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1.
Curr HIV Res ; 22(1): 53-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38310469

RESUMO

BACKGROUND: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. OBJECTIVE: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. METHODS: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. RESULTS: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. CONCLUSION: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.


Assuntos
Farmacorresistência Viral , Infecções por HIV , HIV-1 , Mutação , Carga Viral , Humanos , Masculino , HIV-1/efeitos dos fármacos , HIV-1/genética , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Irã (Geográfico)/epidemiologia , Estudos Transversais , Farmacorresistência Viral/genética , Adulto , Pessoa de Meia-Idade , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Adulto Jovem , Contagem de Linfócito CD4 , Falha de Tratamento
2.
J Cancer Res Clin Oncol ; 149(8): 4253-4267, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36063222

RESUMO

INTRODUCTION: Recent developments in genomic sequencing have led to the identification of somatic mutations in isocitrate dehydrogenase 1 (IDH1) in various malignancies. IDH1 R132H is the most common mutation of IDH1, which affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This study is designed to evaluate the association between the expression of IDH1 R132H and clinicopathological characteristics in laryngeal squamous cell carcinoma (LSCC). METHODS: The expression pattern and clinical significance of IDH1 R132H were investigated in tissue microarrays (TMAs) of 50 LSCC tumors as well as adjacent normal tissues using immunohistochemistry. Then the exons of the 12 tumor samples with negative/weak positive staining were sequenced by applying polymerase chain reaction (PCR). RESULTS: The results demonstrated that the cytoplasmic expression of IDH1 R132H was downregulated in tumor cells compared to adjacent normal tissues. A statistically significant association was found between a low level of cytoplasmic expression of IDH1 R132H protein and an increase in histological grade (p < 0.001), perineural invasion (p = 0.019), and lymph node involvement (p < 0.001). The exon4 sequencing results showed that only one sample was positive for IDH1 R132H mutation. IDH1 R132H expression was observed in 39 (78.0%) LSCC samples. CONCLUSION: These findings indicate that low cytoplasmic expression of IDH1 R132H may have clinical significance in LSCC patients and is associated with more aggressive tumor behavior and progression of the disease, which can help improve potential treatment in patients with LSCC. Further investigations are needed to understand the biological function of IDH1 R132H and larger sample size to confirm our findings.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias de Cabeça e Pescoço , Humanos , Glioma/patologia , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Mutação , Neoplasias Encefálicas/patologia
3.
Appl Immunohistochem Mol Morphol ; 31(6): 390-398, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37278280

RESUMO

Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Oligodendroglioma , Humanos , Proteína Supressora de Tumor p53/genética , Imuno-Histoquímica , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteína Nuclear Ligada ao X/genética , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Glioblastoma/patologia , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética , Oligodendroglioma/patologia , Mutação , Aberrações Cromossômicas , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo
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