【Objective】 To explore the maximum tolerated dose(MTD) of pegylated liposome doxorubicin(PLD) when combined with cisplatin as a modified regimen for osteosarcoma. 【Methods】 A total of 14 patients with pathologically confirmed metastatic or unresectable osteosarcoma received one cycle of PLD combined with cisplatin therapy. The study used a traditional 3+3 design, with three PLD dose levels(40, 50, and 60 mg/ m², day 1). It was designed to recruit three patients initially at each dose level. Cisplatin was given at a dose of 100 mg/m²(administered within four days) for each patients. Patients received prophylactic granulocyte stimulating factor therapy 48 h after chemotherapy. Toxicities were documented according to the the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0(NCI CTCAE v4.0) . 【Results】 Of the 14 patients, 9 were male and 5 female, with a median age of 20 years(range 14~43). Both of the patients at dose level of 60 mg/m² experienced dose-limiting toxicity(DLT) (grade 3 oral mucositis and grade 4 neutropenic fever). Only 1 of the 9 patients at dose level of 50 mg/m² experienced DLT(grade 4 thrombocytopenia lasting for more than 3 days) and thus the MTD was 50 mg/m². Most common grade 3~4 adverse events across all cohorts included neutropenia(12 cases, 12/14), thrombocytopenia(7 cases, 7/14), anemia(4 cases, 4/14) and oral mucositis(2 cases, 2/14). All the adverse events were relieved after symptomatic and supportive treatment. No treatment-related death was observed. 【Conclusions】 For advanced osteosarcoma, when combined with cisplatin, the MTD of PLD was 50 mg/m². The main DLT was oral mucositis and neutropenic fever. The adverse events can be relieved after symptomatic treatment.

Background:Reduced expression of tripartite motif-containing 3 (TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma (HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines (SK-Hep1,Hep3B,Huh7,HepG2,Bel-7402) and one normal liver cell line (L02) were detected with Western blotting.HepG2 and Bel-7402 cells with IowTRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3 (LV-TRIM3),whereas Huh7 and Hep3B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA (siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect of TRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed thatTRIM3 overexpression induced G0/G1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3B cells by siTRIM3 led to significantly decreased percentages of both cells in the G0/G1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed thatTRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G0/G1 phase.

BACKGROUNDThis study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China.

METHODSThis study was conducted in 12 hospitals located in geographically and industrially different cities in China. A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment. A regional network (system) efficiently integrating prehospital rescue, emergency room treatments, and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments. Treatment outcomes were compared between before and 1 year after the implementation of the SRP.

RESULTSThe outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP. Implementation of the SRP led to efficient cooperation and information sharing of different treatment services. The emergency response time, prehospital transit time, emergency rescue time, consultation call time, and mortality rate of patients were 24.24 ± 4.32 min, 45.69 ± 3.89 min, 6.38 ± 1.05 min, 17.53 ± 0.72 min, and 33.82% ± 3.87% (n = 441), respectively, before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min, 22.39 ± 4.32 min, 3.26 ± 0.89 min, 3.45 ± 0.45 min, and 20.49% ± 3.11%, separately (n = 495, P < 0.05) after that.

CONCLUSIONSStaff training and SRP can significantly improve the efficiency of severe trauma treatments in China.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Emergency Medical Services ; standards ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Wounds and Injuries ; Young Adult

Gastrointestinal carcinomas are among the malignancies with highest morbidity and mortality. The survival rates of these tumors remain pretty low in spite of advancements of traditional treatments. As the fourth treatment method besides surgery, radiotherapy and chemotherapy, biotherapy has shown promising prospect in improving the prognosis of gastrointestinal carcinomas. In this manuscript, we summarized the current progress of biotherapy in gastrointestinal tumors including gene therapy, immune therapy and molecular targeted therapy.
Biological Therapy ; Gastrointestinal Neoplasms ; therapy ; Genetic Therapy ; Humans ; Immunotherapy

Chuankezhi (CKZ), a new Chinese medicine, plays an important role in immunoregulation. Cytokine-induced killer (CIK) cells have been commonly used for immunotherapy in recent years. In this study, we aimed to investigate the immunoregulatory effect of CKZ on CIK cells. Peripheral blood monocytes were isolated from healthy donors, and CIK cells were generated by culturing monocytes with interferon-gamma (IFN-γ) and interleukin 2. Different concentrations of CKZ were added on day 2. After incubation for 14 days in culture, the antitumor effects of CIK cells were measured by cytotoxicity assay. Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype, intracellular cytokine production, and apoptosis. The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated. CKZ increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. CKZ-conditioned CIK cells showed a greater ability to kill tumor cells, as well as a higher frequency of IFN-γ and TNF-α production, compared with the CIK cells in the control group. CKZ also suppressed the apoptosis of CIK cells in vitro. Furthermore, CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK, CKZ, or normal saline control groups. Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.
Animals ; Apoptosis ; drug effects ; CD3 Complex ; metabolism ; CD56 Antigen ; metabolism ; Cell Line, Tumor ; drug effects ; Cytokine-Induced Killer Cells ; cytology ; drug effects ; immunology ; Cytotoxicity, Immunologic ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Epimedium ; chemistry ; Female ; Humans ; Interferon-gamma ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Morinda ; chemistry ; Neoplasm Transplantation ; Plants, Medicinal ; chemistry ; Tumor Burden ; Tumor Necrosis Factor-alpha ; metabolism

In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
Child ; Child, Preschool ; Cytokine-Induced Killer Cells ; immunology ; Epstein-Barr Virus Infections ; therapy ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunotherapy, Adoptive ; Infant ; Killer Cells, Natural ; immunology ; Lymphoproliferative Disorders ; therapy ; virology ; Male ; Neuroblastoma ; therapy ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo investigate the effect of hepatitis B virus(HBV) X gene on the expression of SPG21.

METHODSThe expressions of SPG21 mRNA and protein in HepG2 and HepG2.2.15 cells were tested by RT-PCR and western blot. HepG2 cells were co-transfected with reporter plasmid pGL3-SPG21 and plasmids carrying individual genes of HBV, the luciferase activity was measured and the expressions of SPG21 were detected by RT-PCR and western blot.

RESULTSThe expressions of SPG21 mRNA and protein were higher in HepG2.2.15 cells than in HepG2 cells (0.36+/-0.06 vs 0.21+/-0.05, P value is less than 0.05). The activity of SPG21 in HepG2 cells transfected with pCMV-X was higher (875+/-27 vs 67+/-12, P value is less than 0.01) as compared to blank control group (transfected with pCMV-tag2B). HBV X gene enhanced SPG21 gene promoter activity, SPG21 mRNA expression and SPG21 protein production in HepG2 cells in a dose-dependent manner.

CONCLUSIONHBV X gene can specially activate SPG21 expression.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; DNA, Viral ; genetics ; Hep G2 Cells ; Hepatitis B virus ; genetics ; Humans ; RNA, Messenger ; genetics ; Trans-Activators ; genetics ; Transfection

OBJECTIVETo investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD.

METHODSIn total 1,397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China.

RESULTSMean patient age was 63.7 +/- 8.2 years and mean duration of diabetes mellitus was 9.39 +/- 7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI < 0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin A1c, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI.

CONCLUSIONSPAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.

Aged ; China ; epidemiology ; Diabetic Angiopathies ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Peripheral Vascular Diseases ; epidemiology ; Prevalence ; Risk Factors ; Urban Population ; statistics & numerical data

OBJECTIVETo define the clinicopathological features of primary cardiac large B-cell lymphoma.

METHODA case of primary cardiac large B-cell lymphoma was studied with conventional histopathological and immunohistochemical staining in combination with literature review.

RESULTSThe lesion appeared to originate in the right atrium and involved the venae cavae and the left atrium. Microscopic examination showed diffuse proliferation of large atypical lymphocytes with abundant cytoplasm, vestiealer nuelei, thick nuclear membrane and conspicuous nucleoli. Giant tumor cells scattered in the lesion. The neoplastic cells were positive for CD20 and CD79a.

CONCLUSIONPrimary cardiac lymphoma is extremely rare, and its pathogenesis remains unclear. With non-specific clinical manifestations, the majority of primary cardiac lymphomas are of B-cell lineage and a bad prognosis.

Aged ; Antigens, CD20 ; analysis ; CD79 Antigens ; analysis ; Female ; Heart Neoplasms ; metabolism ; pathology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology

OBJECTIVETo observe the growth and cell cycle changes of nasopharyngeal carcinoma cell 5-8F in response to silencing of the expression of epidermal growth factor receptor (EGFR) with RNA interference (RNAi), and explore the possible relationships between EGFR and the occurrence, differentiation and progression of nasopharyngeal carcinoma.

METHODThree EGFR-specific small interfering RNAs (siRNAs) were obtained by in vitro transcription and synthesis and were transiently transfected into 5-8F cells. The EGFR expression levels in the transfected cells were detected by reverse transcription (RT)-PCR and Western blotting, respectively. After EGFR expression silencing, the growth and cell cycle changes of the cells were observed.

RESULTSEGFR mRNA contents and protein levels decreased by approximately 67.5% and 77%, respectively, after RNAi of 5-8F cells, and the cell proliferation decreased and cell cycle arrest at G1 phase occurred in association with EGFR silencing.

CONCLUSIONEGFR silencing by RNAi can reduce the proliferation of nasopharyngeal carcinoma cells and induce cell cycle arrest at G1 phase, which sheds light on the possible use of RNAi for further investigation of the pathogenesis and gene therapy of nasopharyngeal carcinoma.

Cell Line, Tumor ; Cell Proliferation ; Genetic Therapy ; Humans ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; genetics ; Receptor, Epidermal Growth Factor ; biosynthesis ; genetics ; Transfection