BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cisplatin ; administration & dosage ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Female ; Humans ; Interleukin Receptor Common gamma Subunit ; deficiency ; genetics ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; pathology ; Transplantation, Heterologous ; methods ; Xenograft Model Antitumor Assays

BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) has been reported as an effective treatment for advanced hepatocellular carcinoma. The aim of this study is to compare the effect and safety between a high-dose regimen (750 mg/m2 5-fluorouracil [FU] and 25 mg/m2 cisplatin on day 1–4) and a low-dose regimen (500 mg/m2 5-FU on day 1–3 with 60 mg/m2 cisplatin on day 2). METHODS: A total of 48 patients undergoing HAIC were retrospectively analyzed. Thirty-two patients were treated with the high-dose and 16 patients with the low-dose regimen. RESULTS: Complete response (CR), partial response (PR), stable disease (SD), and progressive disease were noted in one (3.1%), 15 (46.9%), three (9.4%), and 13 patients (40.6%) in the highdose group, and 0 (0%), one (6.3%), eight (50%), and seven patients (43.8%) in the low-dose group (P=0.002). The disease control rate (CR, PR, and SD) did not differ between groups (59.4% vs. 56.3%, P=1.000), but the objective response rate (CR and PR) was significantly higher in the high-dose group (50.0% vs. 6.3%, P=0.003). The median progression free survival did not differ between groups (4.0 vs. 6.0, P=0.734), but overall survival was significantly longer in the high-dose group (not reached vs. 16.0, P=0.028). Fourteen (43.8%) patients in the high-dose group and two patients (12.5%) in the low-dose group experienced grade 3–4 toxicities (P=0.050). CONCLUSIONS: High dose HAIC may achieve better tumor response and may improve overall survival compared to a low-dose regimen. However, the high-dose regimen should be administered cautiously because of the higher incidence of adverse events.
Administration, Metronomic ; Carcinoma, Hepatocellular ; Chemotherapy, Cancer, Regional Perfusion ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Humans ; Incidence ; Retrospective Studies

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8 T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8 T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.
Abietanes ; administration & dosage ; Animals ; Antineoplastic Agents ; administration & dosage ; CD8-Positive T-Lymphocytes ; drug effects ; immunology ; Carcinoma, Lewis Lung ; drug therapy ; genetics ; immunology ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; Drug Synergism ; Humans ; Interferon-gamma ; genetics ; immunology ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; Matrix Metalloproteinase 9 ; genetics ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells ; drug effects ; immunology ; Plant Extracts ; administration & dosage ; Rosmarinus ; chemistry

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Cytarabine ; administration & dosage ; Dexamethasone ; administration & dosage ; Humans ; Induction Chemotherapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; mortality ; Neoplasm Recurrence, Local ; drug therapy ; mortality ; Retrospective Studies ; Salvage Therapy ; methods ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vinorelbine

OBJECTIVE: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. METHODS: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. RESULTS: The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. CONCLUSION: Rikkunshito provided additive effect for the prevention of CINV and anorexia.
Administration, Oral ; Anorexia* ; Antiemetics ; Appetite ; Cisplatin* ; Drug Therapy ; Dyspepsia ; Eating ; Herbal Medicine* ; Humans ; Japan ; Nausea* ; Paclitaxel* ; Time-to-Treatment ; Vomiting*

BACKGROUNDThe aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).

METHODSPertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.

RESULTSTwelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m 2 , combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05-1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30-0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m 2 , no significant differences in efficiency (RR = 1.11, 95% CI [0.87-1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71-1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.

CONCLUSIONSAidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; psychology ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Injections ; Lung Neoplasms ; drug therapy ; psychology ; Publication Bias ; Quality of Life ; Vinblastine ; administration & dosage ; analogs & derivatives

OBJECTIVETo explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients.

METHODSOne hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups.

RESULTSThe baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ=5.382, P=0.020; 58.4% vs. 34.4%, χ=6.636, P=0.010).

CONCLUSIONRegional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Celiac Artery ; Chemotherapy, Cancer, Regional Perfusion ; adverse effects ; methods ; mortality ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Fluorine ; administration & dosage ; adverse effects ; therapeutic use ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Gastrectomy ; Humans ; Leucovorin ; therapeutic use ; Lymph Node Excision ; Neoplasm Recurrence, Local ; prevention & control ; Organoplatinum Compounds ; therapeutic use ; Postoperative Complications ; Recovery of Function ; Stomach Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

To investigate the effect of RAD18-siRNA on cell proliferation and chemotherapy sensitivity of esophageal squamous cell carcinoma (ESCC) ECA-109 cells.RAD18-siRNA was transfected into human ECA-109 cells by Lipofectamine 3000. Quantitative PCR and Western blot were performed to detect RAD18 and CyclinD1 expression; CCK-8 assay was used to determine cell proliferation and chemotherapy drug sensitivity; flow cytometry was used to determine cell cycle. Correlation between RAD18 and CyclinD1 mRNA expression was analyzed by Pearson's correlation.Compared with non-transfected cells, the expression of RAD18 in RAD18-siRNA group was significantly decreased (<0.05). The cell proliferation was inhibited (<0.05) and the cell number of G1 phase was increased, G2/M phase cells decreased (<0.05) in RAD18-siRNA group. After treatment with different concentrations of cisplatin or 5-FU, the survival rate of the two cell groups was reduced (all<0.05), and the IC50 of RAD18-siRNA group was significantly lower than that of non-transfected group (<0.05). The mRNA expression of RAD18 was positively correlated with CyclinD1 expression in ESCC tissues(=0.478,<0.01).Down-regulated expression of RAD18 can decrease the cell proliferation and increase chemo-sensitivity of ESCC cells, and CyclinD1 may participate in the process.
Adjuvants, Pharmaceutic ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; physiopathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Cyclin D1 ; drug effects ; genetics ; DNA-Binding Proteins ; administration & dosage ; pharmacology ; Down-Regulation ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Drug Synergism ; Esophageal Neoplasms ; drug therapy ; physiopathology ; Fluorouracil ; pharmacology ; G1 Phase ; drug effects ; G2 Phase ; drug effects ; Humans ; Metaphase ; drug effects ; RNA, Small Interfering ; administration & dosage ; pharmacology ; Transfection ; Ubiquitin-Protein Ligases ; administration & dosage ; pharmacology

OBJECTIVETo evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.

METHODSTwenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.

RESULTSWith a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).

CONCLUSIONCisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.

Anthracyclines ; administration & dosage ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bridged-Ring Compounds ; administration & dosage ; Capecitabine ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Disease-Free Survival ; Female ; Hand-Foot Syndrome ; Humans ; Leukopenia ; chemically induced ; Neutropenia ; chemically induced ; Prospective Studies ; Taxoids ; administration & dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology

OBJECTIVETo improve the diagnosis and treatment of testicular teratoma in children by analysis of clinical data.

METHODSWe retrospectively analyzed the clinical data about 64 cases of testicular teratoma treated in the Children's Hospital of Chongqing Medical University from 1995 to 2014.

RESULTSSixty-one of the cases presented painless scrotal mass with a sense of bearing down and the other 3 cases were confirmed because of empty scrotum diagnosed as cryptorchidism. The level of serum alpha fetal protein ( AFP) was obviously increased in 46 cases but normal in the other 18 preoperatively. Ultrasonography manifested abnormal inhomogeneous echo zones with calcification or necrosis. X-ray examination presented patchy or curvilinear high-density shadows in 28 cases. Forty-one of the patients underwent testis-sparing surgery (TSS) , 20 received high inguinal orchiectomy, and 3 refused surgical treatment. Pathological examination revealed 3 mature germinal layers in the 49 cases of mature teratoma and immature germinal tissue, including the original neural tube, and 11 cases of immature teratoma. The mature cases were exempted from chemotherapy, while the immature cases received the combination of cisplatin, etoposide, and bleomycin (PEB). The patients were followed up for 2 years postoperatively, which revealed no recurrence or metastasis.

CONCLUSIONMost children with testicular teratoma presented painless scrotal mass with a sense of bearing down and with abnormal serum AFP in most cases. Ultrasonography and plain radiography of the scrotum contribute to the diagnosis of the tumor. TSS is the main treatment option and intraoperative frozen-section can help the surgeons decide on the surgical mode. Postoperative chemotherapy is necessitated for immature teratoma but not for mature cases.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Child ; Cisplatin ; administration & dosage ; Cryptorchidism ; diagnosis ; Etoposide ; administration & dosage ; Gonadal Dysgenesis, 46,XY ; diagnosis ; Humans ; Male ; Orchiectomy ; methods ; Retrospective Studies ; Scrotum ; Teratoma ; blood ; diagnosis ; pathology ; therapy ; Testicular Neoplasms ; blood ; diagnosis ; pathology ; therapy ; Testis ; abnormalities ; alpha-Fetoproteins ; analysis