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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124382, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38701579

ABSTRACT

MXene sheets with the unique electrical and optical properties show the excellent potential for surface-enhanced Raman spectroscopy (SERS) applications. In this study, we chose Ti3C2Tx, a type of MXene, to decorate silver nanoparticles (Ag NPs) on the ultrathin two-dimensional (2D) MXene sheets. The designed Ag-MXene substrates with SERS activity showed high sensitivity, high stability, and reproducibility. The SERS signal was enhanced by the synergistic contribution of both charge-transfer (CT) and surface plasmon resonance (SPR) involving the Ag NPs and the MXene sheets. Due to the strong interaction between the probe molecules and Ag NPs which provided the nanoscale gap, the substrate exhibited remarkable SERS performance. A novel experimental strategy was developed to facilitate the controlled synthesis of noble metal NPs and MXene sheets and provide insights for further improving the practical applications of these materials in SERS detection.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124059, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38422932

ABSTRACT

Continuously monitorable fluorescence sensors can provide fast, immediate, in-field detection of analytes without tedious process. A simple fluorescent sensor (BN) constructed from naphthol Schiff base was developed for reversible monitoring of F- and trace water. Sensor BN showed specific selectivity toward F- over other anions giving rise to a fluorescence "turn-on" response. After added F-, the BN solution caused a dramatically observable color change from non-fluorescence to blue-green, and the limit of detection reached 78.5 nM. The Job's and 1H NMR analysis confirmed that the recognition mechanism could be concluded to F- caused deprotonation of sensor BN by hydrogen bonding interaction. Moreover, the deprotonated form BN∙F obtained by using F- was acted as excellent sensitivity sensor for trace water detection with instant response through reprotonation. After addition of trace water, the emission color and spectral signal of BN∙F reverted to the original BN sate with the limit of detection of 0.0011 %. The reversible detection characteristic was conducive to the development of an inkless writing and encryption device. And importantly, BN∙F was utilized as a promising fluorescent sensor in the quantitative determination of water content in routinely chemical reagents.

3.
Curr Oncol ; 30(9): 7874-7890, 2023 08 27.
Article in English | MEDLINE | ID: mdl-37754487

ABSTRACT

Background: Recent studies have found that patients with incurable gastric cancer might benefit from palliative gastrectomy, but the impact of palliative gastrectomy on metastatic early-onset gastric cancer (mEOGC) patients remains unclear. Methods: We analyzed mEOGC patients enrolled in the Surveillance, Epidemiology, and End Results registry from January 2004 to December 2018. Propensity score matching (PSM) analysis with 1:1 matching and the nearest-neighbor matching method were used to ensure well-balanced characteristics between the groups of patients with palliative gastrectomy and those without surgery. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to evaluate the overall survival (OS) and cause-specific survival (CSS) risk with corresponding 95% confidence intervals (CIs). Results: Of 3641 mEOGC patients, 442 (12.1%) received palliative gastrectomy. After PSM, 596 patients were included in the analysis, with 298 in each group. For the matched cohort, the median survival was 8 months, and the 5-year survival was 4.0%. The median OS of mEOGC patients undergoing palliative gastrectomy was significantly longer than that of patients without surgery (13 months vs. 6 months, p < 0.001), and palliative gastrectomy remained an independent protective factor after adjusting for confounders (HR 0.459, 95% CI 0.382-0.552, p < 0.001), and the protective effect was robust in the subgroup analysis. Similar results were indicated in CSS. Stratified analyses by treatment modality also warranted the superiority of palliative-gastrectomy-based treatment in improving OS and CSS. Conclusions: mEOGC patients with palliative gastrectomy had a significantly longer survival time than patients without surgery. Exploratory analysis confirmed that surgery-based therapy modality was superior in improving survival time.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Retrospective Studies , Gastrectomy , Kaplan-Meier Estimate , Palliative Care
4.
Food Chem ; 420: 136138, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37062081

ABSTRACT

A sophisticated fluorescent chemosensor, 2-(4-nitrophenyl)-4,5-diphenyl-1H-imidazole (NPDI), was designed and synthesized through a one-step condensation reaction. NPDI exhibited a fluorescence enhancement response toward Al3+, accompanied by significant emission color change without interference from other tested metal ions. The binding stoichiometry and mechanism was corroborated using various techniques. The limit of detection (LOD) for Al3+ could reach 7.25 × 10-8 mol/L and the binding constant was found to be 1.47 × 105 L/mol. Furthermore, the in-situ formed NPDI·Al complex functioned a secondary chemosensor for water by quenching effect. The fluorescence quenching mechanism could be attributed to hydrogen bonding interaction of nitro substituent with water. The LOD was calculated to be 0.012 %, indicating NPDI·Al heightened sensitivity to water. Additionally, NPDI·Al complex was employed for the moisture detection in the surroundings. Finally, the practical application of NPDI·Al complex had been successfully used in the determination of water content in food products.


Subject(s)
Water , Imidazoles , Ions/chemistry , Spectrometry, Fluorescence/methods , Water/chemistry
5.
World J Clin Cases ; 11(8): 1862-1868, 2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36969994

ABSTRACT

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy is a common treatment for patients with early-stage lung cancer. Some patients can experience slight gastrointestinal discomfort after lobectomy for a moment. Gastroparesis is a gastrointestinal disorder that can be severe; it is associated with an increased risk of aspiration pneumonia and impaired postoperative recovery. Here, we report a rare case of gastroparesis after VATS lobectomy. CASE SUMMARY: A 61-year-old man underwent VATS right lower lobectomy uneventfully but had an obstruction of the upper digestive tract 2 d after surgery. Acute gastroparesis was diagnosed after emergency computed tomography and oral iohexol X-ray imaging. After gastrointestinal decompression and administration of prokinetic drugs, the patient's gastrointestinal symptoms improved. Since perioperative medication was applied according to the recommended dose and there was no evidence of electrolyte imbalance, intraoperative periesophageal vagal nerve injury was the most likely underlying cause of gastroparesis. CONCLUSION: Although gastroparesis is a rare perioperative complication following VATS, clinicians should be on the alert when patients complain about gastrointestinal discomfort. When surgeons resect paraesophageal lymph nodes with electrocautery, excessive ambient heat and compression of paraesophageal hematoma might induce vagal nerve dysfunction.

6.
Front Immunol ; 14: 1064704, 2023.
Article in English | MEDLINE | ID: mdl-36756126

ABSTRACT

Background: Numerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD). Methods: Based on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments. Results: Using autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A. Conclusion: Autophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Prognosis , B7-H1 Antigen , Cisplatin , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Biomarkers, Tumor/genetics , Autophagy/genetics , Glucosamine , Interferon-gamma
7.
ACS Appl Mater Interfaces ; 15(8): 11304-11313, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36790371

ABSTRACT

In this work, we cosputtered Ag and ZnSe on a polystyrene template to form a three-dimensional (3D) Ag@ZnSe (x) structure. The 3D surface morphology and material composition that provided abundant "hot spots" were controlled by adjusting the sputtering power of the ZnSe, which was confirmed by finite-difference time-domain (FDTD) simulation. The introduction of ZnSe into the noble metal Ag also introduced a charge-transfer (CT) effect into the system, and the CT path was proven with the two-dimensional correlation spectroscopy (2D-COS)-surface-enhanced Raman scattering (SERS) technique. In addition, the substrate exhibited excellent catalytic activity due to the CT effect. The catalyzed degradation of malachite green (MG) was due to the CT effect in the system, and the catalytic process was successfully monitored by in situ SERS. Most importantly, the catalytic degradation by Ag@ZnSe (x) with different parameters was proportional to the degree of CT (ρCT). The SERS and catalytic mechanisms were analyzed in depth with the 2D-COS-SERS technique, which was also useful in verifying the CT process. The catalytic sites for MG were successfully monitored with the 2D-COS-SERS technique. This study provides a reference for studies of the synergistic effects of the electromagnetic mechanism and CT, as well as a new perspective on photocatalysis with dye molecules and monitoring of the catalytic processes.

8.
J Adv Res ; 44: 201-212, 2023 02.
Article in English | MEDLINE | ID: mdl-36725190

ABSTRACT

INTRODUCTION: Lipopolysaccharide (LPS) causes lesions of the epithelial barrier, which allows translocation of pathogens from the intestinal lumen to the host's circulation. Hydrogen sulfide (H2S) regulates multiple physiological and pathological processes in colonic epithelial tissue, and CBS-H2S axis involved in multiple gastrointestinal disorder. However, the mechanism underlying the effect of the CBS-H2S axis on the intestinal and systemic inflammation in colitis remains to be illustrated. OBJECTIVES: To investigate the effect of CBS-H2S axis on the intestinal and systematic inflammation related injuries in LPS induced colitis and the underlying mechanisms. METHODS: Wild type and CBS-/+ mice were used to evaluate the effect of endogenous and exogenous H2S on LPS-induced colitis in vivo. Cytokine quantitative antibody array, western blot and real-time PCR were applied to detect the key cytokines in the mechanism of action. Biotin switch of S-sulfhydration, CRISPR/Cas9 mediated knockout, immunofluorescence and ActD chase assay were used in the in vitro experiment to further clarify the molecular mechanisms. RESULTS: H2S significantly alleviated the symptoms of LPS-induced colitis in vivo and attenuated the increase of COX-2 expression. The sulfhydrated HuR increased when CBS express normally or GYY4137 was administered. While after knocking kown CBS, the expression of COX-2 in mice colon increased significantly, and the sulfhydration level of HuR decreased. The results in vitro illustrated that HuR can increase the stability of COX-2 mRNA, and the decrease of COX-2 were due to increased sulfhydration of HuR rather than the reduction of total HuR levels. CONCLUSION: These results indicated that CBS-H2S axis played an important role in protecting intestinal barrier function in colitis. CBS-H2S axis increases the sulfhydration level of HuR, by which reduces the binding of HuR with COX-2 mRNA and inhibited the expression of COX-2.


Subject(s)
Colitis , Hydrogen Sulfide , Humans , Mice , Animals , Cyclooxygenase 2 , Lipopolysaccharides , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Colitis/chemically induced , Colitis/drug therapy , Inflammation
9.
Cancer Res ; 83(4): 595-612, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36525473

ABSTRACT

Immunotherapy can elicit robust anticancer responses in the clinic. However, a large proportion of patients with colorectal cancer do not benefit from treatment. Although previous studies have shown that hydrogen sulfide (H2S) is involved in colorectal cancer development and immune escape, further insights into the mechanisms and related molecules are needed to identify approaches to reverse the tumor-supportive functions of H2S. Here, we observed significantly increased H2S levels in colorectal cancer tissues. Decreasing H2S levels by using CBS+/- mice or feeding mice a sulfur amino acid-restricted diet (SARD) led to a marked decrease in differentiated CD4+CD25+Foxp3+ Tregs and an increase in the CD8+ T-cell/Treg ratio. Endogenous or exogenous H2S depletion enhanced the efficacy of anti-PD-L1 and anti-CTLA4 treatment. H2S promoted Treg activation through the persulfidation of ENO1 at cysteine 119. Furthermore, H2S inhibited the migration of CD8+ T cells by increasing the expression of AAK-1 via ELK4 persulfidation at cysteine 25. Overall, reducing H2S levels engenders a favorable immune microenvironment in colorectal cancer by decreasing the persulfidation of ENO1 in Tregs and ELK4 in CD8+ T cells. SARD represents a potential dietary approach to promote responses to immunotherapies in colorectal cancer. SIGNIFICANCE: H2S depletion increases the CD8+ T-cell/Treg ratio and enhances the efficacy of anti-PD-L1 and anti-CTLA4 treatment in colon cancer, identifying H2S as an anticancer immunotherapy target.


Subject(s)
Colonic Neoplasms , Hydrogen Sulfide , Tumor Microenvironment , Animals , Mice , CD8-Positive T-Lymphocytes , Colonic Neoplasms/etiology , Colonic Neoplasms/pathology , Cysteine , Hydrogen Sulfide/pharmacology , Hydrogen Sulfide/metabolism , Immunotherapy , Tumor Microenvironment/immunology
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 121995, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36283206

ABSTRACT

The Ag and MoO3 layer-by-layer sputtering method was employed to fabricate Ag/MoO3 coated on a polystyrene (PS) array (Ag/MoO3@PS), which exhibited excellent surface-enhanced Raman scattering (SERS) activity. The thickness of the MoO3 layer was controlled by changing the sputtering power. The SERS intensity of 4-aminothiophenol (PATP) on Ag/MoO3@PS with a 2 nm thickness of the MoO3 layer was comparable to that on pure Ag coated on the PS array (Ag@PS). This is possible because hot electrons were injected from Ag into the MoO3 layer to enhance the photocatalyst reaction; thus, the SERS spectra of coupled PATP were obtained. The transport of hot electrons rapidly decayed and was blocked with increasing thickness of the MoO3 layer from 2 nm to 9 nm. Thus, the SERS intensity decreased, and interestingly, the b2 mode of PATP decreased and nearly disappeared. This study provides new insight into the control of hot electron reduction for catalytic reduction process monitoring.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121867, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36108408

ABSTRACT

Fluorescent material exhibiting aggregation-induced emission (AIE) has demonstrated to be a facile and effective method to detect 2,4,6-trinitrophenol (TNP) due to its excellent features. In this study, a novel diphenyl imidazole-based fluorescent material (DINP) was successfully synthesized via a facile method. Fluorescence spectra showed that DINP had a typical AIE effect in DMSO/water solution, and the fluorescence emission was effectively quenched by TNP without being affected by other explosives. The Stern-Volmer quenching constant of 2.70 × 105 M-1 and detection limit of 7.2 × 10-8 M demonstrated that the DINP aggregates could serve as potential chemosensor for TNP detection. The mechanism behind the quenching of fluorescence could be ascribed to the formation of ground state complex. In addition, fluorescent test strips and TLC plate prepared with the aggregates provided an easy and low cost method for TNP detection in the aqueous solution. Especially, DINP was applied to quantitatively detect the content of TNP in real water samples. Furthermore, the aggregates exhibited good selective adsorptive performance to rhodamine B dye in aqueous solution with high adsorption efficiency of 98 % in a few minutes.


Subject(s)
Fluorescent Dyes , Water , Spectrometry, Fluorescence/methods , Imidazoles
12.
Am J Cancer Res ; 12(11): 5095-5104, 2022.
Article in English | MEDLINE | ID: mdl-36504890

ABSTRACT

Despite advances in rectal cancer treatments, its local recurrence rate is still 4-10 percent. And an evidence-based definition of early recurrence is lacking. Our study hopes to establish a clear threshold to distinguish early and late recurrence, and analyze risk and prognostic factors for them. Rectal cancer patients who underwent proctectomy from 2009 to 2019 were included. Patients who received neoadjuvant treatment and with incomplete records were excluded. The optimal interval was obtained using the minimum P value approach. Risk factors for early recurrence were analyzed by logistic regression models, and prognostic factors associated with additional surgery were assessed by Cox proportional hazards models. The optimal interval for the definition of early recurrence was 26 months based on the subsequent prognosis (P < 0.001). The 5-year survival rate of early and late recurrence cohort was 32.5% and 57.1%, respectively (P < 0.001). Adjuvant radiotherapy was the independent protective factor for early recurrence. And the presence of lymphovascular invasion, positive surgical margin, and no re-neoadjuvant radiotherapy were independent prognostic factors for the survival of LRRC patients under additional surgery.

13.
J Gastrointest Oncol ; 13(5): 2293-2305, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36388673

ABSTRACT

Background: Patients with stage IIA rectal cancer have a higher survival rate but side effects from chemoradiotherapy; thus, whether neoadjuvant therapy should be performed for stage IIA rectal cancer is controversial. This study aimed to compare the survival outcomes of patients with stage IIA rectal cancer with or without neoadjuvant chemoradiotherapy. Methods: Patients with stage IIA rectal cancer between 2010 and 2015 were included through the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to reduce the impact of confounding factors. Survival curves were plotted using the Kaplan-Meier method, and survival differences were assessed using the log-rank test. Results: There were no significant differences in overall survival and cancer-specific survival between the neoadjuvant chemoradiotherapy and surgery groups (P=0.973 and 0.983). Compared with the surgery group, the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had a better overall survival (P=0.007). Subgroup analysis showed that the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had better overall survival compared to the surgery group in the subgroup containing preoperative high-risk factors (P=0.003) but not in the low-risk subgroup (P=0.685). Conclusions: There is no evidence that neoadjuvant chemoradiotherapy + surgery can improve overall survival and cancer-specific survival compared to surgery alone in patients with stage IIA rectal cancer. Neoadjuvant chemoradiotherapy + surgery + chemotherapy can improve overall survival compared to surgery alone, but only in patients with preoperative high-risk factors. We suggest that patients with no preoperative high-risk factors may be considered for surgery alone, neoadjuvant chemoradiotherapy + surgery + chemotherapy is recommended for patients with preoperative risk factors.

14.
Syst Rev ; 11(1): 136, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35788246

ABSTRACT

BACKGROUND: Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments. METHODS/DESIGN: This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes. DISCUSSION: The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4202123718.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Stomach Neoplasms , Adenocarcinoma/etiology , Humans , Neoadjuvant Therapy/methods , Quality of Life , Stomach Neoplasms/therapy
15.
World J Clin Cases ; 10(10): 3241-3250, 2022 Apr 06.
Article in English | MEDLINE | ID: mdl-35647117

ABSTRACT

BACKGROUND: Appendico-vesicocolonic fistulas and appendiceal-colonic fistulas are two kinds of intestinal and bladder diseases that are rarely seen in the clinic. To our knowledge, no more than 4 cases of appendico-vesicocolonic fistulas have been publicly reported throughout the world, and no more than 100 cases of appendiceal-colonic fistulas have been reported. Although the overall incidence is low, an early diagnosis is difficult due to their atypical initial symptoms, but these diseases still require our attention. CASE SUMMARY: Here, we report a case of a 77-year-old male patient diagnosed with an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula. The main manifestations were diarrhea and urine that contained fecal material. The diagnosis was confirmed by multiple laboratory and imaging examinations. A routine urinalysis showed red blood cells and white blood cells. Abdominal and pelvic computed tomography scans showed close adhesions between the bowels and the bladder, and fistulas could be seen. Colonoscopy and cystoscopy and some other imaging examinations clearly showed fistulas. The preoperative diagnoses were a colovesical fistula and an appendiceal-colonic fistula. The fistulas were repaired by laparoscopic surgical treatment. The diseased bowel and part of the bladder wall were removed, followed by a protective ileostomy. The postoperative diagnosis was an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula, and the pathology suggested inflammatory changes. The patient recovered well after surgery, and all his symptoms resolved. CONCLUSION: The final diagnosis in this case was a double fistula consisting of an appendico-vesicocolonic fistula combined with an appendiceal-colonic fistula.

16.
Stem Cell Res Ther ; 13(1): 244, 2022 06 09.
Article in English | MEDLINE | ID: mdl-35681225

ABSTRACT

BACKGROUND: It is generally accepted that colorectal cancer (CRC) originates from cancer stem cells (CSCs), which are responsible for CRC progression, metastasis and therapy resistance. The high heterogeneity of CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy. METHODS: Twenty-six stem cell gene sets were acquired from StemChecker database. Consensus clustering algorithm was applied for stemness subtypes identification on 1,467 CRC samples from TCGA and GEO databases. The differences in prognosis, tumor microenvironment (TME) components, therapy responses were evaluated among subtypes. Then, the stemness-risk model was constructed by weighted gene correlation network analysis (WGCNA), Cox regression and random survival forest analyses, and the most important marker was experimentally verified. RESULTS: Based on single-sample gene set enrichment analysis (ssGSEA) enrichments scores, CRC patients were classified into three subtypes (C1, C2 and C3). C3 subtype exhibited the worst prognosis, highest macrophages M0 and M2 infiltrations, immune and stromal scores, and minimum sensitivity to immunotherapies, but was more sensitive to drugs like Bosutinib, Docetaxel, Elesclomol, Gefitinib, Lenalidomide, Methotrexate and Sunitinib. The turquoise module was identified by WGCNA that it was most positively correlated with C3 but most negatively with C2, and five hub genes in turquoise module were identified for stemness model construction. CRC patients with higher stemness scores exhibited worse prognosis, more immunosuppressive components in TME and lower immunotherapeutic responses. Additionally, the model's immunotherapeutic prediction efficacy was further confirmed from two immunotherapy cohorts (anti-PD-L1 in IMvigor210 cohort and anti-PD-1 in GSE78220 cohort). Mechanistically, Gene Set Enrichment Analysis (GSEA) results revealed high stemness score group was enriched in interferon gamma response, interferon alpha response, P53 pathway, coagulation, apoptosis, KRAS signaling upregulation, complement, epithelial-mesenchymal transition (EMT) and IL6-mediated JAK-STAT signaling gene sets. CONCLUSIONS: Our study characterized three stemness-related subtypes with distinct prognosis and TME patterns in CRC patients, and a 5-gene stemness-risk model was constructed by comprehensive bioinformatic analyses. We suggest our stemness model has prospective clinical implications for prognosis evaluation and might facilitate physicians selecting prospective responders for preferential use of current immune checkpoint inhibitors.


Subject(s)
Colorectal Neoplasms , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/therapy , Humans , Immunotherapy , Neoplastic Stem Cells/metabolism , Prognosis , Prospective Studies , Tumor Microenvironment/genetics
17.
Aging (Albany NY) ; 14(9): 4137-4157, 2022 05 10.
Article in English | MEDLINE | ID: mdl-35537818

ABSTRACT

BACKGROUND: We previously identified a novel lncRNA, CRART16, that could induce cetuximab resistance in colorectal cancer cells. This study explored the relationship of CRART16 expression to gastric cancer progression and the molecular mechanisms involved. METHODS: We evaluated CRART16 expression in gastric cancer tissues and adjacent normal tissues from the TCGA database and our hospital. Besides, we assessed its relationship with the overall survival (OS) of patients with gastric cancer. The effects of CRART16 on gastric cancer angiogenesis were determined by endothelial tube formation assay, spheroid sprouting assay, HUVEC invasion assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the lncRNA CRART16/miR-122-5p/FOS axis was analyzed by western blotting and dual-luciferase reporter assay. The functions of CRART16 were confirmed in xenograft mouse models. RESULTS: We found that CRART16 was substantially overexpressed in gastric cancer tissues compared with normal tissues, based on the TCGA database and our clinical samples. High expression of CRART16 correlated with more advanced tumor stages and poor prognosis. Overexpression of CRART16 in gastric cancer cells promoted proliferation, colony formation, angiogenesis, and bevacizumab resistance in vitro, and it promoted tumor growth and angiogenesis in vivo, and vice versa. CRART16 was found to downregulate miR-122-5p by acting as a sponge, upregulating the target oncogene FOS. Afterward, the increased FOS expression led to the upregulation of VEGFD. CONCLUSION: Our findings demonstrate that CRART16 promotes angiogenesis in vitro and in vivo, and CRART16 is a prognostic marker and therapeutic target in gastric cancer.


Subject(s)
MicroRNAs , Proto-Oncogene Proteins c-fos , RNA, Long Noncoding , Stomach Neoplasms , Vascular Endothelial Growth Factor D , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Chick Embryo , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells , Humans , Mice , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Proto-Oncogene Proteins c-fos/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/pathology , Vascular Endothelial Growth Factor D/genetics
18.
J Gastrointest Surg ; 26(8): 1791-1803, 2022 08.
Article in English | MEDLINE | ID: mdl-35501549

ABSTRACT

BACKGROUND: It is generally accepted that the distal resection margin of intermediate- to low-lying rectal cancer should be greater than 2 cm and at least 1 cm in special cases. This study intends to investigate whether a distal resection margin ≤ 1 cm affects tumor outcomes for patients with intermediate- to low-lying rectal cancer. METHODS: A systematic review of the literature was conducted. Sixteen studies included data for distal resection margins ≤ 1 cm (1684 cases) and > 1 cm (5877 cases), and 5 studies included survival data. Meta-analysis was used to compare the local recurrence rate and long-term survival of patients with distal resection margins > or ≤ 1 cm. RESULTS: The local recurrence rate in the ≤ 1-cm margin group (9.5%) was 2.3% higher than that in the > 1-cm margin group (7.2%) according to a fixed-effects model (RR [95% CI] 1.42 [1.18, 1.70], P < 0.001). The overall survival results of the five 1-cm margin studies showed an HR (95% CI) of 0.96 (0.75, 1.24) (P = 0.78). Subgroup analysis showed that the local recurrence rate in the subgroup with perioperative treatment was 1.2% lower in the ≤ 1-cm margin group (8.3%) than in the > 1-cm margin group (9.5%) (RR [95% CI] 0.97 [0.63, 1.49], P = 0.90). In the surgery alone subgroup, the local recurrence rate was 4.7% higher in the ≤ 1-cm margin group (12.4%) than in the > 1-cm group (7.7%) (RR [95% CI] 1.76 [1.09, 2.83], P = 0.02). CONCLUSIONS: For patients with intermediate- to low-lying rectal cancer undergoing surgery alone, a distal resection margin ≤ 1 cm may be not safe.


Subject(s)
Margins of Excision , Rectal Neoplasms , Humans , Neoplasm Recurrence, Local/pathology , Rectal Neoplasms/pathology , Treatment Outcome
19.
J Int Med Res ; 50(3): 3000605221080679, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35277104

ABSTRACT

OBJECTIVE: The vascular anatomic variations of the right colon present a challenge for colorectal surgeons. However, there have been few detailed studies of the variations in the anterosuperior pancreaticoduodenal vein (ASPDV). METHODS: We studied consecutive patients with right colon cancer who underwent laparoscopic right hemicolectomy at Peking University First Hospital (N = 117) between January 2018 and June 2021. RESULTS: The variations in the ASPDV were classified as type I (n = 101, (86.3%)), defined as ASPDVs draining into the gastrocolic trunk of Henle (GCT); type II (n = 10, (8.5%)), defined as ASPDVs draining into the superior mesenteric vein (SMV); or type III, defined as ASPDVs draining into both the GCT and SMV. For type I, subtypes were defined according to the branching of the ASPDVs: subtype a, with one branch (n = 87, (86.1%)); subtype b, with two branches (n = 12, (11.9%)); and subtype c, with more than two branches (n = 2, (2.0%)). Type I was also subtyped according to the confluence of the ASPDV and GCT, with subtype 1 being defined by a proximal site (n = 96, 95%) and subtype 2 by a distal site (n = 5, 5.0%). CONCLUSIONS: We have characterized the variations in ASPDVs encountered during laparoscopic right hemicolectomy, which should provide a reference for colorectal surgeons.


Subject(s)
Laparoscopy , Mesenteric Veins , Colectomy , Colon/surgery , Humans , Mesenteric Veins/surgery , Retrospective Studies
20.
Cancer Cell Int ; 22(1): 85, 2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35172821

ABSTRACT

BACKGROUND: The role of hydrogen sulfide (H2S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H2S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H2S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. METHODS: Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H2S was detected by H2S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA-protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. RESULTS: Overexpression of CBS and exogenous H2S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H2S axis on colon cancer cells. CONCLUSIONS: Overexpression of CBS and exogenous provision of H2S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.

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