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1.
Pharmacol Res ; 203: 107185, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615875

RESUMO

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Animais , Microbioma Gastrointestinal , Microbiota , Imunoterapia/métodos
2.
Langenbecks Arch Surg ; 409(1): 148, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695994

RESUMO

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.


Assuntos
Anastomose Cirúrgica , Gastrectomia , Procedimentos de Cirurgia Plástica , Neoplasias Gástricas , Humanos , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Anastomose Cirúrgica/métodos , Procedimentos de Cirurgia Plástica/métodos , Junção Esofagogástrica/cirurgia , Retalhos Cirúrgicos , Jejuno/cirurgia
3.
Angew Chem Int Ed Engl ; 62(40): e202309831, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37594921

RESUMO

Self-assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis of a new series of carboxylic acid-functionalized porphyrin derivatives, namely AC-1, AC-3, and AC-5, and present, for the first time, a strategy to exploit the large π-moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron-rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double-anchored AC-3 and AC-5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC-5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.

4.
J Cell Biochem ; 121(8-9): 3854-3860, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31709598

RESUMO

This study aimed to identify prognostic long noncoding RNAs (lncRNAs) signature for predicting the prognosis of patients with rectal cancer. LncRNA-sequencing data and clinicopathological data of patients with rectal cancer were retrieved from The Cancer Genome Atlas database. Univariate and multivariate Cox proportional hazards regression analysis, the least absolute shrinkage, and selection operator analysis and the Kaplan-Meier curve method were employed to identify prognostic lncRNAs and construct multi-lncRNA signature. Finally, five lncRNAs (AC079789.1, AC106900.2, AL121987.1, AP004609.1, and LINC02163) were identified to construct a five-lncRNA signature. According to the five-lncRNA signature, patients with rectal cancer were divided into a high-risk group and low-risk group. Patients with rectal cancer had significantly poorer overall survival in the high-risk group than in the low-risk group. We used a time-dependent receiver operating characteristic curve to assess the power of the five-lncRNA signature by calculating the area under the curve (AUC). The AUCs for predicting 3-year survival and 5-year survival were 0.742 and 0.935, respectively, which indicated a good performance of the five-lncRNA signature. The five-lncRNA signature was independently associated with the prognosis of patients with rectal cancer through using univariate and multivariate Cox regression analysis. The biological function of the five lncRNAs was enriched in some cancer-related biological processes and pathways by performing functional enrichment analysis of their correlated protein-coding genes. In conclusion, we developed a five-lncRNA signature as a potential indicator for rectal cancer.

5.
Cell Immunol ; 349: 104063, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32087929

RESUMO

Extracellular vesicles (EVs), including exosomes, ectosomes and apoptotic vesicles, play an essential role in communication between cells of the innate and adaptive immune systems. Recent studies showed that EVs released after transplantation of allogeneic tissues and organs are involved in the immune recognition and response leading to rejection or tolerance in mice. After skin, pancreatic islet, and solid organ transplantation, donor-derived EVs were shown to initiate direct inflammatory alloresponses by T cells leading to acute rejection. This occurred through presentation of intact allogeneic MHC molecules on recipient antigen presenting cells (MHC cross-dressing) and subsequent activation of T cells via semi-direct allorecognition. On the other hand, some studies have documented the role of EVs in maternal tolerance of fetal alloantigens during pregnancy and immune privilege associated with spontaneous tolerance of liver allografts in laboratory rodents. The precise nature of the EVs, which are involved in rejection or tolerance, and the cells which produce them, is still unclear. Nevertheless, several reports showed that EVs released in the blood and urine by allografts can be used as biomarkers of rejection. This article reviews current knowledge on the contribution of EVs in allorecognition by T cells and discusses some mechanisms underlying their influence on T cell alloimmunity in allograft rejection or tolerance.


Assuntos
Aloenxertos/imunologia , Vesículas Extracelulares/imunologia , Rejeição de Enxerto/imunologia , Tolerância ao Transplante/imunologia , Imunidade Adaptativa , Animais , Apresentação de Antígeno , Células Apresentadoras de Antígenos/imunologia , Biomarcadores , Quimerismo , Vesículas Extracelulares/metabolismo , Feminino , Xenoenxertos/imunologia , Humanos , Imunidade Inata , Isoantígenos/imunologia , Masculino , Troca Materno-Fetal/imunologia , Camundongos , Gravidez
6.
Exp Cell Res ; 363(2): 218-226, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29331390

RESUMO

The poor outcome of hepatocellular carcinoma (HCC) is mainly due to the development of fast growth, invasion and metastasis. The role of TET2 has been implicated in some cancer types, but its role and mechanisms in HCC remains elusive. In this study, our findings indicated that TET2 expression frequently increased in HCC and that TET2 expressional upregulation correlated with HCC progression. TET2 knockdown inhibited HCC cells proliferation in vitro and growth in vivo, and inhibited the invasion potential of HCC cells. Mechanically, TET2 knockdown upregulated E-cadherin expression and then attenuated ß-catenin transactivation in HCC cells. TET2 repressed E-cadherin expression via recruited HDAC1 to E-cadherin promoter to reduce the H3K9Ac and H4K16Ac levels. Moreover, ß-catenin signaling transcriptionally regulated TET2 expression to form a positive feedback in HCC cells. These findings indicate that the dysregulation of TET2/E-cadherin/ß-catenin regulatory loop is a critical oncogenic event in HCC progression.


Assuntos
Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas/metabolismo , beta Catenina/metabolismo , Idoso , Carcinoma Hepatocelular/patologia , Dioxigenases , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia
7.
Curr Opin Organ Transplant ; 23(1): 22-27, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29189413

RESUMO

PURPOSE OF REVIEW: This article reviews recent literature on the nature of extracellular vesicles released by allogeneic transplants and examine their role in T-cell alloimmunity involved in rejection and tolerance of these grafts. RECENT FINDINGS: Donor cells release extracellular vesicles, including exosomes, after transplantation of allogeneic organs and tissues. Consequently, recipient APCs take up these exosomes and present donor MHC antigens on their surface (allo-MHC cross-dressing) thus, activating some alloreactive T cells via a mechanism called semi-direct pathway of allorecognition. In addition, one study shows that exosomes carrying noninherited maternal antigens are associated with maternal microchimerism and tolerance in offspring. Finally, a few studies describe potential utilization of exosomes as modulators of alloimmunity and biomarkers of rejection in allotransplantation. SUMMARY: Extracellular vesicles, including exosomes, released by allografts contribute to recognition of donor antigens by T cells after allotransplantation. This occurs through cross-dressing of recipient APCs with donor MHC antigens and subsequent activation of T cells, a process called semi-direct alloreactivity. The relevance of this phenomenon in rejection and tolerance of allografts and the potential utilization of exosomes as biomarkers in transplantation are discussed.


Assuntos
Aloenxertos/imunologia , Apresentação de Antígeno/imunologia , Exossomos/imunologia , Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade/imunologia , Isoantígenos/imunologia , Doadores de Tecidos , Animais , Humanos , Transplante Homólogo
8.
Med Sci Monit ; 23: 3904-3912, 2017 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-28802099

RESUMO

BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts. TNBC cells growth was detected by MTT assay, and epithelial-mesenchymal transition (EMT) regulated by CAFs was evaluated by Western blot assay. RESULTS CAFs were identified by the high expression of α-smooth muscle actin (α-SMA) protein. Autophagy-relevant Beclin 1 and LC3-II/I protein conversion levels in CAFs were higher than those in NFs (P<0.05). TNBC cells migration, invasion, and proliferation levels were significantly improved in the CAFs-conditioned medium (CAFs-CM) group, compared with the other 3 groups (P<0.05). TNBC cells vimentin and N-cadherin protein levels were upregulated and E-cadherin protein level was downregulated in the CAFs-CM group compared with the control group (P<0.05). Further study indicated b-catenin and P-GSK-3ß protein levels, which are the key proteins in the Wnt/ß-catenin pathway, were upregulated in the CAFs-CM group compared with the control group (P<0.05). CONCLUSIONS Our data demonstrated CAFs autophagy can enhance TNBC cell migration, invasion, and proliferation, and CAFs autophagy can induce TNBC cells to engage in the EMT process through the Wnt/ß-catenin pathway.


Assuntos
Actinas/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Actinas/análise , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Caderinas/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/fisiologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , China , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/metabolismo , Neoplasias de Mama Triplo Negativas/fisiopatologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/efeitos dos fármacos , beta Catenina/metabolismo
9.
Mar Drugs ; 15(5)2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28445442

RESUMO

Cyanobacteria are rich sources of structurally-diverse molecules with promising pharmacological activities. Marine cyanobacteria have been proven to be true producers of some significant bioactive metabolites from marine invertebrates. Macrolides are a class of bioactive compounds isolated from marine organisms, including marine microorganisms in particular. The structural characteristics of macrolides from cyanobacteria mainly manifest in the diversity of carbon skeletons, complexes of chlorinated thiazole-containing molecules and complex spatial configuration. In the present work, we systematically reviewed the structures and pharmacological activities of macrolides from cyanobacteria. Our data would help establish an effective support system for the discovery and development of cyanobacterium-derived macrolides.


Assuntos
Cianobactérias/química , Macrolídeos/química , Macrolídeos/farmacologia , Animais , Organismos Aquáticos/química , Fatores Biológicos/química , Fatores Biológicos/farmacologia , Humanos , Relação Estrutura-Atividade
10.
Phytomedicine ; 128: 155535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537442

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.


Assuntos
Flavonoides , Hipertensão Arterial Pulmonar , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Animais , Hipertensão Pulmonar/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos
11.
Drug Discov Today ; 29(2): 103875, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176674

RESUMO

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Medicina Tradicional , Adenosina , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
12.
Front Med (Lausanne) ; 11: 1303855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384412

RESUMO

Background: SARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection. Methods: The clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported. Results: Female patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto's thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto's thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable "thyrotoxicosis" after infection, suggesting the diagnosis of painless thyroiditis. Conclusion: The five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.

13.
Clin Transl Oncol ; 26(6): 1446-1458, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38190035

RESUMO

BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.


Assuntos
Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Antígeno B7-H1/antagonistas & inibidores , Adulto , Idoso de 80 Anos ou mais , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Taxa de Sobrevida
14.
Heliyon ; 9(8): e19308, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664726

RESUMO

Pulmonary fibrosis is an enduring and advancing pulmonary interstitial disease caused by multiple factors that ultimately lead to structural changes in normal lung tissue. Currently, pulmonary fibrosis is a global disease with a high degree of heterogeneity and mortality rate. Nitidine and pirfenidone have been approved for treating pulmonary fibrosis, and the quest for effective therapeutic drugs remains unabated. In recent years, the anti-pulmonary fibrosis properties of natural flavonoids have garnered heightened attention, although further research is needed. In this paper, the resources, structural characteristics, anti-pulmonary fibrosis properties and mechanisms of natural flavonoids were reviewed. We hope to provide potential opportunities for the application of flavonoids in the fight against pulmonary fibrosis.

15.
Cancer Res Treat ; 55(3): 1023-1030, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36758956

RESUMO

PURPOSE: This study aimed to explore the impact of ABL1-tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients' prognosis from TKIs intake practices. Materials and Methods: Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. RESULTS: Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. CONCLUSION: TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Inibidores de Proteínas Quinases , Adolescente , Humanos , Criança , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Adesão à Medicação
16.
Biomed Res Int ; 2022: 7713355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35224100

RESUMO

Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3ß, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Codonopsis , Medicamentos de Ervas Chinesas/farmacologia , Disbiose/tratamento farmacológico , Fitoterapia/métodos , Polímero Poliacetilênico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Raízes de Plantas/química , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Front Cell Infect Microbiol ; 12: 969526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051242

RESUMO

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Disbiose/prevenção & controle , Medicina Herbária , Humanos , Inflamação
18.
Biosci Rep ; 41(2)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33492335

RESUMO

Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan-Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4+ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.


Assuntos
Mutação , Neoplasias Gástricas/patologia , Microambiente Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia
19.
Ann Palliat Med ; 10(3): 2971-2978, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752422

RESUMO

BACKGROUND: Although the peripherally inserted central catheter (PICC) has been widely utilized, there is still a lack of large sample size-based relevant risk factor investigation for the children with blood diseases in a single center of China. METHODS: We performed a retrospective cohort study through including a total of 2,974 cases aged 0-18 years with blood diseases and PICC insertion. Success rates of different PICC operation techniques were compared. Targeting the common PICC-related complications, we performed the univariate and multivariate logistic regression analyses. Then, based on the screened risk factors, the prediction modeling analysis of binary logistic regression was conducted. RESULTS: The "B-ultrasound plus Seldinger technology" showed a higher success rate of PICC placement than the "non-assistive blind insertion". The catheter type was closely linked to the occurrence of catheter occlusion. The age, insertion site, and catheter type might be the risk factors of phlebitis, while the insertion site, operation season, and catheter type might be associated with catheter fracture. Furthermore, based on these risk factors, we established the nomogram prediction models of phlebitis, rash occurrence, and catheter fracture, respectively, which shows a good predictive ability and a moderate level of predictive accuracy. CONCLUSIONS: Our findings first shed new light on the preoperative estimation of the risk factors of PICCrelated complications for the children with blood diseases in China.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Doenças Hematológicas , Adolescente , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Catéteres , Criança , Pré-Escolar , China , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Fatores de Risco
20.
Cancer Manag Res ; 12: 10449-10459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122944

RESUMO

BACKGROUND: Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2), also known as (pro)renin receptor, is implicated in tumorigenesis and the progression of several types of cancer. This study investigated the role of ATP6AP2 in breast cancer. METHODS: UALCAN and ONCOMINE datasets were utilized to compare transcript levels of ATP6AP2 in breast cancer and normal tissues. GOBO datasets were applied to examine ATP6AP2 expression in different breast cancer cell lines. We used the cBioPortal website to explore the gene alterations and copy number alterations of ATP6AP2 in breast cancer. Cell Counting Kit-8 and transwell assays were conducted to evaluate ATP6AP2 function in MCF-7 breast cancer cells. Finally, we used the cBioPortal website to establish the interaction network of ATP6AP2 in breast cancer and performed functional enrichment analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. RESULTS: ATP6AP2 was overexpressed in breast cancer tissues and breast cancer cell lines in the UALCAN, ONCOMINE, and GOBO datasets. The major type of ATP6AP2 alteration was mRNA upregulation. Moreover, ATP6AP2 was most highly expressed in luminal type breast cancer. Finally, ATP6AP2 knockdown reduced MCF-7 cell proliferation, invasion and migration. Functional enrichment analysis suggested that ATP6AP2 regulates several cancer-related pathways, especially the Wnt/ß-catenin signaling pathway. CONCLUSION: Applying multi-dimensional analytical methods, we demonstrate that ATP6AP2 is upregulated in breast cancer and may promote its development and progression.

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