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Introduction Bladder cancer is a significant health issue with an increased recurrence and progression rate, requiring invasive follow-up, which shows a poor prognosis. In addition, the prognostic role of mutant fibroblast growth factor receptor 3 (FGFR3) and tumor protein P53 (TP53) is controversial; therefore, we investigated the methylation status and their altered gene expression in low- and high-grade non-muscle-invasive bladder cancer (NMIBC) subjects. Materials and methods This case-control study was conducted between 2020 and 2023, in which n = 115 tumor tissues (NMIBC n = 85) and (controls n = 30) were examined for FGFR3 and FGFR promoter methylation and expression using methylation-specific PCR (MSP) and real-time PCR. The multivariate regression analysis and Kaplan-Meier (KM) plots were used to establish the association of FGFR3 and TP53 with clinicopathological features and survival outcomes of NMIBC patients. Results High-grade NMIBC tumors showed substantial methylation patterns, with TP53 hypomethylated (p = 0.034) and FGFR3 hypermethylated (p = 0.046), as well as significant mRNA expression of Tp53 and FGFR3 (p = 0.001). The multivariate analysis shows FGFR3 and Tp53 were associated with recurrence-free survival with sensitivity (p = 0.045 (78%); 0.034 (70.7%)) and progression-free survival (p = 0.022(61.5%); 0.038 (69.2%)). Conclusion The findings of this investigation indicate that FGFR3 hypermethylation and TP53 hypomethylation are independent prognostic indicators that aid in the evaluation of disease outcomes in high-grade NMIBC tumors.
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In this report, retrospectively, we analyzed fifteen histo-pathologically characterized FFPE based Wilms' Tumor (WT) samples following an integrative approach of copy number (CN) and loss of heterozygosity (LOH) imbalances. The isolated-DNA was tested on CN and somatic-mutation related Molecular-Inversion-Probe based-Oncoscan Array™ and was analyzed through Nexus-Express OncoScan-3.0 and 7.0 software. We identified gain of 3p13.0-q29, 4p16.3-14.0, 7, 12p13.33-q24.33, and losses of 1p36.11-q44, 11p15.5-q25, 21q 22.2-22.3 and 22q11.21-13.2 in six samples (W1-6) and validated them in nine more samples (W7-9, W12-15, W17-18). Some observed that discrete deletions (1p, 1q, 10p, 10q, 13q, 20p) were specific to our samples. Maximum-LOH was observed in Ch11 as reported in previous studies. However, LOH was also observed in different regions of Ch7 including some cancer genes. The identified LOH-regions (1q21.2-q21.3, 2p24.1-23.3, 2p24.3-24.3, 3p21.3-21.1, 4p16.3, 7p11.2-p11.1, 7q31.2-31.32, 7q34-q35 and Ch 8) in W1-W6 were also validated in W7-9, W12-15 and W18. In addition, previously reported LOH of 1p and 16q region was also observed in our cases. The proven and novel onco (OG)- and tumor-suppressor genes (TSGs) involved in the CNV regions affected the major pathways like Chromatin Modification, RAS, PI3K; RAS in 14/15 cases, NOTCH/TGF-ß and Cell Cycle Apoptosis in 10/15 cases, APC in 9/15 cases and Transcriptional Regulation in 7/15 cases, PI3K and genome maintenance in 6/15 cases. This exhaustive profiling of OG and TG may help in prognosis and diagnosis of the disease after validation of all the relevant results, especially the novel ones, obtained in this research in a larger number of samples.
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Inversão Cromossômica/genética , Dosagem de Genes/genética , Neoplasias Renais/genética , Sondas Moleculares/genética , Mutação/genética , Tumor de Wilms/genética , Apoptose/genética , Ciclo Celular/genética , Cromatina/genética , Cromossomos Humanos/genética , Genes Supressores de Tumor , Genoma/genética , Humanos , Perda de Heterozigosidade/genética , Análise em Microsséries/métodos , Fosfatidilinositol 3-Quinases/genética , Estudos Retrospectivos , Software , Fator de Crescimento Transformador beta/genéticaRESUMO
Labeo rohita (Ham.) also called rohu is the most important freshwater aquaculture species on the Indian sub continent. Monsoon dependent breeding restricts its seed production beyond season indicating a strong genetic control about which very limited information is available. Additionally, few genomic resources are publicly available for this species. Here we sought to identify reproduction-relevant genes from normalized cDNA libraries of the brain-pituitary-gonad-liver (BPGL-axis) tissues of adult L. rohita collected during post preparatory phase. 6161 random clones sequenced (Sanger-based) from these libraries produced 4642 (75.34%) high-quality sequences. They were assembled into 3631 (78.22%) unique sequences composed of 709 contigs and 2922 singletons. A total of 182 unique sequences were found to be associated with reproduction-related genes, mainly under the GO term categories of reproduction, neuro-peptide hormone activity, hormone and receptor binding, receptor activity, signal transduction, embryonic development, cell-cell signaling, cell death and anti-apoptosis process. Several important reproduction-related genes reported here for the first time in L. rohita are zona pellucida sperm-binding protein 3, aquaporin-12, spermine oxidase, sperm associated antigen 7, testis expressed 261, progesterone receptor membrane component, Neuropeptide Y and Pro-opiomelanocortin. Quantitative RT-PCR-based analyses of 8 known and 8 unknown transcripts during preparatory and post-spawning phase showed increased expression level of most of the transcripts during preparatory phase (except Neuropeptide Y) in comparison to post-spawning phase indicating possible roles in initiation of gonad maturation. Expression of unknown transcripts was also found in prolific breeder common carp and tilapia, but levels of expression were much higher in seasonal breeder rohu. 3631 unique sequences contained 236 (6.49%) putative microsatellites with the AG (28.16%) repeat as the most frequent motif. Twenty loci showed polymorphism in 36 unrelated individuals with allele frequency ranging from 2 to 7 per locus. The observed heterozygosity ranged from 0.096 to 0.774 whereas the expected heterozygosity ranged from 0.109 to 0.801. Identification of 182 important reproduction-related genes and expression pattern of 16 transcripts in preparatory and post-spawning phase along with 20 polymorphic EST-SSRs should be highly useful for the future reproductive molecular studies and selection program in Labeo rohita.
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Carpas/genética , Etiquetas de Sequências Expressas , Proteínas de Peixes/genética , Repetições de Microssatélites , Reprodução/genética , Testículo/citologia , Animais , Encéfalo/citologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Frequência do Gene , Biblioteca Gênica , Loci Gênicos , Heterozigoto , Fígado/citologia , Masculino , Ovário/citologia , Hipófise/citologia , Polimorfismo Genético , Reação em Cadeia da Polimerase em Tempo Real , Estações do AnoRESUMO
BACKGROUND: Sufentanil added to intrathecal bupivacaine for cesarean section has shown to improve intraoperative and postoperative analgesia with no adverse effects on the mother and neonate. We compared the effects of intrathecal sufentanil 5 mcg and placebo when administered with hyperbaric bupivacaine 0.5% 11 mg for cesarean section. PATIENTS AND METHODS: Sixty parturients of ASA grading I and II of age between 18 to 45 years scheduled for elective cesarean section under subarachnoid block were randomly allocated into one of the two groups to receive 5µg sufentanil + 0.2ml sterile, preservative- free normal saline (Group S) and 0.3ml sterile, preservative-free normal saline (Group C) along with 2.2ml 0.5% hyperbaric bupivacaine making total volume to 2.5 ml. RESULTS: The two groups were compared with respect to their sensory and motor block characteristics, duration of analgesia, intraoperative haemodynamic changes, adverse effects and effect on neonatal Apgar score. Postoperative pain was assessed using the visual analog scale (VAS). Duration of analgesia was defined as the time taken for a VAS score of 4 to be achieved. Mean duration of analgesia was significantly prolonged in sufentanil group (184.0 + 51.50 minutes) than the control group (107.0 ± 46.40 minutes). There is faster onset of sensory and motor block in the sufentanil group. The incidences of bradycardia and hypotensive episodes were similar in the two groups. There was no evidence of respiratory depression in any of the patients in any groups. Pruritus was observed in 6 (20.0%) patients in Group S which was statistically significant. There was no significant effect on Apgar score of the neonate. CONCLUSION: Thus the addition of Sufentanil (5 mcg) intrathecally provides improved postoperative analgesia and haemodynamic stability with minimal side effects.
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We have described an unusual presentation of lupus retinopathy in the form of macular arterio-arterial and arterio-venular shunts with extensive macular ischemia as a presenting sign.
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Lúpus Eritematoso Sistêmico/complicações , Doenças Retinianas/diagnóstico , Adulto , Feminino , Angiofluoresceinografia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Retinianas/complicaçõesRESUMO
PURPOSE: To report a variant form of serpiginous choroiditis, that initially or predominantly involved the macular area. METHODS: Nine eyes of 6 patients with the macular form of serpiginous choroiditis were evaluated clinically and angiographically in a longitudinal fashion for a period of 12-36 months. The active stage and the recurrences were treated by oral and periocular cortico steroids; and two patients were supplemented with oral azathioprine. Most of these patients were referred to our center with varied diagnoses. RESULTS: In this group, 4 were male and 2 were female with an average age of 30.5 years. Three patients had bilateral macular lesions, two had typical serpiginous choroiditis in the fellow eye and the remaining one had unilateral macular involvement alone. The initial visual acuity was 6/60 or less in 60% eyes whereas the final visual acuity was 6/18 or better in 66% eyes. Angiographic findings were typical of serpiginous choroiditis characterised by early hypofluorescence followed by leakage and staining of the borders and the lesion itself without any evidence of choroidal ischaemia or retinal vascular abnormalities. CONCLUSION: The macular variant of serpiginous choroiditis can mimic many other macular pathologic lesions, thus posing a diagnostic dilemma. Because of its relentless destructive course, early diagnosis and prompt treatment is required to prevent sight-threatening complications.
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Corioidite/patologia , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Corioide/irrigação sanguínea , Corioidite/diagnóstico por imagem , Corioidite/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Angiofluoresceinografia , Humanos , Imunossupressores/uso terapêutico , Injeções , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado Ocular/diagnóstico por imagem , Epitélio Pigmentado Ocular/patologia , Prednisolona/uso terapêutico , Prognóstico , Radiografia , Recidiva , Estudos Retrospectivos , Triancinolona/administração & dosagem , Triancinolona/uso terapêutico , Acuidade VisualRESUMO
This first report from India describes 5 cases of Bietti's crystalline dystrophy without corneal involvement.