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N6-Methyladenosine (m6A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A axis in AEG cells.
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Adenocarcinoma , Adenosina , Ciclo Celular , Neoplasias Esofágicas , Proteínas de Ligação a RNA , Fosfatases cdc25 , Humanos , Fosfatases cdc25/metabolismo , Fosfatases cdc25/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Animais , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Linhagem Celular Tumoral , Camundongos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Camundongos Nus , Metiltransferases/metabolismo , Metiltransferases/genéticaRESUMO
The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single-cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor-intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over-expression suppresses the tumor-intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA-MAVS-IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti-PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV-MAVS-IFN axis.
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OBJECTIVE: This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after experiencing immune-related adverse events (irAEs). METHODS: A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted to identify studies investigating the safety and efficacy of restarting ICIs in NSCLC patients after irAEs. Outcome measures, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) after ICI restarting, were extracted. Meta-analysis was performed using the R meta-package. RESULTS: Four studies involving a total of 326 subjects were included, comprising 137 patients who restarted ICI treatment after irAEs and 189 patients who did not restart ICI treatment. The results revealed that ICI restarting was associated with an increased ORR (OR = 2.36, 95% CI 1.49-3.84), prolonged PFS (HR = 0.60, 95% CI 0.42-0.86), and prolonged OS (HR = 0.65, 95% CI 0.43-0.99) compared to non-restarting. The incidence of irAEs after ICI restarting was 45% (95% CI 0.27-0.63). CONCLUSION: Restarting ICI treatment after discontinuation due to previous irAEs appears to be a reasonable option for NSCLC patients. However, a comprehensive assessment of the potential benefits and risks to individual patients is crucial, and close monitoring of irAEs is warranted.
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Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence is commonly observed due to OXA resistance. OXA resistance is associated with a number of factors, including abnormal regulation of pyroptosis. It is therefore important to elucidate the abnormal regulatory mechanism underlying pyroptosis. Here, we identified that the circular RNA circPDIA3 played an important role in chemoresistance in CRC. CircPDIA3 could induce chemoresistance in CRC by inhibiting pyroptosis both in vitro and in vivo. Mechanistically, RIP, RNA pull-down and co-IP assays revealed that circPDIA3 directly bonded to the GSDME-C domain, subsequently enhanced the autoinhibitory effect of the GSDME-C domain through blocking the GSDME-C domain palmitoylation by ZDHHC3 and ZDHHC17, thereby restraining pyroptosis. Additionally, it was found that the circPDIA3/miR-449a/XBP1 positive feedback loop increased the expression of circPDIA3 to induce chemoresistance. Furthermore, our clinical data and patient-derived tumor xenograft (PDX) models supported the positive association of circPDIA3 with development of chemoresistance in CRC patients. Taken together, our findings demonstrated that circPDIA3 could promote chemoresistance by amplifying the autoinhibitory effect of the GSDME-C domain through inhibition of the GSDME-C domain palmitoylation in CRC. This study provides novel insights into the mechanism of circRNA in regulating pyroptosis and providing a potential therapeutic target for reversing chemoresistance of CRC.
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Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Lipoilação , MicroRNAs , Piroptose , RNA Circular , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Piroptose/efeitos dos fármacos , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Camundongos , Lipoilação/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/metabolismo , Proteína 1 de Ligação a X-Box/genética , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Oxaliplatina/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Camundongos Nus , Aciltransferases/genéticaRESUMO
Because of the considerable tumor heterogeneity in gastric cancer (GC), only a limited group of patients experiences positive outcomes from immunotherapy. Herein, we aim to develop predictive models related to glycosylation genes to provide a more comprehensive understanding of immunotherapy for GC. RNA sequencing (RNA-seq) data and corresponding clinical outcomes were obtained from GEO and TCGA databases, and glycosylation-related genes were obtained from GlycoGene DataBase. We identified 48 differentially expressed glycosylation-related genes and established a prognostic model (seven prognosis genes including GLT8D2, GALNT6, ST3GAL6, GALNT15, GBGT1, FUT2, GXYLT2) based on these glycosylation-related genes using the results from Cox regression analysis. We found that these glycosylation-related genes revealed a robust correlation with the abundance of Tumor Infiltrating Lymphocytes (TILs), especially the GLT8D2 which is associated with many TILs. Finally, we employed immunohistochemistry and Multiplex Immunohistochemical to discover that GLT8D2 serves as a valuable prognostic biomarker in GC and is closely associated with macrophage-related markers. Collectively, we established a prognostic model based on glycosylation-related genes to provide a more comprehensive understanding of prediction for GC prognosis, and identified that GLT8D2 is closely correlated with adverse prognosis and may underscore its role in regulating immune cell infiltration in GC patients.
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Biomarcadores Tumorais , Linfócitos do Interstício Tumoral , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/genética , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Glicosilação , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Microambiente Tumoral/imunologiaRESUMO
Chondroitin sulfate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but its role in tumors has not been determined. Here, we showed that high CHSY3 expression promotes proliferation in gastric cancer (GC) cells and is associated with poor prognosis in GC patients. We analyzed the immunohistochemistry data of 150 gastric cancer patients to determine the clinicopathological and survival significance of CHSY3. Immunofluorescence was used to detect the colocalization of CHSY3 with infiltrating immune cells. Additionally, CHSY3 was predominantly found in tumor tissues and showed higher abundance compared to matched adjacent tissues. High CHSY3 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis revealed that CHSY3 expression was significantly positively correlated with tumor-associated macrophage (TAM) infiltration. Moreover, after knocking down CHSY3, the proliferation of cells was decreased, and the migration ability was reduced, as shown by scratch, monoclonal and transwell assays. In conclusion, this study revealed that CHSY3 has a tumor-promoting effect on GC, suggesting a novel therapeutic strategy against this disease.
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Proliferação de Células , Neoplasias Gástricas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismoRESUMO
OBJECTIVES: Obesity and hypercholesterolemia are linked to unfavor clinical outcomes. Recent studies declared the paradox that high body mass index (BMI) and serum cholesterol were independently connected to better clinical outcome of immune checkpoint inhibitors (ICIs) monotherapy in non-small cell lung cancer (NSCLC). The aim of the study is to investigate the prognosis of BMI and serum cholesterol in ICIs-based therapy. METHODS: This is a retrospective study of 95 NSCLC patients treated with ICIs-based therapy at the Department of Oncology and Lung Cancer Center of China-Japan Friendship Hospital. Treatment efficacy was assessed using durable clinical benefit (DCB) versus nondurable benefit (NDB), best response (active vs. nonactive), and progression-free survival (PFS). The prognostic value of BMI, LDL-C, and RC was determined by multivariate regression analyses, while controlling for confounding factors including age, gender, diabetes status, smoking history, and statin usage. BMI was considered a confounding factor in the analysis when examining the impact of lipoproteins. RESULTS: In our study, we found that in the whole group, BMI ≥25 kg/m2 was linked to a higher risk of poor therapeutic response (OR = 5.92, 95% CI 1.99-19.51, p.val = 0.002) and shorter progression-free survival (HR = 3.00, 95% CI 1.59-5.68, p.val = 0.001). In addition, low levels of RC were associated with better therapeutic response (OR = 0.12, 95% CI 0.02-0.64, p.val = 0.019), while low levels of serum LDL-C were found to predict longer PFS (HR = 0.40, 95% CI 0.19-0.82, p.val = 0.012). These associations were consistent in advanced NSCLC patients receiving ICIs and chemotherapy. CONCLUSIONS: Our study suggest that BMI ≥25 kg/m2 and elevated levels of apoB-containing lipoproteins, including LDL-C and RC, could potentially serve as useful prognostic markers for predicting poor treatment outcomes in advanced NSCLC patients treated with the combination of chemotherapy and ICIs.
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Índice de Massa Corporal , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/sangue , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Idoso , Prognóstico , Resultado do Tratamento , Intervalo Livre de Progressão , Colesterol/sangue , Adulto , Idoso de 80 Anos ou mais , Obesidade/complicaçõesRESUMO
Background: Some patients with high-risk gastrointestinal stromal tumor (GIST) experience disease progression after complete resection and adjuvant therapy. It is of great significance to distinguish these patients among those with high-risk GIST. Radiomics has been demonstrated as a promising tool to predict various tumors prognosis. Methods: From January 2006 to December 2018, a total of 100 high-risk GIST patients (training cohort: 60; validation cohort: 40) from Guangdong Provincial People's Hospital with preoperative enhanced computed tomography (CT) images were enrolled. The radiomics features were extracted and a risk score was built using least absolute shrinkage and selection operator-Cox model. The clinicopathological factors were analyzed and a nomogram was established with and without radiomics risk score. The concordance index (C-index), calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomograms. Results: We selected 11 radiomics features associated with recurrence or metastasis. The risk score was calculated and significantly associated with disease-free survival (DFS) in both the training and validation group. Cox regression analysis showed that Ki67 was an independent risk factor for DFS [P=0.004, hazard ratio 4.615, 95% confidence interval (CI): 1.624-13.114]. The combined radiomics nomogram, which integrated the radiomics risk score and significant clinicopathological factors, showed good performance in predicting DFS, with a C-index of 0.832 (95% CI: 0.761-0.903), which was better than the clinical nomogram (C-index 0.769, 95% CI: 0.679-0.859) in training cohort. The calibration curves and the DCA plot suggested satisfying accuracy and clinical utility of the model. Conclusions: The CT-based radiomics nomogram, combined with the clinicopathological factors and risk score, has good potential to assess the recurrence or metastasis of patients with high-risk GIST.
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BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.
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Neoplasias Colorretais , Infecções por Papillomavirus , Microambiente Tumoral , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/virologia , Neoplasias Colorretais/patologia , Microambiente Tumoral/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Feminino , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/imunologia , Proliferação de Células , Idoso , Estudos de Coortes , PrevalênciaRESUMO
Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.
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Adenocarcinoma , Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Adenocarcinoma/genética , Neoplasias Gástricas/genética , Junção Esofagogástrica , Análise de Célula Única , Microambiente TumoralRESUMO
PURPOSE: Malignancies of the upper gastrointestinal tract are rare in early-onset patients outside the hereditary genetic disorders. There are few reports describing adenocarcinoma of the esophagogastric junction (AEG) in extremely early-onset patients aged under 50 years old. The aim of this study was to describe the clinicopathological features and prognosis of adenocarcinoma of esophagogastric junction (AEG) in early-onset patients among three successive periods: 1975-1989 (period 1), 1990-2004 (period 2), and 2005-2017 (period 3). METHODS: Between 1975 and 2017, data were extracted from the Surveillance, Epidemiology, and End Results database, and 18,278 patients with AEG were enrolled. Three age groups of patients were identified: < 50, 50-69, and ≥ 70 years of age. Clinicopathological characteristics and prognostic outcomes were reviewed and compared among three groups over three periods (1975-89, 1990-04, and 2005-2017). Multivariate Cox regression analysis was performed to adjust for covariate effects related to both overall survival (OS) and cancer-specific survival (CSS). RESULTS: Among three age groups, early-onset patients were more likely to present with higher tumor grade, advanced nodal, and distant metastatic disease at diagnosis than other groups (p < 0.01 for both). In comparison to the older group, a higher proportion of patients in the early-onset group received chemotherapy and radiation treatment. After adjusting for covariates, early-onset patients had a better CSS and OS than elderly patients. CONCLUSIONS: Early-onset AEG patients were more likely than other age groups to present with advanced disease upon diagnosis. However, the prognosis of early-onset patients was better than their older counterparts after adjustment for covariates. The dissimilarities in tolerance to treatment among early-onset, middle-aged, and elderly patients could be the reason for this difference.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Idoso , Pessoa de Meia-Idade , Humanos , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/terapia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/terapia , Junção Esofagogástrica/patologia , Estudos RetrospectivosRESUMO
Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.
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Background: Lung squamous cell carcinoma (LUSC) shares less typical onco-drivers and target resistance, but a high overall mutation rate and marked genomic complexity. Mismatch repair (MMR) deficiency leads to microsatellite instability (MSI) and genomic instability. MSI is not an ideal option for prognosis of LUSC, whereas its function deserves exploration. Method: MSI status was classified by MMR proteins using unsupervised clustering in the TCGA-LUSC dataset. The MSI score of each sample was determined by gene set variation analysis. Intersections of the differential expression genes and differential methylation probes were classified into functional modules by weighted gene co-expression network analysis. Least absolute shrinkage and selection operator regression and stepwise gene selection were performed for model downscaling. Results: Compared with the MSI-low (MSI-L) phenotype, MSI-high (MSI-H) displayed higher genomic instability. The MSI score was decreased from MSI-H to normal samples (MSI-H > MSI-L > normal). A total of 843 genes activated by hypomethylation and 430 genes silenced by hypermethylation in MSI-H tumors were classified into six functional modules. CCDC68, LYSMD1, RPS7, and CDK20 were used to construct MSI-related prognostic risk score (MSI-pRS). Low MSI-pRS was a protective prognostic factor in all cohorts (HR = 0.46, 0.47, 0.37; p-value = 7.57e-06, 0.009, 0.021). The model contains tumor stage, age, and MSI-pRS that showed good discrimination and calibration. Decision curve analyses indicated that microsatellite instability-related prognostic risk score added extra value to the prognosis. A low MSI-pRS was negatively correlated with genomic instability. LUSC with low MSI-pRS was associated with increased genomic instability and cold immunophenotype. Conclusion: MSI-pRS is a promising prognostic biomarker in LUSC as the substitute of MSI. Moreover, we first declared that LYSMD1 contributed to genomic instability of LUSC. Our findings provided new insights in the biomarker finder of LUSC.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Prognóstico , Estadiamento de Neoplasias , Linfonodos/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Junção Esofagogástrica/cirurgia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: This study aims to explore the minimum number of lymph nodes (LNs) necessary for assessing the postoperative staging of adenocarcinoma of esophagogastric junction (AEG). METHODS: We extracted the data of patients from the Surveillance Epidemiology and End Results (SEER) database, who were pathologically diagnosed with AEG between 2000 and 2017. We explored the associations between the number of LNs and overall survival (OS) by univariate and multivariate analyses and determined the proper cutoff value of the number of LNs necessary for accurate postoperative staging. RESULTS: Of the patients with AEG in the SEER database, 2668 met our inclusion criteria. The total number of regional LNs dissected was found to be significantly associated with survival in analyses stratified by T stage. Univariate and multivariate regression showed that age, grade, positive LNs, number of LNs examined, and T stage were independently associated with OS. For patients with T1-2 tumors, the 5-year survival rate was 58.7%, and patients with more than 11 LNs examined obtained a greater survival benefit. Among patients with T3-4 tumors, the 5-year survival rates were 28.9% and 39.7% for those with 1-16 LNs examined and for those with more than 17 LNs examined, respectively. CONCLUSION: To accurately determine the pathological stage of patients with AEG, no less than 11 LNs must be resected for patients with stage T1-2 disease, and no less than 16 LNs must be resected for patients with stage T3-4 disease.
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Adenocarcinoma , Excisão de Linfonodo , Humanos , Prognóstico , Estudos Retrospectivos , Metástase Linfática/patologia , Linfonodos/patologia , Adenocarcinoma/patologia , Junção Esofagogástrica/cirurgiaAssuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Mediastino/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Excisão de LinfonodoRESUMO
In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography-mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota.
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Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, is highly prone to recurrence, and has a short survival period. It is very difficult to achieve long-term survival in ES-SCLC, which has not been significantly improved in the last 20 years. For a long time, platinum-based chemotherapy has occupied the core position in the treatment of small-cell lung cancer (SCLC), but there are few options for treatment drugs or regimens, and if disease progression occurs, the options for follow-up regimens are obviously limited. The advent of immunotherapy has changed this situation to some extent, and immunotherapy has shown some effects in improving efficiency and prolonging survival, whether in first- or third-line therapy, but it is still unsatisfactory. Case presentation: A 57-year-old patient with ES-SCLC experienced disease progression after four lines of treatment including synchronous radiotherapy, chemotherapy, and antiangiogenesis. However, the patient still benefited when switching to the programmed cell death receptor-1 (PD-1) inhibitor toripalimab in combination with chemotherapy in the fifth line. Even after the development of immune resistance, the patient still benefited after switching to tislelizumab in combination with different chemotherapy regimens or alone in the sixth and seventh lines. Following the progression of tislelizumab in combination with chemotherapy, the patient again profited after switching to durvalumab in combination with anlotinib and again achieved a progressive-free survival (PFS) of 11 months. Overall, the patient achieved a total of 45 months of PFS and 50 months of overall survival (OS), with a shocking and exciting 30 months of PFS achieved in the immune combination phase alone. Conclusion: We report a patient with ES-SCLC who achieved long-term survival after at least eight lines of therapy including chemotherapy, antiangiogenesis, and different immune checkpoint inhibitors (ICIs). This suggests that long-term survival in SCLC is possible with aggressive, combined, and standardized treatment. Otherwise, immunotherapy postline enablement can still benefit patients, rechallenge after immune resistance is also possible in SCLC, and combination with chemotherapy or antiangiogenic therapy can improve the efficacy and prolong the survival. This will provide new ideas and options for the selection of treatment options for SCLC.