Digestive Cancers Research Articles

Integrin α2 in the microenvironment and the tumor compartment of digestive (gastrointestinal) cancers: emerging regulators and therapeutic opportunities

Integrins are a family of cell surface membrane receptors and play a crucial role in facilitating bidirectional cell signaling. Integrin α2 (ITGA2) is expressed across a range of cell types, including epithelial cells, platelets, megakaryocytes, and fibroblasts, where it functions as a surface marker and it is implicated in the cell movements. The most recent findings have indicated that ITAG2 has the potential to function as a novel regulatory factor in cancer, responsible for driving tumorigenesis, inducing chemoresistance, regulating genomic instability and remodeling tumor microenvironment. Hence, we primarily focus on elucidating the biological function and mechanism of ITGA2 within the digestive tumor microenvironment, while highlighting its prospective utilization as a therapeutic target for cancer therapy.

Shared and specific competing endogenous RNAs network mining in four digestive system tumors

BackgroundDigestive system malignancies, including esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), liver hepatocellular carcinoma (LIHC), and colon adenocarcinoma (COAD), pose significant global health challenges. Identifying shared and distinct regulatory mechanisms across these cancers can lead to improved therapies. This study aims to construct and compare competing endogenous RNA (ceRNA) networks across ESCA, STAD, LIHC, and COAD to identify RNA biomarkers that could serve as precision therapeutic targets to enhance clinical outcomes and advance personalized cancer care. MethodsClinical and transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed to predict differentially expressed RNAs using edgeR package. The ceRNA networks were constructed using the miRcode and ENCORI databases. Functional enrichment analysis and prognostic RNA screening were performed with ConsensusPathDB and univariate Cox regression analysis. Resultswe identified 6, 88, 55, and 41 RNA biomarkers in ESCA, STAD, LIHC, and COAD, respectively. Network analysis revealed shared and specific elements, with shared nodes enriched in cell cycle and mitotic processes. Several biomarkers, including HMGB3 and RGS16 (ESCA), COL4A1 and COL6A3 (STAD), CDCA5 and CDCA8 (LIHC), and LIMK1 and OSBPL3 (COAD), were consistent with prior studies, while novel biomarkers, such as C3P1 (ESCA), P2RY6 (STAD), and N4BP2L1 and PPP1R3B (LIHC), were discovered. Based on RNA correlation analysis, 1, 23, and 2 potential ceRNA regulatory axes were identified in STAD (PVT1/miR-490-3p/HMGA2), LIHC (DLX6-AS1/miR-139-5p/TOP2A, etc.), and COAD (STRCP1 & LINC00488/miR-142-3p/GAB1), respectively. ConclusionsThis study advances the understanding of ceRNA networks in digestive cancers, highlighting RNA biomarkers with potential as therapeutic targets for personalized treatment strategies.

Environmental Protection for Bureaucratic Promotion: Water Quality Performance Review of Provincial Governors in China

We show including quantitative environmental targets for bureaucratic promotion incentivizes government officials to enforce environmental regulation but at significant economic costs. Taking advantage of the gradual expansion of China’s water quality performance review (WQPR) over time and space, we find that WQPR significantly reduced ambient concentrations of criteria pollutants, digestive cancer mortality, and GDP growth rate. WQPR’s effects are more pronounced along provincial borders, which are targeted by WQPR, and when provincial governors have more promotion potential. An important mechanism is investment in wastewater treatment facilities. There is evidence that WQPR passed the benefit-cost test, especially in rural areas.

Cancer and mortality risks among people with multiple sclerosis: A population-based study in Isfahan, Iran.

Multiple sclerosis (MS) and cancer present substantial global health challenges. Understanding cancer patterns among people with MS (PwMS) is crucial due to potential variations across demographics and geographic regions. Isfahan province in Iran, known for its high MS incidence ratio, offers a significant population for comprehensive studies on MS. In this study, we aim to investigate the association between risk of cancer and MS. Data on PwMS were collected utilizing the National Multiple Sclerosis Registry System of Iran (NMSRI), with diagnoses confirmed using McDonald criteria by neurologists specialized in MS. Cancer incidence was investigated using the Iranian National Population-Based Cancer Registry (INPCR) data, collected following international protocols. Descriptive statistics and regression analyses were employed to assess factors associated with cancer and mortality risks among PwMS. Survival analysis was conducted using Kaplan-Meier curves. Out of 10,049 PwMS, 123 were diagnosed with cancer, with an mean age at the time of cancer diagnosis being 40.41 years and a mean MS duration of 6.76 years. The majority had relapsing-remitting MS (81.2%), and Interferon-β was the most common disease-modifying therapy (DMT) (42.4%). Cancer incidence was 125.6 per 100,000 person-years, peaking at ages 60-64 (677.9 per 100,000 person-years). Receiving monoclonal antibody medications and older age were significantly associated with higher cancer risk (OR:1.542 (1.009-2.357), OR:1.033 (1.015-1.051), respectively). Female breast cancer had the highest incidence ratio among PwMS (40.17 per 100,000 person-years), followed by thyroid (18.38 per 100,000 person-years) and digestive system cancers (17.36 per 100,000 person-years). Breast cancer was the predominant cancer in women, while digestive system cancers were most common among men. Being male and having longer MS duration were linked to higher cancer mortality risk (HR: 2.683, 1.087, respectively). Cancer incidence among 10,049 people with multiple sclerosis was significant, especially in older individuals, with breast cancer being the most common. Male gender and longer MS duration were linked to higher cancer mortality risk.

Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.

Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Tumor-associated macrophages confer resistance to chemotherapy (Trifluridine/Tipiracil) in digestive cancers by overexpressing thymidine phosphorylase

Pyrimidine analogs are part of the first-line chemotherapy regimen for gastrointestinal cancers. Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. Despite its promise, we report that macrophage-specific overexpression of thymidine phosphorylase results in macrophage-induced chemoresistance to TAS-102 that is insensitive to tipiracil inhibition. Furthermore, we illustrate the human-specific nature of this mechanism, as mouse macrophages do not express substantial levels of thymidine phosphorylase, which constrains the applicability of mouse models. To study the importance of macrophages in chemoresistance to trifluridine, we developed a humanized mouse model with tumor-implanted human macrophages and demonstrated their important role in treatment resistance to pyrimidine analogs. Additionally, our findings revealed that macrophages represent a significant source of thymidine phosphorylase expression, comprising over 40 % of the expressing cells, in human colorectal cancer, thereby contributing to chemoresistance.

Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE)

IntroductionCachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic...

Graded association of muscle strength with all-cause and cause-specific mortality in older adults with diabetes: Prospective cohort study across 28 countries.

The worldwide prevalence of diabetes is increasing, particularly among older adults. Understanding the association between muscle strength and mortality in this population is crucial for developing targeted exercise recommendations. To assess the prospective association of muscle strength with mortality in older adults with diabetes. From the Survey of Health, Ageing and Retirement in Europe (SHARE) study, spanning 28 countries, we included 16 149 diabetic adults aged 50 years and older (mean age 68.2 [standard deviation, SD, 9.2] years). Participants fulfilled two criteria: (1) diabetes diagnosis (ever) and (2) current use of diabetes medication. Muscle strength was assessed using handgrip dynamometry (unit: kg). Using time-varying Cox regression with restricted cubic splines, we determined the prospective association of muscle strength with all-cause and cause-specific mortality, controlling for various confounders. Over a mean follow-up of 5.9 years (SD 3.8), 2754 participants died (17%). Using the median level of muscle strength as reference (30 kg), lower and higher levels were associated in a curvilinear fashion with higher and lower all-cause mortality risk, respectively. The 10th percentile of muscle strength (17 kg) showed a hazard ratio (HR) of 1.65 (95% confidence interval (CI) 1.53-1.79). The 90th percentile (47 kg) of muscle strength showed a HR of 0.55 (95% CI 0.49-0.63). A somewhat similar pattern, with varying strength of associations, was seen for mortality due to cardiovascular disease (CVD), respiratory disease, severe infectious disease, digestive system disease and cancer. Muscle strength is gradually and inversely associated with all-cause and cause-specific mortality risk in older adults with diabetes. As muscle strength is highly adaptable to resistance training at all ages, the present findings highlight the importance of improving muscle strength in older adults with diabetes.

A Mendelian analysis of the causality between inflammatory cytokines and digestive tract cancers.

In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs. In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds. Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin. This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs. Key message What is already known on this topic The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.

Para-Aortic Lymphadenectomy in Ovarian, Endometrial, Gastric, and Bladder Cancers: A Systematic Review of Randomized Controlled Trials.

Para-aortic lymphadenectomy can be used for both diagnostic and therapeutic purposes as it aids in staging, provides prognostic data, and influences the patient's options for adjuvant therapy. However, there is still contention over its potential in treating cancer. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. Five different electronic databases, including PubMed, Cochrane Library, Clinical trials.gov, ICTRP, and Embase, were used to conduct a comprehensive search. Original RCTs reporting on the impact of lymphadenectomy on the overall survival in various cancers were included. Information related to the study population, intervention, type of cancer, primary endpoints, and key findings of the study were extracted. Quality assessment of the selected studies was conducted using the Revised Cochrane Risk of Bias Tool Rob 2 for randomized trials. A total of 1693 citations, with 1511 from PubMed, 80 from the Cochrane Library, 67 from Embase, 18 from ICTRP, and 17 from Clinicaltrials.gov were retrieved. Preliminary screening was performed, and after applying selection criteria, nine articles were included in the final qualitative analysis. The total number of patients was 4231, and the sample size ranged from 70 to 1408. Among these nine studies, four studies were on genital cancers (two ovarian cancers, one endometrial cancer, and one cervical cancer); four on digestive cancers (advanced gastric cancers); and one on urinary cancer (advanced bladder cancer). These studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. SNB could be an alternative to lymphadenectomy for ovarian cancer in the future. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it.

Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development

BackgroundUnderstanding the resistance mechanisms of tumor is crucial for advancing cancer therapies. The prospective MATCH-R trial (NCT02517892), led by Gustave Roussy, aimed to characterize resistance mechanisms to cancer treatments through molecular analysis of fresh tumor biopsies. This report presents the genomic data analysis of the MATCH-R study conducted from 2015 to 2022 and focuses on targeted therapies.MethodsThe study included resistant metastatic patients (pts) who accepted an image-guided tumor biopsy. After evaluation of tumor content (TC) in frozen tissue biopsies, targeted NGS (10 < TC < 30%) or Whole Exome Sequencing and RNA sequencing (TC > 30%) were performed before and/or after the anticancer therapy.Patient-derived xenografts (PDX) were established by implanting tumor fragments into NOD scid gamma mice and amplified up to five passages.ResultsA total of 1,120 biopsies were collected from 857 pts with the most frequent tumor types being lung (38.8%), digestive (16.3%) and prostate (14.1%) cancer. Molecular targetable driver were identified in 30.9% (n = 265/857) of the patients, with EGFR (41.5%), FGFR2/3 (15.5%), ALK (11.7%), BRAF (6.8%), and KRAS (5.7%) being the most common altered genes. Furthermore, 66.0% (n = 175/265) had a biopsy at progression on targeted therapy. Among resistant cases, 41.1% (n = 72/175) had no identified molecular mechanism, 32.0% (n = 56/175) showed on-target resistance, and 25.1% (n = 44/175) exhibited a by-pass resistance mechanism. Molecular profiling of the 44 patients with by-pass resistance identified 51 variants, with KRAS (13.7%), PIK3CA (11.8%), PTEN (11.8%), NF2 (7.8%), AKT1 (5.9%), and NF1 (5.9%) being the most altered genes. Treatment was tailored for 45% of the patients with a resistance mechanism identified leading to an 11 months median extension of clinical benefit.A total of 341 biopsies were implanted in mice, successfully establishing 136 PDX models achieving a 39.9% success rate. PDX models are available for EGFR (n = 31), FGFR2/3 (n = 26), KRAS (n = 18), ALK (n = 16), BRAF (n = 6) and NTRK (n = 2) driven cancers. These models closely recapitulate the biology of the original tumors in term of molecular alterations and pharmacological status, and served as valuable models to validate overcoming treatment strategies.ConclusionThe MATCH-R study highlights the feasibility of on purpose image guided tumor biopsies and PDX establishment to characterize resistance mechanisms and guide personalized therapies to improve outcomes in pre-treated metastatic patients.Graphical

The 14-bp insertion/deletion as a promising gene polymorphism to understand cancer risk: Evidence from a systematic review and comprehensive meta-analysis

BackgroundHLA-G is associated with cancer cell escape. The 3’UTR polymorphism is involved in the regulation of membrane-bound HLA-G and soluble HLA-G proteins. The aim of our study was to assess the association of the HLA-G 14-bp insertion (I)/deletion (D) polymorphism with cancer susceptibility and its interaction with clinicopathological features and environmental factors. MethodsA meta-analysis was performed to investigate the association between the HLA-G 14-bp I/ D polymorphism and different types of cancers according to the Prisma guidelines. ResultsThirty-nine publications that studied the 14-bp I/D polymorphism in cancers met our inclusion criteria. The findings of the meta-analysis showed a significant association between the 14-bp I/D polymorphism and cancer risk under the allelic contrast model D vs. I (OR=1.112, 95% CI= 1.009-1.227, P = 0.033) suggesting that the D allele was a risk factor for cancer susceptibility. Stratification by cancer type demonstrated a significant association of the 14-bp I/D polymorphism with breast cancer under the D vs. I contrast allele model (OR=1.267, 95% CI= 1.028-1.563, P=0.027). No significant association was found for digestive, cervical, haematological and thyroid cancers. A comparison of groups stratified by ethnicity showed a significant association for Caucasians under the D vs. I model (OR=1.147, 95% CI= 1.002-1.313, P=0.047); and for mixed ethnicities under the DD+DI vs. II (OR=1.388, 95% CI= 1.083-1.780, P=0.010) and DI vs. II (OR= 1.402, 95% CI=1.077-1.824, P=0.012) models. A comparison of cancer risks associated with the 14-bp I/D polymorphism according to geographic location revealed significant risks for the D allele and DD genotype in North Africa, the Middle East and South America. However, no significant susceptibility to cancer associated with the 14-bp I/D polymorphism was shown for Europe and North Asia. The findings of a meta-analysis of subgroups by disease stage showed a significant association in both early and advanced stages, with the 14-bp deletion variant being a risk factor. Similarly, a significant cancer risk was shown for the 14-bp deletion variant in both low- and high-grade cancers. Finally, the risk associated with the 14-bp I/D polymorphism was higher in cancers with concomitant viral infection with human papillomavirus (HPV), hepatitis B virus (HBV) or hepatitis C virus (HCV). ConclusionThe findings of the overall meta-analysis showed a significant association between the HLA-G 14-bp I/D polymorphism and cancer susceptibility. The findings stratified analysis and subgroup comparisons showed that the 14-bp I/D deletion variant was associated with an increased risk of breast cancer. The HLA-G 14-bp I/D polymorphism may interact with individual and clinicopathological factors to alter cancer risk. These promising findings for cancer risk provide the basis for further studies that explore 14bp I/D polymorphism in cancer screening and immunotherapeutic approach.

Body shape phenotype, triglyceride-glucose index trajectory and the risk of digestive system cancers: a prospective cohort study

Body shape phenotype, triglyceride-glucose index trajectory and the risk of digestive system cancers: a prospective cohort study

Personalized nutritional risk assessment of digestive cancer–A systematic review and meta-analysis of data from 171,739 patients

Personalized nutritional risk assessment of digestive cancer–A systematic review and meta-analysis of data from 171,739 patients

Emerging lessons from experiences at transitions in care among hospitalised patients with cancer with postdischarge frequent emergency department use: a qualitative study using linked clinical and patient-reported interview data from Quebec, Canada

BackgroundWhile teamwork is essential to providing high-quality patient-centred care, challenges in interprofessional collaboration and decision-making in hospital settings are common, especially for patients with cancer. The purpose of this qualitative...

Restrictive Diets in Digestive Cancers: Prevalence, Contributing Factors, Foods Concerned and Patients' Beliefs (Prospective Study of 100 Cases)

Cancer is a major cause of disease-related malnutrition; the prevalence of malnutrition and muscle loss is high in digestive cancers and is thought to be associated with a poor prognosis. The aim of this prospective study is to investigate changes in dietary habits following a diagnosis of gastrointestinal cancer that are likely to cause or aggravate malnutrition, to assess the existence of restrictive diets involving the permanent elimination of certain essential aliments (meat, dairy products, etc.), to identify the factors that influence patients to adopt them, and to assess the degree to which patients believe in the effectiveness of these diets in curing cancer.  Materials and Methods: 100 patients aged 18 and over, diagnosed with one of the following digestive cancers: colorectal, gastric, pancreatic, oesophageal, hepatocellular carcinoma or biliary tract cancer; were interviewed using an electronic questionnaire.  Results: Among the patients we interviewed, 69% had adopted a restrictive diet following the diagnosis of digestive cancer. The products permanently eliminated included white sugar and/or sweetened foods in 83% of cases, red meat in 80%, tinned food in 77%, dairy products in 61%, spices in 54%, fried food in 49%, white meat and eggs not produced organically in 44%, processed meat in 33%, and all white meat and eggs in 17% and 14% respectively; This diet was recommended mainly by the patient’s entourage (friends and family) in 81% of cases, by other patients and their relatives (58%) and by personal research on the internet in 36% of cases. In addition, 37% of patients believe that this type of diet contributes to curing cancer.  Conclusion: 69% of patients in the study were on a restrictive diet, and more than a third of them believed that this diet could help cure their digestive cancers. Raising awareness among patients and their families is essential to prevent malnutrition and muscle loss, and thus improve the outcome of the cancer.

Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.

Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.

The VEGFA-Induced MAPK-AKT/PTEN/TGFβ Signal Pathway Enhances Progression and MDR in Gastric Cancer.

Gastric cancer (GC) is a globally frequent cancer, in particular leading in mortality caused by digestive tract cancers in China. Vascular endothelial growth factor A (VEGFA) is excessively expressed in cancers including GC; its involvement in GC development, particularly in multidrug resistance (MDR), and the signal route it affects in GC remain unknown. To explore the roles VEGFA plays during progression and MDR formation in GC, we studied its function in a VEGFA-deleted GC cell platform. We initially assessed the importance of VEGFA in GC and MDR using database analysis. Then, using CCK8, wound healing, transwell, scanning electron microscopy, immunofluorescence, flow cytometry, and other techniques, the alterations in tumor malignancy-connected cell behaviors and microstructures were photographed and evaluated in a VEGFA-gene-deleted GC cell line (VEGFA-/-SGC7901). Finally, the mechanism of VEGFA in GC progression and MDR was examined by Western blot. Database analysis revealed a strong correlation between high VEGFA expression and a poor prognosis for GC. The results showed that VEGFA deletion reduced GC cell proliferation and motility and altered microstructures important for motility, such as the depolymerized cytoskeleton. VEGFA deletion inhibited the growth of pseudopodia/filopodia and suppressed the epithelial-mesenchymal transition (EMT). The occurrence of MDR is induced by overactivation of the MAPK-AKT and TGFβ signaling pathways, while PTEN inhibits these pathways. All findings suggested that VEGFA acts as a cancer enhancer and MDR inducer in GC via the MAPK-AKT/PTEN/TGFβ signal pathway.

Effects of a reminiscence therapy-involved program on anxiety, depression, and the quality of life in cancer patients: a meta-analysis of randomized controlled trials.

Reminiscence therapy is increasingly being utilized for cancer patients to address psychological pressure and enhance their quality of life. This meta-analysis aimed to comprehensively evaluate the effect of a reminiscence therapy-involved program (RTIP) on anxiety, depression, and quality of life in cancer patients. A systematic literature search was conducted in the Web of Science, PubMed, Embase, and Cochrane Library databases until December 2023 to screen randomized control trials (RCTs) comparing the effect of RTIP and control care. A total of 16 RCTs published from 2013 to 2023 were included, with 1,963 cancer patients undergoing RTIP with or without control care (RTIP group, N = 984) or control care (control group, N = 979). The results showed the the anxiety score [standardized mean differences (SMD) = -0.539; 95% confidence interval (CI) = -0.700, -0.378; P < 0.001], anxiety rate [relative risk (RR) = 0.736; 95% CI: 0.627, 0.865; P < 0.001], depression score (SMD = -0.664; 95% CI: -0.967, -0.361; P < 0.001), and depression rate (RR = 0.632; 95% CI = 0.532, 0.750; P < 0.001) were significantly reduced in the RTIP group compared to the control group. Furthermore, overall quality of life was increased in the RTIP group than in the control group (SMD = 0.501; 95% CI: 0.314, 0.689; P < 0.001). In digestive system cancer patients, anxiety/depression scores and rates were reduced, and the overall quality of life was elevated in the RTIP group in comparison with the control group (all P < 0.050). The quality of evidence was generally high, with a low risk of bias in most studies and no publication bias in any outcomes (all P > 0.050). RTIP attenuates anxiety and depression and improves the quality of life in cancer patients, benefitting their overall health condition. This meta-analysis was registered at PROSPERO with registration number CRD42024563266.

Health text simplification: An annotated corpus for digestive cancer education and novel strategies for reinforcement learning

Objective:The reading level of health educational materials significantly influences the understandability and accessibility of the information, particularly for minoritized populations. Many patient educational resources surpass widely accepted standards for reading level and complexity. There is a critical need for high-performing text simplification models for health information to enhance dissemination and literacy. This need is particularly acute in cancer education, where effective prevention and screening education can substantially reduce morbidity and mortality. Methods:We introduce Simplified Digestive Cancer (SimpleDC), a parallel corpus of cancer education materials tailored for health text simplification research, comprising educational content from the American Cancer Society, Centers for Disease Control and Prevention, and National Cancer Institute. The corpus includes 31 web pages with the corresponding manually simplified versions. It consists of 1183 annotated sentence pairs (361 train, 294 development, and 528 test). Utilizing SimpleDC and the existing Med-EASi corpus, we explore Large Language Model (LLM)-based simplification methods, including fine-tuning, reinforcement learning (RL), reinforcement learning with human feedback (RLHF), domain adaptation, and prompt-based approaches. Our experimentation encompasses Llama 2, Llama 3, and GPT-4. We introduce a novel RLHF reward function featuring a lightweight model adept at distinguishing between original and simplified texts when enables training on unlabeled data. Results:Fine-tuned Llama models demonstrated high performance across various metrics. Our RLHF reward function outperformed existing RL text simplification reward functions. The results underscore that RL/RLHF can achieve performance comparable to fine-tuning and improve the performance of fine-tuned models. Additionally, these methods effectively adapt out-of-domain text simplification models to a target domain. The best-performing RL-enhanced Llama models outperformed GPT-4 in both automatic metrics and manual evaluation by subject matter experts. Conclusion:The newly developed SimpleDC corpus will serve as a valuable asset to the research community, particularly in patient education simplification. The RL/RLHF methodologies presented herein enable effective training of simplification models on unlabeled text and the utilization of out-of-domain simplification corpora.