OBJECTIVETo compare the efficacy and safety of standard or reduced doses of bortezomib combined with adriamycin and dexamethasone (PAD) in patients with multiple myeloma (MM).

METHODSEighty-two newly diagnosed or refractory/relapsed patients received bortezomib [either 1.2-1.3 mg/m(2) (standard dose) or 1.0-1.1 mg/m(2) (reduced dose) on day 1, 4, 8 and 11], and adriamycin (10 mg/m(2)) plus dexamethasone (40 mg/m(2)) on day 1-4 at 3-week intervals for 1 to 6 courses. The International Myeloma Working Group Criteria were used to evaluate the response. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (Version 3.0).

RESULTSTwo courses of standard dose of PAD resulted in a similar response rate of partial and very good partial complete remissions (PR) compared with reduced dose (80.0% vs 80.8%, P=0.728). Grade III- Ⅳ neutropenia and thrombocytopenia were higher with standard dose than that with reduced doses of PAD (21.1% vs11.1%, P=0.270; 10.5% vs 6.3%, P=0.619, respectively). Grade III-Ⅳ bortezomib-induced peripheral neuropathy, herpes zoster, fatigue or abdominal distention were significantly higher with standard dose than that with reduced dose of PAD (15.8% vs 1.6%, P=0.037; 26.3% vs 6.3%, P=0.028; 36.8% vs 14.3%, P=0.046; 15.8% vs 1.6%, P=0.037, respectively).

CONCLUSIONReduced dose of PAD appears to result in a similar overall response rate, but a better tolerance and safety compared with standard dose.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; Doxorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome

To evaluate the use of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for treatment of acute and chronic leukemia, from March 1997 to January 2003, 21 adult patients with malignant hematopoietic diseases underwent allo-PBSCT from HLA-identical siblings (19 patients) and haplo-identical mother (one) and one B point site mismatched sibling (one). All donors were mobilized with G-CSF for 4 days and peripheral blood stem cells were collected by CS-3000 separator. The conditioning regimen included the high dose combination chemotherapy and TBI. Cyclosporine-A (CsA) plus a short course of MTX was used for GVHD prophylaxis in all patients. The results showed that after trans plantation, median time for the recovery of granuocyte > or = 0.5 x 10(9)/L and platelets > or = 20 x 10(9)/L were 12 (10 - 20) and 15 (11 - 35) days, respectively. Acute GVHD was observed in 8/17 patients (47%), of which one transplanted from HLA-haploidentical mother. Chronic GVHD occurred in 12/17 patients (70%). All of four female survivals did not show acute and chronic GVHD. Day 100 transplantation-related mortality was 14% (3/21). Relapse occurred in two patients (9.5%) who underwent allo-PBSCT in stage of non-remission at one and six months. After follow-up of 40 (15 - 70) months, 11 patients (52.4%) are still disease-free survival. These results suggested that peripheral blood stem cells produce a faster hematopoietic recovery and a lower relapse of leukemia. The rate of aGVHD is not increased when using the peripheral blood as source of stem cells; however, cGVHD continues to be a significant problem. Donors tolerated the procurement procedure without complications.
Adolescent ; Adult ; Female ; Graft vs Host Disease ; etiology ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Transplantation, Homologous ; Treatment Outcome

BACKGROUNDTo serially observe the pathologic changes in livers of tree shrews and macaca assamensises infected with HHBV.

METHODS10 adult tree shrews and 28 macaca assamensises were inoculated with HBV rich human sera. The liver of the animals were regularly biopsied. The liver samples were examined histopathologically by HE staining. Some samples were stained for HBsAg by immunohistochemistry (IH), and HBV DNA by in situ hybridization (ISH).

RESULTSHBsAg in 80% of tree shrews infected with HHBV can be detected by IH, HBV DNA in 50% of those can be found by ISH.The positive rates of HBsAg in macaca assamensises' livers were 25% by IH, none HBV DNA was detected.

CONCLUSIONThe tree shrew model seems to be applicable for the research of human hepatitis B.

Animals ; Antibodies, Viral ; immunology ; Disease Models, Animal ; Female ; Hepatitis B ; immunology ; pathology ; virology ; Hepatitis B virus ; immunology ; physiology ; Humans ; Liver ; pathology ; virology ; Macaca ; Male ; Tupaiidae

OBJECTIVETo study the effect of Shenfu Injection (SF) on the apoptosis of prostate cancer PC-3 cells and its possible mechanism.

METHODSWe divided prostate cancer PC-3 cells into a blank control group and three experimental groups, the latter treated with SF at 50, 100, and 200 microl/ml, respectively, for 24, 48, and 72 hours. Then we determined the proliferation of the cells by MTT assay, measured their apoptosis by Annexin V/PI flow cytometry, and detected the expression of P53 mRNA by RT-qPCR.

RESULTSCompared with the blank control group, the survival rates of the prostate cancer PC-3 cells in the 50, 100, and 200 microl/ml SF groups were (93.76 +/- 2.63)%, (81.21 +/- 1.80)% and (18.01 +/- 3.84)% at 24 hours, (94.67 +/-1.11)%, (78.33 +/- 2.89)% and (10.34 +/- 1.44)% at48 hours, and (91.30 +/- 0.47)%, (36.67 +/- 1.56)% and (1.33 +/- 0.32)% at 72 hours, all significantly increased in a dose- and time-dependent manner (P < 0.05). The expression of p53 mRNA was also markedly increased in all the three experimental groups at 48 hours (P < 0. 05).

CONCLUSIONSF can inhibit the proliferation and induce the apoptosis of PC-3 cells, which may due to its upregulation of the p53 mRNA expression.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm. Methods: From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively. 18 patients received RIC while 12 patients received MAC conditioning regiments consisted of Busulfan, cytarabine, fludarabine or clarithromycin±TBI, respectively. Results: Five patients died early in the conditioning stage, 24 patients successfully engrafted. The median time of neutrophil engraftment was 14(10-18) d, whereas platelet engraftment was 15(10-19) d. Six cases (25%) experienced aGVHD grades Ⅱ, 8 cases (32%) cGVHD, including moderate to severe cGVHD in 2 cases (8%). Seven, 7 and 5 cases developed CMV viremia, pneumonia and herpeszoster, respectively after transplantation, but no patients died of infections. The median follow-up time of the patients was 7(0.5-38) months. Twenty-one patients were still alive. The estimated 2 years OS and LFS were 62.5% (95% CI 39.2%-85.8%) and 59.2% (95% CI 26.9%-91.5%), respectively. Univariate analysis showed that HCT-CI was the only factor influencing OS. Conclusion: Allogeneic hematopoietic stem cell transplantation could improve the survival of elderly patients with myeloid neoplasm.
Aged ; Busulfan ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Retrospective Studies ; Transplantation Conditioning

OBJECTIVETo investigate the efficacy and safety of PAD [bortezomib (PS-341), doxorubicin and dexamethasone] regimen for relapsed or refractory multiple myeloma (MM).

METHODSSeventeen patients with relapsed or refractory MM received two to four 21-day cycles of PAD: an intravenous bolus of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11; doxorubicin 10 mg per day on days 1 to 4, and dexamethasone 40 mg on days 1-4. Response was evaluated according to International Myeloma Working Group Criteria (IMWG 2006), toxicity was graded according to NCI CTCAE (common terminology criteria for adverse events) v 3.0.

RESULTSAfter 2-4 courses of PAD, 14 patients (82.4%) response, including complete response (CR) in 4 (23.5%), very good partial response (VGPR) in 4 (23.5%), partial response (PR) in 6 (35.3%) and stable disease (SD) in 3 (17.6%). Median time to progression was 9.5 months. The median course to response was 1.6 (1-3). All of 5 patients with extramedullary plasmacytoma achieved at least PR after the first cycle therapy; the plasmacytoma disappeared after 1-2 cycles of PAD. The efficacy was independent of other prognostic factors such as beta2-MG. Adverse events included thrombocytopenia in 9 patients (52.9%), leukopenia in 4 (23.5%), peripheral neuropathy in 4 (23.5%), varicella herpes zoster in 3 (17.6%), fatigue in 6 (35.3%) and diarrhea in 2 (11.7%). All of these adverse reactions could be controlled with routine supportive treatment, only one patient died from respiratory failure during his fifth PAD cycle.

CONCLUSIONSPAD regimen should be considered as an appropriate treatment for relapsed or refractory MM, especially for MM with extramedullary plasmacytoma. Its efficacy is independent of traditional prognostic factors. The side effects are usually manageable.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; Bortezomib ; Dexamethasone ; administration & dosage ; adverse effects ; Doxorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; Treatment Outcome

OBJECTIVE: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. METHODS: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. RESULTS: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36+/-128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. CONCLUSION: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.
Antipsychotic Agents ; China ; Clozapine ; Data Collection ; Educational Status ; Hospitalization ; Humans ; Logistic Models ; Male ; Prescriptions ; Recurrence ; Sampling Studies ; Schizophrenia

OBJECTIVETo evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC).

METHODS141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles.

RESULTSOf the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death.

CONCLUSIONCapecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Foot Dermatoses ; chemically induced ; Hand Dermatoses ; chemically induced ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Vomiting ; chemically induced ; Young Adult

BACKGROUNDHepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.

METHODSTwenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day: infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.

RESULTSA total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia.

CONCLUSIONSThe Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Leucovorin ; administration & dosage ; adverse effects ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; adverse effects

OBJECTIVETo analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.

RESULTSThe objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).

CONCLUSIONSCompared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Disease-Free Survival ; Double-Blind Method ; Endostatins ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Quality of Life ; Remission Induction