Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
Acupuncture Therapy ; Amphibian Venoms ; therapeutic use ; China ; Combined Modality Therapy ; standards ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Integrative Medicine ; standards ; Liver Neoplasms ; drug therapy ; pathology ; therapy ; Medicine, Chinese Traditional ; standards ; Neoplasm Staging ; Practice Guidelines as Topic

AIM:To investigate the effects of xeroderma pigmentosum group D ( XPD) gene on the prolifera-tion of human umbilical arterial smooth muscle cells ( HUASMCs) induced by oxidized low-density lipoprotein ( Ox-LDL) . METHODS:The recombinant plasmid pEGFP-N2/XPD was transfected into HUASMCs by liposome .The cells were di-vided into blank control group , pEGFP-N2 group, pEGFP-N2/XPD group, Ox-LDL group, Ox-LDL+pEGFP-N2 group and Ox-LDL+pEGFP-N2/XPD group.The proliferation rate of the cells was detected by MTT and EdU assays .The apop-totic rate and cell cycle distribution were analyzed by flow cytometry .The protein levels of XPD, caspase-3, Bcl-2 and Bax were determined by Western blot .RESULTS:Compared with blank control group , the expression of XPD was increased in pEGFP-N2/XPD group (P<0.05).According to the results of MTT and EdU assays , the cell proliferation in pEGFP-N2/XPD group was reduced compared with blank control group (P<0.05).Compared with Ox-LDL group, the cell prolifera-tion in Ox-LDL+pEGFP-N2/XPD group was significantly inhibited (P<0.05).According to the results of flow cytome-try, the cell proportion of S phase decreased and the G 0/G1-phase cell proportion increased significantly in pEGFP-N2/XPD group and Ox-LDL+pEGFP-N2/XPD group compared with blank control group and Ox-LDL group, repectively (P<0.05).Compared with blank control group and Ox-LDL group, the protein level of Bcl-2 decreased and the protein levels of Bax and cleaved caspase-3 increased in pEGFP-N2/XPD group and Ox-LDL +pEGFP-N2/XPD group, respectively (P<0.05).CONCLUSION:XPD inhibits the proliferation of HUASMCs and promotes their apoptosis , and reduces the promoting effect of Ox-LDL on the proliferation of HUVSMCs .XPD may be the target for treatment of atherosclerosis .

OBJECTIVETo evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

METHODSFifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.

RESULTSEighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.

CONCLUSIONSAddition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Aged ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; China ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Esophageal Neoplasms ; drug therapy ; pathology ; Esophagogastric Junction ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Trastuzumab ; Vomiting ; chemically induced

OBJECTIVETo observe three-dimensional space position change of nucleus pulposus and nerve root before and after treatment of lumbar disc herniation by spinal fixed-point rotating reduction, and explore the mechanisms.

METHODSTotally 52 patients with L5S1 lumbar disc hernation treated by spinal fixed-point rotating reduction were collected from April 2009 to June 2011. There were 33 males and 19 females with an average age of 34.6 years old (ranged, 19 to 55). Three-dimensional MRI were performed to observe relationship between nucleus pulposus and related nerve root,configuration change of spine and pelvic on coronary MRI.

RESULTSMRI showed relationship between nucleus pulposus and related nerve root mainly located on axillary, shoulder, front and surround. Vertebral displacement disappeared, lumbocrural pain alleviated after manipulative therapy. All patients were followed up from 2 to 28 months with an average of 12 months, and no recurred. All patients recovered work. Nucleus pulposus had no change,while lumbral spinal and pelvic curve changed before and after admission.

CONCLUSIONLumbar disc herniation combined with single (multiple) vertebral displacement,can cause biomechanical properties of nucleus puplosus and related nerve root, while spinal fixed-point rotating reduction can correct vertebral displacement, recover balance between inside and outside of spinal.

Adult ; Female ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc Displacement ; diagnosis ; diagnostic imaging ; physiopathology ; therapy ; Lumbar Vertebrae ; diagnostic imaging ; physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Rotation ; Young Adult

BACKGROUNDThree randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.

METHODSIn the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.

RESULTSOf 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.

CONCLUSIONSWe found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bevacizumab ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; Bridged-Ring Compounds ; adverse effects ; therapeutic use ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo measure position changes of lumber disk herniation before and after treatment of Feng's spinal manipulation to study the mechanism of the manipulation for lumber disk herniation.

METHODSIn 2010, 8 patients with lumber disk herniation were treated by Feng's spinal manipulation, including 3 males and 5 females who ranged in age from 14 to 53 years with a mean of 35.4 years. The patients received CT scan before and after treatment. All images were reconstructed to measure the distance between the apex of the calcified lumber disk herniation and the top of the next adjacent spinal process.

RESULTSThe position of calcified lumber disk herniation underwent change after Feng's spinal manipulation, with a slight subluxation between the two adjacent vertebrae.

CONCLUSIONIf subluxation is restored,the relation between the nerve root and the hernation will undergo change, followed by subsequent change of the hernation mass, thus restoring the inner-outer balance of the spinal column system.

Adolescent ; Adult ; Female ; Humans ; Imaging, Three-Dimensional ; methods ; Intervertebral Disc Displacement ; therapy ; Lumbar Vertebrae ; Male ; Manipulation, Spinal ; methods ; Middle Aged ; Tomography, X-Ray Computed ; methods

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.
Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Bevacizumab ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Leucovorin ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Neoplasm Metastasis ; Neutropenia ; chemically induced ; Prospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well.

METHODSHuman hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2.5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope (TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.

RESULTSThe tumor weight and volume were 0.65 +/- 0.25 g and 0.44 +/- 0.14 cm3 in GB, 0.70 +/- 0.27 g and 0.46 +/- 0.19 cm3 in GC, 0.42 +/- 0.16 g and 0.26 +/- 0.11 cm3 in GD, all significantly lower than those in GA (1.06 +/- 0.25 g and 0.67 +/- 0.17 cm3, P < 0.05). The coefficient of drug interaction (CDI) on tumor weight was 0.97 and that on tumor size was 0.86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed.

CONCLUSIONSAs2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the angiogenesis in tumor. Combined use of the two had no obvious toxicity to the hepatic, renal and hematopoietic systems.

Amphibian Venoms ; pharmacology ; therapeutic use ; Angiogenesis Inhibitors ; Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; blood supply ; drug therapy ; Cell Line, Tumor ; Drug Synergism ; Humans ; Liver Neoplasms ; blood supply ; drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; drug therapy ; Oxides ; pharmacology ; therapeutic use ; Phytotherapy ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo explore the feasibility of IGF2 imprinting system in target gene therapy for tumors.

METHODSThe mouse H19 enhancer, DMD and promoter H19 were amplified by PCR from mouse genomic DNA and then cloned into the plasmid pDC312. The EGFP and DT-A fragments were amplified by PCR and cloned into the recombinant plasmid, and then the shuttle plasmid were transfected into HEK293 cells together with the adenoviral vector Ad5, namely, Ad-EGFP and Ad-DT-A. Adenovirus hexon gene expression was applied to confirm the presence of adenovirus infections. The effect of the IGF2 imprinting system was tested by fluorescence microscopy. RT-PCR and Western blotting after transfection of the recombinant adenoviral vectors into cancer cells were used to show loss of IGF2 imprinting (LOI) and maintenance of IGF2 imprinting (MOI), respectively. The anti-tumor effect was assessed by MTT and flow cytometry after the HCT-8 (LOI). Human breast cancer cell line MCF-7 (MOI) and human normal gastric epithelial GES-1 (MOI) cell line were transfected with Ad-DT-A in vitro. The anti-tumor effect was detected by injecting the Ad-DT-A in nude mice carrying HCT-8 tumors.

RESULTSThe expression of EGFP protein, DT-A mRNA and DT-A protein were seen to be positive only in the HCT-8 tumor cell line. Infection with Ad-DT-A resulted in obviously growth inhibition in HCT-8 cells (75.4 ± 6.4)% compared with that in the control group, and increased the percentage of apoptosis in the HCT-8 cells (20.8 ± 5.9)%. The anti-tumor effect was further confirmed by injecting the recombinant adenoviruses in HCT-8 tumor-bearing nude mice, and the results showed that the Ad-DT-A inhibited the tumor growth, with on inhibition rate of 36.4%.

CONCLUSIONSThe recombinant adenoviruses carrying IGF2 imprinting system and DT-A gene have been successfully constructed, while Ad-DT-A can effectively kill the tumor cells showing loss of IGF2 imprinting. It might play an important role in future target gene therapy against malignant tumors based on loss of IGF2 imprinting.

Adenoviridae ; genetics ; Animals ; Apoptosis ; Breast Neoplasms ; genetics ; pathology ; Colonic Neoplasms ; genetics ; pathology ; therapy ; Diphtheria Toxin ; biosynthesis ; genetics ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; Genomic Imprinting ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Insulin-Like Growth Factor II ; genetics ; metabolism ; MCF-7 Cells ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; RNA, Messenger ; metabolism ; Random Allocation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Transfection