Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.
Adenocarcinoma/surgery* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Capecitabine/administration & dosage* ; Chemotherapy, Adjuvant ; Drug Combinations ; Humans ; Neoadjuvant Therapy ; Oxaliplatin/administration & dosage* ; Oxonic Acid/administration & dosage* ; Radiotherapy ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Tegafur/administration & dosage* ; Treatment Outcome

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.
Adenocarcinoma/surgery* ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant ; Dissection ; Drug Combinations ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Male ; Middle Aged ; Neoplasm Staging ; Oxaliplatin/administration & dosage* ; Oxonic Acid/administration & dosage* ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Tegafur/administration & dosage* ; Treatment Outcome

BACKGROUND: There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens. METHODS: We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS). RESULTS: 42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042). CONCLUSIONS S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.
Adult ; Aged ; Antineoplastic Agents ; adverse effects ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Combinations ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Oxonic Acid ; adverse effects ; pharmacology ; therapeutic use ; Retrospective Studies ; Safety ; Survival Analysis ; Tegafur ; adverse effects ; pharmacology ; therapeutic use ; Treatment Outcome

Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.
Carcinoma, Hepatocellular* ; Disease Progression ; Humans ; Salvage Therapy ; Tegafur* ; Treatment Failure

OBJECTIVETo observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.

METHODSA total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.

RESULTSThe objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.

CONCLUSIONSBoth CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; administration & dosage ; adverse effects ; Capsules ; Dihydrouracil Dehydrogenase (NADP) ; metabolism ; Disease Progression ; Humans ; Neoplasm Proteins ; metabolism ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pyridines ; administration & dosage ; adverse effects ; Stomach Neoplasms ; drug therapy ; metabolism ; mortality ; pathology ; Tegafur ; administration & dosage ; adverse effects ; Thymidine Phosphorylase ; metabolism

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m·d on day 1-14, 21 days as a cycle of treatment and repeated until either pro- gressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response (CR+PR) rate was 22.4% (17/76) and disease control (CR+PR+SD) rate was 61.8% (47/76) respectively. The median follow-up time was 20 months (range from 9 to 44 months). The median progression-free survival (PFS) was 4.9 months (95% CI 4.4-5.5) and the median overall survival (OS) was 8.1 months (95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months (95% CI 3.3 to 6.3) and 8.5 months (95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence (median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis (median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia (84.2%), grade I-II hand and foot syndrome (51.3%), grade I-II nausea (48.7%), mild epistaxis (30.1%) and mild vomiting (14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient (1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; administration & dosage ; adverse effects ; Drug Combinations ; Esophageal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Humans ; Male ; Middle Aged ; Oxonic Acid ; administration & dosage ; adverse effects ; Tegafur ; administration & dosage ; adverse effects

OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for > or =90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.
Administration, Oral ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Retrospective Studies ; Tegafur/administration & dosage/adverse effects ; Treatment Outcome ; Uracil/administration & dosage/adverse effects ; Uterine Cervical Neoplasms/*drug therapy/mortality

Biliary papillomatosis is rare, and its pathogenic mechanisms are not yet clear. Because of its high risk for malignancy transformation, surgical resection is regarded as a standard treatment. Photodynamic therapy (PDT) has been used by the intravenous administration of hematoporphyrin derivative followed by laser exposure. A photochemical process causes disturbance of the microvascular structure and degradation of membrane. Cholangitis is a major complication after PDT. A healthy 56-year-old man was diagnosed with biliary papillomatosis involving the common hepatic duct, both proximal intrahepatic bile ducts (IHD), and the right posterior IHD. After biliary decompression by endoscopic nasobiliary drainage, PDT was performed to avoid extensive liver resection and recurrence using endoscopic retrograde cholangiographic guidance. After portal vein embolization, the patient underwent extended right hemihepatectomy. Following administration of chemoradiation therapy with tegafur-uracil and 45 Gy due to local recurrence at postoperative 13 months, there was no local recurrence or distant metastases. This is the first case report on PDT for biliary papillomatosis in Korea. Preoperative PDT is beneficial for reducing the lesion in diffuse or multifocal biliary papillomatosis and may lead to curative and volume reserving surgery. Thus, PDT could improve the quality of life and prolong life expectation for biliary papillomatosis patients.
Antineoplastic Agents/therapeutic use ; Bile Duct Neoplasms/*diagnosis/drug therapy/surgery ; Bile Ducts, Intrahepatic/pathology ; Embolization, Therapeutic ; Gamma Rays ; Hepatectomy ; Hepatic Duct, Common/pathology ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Papilloma/*diagnosis/drug therapy/surgery ; Photochemotherapy ; Tegafur/therapeutic use ; Uracil/therapeutic use

OBJECTIVETo evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.

METHODSA retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.

RESULTSThe efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.

CONCLUSIONSGemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Administration Schedule ; Drug Combinations ; Humans ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Tegafur ; administration & dosage ; adverse effects

OBJECTIVEThis study was to investigate the molecular biomarkers of apoptosis induced by BH3 mimetic S1 in human primary AML cells.

METHODSMononuclear cells were isolated from 27 newly diagnosed AML samples. Apoptosis was analyzed by flow cytometry. IC(50) value of S1 on these samples was determined by XTT assay. The expression level of BCL-2 family members and phosphorylated BCL-2 were assessed by Western blot with subsequent semi-quantitatively densitometric analysis. XTT assay was performed to determine the cell viability of the combined use of S1 and MEK/ERK inhibitor PD98059. The interactions between BCL-2 and pro-apoptosis proteins were tested by co-immunoprecipitation.

RESULTSThe flow-cytometry detection showed that S1 induced the apoptosis of primary AML cells. Based on the responses, 27 primary samples could be classified into three groups: (1) a sensitive group (12 of 27 cases) with IC(50)<14 µmol/L, (2) an intermediate group (8 of 27 cases) with IC(50) of 14-30 µmol/L and (3) a resistant group (7 of 27 cases) with IC(50)>30 µmol/L. The ratio of pBCL-2/(BCL-2+MCL-1) showed a good linear correlation with the IC(50) values. (R(2) = 0.71, P < 0.0001). PD98059 suppressed BCL-2 phosphorylation. When PD98059 suppressed BCL-2 phosphorylation, the apoptotic rate of drug-resistant cells induced by S1 increased from 9.8% to 64.5% (combination index, CI = 0.4), accompanied by more dissociation of BCL-2 heterodimers.

CONCLUSIONThe combination of S1 with PD98059 decrease pBCL-2 level of AML patients and inhibits of the anti-apoptotic function of BCL-2 through enhancing the dissociation of BCL-2 heterodimers.

Antimetabolites, Antineoplastic ; Apoptosis ; Cell Line, Tumor ; Drug Combinations ; Humans ; Leukemia, Myeloid, Acute ; Molecular Mimicry ; Oxonic Acid ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; Tegafur