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1.
J Dig Dis ; 25(1): 27-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38342693

RESUMO

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Metaplasia , Ácido Fólico/uso terapêutico , Mucosa Gástrica/patologia
2.
J Dig Dis ; 25(1): 44-60, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38126957

RESUMO

OBJECTIVE: The intestine is responsible for approximately one-third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. METHODS: The 16S rRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast-rich forage and 250 mg·kg-1 ·day-1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. RESULTS: Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short-chain fatty acid levels were increased, and intestinal inflammation was ameliorated. CONCLUSIONS: Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine.


Assuntos
Microbioma Gastrointestinal , Hiperuricemia , Camundongos , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Enterococcus faecalis , RNA Ribossômico 16S , Purinas
3.
World J Gastrointest Oncol ; 15(11): 1852-1863, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38077649

RESUMO

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

4.
J Dig Dis ; 24(8-9): 461-471, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37548312

RESUMO

OBJECTIVE: To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota. METHODS: An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment. RESULTS: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone. CONCLUSIONS: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.

5.
Medicine (Baltimore) ; 102(13): e33443, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37000057

RESUMO

RATIONALE: Gastric hamartomatous inverted polyps (GHIP) is not a common disease, and it has rarely been reported in the literature. Preoperative diagnosis is difficult due to the deep position and surface covered with normal gastric mucosa. However, with the progress of endoscopic technology, endoscopic submucosal dissection (ESD) can play a crucial role in the diagnosis and treatment of GHIP. PATIENT CONCERNS: A 61-year-old Chinese man underwent gastroscopy due to abdominal pain 2 months prior that revealed chronic superficial nonatrophic gastritis with erosion and a submucosal tumor in the gastric body (an ultrasound gastroscopy was recommended). Therefore, he was admitted to our hospital for further diagnosis and treatment. DIAGNOSES: A hemispherical submucosal tumor was found in the middle segment of the stomach, with a size of approximately 30 mm × 35 mm and a smooth surface without central ulceration or mucosal bridge formation. Ultrasound gastroscopy showed that the lesion was a hypoechoic mass with uniform internal echo originating from the muscularis propria. INTERVENTIONS: The tumor was completely removed by using ESD. The postoperative pathological results indicated a monocystic structure in the submucosa that was not connected with the surface mucosa. The surface of the cyst was covered with foveolar cells and mucous-neck cells (part of which had low-grade intraepithelial neoplasia), and GHIP was considered to be diagnosed. OUTCOMES: According to the abovementioned endoscopic and pathological features, the patient was finally diagnosed with GHIP. The patient was successfully discharged after surgery and received regular follow-up observations. LESSONS: GHIP is located in the submucosa layer and has the potential risk of malignant transformation. However, it is not easy to diagnose by using gastroscopy and ultrasound gastroscopy. ESD can obtain complete specimens, which contributes to the diagnosis and treatment of GHIP.


Assuntos
Pólipos Adenomatosos , Ressecção Endoscópica de Mucosa , Hamartoma , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Gastroscopia/métodos , Pólipos Adenomatosos/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Hamartoma/diagnóstico , Hamartoma/cirurgia , Hamartoma/patologia
6.
Eur J Gastroenterol Hepatol ; 35(4): 376-383, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36827532

RESUMO

BACKGROUND AND PURPOSE: Although endoscopic submucosal dissection (ESD) is considered standard treatment for early gastric cancer (EGC), patients with non-curative resection (NCR) of ESD may still require gastrectomy. The systemic immune-inflammation index (SII) showed great potential in predicting the prognosis of gastric cancer patients. This study aims to investigate the predictive validity of SII of NCR in EGC patients. METHODS: We reviewed data from EGC patients who underwent ESD in the past. The relationship between SII and clinicopathologic features was investigated. We used Receiver operating characteristic curves to compare the predictive values of NCR between SII and other inflammation indices. Binary logistic analysis was used to identify independent risk factors for NCR. These factors were then used to construct a predictive nomogram. RESULTS: SII was associated with larger tumor size, male gender, older age, submucosal invasion, and a greater risk of NCR. SII showed better predictivity of NCR than platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). SII [odds ratio (OR) = 1.003, P = 0.001], NLR (OR = 1.520, P = 0.029), PLR (OR = 1.009, P = 0.010), upper stomach tumors (OR = 16.393, P < 0.001), poorly differentiated type (OR = 29.754, P < 0.001), ulceration (OR = 4.814, P = 0.001), and submucosal invasion (OR = 48.91, P < 0.001) were independent risk factors for NCR. The nomogram model based on these factors exhibited superior concordance and accuracy. CONCLUSION: SII could be considered a simple and effective predictor of NCR of ESD in EGC patients.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Masculino , Mucosa Gástrica/patologia , Inflamação/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Feminino
7.
World J Gastroenterol ; 29(48): 6208-6221, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38186862

RESUMO

BACKGROUND: Endoscopic evaluation in diagnosing and managing ulcerative colitis (UC) is becoming increasingly important. Several endoscopic scoring systems have been established, including the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score and Mayo Endoscopic Subscore (MES). Furthermore, the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score for UC has recently been proposed; however, its clinical value remains unclear. AIM: To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES. METHODS: This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University (Qingdao, China). We retrospectively analysed endoscopic scores, laboratory and clinical data, treatment, and readmissions within 1 year. Spearman's rank correlation coefficient, receiver operating characteristic curve, and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, United States) and GraphPad Prism version 9.0.0 for Windows (GraphPad Software, Boston, Massachusetts, United States). RESULTS: The TIGER score significantly correlated with the UCEIS score and MES (r = 0.721, 0.626, both P < 0.001), showed good differentiating values for clinical severity among mild, moderate, and severe UC [8 (4-112.75) vs 210 (109-219) vs 328 (219-426), all P < 0.001], and exhibited predictive value in diagnosing patients with severe UC [area under the curve (AUC) = 0.897, P < 0.001]. Additionally, the TIGER (r = 0.639, 0,551, 0.488, 0.376, all P < 0.001) and UCEIS scores (r = 0.622, 0,540, 0.494, and 0.375, all P < 0.001) showed stronger correlations with laboratory and clinical parameters, including C-reactive protein, erythrocyte sedimentation rate, length of hospitalisation, and hospitalisation costs, than MES (r = 0.509, 0,351, 0.339, and 0.270, all P < 0.001). The TIGER score showed the best predictability for patients' recent advanced treatment, including systemic corticosteroids, biologics, or immunomodulators (AUC = 0.848, P < 0.001) and 1-year readmission (AUC = 0.700, P < 0.001) compared with the UCEIS score (AUC = 0.762, P < 0.001; 0.627, P < 0.05) and MES (AUC = 0.684, P < 0.001; 0.578, P = 0.132). Furthermore, a TIGER score of ≥ 317 was identified as an independent risk factor for advanced UC treatment (P = 0.011). CONCLUSION: The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment, guiding therapeutic decision-making, and predicting short-term prognosis.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Estudos Retrospectivos , Colonoscopia , Adjuvantes Imunológicos
9.
Front Genet ; 13: 833857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571069

RESUMO

Gastric cancer (GC) has a high incidence worldwide, and when detected, the majority of patients have already progressed to advanced stages. Long non-coding RNAs (lncRNAs) have a wide range of biological functions and affect tumor occurrence and development. However, the potential role of lncRNAs in GC diagnosis remains unclear. We selected five high-quality samples from each group of chronic non-atrophic gastritis, gastric mucosal intraepithelial neoplasia, and GC tissues for analysis. RNA-seq was used to screen the differentially expressed lncRNAs, and we identified 666 differentially expressed lncRNAs between the chronic non-atrophic gastritis and GC groups, 13 differentially expressed lncRNAs between the gastric mucosal intraepithelial neoplasia and GC groups, and 507 differentially expressed lncRNAs between the chronic non-atrophic gastritis and gastric mucosal intraepithelial neoplasia groups. We also identified six lncRNAs (lncRNA H19, LINC00895, lnc-SRGAP2C-16, lnc-HLA-C-2, lnc-APOC1-1, and lnc-B3GALT2-1) which not only differentially expressed between the chronic non-atrophic gastritis and GC groups, but also differentially expressed between the gastric mucosal intraepithelial neoplasia and GC groups. Furthermore, RT-qPCR was used to verify the differentially co-expressed lncRNAs. LncSEA was used to conduct a functional analysis of differentially expressed lncRNAs. We also predicted the target mRNAs of the differentially expressed lncRNAs through bioinformatics analysis and analyzed targeting correlations between three differentially co-expressed lncRNAs and mRNAs (lncRNA H19, LINC00895, and lnc-SRGAP2C-16). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to explore the functions of target mRNAs of differentially expressed lncRNAs. In conclusion, our study provides a novel perspective on the potential functions of differentially expressed lncRNAs in GC occurrence and development, indicating that the differentially expressed lncRNAs might be new biomarkers for early GC diagnosis.

10.
World J Clin Cases ; 10(7): 2307-2314, 2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35321167

RESUMO

BACKGROUND: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma (MM). Amyloidosis (light chain) (AL) is the most common form of systemic amyloidosis. There are few reports of SMM coexisting with AL involving the digestive tract. CASE SUMMARY: A 63-year-old woman presented with lower limb edema, abdominal distension, abdominal pain, and hematochezia. Gastroscopy showed gastric retention, gastric angler mucosal coarseness, hyperemia, and mild oozing of blood. Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers, submucosal ecchymosis, and hematoma. Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining. MM was confirmed by bone marrow biopsy and immunohistochemistry. The patient had no hypercalcemia, renal dysfunction, anemia, bone lesions or biomarkers of malignancy defined as plasma cells > 60% in bone marrow. Additionally, no elevated serum free light chain ratio, or presence of bone marrow lesions by magnetic resonance imaging (SLiM criteria) were detected. The patient was finally diagnosed with SMM coexisting with AL. She received chemotherapy and was discharged when the symptoms were relieved. She is doing well at nearly five years of follow up. CONCLUSION: This case highlights that high index of suspicion is required to diagnose gastrointestinal AL. It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa, ecchymosis, and submucosal hematoma. Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.

12.
Gastroenterol Rep (Oxf) ; 9(6): 533-542, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34925850

RESUMO

BACKGROUND: The significance of endoscopic evaluation in the diagnosis and management of ulcerative colitis (UC) has been widely recognized. Over the years, scholars have established several endoscopic scores. Herein, we assessed the clinical application value of the Mayo Endoscopic Subscore (Mayo ES), the Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score in UC patients, by comparing their correlation with disease activity and their predictive potential for treatment response and clinical outcomes. METHODS: UC patients hospitalized from September 2015 to September 2019 were retrospectively analysed. We employed Spearman's rank correlation coefficient to assess the linear association of the assessed endoscopic scores with the clinical parameters. The receiver-operating characteristic curve was applied to evaluate the predictive capabilities of the endoscopic scores for treatment escalation and 1-year readmission. RESULTS: A total of 178 patients were enrolled; most of them (82%) suffered moderate or severe colitis. Among them, 48 (27%) patients received treatment escalation and 59 (33%) were readmitted within 1 year. The DUBLIN and UCEIS scores demonstrated higher correlations with clinical parameters than the Mayo ES. The DUBLIN scores significantly differed between patients with mild, moderate, and severe colitis (all P < 0.001). The UCEIS scores demonstrated the best predictabilities for treatment escalation and 1-year readmission with an area under the curve of 0.88 and 0.75, respectively. Compared to the UCEIS and DUBLIN scores, the predictive capabilities of the Mayo ES for treatment escalation (both P < 0.001) and 1-year readmission (P < 0.001 and P = 0.002, respectively) were lower. The UCEIS scores exhibited a significant difference between the steroid-responsive group and the steroid-dependent or steroid-refractory group (both P < 0.001), while no significant differences in the Mayo ES and DUBLIN scores were found among the three groups (both P > 0.05). CONCLUSION: This study demonstrates that both the DUBLIN and UCEIS scores outperform the Mayo ES in assessing disease severity and predicting treatment response and clinical outcomes in UC patients.

13.
J Dig Dis ; 22(11): 622-629, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34633753

RESUMO

OBJECTIVES: Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with functional constipation were randomized to receive either lubiprostone (24 mcg twice daily) or placebo for 4 weeks. The primary end-point was the frequency of spontaneous bowel movements (SBMs) during the first week of treatment. The secondary end-points included the median time of the first SBM, SBM frequency at weeks 2, 3 and 4, weekly response rate of SBMs, the stool consistency score and average number of complete spontaneous bowel movements (CSBMs) per week. RESULTS: In total, 259 patients were randomized, with 130 in the lubiprostone group and 129 in the placebo group. SBM frequency was higher in the lubiprostone group (4.88 ± 4.09/wk) than that in the placebo group (3.22 ± 2.01/wk) at week 1 (P < 0.0001). SBM frequency was also higher in the lubiprostone group at weeks 2, 3 and 4. The average number of CSBMs and the stool consistency score in the lubiprostone group were significantly higher than that in the placebo group at each week. No drug-related serious adverse events (AEs) occurred. The most commonly reported AE was nausea. CONCLUSION: Lubiprostone was superior to placebo in treating Chinese patients with functional constipation, together with good safety profile.


Assuntos
Agonistas dos Canais de Cloreto , Constipação Intestinal , Adulto , China , Agonistas dos Canais de Cloreto/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Defecação , Método Duplo-Cego , Humanos , Lubiprostona , Resultado do Tratamento
14.
Front Oncol ; 11: 619592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249675

RESUMO

BACKGROUND: Sarcopenia is a poor prognostic factor in patients with esophageal cancer (EC). It can be aggravated by neoadjuvant therapy (NAT) that improves the prognosis of patients with EC. Until now, the impact of preoperative sarcopenia on survival prognosis in patients receiving NAT for EC remains unclear. METHODS: We systematically researched relevant studies in the PubMed, EMBASE, Web of Science, the Cochrane Library databases up to March 8, 2020. Prevalence of sarcopenia before and after NAT, overall survival (OS) and disease-free survival (DFS) were collected for analysis. Finally, eleven cohort studies were included. RESULTS: Pooled analysis indicated that preoperative sarcopenia was negatively associated with OS. (HR = 1.290; 95% CI [1.078-1.543]; P = 0.005; I 2 = 0.0%) and DFS (HR = 1.554; 95% CI [1.177-2.052]; P = 0.002; I 2 = 0.0%) in the patients with EC receiving NAT. The prevalence of sarcopenia increased by 15.4% following NAT (95%CI [12.9%-17.9%]). Further subgroup analysis indicated that sarcopenia diagnosed following NAT (HR = 1.359; 95% CI [1.036-1.739]; P = 0.015; I 2 = 6.9%) and age >65 years (HR = 1.381; 95% CI [1.090- 1.749]; P = 0.007; I 2 = 0.0%) were the independent risk factors for decreased OS. CONCLUSIONS: Clinicians should strengthen the screening of preoperative sarcopenia in patients of EC both receiving NAT and older than 65 years and give active nutritional support to improve the prognosis of patients. SYSTEMATIC REVIEW REGISTRATION: International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202050057.

15.
Front Oncol ; 11: 790589, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35070998

RESUMO

Cancer is a major threat to human health and longevity. Chemotherapy is an effective approach to inhibit cancer cell proliferation, but a growing number of cancer patients are prone to develop resistance to various chemotherapeutics, including platinum, paclitaxel, adriamycin, and 5-fluorouracil, among others. Significant progress has been made in the research and development of chemotherapeutic drugs over the last few decades, including targeted therapy drugs and immune checkpoint inhibitors; however, drug resistance still severely limits the application and efficacy of these drugs in cancer treatment. Recently, emerging studies have emphasized the role of circular RNAs (circRNAs) in the proliferation, migration, invasion, and especially chemoresistance of cancer cells by regulating the expression of related miRNAs and targeted genes. In this review, we comprehensively summarized the potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair, among others. Furthermore, we highlighted the potential value of circRNAs as new therapeutic targets and prognostic biomarkers for cancer.

16.
Front Oncol ; 11: 810893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35071016

RESUMO

Long non-coding RNAs (ncRNAs), which do not encode proteins, regulate cell proliferation, tumor angiogenesis, and metastasis and are closely associated with the development, progression, and metastasis of many cancers. Tumor-associated macrophages (TAMs) in the tumor microenvironment play an important role in cancer progression. The Hippo signaling pathway regulates cell proliferation and apoptosis, maintains tissue and organ size, and homeostasis of the internal environment of organisms. Abnormal expression of Yes-associated protein (YAP), the Hippo signaling pathway key component, is widely observed in various malignancies. Further, TAM, lncRNA, and YAP are currently valuable targets for cancer immunotherapy. In this review, we have logically summarized recent studies, clarified the close association between the three factors and tumorigenesis, and analyzed the outlook of tumor immunotherapy.

17.
Ann Surg Oncol ; 28(4): 2407-2417, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32975685

RESUMO

BACKGROUND: When the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration. PATIENTS AND METHODS: We retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed. RESULTS: LNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI [odds ratio (OR) = 16.761, P < 0.001], SM1 invasion (OR = 2.159, P = 0.028), and SM2 invasion (OR = 3.230, P < 0.001) were independent risk factors for LNM. LNM occurred in undifferentiated mucosal tumors, with ulceration being 1.7% (2/116) when the lesion was smaller than 20 mm. Further stratification revealed that among lesions < 30 mm in size, undifferentiated tumors with SM1 invasion had a higher rate of LNM and a lower disease-free survival rate than differentiated tumors with SM1 invasion and tumors limited to the mucosal layer. CONCLUSIONS: Depth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC < 30 mm in size, and additional investigation is needed to evaluate its safety.


Assuntos
Neoplasias Gástricas , Estudos de Viabilidade , Gastrectomia , Mucosa Gástrica , Humanos , Excisão de Linfonodo , Metástase Linfática , Invasividade Neoplásica , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia
18.
J Cell Physiol ; 236(2): 889-899, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33020901

RESUMO

Long intergenic noncoding RNAs (lincRNAs) play a vital role in the occurrence and progression of cancer. The mechanism of lincRNAs in colorectal cancer (CRC) has not been fully elucidated. In this context, an integrated comparative long noncoding RNA (lncRNA) microarray technology was used to determine the expression profile of lncRNAs in CRC. The roles of LINC00908 are unclear. We found that LINC00908 was significantly upregulated in CRC. Inhibition of LINC00908 resulted in reduced cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma. Moreover, inhibition of LINC00908-induced apoptosis through the intrinsic apoptosis signaling pathway, as shown by the activation of caspase-9 and caspase-3. Mechanistically, miR-143-3p directly bound to LINC00908. miR-143-3p expression was negatively correlated with LINC00908 expression in CRC tissue. Functional experiments revealed opposing roles for miR-143-3p and LINC00908, suggesting that LINC00908 negatively regulates miR-143-3p. Mechanistically, miR-143-3p directly targets LINC00908. The KLF5 inhibitor ML264 affected proliferation and apoptosis, indicating that LINC00908 may act as a competing endogenous RNA to facilitate the expression of the miR-143-3p target gene KLF5. Thus, LINC00908 has an important proliferative and antiapoptotic role in CRC by regulating the cell cycle and intrinsic apoptosis. LINC00908 could be a potential biomarker and a new therapeutic target for CRC.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , Fatores de Transcrição Kruppel-Like/genética , RNA Longo não Codificante/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Células HCT116 , Humanos , Transdução de Sinais/genética , Regulação para Cima/genética
19.
World J Clin Cases ; 8(22): 5781-5789, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33344574

RESUMO

BACKGROUND: Enteropathy-associated T-cell lymphoma (EATL) is a rare invasive lymphoma derived from gastrointestinal epithelial T lymphocytes. EATL involving the whole gastrointestinal tract accompanied with early colon cancer is extremely rare. CASE SUMMARY: We present the case of a 67-year-old man with diarrhea for more than 5 mo whose colonoscopy in another hospital showed multiple colonic polyps, which indicated moderate to severe dysplasia and focal early cancer. Therefore, he was referred to our hospital for further endoscopic treatment. Colonoscopy after admission showed that the mucosa of the terminal ileum and the entire colon were slightly swollen and finely granular. Endoscopic mucosal resection was performed for colonic polyps located in the liver flexure of the colon and descending colon, respectively. Histopathological findings revealed diffuse infiltration of medium-sized lymphoid cells in the colonic mucosa and visible lymphoepithelial lesions. The histopathology of the polyp in the descending colon indicated moderately differentiated adenocarcinoma limited to the mucosa with negative resection margins. Additionally, immunohistochemical analysis showed positive staining for CD7 and CD8. Therefore, we arrived at a diagnosis of EATL with early colon cancer. Subsequently, the patient was transferred to the hematology department for chemotherapy. The patient's diarrhea was not significantly relieved after receiving chemotherapy, and he ultimately died of severe myelosuppression. CONCLUSION: EATL should be considered in unexplained chronic diarrhea. EATL progresses rapidly with a poor prognosis, especially when accompanied with early colon cancer.

20.
Int J Mol Med ; 45(4): 1250-1260, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124944

RESUMO

The problems caused by diabetes mellitus (DM) and its related complications are gaining increasing attention. In our previous study, the abnormal proliferation of small intestinal epithelial cells (IECs) were observed in diabetic mice. However, little is known regarding the potential underlying mechanism. In the present study, the abnormal proliferation of IECs in DM and the marked upregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was observed. Additionally, knockdown of MALAT1 significantly reduced abnormal IESC proliferation in DM mice. Bioinformatics analysis and luciferase reporter assays revealed that microRNA (miR)­129­5p was directly targeted by MALAT1. Moreover, the results of the bioinformatics prediction and luciferase assays demonstrated that MALAT1 directly interacted with SRY­box 9 (SOX9). Furthermore, MALAT1 silencing was observed to attenuate the abnormal proliferation of IESCs through the SOX9­mediated WNT/ß­catenin signaling pathway. Knockdown of MALAT1 downregulated SOX9 expression by binding to miR­129­5p, thereby inhibiting the abnormal proliferation of IESCs via the WNT/ß­catenin signaling pathway.


Assuntos
Proliferação de Células , Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Células Epiteliais/metabolismo , Intestino Delgado/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Diabetes Mellitus Experimental/patologia , Células Epiteliais/patologia , Intestino Delgado/patologia , Masculino , Camundongos
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