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1.
Sci Rep ; 13(1): 19107, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925591

RESUMO

TGFB1, which encodes TGF-ß1, a potent cytokine regulating varies cellular processes including immune responses. TGF-ß1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.


Assuntos
Neoplasias Hematológicas , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Citocinas , Prognóstico , Neoplasias Hematológicas/genética , Microambiente Tumoral/genética , Imunoterapia
2.
Medicine (Baltimore) ; 102(28): e34333, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37443507

RESUMO

RATIONALE: To investigate the clinical efficacy of the axillary approach in the surgical treatment of Ideberg type I and II scapular glenoid fractures. PATIENT CONCERNS AND DIAGNOSIS: Retrospective analysis of 13 cases of scapular glenoid fracture treated in the affiliated Hospital of Jining Medical College, Jiaxiang County People hospital, Zoucheng City people Hospital, Yanzhou District People Hospital, and Juancheng County people Hospital from December 2020 to January 2022. Eight males (including 1 bilateral) and 5 females, with an average age of 57.5 years (range from 33 to 75 years). According to Ideberg classification, there were 10 cases of type I a, 1 case of type I a combined with type I b, and 2 cases of type II. All patients were treated with axillary approach surgery and 7 patients with combined anterior shoulder dislocation were treated by first-stage manipulation and second-stage reoperation. Seven patients were fixed with a wire anchor, 3 patients with type I a were fixed with a "T" plate, and 5 patients were complicated with rotator cuff tear and were repaired with a wire anchor. At the last follow-up, the Constant-Murley shoulder function score, visual analog score, DASH score, and Hawkins grade were used to evaluate shoulder function, pain, and stability after treatment. INTERVENTION: The intervention was to treat patients with Ideberg type I and II scaphoid fractures using an axillary approach. OUTCOMES: All 13 patients in this group were followed up thoroughly, and the follow-up time was 12 to 25 months, with an average of 18.6 months. The operation time was 65 to 135 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 to 120 mL, averaging 55.6 mL. The duration of hospitalization ranged from 7 to 22 days, with an average of 9.6 days. The surgical incisions of all patients were grade-A healing. Bone healing of glenoid fractures was observed 3 months after the operation. LESSONS: The axillary approach for Ideberg type I and II scapular glenoid fractures is a feasible surgical approach with complete access through the muscle gap, minimal surgical trauma, mild postoperative pain, and satisfactory clinical results.


Assuntos
Fixação Interna de Fraturas , Fraturas do Ombro , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Escápula/cirurgia , Escápula/lesões , Ombro/cirurgia , Fraturas do Ombro/cirurgia , Resultado do Tratamento
3.
Aging (Albany NY) ; 15(9): 3498-3523, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37179124

RESUMO

Recent research revealed methionine metabolism as a key mediator of tumor initiation and immune evasion. However, the relationship between methionine metabolism and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unknown. Here, we comprehensively analyzed the genomic alterations, expression patterns, and prognostic values of 68 methionine-related regulators (MRGs) in LUAD. We found that most MRGs were highly prognostic based on 30 datasets including 5024 LUAD patients. Three distinct MRG modification patterns were identified, which showed significant differences in clinical outcomes and TME characteristics: The C2 subtype was characterized by higher immune score, while the C3 subtype had more malignant cells and worse survival. We developed a MethScore to measure the level of methionine metabolism in LUAD. MethScore was positively correlated with T-cell dysfunction and tumor-associated macrophages (TAMs), indicating a dysfunctional TME phenotype in the high MethScore group. In addition, two immunotherapy cohorts confirmed that patients with a lower MethScore exhibited significant clinical benefits. Our study highlights the important role of methionine metabolism in modeling the TME. Evaluating methionine modification patterns will enhance our understanding of TME characteristics and can guide more effective immunotherapy strategies.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Metionina , Racemetionina , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Imunoterapia , Microambiente Tumoral/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia
4.
Aging (Albany NY) ; 13(8): 11096-11119, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33744857

RESUMO

Although a previous pan-cancer study has reported the expression patterns of ITIHs in various tumors, their analyses have been restricted to limited cancer types. We thus comprehensively analyzed the expression profiles and clinical significances of ITIHs in a broader spectrum of cancers from TCGA. Our results showed that ITIHs were primarily down-regulated in tested cancers. The ITIH members were associated with either survival advantage or disadvantage, depending on the cancer type tested and the genes queried. Importantly, we for the first time demonstrated that ITIH1 had substantially decreased expression in liver hepatocellular carcinoma (LIHC) compared with corresponding normal tissue, and its down-regulation adversely impacted patient outcome. Moreover, ITIH1 expression was consistently declining during the progression of LIHC. Further analysis revealed that ITIH1 may be involved in cellular metabolic processes. Our findings established ITIH1 as a potential diagnostic and prognostic biomarker for LIHC, which awaits future experimental validation.


Assuntos
alfa-Globulinas/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , alfa-Globulinas/análise , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Conjuntos de Dados como Assunto , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Intervalo Livre de Progressão
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