Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.541
Filtrar
1.
Mol Med Rep ; 30(5)2024 11.
Artigo em Inglês | MEDLINE | ID: mdl-39239742

RESUMO

The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system­related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed.


Assuntos
Neoplasias do Sistema Digestório , Tetraspaninas , Humanos , Tetraspaninas/metabolismo , Tetraspaninas/genética , Neoplasias do Sistema Digestório/metabolismo , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/patologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais
2.
Eur J Med Res ; 29(1): 447, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39218950

RESUMO

The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.


Assuntos
Neoplasias do Sistema Digestório , RNA Longo não Codificante , Via de Sinalização Wnt , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Via de Sinalização Wnt/genética , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/metabolismo , Regulação Neoplásica da Expressão Gênica , Resistencia a Medicamentos Antineoplásicos/genética , Proliferação de Células/genética
3.
Oncol Res ; 32(9): 1389-1399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220125

RESUMO

Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1ß, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.


Assuntos
Neoplasias do Sistema Digestório , Resveratrol , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Humanos , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/prevenção & controle , Animais , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico
4.
Front Immunol ; 15: 1393404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206183

RESUMO

Objective: To systematically evaluate the efficacy and safety of anlotinib targeted therapy for the treatment of patients with advanced digestive system neoplasms (DSNs). Methods: Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and the Wanfang database up to October 2023. Outcome measures, including therapeutic efficacy, quality of life (QOL) and adverse events, were extracted and evaluated. Results: Twenty trials, including 1,613 advanced DSNs patients, were included. The results indicated that, compared with conventional treatment alone, the combination of anlotinib targeted therapy with conventional treatment significantly improved the patients' 6-months overall survival (OS, OR=1.76, CI=1.53 to 2.02, P<0.00001), overall response (ORR, OR=1.76, CI=1.53 to 2.02, P<0.00001) and disease control rate (DCR, OR=1.51, 95% CI=1.25 to 1.84, P<0.0001). Moreover, the group that received the combined therapy had higher rates of hypertension (P<0.00001), proteinuria (P<0.00001), fatigue (P<0.00001), diarrhea (P<0.00001), hypertriglyceridemia (P=0.02), alanine aminotransfease (ALT)increased (P=0.004), aspartate transaminase (AST) increased (P=0.006), anorexia (P<0.00001), weight loss (P=0.002), abdominal pain (P=0.0006), hypothyroidism (P=0.02), prolonged QT interval (P=0.04). Analyses of other adverse events, such as gastrointestinal reaction, leukopenia, and neutropenia, did not reveal significant differences (P>0.05). Conclusion: The combination of anlotinib targeted therapy and conventional treatment is more effective for DSNs treatment than conventional treatment alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria and hand-foot syndrome. Therefore, the benefits and risks should be considered before treatment.


Assuntos
Neoplasias do Sistema Digestório , Indóis , Quinolinas , Humanos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/psicologia , Indóis/administração & dosagem , Indóis/efeitos adversos , Qualidade de Vida , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Resultado do Tratamento , /efeitos adversos
5.
Biomed Phys Eng Express ; 10(5)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39142294

RESUMO

Purpose. This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives.Methods. This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances.Results. This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review.Conclusion. Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives.


Assuntos
Dispositivos Lab-On-A-Chip , Engenharia Tecidual , Microambiente Tumoral , Humanos , Engenharia Tecidual/métodos , Microfluídica/métodos , Neoplasias do Sistema Digestório , Modelos Biológicos , Hidrogéis/química , Animais
6.
Arq Bras Cir Dig ; 37: e1817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39166654

RESUMO

Postoperative infectious complications are extremely important to surgeons and the entire medical care team. Among these complications, surgical site infection (SSI) appears to be one of the earliest and most prevalent events and is considered an inherent complication of surgical procedures. In oncological patients submitted to resections of digestive system tumors, there is a confluence of several risk factors for SSI, making it necessary to establish measures to maximize the control of this condition to provide a better prognosis for these patients. Some risk factors for SSI are the manipulation of structures hosting the highest density of pathogenic microorganisms, such as the colon, the patient's performance status, the patient's nutritional status, the use of chemotherapy and/or radiotherapy, and the surgical procedure itself, which tends to last longer and be more complex than surgeries for benign conditions of the digestive system. Therefore, this review sought to provide a qualitative analysis and a summary of the literature regarding the SSI of postoperative tumor patients who underwent surgical resection and were well-structured postoperatively, to provide objective data on this problem, and alert about the well-structured needs of individualized pre-, peri-, and post-protocols to avoid the development of these events.


Assuntos
Neoplasias do Sistema Digestório , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Neoplasias do Sistema Digestório/cirurgia , Fatores de Risco , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos
7.
World J Gastroenterol ; 30(26): 3206-3209, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39086639

RESUMO

In this editorial, we review the work of Razali et al published in World J Gastroenterology, with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase (PI3K) pathway and buparlisib on colitis-associated cancer. The role of PI3K in promoting cancer progression has been widely recognized, as it is involved in regulating the survival, differentiation, and proliferation of cancer cells. The complement Clq/TNF-related protein 6 (CTRP6) is a newer tumor-associated factor. Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer, hepatocellular carcinoma, colorectal cancer, and other gastrointestinal tumors through the PI3K pathway. This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.


Assuntos
Fosfatidilinositol 3-Quinase , Transdução de Sinais , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/metabolismo
8.
Eur J Surg Oncol ; 50(9): 108509, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38959846

RESUMO

BACKGROUND: Preoperative geriatric-specific variables (GSV) influence short-term morbidity in surgical patients, but their impact on long-term survival in elderly patients with cancer remains undefined. STUDY DESIGN: This observational cohort study included patients ≥65 years who underwent hepatopancreatobiliary or colorectal operations for malignancy between 2014 and 2020. Individual patient data included merged ACS NSQIP data, Procedure Targeted, and Geriatric Surgery Research variables. Patients were stratified by age: 65-74, 75-84, and ≥85 and presence of these GSVs: mobility aid, preoperative falls, surrogate signed consent, and living alone. Bivariable and multivariable analyses were used to evaluate 1-year mortality and postoperative discharge to facility. RESULTS: 577 patients were included: 62.6 % were 65-74 years old, 31.7 % 75-84, and 5.7 % ≥ 85. 96 patients were discharged to a facility with frequency increasing with age group (11.4 % vs 22.4 % vs 42.4 %, respectively, p < 0.001). 73 patients (12.7 %) died during 1-year follow-up, 32.9 % from cancer recurrence. One-year mortality was associated with undergoing hepatopancreatobiliary operations (p = 0.017), discharge to a facility (p = 0.047), and a surrogate signing consent (p = 0.035). Increasing age (p < 0.001), hepatopancreatobiliary resection (p = 0.002), living home alone (p < 0.001), and mobility aid use (p < 0.001) were associated with discharge to a facility. CONCLUSION: Geriatric-specific variables, living alone and use of a mobility aid, were associated with discharge to a facility. A surrogate signing consent and discharge to a facility were associated with 1-year mortality. These findings underscore the importance of preoperative patient selection and optimization, efficacious discharge planning, and informed decision-making in the care of elderly cancer patients.


Assuntos
Neoplasias Colorretais , Neoplasias Pancreáticas , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Avaliação Geriátrica , Fatores Etários , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Alta do Paciente , Hepatectomia , Seleção de Pacientes , Neoplasias do Sistema Biliar/cirurgia , Neoplasias do Sistema Biliar/mortalidade , Taxa de Sobrevida , Neoplasias do Sistema Digestório/cirurgia , Neoplasias do Sistema Digestório/mortalidade
9.
Environ Res ; 260: 119643, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39053758

RESUMO

Arsenic is a known carcinogen for the lungs, the bladder, and the skin, while systematic evidence on other cancer types is lacking, especially for occupational exposure. Thus, we aimed to systematically summarize current evidence on the association between occupational arsenic exposure and digestive cancers, including head and neck cancer (HNC). We conducted a systematic review on Pubmed, Web of Science, and Embase search engines. We computed pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) using DerSimonian and Laird random-effects model. Occurrence of publication bias was assessed using contour-enhanced funnel plots and Egger's test. Twenty-two studies on digestive cancers and 11 on HNC were included in the meta-analysis. RRs for the association with occupational exposure to arsenic of 1.23 (95% CI: 1.07-1.40; I2 = 72.3%, p < 0.001) and 1.08 (95% CI: 0.76-1.53; I2 = 76.6%, p < 0.001) for digestive cancer and HNC, respectively, were observed. As for specific cancer types, arsenic was associated with rectal cancer (RR: 1.51; 95% CI: 1.003-2.28; I2 = 37.0%, p = 0.174), but not with other investigated cancer types. No clear evidence of publication bias was found. The results of our study suggest that the observed association between occupational arsenic exposure and digestive cancer might be mainly driven by a positive association for rectal cancer, while arsenic exposure did not appear to be associated with HNC. However, further high-quality studies with detailed assessment of arsenic exposure are warranted to clarify the potential association of arsenic with digestive cancers and HNC.


Assuntos
Arsênio , Neoplasias do Sistema Digestório , Neoplasias de Cabeça e Pescoço , Exposição Ocupacional , Arsênio/análise , Arsênio/toxicidade , Arsênio/efeitos adversos , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Exposição Ocupacional/efeitos adversos , Neoplasias do Sistema Digestório/induzido quimicamente , Neoplasias do Sistema Digestório/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia
10.
Support Care Cancer ; 32(8): 501, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985345

RESUMO

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.


Assuntos
Suplementos Nutricionais , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Autoeficácia , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Inquéritos e Questionários , Idoso , Adulto , Neoplasias do Sistema Digestório/cirurgia , Neoplasias do Sistema Digestório/psicologia , Apoio Social , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/psicologia , Período Pós-Operatório
11.
Food Funct ; 15(16): 8217-8237, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39039956

RESUMO

Experimental studies have shown that vitamin C has anti-cancer effects, but previous meta-analyses have indicated that the role of vitamin C in digestive system cancers (DSCs) is controversial. In this study, a systematic review and meta-analysis of the relationship between dietary intake/plasma concentration of vitamin C and the risk of DSC was conducted, evaluating 32 prospective studies with 1 664 498 participants. Dose-response and subgroup analyses were also performed. Systematic literature searches were performed in PubMed, EMBASE and Web of Science databases until 9th September 2023. Vitamin C intake significantly reduced DSCs risk (RR = 0.88, 95% confidence interval (CI) 0.83 to 0.93). The subgroup analyses showed the risks of oral, pharyngeal, and esophageal (OPE) cancers (0.81, 0.72 to 0.93), gastric cancer (0.81, 0.68 to 0.95), and colorectal cancer (0.89, 0.82 to 0.98) were negatively correlated with vitamin C intake, and the effect of vitamin C was different between colon cancer (0.87, 0.77 to 0.97) and rectal cancer (1.00, 0.84 to 1.19). However, plasma vitamin C concentration was only inversely associated with gastric cancer risk (0.74, 0.59 to 0.92). Dose-response analysis revealed that 250 and 65 mg day-1 vitamin C intakes had the strongest protective effect against OPE and gastric cancers respectively. These estimates suggest that vitamin C intake could significantly reduce gastrointestinal cancer incidence, including OPE, gastric, and colon cancers. Plasma vitamin C has a significant reduction effect on the incidence of gastric cancer only, but additional large-scale clinical studies are needed to determine its impact on the incidence of DSCs.


Assuntos
Ácido Ascórbico , Neoplasias do Sistema Digestório , Humanos , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Neoplasias do Sistema Digestório/sangue , Neoplasias do Sistema Digestório/prevenção & controle , Neoplasias do Sistema Digestório/epidemiologia , Estudos Prospectivos , Dieta , Fatores de Risco , Masculino , Feminino
12.
Chin Med J (Engl) ; 137(16): 1957-1964, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38958046

RESUMO

BACKGROUND: Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality. METHODS: We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China. RESULTS: In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively. CONCLUSIONS: Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.


Assuntos
Neoplasias do Sistema Digestório , Humanos , China/epidemiologia , Neoplasias do Sistema Digestório/epidemiologia , Incidência , Masculino , Feminino , Neoplasias Pancreáticas/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias da Vesícula Biliar/epidemiologia
13.
BMC Med Res Methodol ; 24(1): 154, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030498

RESUMO

BACKGROUND: New therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity. METHODS: We considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted to evaluate the operating characteristics of all designs. RESULTS: Design approaches allowing continuous accrual, such as the time-to-event Bayesian Optimal Phase II design (TOP), showed good operating characteristics while ensuring a reduced trial duration. All designs were sensitive to the specification of the correlation between efficacy and toxicity during planning, but TOP can take that correlation into account more easily. CONCLUSIONS: While specifying design working hypotheses requires caution, Bayesian approaches such as the TOP design had desirable operating characteristics and allowed incorporating concomittant information, such as toxicity data from concomitant observations in another relevant patient population (e.g., defined by mutational status).


Assuntos
Teorema de Bayes , Projetos de Pesquisa , Humanos , Ensaios Clínicos Fase II como Assunto/métodos , Neoplasias do Sistema Digestório/tratamento farmacológico , Imunoterapia/métodos , Antineoplásicos/uso terapêutico , Simulação por Computador
14.
Sci Rep ; 14(1): 16689, 2024 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030227

RESUMO

Associations between psychiatric disorders and digestive tract cancers have been proposed. However, the causal link between these factors remains unclear. This study pioneers Mendelian randomization (MR) analysis to explore the genetic link between psychiatric disorders and digestive tract cancers risk. We analysed data on six psychiatric disorders [schizophrenia, bipolar disorder, major depressive disorder (MDD), attention deficit hyperactivity disorder, autism spectrum disorder, and panic disorder (PD)] and digestive tract cancers [esophagus cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)] from genome-wide association studies databases. Using instrumental variables identified from significant single nucleotide polymorphism associations, we employed the inverse variance weighted (IVW) method alongside the weighted median (WM) method and MR-Egger regression. The results revealed no causal link between psychiatric disorders and the risk of EC or GC. Psychiatric disorders were not identified as risk factors for CRC. Notably, PD demonstrated a lower CRC risk (OR = 0.79, 95% CI 0.66-0.93, P = 0.01). This MR analysis underscores the lack of a causal association between psychiatric disorders and digestive tract cancers risk while suggesting a potential protective effect of PD against CRC.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos Mentais , Polimorfismo de Nucleotídeo Único , Humanos , Transtornos Mentais/genética , Transtornos Mentais/epidemiologia , Fatores de Risco , Predisposição Genética para Doença , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/epidemiologia , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/etiologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia
15.
Front Immunol ; 15: 1404974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919615

RESUMO

Foxp3+ regulatory T cells (Foxp3+ Treg) play a role in regulating various types of tumors, but uncertainty still exists regarding the exact mechanism underlying Foxp3+ Treg activation in gastrointestinal malignancies. As of now, research has shown that Foxp3+ Treg expression, altered glucose metabolism, or a hypoxic tumor microenvironment all affect Foxp3+ Treg function in the bodies of tumor patients. Furthermore, it has been demonstrated that post-translational modifications are essential for mature Foxp3 to function properly. Additionally, a considerable number of non-coding RNAs (ncRNAs) have been implicated in the activation of the Foxp3 signaling pathway. These mechanisms regulating Foxp3 may one day serve as potential therapeutic targets for gastrointestinal malignancies. This review primarily focuses on the properties and capabilities of Foxp3 and Foxp3+Treg. It emphasizes the advancement of research on the regulatory mechanisms of Foxp3 in different malignant tumors of the digestive system, providing new insights for the exploration of anticancer treatments.


Assuntos
Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Microambiente Tumoral/imunologia , Animais , Transdução de Sinais , Neoplasias do Sistema Digestório/imunologia , Neoplasias Gastrointestinais/imunologia
16.
Curr Oncol ; 31(6): 3513-3528, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38920742

RESUMO

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.


Assuntos
Ensaios Clínicos Fase II como Assunto , Humanos , Ensaios Clínicos Fase II como Assunto/métodos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gastrointestinais/tratamento farmacológico , Projetos de Pesquisa , Neoplasias do Sistema Digestório/tratamento farmacológico
17.
Lipids Health Dis ; 23(1): 202, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937739

RESUMO

BACKGROUND: Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear. METHODS: Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results. RESULTS: Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1_20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2_0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships. CONCLUSION: Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application.


Assuntos
Neoplasias do Sistema Digestório , Análise da Randomização Mendeliana , Humanos , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/sangue , Estudo de Associação Genômica Ampla , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Lipídeos/genética , Fatores de Risco , Lipidômica , Predisposição Genética para Doença , Esfingomielinas/sangue , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/epidemiologia
18.
J Transl Med ; 22(1): 545, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849871

RESUMO

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.


Assuntos
Bactérias , Neoplasias do Sistema Digestório , Humanos , Neoplasias do Sistema Digestório/microbiologia , Neoplasias do Sistema Digestório/terapia , Bactérias/metabolismo , Microbioma Gastrointestinal , Animais
19.
Biomed Environ Sci ; 37(5): 445-456, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843918

RESUMO

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.


Assuntos
Neoplasias do Sistema Digestório , Predisposição Genética para Doença , Receptores para Leptina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , China/epidemiologia , Neoplasias do Sistema Digestório/genética , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/genética , Fatores de Risco , População do Leste Asiático/genética
20.
Sci Rep ; 14(1): 13036, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844600

RESUMO

The role of skeletal muscle and adipose tissue in the progression of cancer has been gradually discussed, but it needs further exploration. The objective of this study was to provide an in-depth analysis of skeletal muscle and fat in digestive malignancies and to construct novel predictors for clinical management. This is a retrospective study that includes data from Cancer Center, the First Hospital of Jilin University. Basic characteristic information was analyzed by T tests. Correlation matrices were drawn to explore the relationship between CT-related indicators and other indicators. Cox risk regression analyses were performed to analyze the association between the overall survivals (OS) and various types of indicators. A new indicator body composition score (BCS) was then created and a time-dependent receiver operating characteristic curve was plotted to analyze the efficacy of the BCS. Finally, a nomogram was produced to develop a scored-CT system based on BCS and other indicators. C-index and calibration curve analyses were performed to validate the predictive accuracy of the scored-CT system. A total of 575 participants were enrolled in the study. Cox risk regression model revealed that VFD, L3 SMI and VFA/SFA were associated with prognosis of cancer patients. After adjustment, BCS index based on CT was significantly associated with prognosis, both in all study population and in subgroup analysis according to tumor types (all study population: HR 2.036, P < 0.001; colorectal cancer: HR 2.693, P < 0.001; hepatocellular carcinoma: HR 4.863, P < 0.001; esophageal cancer: HR 4.431, P = 0.008; pancreatic cancer: HR 1.905, P = 0.016; biliary system malignancies: HR 23.829, P = 0.035). The scored-CT system was constructed according to tumor type, stage, KPS, PG-SGA and BCS index, and it was of great predictive validity. This study identified VFD, L3 SMI and VFA/SFA associated with digestive malignancies outcomes. BCS was created and the scored-CT system was established to predict the OS of cancer patients.


Assuntos
Tecido Adiposo , Composição Corporal , Neoplasias do Sistema Digestório , Músculo Esquelético , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/diagnóstico por imagem , Neoplasias do Sistema Digestório/mortalidade , Estudos Retrospectivos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Idoso , Adulto , Curva ROC , Modelos de Riscos Proporcionais , Nomogramas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA