Kragcantrell3880

001) or KRAS codon 12 mutations (P = 0.003). Conclusions In KRAS-mutated CRC, exon 3 mutations predict the worst prognosis, while exon 4 mutations predict the best prognosis. Among KRAS exon 2 mutated patients, codon 13 mutations predict worse prognosis than codon 12 mutations. Mutations of different KRAS exons should be analyzed separately.Hepatocellular carcinoma (HCC) is one of the most common solid tumors globally. Our previous studies revealed that miR-627-5p suppresses HCC progression via targeting BCL3/CCND1 pathway. However, the molecular mechanism by which miR-627-5p was downregulated in HCC remains to be further elucidated. As a hallmark of solid tumors, hypoxia results in the rapid growth, strongly potential invasion and high frequent metastasis of cancer cells. Hypoxia-inducible factors (HIFs), mainly including HIF-1 and HIF-2, are the classical transcription factors which mediate hypoxia-related gene transcription. Here, we demonstrated that miR-627-5p was repressed by hypoxia in a HIF-1-dependent manner in HCC cells. But HIF-1 regulated miR-627-5p expression not directly through the hypoxia-response element (HRE) sites of MIR627 gene. In contrast, histone deacetylase 3 (HDAC3) was identified as a HIF-1 target gene, and the occupancy of HIF-1 to HRE site was essential for hypoxia-mediated HDAC3 induction. click here And upregulated HDAC3 was closely related to the malignant clinical and pathological characteristics and worse prognosis of HCC. Furthermore, HDAC3-mediated histone deacetylation in promoter region of MIR627 was critical for hypoxia-mediated miR-627-5p repression. And miR-627-5p mediated the effects of hypoxic condition on HCC progression. Thus, this study has revealed that miR-627-5p was repressed by hypoxia under the mediation of HDAC3 in HCC, and there existed a HIF-1α/HDAC3/miR-627-5p/BCL3/CCND1 signal pathway in HCC.Gefitinib has shown good efficacy in treating recurrent or advanced non-small cell lung cancer (NSCLC), but the drug resistance remains a clinical challenge in medical oncology. In addition, the complex interaction between tumor cells and heterogeneous stromal cells in the adjacent tumor microenvironment (TME) is also an important contributor to drug resistance. So, it is very necessary to detect the related target genes before and after gefitinib treatment dynamically. In this study, the relationship between Trop2 and gefitinib resistance in NSCLC was investigated, and the underlying mechanism was explored. Results showed that Trop2 was associated with EGFR gene mutation and drug resistance in clinical tissues. Trop2 was confirmed to induce gefitinib resistance in NSCLC, and Trop2 binding IGF2R promoted the IGF2-IGF1R-Akt axis to enhance gefitinib resistance and remodeling the TME in NSCLC. Notably, silencing of Trop2 in cancer cells combined with IGF1R inhibitor significantly decreased the proliferation of tumor cells and reshaped the NSCLC TME in vivo and in vitro, including the recruitment of macrophages. These findings deepened the understanding of the function of Trop2 and the involved mechanisms of gefitinib resistance, and may provide new molecular targets for NSCLC with gefitinib resistance.Non-coding microRNAs (miRNAs) have been proposed to play diverse roles in cancer biology, including epithelial-mesenchymal transition (EMT) crucial for cancer progression. Previous comparative studies revealed distinct expression profiles of miRNAs relevant to tumorigenesis and progression of oral cancer. With putative targets of these miRNAs mostly validated in vitro, it remains unclear whether similar miRNA-target relationships exist in vivo. In this study, we employed a hybrid approach, utilizing both Drosophila melanogaster and human oral cancer cells, to validate projected miRNA-target relationships relevant to EMT. Notably, overexpression of dme-miR-133 resulted in significant tissue growth in Drosophila larval wing discs. The RT-PCR analysis successfully validated a subset of its putative targets, including Pde1c. Subsequent experiments performed in oral cancer cells confirmed conserved targeting of human PDE1C by hsa-miR-133. Furthermore, the elevated level of miR-133 and its targeting of PDE1C was positively correlated with enhanced migrative ability of oral cancer cells treated with LPS, along with the molecular signature of a facilitated EMT process induced by LPS and TGF-β. The analysis on the RNAseq data also revealed a negative correlation between the expression level of hsa-miR-133 and the survival of oral cancer patients. Taken together, our mammal-to-Drosophila-to-mammal approach successfully validates targeting of PDE1C by miR-133 both in vivo and in vitro, underlying the promoted EMT phenotypes and potentially influencing the prognosis of oral cancer patients. This hybrid approach will further aid to widen our scope in investigation of intractable human malignancies, including oral cancer.Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protetial therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.Objective This retrospective study analyzed the factors affecting recurrence in patients after surgery with borderline ovarian tumors and postoperative recurrence and pregnancy after fertility-sparing surgery (FSS), to provide guidance for clinical treatment of borderline ovarian tumors and propose a therapeutic strategy for fertility protection. Methods A total of 415 patients with borderline ovarian tumors were initially operated on in the gynecology ward of Shengjing Hospital Affiliated with China Medical University from September 1, 2013, to September 1, 2019. Central pathology review and prospective follow-up were carried out. The clinical and pathological data were consulted through the medical record query system of our hospital. The recurrence and pregnancy of the patients were investigated through telephone follow-up and outpatient and inpatient medical records. The influence of clinical and pathological variables on recurrence and pregnancy were evaluated using univariate/multivariate analyses. Resuperation. Adjuvant chemotherapy does not reduce the recurrence rate. While omentectomy and chemotherapy had an impact on the pregnancy rate, and both of them should be carried out more carefully in patients with fertility requirements.To evaluate the clinical efficacy of continuing cetuximab vs bevacizumab plus chemotherapy crossover after first progression to cetuximab regimen in wild-type KRAS, NRAS and BRAF V600E mCRC, we conducted this prospective, open-label and randomized phase 2 trial in three cancer centers from Oct 1, 2016 to July 1, 2020. Eligibility criteria included documented progressive disease during or after first-line treatment with cetuximab regimen; second biopsy confirmed as KRAS, NRAS and BRAF V600E wild-type mCRC. Patients were randomized to arm A (cetuximab+chemo) or arm B (bevacizumab+chemo) with second-line chemotherapy crossover. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), overall survival (OS) and toxicity. Tissue VEGFA, ERBB2 and MET mRNA were examined by real time RT-PCR. A total of 104 patients (53 in arm A and 51 in arm B) were enrolled. Median PFS was 7.7 months (95% CI 6.5-8.9) for arm A and 6.3 months (95% CI 4.5-8.1) for arm B (p=0.931). Median OS was 18.2 months (95% CI 14.5-21.9) for arm A and 16.4 months (95% CI 14.2-18.6) for arm B (p=0.339). The ORR was 28.3% and 19.6% in arm A and arm B (p=0.31), respectively. MET mRNA was highly expressed in the cetuximab-progressed tumors, but treatment responsiveness to cetuximab or bevacizumab in each arm was not correlated with the MET expression level. The results showed no significant difference in PFS, OS and ORR between the two arms, but a trend in favor of the cetuximab continuation plus chemotherapy crossover was examined in all end points. High expression of MET in cetuximab-progressed tumors may indicate an existence of MET-dependent tumor cell population.Objective To validate and compare the predictive ability of albumin-bilirubin model (ALBI) with other 5 liver functional reserve models (APRI, FIB4, MELD, PALBI, King's score) for posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) who underwent major hepatectomy. Methods Data of patients undergoing major hepatectomy for HCC from 4 hospitals between January 01, 2008 and December 31, 2019 were retrospectively analyzed. PHLF was evaluated according to the definition of the 50-50 criteria. Performances of six liver functional reserve models were determined by the area under the receiver operating characteristic curve (AUC), calibration plot and decision curve analysis. Results A total of 745 patients with 103 (13.8%) experienced PHLF were finally included in this study. Among six liver functional reserve models, ALBI showed the highest AUC (0.64, 95% CI 0.58-0.69) for PHLF. All models showed good calibration and greater net benefit than treating all patients at a limit range of threshold probabilities, but the ALBI demonstrated net benefit across the largest range of threshold probabilities. Subgroup analysis also showed ALBI had good predictive performance in cirrhotic (AUC=0.63) or non-cirrhotic (AUC=0.62) patients. Conclusion Among the six models, the ALBI model shows more accurate predictive ability for PHLF in HCC patients undergoing major hepatectomy, regardless of having cirrhosis or not.In the present study, quercetin was examined against lung human cancer cells using A549 and H69 cancer cell lines in addition to normal non cancer cells (W138). Two genes Bax and Bcl-2 that play an important role in apoptosis pathways were investigated. Also Immunohistochemical study for caspase-3 which is considered as indicator for apoptosis was performed. Quercetin showed good anti proliferative activity against tested lung cancer cell lines, IC50 values on A549 are 8.65, 7.96 and 5.14 µg/ml at 24, 48 and 72h respectively. Also significant effects of quercetin on Bax, Bcl-2 and caspase-3 were observed, that can prove its ability to induce apoptosis. On the other hand quercetin showed good therapeutic effects against cyclophosphamide induced lung toxicity that were observed in the histopathology study. In vitro studies were also performed such as cell cycle analysis through flowcytometry. The obtained results from all these performed analysis proved that quercetin can induce apoptosis in human lung cancer cells, additionally quercetin showed ability to reduce MDA and increase SOD and GSHP levels which indicates its ability in suppressing oxidative stress, Quercetin has played a therapeutic role in cyclophosphamide induced lung toxicity as it has improved restoring of the damaged lung tissue as discussed in this research work.