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ObjectiveThe purpose of this study was to evaluate the clinical effect of mixed nutrition and parenteral nutrition support on postoperative patients with esophageal cancer.MethodBy searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures until March 2024 about the comparison of randomized controlled Trial (RCT) of mixed nutrition and parenteral nutrition support in postoperative patients with esophageal cancer were screened. The inclusion criteria were that the patients were from randomized controlled trials or clinical trials in China, and the patients were all diagnosed with esophageal cancer by pathological biopsy. The exclusion criteria were the literature other than the above, including repeated published literature, non-Chinese and English literature, incomplete or missing analysis data, etc. After two researchers independently screened the literature, extracted the data and evaluated the risk of bias according to the criteria, Meta-analysis was carried out with RevMan 5.4 software.ResultsA total of 11 studies were included, including 1216 patients. Meta-analysis showed that, compared with parenteral nutrition, mixed nutrition can improve the levels of transferrin, serum albumin, prealbumin and lymphocyte counts in patients with esophageal cancer after surgery, shorten the time of anal recovery of exhaust, defecation and hospital stay after surgery, and reduce the incidence of pulmonary infection, abdominal distension, incision infection and anastomotic fistula, with statistical significance between the two groups (P < 0.05). The heterogeneity of individual results in this study is relatively high, the analysis comes from clinical heterogeneity, and the publication bias is analyzed through Funnel plot. Taking the incidence of lung infection as an example, the results are evenly distributed on both sides of the Funnel plot, and the publication bias has little impact on the results of the study.ConclusionCompared with parenteral nutrition, mixed nutrition can improve the prognosis of postoperative patients with esophageal cancer and reduce the incidence of related adverse events.

ObjectiveThe optimal first-line immunotherapy regimen for patients with PD-L1 expression ≥50% in squamous non-small cell lung cancer (Sq-NSCLC) remains uncertain. This study utilized net-work meta-analysis (NMA) to indirectly compare the efficacy of various first-line immuno-therapy regimens in this patient subset.MethodsSystematic searches were conducted across PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) outcomes. The search spanned from database inception to November 3, 2023. Bayesian network meta-analysis was employed for a comprehen-sive analysis. To ensure scientific rigor and transparency, this study is registered in the Interna-tional Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022349712.ResultsThe NMA encompassed 9 randomized controlled trials (RCTs), involving 2170 patients and investigating 9 distinct immunotherapy regimens. For OS, the combination of camrelizumab and chemotherapy demonstrated the highest probability (36.68%) of efficacy, fol-lowed by cemiplimab (33.86%) and atezolizumab plus chemotherapy (23.87%). Regarding PFS, the camrelizumab and chemotherapy combination had the highest probability (39.70%) of efficacy, followed by pembrolizumab (22.88%) and pembrolizumab plus chemotherapy (17.69%). Compared to chemotherapy, first-line treatment with immune checkpoint inhibitors (ICIs) in Sq-NSCLC pa-tients exhibited significant improvements in OS (HR 0.59, 95% CI 0.47-0.75) and PFS (HR 0.44, 95% CI 0.37-0.52).ConclusionThis study suggests that, for Sq-NSCLC patients with PD-L1 expression ≥50%, the first-line immunotherapy regimen of camrelizumab plus chemotherapy provides superior OS and PFS outcomes. Furthermore, ICIs demonstrate enhanced efficacy compared to chemotherapy in this patient population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD 42022349712.

IntroductionRUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.MethodsThe qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.ResultsRUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.ConclusionCollectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.

ObjectiveTo evaluate the efficacy and safety of anlotinib-based treatment in metastatic breast cancer (MBC) patients with failure of standard treatment.MethodsWe collected the medical data of 56 female patients with the diagnosis of MBC and had failed the standard treatment before. These patients received at least two cycles of anlotinib-based treatment as the second-line or beyond treatment between October 2019 and April 2022 in Jiangsu Cancer Hospital. The primary endpoint of our study was progression-free survival (PFS), and it was estimated with Kaplan-Meier. The second end points were disease control rate (DCR), objective response rate (ORR), and side effects.ResultsThe median PFS time of a total of 56 patients was 5.7 months (95% CI, 3.17-8.23 months). The ORR and DCR was 28.6% and 71.4%, respectively. In second-line, third-line, and beyond treatment, the median PFS was 11.7 months, 8.7 months, and 4.7 months, respectively. In different subtype of breast cancer, the median PFS was 5.6 months, 5.7months, and 6.4 months in human epidermal growth factor receptor 2 positive (HER2+), hormone receptor positive and HER2 negative (HR+/HER2-), and triple negative breast cancer (TNBC) patients, respectively. Most adverse effects were clinically manageable, and the most common events were platelet count decrease (35.7%), hand-foot syndrome (19.6%), diarrhea (19.6%), and fatigue (17.9%). The most common grade 3 and 4 adverse events were platelet count decrease (10.7%), diarrhea (7.1%), and oral mucositis (5.4%).ConclusionAnlotinib-based treatment showed good efficacy and manageable toxicity in multi-line treatment of MBC patients who failed the standard treatment.

PurposeFatty acid metabolism plays key role in cancer development, and free fatty acid receptors (FFARs) are involved in many cancers. However, the correlation between serum free fatty acids (FFAs)/FFARs levels and ovarian cancer (OC) prognosis remains largely unclear.MethodsA retrospective review of 534 primary OC patients and 1049 women with benign ovarian tumors was performed. Serum FFA levels data were extracted from the electronic medical record system. Repeated FFA results of 101 OC patients treated with standard chemotherapy were collected. The effects of FFAs on cells migration were evaluated in OC cell lines by Transwell assay. Gene Expression Profiling Interactive Analysis (GEPIA) was used to compare FFAR mRNA expression levels in cancer and noncancer tissues. Kaplan-Meier (KM) plotter was employed to analyze their prognostic values. SPSS 23.0 and Graphpad prism 7.0 software was used for analysis and graph construction.ResultsFFA levels in the serum of epithelial ovarian cancer (EOC) women were higher than in women with benign ovarian tumors independent of pathology, tumor stage,and grade. FFA levels decreased gradually after chemotherapy. FFAs enhanced the migration of OVCAR3 cells. FFAR1 mRNA expression was lower in OC cells than in control cells. FFAR3 was related to a better prognosis, and FFAR4 was related to poor prognosis in TP-53wild-type and mutated type OC, while FFAR1 and FFAR2 were related to a better prognosis in TP53 wild-type OC but FFAR2 was related to a poor prognosis in TP53-mutant OC.ConclusionThe FFA levels are increased in OC and decreased with chemotherapy. High expression of FFARs was related to the prognosis of OC. The prognostic value of different FFARs differs depending on whether it is a TP53 wild or TP53 mutant ovarian cancer.Targeting FFARs may be an attractive treatment strategy for EOC.

Patients with non-small cell lung cancer harboring the epidermal growth factor receptor (EGFR)-sensitive mutations are known to benefit significantly from EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, icotinib, or afatinib. However, the efficacy of EGFR-TKIs against rare mutations has not yet been well investigated. Here, we report a female patient with advanced lung adenocarcinoma (LUAD), carrying a rare mutation of EGFR Exon19 E746_L747delinsIP, who was administered first-generation EGFR-TKIs as the first-line treatment. The patient continued to progress slowly until peritoneal metastases have occurred. Subsequently, the patient was treated with anlotinib for 5 months until disease progression. Given the finding of the same EGFR rare mutation in peritoneal effusion without other EGFR-TKI resistance mutations, the patient received afatinib with a tremendous response. Our results may be of clinical relevance for patients with LUAD carrying this rare mutation, and these findings warrant further investigation.

Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.

BackgroundHER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes.MethodsA total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS).ResultsThe median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%).ConclusionPyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

PurposeTo evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment.Materials and MethodsTwo hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin

Chemoresistance has been a significant problem affecting the efficacy of drugs targeting tumors for decades. MGMT, known as O6-methylguanine-DNA methyltransferase, is a DNA repair enzyme that plays an important role in chemoresistance to alkylating agents. Hence, MGMT is considered a promising target for tumor treatment. Several methods are employed to detect MGMT, each with its own advantages and disadvantages. Some of the detection methods are; immunohistochemistry, methylation-specific PCR (MSP), pyrophosphate sequencing, MGMT activity test, and real-time quantitative PCR. Methylation of MGMT promoter is a key predictor of whether alkylating agents can effectively control glioma cells. The prognostic value of MGMT in glioma is currently being explored. The expression of MGMT gene mainly depends on epigenetic modification–methylation of CpG island of MGMT promoter. CpG island covers a length of 762 bp, with 98 CpG sites located at the 5' end of the gene, ranging from 480 to 1,480 nucleotides. The methylation sites and frequencies of CpG islands vary in MGMT-deficient tumor cell lines, xenografts of glioblastoma and in situ glioblastoma. Methylation in some regions of promoter CpG islands is particularly associated with gene expression. The change in the methylation status of the MGMT promoter after chemotherapy, radiotherapy or both is not completely understood, and results from previous studies have been controversial. Several studies have revealed that chemotherapy may enhance MGMT expression in gliomas. This could be through gene induction or selection of high MGMT-expressing cells during chemotherapy. Selective survival of glioma cells with high MGMT expression during alkylating agent therapy may change MGMT status in case of recurrence. Several strategies have been pursued to improve the anti-tumor effects of temozolomide. These include the synthesis of analogs of O6-meG such as O6-benzylguanine (O6-BG) and O6-(4-bromothenyl) guanine (O6-BTG), RNAi, and viral proteins. This review describes the regulation of MGMT expression and its role in chemotherapy, especially in glioma. Targeting MGMT seems to be a promising approach to overcome chemoresistance. Further studies exploring new agents targeting MGMT with better curative effect and less toxicity are advocated. We anticipate that these developments will improve the current poor prognosis of glioma patients.

Objective: The optimal first-line immunotherapy regimen for patients with PD-L1 expression =50% in squamous non-small cell lung cancer (Sq-NSCLC) remains uncertain. This study utilized net-work meta-analysis (NMA) to indirectly compare the efficacy of various first-line immuno-therapy regimens in this patient subset. Methods: Systematic searches were conducted across PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) outcomes. The search spanned from database inception to November 3, 2023. Bayesian network meta-analysis was employed for a comprehen-sive analysis. To ensure scientific rigor and transparency, this study is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022349712. Results: The NMA encompassed 9 randomized controlled trials (RCTs), involving 2170 patients and investigating 9 distinct immunotherapy regimens. For OS, the combination of camrelizumab and chemotherapy demonstrated the highest probability (36.68%) of efficacy, fol-lowed by cemiplimab (33.86%) and atezolizumab plus chemotherapy (23.87%). Regarding PFS, the camrelizumab and chemotherapy combination had the highest probability (39.70%) of efficacy, followed by pembrolizumab (22.88%) and pembrolizumab plus chemotherapy (17.69%). Compared to chemotherapy, first-line treatment with immune checkpoint inhibitors (ICIs) in Sq-NSCLC pa-tients exhibited significant improvements in OS (HR 0.59, 95% CI 0.47-0.75) and PFS (HR 0.44, 95% CI 0.37-0.52). Conclusion: This study suggests that, for Sq-NSCLC patients with PD-L1 expression =50%, the first-line immunotherapy regimen of camrelizumab plus chemotherapy provides superior OS and PFS outcomes. Furthermore, ICIs demonstrate enhanced efficacy compared to chemotherapy in this patient population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of anlotinib-based treatment in metastatic breast cancer (MBC) patients with failure of standard treatment. Methods: We collected the medical data of 56 female patients with the diagnosis of MBC and had failed the standard treatment before. These patients received at least two cycles of anlotinib-based treatment as the second-line or beyond treatment between October 2019 and April 2022 in Jiangsu Cancer Hospital. The primary endpoint of our study was progression-free survival (PFS), and it was estimated with Kaplan-Meier. The second end points were disease control rate (DCR), objective response rate (ORR), and side effects. Results: The median PFS time of a total of 56 patients was 5.7 months (95% CI, 3.17-8.23 months). The ORR and DCR was 28.6% and 71.4%, respectively. In second-line, third-line, and beyond treatment, the median PFS was 11.7 months, 8.7 months, and 4.7 months, respectively. In different subtype of breast cancer, the median PFS was 5.6 months, 5.7months, and 6.4 months in human epidermal growth factor receptor 2 positive (HER2+), hormone receptor positive and HER2 negative (HR+/HER2-), and triple negative breast cancer (TNBC) patients, respectively. Most adverse effects were clinically manageable, and the most common events were platelet count decrease (35.7%), hand-foot syndrome (19.6%), diarrhea (19.6%), and fatigue (17.9%). The most common grade 3 and 4 adverse events were platelet count decrease (10.7%), diarrhea (7.1%), and oral mucositis (5.4%). Conclusion: Anlotinib-based treatment showed good efficacy and manageable toxicity in multi-line treatment of MBC patients who failed the standard treatment. [ABSTRACT FROM AUTHOR]