JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma.

The polycomb group (PcG) comprises a set of proteins that exert epigenetic regulatory effects and play crucial roles in diverse biological processes, ranging from pluripotency and development to carcinogenesis. Among these proteins, enhancer of zeste homolog 2 (EZH2) stands out as a catalytic component of polycomb repressive complex 2 (PRC2), which plays a role in regulating the expression of homologous (Hox) genes and initial stages of x chromosome inactivation. In numerous human cancers, including head and neck squamous cell carcinoma (HNSCC), EZH2 is frequently overexpressed or activated and has been identified as a negative prognostic factor. Notably, EZH2 emerges as a significant gene involved in regulating the STAT3/HOTAIR axis, influencing HNSCC proliferation, differentiation, and promoting metastasis by modulating related oncogenes in oral cancer. Currently, various small molecule compounds have been developed as inhibitors specifically targeting EZH2 and have gained approval for treating refractory tumors. In this review, we delve into the epigenetic regulation mediated by EZH2/PRC2 in HNSCC, with a specific focus on exploring the potential roles and mechanisms of EZH2, its crucial contribution to targeted drug therapy, and its association with cancer markers and epithelial-mesenchymal transition. Furthermore, we aim to unravel its potential as a therapeutic strategy for oral squamous cell carcinoma.

Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods.

Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC. Further, it explores the mechanisms involved in the interaction of this pathway with exosomes and protein-protein interactions, and concludes with potential future OSCC therapeutic strategies.

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme-Induced Proximity Labeling.

Achieving increasingly finely targeted drug delivery to organs, tissues, cells, and even to intracellular biomacromolecules is one of the core goals of nanomedicines. As the delivery destination is refined to cellular and subcellular targets, it is essential to explore the delivery of nanomedicines at the molecular level. However, due to the lack of technical methods, the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date. Here, we develop an enzyme-induced proximity labeling technology in nanoparticles (nano-EPL) for the real-time monitoring of proteins that interact with intracellular nanomedicines. Poly(lactic-co-glycolic acid) nanoparticles coupled with horseradish peroxidase (HRP) were fabricated as a model (HRP(+)-PNPs) to evaluate the molecular mechanism of nano delivery in macrophages. By adding the labeling probe biotin-phenol and the catalytic substrate H2O2 at different time points in cellular delivery, nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles. Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP (+)-PNPs in macrophages over time. Based on dynamic clustering analysis of these proteins, we further discovered that different organelles, including endosomes, lysosomes, the endoplasmic reticulum, and the Golgi apparatus, are involved in delivery with distinct participation timelines. More importantly, the engagement of these organelles differentially affects the drug delivery efficiency, reflecting the spatial-temporal heterogeneity of nano delivery in cells. In summary, these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation.

Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccine-induced immunity and prolong the time-effectiveness, we design a priming-boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&-)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&-) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&-), BNV(-) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.

Remodeling of intestinal epithelium derived extracellular vesicles by nanoparticles and its bioeffect on tumor cell migration.

Extracellular vesicles (EVs) are an effective tool to elucidate the bioeffect of nanomedicines. To clarify the interaction between oral nanomedicines and intestinal epithelial cells, and their bioeffects on downstream cells, polystyrene nanoparticles (PS-NPs) with different sizes were used as the model nanomedicines for EVs induction. Caco-2 monolayers were selected as the model of the intestinal epithelium and DLD-1 cells as the colorectal cancer model proximal to the gastrointestinal tract. It is found that compared with small-sized (25, 50, 100 nm) PS-NPs, the large-sized (200 and 500 nm) exhibited higher co-localization with multivesicular bodies and lysosomes, and more significant reduction of lysosomal acidification in Caco-2 cells. Proteomic and western-blotting analysis showed that the EVs remodeled by large-sized PS-NPs exhibited a higher extent of protein expression changes. The in vitro and in vivo signaling pathway detection in DLD-1 cells and DLD-1 cell xenograft nude mice showed that the remodeled EVs by large-sized PS-NPs inhibited the activation of multiple signaling pathways including Notch3, EGF/EGFR, and PI3K/Akt pathways, which resulted in the inhibition of tumor cell migration. These results primarily clarify the regulation mechanisms of nanomedicines-EVs-receptor cells chain. It provides a new perspective for the rational design and bioeffect evaluation of oral drug nanomaterials and sets up the fundamental knowledge for novel tumor therapeutics in the future.

Comparison of Postoperative Outcome and Prognosis Among Laparoscopic Left Colectomy and Laparoscopic Sigmoidectomy in Sigmoid Colon Cancer Patients: A Propensity Score Matching Study.

PURPOSE: The purpose of this study was to investigate the effect of laparoscopic left colectomy (LLC) and laparoscopic sigmoidectomy (LSD) on short-term outcomes and prognosis of sigmoid colon cancer (SCC) patients using propensity score matching (PSM). METHODS: In this retrospective study, the SCC patients who underwent LLC or LSD surgery were collected from a single clinical center from Jan 2011 to Dec 2019. Short-term outcomes and prognosis were compared between patients who received LSD surgery and LLC surgery. RESULTS: A total of 356 patients were included in this study. After 1:1 PSM analysis, there were 50 patients who underwent LLC surgery and 50 patients who underwent LSD surgery left in this study. No significant difference was found in baseline characteristics after PSM (P > .05). In comparison with the LLC surgery group, the LSD surgery group had shorter operation time (P = .003) after PSM. Moreover, the surgical procedure was not an independent predictor for overall survival (OS) (P = .918, 95% CI = .333-2.688) and disease-free survival DFS (P = .730, 95% CI = .335-2.150), but age (OS: P = .009, 95% CI = 1.010-1.075; DFS: P = .014, 95% CI = 1.007-1.061) and tumor stage (OS: P = .004, 95% CI = 1.302-3.844; DFS: P < .01, 95% CI = 1.572-4.171) were the independent risk factors for OS and DFS in SCC patients. CONCLUSION: There was no significant difference between the two surgical procedures for prognosis of SCC patients. However, the possible reasons for changing the surgical procedures should be cautious by surgeons.

The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization.

OBJECTIVE: Cachexia, marked by muscle atrophy, poses substantial challenges for prevention and treatment. This study delves into the unclear role of butyrate, a gut microbiota metabolite, in cachexia by examining gut microbiota and short-chain fatty acid (SCFA) profiles in human and mouse fecal samples. METHODS: We analyzed cachexia-associated gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomic techniques. Mouse cachexia models were developed with C26 cells, and LPS was used to induce muscle cell atrophy in C2C12 cells. We evaluated butyrate's in vivo effects on intestinal health, muscle preservation, inflammation, and macrophage activity. In vitro studies focused on butyrate's influence on macrophage polarization and the subsequent effects on muscle cells. RESULTS: Both cachexia patients and mice exhibited gut microbiota imbalances, irregular butyrate concentrations, and a decline in butyrate-producing bacteria. In vivo tests showed that butyrate counteract cachexia-induced muscle atrophy by adjusting the Akt/mTOR/Foxo3a and Fbox32/Trim63 pathways. These butyrate also bolstered intestinal barrier integrity, minimized endotoxin migration, and mitigated oxidative stress. Furthermore, butyrate curtailed inflammation and macrophage penetration in muscles. In vitro experimental results demonstrate that butyrate inhibit macrophage polarization towards the M1 phenotype and promote polarization towards the M2 phenotype. Both M1 and M2 macrophages influence the aforementioned pathways and oxidative stress, participating in the regulation of muscle cell atrophy. CONCLUSION: Our study delineates the intricate interplay between gut microbiota dysbiosis, butyrate fluctuations, and cachexia progression. Butyrate not only reinforces the intestinal barrier but also orchestrates macrophage polarization, mitigating muscle atrophy and averting cachexia-induced muscle deterioration. Concurrently, the M1 and M2 macrophages play pivotal roles in modulating skeletal muscle cell atrophy. This highlights the potential of utilizing the gut-derived metabolite butyrate as a promising therapeutic approach for addressing cachexia-related issues.

Unraveling the gut microbiota and short-chain fatty acids characteristics and associations in a cancer cachexia mouse model.

OBJECTIVE: Cachexia is a common pathological condition in cancer patients, affecting prognosis and treatment outcomes. The relationship between cachexia and gut microbiota and short-chain fatty acids (SCFAs) remains understudied. This research aimed to establish a cachexia mouse model and explore the gut microbiota-SCFAs connection. The study provides fundamental insights into the regulatory mechanisms of cancer cachexia and potential therapeutic strategies. METHODS: A cachexia mouse model was created using C26 cells, with relevant indicators measured. Histological and immunohistochemical analyses assessed muscle structure and protein expression. ELISA was performed to detect the levels of IL-1ß, IL-6, TNF-α, and LPS in serum to evaluate inflammation.16S rDNA sequencing and GC-MS quantified gut microbiota and SCFAs. Bioinformatics analysis identified indicator species and explored microbiota-SCFAs correlations.ROC analysis was performed to assess the potential of gut microbiota and SCFAs in identifying cachexia. RESULTS: The cachexia mouse model exhibited weight loss, muscle atrophy, and elevated inflammatory factors. Gut microbiota in cachexia mice showed decreased diversity and imbalance. Fourteen bacterial genera were identified as potential cachexia indicators. Functional prediction indicated alterations in the functional composition of gut microbial communities in cachexia mice, particularly in carbohydrate and lipid metabolism pathways. Four SCFAs showed significant changes, potentially serving as diagnostic factors. Specific microbial taxa were positively or negatively correlated with changes in SCFAs, and these microbial taxa and differential SCFAs were also correlated with inflammatory cytokines. CONCLUSION: Our study uncovers the gut microbiota and SCFAs features in a cachexia mouse model, revealing novel correlations between them. These newfound insights into the interplay between cachexia, gut microbiota, and SCFAs provide a crucial foundation for understanding the mechanisms behind cancer cachexia development and potential therapeutic approaches.

Mitophagy-mediated inflammation and oxidative stress contribute to muscle wasting in cancer cachexia.

Cancer cachexia is commonly seen in patients with malignant tumors, which usually leads to poor life quality and negatively affects long-term prognosis and survival. Mitochondria dysfunction and enhanced autophagy are well-established to play an important role in skeletal muscle wasting. However, whether mitophagy is engaged in the pathogenesis of cancer cachexia requires further investigation. This study comprised a clinical study and animal experimentation. Clinical data such as CT images and laboratory results were obtained and analyzed. Then mice model of cancer cachexia and mitophagy inhibition were established. Data including skeletal muscle mass and function, mitochondria structure and function, inflammatory factors as well as ROS concentration. Mitophagy was enhanced in cancer cachexia patients with increased inflammatory factors. Greater disruption of skeletal muscle fiber and mitochondria structure were seen in cancer cachexia, with a higher level of inflammatory factors and ROS expression in skeletal muscle. Meanwhile, ATP production was undermined, indicating a close relationship with mitophagy, inflammation, and oxidative stress in the skeletal muscle of cancer cachexia mice models. In conclusion, mitophagy is activated in cancer cachexia and may play a role in skeletal muscle atrophy, and inflammation and oxidative stress might participate in mitophagy-related skeletal muscle injury.

Macrophage polarization in bone implant repair: A review.

Macrophages (MΦ) are highly adaptable and functionally polarized cells that play a crucial role in various physiological and pathological processes. Typically, MΦ differentiate into two distinct subsets: the proinflammatory (M1) and anti-inflammatory (M2) phenotypes. Due to their potent immunomodulatory and anti-inflammatory properties, MΦ have garnered significant attention in recent decades. In the context of bone implant repair, the immunomodulatory function of MΦ is of paramount importance. Depending on their polarization phenotype, MΦ can exert varying effects on osteogenesis, angiogenesis, and the inflammatory response around the implant. This paper provides an overview of the immunomodulatory and inflammatory effects of MΦ polarization in the repair of bone implants.

The Effect of Metabolic Syndrome on Colorectal Cancer Prognosis after Primary Surgery.

PURPOSE: The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis. METHODS: The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group. RESULTS: The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49, P = 0.21). Four studies compared DFS between the MetS group and the non-MetS group after pooling all the HRs, and there was no difference between the MetS group and the non-MetS group (HR = 1.05, 95% CI = 0.74 to 1.49, P = 0.21). Among the specific components of MetS, high fasting plasma glucose levels (HR = 1.25, 95% CI = 1.00 to 1.58, P = 0.05) had a marginally significant association with poor OS. CONCLUSION: MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.

MAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy.

Oral squamous cell carcinoma accounts for 95% of human head and neck squamous cell carcinoma cases. It is highly malignant and aggressive, with a poor prognosis and a 5-year survival rate of <50%. In recent years, basic and clinical studies have been performed on the role of the mitogen-activated protein kinase (MAPK) signaling pathway in oral cancer. The MAPK signaling pathway is activated in over 50% of human oral cancer cases. Herein, we review research progress on the MAPK signaling pathway and its potential therapeutic mechanisms and discuss its molecular targeting to explore its potential as a therapeutic strategy for oral squamous cell carcinoma.

Effect of hypoalbuminemia on short-term outcomes after colorectal cancer surgery: A propensity score matching analysis.

Purpose: The purpose of our study was to investigate the effect of pre-operative hypoalbuminemia on the short-term outcomes after primary colorectal cancer (CRC) surgery. Materials and methods: The retrospective study enrolled CRC patients who underwent primary surgery from January 2011 to December 2021 in a single teaching hospital. The short-term outcomes were compared between the hypoalbuminemia group and the normal group using propensity score matching (PSM). Univariate and multivariate logistic regression analyses were used for analyzing independent predictors of overall complications and major complications. Results: A total of 7,072 patients from a single center were enrolled in this study. There were 1,078 (15.2%) patients in the pre-operative hypoalbuminemia group and 5,994 (84.8%) patients in the normal pre-operative albumin group. After 1:1 PSM, there were 1,028 patients in the hypoalbuminemia group and 1,028 patients in the normal group. No significant differences were found in baseline information between the two groups after PSM. In terms of short-term outcomes, the hypoalbuminemia group had a longer operation time (p = 0.003), greater volume of blood loss (p = 0.036), longer hospital stays (p < 0.01), higher proportion of overall complications (p = 0.003), major complications (p = 0.016), higher incidence of pneumonia and abdominal infection (p = 0.001) than the normal group after PSM. Furthermore, hypoalbuminemia was an independent predictor for overall complications (p = 0.008) and major complications (p = 0.016). Conclusion: Pre-operative hypoalbuminemia increased overall complications and major complications after primary CRC surgery. Furthermore, hypoalbuminemia was an independent predictor for overall complications and major complications.

Factors associated with hypertension remission after gastrectomy for gastric cancer patients.

BACKGROUND: Previous studies reported hypertension remission after gastrectomy for gastric cancer patients, and the remission rate was 11.1%-93.8%. We have reported the factors of hypertension remission previously, however, the follow-up time was six months. It is necessary to identify risk factors for hypertension for a relatively longer follow-up time. AIM: To analyze the predictive factors for hypertension remission one year after gastrectomy of gastric cancer patients and to construct a risk model for hypertension remission. METHODS: We retrospectively collected the medical information of patients with concurrent gastric cancer and hypertension in a single clinical center from January 2013 to December 2020. Univariate and multivariate logistic regression of hypertension remission were conducted, and a nomogram model was established. RESULTS: A total of 209 patients with concurrent gastric cancer and hypertension were included in the current study. There were 108 patients in the remission group and 101 patients in the non-remission group. The hypertension remission rate was 51.7% one year after gastrectomy. The remission group had younger aged patients (P = 0.001), larger weight loss (P = 0.001), lower portion of coronary heart disease (P = 0.017), higher portion of II-degree hypertension (P = 0.033) and higher portion of total gastrectomy (P = 0.008) than the non-remission group. Younger age (P = 0.011, odds ratio = 0.955, 95%CI: 0.922-0.990), higher weight loss (P = 0.019, odds ratio = 0.937, 95%CI: 0.887-0.989) and total gastrectomy (P = 0.039, odds ratio = 2.091, 95%CI: 1.037-4.216) were independent predictors for hypertension remission. The concordance index of the model was 0.769 and the calibration curve suggested great agreement. Furthermore, decision curve analysis showed that the model was clinically useful. CONCLUSION: Younger age, higher weight loss and total gastrectomy were independent predictors for hypertension remission after gastrectomy for gastric cancer patients. The nomogram could visually display these results.

Does chronic kidney disease affect the complications and prognosis of patients after primary colorectal cancer surgery?

BACKGROUND: The effect of chronic kidney disease (CKD) on the outcomes of colorectal cancer (CRC) patients after primary CRC surgery is controversial. AIM: To analyze whether CKD had specific effect on the outcomes after CRC surgery. METHODS: We searched the PubMed, Embase, Cochrane Library databases and CNKI, from inception to March 14, 2022. Newcastle-Ottawa Scale was used for the quality assessment in this meta-analysis, and we used RevMan 5.3 was used for data analysis. RESULTS: A total of nine studies including 47771 patients were eligible for this meta-analysis. No significant difference was found in terms of overall postoperative complications [odds ratio (OR) = 1.78, 95%CI: 0.64-4.94, P = 0.27]. We analyzed the specific complications and found that the CKD group had higher rates of pulmonary infection (OR = 2.70, 95%CI: 1.82-4.00, P < 0.01), cardiovascular complications (OR = 3.39, 95%CI: 2.34-4.91, P < 0.01) and short-term death (OR = 3.01, 95%CI: 2.20-4.11, P < 0.01). After pooling the hazard ratio (HR), the CKD group had worse overall survival (OS) (HR = 1.51, 95%CI: 1.04-2.20, P = 0.03). We performed subgroup analyses of the dialysis and non-dialysis groups, and no significant difference was found in the non-dialysis group (HR = 1.20, 95%CI: 0.98-1.47, P = 0.08). The dialysis group had worse OS (HR = 3.36, 95%CI: 1.92-5.50, P < 0.01) than the non-dialysis group. The CKD group had worse disease-free survival (DFS) (HR = 1.41, 95%CI: 1.12-1.78, P < 0.01), and in the subgroup analysis of the dialysis and non-dialysis groups, no significant difference was found in the non-dialysis group (HR = 1.27, 95%CI: 0.97-1.66, P = 0.08). The dialysis group had worse OS (HR = 1.95, 95%CI: 1.23-3.10, P < 0.01) than the non-dialysis group. CONCLUSION: Preexisting CKD was associated with higher rates of pulmonary infection, higher rates of short-term death, and worse OS and poorer DFS following CRC surgery.

Clinical significance of aberrant left hepatic artery during gastrectomy: A systematic review.

BACKGROUND: Vascular variations are frequently encountered during surgery. Approximately thirty percent of these variations are aberrant left hepatic arteries originating from the left gastric artery. AIM: To summarize the safety and feasibility of aberrant left hepatic arteries (ALHA) ligation in gastric cancer patients who underwent laparoscopic-assisted gastrectomy (LAG). METHODS: The literature search was systematically performed on databases including PubMed, Embase, and Cochrane Library. The publishing date of eligible studies was from inception to June 2021. RESULTS: A total of nine studies were included according to the inclusion and exclusion criteria in this review. The variation rate of ALHA ranged from 7.00% to 20.70%, and four studies compared the differences between the ALHA ligation group and the preservation group. Only one study showed worse postoperative outcomes in the ALHA ligation group. In all the included studies, a significant difference was found between the ALHA ligation group and the preservation group in terms of postoperative liver enzymes after LAG. However, there was no significant difference in the number of retrieved lymph nodes between the two groups. CONCLUSION: In conclusion, it is not always safe and feasible for surgeons to ligate the ALHA during LAG surgery, and it is necessary for gastric cancer patients to undergo preoperative examination to clarify the ALHA subtypes, measure the diameter of the ALHA, and determine whether the patients have chronic liver disease.

Higher body mass index was associated with better prognosis in diabetic patients with stage II colorectal cancer.

PURPOSE: The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM). METHODS: Patients who underwent primary radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group. RESULTS: A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p < 0.01) and coronary heart disease (CHD) (p < 0.01). Furthermore, the higher BMI group had better OS (p = 0.016) and DFS (p = 0.040) than the lower BMI group in stage II CRC. In multivariate analysis, age (OS: p = 0.002, HR = 2.016, 95% CI = 1.307-3.109/ DFS: p = 0.003, HR = 1.847, 95% CI = 1.230-2.772), TNM stage (OS: p < 0.01, HR = 1.667, 95% CI = 1.281-2.169/ DFS: p = 0.001, HR = 1.545, 95% CI = 1.207-1.977), overall complications (OS: p = 0.004, HR = 1.837, 95% CI = 1.218-2.880/ DFS: p = 0.006, HR = 1.783, 95% CI = 1.184-2.686) and major complications (OS: p = 0.005, HR = 2.819, 95% CI = 1.376-5.774/ DFS: p = 0.014, HR = 2.414, 95% CI = 1.196-4.870) were independent factors of OS and DFS. Moreover, BMI (p = 0.019, HR = 0.413, 95% CI = 0.197-0.864) was an independent factor of OS in stage II CRC. CONCLUSION: Higher BMI was associated with better OS in diabetic patients with stage II CRC.

The Effect of Complications on Oncological Outcomes of Colorectal Cancer Patients After Primary Surgery: A Propensity Score Matching Analysis.

Purpose: The purpose of this study is to explore the oncologic outcomes of complications on colorectal cancer (CRC) patients who underwent primary surgery using a propensity score matching (PSM) analysis. Methods: A retrospective study was conducted from Jan 2011 to Jan 2020 in a clinical center. The overall survival (OS) and disease-free survival (DFS) were compared among the no complications group, the major complications group and the minor complications group. Results: A total of 4250 CRC patients who underwent radical primary surgery were included in the current study. Among them, 927 (21.8%) patients suffered complications. After 1:1 ratio PSM, there were 98 patients in the major complications group and in the minor complications group, and 911 patients in the overall complications group and in the no complications group. There was no significant difference in terms of baseline information after PSM (p>0.05). Complications were independent predictors of OS (p=0.000, HR=1.693, 95% CI=1.476-1.941) and DFS (p=0.000, HR=1.555, 95% CI=1.367-1.768). In terms of specific tumor stage, the no complications group had better OS on all stages (p=0.006) and stage III (p=0.003) CRC than the complications group after PSM. Furthermore, the no complications group had better DFS on all stages (p=0.005) and stage III (p=0.021) CRC than the complications group after PSM. However, there was no significant difference between the minor complications group and the major complications group in different tumor stages (p>0.05). Conclusion: Complications were associated with poor prognosis of CRC and surgeons should be cautious of the adverse events.

Nanoparticulates reduce tumor cell migration through affinity interactions with extracellular migrasomes and retraction fibers.

Nano-tumor interactions are fundamental for cancer nanotherapy, and the cross-talk of nanomedicines with the extracellular matrix (ECM) is increasingly considered essential. Here, we specifically investigate the nano-ECM interactivity using drug-free nanoparticulates (NPs) and highly metastatic cancer cells as models. We discover with surprise that NPs closely bind to specific types of ECM components, namely, retraction fibers (RFs) and migrasomes, which are located at the rear of tumor cells during their migration. This interaction is observed to alter cell morphology, limit cell motion range and change cell adhesion. Importantly, NPs are demonstrated to inhibit tumor cell removal in vitro, and their anti-metastasis potential is preliminarily confirmed in vivo. Mechanically, the NPs are found to coat and form a rigid shell on the surface of migrasomes and retraction fibers via interaction with lipid raft/caveolae substructures. In this way, NPs block the recognition, endocytosis and elimination of migrasomes by their surrounding tumor cells. Thereby, NPs interfere with the cell-ECM interaction and reduce the promotion effect of migrasomes on cell movement. Additionally, NPs trigger alteration of the expression of proteins related to cell-cell adhesion and cytoskeleton organization, which also restricts cell migration. In summary, all the findings here provide a potential target for anti-tumor metastasis nanomedicines.