Adjuvant Chemotherapy for Older Patients With Stage III Colorectal Cancer: A Real-World Analysis of Treatment Recommendations, Treatment Administered and Impact on Cancer Recurrence.

BACKGROUND: A substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone. PATIENTS AND METHODS: We analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined. RESULTS: One thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 months. Compared to the 827 YP, the 685 OP were less likely to be offered AC (71.5% vs. 96.5%, P < .0001) and when offered, were more likely to decline treatment (15.1% vs. 2.8%, P < .0001). Ultimately, 60.0% of OP and 93.7% of YP received AC (P < .0001). OP were less likely to receive oxaliplatin (27.5% vs. 84.7%, P < .0001) and to complete AC (75.9% vs. 85.7%, P < .0001). The probability of remaining recurrence-free was significantly higher in OP who received AC compared to those not treated (HR 0.73, P = .04) but not significantly improved with the addition of oxaliplatin (HR 0.75, P = .18). CONCLUSION: OP were less likely than YP to receive AC. Receipt of AC reduced recurrences in OP, supporting its use, although no significant benefit was observed from the addition of oxaliplatin.

Research progress on the biological basis of Traditional Chinese Medicine syndromes of gastrointestinal cancers.

Gastrointestinal cancers account for 11.6 % of all cancers, and are the second most frequently diagnosed type of cancer worldwide. Traditional Chinese medicine (TCM), together with Western medicine or alone, has unique advantages for the prevention and treatment of cancers, including gastrointestinal cancers. Syndrome differentiation and treatment are basic characteristics of the theoretical system of TCM. TCM syndromes are the result of the differentiation of the syndrome and the basis of treatment. Genomics, transcriptomics, proteomics, metabolomics, intestinal microbiota, and serology, generated around the central law, are used to study the biological basis of TCM syndromes in gastrointestinal cancers. This review summarizes current research on the biological basis of TCM syndrome in gastrointestinal cancers and provides useful references for future research on TCM syndrome in gastrointestinal cancers.

Autotaxin inhibitor IOA-289 reduces gastrointestinal cancer progression in preclinical models.

BACKGROUND: Autotaxin (ATX) is a secreted enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA stimulates cell proliferation and migration and promotes wound repair following tissue damage. ATX levels are directly correlated with stage and grade in several human cancers. Several small molecule ATX inhibitors have been developed in recent years. IOA-289 is a potent ATX inhibitor, developed to treat cancers containing fibrosis. In this study, we tested IOA-289 treatment on different gastrointestinal tract tumor cell lines, in order to evaluate its effects on viability and motility. METHODS: To determine the effects on cell viability and proliferation of treatment with increasing concentrations of IOA-289, we used the crystal violet assay, a clonogenic assay in matrigel, and we evaluated the inhibitor's effect on formation of 3D spheroids in an in vitro model. The effect of IOA-289 on cell cycle phases was analysed with a redox dye reagent. Cell migration capacity was evaluated by wound healing assay and transwell migration assay. To evaluate the pro-apoptotic effect of the inhibitor, cells were stained with Annexin V and immunofluorescence and flow cytometry analysis were performed. An antibody array was also used, to discriminate, in various samples, the differential expression of 43 proteins involved in the apoptosis pathway. RESULTS: We found that IOA-289 is able to inhibit both growth and migration of gastrointestinal tract tumor cell lines, both in 2D (crystal violet assay) and 3D in vitro models (spheroid formation and clonogenic assay in matrigel). This effect is dose-dependent, and the drug is most effective when administered in FBS-free culture medium. The inhibitory effect on cell growth is due to a pro-apoptotic effect of IOA-289. Staining with FITC-conjugated Annexin V showed that IOA-289 induced a dose-dependent increase in fluorescence following incubation for 24 h, and apoptotic cells were also distinguished in flow cytometry using Annexin/PI staining. The antibody array shows that treatment with IOA-289 causes the increased expression of several pro-apoptotic proteins in all tested cell lines. CONCLUSIONS: These results indicate that IOA-289 may be an effective drug for the treatment of tumors of the gastrointestinal tract, particularly those characterized by a high degree of fibrosis.

Side-effects of hyperthermic intraperitoneal chemotherapy in patients with gastrointestinal cancers.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) produces unwanted side-effects that are mainly caused by chemotherapeutic drugs in the treatment of gastrointestinal (GI) cancers, and these effects have not been systematically summarized. The aim of this article was to provide a comprehensive overview of the side-effects of HIPEC for GI cancers and propose practical strategies for adverse event management. Methodology: PubMed, Web of Science, and the Cochrane Library were systematically searched for side-effects of HIPEC in GI cancers prior to October 20, 2022. A total of 79 articles were included in this review. Results: Adverse events, such as enterocutaneous digestive fistulas, GI tract perforation, neutropenia, postoperative bleeding, ventricular tachycardia, hyperglycemia, hypocalcemia, renal impairment, encapsulating peritoneal sclerosis, scrotal ulceration, and sarcopenia were described, and their clinical management was discussed. These side-effects involve the digestive, hematopoietic, circulatory, metabolic, and urinary systems. Effective methods for adverse event management included an expert multidisciplinary team, replacing chemotherapy drugs, using Chinese medicine, and careful preoperative assessments. Conclusion: The side-effects of HIPEC are frequent and can be minimized by several effective methods. This study proposes practical strategies for adverse event management of HIPEC to assist physicians in choosing the optimal treatment method.

The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress?

The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.

A network meta-analysis to evaluate the efficacy of traditional Chinese medicine on intestinal flora in patients with gastrointestinal cancer.

Background and Purpose: Traditional Chinese medicine (TCM) can regulate intestinal flora so as to affect the occurrence, progression, and prognosis of gastrointestinal cancer. According to clinical studies, TCM oral administration, TCM external treatment, and TCM injections, can adjust intestinal flora disorders in patients with gastrointestinal cancer. This network meta-analysis aims to evaluate the effect of three treatments on the intestinal flora in gastrointestinal cancer patients. Methods: This meta-analysis was registered in PROSPERO (CRD42022332553). Six electronic databases, namely CNKI, Wanfang, CSTJ, PubMed, Cochrane Library, and EMBASE, were searched from their inception to 1 April 2022. We identified randomized controlled trials (RCT) used to compare the efficacy of three TCM treatment methods-oral administration, external therapy and injections-on the intestinal flora in gastrointestinal cancer patients. The main outcome indicators were Bifidobacteria, Lactobacilli, Escherichia coli, and Enterococci. Stata (15.1) and the Cochrane risk of bias assessment tool were employed. Results: We identified 20 eligible RCTs with a total of 1,774 patients. According to network meta-analysis results, TCM injection plus common treatment (CT) or oral administration of TCM plus CT was superior to CT alone for supporting Bifidobacterium. In supporting Lactobacillus, TCM injection plus CT demonstrated more obvious effect relative to oral administration of TCM plus CT; TCM injection plus CT was more effective than CT only; and oral administration of TCM plus CT was superior to CT only.The inhibitory effect of TCM injection plus CT on Escherichia coli was better compared with CT only. In terms of inhibiting Enterococci, oral administration of TCM plus CT was superior to CT only.The difference in efficacy among the above treatments was statistically significant. In the SUCRA probability ranking, TCM injection plus CT had the best ranking curve among the three treatments and was the most effective in supporting Bifidobacteria (Sucra = 90.08%), Lactobacilli (Sucra = 96.4%), and regulating Escherichia coli (Sucra = 86.1%) and Enterococci (Sucra = 87.1%). Conclusion: TCM injections plus CT is the most effective therapy in balancing the intestinal flora of gastrointestinal cancer patients. However, the current results deserve further validation through high-quality research. Systematic Review Registration: http://www.prisma-statement.org/, identifier 10.1136/bmj.n71.

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.

Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.

Medicinal Plants for the Treatment of Gastrointestinal Cancers From the Metabolomics Perspective.

Gastrointestinal cancer (GIC), primarily including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, is one of the most common causes of cancer-related deaths with increasing prevalence and poor prognosis. Medicinal plants have been shown to be a great resource for the treatment of GIC. Due to their complex manifestations of multi-component and multi-target, the underlying mechanisms how they function against GIC remain to be completely deciphered. Cell metabolism is of primary importance in the initialization and development of GIC, which is reported to be a potential target. As an essential supplement to the newest "omics" sciences, metabolomics focuses on the systematic study of the small exogenous and endogenous metabolites involved in extensive biochemical metabolic pathways of living system. In good agreement with the systemic perspective of medicinal plants, metabolomics offers a new insight into the efficacy assessment and action mechanism investigation of medicinal plants as adjuvant therapeutics for GIC therapy. In this review, the metabolomics investigations on metabolism-targeting therapies for GIC in the recent 10 years were systematically reviewed from five aspects of carbohydrate, lipid, amino acid, and nucleotide metabolisms, as well as other altered metabolisms (microbial metabolism, inflammation, and oxidation), with particular attention to the potential of active compounds, extracts, and formulae from medicinal plants. Meanwhile, the current perspectives and future challenges of metabolism-targeting therapies of medicinal plants for GIC were also discussed. In conclusion, the understanding of the action mechanisms of medicinal plants in GIC from the metabolomics perspective will contribute to the clinical application of potential candidates from the resourceful medicinal plants as novel and efficient adjuvant therapeutics for GIC therapy.

OMICS Applications for Medicinal Plants in Gastrointestinal Cancers: Current Advancements and Future Perspectives.

Gastrointestinal cancers refer to a group of deadly malignancies of the gastrointestinal tract and organs of the digestive system. Over the past decades, considerable amounts of medicinal plants have exhibited potent anticancer effects on different types of gastrointestinal cancers. OMICS, systems biology approaches covering genomics, transcriptomics, proteomics and metabolomics, are broadly applied to comprehensively reflect the molecular profiles in mechanistic studies of medicinal plants. Single- and multi-OMICS approaches facilitate the unravelling of signalling interaction networks and key molecular targets of medicinal plants with anti-gastrointestinal cancer potential. Hence, this review summarizes the applications of various OMICS and advanced bioinformatics approaches in examining therapeutic targets, signalling pathways, and the tumour microenvironment in response to anticancer medicinal plants. Advances and prospects in this field are also discussed.

Therapeutic Potential of Emodin for Gastrointestinal Cancers.

Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given their distinct advantage of manipulating multiple pathways to both suppress tumor growth and alleviate cancer comorbidities; however, concerns regarding efficacy, bioavailability, and safety are barriers to their development for clinical use. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a Chinese herb-derived anthraquinone, has been shown to exert anti-tumor effects in colon, liver, and pancreatic cancers. While the mechanisms underlying emodin's tumoricidal effects continue to be unearthed, recent evidence highlights a role for mitochondrial mediated apoptosis, modulated stress and inflammatory signaling pathways, and blunted angiogenesis. The goals of this review are to (1) highlight emodin's anti-cancer properties within GI cancers, (2) discuss the known anti-cancer mechanisms of action of emodin, (3) address emodin's potential as a treatment complementary to standard chemotherapeutics, (4) assess the efficacy and bioavailability of emodin derivatives as they relate to cancer, and (5) evaluate the safety of emodin.

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Therapeutic effect of curcumin in gastrointestinal cancers: A comprehensive review.

Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers.

The effect of massage therapy on fatigue after chemotherapy in gastrointestinal cancer patients.

INTRODUCTION: Gastrointestinal cancer patients undergoing chemotherapy usually suffer from fatigue, which may affect different aspects of their lives. OBJECTIVE: The current study aimed to investigate the effect of massage therapy on fatigue after chemotherapy in gastrointestinal cancer patients. METHOD: In this quasi-experimental study, 88 gastrointestinal cancer patients were randomly allocated into two groups of intervention and control. Patients received the chemotherapy for 3 h. The intervention group received four sessions of foot massage with an interval of 40 min during the chemotherapy. The massage duration was 7 min for each foot. Fatigue was measured using the visual analogue scale to evaluate fatigue severity just after and 24 h after the chemotherapy. Friedman and Mann-Whitney U tests were used to analyze the data. RESULTS: The mean age of patients was 59/18 ± 9/35, and the most common type of cancer was gastric cancer (40%). There was a significant difference in the mean score of fatigue between the two groups immediately after (P > 0.001) and 24 h after chemotherapy (P < 0.001). In the intervention group, fatigue score decreased gradually (P = 0.031), while it increased in the control group (P = 0.001). CONCLUSION: This study demonstrated that foot massage, as a simple method, could reduce chemotherapy-induced fatigue.

Use of Molecular Assays and Circulating Tumor DNA in Early-Stage Colorectal Cancer: A Roundtable Discussion of the Gastrointestinal Cancer Therapy Expert Group.

The use of genomic testing is rapidly emerging as an important clinical tool both for cancer diagnosis and for guiding treatment decisions in a wide range of malignancies, including gastrointestinal (GI) cancers such as colorectal cancer (CRC). Advances in technologies such as polymerase chain reaction and next-generation sequencing methods have made it possible to noninvasively screen for CRC through, for example, the use of blood- or stool-based testing, with high specificity. Tests are also available that can provide prognostic information beyond traditional clinicopathologic factors such as tumor size, grade, and nodal status, which can enable clinicians to more accurately risk stratify patients for recurrence. Lastly, in the setting of resected CRC, tests are now available that can detect circulating tumor DNA as a means for noninvasive minimal/molecular residual disease monitoring, thereby potentially guiding the use of adjuvant chemotherapy and/or escalating or de-escalating therapy. The Gastrointestinal Cancer Therapy Expert Group (GICTEG) recently convened a virtual meeting to discuss current issues related to genomic testing in GI cancer, with the goal of providing guidance on the use of these tests for the practicing community oncologist, for whom GI cancer may be only one of many tumor types encountered. This article provides a summary of the discussion and highlights the key opinions of the GICTEG on this topic. IMPLICATIONS FOR PRACTICE: The Gastrointestinal Cancer Therapy Expert Group seeks to provide practical guidance and opinion on the treatment of gastrointestinal malignancies, including colorectal cancer (CRC), for the practicing community oncologist in situations for which guidelines from established bodies, such as the National Comprehensive Cancer Network and the American Society of Clinical Oncology, may be less clear. In the present report, clinical guidance on the use of molecular assays for a range of clinical indications in CRC is presented, including the use of circulating tumor DNA to detect minimal/molecular residual disease in patients with successfully resected early-stage CRC.

Vitamin and herbal supplements' use among patients with advanced gastrointestinal cancers included in eight clinical trials.

OBJECTIVE: To evaluate the patterns of vitamin and herbal supplement use among patients with advanced gastrointestinal (GI) cancers and the association of such behavior with the efficacy and toxicity of systemic anticancer treatment. METHODS: Project data sphere (PDS) was used to access de-identified datasets of eight clinical trials of advanced GI cancers. Multivariable logistic regression analysis was used to identify factors predicting the use of supplements. Kaplan-Meier survival estimates were used to evaluate the association of supplement use with overall and progression-free survival. Results were stratified according to the site of the primary tumor [pancreatic, gastric, colorectal or hepatocellular carcinoma (HCC)] The association between supplement use and selected chemotherapy side effects was evaluated through Chi-squared testing and subsequent logistic regression. RESULTS: A total of 3441 patients were included in the analysis. Of these, 775 patients reported use of supplements and 2666 patients reported no use of supplements. Higher ECOG performance score (Odds ratio: OR for ECOG 1 versus 0: 1.629; 95% CI 1.363-1.947; P < 0.001) and pancreatic primary site (OR for gastric cancer versus pancreatic cancer: 0.538; 95% CI 0.408-0.709; P < 0.001) was associated with greater use of these supplements. Supplement use was associated with a better overall survival among patients with pancreatic cancer (P = 0.002) but not other GI malignancies. Supplement use was associated with a higher probability of anemia and diarrhea among patients with pancreatic cancer (P < 0.001 for both), gastric cancer (P = 0.016; P = 0.036, respectively) and colorectal cancer (P < 0.001 for both). CONCLUSIONS: There is an association between the use of vitamin and herbal supplements and a higher probability of hematologic and gastrointestinal toxicities. There is a need for more studies to confirm the association between such behavior and better overall survival among patients with pancreatic cancer.

Application of organoids in translational research of human diseases with a particular focus on gastrointestinal cancers.

Gastrointestinal (GI) cancers constitute the largest portion of all human cancers and represent a significant health burden on modern society. Conventional therapeutic approaches such as chemotherapy and surgical resections often fail due to poor treatment response or tumour relapse. Unfortunately, drug discovery for GI cancers has stalled as current cancer models fail to recapitulate critical features of the parent tumour, leading to poor translation from bench to bedside. Recent advances in three-dimensional (3D) cell culturing techniques have driven the surge of interest in stem cell-derived organoid models, a promising platform with a plethora of potential applications due to its ability to retain crucial architectural, genomic and transcriptional properties of the native tissue. In this review article, we discuss current applications and advantages of organoid models in the translational research of GI cancers with a particular focus on primary liver cancer that currently lack effective curative treatments.

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis.

BACKGROUND: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. METHODS: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). RESULTS: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were - 0.43 (95% CI: - 0.77 to - 0.09) days for the time to first postoperative flatus, - 0.29 (95% CI: - 0.59 to 0.01) days for the time to first postoperative BM, and - 0.95 (95% CI: - 1.70 to - 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35-1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. CONCLUSION: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

Single-chain Antibody Against Reg4 Suppresses Gastric Cancer Cell Growth and Enhances 5-FU-induced Cell Death in vitro.

BACKGROUND: Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein. METHODS: This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay. RESULTS: The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed. CONCLUSION: The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.