Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration.

PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.

Prognostic Signature in Osteosarcoma Based on Amino Acid Metabolism-Associated Genes.

Background: Osteosarcoma (OS) is undeniably a formidable bone malignancy characterized by a scarcity of effective treatment options. Reprogramming of amino acid (AA) metabolism has been associated with OS development. The present study was designed to identify metabolism-associated genes (MAGs) that are differentially expressed in OS and to construct a MAG-based prognostic risk signature for this disease. Methods: Expression profiles and clinicopathological data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena databases. A set of AA MAGs was obtained from the MSigDB database. Differentially expressed genes (DEGs) in GEO dataset were identified using "limma." Prognostic MAGs from UCSC Xena database were determined through univariate Cox regression and used in the prognostic signature development. This signature was validated using another dataset from GEO database. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, single sample gene set enrichment analysis, and GDSC2 analyses were performed to explore the biological functions of the MAGs. A MAG-based nomogram was established to predict 1-, 3-, and 5-year survival. Real-time quantitative polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of MAGs in primary OS and paired adjacent normal tissues. Results: A total of 790 DEGs and 62 prognostic MAGs were identified. A MAG-based signature was constructed based on four MAGs: PIPOX, PSMC2, SMOX, and PSAT1. The prognostic value of this signature was successfully validated, with areas under the receiver operating characteristic curves for 1-, 3-, and 5-year survival of 0.714, 0.719, and 0.715, respectively. This MAG-based signature was correlated with the infiltration of CD56dim natural killer cells and resistance to several antiangiogenic agents. The nomogram was accurate in predictions, with a C-index of 0.77. The expression of MAGs verified by experiment was consistent with the trends observed in GEO database. Conclusion: Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.

Development and validation of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy: A study protocol.

AIM: This study aims to develop and validate a clinical nutrition risk screening tool to predict nutrition risk in home for the patients with gastric cancer after surgery at home so that high-risk patients can be targeted for preventive nutrition care. DESIGN: The development of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy (SNRSGC) through literature review, expert panel ratings and cognitive interview; the validation of SNRSGC is evaluated through prospective research on participants. METHODS: This research is divided into four parts: Step 1, Identification of a potential referred nutritional risk screening; Step 2, Item generation and scoring are selected through literature review methods to screen sensitive indicators which can reflect the nutritional characteristics of patients after gastric cancer surgery, establish the frame and update according to the latest guidelines; Step 3, Item reduction is determined by the rating of SNRSGC items by an expert panel and cognitive interview; Step 4, During the validation stage, we conducted research design based on the Consensus-based Standards for the selection of health Measurement Instruments checklist to evaluate the validity, reliability, interpretability and acceptability of SNRSGC. RESULTS: SNRSGC is the first screening tool specifically to predict nutrition risk for stay-at-home postoperative patients with gastric cancer, which can help patients at home detect nutritional risks at home in time and guide patients to seek medical treatment as soon as possible to improve their nutritional status.

Nursing student learning of evidence-based nursing through case-based learning and flipped learning: A mixed study.

AIM: To evaluate a teaching experience in evidence-based nursing learning through case-based learning (CBL) and flipped learning (FL). DESIGN: Embedded mixed methods study. METHODS: In the first phase, a questionnaire on utility, satisfaction and perceived competency development is used to collect quantitative data, and the open question instrument is used to collect qualitative data. After the first phase, an in-depth semi-structured interview is used. RESULTS: Five themes are identified: the enhancement of learning content, knowledge integration and transfer, the development of teamwork competency, the didactic support of FL and the difficulties and challenges faced by students. Regarding utility, 'combine theory and practice' and 'select the best evidence from what is found in the search' have the highest values. The most developed skills are communication and critical thinking ability. Finally, most participants are satisfied. CONCLUSIONS: The combination of CBL and FL is an innovative strategy for learning evidence-based nursing courses. No Patient or Public Contribution.

Modelling the case-based learning preferences of undergraduate nursing students using a discrete choice experiment in China.

PURPOSE: To investigate the preferences for case-based learning programmes among undergraduate nursing students. METHOD: A questionnaire was designed based on a discrete choice experiment, and 227 undergraduate nursing students were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULT: All attributes in our study were found to have a significant influence on undergraduate nursing students' preferences for case-based learning programmes. The students' preference for the CBL programme was influenced by the clinical internship experience and type of university. Furthermore, the most ideal scenario was found to be video case modality, unfolding delivery, provided by academic experts and clinical instructors, group size 9-11, adequate feedback, and fragmented case content. CONCLUSION: The undergraduate nursing students' preferences for case-based learning programmes were affected by the provider, case modality, modality, group size, feedback, and case content. Our results can provide useful information for nursing educators to gain insight into student preferences and formulate case-based learning programs.

MTA1 localizes to the mitotic spindle apparatus and interacts with TPR in spindle assembly checkpoint regulation.

We previously identified a cell cycle-dependent periodic subcellular distribution of cancer metastasis-associated antigen 1 (MTA1) and unraveled a novel role of MTA1 in inhibiting spindle damage-induced spindle assembly checkpoint (SAC) activation in cancer cells. However, the more detailed subcellular localization of MTA1 in mitotic cells and its copartner in SAC regulation in cancer cells are still poorly understood. Here, through immunofluorescent colocalization analysis of MTA1 and alpha-tubulin in mitotic cancer cells, we reveal that MTA1 is dynamically localized to the spindle apparatus throughout the entire mitotic process. We also demonstrated a reversible upregulation of MTA1 expression upon spindle damage-induced SAC activation, and time-lapse imaging assays indicated that MTA1 silencing delayed the mitotic metaphase-anaphase transition in cancer cells. Further investigation revealed that MTA1 interacts and colocalizes with Translocated Promoter Region (TPR) on spindle microtubules in mitotic cells, and this interaction is attenuated on SAC activation. TPR is well-implicated in SAC regulation via binding the MAD1-MAD2 complex, however, no interactions between MTA1 and MAD1 or MAD2 were detected in our coimmunoprecipitation (co-IP) assays, suggesting that the MTA1-TPR may represent a distinct SAC-associated complex separate from the previously reported TPR-MAD1/MAD2 complex. Our data provide new insights into the subcellular localization and molecular function of MTA1 in SAC regulation in cancer, and indicate that intervention of the MTA1-TPR interaction may be effective to modulate SAC and hence chromosomal instability (CIN) in tumorigenesis.

Construction of a novel immune response prediction signature to predict the efficacy of immune checkpoint inhibitors in clear cell renal cell carcinoma patients.

Background: Immune checkpoint inhibitor (ICI) treatment has enhanced survival outcomes in clear cell renal cell carcinoma (ccRCC) patients. Nevertheless, the effectiveness of immunotherapy in ccRCC patients is restricted and we intended to develop and characterize an immune response prediction signature (IRPS) to forecast the efficacy of immunotherapy. Methods: RNA-seq expression profile and clinicopathologic characteristics of 539 kidney cancer and 72 patients with normal specimens, were downloaded from the Cancer Genome Atlas (TCGA) database, while the Gene Expression Omnibus (GEO) database was used as the validation set, which included 24 ccRCC samples. Utilization of the TCGA data and immune genes databases (ImmPort and the InnateDB), we explored through Weighted Gene Co-expression Network Analysis (WGCNA), along with Least Absolute Shrinkage and Selection Operator method (LASSO), and constructed an IRPS for kidney cancer patients. GSEA and CIBERSORT were performed to declare the molecular and immunologic mechanism underlying the predictive value of IRPS. The Human Protein Atlas (HPA) was deployed to verify the protein expressions of IRPS genes. Tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS) were computed to determine the risk of immune escape and value the discrimination of IRPS. A ccRCC cohort with anti-PD-1 therapy was obtained as an external validation data set to verify the predictive value of IRPS. Results: We constructed a 10 gene signature related to the prognosis and immune response of ccRCC patients. Considering the IRPS risk score, patients were split into high and low risk groups. Patients with high risk in the TCGA cohort tended towards advanced tumor stage and grade with poor prognosis (p < 0.001), which was validated in GEO database (p = 0.004). High-risk group tumors were related with lower PD-L1 expression, higher TMB, higher MSIsensor score, lower IPS, higher TIDE score, and enriched Treg cells, which might be the potential mechanism of immune dysfunction and exclusion. Patients in the IRPS low risk group had better PFS (HR:0.73; 95% CI: 0.54-1.0; P = 0.047). Conclusion: A novel biomarker of IRPS was constructed to predict the benefit of immunotherapy, which might lead to more individualized prognoses and tailored therapy for kidney cancer patients.

Design of online formative assessment of nursing humanities curriculum during the COVID-19 pandemic: A teaching practice research.

BACKGROUND: Under the digital transformation trend nursing education, online formative assessment (OFA) provides a new opportunity. However, the OFA of nursing humanities course lacks design and practice, and faces the challenge of enhancing effective communication between teachers and students, student participation and autonomous learning. OBJECTIVES: To enhance the reliability of OFA in nursing humanities courses and provide practical experience for online teaching in the nursing profession. DESIGN: A quantitative research approach was used. SETTING: This study was conducted in a comprehensive university in China. PARTICIPANTS: We conducted teaching practice on 185 nursing undergraduates, with 89 students in the experimental group, and 96 students in the control group. METHODS: In the 2020-2021 multicultural nursing course, student learning outcomes and questionnaires were analyzed through the online learning tool Superstar Learning, student feedback and satisfaction questionnaires, and descriptive analysis and independent sample t-tests were conducted using SPSS 25.0 software. RESULTS: The OFA of students using Superstar Learning differed in learning performance and time to receive feedback from teachers between the experimental and control groups, and both groups had higher satisfaction levels. The experimental group's instructional design contained a synchronous classroom discussion module with better participation. CONCLUSIONS: During the COVID-19 pandemic, the use of online learning tools can support the implementation of OFA, build an environment where teachers and students participate together, have a positive impact on the continuous updating of teachers' teaching programs and students' learning outcomes. Simultaneous classroom discussions are expected to be an effective way to improve the reliability of OFA. Our instructional design, provides best practice suggestions for future online teaching and learning.

Selected cutaneous adverse events in patients treated with ICI monotherapy and combination therapy: a retrospective pharmacovigilance study and meta-analysis.

Introduction: Cutaneous adverse events are commonly reported immune-related adverse events (irAEs), some of which are serious or even life-threatening, and it is essential to study these specific cutaneous AEs to understand their characteristics and risk. Methods: We performed a meta-analysis of published clinical trials for immune checkpoint inhibitors (ICIs) to evaluate the incidence of cutaneous adverse events, using data from PubMed, Embase, and the Cochrane Library databases. Results: A total of 232 trials with 45,472 patients were involved. Results showed that anti-PD-1 and targeted therapy combinations were associated with higher risk for most of the selected cutaneous adverse events. In addition, a retrospective pharmacovigilance study was conducted using the Food and Drug Administration (FDA) Adverse Events System database. Reporting odds ratio (ROR) and Bayesian information components (IC) were used to perform the disproportionality analysis. Cases were extracted from January 2011 to September 2020. We identified 381 (20.24%) maculopapular rash, 213 (11.32%) vitiligo, 215 (11.42%) Stevens-Johnson syndrome (SJS), and 165 (8.77%) toxic epidermal necrolysis (TEN) cases. For vitiligo, anti-PD-1/L1 combined with anti-CTLA-4 therapy showed the strongest signal (ROR: 55.89; 95% CI: 42.34-73.78; IC025: 4.73). Palmar-plantar erythrodysesthesia (PPE) was reported with the most significant association with combined anti-PD-1/L1 and VEGF (R)-TKIs (ROR: 18.67; 95% CI: 14.77-23.60; IC025: 3.67). For SJS/TEN, antiPD-1 inhibitors showed the strongest signal (ROR: 3.07; 95% CI: 2.68-3.52; IC025: 1.39). The median onset time of vitiligo and SJS/TEN was 83 and 24 days, respectively. Conclusion: Overall, in selected cutaneous AEs, each of them showed specific characteristics. It is necessary to realize their differences and take appropriate interventions in patients with different regimens.

Unsupervised Monocular Depth and Camera Pose Estimation with Multiple Masks and Geometric Consistency Constraints.

This paper presents a novel unsupervised learning framework for estimating scene depth and camera pose from video sequences, fundamental to many high-level tasks such as 3D reconstruction, visual navigation, and augmented reality. Although existing unsupervised methods have achieved promising results, their performance suffers in challenging scenes such as those with dynamic objects and occluded regions. As a result, multiple mask technologies and geometric consistency constraints are adopted in this research to mitigate their negative impacts. Firstly, multiple mask technologies are used to identify numerous outliers in the scene, which are excluded from the loss computation. In addition, the identified outliers are employed as a supervised signal to train a mask estimation network. The estimated mask is then utilized to preprocess the input to the pose estimation network, mitigating the potential adverse effects of challenging scenes on pose estimation. Furthermore, we propose geometric consistency constraints to reduce the sensitivity of illumination changes, which act as additional supervised signals to train the network. Experimental results on the KITTI dataset demonstrate that our proposed strategies can effectively enhance the model's performance, outperforming other unsupervised methods.

Case-based learning interventions for undergraduate nursing students in a theoretical course: A review of design, implementation, and outcomes.

BACKGROUND: Case-based learning (CBL) is a contextualized learning and teaching method that can facilitate active and reflective learning to develop critical thinking and problem-solving skills. However, nursing educators have some difficulty in creating a CBL environment that matches the diverse professional nursing curriculum and students' needs, including developing relevant cases and appropriate CBL implementation processes. OBJECTIVE: To summarize the case design, implementation process, and their relationship with CBL effectiveness. METHODS: Electronic databases of PubMed, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI) and Wanfang Data (a Chinese database) were searched from inception until January 2022. Study quality was assessed using the Mixed Methods Appraisal Tool. A qualitative synthesis was then conducted to summarize the study findings. RESULTS: The systematic mixed studies review included twenty-one quantitative studies, five qualitative studies and two mixed methods studies. The case design and implementation process were indispensable parts of each study, but the application process of CBL in each study was slightly different, basically including case design, preparation, small-group interaction and exploration, collaborative efforts, teacher summary, assignment and teacher feedback. There were three themes in this review that indicate the effect of CBL on students, namely, knowledge, competence and attitude. CONCLUSION: The present review analyzes the available literature and suggests that there is no common format for the case design and CBL implementation process, but demonstrates that they are an indispensable part of each study. This review provides conceptual procedures for nurse educators to design and implement CBL in nursing theoretical courses to improve the effectiveness of CBL.

Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling.

Triple-negative breast cancer (TNBC) exhibits the poorest outcomes among breast cancer subtypes due to the high heterogeneity and a lasting scarcity of effectual treatments. Targeted therapies based on molecular subtypes of TNBC are critical step toward tailoring treatments to improve clinical outcomes. Gastrointestinal cancer stem cell (CSC) marker DCLK1 was reported to be highly expressed in stem cell-rich subtype of TNBC. Here, we firstly explored the impacts of DCLK1 on tumor cells as well as their immune microenvironment in TNBC and potential therapeutic strategies for TNBC patients with high DCLK1 expression. Our results disclosed that DCLK1 overexpression promoted, while knockout of DCLK1 suppressed the CSC-like traits of TNBC cells and resistance to chemotherapeutics. Besides, DCLK1 supported immune escape by inhibiting intratumoral cytotoxic T cell infiltration in TNBC and hence limited immune checkpoint inhibitors efficacy. Mechanistically, bioinformatics analysis revealed that IL-6/STAT3 signaling was significantly enriched in high DCLK1-expressing patients, and our results further revealed that DCLK1 enhanced IL-6 expression and STAT3 activation in TNBC cells, which finally gave rise to upregulated CSC traits and suppressed CD8+ T-cell activity. Inhibiting IL-6/STAT3 pathway by IL-6R antagonist, Tocilizumab or STAT3 inhibitor, S31-201 could abolish DCLK1-promoted malignant phenotypes of TNBC cells. Finally, DCLK1 was identified to be specifically and highly expressed in the mesenchymal-like subtype of TNBC and targeting DCLK1 could improve chemotherapy efficacy and activate antitumor immunity. Overall, our study revealed the potential clinical benefits of targeting DCLK1 in TNBC treatment.

Reflection on the teaching of student-centred formative assessment in medical curricula: an investigation from the perspective of medical students.

BACKGROUND: Formative assessment (FA) is becoming increasingly common in higher education, although the teaching practice of student-centred FA in medical curricula is still very limited. In addition, there is a lack of theoretical and pedagogical practice studies observing FA from medical students' perspectives. The aim of this study is to explore and understand ways to improve student-centred FA, and to provide a practical framework for the future construction of an FA index system in medical curricula. METHODS: This study used questionnaire data from undergraduate students in clinical medicine, preventive medicine, radiology, and nursing at a comprehensive university in China. The feelings of medical students upon receiving student-centred FA, assessment of faculty feedback, and satisfaction were analysed descriptively. RESULTS: Of the 924 medical students surveyed, 37.1% had a general understanding of FA, 94.2% believed that the subject of teaching assessment was the teacher, 59% believed that teacher feedback on learning tasks was effective, and 36.3% received teacher feedback on learning tasks within one week. In addition, student satisfaction results show that students' satisfaction with teacher feedback was 1.71 ± 0.747 points, and their satisfaction with learning tasks was 1.83 ± 0.826 points. CONCLUSION: Students as participants and collaborators in FA provide valid feedback for improving student-centred FA in terms of student cognition, empowered participation, and humanism. In addition, we suggest that medical educators avoid taking student satisfaction as a single indicator for measuring student-centred FA and to try to build an assessment index system of FA, to highlight the advantages of FA in medical curricula.

The effectiveness of health education based on the 5Ts for teach-back on oral nutritional supplements compliance of post-discharge patients after surgery for gastric cancer: a randomized controlled trial.

OBJECTIVE: This study aims to explore the 5Ts teach-back(5Ts) to improve oral nutritional supplements (ONS) compliance of discharged patients after gastric cancer surgery. SETTING AND METHODS: Patients were recruited from the Bethune First Hospital of Jilin University. The patients were randomly assigned to 5Ts (n = 54) and routine health education (n = 54). Weekly ONS compliance was collected by "weekly ONS diary." ONS knowledge, health literacy, and health education satisfaction were collected at baseline and 5 weeks after discharge. Chi-square test, Mann-Whitney U test, and T test were used for data analysis. RESULTS: At the end of the intervention, there were 41 and 40 patients in intervention and control group. 5Ts significantly improve ONS compliance, ONS knowledge level (P = 0.000), health literacy level (P = 0.011), and health education satisfaction (P = 0.009) of patients. At the end of follow-up, there were 30 and 27 patients in two groups, and no significant difference in ONS compliance (P = 0.728). CONCLUSION: The 5Ts can significantly improve patients' ONS compliance and the effect of health education. TRIAL REGISTRATION NUMBER: This prospective trial was registered in the Chinese Clinical Trial Registry at ChiCTR2000040986 ( http://www.chictr.org.cn ). PATIENT OR PUBLIC CONTRIBUTION: Jia Wang and Haiyan Hu contributed to the performance of the study, analysis and interpretation the data, and drafted the manuscript; Jianan Sun and Qing Zhang contributed to the supervision of the study and interpreted the data; Zhiming Chen contributed to the analysis and interpretation the data; Qiuchen Wang contributed to the performance of the study and revised the manuscript; Mingyue Zhu contributed to interpretation the data; Jiannan Yao contributed to revise the manuscript; Hua Yuan and Xiuying Zhang contributed to the conception of the study, performed the study, interpreted the data, and significantly revised the manuscript. All authors screened the final version of the manuscript.

Effect of abdominal massage on feeding intolerance in patients receiving enteral nutrition: A systematic review and meta-analysis.

AIM: This study aimed to evaluate the effect of abdominal massage (AM) on feeding intolerance (FI) in patients receiving enteral nutrition (EN). DESIGN: A systematic review and meta-analysis. METHODS: We searched seven electronic databases to September 2021. STATA and RevMan were used to analyse the data. RESULTS: Eleven studies were included. The results revealed that AM could significantly reduce gastric residual volume and abdominal circumference difference, and reduce the incidence of gastric retention, vomiting, abdominal distention (all p < 0.001), diarrhoea (p = 0.02) and constipation (p = 0.002) in the experimental group. One study reported the incidence of aspiration in the control group was higher, but this was not statistically significant (p = 0.07). The meta-regression analysis showed there was a statistically significant correlation between intervention personnel and gastric residual volume (p = 0.035). CONCLUSION: AM could reduce the amount and incidence of gastric retention and the changes in abdominal circumference, and significantly reduce the incidence of gastrointestinal symptoms, without increasing the incidence of aspiration for EN patients. No Patient or Public Contribution.

DCLK1 Suppresses Tumor-Specific Cytotoxic T Lymphocyte Function Through Recruitment of MDSCs via the CXCL1-CXCR2 Axis.

BACKGROUND & AIMS: Gastrointestinal cancer stem cell marker doublecortin-like kinase (DCLK1) is strongly associated with poor outcomes in colorectal cancer (CRC). Although DCLK1's regulatory effect on the tumor immune microenvironment has been hypothesized, its mode of action has not been shown previously in vivo, which hampers the potential intervention based on this molecule for clinical practice. METHODS: To define the immunomodulatory mechanisms of DCLK1 in vivo, we generated DCLK1-/- tumor cells by Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) and developed subcutaneous and intestinal orthotopic transplantation tumor models. Tumor tissues were harvested and subjected to immunofluorescence staining, flow cytometry analysis of tumor-infiltrating immune cell populations, tumor myeloid-derived suppressor cell (MDSC) sorting by isolation kit and then co-culture with spleen T cells, and RNA sequencing for transcriptomic analysis. RESULTS: We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Collectively, we validated that DCLK1 promotes tumor growth in CRC through recruitment of T-cell-suppressive MDSCs. CONCLUSIONS: DCLK1-mediated immune suppression in tumor models allows escaping from the host's antitumor response. Because DCLK1 is one of the most common markers in gastrointestinal tumors, these results identify a precise therapeutic target for related clinical interventions.

A targetable MYBL2-ATAD2 axis governs cell proliferation in ovarian cancer.

The chromatin-modifying enzyme ATAD2 confers oncogenic competence and proliferative advantage in malignances. We previously identified ATAD2 as a marker and driver of cell proliferation in ovarian cancer (OC); however, the mechanisms whereby ATAD2 is regulated and involved in cell proliferation are still unclear. Here, we disclose that ATAD2 displays a classical G2/M gene signature, functioning to facilitate mitotic progression. ATAD2 ablation caused mitotic arrest and decreased the ability of OC cells to pass through nocodazole-arrested mitosis. ChIP-seq data analyses demonstrated that DREAM and MYBL2-MuvB (MMB), two switchable MuvB-based complexes, bind the CHR elements in the ATAD2 promoter, representing a typical feature and principle mechanism of the periodic regulation of G2/M genes. As a downstream target of MYBL2, ATAD2 deletion significantly impaired MYBL2-driven cell proliferation. Intriguingly, ATAD2 silencing also fed back to destabilize the MYBL2 protein. The significant coexpression of MYBL2 and ATAD2 at both the bulk tissue and single-cell levels highlights the existence of the MYBL2-ATAD2 signaling in OC patients. This signaling is activated during tumorigenesis and correlated with TP53 mutation, and its hyperactivation was found especially in high-grade serous and drug-resistant OCs. Disrupting this signaling by CRISPR/Cas9-mediated ATAD2 ablation inhibited the in vivo growth of OC in a subcutaneous tumor xenograft mouse model, while pharmacologically targeting this signaling with an ATAD2 inhibitor demonstrated high therapeutic efficacy in both drug-sensitive and drug-resistant OC cells. Collectively, we identified a novel MYBL2-ATAD2 proliferative signaling axis and highlighted its potential application in developing new therapeutic strategies, especially for high-grade serous and drug-resistant OCs.

Factors influencing adherence to healthy eating behaviors among adult colorectal cancer survivors: a systematic mixed method review.

PURPOSE: Under the umbrella of social cognitive theory, we examined the influences of personal, environmental, and behavioral factors on adherence to healthy eating behaviors among colorectal cancer survivors. METHODS: Based on Pluye and Hong's framework, a systematic mixed studies review was conducted. An extensive search strategy was applied in PubMed, Web of Science, Embase, CINAHL, and PsycINFO (from date of record to 2022 January 22). The pillar integration process was employed to integrate the extracted data. The Mixed Methods Appraisal Tool was used to appraise the quality of all retained studies. RESULTS: Twenty-eight studies with a total sample size of 5106 were included in the analysis, with 15 quantitative studies, 12 qualitative studies, and 1 mixed method study. The critical appraisal showed that 22 of the 28 studies (79%) were rated with five stars, while 6 (21%) were rated with four stars. The personal factors influencing adherence to healthy eating behaviors among colorectal cancer survivors included outcome expectancies, self-efficacy, psychological factors, knowledge about healthy eating, demographic and disease characteristics, environmental factors incorporated outside information on healthy eating, power of surrounding people, social activities, cultural milieus, socioeconomic status, and education. The behavioral factors included self-regulation of diet, goals, and other behaviors closely related to healthy eating behaviors. CONCLUSIONS: Adherence to healthy eating behaviors among colorectal cancer survivors was influenced collectively by personal factors, environmental factors and behavioral factors.