potential mechanism of action by which C allele imposes its oncogenic impact.

16.
Cell Mol Biol (Noisy-le-grand) ; 64(9): 58-63, 2018 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-30030958

RESUMEN

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22) (q34;q11.2) encoding for the BCR-ABL fusion oncogene. Growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. The significant of therapeutic role in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms.  This article focused on the CML and epigenetic and clinical significance. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, cancer, Google scholar, self-experience and PubMed databases. The keywords included leukemia, cancer, illness, epigenetic. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. Current progress in molecular biology and bioinformatics offer novel promising experiments namely as next generation sequencing for new development in epigenetic figures characterization and more understanding of the epigenetic mechanisms to be successfully utilized for personalized CML therapy in the next coming years.


Asunto(s)
ADN/metabolismo , Epigénesis Genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Metilación de ADN , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-crk/metabolismo
17.
Toxicol Mech Methods ; 27(8): 622-630, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28651465

RESUMEN

Euphorbia species have been used in traditional medicine in many countries for the treatment of cancer. This article aims to evaluate the capability of a new lathyrane diterpene isolated from Euphorbia aellenii to induce apoptosis in the Caov-4 cell line to determine the underlying mechanism of its anticancer effects. A new 6(17)-epoxylathyrane diterpenes: aellinane from Euphorbia aellenii was evaluated for viability of Caov-4 cells by MTT method. Apoptosis induction by lathyrane diterpene was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. The Bcl2 and Bax protein content were detected by Western blot analysis. Finally, we employed the fluorescent ROS detection kit and fluorochrome JC-1 to determine ROS levels and loss of mitochondria membrane potential (ΔΨm) in Caov-4 cells, respectively. The results show that lathyrane diterpene has significant cytotoxic effect against Caov-4 cells. The IC50 value was 45 µM. Annexin V/propidium iodide (PI) staining and caspase-6 activity assay confirmed that lathyrane diterpene is able to induce apoptosis in Caov-4 cells. The results also demonstrate that lathyrane diterpene up-regulated Bax and down-regulated Bcl-2 proteins. Moreover, apoptotic effect of lathyrane diterpene was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). This study demonstrated that lathyrane diterpene has profound activity against Caov-4 cells. Analysis of apoptosis-related proteins revealed that lathyrane diterpene triggered the mitochondrion-mediated apoptosis pathway, which led to the loss of mitochondrial membrane potential (ΔΨm) and activation of caspase-6. Therefore, we believe that lathyrane diterpene might be a promising natural compound in ovarian cancer therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Euphorbia/química , Mitocondrias/efectos de los fármacos , Neoplasias Ováricas/patología , Western Blotting , Línea Celular Tumoral , Femenino , Humanos , Concentración 50 Inhibidora , Especies Reactivas de Oxígeno/metabolismo
18.
J Chem Phys ; 141(2): 024111, 2014 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-25028003

RESUMEN

We study the multipole plasmon mode frequencies of a pair of C60 molecules by means of the linearized hydrodynamic theory for electronic excitations on the each C60 surface. We apply the two-center spherical coordinate system for mathematical convenience and find an explicit form of the surface plasmon energies. Numerical result shows when approaching the two C60 molecules, the coupling between the bare plasmon modes leads to the appearance of additional modes having energies that are different from those of the isolated C60 molecules.

19.
J Chem Phys ; 141(12): 124121, 2014 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-25273426

RESUMEN

An analytical approach describing the surface plasmon modes of a nanoegg (a nanoshell with a nonconcentric core) above a substrate is presented. The bispherical coordinate system is used for mathematical convenience. A general dispersion relation for the coupled modes as function of geometrical characteristics of the system is obtained. In the special case (in the limit of a very large separation between the nanoegg and substrate) dispersion relation of the plasmon modes of an isolated nanoegg is derived. It is shown that the coupled plasmon modes exhibit excellent numerical convergence.

20.
J Pak Med Assoc ; 64(10): 1151-3, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25823155

RESUMEN

OBJECTIVES: To investigate the effects of magnesium sulphate on succinylcholine-induced fasciculation in patients during the induction of general anaesthesia. METHODS: The double-blind randomised clinical trial was conducted in 2012 at Tohid and Besat Hospitals in Sanandaj, Iran, on patients who were candidates for surgery under general anaesthesia. Patients were selected and divided into two equal groups of cases and controls using block randomisation. The cases received magnesium sulphate, while the controls received normal saline. SPSS 18 was used for statistical analysis. RESULTS: Of the 100 subjects in the study, 49 (49%) were men and 51 (51%) were women (p < 0.072). The mean age of the two groups were 37.5 ± 12.2 years and 37.7 ± 12 years (p < 0.9). There was significant difference between the two groups in terms of the degree of fasciculation and muscle fasciculation (p< 0.001). The difference between potassium levels in the two groups was not significant before anaesthesia (p > 0.05), but it was significant after anaesthesia (p < 0.001). CONCLUSIONS: Magnesium sulphate can prevent and reduce the degree of fasciculation after anaesthesia. Therefore it can be used to prevent fasciculation.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Fasciculación/inducido químicamente , Fasciculación/prevención & control , Sulfato de Magnesio/uso terapéutico , Fármacos Neuromusculares Despolarizantes/efectos adversos , Succinilcolina/efectos adversos , Adulto , Anestesia General , Método Doble Ciego , Fasciculación/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Potasio/sangre
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