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1.
China Pharmacy ; (12): 622-627, 2022.
Article in Chinese | WPRIM | ID: wpr-920735

ABSTRACT

OBJECTIVE To reevaluate the system atic evaluation of g emcitabine combined with cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC),in order to provide evidence-based evidence for the treatment of NSCLC. METHODS Retrieved from Wanfang database ,CNKI,VIP,PubMed,Embase,systematic evaluation of gemcitabine combined with cisplatin versus pemetrexed/vinorelbine combined with cisplatin in the treatment of advanced NSCLC was included from the inception to Dec. 2021. RevMan 5.3 system evaluation software was used for meta-analysis of various outcome indicators ; AMSTAR2 scale was used for methodological quality evaluation ,and GRADE tool was used for evidence quality evaluation. RESULTS A total of 9 literatures were included. Meta-analysis showed that the effective rate of gemcitabine combined with cisplatin was significantly lower than pemetrexed combined with cisplatin ,but was similar to vinorelbine combined with cisplatin. The 1-year survival rate of gemcitabine combined with cisplatin was equivalent to that of pemetrexed combined with cisplatin ,but was superior to vinorelbine combined with cisplatin. There was no significant difference in the incidence of nausea and vomiting between gemcitabine combined with cisplatin and pemetrexed/vinorelbine combined with cisplatin. Gemcitabine combined with cisplatin had a higher incidence of thrombocytopenia than pemetrexed/vinorelbine combined with cisplatin. The incidence of neutropenia and leukopenia in gemcitabine combined with cisplatin were higher than pemetrexed combined with cisplatin ,but were significantly lower than vinorelbine combined with cisplatin. The evaluation results of AMSTAR 2 scale showed that 6 systematic evaluation were of low quality in methodology and 3 were of very low quality. The results of the GRADE tool showed that 31% of the outcome indicators were of medium quality (14 items),27% were of low quality (12 items),and 42% were of very low quality(19 items). Research limitations and publication bias were the most frequently downgraded factors. CONCLUSIONS Gemcitabine combined with cisplatin has advantages over 154854280@qq.com vinorelbine combined with cisplatin in the efficacy and safety of ad vanced NSCLC ,especially in the 1-year survival rate ,the incidence of neutropenia and leucopenia. The efficacy and safety of gemcitabine combined with cisplatin are inferior to those of pemetrexed combined with cisplatin. However ,the methodological quality and evidence level of systematic evaluation are not high on the whole ,and the overall quality of research needs to be improved.

2.
Clinical Medicine of China ; (12): 129-134, 2022.
Article in Chinese | WPRIM | ID: wpr-932157

ABSTRACT

Objective:To investigate the effect of different chemotherapy drugs combined with DNA methylase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) on the apoptosis of lung adenocarcinoma cells.Methods:In the prospective randomized controlled study, lung adenocarcinoma A549 cells were treated with cisplatin plus paclitaxel (TP) or gemcitabine (GP) with or without 5-Aza-dC. According to different drug intervention methods, they were divided into control group, cisplatin combined with paclitaxel (TP) group, cisplatin combined with gemcitabine (GP) group, and 5-Aza-dC combined with TP group, 5-Aza-dC combined with GP group. CCK-8 assay was used to detect the proliferation of A549 cells. Transwell migration and invasion assay were used to detect the effect that each group of drugs on the migration and invasion ability of A549 cells. Quantitative Real-time Polymerase Chain Reaction was used to evaluate the effect of each treatment on the expression of apoptotic genes. One-way analysis of variance was used to compare the degree of cell proliferation in different drug treatment groups, and LSD- t method was used for pairwise comparison within groups. Results:The inhibition rates of lung adenocarcinoma cells in the TP regimen at different time points at 24, 48, and 72 h were as follows (20.00±4.23) %, (35.00±2.80) %, and (56.00±3.11) %. The inhibition rate of 5-Aza-dC combined with TP regimen on lung adenocarcinoma cells was significantly increased, at different time points of 24, 48 and 72 h, respectively (38.00±3.80) %, (50.00±3.25) %, (93.00±4.33) %. The inhibition rates of cells at different time points at 24, 48, and 72 h in the GP regimen were (33.00±5.10) %, (54.00±3.80) %, and (74.00±2.82) %, respectively; while 5-Aza-dC combined with GP regimen could significantly reduce the rate of cell growth, the inhibition rates of cells at 24, 48, and 72 h different time points were as follows (54.00±3.00) %, (67.00±5.30) %, and (95.00±1.13) %. The inhibitory effect of the same drug on lung adenocarcinoma cells increased with time (TP group: F=35.93, P<0.001; 5-Aza-dC combined with TP group: F=97.33, P<0.001; GP group: F =41.73, P<0.001; 5-Aza-dC combined with GP group: F=79.00, P<0.001), and at different time points, the differences were statistically different (all P<0.05). 5-Aza-dC combined with TP and GP chemotherapy regimens can inhibit the migration and invasion of lung adenocarcinoma cell A549, and the inhibitory effect is stronger than that of TP or GP regimens alone. The expression of Caspase 8 was significantly elevated ( t=5.87, P=0.004) in cells treated with 5-Aza-dC combined with GP when compared with GP regimen alone. The expression of Caspase 8 ( t=3.94, P=0.017), Caspase 6 ( t=5.81, P=0.004) and BBC3 (BCL-2 binding component 3) ( t=6.53, P=0.003) were increased when drugged with 5-Aza-dC combined TP regimen compared with TP regimen alone. Conclusion:5-Aza-dC might serve as a chemotherapeutic sensitizer to increase the sensitivity of lung adenocarcinoma cells.

3.
Article in Chinese | WPRIM | ID: wpr-930530

ABSTRACT

Objective:To investigate the efficacy of anti-CD 20 monoclonal antibody in combination with Gemcitabine-based chemotherapy regimen in children with recurrent diffuse large B-cell lymphoma (DLBCL). Methods:The clinical data of 62 children with DLBCL admitted to the Department of Pediatrics, Yantai Mountain Hospital of Yantai City and the Department of Pediatrics, Muping District Traditional Chinese Medicine Hospital in Yantai City from January 2010 to January 2018 were analyzed retrospectively.Different treatment options were selected according to the children′s stage and the presence of risk factors such as huge tumors.Among them, 32 cases in the control group were treated with the Gemcitabine-based treatment plan (Gemcitabine+ Cisplatin+ Dexamethasone treatment). Thirty patients in the study group were treated with anti-CD 20 monoclonal antibody on the basis of the control group for a total of 4 cycles (21 d per cycle). After 4 cycles of treatment, the clinical efficacy, the positive expression of forkhead box protein P1 (FOXP1) and B-cell lymphoma factor-6 (Bcl-6) before and after treatment, the occurrence of adverse reactions and survival[3-year progression-free survival (PFS), 3-year overall survival (OS)] were evaluated.The measurement data that meets the normal distribution is expressed that the t test is used, and the counting data is represented by (%), and the χ2 test is used.Level data is compared with ranking and inspection. Results:All patients were followed up to March 2021.The total response rate (RR) and disease control rate (DCR) of the study group were 93.33% (28/30 cases) and 96.67% (29/30 cases), respectively.The RR and DCR of the control group were 68.75% (22/32 cases) and 81.25% (26/32 cases), respectively.The RR of the study group was higher than that of the control group ( χ2=5.995, P<0.05), and there was no statistical difference in DCR between the two groups ( χ2=3.674, P>0.05). After treatment, the positive expression rate of FOXP1 in the study group and the control group was lower than before treatment[23.33% (7/30 cases) vs. 76.67% (23/30 cases); 50.00% (16/32 cases) vs. 75.00% (24/32 cases), χ2=17.067, 4.267, all P<0.05], and the positive expression rate of the study group was lower than that of the control group ( χ2=4.179, P<0.05). After treatment, the positive expression rate of Bcl-6 in the study group and the control group was higher than before treatment[86.67% (26/30 cases) vs. 26.67% (8/30 cases); 62.50% (20/32 cases) vs. 31.25% (10/32 cases), χ2=21.991, 6.275, all P<0.05], and the positive expression rate of the study group was higher than that of the control group ( χ2=4.723, P<0.05). There was no significant difference between the study group and the control group in the level of gastrointestinal reactions, elevated transa-minase, and decreased white blood cell ( Z=-1.074, -1.078, -0.834, all P>0.05). There was a difference between the 3-year PFS survival curve and the 3-year OS survival curve between the two groups ( χ2=3.997, 4.723, all P<0.05). Conclusions:Anti-CD 20 monoclonal antibody combined with Gemcitabine-based chemotherapy is effective for children with DLBCL, and will not significantly increase the adverse reactions in children.

4.
Acta Pharmaceutica Sinica B ; (6): 1339-1350, 2022.
Article in English | WPRIM | ID: wpr-929373

ABSTRACT

DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins. Mechanistically, shikonin inhibited the activation of ataxia telangiectasia mutated (ATM), and to a lesser degree ATM and RAD3-related (ATR), two master upstream regulators of the DDR signal, through inducing degradation of ATM and ATR-interacting protein (ATRIP), an obligate associating protein of ATR, respectively. As a result of DDR inhibition, shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models. While degradation of ATRIP is proteasome dependent, that of ATM depends on caspase- and lysosome-, but not proteasome. Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs. These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin. Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

5.
Acta Pharmaceutica Sinica B ; (6): 1148-1162, 2022.
Article in English | WPRIM | ID: wpr-929354

ABSTRACT

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

6.
Acta Pharmaceutica Sinica B ; (6): 451-466, 2022.
Article in English | WPRIM | ID: wpr-929306

ABSTRACT

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

7.
Article in Chinese | WPRIM | ID: wpr-906148

ABSTRACT

Objective:To explore the application value of modified Buzhong Yiqitang (BZYQT) in the treatment of postoperative patients with non-small cell lung cancer (Qi deficiency in lung and spleen) after chemotherapy, and to observe its effect on tumor angiogenesis, immune function, tumor indicators, and lung function indicators. Method:Ninety-six patients who were treated in the Kunming municipal hospital of traditional Chinese medicine from March 2018 to February 2020 due to postoperative chemotherapy for non-small cell lung cancer were selected and assigned into a control group (<italic>n</italic>=48, western medicine) and an observation group (<italic>n</italic>=48, western medicine+modified BZYQT) by the random number table. The curative efficacies were compared after the treatment. Result:After treatment, the serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), serum insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor(TGF)-<italic>β</italic><sub>1</sub> in the observation group were lower than those in the control group (<italic>P</italic><0.05), while the serum CD4<sup>+</sup>/CD8<sup>+</sup>,CD4<sup>+</sup> cells, immunoglobulin G (IgG) levels, forced expiratory volume in one second (FEV<sub>1</sub>),and FEV<sub>1</sub>/forced vital capacity (FVC) in the observation group were higher than those in the control group (<italic>P</italic><0.05). A significant difference was observed in the total response rate between the observation group [56.25% (27/48)] and the control group [35.42% (17/48)] (<italic>χ</italic><sup>2</sup>=4.191,<italic>P</italic><0.05). For adverse reactions,the incidence of bone marrow suppression(<italic>χ</italic><sup>2</sup>=4.002), gastrointestinal reaction (<italic>χ</italic><sup>2</sup>=7.069),and hepatic and renal injury (<italic>χ</italic><sup>2</sup>=5.151) was lower in the observation group than in the control group (<italic>P</italic><0.05). Conclusion:For postoperative patients with non-small cell lung cancer (Qi deficiency in lung and spleen) after chemotherapy, western medicine combined with modified BZYQT could ameliorate immune function, promote pulmonary function recovery, improve clinical efficacy, and reduce the incidence of adverse reactions.

8.
Acta Pharmaceutica Sinica ; (12): 1988-1998, 2021.
Article in Chinese | WPRIM | ID: wpr-887013

ABSTRACT

Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.

9.
Acta Pharmaceutica Sinica B ; (6): 55-70, 2021.
Article in English | WPRIM | ID: wpr-881124

ABSTRACT

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.

10.
International Journal of Surgery ; (12): 590-595, 2021.
Article in Chinese | WPRIM | ID: wpr-907487

ABSTRACT

Objective:To investigate the clinical outcomes of neoadjuvant chemotherapy with Gemcitabine and Cisplatin (GC) for muscle-invasive bladder cancer (MIBC).Methods:Retrospective analysis of 67 MIBC patients admitted to Beijing Friendship Hospital, Capital Medical University from December 2010 to June 2020. Fifty-five MIBC patients (cT2-T4aN0M0) underwent GC plus radical cystectomy-pelvic lymph node dissection. Pathological responses, prognosis and chemotherapy toxicities were analyzed. The Chi-square test and Fisher′s exact probability method were used to compare the count data between groups. The overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier survival curve, and the Log-rank test was used to evaluate the difference between groups in the survival curve. Prognostic analysis adopts Cox proportional hazards regression model.Results:Fifty-five MIBC patients received GC plus radical cystectomy-pelvic lymph node dissection. The 81.8% patients ( n=45) received 2 cycles GC and 18.2% patients ( n=10) received 3 cycles. The complete pathological response (pT0N0M0) rate was 30.9% ( n=17) and partial response (pT 1/Tis/T aN 0M 0) rate was 10.9% ( n=6). Overall pathological response rate was 41.8%. The median follow-up was (47.0±37.7) months, 5-year OS were 82.2% and 22.1% (<pT 2 versus ≥pT 2, P<0.001), and DFS were 86.1% and 32.1% (<pT 2 versus ≥pT 2, P<0.001). Pathological response and positive lymph nodes were independent risk factors of overall survival and disease-free survival on multivariable analysis ( P<0.05). The most common chemotherapy toxicities were hematologic toxicities and gastrointestinal reactions, and none delayed surgery due to toxicities. Conclusion:Neoadjuvant GC plus radical cystectomy-pelvic lymph node dissection has a significant clinical benefit in MIBC patents and chemotherapy toxicities are well tolerated.

11.
Article in Chinese | WPRIM | ID: wpr-817811

ABSTRACT

Objective Based on the data of gemcitabine adverse reactions (ADR), the characteristics and patterns of ADR occurrence were analyzed. The guidance for the rational clinical use of gemcitabine was provided. Methods From our information system, the patients treated by gemcitabine chemotherapy from September 2008 to September 2018 were selected and their related ADRs were summarized and statistically analyzed by using SPSS 18.0. Results Among the 750 cases, there were 312 ADRs related to gemcitabine treatment, of which the incidence of ADR was higher in female patients than in male patients (48.68% vs 36.77%) and the highest incidence in the age group of 50-69 years (44.14%). The patients with lower status (KPS) scores were more sensitive to chemotherapeutic drugs, and more likely to develop ADR. During the combination therapy, gemcitabine+paclitaxel chemotherapy had the highest incidence of ADR (61.54%) and the highest incidence of ADR in thymic carcinoma (62.50%), followed by hematological and reproductive system tumors (58.62% and 57.14%, respectively); ADR involvement in organs/systems is mainly caused by hematological toxicity. The bone marrow suppression is common, followed by digestive system damage. The major clinical symptoms were nausea and vomit. Conclusion Gemcitabine-related ADR has a large individualized difference and is affected by many factors. Chemotherapy should be used according to individual conditions to improve clinical safety and rational use of drugs.

12.
Article in Chinese | WPRIM | ID: wpr-865469

ABSTRACT

Objective To evaluate the clinical efficacy of gemcitabine plus cisplatin (GP) regimen and paclitaxel plus cisplatin (TP) regimen in the treatment of recurrent or metastatic nasopharyngeal carcinoma.Methods One hundred and thirty patients with recurrent or metastatic nasopharyngeal carcinoma of Qinhuangdao Harbor Hospital,Hebei Province between September 2012 and December 2017 were chosen,and were divided into GP group (68 cases) and TP group (62 cases)according to the selection of treatment.GP group was treated with GP regimen,and TP group was treated with TP regimen.The clinical efficacy and adverse reactions of the two groups were observed,and the serum epithelial cadherin (SE-CAD) and platelet-derived growth factor (PDGF-BB) were measured before and after chemotherapy.Results There was no significant difference in short-term efficacy between GP group and TP group (P>0.05),and the total effective rates were 88.24% (60/68) and 79.03% (49/62) respectively;1 month after treatment,SE-CAD in GP group and TP group were (2.57 ± 0.81) and (2.50 ± 0.96) g/L,PDGF-BB were (102.22 ± 31.18) and (110.15 ± 37.21) ng/L,and the difference was not statistically significant (P>0.05);progression-free survival (PFS) in GP group and TP group were 13 and 12 months,and overall survival (OS) were 17 and 16 months,and the difference was not statistically significant (P>0.05);there were no significant difference in leucopenia,hemoglobin,thrombocytopenia and abnormal liver and kidney function between GP group and TP group (P>0.05);the incidence of gastrointestinal reactions in GP group was 16.18% (11/68),which was significantly lower than that in TP group was 38.71%(24/62),and the difference was statistically significant (P<0.01).Conclusions GP and TP regimens are effective in the treatment of recurrent or metastatic nasopharyngeal carcinoma.There is no significant difference in SE-CAD and PDGF-BB levels between the two regimens after treatment,but GP regimen has a lower incidence of gastrointestinal reactions.

13.
Article in Chinese | WPRIM | ID: wpr-827805

ABSTRACT

To explore the effects of obatoclax(OBX) combined with gemcitabine(GEM) on breast cancer cells MCF-7 and BT-20 cell activity, migration, invasion and apoptosis under hypoxia condition. Breast cancer cells MCF-7 and BT-20 were divided into normal group, hypoxia group, GEM group, OBX+GEM group. Normal group: Cells were cultured at 37℃, 5% CO for 24 h and 48 h; Hypoxia group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N for 24 h and 48 h; GEM group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N, adding 10 μmol/L GEM for 24 h and 48 h; OBX + GEM group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N, adding 10 μmol/L GEM and 50 nmol/L OBX for 24 h and 48 h. Western blot method was used to detect the expressions of HIF-1α in MCF-7 and BT-20 cells under normal oxygen and hypoxia condition. CCK-8 method was used to detect cancer cell activity, each group was provided with 15 compound holes. Scratch experiment was used to detect cells migration ability, each group was provided with 6 compound holes. Western blot method was used to detect the expressions of vimentin, E-Cadherin and p53 protein in cells of each group. Under hypoxia condition, the expression of HIF-1α in MCF-7 and BT-20 cells was much higher than that under normal oxygen(P<0.05). Compared with hypoxia group, GEM could reduce MCF-7 and BT-20 cells migration ability(P<0.01)and cell activity(P<0.05), while decrease the expression of vimentin protein(P<0.01)and promote the expressions of E-Cadherin (P<0.01)and p53 protein(P<0.01) in tumor cells under hypoxia condition. In OBX combined with GEM group, the cell activity and the migration ability of MCF-7 and BT-20 were reduced significantly(P<0.01). The expression of vimentin in cells was further reduced(P<0.01). The expressions of E-Cadherin(P<0.01)and p53(P<0.01) protein were increased significantly compared with GEM group. Under hypoxia condition, OBX combined with a low-dose of GEM can significantly inhibit the growth, migration and invasion of breast cancer cells, and enhance the pro-apoptotic effect of GEM, but the specific mechanism needs further study.

14.
Article in Chinese | WPRIM | ID: wpr-880764

ABSTRACT

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.


Subject(s)
Animals , Bile Duct Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/genetics , Cytoskeletal Proteins , Heterografts , Humans , Imidazoles , Mice , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Pyridazines , Receptor, Fibroblast Growth Factor, Type 2 , Xenograft Model Antitumor Assays
15.
Article in Japanese | WPRIM | ID: wpr-826241

ABSTRACT

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p<0.05) in the GEM group, and manycases of nausea (p=0.08) and rash (p=0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.

16.
Journal of Clinical Hepatology ; (12): 153-157, 2020.
Article in Chinese | WPRIM | ID: wpr-780533

ABSTRACT

ObjectiveTo evaluate the clinical effect and safety of high-intensity focused ultrasound (HIFU) combined with gemcitabine in the treatment of advanced pancreatic cancer. MethodsSCI, Cochrane Library, Embase, PubMed, Wanfang Data, CNKI, CBM, and VIP were searched for randomized controlled trials (RCTs) of HIFU combined with gemcitabine in the treatment of advanced pancreatic cancer, with the assistance of expanded search, and these RCTs were screened according to the inclusion criteria. Review Manager 5.3 was used to perform the Meta-analysis. A fixed effects model was used for non-heterogeneous data; heterogeneity was explained by subgroup analysis based on intervention methods, and if it could not be explained by subgroup analysis, a random effects model was used. Relative risk (RR) and 95% confidence interval (CI) were used as evaluation indices, and funnel plots were generated based on the outcome measure involved in the highest number of studies. ResultsA total of 8 RCTs with 474 patients were included. The patients in the experimental group received gemcitabine-based chemotherapy and HIFU, and those in the control group received gemcitabine-based chemotherapy alone. Compared with the control group, the experimental group had significantly better results in 3-, 6-, and 12-month survival rates (3-month: RR=1.07, 95%CI: 1.00-1.14, P<0.05; 6-month: RR=2.19, 95%CI: 1.75-2.75, P<0.05; 12-month: RR=235, 95%CI: 1.07-5.14, P<0.05), tumor control (RR=1.64, 95%CI: 1.21-2.24, P=0.002), and pain control (RR=3.15, 95%CI: 2.45-4.05, P<0.05). There were no significant differences between the two groups in the incidence rates of leukopenia (RR=1.05, 95%CI: 0.85-1.30, P>0.05), gastrointestinal reactions (RR=0.89, 95%CI: 0.56-1.42, P>0.05), and liver injury (RR=1.29, 95%CI: 0.95-1.75, P>0.05). Since the outcome measure of pain control was involved in the highest number of studies, funnel plots were generated and showed no significant risk of bias. ConclusionCompared with gemcitabine alone, HIFU combined with gemcitabine can increase patients’ survival rate and improve their symptoms, with a similar incidence rate of adverse effects. Further studies are needed for this combined therapy.

17.
Chinese Pharmacological Bulletin ; (12): 550-555, 2020.
Article in Chinese | WPRIM | ID: wpr-857001

ABSTRACT

Aim To investigate the synergy effects of deoxyschizandrin and gemcitabine (GEM) on the proliferation of HepG2 human hepatocellular carcinoma cells in vitro and the underlying mechanism. Methods CCK8 method and colony formation assay were used to detect the effects of deoxyschizandrin monotherapy, GEM monotherapy and combination therapy on the proliferation of HepG2 cells. Flow cytometry was used to detect the change of apoptosis rate of HepG2 cells after treatment with single drug or the combination use of two drugs. Western blot was performed to detect the expression of BCL2, BAX, pro-caspase3, caspase3, pro-caspase9, caspase9, ß-catenin and TCF-4. Results Deoxyschizandrin, GEM and combination group significantly inhibited the proliferation of HepG2 cells and promoted cell apoptosis. The effects of the combination group on HepG2 cells were significantly stronger than those of single-drug groups (P < 0. 05). Western blot results showed the expression of pro-caspase3 and pro-caspase9 was changed slightly within deoxyschizandrin, GEM and combination groups compared with that of normal control, while the expression of B C L 2, ß-catenin and TCF-4 protein expression was down-regulated significantly (P < 0. 05). The expression of B A X, cleaved-caspase3 and cleaved-caspase 9 protein increased significantly after treatment with deoxyschizandrin, GEM and combination group (P < 0. 05). Specially, the increasing effect of the expression of the protein in combined group was more significant than that of single drug groups (P < 0. 05). Conclusions The combination of deoxyschizandrin and GEM significantly inhibited the proliferation of HepG2 cells and induced cell apoptosis, as well as suppressed the ß-catenin/TCF-4 pathway.

18.
China Pharmacy ; (12): 1990-1996, 2019.
Article in Chinese | WPRIM | ID: wpr-817220

ABSTRACT

OBJECTIVE: To systematically evaluate the efficacy and safety of Endostar combined with gemcitabine and cisplatin in the treatment of non-small cell lung cancer (NSCLC), and to provide evidence-based reference for clinical drug use. METHODS: Retrieved from Cochrane Library, PubMed, Embase, ClinicalTrials, CNKI, Wanfang and VIP database, randomized controlled trials (RCT) about Endostar combined with gemcitabine and cisplatin(trial  group) vs. gemcitabine combined with cisplatin (control group) for NSCLC were collected. After literature screening, data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale, Meta-analysis was performed by using Rev Man 5.3 software. RESULTS: A total of 27 RCTs were included, involving 1 646 patients. Results of Meta-analysis showed that response rate [RR=1.67, 95%CI(1.48,1.89),P<0.000 01] and clinical benefit rate [RR=1.26, 95%CI (1.20, 1.33),P<0.000 01] of trial group were significantly higher than those of control group. There was no statistical significance in the incidence of leucopenia [RR=0.98,95%CI(0.88, 1.11),P=0.79], thrombocytopenia [RR=1.07, 95%CI(0.91, 1.26),P=0.39] and gastrointestinal reaction [RR=1.01, 95%CI(0.90, 1.14),P=0.85] between 2 groups. CONCLUSIONS: Endostar combined with gemcitabine and cisplatin can improve therapeutic efficacy of NSCLC patients, without increasing the incidence of ADR.

19.
China Pharmacy ; (12): 1192-1197, 2019.
Article in Chinese | WPRIM | ID: wpr-816962

ABSTRACT

OBJECTIVE: To study the effects of curcumin on gemcitabine (GEM)-resistant pancreatic cancer SW1990 cells and its mechanism. METHODS: CCK8 assay was used to detect the effects of different concentrations of GEM (50, 100, 150, 200, 250 μmol/L) on the survival rate of SW1990 cells and GEM-resistant SW1990 cells (SW1991/GEM resistant cells); half inhibitory concentration (IC50) and drug resistance multiple were calculated. CCK8 assay was performed to detect the effects of different concentrations of curcumin (1, 5, 10, 20, 40 μmol/L) on survival rate of SW1990/GEM resistant cells, and IC50 was calculated. CCK8 assay was used to detect the effects of curcumin 2.41 μmol/L combined with different concentrations of GEM (25, 50, 75, 100, 125 μmol/L) on the survival rate of SW1990 cells and SW1990/GEM resistant cells, and IC50 and drug resistance reversal fold of GEM were calculated. Flow cytometry was carried out to detect the cell cycle distribution and apoptosis rate of SW1990 after treated with GEM alone or curcumin (2.41 μmol/L) combined with GEM using IC50 of GEM as drug concentration. Western blot assay was used to the protein expression of FAS, AKT, p-AKT, PI3K, p-PI3K, Caspase-3, Bcl-2 and related X protein (Bax). RT-PCR was used to detect mRNA expression. RESULTS: IC50 of GEM to SW1990 cells was 92 μmol/L. IC50 of GEM to SW1990/GEM resistant cells was 216 μmol/L, and drug resistance multiple SW1990 cells to GEM was 2.35. IC50 of curcumin to SW1990/GEM resistant cells was 9.2 μmol/L. Under 2.41 μmol/L curcumin, IC50 of GEM to SW1990 cells was 75  μmol/L, and IC50 of GEM to SW1990/GEM resistant cells was 98 μmol/L; drug resistance reversal multiple of SW1990/GEM resistant cells to GEM was 2.2. Compared with GEM alone, the apoptosis rate of SW1990 cells and SW1990/GEM resistant cells were increased significantly after curcumin combined with GEM (P<0.05), blocking at G0/G1 phase; the protein expression of FAS, p-AKT, p-PI3K and Bcl-2 and mRNA expression of FAS and Bcl-2 were decreased significantly  (P<0.05); the protein and mRNA expression of Bax      and Caspase-3 were increased significantly (P<0.05). CONCLUSIONS: Curcumin can reverse drug resistance of SW1990 cells to GEM, the mechanism of which may be associated with PI3K/AKT pathway.

20.
Article in Chinese | WPRIM | ID: wpr-802661

ABSTRACT

Objective@#To evaluate the recent efficacy and safety of gemcitabine combined with S-1 in the treatment of advanced biliary tract cancer.@*Methods@#From August 2014 to May 2017, 27 patients with advanced biliary tract cancer confirmed by pathology in the First People's Hospital of Zhengzhou received gemcitabine(1 000mg/m2, day 1 and 8) and S-1(80mg/m2, day 1-14) every three weeks.The recent efficacy and toxicities were observed after two cycles of chemotherapy.@*Results@#All of the 27 patients were evaluated, 1 patient(3.7%) achieved CR, 6 patients(22.2%) with PR, 12 patients(44.4%) with SD, 8 patients(29.6%) with PD.The total response rate was 25.9%(7/27), the disease control rate was 70.4%(19/27). The main toxicities were gastrointestinal reactions and myelosuppression, no chemotherapy-related death was observed.@*Conclusion@#Gemcitabine combined with S-1 in the treatment of advanced biliary tract cancer is safe and effect.

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