ABSTRACT
AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/chemically induced , Helicobacter Infections/drug therapy , Amoxicillin , Proton Pump Inhibitors/adverse effects , Clarithromycin/pharmacology , Esomeprazole , Bismuth/pharmacology , Bismuth/therapeutic use , Prospective Studies , Drug Therapy, Combination , Anti-Bacterial Agents , China , Treatment OutcomeABSTRACT
5-Fluorouracil (5-FU) is a common chemotherapy drug for patients with advanced colorectal cancer; however, many patients develop resistance to 5-FU and suffer from treatment failure. Discoidin domain receptor 1 (DDR1) is upregulated in multiple cancers and positively associated with chemoresistance. We explored the effect of DDR1a on the cytotoxicity induced by 5-FU in LoVo cells and the underlying mechanism. Therefore, DDR1a overexpression (DDR1ahigh) and knockdown in LoVo cell lines (shDDR1a) were constructed to detect cell viability and cytotoxicity induced by 5-FU. The results showed that cell viability of DDR1ahigh cells was higher in comparison with that of the control group. When 5-FU (5 µM) was administered, the percentage of apoptotic cells, cytochrome C release and caspase-3 activity was found to be higher in the shDDR1a group than that in the control group. Both of PI3K and MDM2 proteins level decreased in DDR1ahigh and shDDR1a, but the BAX/Bcl-2 level in the shDDR1a group increased compared to that in the control. Therefore, DDR1a might be a potential therapeutic target for 5-FU chemoresistance in colorectal cancer.
Subject(s)
Colorectal Neoplasms , Phosphatidylinositol 3-Kinases , Apoptosis/genetics , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Discoidin Domain Receptor 1/genetics , Discoidin Domain Receptors , Drug Resistance, Neoplasm/genetics , Fluorouracil/pharmacology , Humans , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
OBJECTIVE: To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients. METHODS: The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves. RESULTS: Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival. CONCLUSION: The proposed nomogram is accurate in predicting the prognosis of patients with MM.