3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.

BACKGROUND: Cancer immunotherapy is receiving worldwide attention for its induction of an anti-tumor response. However, it has had limited efficacy in some patients who acquired resistance. The dynamic and sophisticated complexity of the tumor microenvironment (TME) is the leading contributor to this clinical dilemma. Through recapitulating the physiological features of the TME, 3D bioprinting is a promising research tool for cancer immunotherapy, which preserves in vivo malignant aggressiveness, heterogeneity, and the cell-cell/matrix interactions. It has been reported that application of 3D bioprinting holds potential to address the challenges of immunotherapy resistance and facilitate personalized medication. CONCLUSIONS AND PERSPECTIVES: In this review, we briefly summarize the contributions of cellular and noncellular components of the TME in the development of immunotherapy resistance, and introduce recent advances in 3D bioprinted tumor models that served as platforms to study the interactions between tumor cells and the TME. By constructing multicellular 3D bioprinted tumor models, cellular and noncellular crosstalk is reproduced between tumor cells, immune cells, fibroblasts, adipocytes, and the extracellular matrix (ECM) within the TME. In the future, by quickly preparing 3D bioprinted tumor models with patient-derived components, information on tumor immunotherapy resistance can be obtained timely for clinical reference. The combined application with tumoroid or other 3D culture technologies will also help to better simulate the complexity and dynamics of tumor microenvironment in vitro. We aim to provide new perspectives for overcoming cancer immunotherapy resistance and inspire multidisciplinary research to improve the clinical application of 3D bioprinting technology.

Auraptene Mitigates Colitis Induced by Dextran Sulfate Sodium in Mice by Regulating Specific Intestinal Flora and Repairing the Intestinal Barrier.

Auraptene (AUT) is widely known to possess both antioxidant and anti-inflammatory properties. This study attempted to evaluate the protective effects of AUT in dextran sodium sulfate (DSS)-induced colitis in mice and to determine the underlying molecular mechanisms. Our results suggest that AUT substantially minimizes the severity and worsening of DSS-induced colitis in mice, indicated by the lengthening of the colon, lower disease activity index, reduced oxidation levels, and attenuated inflammatory factors. Molecular studies revealed that AUT reduces the nuclear translocation of nuclear factor-κB (NF-κB), thereby inhibiting the expression of inflammatory factors. Additionally, AUT promotes the diversity of the intestinal flora in mice with colitis by increasing the number of beneficial bacteria such as Lactobacillaceae and lowering the number of harmful bacteria. In conclusion, AUT mitigates DSS-induced colitis by maintaining the integrity of the intestinal barrier and modulating the levels of the intestinal microbial species.

The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review.

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N6-methyladenosine (m6A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m6A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m6A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m6A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m6A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets.

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.

Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells' sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review).

Cancer­testis antigen (CTA) is a well­accepted optimal target library for cancer diagnosis and treatment. Most CTAs are located on the X chromosome and aggregate into large gene families, such as the melanoma antigen, synovial sarcoma X and G antigen families. Members of the CTA subfamily are usually co­expressed in tumor tissues and share similar structural characteristics and biological functions. As cancer vaccines are recommended to induce specific antitumor responses, CTAs, particularly CTA subfamilies, are widely used in the design of cancer vaccines. To date, DNA, mRNA and peptide vaccines have been commonly used to generate tumor­specific CTAs in vivo and induce anticancer effects. Despite promising results in preclinical studies, the antitumor efficacy of CTA­based vaccines is limited in clinical trials, which may be partially attributed to weak immunogenicity, low efficacy of antigen delivery and presentation processes, as well as a suppressive immune microenvironment. Recently, the development of nanomaterials has enhanced the cancer vaccination cascade, improved the antitumor performance and reduced off­target effects. The present study provided an in­depth review of the structural characteristics and biofunctions of the CTA subfamilies, summarised the design and utilisation of CTA­based vaccine platforms and provided recommendations for developing nanomaterial­derived CTA­targeted vaccines.

Association of clinical outcomes and the predictive value of T lymphocyte subsets within colorectal cancer patients.

Introduction: Tumor immunity is a hot topic in tumor research today, and human immunity is closely related to tumor progression. T lymphocyte is an important component of human immune system, and the changes in their subsets may influence the progression of colorectal cancer (CRC) to some extent. This clinical study systematically describes and analyzes the association of CD4+ and CD8+ T-lymphocyte content and CD4+/CD8+ T-lymphocyte ratio with CRC differentiation, clinical pathological stage, Ki67 expression, T-stage, N-stage, carcinoembryonic antigen (CEA) content, nerve and vascular infiltration, and other clinical features, as well as preoperative and postoperative trends. Furthermore, a predictive model is constructed to evaluate the predictive value of T-lymphocyte subsets for CRC clinical features. Methods: Strict inclusion and exclusion criterion were formulated to screen patients, preoperative and postoperative flow cytometry and postoperative pathology reports from standard laparoscopic surgery were assessed. PASS and SPSS software, R packages were invoked to calculate and analyze. Results: We found that a high CD4+ T-lymphocyte content in peripheral blood and a high CD4+/CD8+ ratio were associated with better tumor differentiation, an earlier clinical pathological stage, lower Ki67 expression, shallower tumor infiltration, a smaller number of lymph node metastases, a lower CEA content, and a lower likelihood of nerve or vascular infiltration (P < 0.05). However, a high CD8+ T-lymphocyte content indicated an unpromising clinical profile. After effective surgical treatment, the CD4+ T-lymphocyte content and CD4+/CD8+ ratio increased significantly (P < 0.05), while the CD8+ T-lymphocyte content decreased significantly (P < 0.05). Further, we comprehensively compared the merits of CD4+ T-lymphocyte content, CD8+ T-lymphocyte content, and CD4+/CD8+ ratio in predicting the clinical features of CRC. We then combined the CD4+ and CD8+ T-lymphocyte content to build models and predict major clinical characteristics. We compared these models with the CD4+/CD8+ ratio to explore their advantages and disadvantages in predicting the clinical features of CRC. Discussion: Our results provide a theoretical basis for the future screening of effective markers in reflecting and predicting the progression of CRC. Changes in T lymphocyte subsets affect the progression of CRC to a certain extent, while their changes also reflect variations in the human immune system.

A meta-analysis examined the effect of topical nursing application of antimicrobial as a prophylaxis for the stoppage of surgical wound infection in colorectal surgery.

To assess the impact of topical antimicrobial (TA) as a prophylaxis for the stoppage of surgical wound infection (SWI) in colorectal surgery (CS), we lead a meta-analysis. 9160 participants with CS were enrolled in the chosen studies; 4719 of them used TA, while 4441 served as controls. To assess the effectiveness of TA application in lowering SWIs following CS, odds ratios (OR) with 95% confidence intervals (CIs) were computed with a dichotomous technique with a fixed- or random-effect model. Significantly lower SWIs post CS for TA as whole (OR, 0.50; 95% CI, 0.38-0.64; P < .001), gentamicin collagen sponge and beads (OR, 0.52; 95% CI, 0.32-0.86; P = .01), triclosan impregnated fascial suture (OR, 0.57; 95% CI, 0.38-0.84; P = .005), antibiotic powder, ointment, lavage, or injection for the abdominal wound (OR, 0.35; 95% CI, 0.21-0.59; P < .001), and ionised silver dressing on the closed abdominal wound (OR, 0.45; 95% CI, 0.27-0.77; P = .003) compared to control. Significantly lower SWIs post CS for TA as a whole, gentamicin collagen sponge and beads, triclosan impregnated fascial sutures, antibiotic powder, ointment, lavage, or injection for the abdominal wound, and ionised silver dressing on the closed abdominal wound compared with control. The low sample size of 8 out of the 39 included studies in this meta-analysis calls for precaution when analysing the outcomes.

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions.

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

Effects of exercise on chemotherapy-induced peripheral neuropathy in cancer patients: a systematic review and meta-analysis.

PURPOSE: Summarize and critically evaluate the existing studies to determine the effects of exercise on chemotherapy-induced peripheral neuropathy in cancer patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Library databases for randomized controlled trials reporting exercise intervention in cancer patients with chemotherapy-induced peripheral neuropathy. The outcomes of interest included chemotherapy-induced peripheral neuropathy symptoms, physical function (balance control, muscle strength, and functional status), and quality of life. The Cochrane Collaboration's tool was employed to assess the risk of bias. RESULTS: The search identified 1309 studies, 16 of which eligible. Our meta-analysis revealed that exercise intervention significantly improved the quality of life (SMD = 0.83, 95% CI = 0.58 to 1.08, I2 = 0%, P < 0.00001) and relieved neuropathic pain (MD = - 4.93, 95% CI = - 5.60 to - 4.26, I2 = 0%, P < 0.00001). The muscular strength of the upper (SMD = 1.10, 95% CI = 0.68 to 1.51, I2 = 25%, P < 0.00001) and the lower limbs (SMD = 0.84, 95% CI = 0.42 to 1.26, I2 = 36%, P < 0.00001) increased and balance performance (SMD = 1.05, 95% CI = 0.62 to1.48, I2 = 0%, P < 0.00001) was better in the exercise group than in the group with usual care. However, no evidence was found that exercise intervention could improve CIPN symptoms. CONCLUSIONS: The results of this study showed that combined exercise could be an effective option for improving quality of life, physical function (balance control and muscle strength), and neuropathic pain in cancer patients with chemotherapy-induced peripheral neuropathy. Further exploration of appropriate exercise prescriptions is needed to improve other outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Specific and appropriate exercise intervention for cancer patients with chemotherapy-induced peripheral neuropathy should be recommended because these interventions can improve their quality of life and physical function.

Multifunctional Au Modified Ti3C2-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy.

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on Ti3C2-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging in vivo. Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4+ and CD8+ T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining Ti3C2-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety in vitro and in vivo. Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

The effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy (CIPN). Methods: We searched for relevant randomized controlled trials (RCTs) in PubMed, Cochrane Library, and Embase databases from their inception to 1 April 2022. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory-Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), Numerical Rating Scale (NRS), and adverse events were the outcome measures. All studies had at least one of these outcome measures. Mean differences (MDs) with 95% confidence intervals (CIs) were assessed in the meta-analysis using the RevMan 5.3 software. Results: Five studies were included in the analysis. The results showed that acupuncture and placebo acupuncture were not significantly different in reducing chemotherapy-induced neurotoxicity and functional disability (random-effects estimates; MD: 4.30; 95% CI: -0.85~9.45; P = 0.10; I2 = 74%). Acupuncture was better than placebo acupuncture in reducing pain severity and pain interference with patients' daily function (fixed-effect estimates; MD: -1.14; 95% CI: 1.87 to -0.42; P = 0.002; I2 = 13%). Acupuncture was not significantly different from placebo acupuncture in relieving CIPN symptoms (MD: -0.81; 95% CI: -2.02 to 0.40, P = 0.19). Acupuncture improved quality of life better than placebo acupuncture (MD: 10.10; 95% CI: 12.34 to 17.86, P = 0.01). No severe adverse events were recorded in all five studies. Conclusion: This meta-analysis suggests that acupuncture may be more effective and safer in reducing pain severity and pain interference with patients' daily function than placebo acupuncture. Additionally, acupuncture may improve the quality of life of patients with CIPN. However, large sample size studies are needed to confirm this conclusion. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324930, identifier: CRD42022324930.

The complementary role of lymphovascular invasion and perineural invasion in the TNM staging process of rectal cancer.

The aim of this study is to clarify the association between lymphovascular invasion (LVI) and/or perineural invasion (PNI) and the clinical characteristics and prognostic importance of rectal cancer, to provide a basis for early adjuvant treatment of rectal cancer. We retrospectively analyzed patients diagnosed with rectal cancer. This study involved rectal cancer tissue samples were obtained by surgical methods. Data on histological form, tumor classification, tumor size, gross growth pattern, blood and lymphatic vessel invasion, and PNI of the slice by HE staining were obtained from pathological examination. Immunohistochemical analysis of tissue samples was performed to determine p53 and EGFR expressions. There were 330 rectal cancer patients included in the study. LVI and/or PNI can be used as a high-risk factor for the prognosis of rectal cancer, predict prognostic survival, and guide adjuvant therapy. The detection rates of LVI and PNI were 32.1% and 16.1%. Differentiation grade, Union for International Cancer Control staging, tumor-lymph node-metastasis staging are significantly related to LVI or PNI. Multivariate logistic regression analysis shows that poor differentiation and N ≥ 1 can be used as independent risk factors and predictive factors for LVI. At the same time, poor differentiation and T > 3 is an independent risk factor for PNI. Only poor differentiation is the risk factor for poor prognosis in Cox risk regression analysis. In addition, the simultaneous occurrence of LVI and PNI is an independent prognostic factor.

Ratiometric detection and imaging of endogenous alkaline phosphatase activity by fluorescein-coumarin-based fluorescence probe.

Alkaline phosphatase (ALP) is a type of enzyme that widely exists in various tissues of the human body; it plays an important role in regulating many cell functions. The development of a sensitive and accurate tool to detect the changes of ALP activity in organisms can contribute to research in the fields of biochemistry, cytology, clinical medicine, etc. In this paper, a small organic molecule-based ratiometric fluorescent probe (FCP) was designed based on the hydroxyl electron-donating group in fluorescein-coumarin protected by the phosphate group. ALP can trigger the fluorescence change through the enzyme-catalyzed cleavage of phosphoryl ester groups, and the ratio of ALP can be measured at wavelengths of 465 nm and 530 nm. The probe had high selectivity and sensitivity to ALP, and the detection limit measured under the optimal conditions in an aqueous medium reached 0.006 mU/mL. The ALP activity of human serum samples was determined using the probe and found to be in good agreement with that measured using commercial ALP kits. Finally, the probe was also successfully applied to image ALP in living hepatocytes with good selectivity and sensitivity.

Identification of Key Genes Related With Aspartic Acid Metabolism and Corresponding Protein Expression in Human Colon Cancer With Postoperative Prognosis and the Underlying Molecular Pathways Prediction.

Objective: Colon cancer is one of the most frequent and lethal neoplasias. Altered metabolic activity is a well-known hallmark for cancer. The present study is aiming to screen key genes associated with tumor metabolism and construct a prognostic signature of colon cancer patients. Methods: Glutamine- and UC- metabolism related genes were downloaded from GSEA MsigDB. Three key genes were screened by Cox regression analysis with data samples downloaded from TCGA and GSE29623 database. Consistent clustering based on the prognostic genes identified was employed to divide the colon cancer samples into two clusters with significant OS differences. The mRNA and protein expression of the key genes in colon tissues and matched adjacent noncancerous tissues of 16 patients were detected by IHC, qPCR, and Western blot to validate the constructed clustering model. GO, GSVA, and IPA were used to predict the relevant metabolic pathways. Results: According to the three key genes identified, i.e., ASNS, CEBPA, and CAD, the cohort can be divided into two clusters with prognosis differences. Clinical specimen results confirmed that the risk model established was effective, and the different expression pattern of ASNS and CEBPA was correlated with TNM stage and lymph node metastasis, whilst that of CAD was correlated with post-operative tumor metastasis and recurrence. Molecular mechanism prediction indicated that CREB, insulin, and RNA Pol II were the key nodes affecting CEBPA and ASNS expression. Moreover, TIDE algorithm reflected the better immune response of the cluster with shorter OS. Further immune infiltration and checkpoints analyses provided important reference for clinicians to perform individualized immunotherapy. Conclusion: Differential expression profile of three aspartic acid metabolic-associated genes, ASNS, CEBPA, and CAD, can be considered as a risk model with a good evaluation effect on the prognosis of colon cancer patients.

Induction and application of ferroptosis in cancer therapy.

At present, more than one cell death pathways have been found, one of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent and lipid peroxidation-driven regulated cell death pathway. In the past few years, ferroptosis has been shown to induce tumor cell death, providing new ideas for tumor treatment. In this article, we summarize the latest advances in ferroptosis-induced tumor therapy at the intersection of tumor biology, molecular biology, redox biology, and materials chemistry. First, we state the characteristics of ferroptosis in cells, then introduce the key molecular mechanism of ferroptosis, and describes the relationship between ferroptosis and oxidative stress signaling pathways. Finally, we focused on several types of ferroptosis inducers discovered by scholars, and the application of ferroptosis in systemic chemotherapy, radiotherapy, immunotherapy and nanomedicine, in the hope that ferroptosis can exert its potential in the treatment of tumors.

Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics.

BACKGROUND: Gastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer. METHODS: Ferroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan-Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA). RESULTS: A ferroptosis-related "lncRNA-mRNA" co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients. CONCLUSION: Our prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.

Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells.

Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a "nitrogen reservoir" for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism.

A simple and general strategy for postsurgical personalized cancer vaccine therapy based on an injectable dynamic covalent hydrogel.

Cancer vaccines artificially stimulate the immune system against cancer and are considered the most promising treatment of cancer. However, the current progress in vaccine research against cancer is still limited and slow, partially due to the difficulties in identifying and obtaining tumor-specific antigens. Considering surgery as the first choice for tumor treatment in most cases, the authors evaluated whether the resected tumor can be directly used as a source of tumor antigens for designing personalized cancer vaccines. Based on this idea, herein, the authors report a dynamic covalent hydrogel-based vaccine (DCHVax) for personalized postsurgical management of tumors. The study uses proteins extracted from the resected tumor as antigens, CpG as the adjuvant, and a multi-armed poly(ethylene glycol) (8-arm PEG)/oxidized dextran (ODEX) dynamically cross-linked hydrogel as the matrix. Subcutaneous injection of DCHVax recruits dendritic cells to the matrix in situ and elicits robust tumor-specific immune responses. Thus, it effectively inhibits the postoperative growth of the residual tumor in several murine tumor models. This simple and personalized method to develop cancer vaccines may be promising in developing clinically relevant strategies for postoperative cancer treatment.

Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer Immunotherapy.

Gut bacteria and their metabolites influence the immune microenvironment of liver through the gut-liver axis, thus representing emerging therapeutic targets for liver cancer therapy. However, directly manipulating gut microbiota or their metabolites is not practical in clinic since the safety concerns and the complicated mechanism of action. Considering the dysregulated bile acid profiles associated with liver cancer, here we propose a strategy that directly manipulates the primary and secondary bile acid receptors through nanoapproach as an alternative and more precise way for liver cancer therapy. We show that nanodelivery of bile acid receptor modulators elicited robust antitumor immune responses and significantly changed the immune microenvironment in the murine hepatic tumor. In addition, ex vivo stimulation on both murine and patient hepatic tumor tissues suggests the observation here may be meaningful for clinical practice. This study elucidates a novel and precise strategy for liver cancer immunotherapy.