Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.
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PMID:Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery. 2743

Docetaxel, cisplatin and 5-fluorouracil (DCF regimen) are currently applied as an effective combination treatment for various human malignancies; however, the efficacy of this regimen is impaired by severe adverse events associated with it. Therefore, better-tolerated regimens with comparable efficiency are required for patients with gastric cancer. To explore such possibilities, a phase-I clinical trial was performed to evaluate the safety and tolerability of a modified regimen replacing cisplatin and 5-fluorouracil with oxaliplatin and capecitabine, respectively (DOX program). The maximum-tolerated dose (MTD) and dose-limited toxicity (DLT) of capecitabine in this regimen were determined and a dose for subsequent phase-II clinical trials was identified. A total of 24 patients with advanced gastric cancer were sequentially enrolled in the present capecitabine dose-escalation trial. The patients were treated with docetaxel and oxaliplatin at fixed doses [75 and 100 mg/m2, respectively, intravenously, on day 1 (d1)], and with capecitabine at increasing doses (1,500, 2,000 and 2,500 mg/m2, per os, d1-7). The MTD of capecitabine was 2,000 mg/m2 (d1-7), repeated every 21 days for at least two cycles. The most frequent DLTs for this regimen were leukopenia (15/24, 62.5%, all at grade-III/IV) and neutropenia (13/24, 54.2%, all at grade-III/IV), nausea (14/24, 58.3%, all at grade-III) and vomiting (13/24, 54.2%, all at grade-III). The effective rate of the DOX regimen was 75.0% (18/24). Based on the results, the combination of docetaxel (75 mg/m2, d1), oxaliplatin (100 mg/m2, d1) and capecitabine (2,000 mg/m2, d1-7) is recommended for a future phase-II trial. While these doses for the DOX regimen were generally well tolerated, the efficacy of this modified regimen in patients with advanced gastric cancer remains to be further evaluated in subsequent phase-II trials.
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PMID:Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial. 2841 80

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.
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PMID:Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats. 2921 Feb 93

Gastric cancer is a prevalent cancer and chemotherapy is a main treatment for patients. Docetaxel is commonly used as a chemotherapeutic drug for gastric cancer patients. With the increasing emergence of docetaxel resistance, exploring the mechanism of chemoresistance may improve prognosis of patients. In this study, we found that overexpressed miR-361-5p suppressed chemoresistance to docetaxel of gastric cancer cells (SGC-7901, MKN-28) by decreasing IC50 values of docetaxel while increasing cell apoptosis rate, especially in docetaxel resistant SGC-7901 cells. Further researches revealed that overexpressed miR-361-5p inhibited chemoresistance through inhibiting autophagy with a characteristic of declined number of LC3+ puncta, decreased expression of Beclin-1 and the ratio of LC3 II/I and increased expression of p62. Bioinformatics study and Luciferase reporter assay indicated that FOXM1 was a target of miR-361-5p and FOXM1 was negatively regulated by miR-361-5p in gastric cancer. Simultaneously, overexpression of FOXM1 counteracted the inhibitory effects of miR-361-5p on chemoresistance of gastric cancer cells through activating autophagy, further certifying the targeting relationship between the two. Moreover, overexpressed miR-361-5p activated the PI3K/Akt/mTOR pathway. The adding of PI3K inhibitor LY294002 played an opposite role to miR-361-5p mimic by inducing autophagy and chemoresistance to docetaxel of gastric cancer cells compared with docetaxel + miR-361-5p mimic group, indicating that miR-361-5p suppressed autophagy-induced chemoresistance via the PI3K/Akt/mTOR pathway in gastric cancer cells. In conclusion, we found that miR-361-5p suppressed autophagy-induced chemoresistance of gastric cancer cells through targeting FOXM1 via the PI3K/Akt/mTOR pathway, providing a foundation for the mechanism research and treatment of gastric cancer.
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PMID:MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. 2943 49

The National Comprehensive Cancer Network (NCCN) issued the clinical practice guidelines for gastric cancer 2017 edition version 5, which has been fully updated for the treatment of gastric cancer, including systematic treatment, surgery and radiotherapy. This article review and summarize the updated NCCN clinical practice guidelines for gastric cancer in 2017 and try to interpret it. (1)Biomarkers: mismatch repair defect (dMMR) or high microsatellite instability (MSI-H), programmed death ligand 1 (PD-L1) and tumor Epstein Barr virus (EBV) status should be considered for patients with gastric cancer. (2)Treatment of advanced gastric cancer: the major update is the application of immunotherapy (Pembrolizumab, Nivolumab combined with Ipilimumab). (3)Adjuvant therapy after D2 resection and perioperative treatment: the guidelines recommended Capecitabine combined with Oxaliplatin as adjuvant therapy after radical operation, updated from category 2A to 1; although the 2017 edition of the NCCN guidelines have not yet been adopted, Docetaxel-based FLOT scheme has certain potential in adjuvant therapy for gastric cancer. (4) Radiotherapy: a more detailed definition of radiotherapy for gastric cancer in different locations, especially in high-risk lymphatic drainage areas, was updated. (5) Genetic risk assessment: the guidelines recommended genetic screening for gastric cancer, including hereditary diffuse gastric cancer (HDGC), Lynch syndrome, juvenile polyposis (JPS), Peutz-Jephers syndrome (PJS) and familial adenomatous polyposis (FAP). The NCCN guidelines continue to update based on new evidences, which is the embodiment of precision medicine in the treatment of gastric cancer. The biggest change in the 2017 gastric cancer guidelines is the updates of immunotherapy, which also suggests that the direction of the gastric cancer treatment began to turn to immunotherapy.
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PMID:[Updates and interpretation on NCCN clinical practice guidelines for gastric cancer 2017 version 5]. 2949 14

Docetaxel (TXT) is acknowledged as one of the most important chemotherapy agents for gastric cancer (GC). PI3K/AKT signaling is frequently activated in GC, and its inhibitor LY294002 exerts potent antitumor effects. However, the hydrophobicity of TXT and the poor solubility and low bioavailability of LY294002 limit their clinical application. To overcome these shortcomings, we developed poly(lactic acid/glycolic) (PLGA) nanoparticles loaded with TXT and LY294002. PLGA facilitated the accumulation of TXT and LY294002 at the tumor sites. The in vitro functional results showed that PLGA(TXT+LY294002) exhibited controlled-release and resulted in a markedly reduced proliferative capacity and an elevated apoptosis rate. An in vivo orthotopic GC mouse model and xenograft mouse model confirmed the anticancer superiority and tumor-targeting feature of PLGA(TXT+LY294002). Histological analysis indicated that PLGA(TXT+LY294002) was biocompatible and had no toxicity to major organs. Characterized by the combined slow release of TXT and LY294002, this novel PLGA-based TXT/LY294002 drug delivery system provides controlled release and tumor targeting and is safe, shedding light on the future of targeted therapy against GC.
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PMID:PLGA nanoparticle-based docetaxel/LY294002 drug delivery system enhances antitumor activities against gastric cancer. 3095 95

Introduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC. Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3-4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets. Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218-0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215-3.504) in patients without lymph node metastasis. Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.
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PMID:Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) as preoperative and postoperative chemotherapy compared with surgery followed by chemotherapy for patients with locally advanced gastric cancer: a propensity score-based analysis. 3111 48

Gastric cancer is the fourth common cancer and the second leading cause of cancer death worldwide. Due to lack of adequate information on the side effects of chemotherapy regimens in treatment of gastric cancer, this study was aimed to determine the side effects of two common chemotherapy regimens of gastric cancer. This prospective study was conducted in Emam Khomeini Educational Hospital and Touba Polyclinic; both are affiliated to Mazandaran University of Medical Sciences. The frequency and severity of side effects of chemotherapy were recorded based on the National Cancer Institution (NCI) Toxicity Criteria (version 2). DCF (Docetaxel, Cisplatin, 5FU) and FOLFOX (Folinic acid, 5FU, Oxaliplatin) adverse reactions were compared using SPSS 16 software. One hundred twenty five chemotherapy cycles administered to seventy four patients were assessed. The most common used regimens were DCF (70%) and FOLFOX (16%). The incidence of vomiting was higher with DCF compared to FOLFOX (P = 0.049). In more than 50% of cycles, DCF regimen caused diarrhea, while in FOLFOX regimen it was less than 9% (P = 0.002). Stomatitis, visual changes, nausea, skin reactions, and constipation were not significantly different between the two regimens. It seems that the adverse drug reactions of FOLFOX regimen were more favorable than DCF regimen. The results of this study may help clinicians choosing a more favorable chemotherapy regimen especially in patients with a low performance status who have difficulties in tolerating a chemotherapy regimen with a more severe adverse effect profile.
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PMID:Comparison the Incidence and Severity of Side Effects Profile Of FOLFOX and DCF Regimens in Gastric Cancer Patients. 3153 Oct 83

Three-dimensional (3D) cell culture is more similar to in vivo studies and suitable for studies of interactions between cells and extracellular matrix. CD44 is a cell surface receptor that can relate with the extracellular matrix molecules. CD44 in gastric cancer (GC) is a metastatic and drug resistance marker. In this study the quantity of CD44+ cells in MKN-45 cell line in response to half maximal inhibitory concentration (IC50) dose of Docetaxel (DOC) was measured in 2D and 3D cultures. MKN-45 cell line was cultured in 2D and 3D environments. For 3D culture, rat gastric tissue was separated and decellularized and MKN-45 cells were injected and cultured in the prepared matrix. The frequency of CD44+ cells in 2D and 3D cultures were analyzed before and after treatment with IC50 of DOC by flow cytometry and immunohistochemistry. Despite different environmental conditions, The frequency of CD44+ cells increased significantly in 2D and 3D environments after treatment with IC50 of DOC (P < 0.05). Given the advantages of 3D, this environment seems more appropriate for study about CD44+ cells and drug resistance in GC.
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PMID:Frequency of CD44 positive cells in MKN45 cell line after treatment with docetaxel in two and three-dimensional cell cultures. 3222 52

Recent focus has turned to secretory clusterin (sCLU) as a key contributor to chemoresistance of anticancer agents, but the role of sCLU on chemotherapy drug response to gastric cancer cells is not fully understood. Previous research found that sCLU was overexpressed in the induced multidrug-resistant MGC-803/5-FU cell line, suggesting that sCLU upregulation was closely related to chemoresistance to anticancer agents. In the present study, we aimed to clarify the role and mechanisms of sCLU in regulating the chemoresistance of gastric cancer cells. Cell apoptosis and cell viability were evaluated by annexin V/propidium iodide staining and CCK8. Expression of sCLU and miR-195-5P was detected using quantitative RT-PCR assays. The expression of sCLU in gastric cancer tissues was detected by RT-PCR assays. Upregulating or downregulating sCLU or miR-195-5P in gastric cancer cells was used to evaluate the mechanisms of chemoresistance. We found that sCLU was significantly elevated in the MGC-803/5-FU and SGC-7901 cells, and the downregulating sCLU sensitized MGC-803/5-FU and SGC-7901 cells to cisplatin and Docetaxel by upregulation of miR-195-5P. Upregulating sCLU in MGC-803 and HGC-27 cells was resistant to cisplatin and Docetaxel by downregulating miR-195-5p. Targeting miR-195-5P reduced the sensitivity of MGC-803 cells to 5-FU, and miR-195-5P overexpression enhanced the sensitivity of MGC-803/5-FU cells to 5-FU. The overexpression of sCLU in gastric cancer tissues was associated with chemoresistance. Our findings suggest that overexpression of sCLU induced chemoresistance in gastric cancer cells by downregulating miR-195-5p, thus providing a potential target for the development of agents that targeting sCLU for gastric cancer therapy.
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PMID:Overexpression of secretory clusterin (sCLU) induces chemotherapy resistance in human gastric cancer cells by targeting miR-195-5p. 3225 Jan 92


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