Yellow mustard gum: pilot-scale production and characterization.

BACKGROUND: Yellow mustard gum (YMG), which is extracted from the mucilaginous part of yellow mustard bran, has been considered an emerging natural hydrocolloid gum but lacks commercial development and production. To promote the commercial utilization of YMG, this study developed a pilot-scale YMG production protocol in an economic and environmentally friendly way to produce a clean-label YMG product. This YMG produced at pilot scale (YMW) was characterized in terms of chemical composition, rheological properties, and interaction with a commercial gum, κ-carrageenan, and was compared with purified YMG through ethanol precipitation (YME). RESULTS: The protocol processed up to 100 L of raw material with zero solvent and a minimal number of steps and showed strong quasi-industrial potential. The YMW showed a similar chemical composition as YME. However, the YMW contained a slightly lower amount of carbohydrate and a much larger amount of ash and potassium than the YME. The rheological results concluded that both the YMW and YME solutions exhibited shear-thinning flow behavior and a weak gel, with YME showing higher viscosity and stronger gel structure. Most interestingly, YMW could form unpourable gels when blended with native κ-carrageenan whereas YME barely achieved this despite the equivalent total gum concentration. CONCLUSION: This study demonstrated the feasibility of YMG production at a large scale with economic and green procedures and discovered its new functionality for commercial utilization. The gelling ability of YMG could provide it with wider applications as a result of a new potential synergistic combination. All this information should accelerate the process of full commercialization of YMG as a clean-label functional ingredient. © 2024 His Majesty the King in Right of Canada. Journal of The Science of Food and Agriculture © 2024 Society of Chemical Industry. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Neuronal CFL1 upregulation in head and neck squamous cell carcinoma enhances tumor-nerve crosstalk and promotes tumor growth.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer type, marked by a pronounced nerve density within the tumor microenvironment and a high rate of perineural invasion (PNI). Growing evidence suggests that the nervous system plays a vital role in HNSCC progression. Yet, the mechanisms governing cancer-nerve interactions remain largely elusive. Our research revealed that cofilin-1 (CFL1) is significantly overexpressed in HNSCC and correlates with both PNI and unfavorable prognosis. Utilizing multiplex fluorescent immunohistochemistry, we have localized CFL1 chiefly to the nerves adjacent to tumor sites. Significantly, it is the elevated expression of CFL1 in neuronal structures, rather than in the tumor cells, that aligns with diminished patient survival rates. We observed that HNSCC cells induced the expression of neuronal CFL1 and that the conditional knockout of neuronal CFL1 impedes tumor-nerve interactions. Both Gene Ontology functional enrichment analyses and Gene Set Enrichment Analysis demonstrate that CFL1 expression in HNSCC is associated with specific biological processes, including "RIBOSOME," "PROTEASOME," and "cadherin binding." In summary, HNSCC promotes the expression of CFL1 in nerves, which is essential for cancer-nerve interactions. The neuronal CFL1 is associated with PNI and may be a potential molecular prognostic marker of poor survival in HNSCC.

Identification and functional analysis of differentially expressed proteins in high and low freezing tolerance sheep sperm.

The purpose of this study was to identify proteins associated with differences in the freezing tolerance of sheep sperm and to analyze their functions. Qualified fresh semen from four breeds of rams, the Australian White, white-head Dorper, Black-head Dorper, and Hu sheep breeds, were selected for cryopreservation. The sperm freezing tolerance was investigated by evaluation of the overall vitality, progressive vitality, and rapidly advance vitality of the sperm. A differential model of sperm freezing tolerance was constructed for sheep breeds showing significant differences. Differentially expressed proteins associated with sperm freezing tolerance were identified using iTRAQ and the protein functions were analyzed. It was found that sperm freezing tolerance was best in Hu sheep and worst in white-head Dorper sheep. These two breeds were used for the construction of a model based on differences in freezing tolerance and the identification of sperm proteins expressed differentially before freezing and after thawing. A total of 128 differentially expressed proteins (88 up-regulated and 40 down-regulated) were identified before freezing and after thawing in Hu sheep sperm (fresh/frozen Hu sheep sperm referred to as HL vs. HF), while 219 differentially expressed proteins (106 up-regulated and 113 down-regulated) were identified in white-head Dorper sheep (fresh/frozen white-head Dorper sheep sperm referred to as WL vs. WF). A comparison of these differentially expressed proteins showed that 57 proteins overlapped between the two breeds while 71 were only expressed in Hu sheep and 162 were only expressed in white-head Dorper sheep. Functional annotation and enrichment analyses of differentially expressed proteins down-regulated in Hu sheep involved in phosphorylation of phosphatidylinositol phosphate kinases, regulation of GTPase activity and glycolysis/gluconeogenesis signaling pathway. Up-regulated proteins of Hu sheep participated in oxidoreductase activity and oxidative phosphorylation process of sperm freezing. Furthermore, down-regulated in white-head Dorper sheep involved in the metabolic regulation of carbohydrate and nuclear sugar metabolism. Up-regulated proteins of white-head Dorper sheep involved in the ferroptosis and oxidative phosphorylation pathways. Collectively, These proteins were found to participate mainly in oxidative phosphorylation as well as phosphorylation and metabolic processes in the mitochondria to affect the freezing tolerance of sheep sperm.

The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen Cryptococcus neoformans.

The Complex of Proteins Associated with Set1 (COMPASS) methylates lysine K4 on histone H3 (H3K4) and is conserved from yeast to humans. Its subunits and regulatory roles in the meningitis-causing fungal pathogen Cryptococcus neoformans remain unknown. Here we identified the core subunits of the COMPASS complex in C. neoformans and C. deneoformans and confirmed their conserved roles in H3K4 methylation. Through AlphaFold modeling, we found that Set1, Bre2, Swd1, and Swd3 form the catalytic core of the COMPASS complex and regulate the cryptococcal yeast-to-hypha transition, thermal tolerance, and virulence. The COMPASS complex-mediated histone H3K4 methylation requires H2B mono-ubiquitination by Rad6/Bre1 and the Paf1 complex in order to activate the expression of genes specific for the yeast-to-hypha transition in C. deneoformans. Taken together, our findings demonstrate that putative COMPASS subunits function as a unified complex, contributing to cryptococcal development and virulence.

CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis.

Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients' poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.

A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis.

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

CAV2 promotes the invasion and metastasis of head and neck squamous cell carcinomas by regulating S100 proteins.

More than half of HNSCC patients are diagnosed with advanced disease. Locally advanced HNSCC is characterized by tumors with marked local invasion and evidence of metastasis to regional lymph nodes. CAV2 is a major coat protein of caveolins, important components of the plasma membrane. In this study, CAV2 was found to profoundly promote invasion and stimulate metastasis in vivo and in vitro. CAV2 was demonstrated to be a key regulator of S100 protein expression that upregulates the proteins levels of S100s, which promotes the invasion and migration and downregulates the expression of tumor suppressors. Mechanistically, CAV2 directly interacts with S100s in HNSCC cells, and CAV2 reduces S100A14 protein expression by promoting its ubiquitylation and subsequent degradation via the proteasome. Moreover, we discovered that CAV2 promotes the interaction between S100A14 and the E3 ubiquitin ligase TRIM29 and increases TRIM29 expression. Taken together, our findings indicate that CAV2 promotes HNSCC invasion and metastasis by regulating the expression of S100 proteins, presenting a novel potential target for anticancer therapy in HNSCC.

Phosphorylation of MICAL2 by ARG promotes head and neck cancer tumorigenesis by regulating skeletal rearrangement.

The actin cytoskeletal architecture provides the structural underpinnings for crucial cellular behaviors. In cancer cells, changes in the actin cytoskeleton may serve as prerequisites for proliferation, invasion, and metastatic dissemination. However, the underlying mechanisms remain largely unknown. Here, we show that MICAL2, which is increased in head and neck squamous cell carcinoma (HNSCC) and inversely associated with patient survival, promotes HNSCC growth, invasion, and migration. MICAL2 serves as a flavoprotein monooxygenase and directly induces actin filament depolymerization by specifically oxidizing the methionine 44 and 47 residues of F-actin. The kinase ARG interacts with MICAL2 and augments MICAL2-mediated actin disassembly. Direct phosphorylation assay and mass spectrometry confirmed that ARG phosphorylates MICAL2 at Tyr445, Tyr463, and Tyr488. Substitution of the Tyr445 or Tyr463 residue of purified recombinant MICAL2-redox with phenylalanine (generating a non-phosphorylatable mutant) abolishes the enhanced MICAL2-mediated F-actin disassembly induced by ARG. Consistently, ectopic expression of non-phosphorylatable MICAL2 mutants (MICAL2Y445F and MICAL2Y463F, not MICAL2Y488F) failed to ameliorate HNSCC cell growth, whereas expression of wild-type MICAL2 or MICAL2Y488F rescued the impaired proliferation induced by MICAL2 knockdown. Moreover, CCG-1423, an inhibitor of MICAL2, was shown to inhibit HNSCC cell proliferation, invasion, and migration. Taken together, our findings indicate that phosphorylation of MICAL2 at Tyr445 and Tyr463 by ARG mediates F-actin disassembly and promotes HNSCC progression.

Association of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles: a retrospective cohort study.

BACKGROUND: Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles. METHODS: We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women's Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect. RESULTS: In singletons, couples with prepregnancy BMI ≥25 kg/m2 had higher odds of LGA than those with BMI < 25 kg/m2. The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m2 in IVF cycles (aOR 1.82, 95% CI 1.06-3.10) and maternal BMI ≥25 kg/m2 in ICSI cycles (aOR 4.89, 95% CI 1.45-16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m2 (aOR 4.55, 95% CI 1.32-15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants. CONCLUSIONS: Parental prepregnancy BMI ≥25 kg/m2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m2, particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments.

BCAR3 promotes head and neck cancer growth and is associated with poor prognosis.

Breast cancer anti-estrogen resistance protein 3 (BCAR3) is involved in anti-estrogen resistance and other important aspects of breast cancer. However, the role of BCAR3 in other solid tumors remains unclear. The relationship between the clinicopathologic characteristics of head and neck squamous cell carcinoma (HNSCC) patients and BCAR3 was analyzed using the Wilcoxon's signed-rank test and logistic regression. The association between BCAR3 expression and clinicopathologic features and survival was analyzed using Cox regression and the Kaplan-Meier method. In vivo and in vitro assays were performed to validate the effect of BCAR3 on HNSCC growth. BCAR3-related mRNAs were determined by calculating the Pearson's correlation coefficient based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and gene set enrichment analysis (GSEA) were used to predict the potential functions of BCAR3. BCAR3 expression is overexpressed in HNSCC and was shown to be associated with perineural invasion (PNI) and poor survival. BCAR3 silencing significantly attenuated the proliferation of HNSCC cells, whereas BCAR3 depletion inhibited tumor growth in vitro. GO and KEGG functional enrichment analyses, and GSEA showed that BCAR3 expression in HNSCC was associated with biological processes, such as cell adhesion, actin binding, cadherin binding, and angiogenesis. BCAR3, which promotes HNSCC growth, is associated with perineural invasion and may be a potential molecular prognostic marker of poor survival in HNSCC.

ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma.

BACKGROUND: Glutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation. METHODS: The roles of ASCT2 (SLC1A5) and associated glutamine metabolism were determined by the MTT, colony formation, glutamine uptake, intracellular glutathione, ROS detection, immunofluorescence, immunohistochemistry, and apoptosis enzyme-linked immunosorbent assays as well as animal studies. RESULTS: We found that glutamine is also critical for HNSCC. In this study, ASCT2, an amino acid transporter responsible for glutamine transport, in addition to LAT1 and GLS, is overexpressed in HNSCC and associated with poor survival. Using both in vivo and in vitro models, we found that knocking down ASCT2 by shRNAs or miR-137 or the combination of silencing ASCT2 and pharmacologically inhibiting SNAT2 via a small-molecule antagonist called V-9302 significantly suppressed intracellular glutamine levels and downstream glutamine metabolism, including glutathione production; these effects attenuated growth and proliferation, increased apoptosis and autophagy, and increased oxidative stress and mTORC1 pathway suppression in HNSCC. Additionally, silencing ASCT2 improved the response to cetuximab in HNSCC. CONCLUSIONS: In summary, ASCT2-dependent glutamine uptake and subsequent glutamine metabolism are essential for HNSCC tumorigenesis, and the combination of glutamine uptake inhibitors and cetuximab presents a promising strategy for improving the outcomes of HNSCC patients.

SEMA3C Promotes Cervical Cancer Growth and Is Associated With Poor Prognosis.

Introduction: Aberrant activation of Semaphorin3C(SEMA3C) is widespread in human cancers. We aimed to analyze SEMA3C expression in cervical cancer and investigate the role of SEMA3C in cervical cancer and its underlying mechanism, which is important for exploring new therapeutic targets and prognostic factors. Materials and Methods: The expression of SEMA3C was examined in paraffin-embedded cervical cancer specimens. In vivo and in vitro assays were performed to validate the effect of SEMA3C on cervical cancer cell proliferation and p-ERK pathway activation. Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data set. Results: SEMA3C expression was associated with poor survival in both the TCGA cohort and our cohort. Silencing of SEMA3C suppressed cervical cancer cell proliferation, colony formation ability, and the activation of the p-ERK signaling pathway in vitro. SEMA3C depletion inhibited tumor growth in vitro. GSEA also showed that the epithelial mesenchymal transition (EMT), TGFß signaling pathway, angiogenesis, and extracellular matrix (ECM) receptor interactions are associated with a high SEMA3C expression phenotype. Conclusion: SEMA3C is correlated with poor prognosis of cervical cancer patients and promotes tumor growth via the activation of the p-ERK pathway.

Integrating Clinical and Genetic Analysis of Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

Introduction: Perineural invasion (PNI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), predicts poor survival. However, the associated clinical characteristics remain uncertain, and the molecular mechanisms are largely unknown. Materials and methods: HNSCC gene expression and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA). Prognostic subgroup analysis was performed, and potential PNI risk factors were assessed with logistic regression. PNI-associated gene coexpression modules were identified with weighted gene coexpression network analysis (WGCNA), and key module gene functions and the roles of non-malignant cells in PNI were evaluated with a single-cell transcriptomic dataset (GSE103322). Results: PNI was significantly inversely associated with overall survival (HR, 2.08; 95% CI, 1.27 to 3.40; P = 0.004), especially in advanced patients (HR, 2.62; 95% CI, 1.48 to 4.64; P < 0.001). Age, gender, smoking history, and alcohol history were not risk factors. HPV-positive cases were less likely than HPV-negative cases to develop PNI (OR, 0.28; 95% CI, 0.09 to 0.76; P = 0.017). WGCNA identified a unique significantly PNI-associated coexpression module containing 357 genes, with 12 hub genes (TIMP2, MIR198, LAMA4, FAM198B, MIR4649, COL5A1, COL1A2, OLFML2B, MMP2, FBN1, ADAM12, and PDGFRB). Single-cell transcriptomic data analysis revealed that the genes in the PNI-associated module correlated with the signatures "EMT," "metastasis," and "invasion." Among non-malignant cells, fibroblasts had relatively high expression of the key genes. Conclusion: At the molecular and omic levels, we verified that PNI in HNSCC is a process of invasion rather than simple diffusion. Fibroblasts probably play an important role in PNI. Novelty & Impact Statements  The study is a thorough analysis of PNI in HNSCC from the clinical level to the molecular level and presents the first description of cancer-related PNI from the omics perspective to date as far as we know. We verified that PNI in HNSCC is a process of invasion rather than simple diffusion, at the molecular and omic levels. Fibroblasts were found to probably play an important role in PNI by analyzing single-cell transcriptomic data.

Real-World Study of the Incidence, Risk Factors, and Prognostic Factors Associated with Bone Metastases in Women with Uterine Cervical Cancer Using Surveillance, Epidemiology, and End Results (SEER) Data Analysis.

BACKGROUND The aims of this study were to investigate the incidence and risk factors for the development of bone metastases and prognosis in women with cancer of the uterine cervix using database analysis. MATERIAL AND METHODS The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was analyzed for the incidence and survival rates of women diagnosed with uterine cervical cancer in the United States between 2010-2015. Multivariate logistic regression analysis identified risk factors for bone metastases. Kaplan-Meier analysis estimated the overall survival. Proportional hazard regression analysis estimated prognostic factors associated with bone metastases. RESULTS There were 19,363 women with uterine cervical cancer, and 469 women were diagnosed with bone metastases on initial diagnosis (2.42%). Increased T-stage, N-stage, non-squamous and non-adenocarcinoma histology, high-grade tumors, and the presence of lung, liver, and brain metastases were all significantly associated with early bone metastases. There were 364 patients with cervical cancer and bone metastases on initial diagnosis who were followed-up for at least one year. Multivariate Cox regression analysis showed that unmarried status and lung, liver, and brain metastases were significantly associated with reduced overall survival. No other significant risk or prognostic associations were found. CONCLUSIONS SEER data analysis showed that women with uterine cervical cancer had some standard risk factors associated with bone metastases, and with prognosis, but a heterogeneous group of risk factors was also present. The findings of this study may have clinical application in screening for bone metastases in women with cervical cancer.

TGF-ß1-SOX9 axis-inducible COL10A1 promotes invasion and metastasis in gastric cancer via epithelial-to-mesenchymal transition.

Molecular biomarkers that predict disease progression might promote drug development and therapeutic strategies in aggressive cancers, such as gastric cancer (GC). High-throughput mRNA sequencing (RNA-seq) revealed that collagen type X alpha 1 (COL10A1) is a disease progression-associated gene. Analysis of 103 GC patients showed that high COL10A1 mRNA expression was associated with GC metastasis and reduced survival. We analyzed the COL10A1 promoter using the UCSC genome website and JASPAR database, and we found potential SOX9 binding site. Here, we demonstrated that SOX9 and COL10A1 were both up-regulated in GC. We observed a positive correlation between the expression patterns of SOX9 and COL10A1 in GC cells and tissues. The results of electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay and promoter reporter indicated that SOX9 could directly bind to the COL10A1 gene promoter and activate its transcription. Biological function experiments showed that COL10A1 regulated the migration and invasion of GC cells. Knockdown COL10A1 inhibited lung and abdominal cavity metastasis in a nude mouse model. Moreover, transforming growth factor-ß1 (TGF-ß1) treatment up-regulated the phosphorylation of Smad2 and increased SOX9 and COL10A1 expression. COL10A1 was confirmed to be a potential inducer of epithelial-to-mesenchymal transition (EMT). SOX9 was essential for COL10A1-mediated EMT, and cell migration, invasion and metastasis. Co-expression of SOX9 and COL10A1 was associated with tumor progression and was strongly predictive of overall survival in GC patients. In summary, this study elucidated the mechanistic link between COL10A1 and the TGF-ß1-SOX9 axis. These findings indicated that COL10A1 might play a crucial role in GC progression and serve as a potential biomarker and therapeutic target in GC patients.

Effectiveness between early and late temporary ileostomy closure in patients with rectal cancer: A prospective study.

A temporary stoma is often used in rectal cancer surgery to protect a distal anastomosis, which remains a major concern after rectal cancer surgery, particularly after low anterior resection. The temporary stoma is scheduled for closure. However, the optimal time of closure of the protecting stoma remains unclear because of sparse studies and data. We aimed to detect the efficacy between early and late temporary ileostomy closure in patients with rectal cancer during or after neoadjuvant chemoradiotherapy. We conducted a prospective, 2-group design between early and late ileostomy closure group in patients after rectal cancer surgery with temporary stoma. Participants were recruited in a teaching hospital in Guangzhou, China. A total of 161 patients confirmed diagnosis of rectal cancer underwent curative surgery and temporary ileostomy. Participants with temporary ileostomy received closure surgery after 1 (early) or 6 (late) months were assessed by clinical parameters and quality of life. Patients in late closure group received more adjuvant chemotherapy cycles but with comparable incidence of stoma closure-related complications and length of hospital stay compared to early closure group. Participants in late closure group with standardized postoperative chemotherapy might have a better prognosis compared with those in early closure group. An increased emphasis should be given to choose the optimal closure time of patients with rectal cancer having temporary ileostomy. Colorectal nurses could provide support to physician for observation of prognosis of different closure time.

Assessment of treatment options for rectosigmoid cancer: single-incision plus one port laparoscopic surgery, single-incision laparoscopic surgery, and conventional laparoscopic surgery.

BACKGROUND: The advantages of reduced-port laparoscopic surgery (RPLS) for rectosigmoid cancer treatment have been disputed. This study evaluated the outcomes of RPLS compared to conventional laparoscopic surgery (CLS) for rectosigmoid cancer. METHODS: Data from 211 patients who underwent a selective sigmoidectomy or anterior resection from August 2011 to June 2014 at a single institution were collected and analyzed via propensity score matching. Operative outcomes, inflammatory responses, pain intensity, oncologic outcomes, quality of life, and cosmetic results were compared between groups. RESULTS: After matching, 96 patients (48 CLS and 48 RPLS) were evaluated. Sixteen RPLS cases underwent single-incision laparoscopic surgery (SILS), and 32 underwent single-incision plus one port laparoscopic surgery (SILS + 1). Baseline clinical characteristics were comparable between the RPLS and the CLS groups. Morbidity, pathologic outcomes, and 3-year disease-free survival and overall survival rates were also comparable between the 2 groups. Compared with the CLS group, the RPLS group had a shorter total incision length (p < 0.001); shorter time to liquid diet (p = 0.027), ambulation (p = 0.026), and discharge (p < 0.001); and lower visual analogue scale scores during mobilization at postoperative days 3-5 (p < 0.05). The total operation times, C-reactive protein levels at 24 h and 96 h, and interleukin-6 levels at 24 h postoperatively were significantly lower in the SILS + 1 group than those in the CLS and SILS groups (p < 0.05). Compared with the CLS group, the RPLS group showed better social functioning at 6 months postoperatively (p = 0.011). The SILS and SILS + 1 groups showed similar cosmetic results, and both groups showed better results than the CLS group (p < 0.001). CONCLUSIONS: RPLS for rectosigmoid cancer is feasible, with short-term safety and long-term oncological safety comparable to that of CLS. Better cosmesis and accelerated recovery can be expected. SILS + 1 is a better choice than CLS or SILS for rectosigmoid cancer because it minimizes invasiveness and reduces technical difficulties.

[Efficacy analysis of suprapubic single-incision laparoscopy in the treatment of rectosigmoid cancer].

OBJECTIVE: To evaluate the efficacy and cosmetic result of suprapubic single incision laparoscopic surgery(SSILS) in the treatment of rectosigmoid cancer. METHODS: Clinicopathological data of 16 patients undergoing SSILS and 122 undergoing conventional laparoscopic surgery(CLS) for sigmoid colon and upper rectal cancer in the Nanfang Hospital from August 2011 to July 2012 were retrospectively analyzed. The patients were analyzed with propensity score matching at a ratio of 1 to 2 by logistic regression analysis. The matching covariates included age, gender, body mass index, American Society of Anesthesiologists(ASA) score, tumor location, tumor diameter, pathologic TNM stage, previous abdominal surgery. After matching, 48 patients (16 SSILS and 32 CLS) were enrolled in the study. The SSILS group comprised of 13 (81.3%) males with mean age of (56.4±13.4) years. The CLS group comprised of 23(71.9%) males with mean age of (55.6±13.7) years. Postoperative short-term parameters, oncologic efficacy and cosmetic result were compared between the two groups. RESULTS: The male gender ratio, age, body mass index, ASA score, tumor location, tumor diameter, tumor differentiation, depth of invasion, lymph node metastasis, TNM stage, previous abdominal surgery were comparable between the two groups. As compared to CLS group, less incision length [(4.8±1.5) cm vs. (6.8±1.2) cm, U=63.000, P=0.000], shorter time to ambulation [(2.6±1.0) days vs. (3.9±1.5) days, U=116.500, P=0.002], shorter hospital stay [(8.4±5.3) days vs.(9.2±3.1) days, U=139.000, P=0.010] and less postopertive pain(Visual Analogue Scale: 4.3±1.4 vs. 5.2±1.1 at day 3, t=2.457, P=0.018; 3.7±1.0 vs. 4.6±1.0 at day 4, t=2.700, P=0.010; 3.3±0.8 vs. 4.0±1.0 at day 5, t=2.466, P=0.017) were observed in SSILS group. The other short-term parameters(blood loss, operative time, insertion of additional port rate, time to flatus, defecation, time to liquid and soft diet, complication morbidity, number of lymph nodes harvested, proximal and distal resection margin) were not significantly different between 2 groups(all P>0.05). The median follow-up time was 41(22-49) months. There was no loco-regional recurrence in 2 groups. Distant metastasis was 18.8% (n=3, all liver metastasis) and 6.3% (n=2, one liver metastasis and one peritoneal metastasis) in SSILS and CLS groups (χ(2)=0.698, P=0.404) respectively. Three-year disease-free survival and 3-year overall survival were 81.3% vs 93.0%(χ(2)=1.355, P=0.244) and 100.0% vs 96.9%(χ(2)=0.500, P=0.480) in SSILS and CLS groups, respectively. Photograph questionnaire investigation showed that the cosmetic score was significantly higher in SSILS group than that in CLS group (8.9±1.1 vs. 7.6±1.1, U=100.500, P=0.000). Of 48 patients of 2 groups, 81.3%(39/48) case preferred SSILS. CONCLUSION: In experienced laparoscopic treatment centers, SSILS for rectosigmoid cancer is feasible and safe with quite good oncological efficacy and certain advantages, such as fast recovery, less pain and better cosmetic result.

Suprapubic single-incision versus conventional laparoscopic appendectomy.

BACKGROUND: Suprapubic single-incision laparoscopic appendectomy (SSILA), a promising new approach with potential benefits such as improved cosmetic results, has been preliminarily shown to be safe and feasible in previous single-arm studies. This study used a propensity-matched analysis to compare SSILA and conventional laparoscopic appendectomy (CLA). METHODS: Patients undergoing SSILA between March 2012 and November 2013 were matched with patients undergoing CLA during the same period at a single institution. These patient groups were compared using a propensity score analysis. The model covariates for the propensity scores included gender, age, body mass index, American Society of Anesthesiologists score, history of abdominal operation, and pathology of the resected appendix. The clinical outcomes were compared between the two groups, and the cosmetic results were evaluated via a patient scar assessment questionnaire and an objective scar evaluation scale. RESULTS: No patient in either group required additional port placement or conversion to open surgery. One patient in the SSILA group developed a wound infection, and one patient in the CLA group developed a postoperative intra-abdominal abscess. No significant differences were observed between the groups with respect to the length of hospital stay, time to semi-liquid diet, time to first flatus or hospital cost. The operative time and the number of patients requiring postoperative analgesics were greater with SSILA. Compared with CLA, SSILA was associated with better scores in the patient scar assessment questionnaire consciousness subscale and with similar scores in the appearance, satisfaction with appearance and satisfaction with symptoms subscales. The two approaches yielded similar results for the objective scar evaluation scale. CONCLUSIONS: SSILA is a feasible and safe approach with similar outcomes as CLA. SSILA results in reduced scar consciousness at the expense of relatively longer operative times and more postoperative analgesic use.

A safety study of transumbilical single incision versus conventional laparoscopic surgery for colorectal cancer: study protocol for a randomized controlled trial.

BACKGROUND: Single-incision laparoscopic surgery (SILS) is an emerging minimally invasive surgery to reduce abdominal incisions. However, despite the increasing clinical application of SILS, no evidence from large-scale, randomized controlled trials is available for assessing the feasibility, short-term safety, oncological safety, and potential benefits of SILS compared with conventional laparoscopic surgery (CLS) for colorectal cancer. METHODS/DESIGN: This is a single-center, open-label, noninferiority, randomized controlled trial. A total of 198 eligible patients will be randomly assigned to transumbilical single incision plus one port laparoscopic surgery (SILS plus one) group or to a CLS group at a 1:1 ratio. Patients ranging in age from 18 to 80 years with rectosigmoid cancer diagnosed as cT1-4aN0-2 M0 and a tumor size no larger than 5 cm are considered eligible. The primary endpoint is early morbidity, as evaluated by an independent investigator. Secondary outcomes include operative outcomes (operative time, estimated blood loss, and incision length), pathologic outcomes (tumor size, length of proximal and distal resection margins, and number of harvested lymph nodes), postoperative inflammatory and immune responses (white blood cells [WBC], neutrophil percentage [NE %], C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), postoperative recovery (time to first ambulation, flatus, liquid diet, soft diet, and duration of hospital stay), pain intensity, body image and cosmetic assessment, 3-year disease free survival (DFS), and 5-year overall survival (OS). Follow-up visits are scheduled for 1 and 3 months after surgery, then every 3 months for the first 2 years and every 6 months for the next 3 years. DISCUSSION: This trial will provide valuable clinical evidence for the objective assessment of the feasibility, safety, and potential benefits of SILS plus one compared with CLS for the radical resection of rectosigmoid cancer. The hypothesis is that SILS plus one is feasible for the radical resection of rectosigmoid cancer and offers short-term safety and long-term oncological safety comparable to that of CLS, and that SILS plus one offers better cosmetic results and faster convalescence compared to CLS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02117557 (registered on 16 April 2014).