Enhanced antitumor efficacy by combination treatment with a human umbilical vein endothelial cell vaccine and a tumor cell lysate-based vaccine

Angiogenesis inhibitors combined with other anticancer drugs have been shown to inhibit tumor growth in animal models and some of them were recently used in clinical trials. In the present study, a whole hepatocellular carcinoma cell lysate based vaccine with diphtheria toxin (DT) and two tandem repeats of microbial HSP70 peptide epitope 407-426 (2 mHSP70407-426, M₂) as adjuvant, which was called HDM, was combined with a whole human umbilical vein endothelial cell (HUVEC) vaccine to develop a combination treatment regimen. This combination treatment regimen was named HUVEC-HDM, which was supposed to enhance its antitumor efficiency. HUVEC-HDM was administrated subcutaneously in both prophylactic and therapeutic procedures. Compared to either single vaccine, HUVEC-HDM induced a more significant inhibition on the growth and metastasis of H22 hepatocellular carcinoma in mice and prolonged the survival of tumor-bearing mice. Besides, HUVEC-HDM immunization elicited strong humoral and cellular immune responses targeting tumor cell as well as tumor angiogenesis, which could be responsible for the enhanced antitumor effect. Moreover, histochemistry analysis showed that HUVEC-HDM induced large areas of continuous necrosis within tumors, correlating well with the extent of tumor inhibition. These results not only highlight the superiority of the combined HUVEC-HDM treatment regimen, but also support the translation of such approaches into the clinic for the treatment of patients with hepatocellular carcinoma.     

Association between the NBS1 Glu185Gln polymorphism and breast cancer risk: a meta-analysis

Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability. The NBS1 Glu185Gln (NBS1 E185Q, NBS1 8360G>C, rs1805794) polymorphism has been indicated to be involved in the development of cancer, but results of previous individual studies on the association between NBS1 Glu185Gln polymorphism and breast cancer risk remain controversial and inconclusive. Our meta-analysis investigated this association for the first time by pooling the odds ratios with corresponding 95 % confidence intervals (95 % CIs) of all individual publications available to date. Overall, 14 separate studies with 6,642 cases and 7,138 controls were finally included into the present meta-analysis after a comprehensive literature search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 21, 2012. Overall analysis and subgroup analyses by ethnicity and source of controls were performed. Meta-analysis of total studies showed that the NBS1 Glu185Gln variant carriers were not susceptible to breast cancer (OR_{Gln vs. Glu}?=?1.05, 95 % CI 0.80–1.39, P _OR?=?0.719; OR _{Gln/Gln vs. Glu/Glu}?=?0.82, 95 % CI 0.62–1.08, P _OR?=?0.154; OR _{Glu/Gln vs. Glu/Glu}?=?1.00, 95 % CI 0.90–1.13, P _OR?=?0.939; OR_{Gln/Gln + Glu/Gln vs. Glu/Glu}?=?0.96, 95 % CI 0.83–1.11, P _OR?=?0.551; OR_{Gln/Gln vs. Glu/Glu + Glu/Gln}?=?0.84, 95 % CI 0.67–1.05, P _OR?=?0.134). Similar results were observed in heterogeneity-adjusted meta-analysis of all studies. Furthermore, subgroup analyses by ethnicity and source of controls did not identify any appreciable relationship of the NBS1 Glu185Gln polymorphism with breast cancer susceptibility in any populations. Sensitivity analysis by sequentially omitting individual studies confirmed the stability and reliability of our results. Our meta-analysis of currently available data shows no association between the NBS1 Glu185Gln polymorphism and breast cancer risk.     

Liver tumours in children: diagnostic and therapeutic approach in the Tropics

Liver tumours in children are rare and their prognosis are poor. Through a cross and retrospective study, we examined the epidemiological, clinical and therapeutic aspects on a number of patients in our hospital to try and improve the management of cases. This study involved 66 children admitted to the pediatric oncology unit of University Hospital of Treichville in Abidjan between 1991 and 2007. The average age of children was 7.2 years and the sex ratio of 1.4. 42 children lived in the countryside and 52 children were from disadvantaged areas. 63.2% of children were not vaccinated against hepatitis B. The abdominal mass was the primary sign of discovery and these tumours were dominated in both their primitive and secondary forms by the Burkitt's lymphoma.     

Systematic Chemotherapy for Inoperable,Locally Advanced,Recurrent, or Metastatic Uterine Leiomyosarcoma: A Systematic Review

The goal of this systematic review was to investigate and compare the treatment effects of systemic chemotherapy (i.e. doxorubicin, gemcitabine, gemcitabine plus docetaxel, or trabectedin) in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma. A 2005 systematic review (searching the literature from 1980 to June 2004) on systemic therapy in advanced uterine sarcoma was used as the basis for this updated review. MEDLINE and EMBASE (from January 2004 to June 2011), the Cochrane Library, some main guideline websites and the American Society of Clinical Oncology and the Connective Tissue Oncology Society annual meeting abstracts were searched. One arm from a randomised controlled trial (RCT), four single-arm phase II trials and one abstract were included in this systematic review. The studies of gemcitabine plus docetaxel have reported numerically longer median overall survival (14.7–17.9 months versus 12.1 months) and numerically higher objective response rates (27–53% versus 25%) than those reported in the study of doxorubicin alone. The combination of gemcitabine plus docetaxel resulted in more toxicity than doxorubicin alone. The available study for single-agent gemcitabine reported a tumour response rate of 21%, which is not superior to the 25% response rate with doxorubicin alone. One abstract (pooling data from two RCTs) failed to show the superiority of gemcitabine plus docetaxel over gemcitabine alone for tumour response rate (23% versus 18%) and progression-free survival (6 versus 4.9 months). To date, there is insufficient evidence to support or refute the use of trabectedin in the target patients. Doxorubicin, gemcitabine, and gemcitabine plus docetaxel are treatment options in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma as first- or second-line therapy. Well-designed and good-quality RCTs are required to investigate the efficacy of chemotherapy and quality of life in target patients with uterine leiomyosarcoma.     

Synthesis and cytotoxicity of (3β)-3-acetyloxy-5(6)-androsten-7-one oxime and 3,5(6)-androstadien-7-one oxime

(3β)-3-Acetyloxy-5(6)-androsten-7-one oxime and 3,5(6)-androstadien-7-one oxime were synthesized and their in vitro cytotoxic activities against human epidermoid carcinoma cell line KB, human cervical carcinoma cell line HeLa, human gastric carcinoma cell line MKN-28, and human breast carcinoma cell line MCF-7 were evaluated. The compound (3β)-3-acetyloxy-5(6)-androsten-7-one oxime exhibited significant growth inhibitory properties against cell lines tested and afforded IC₅₀ value 26.0 ± 1.6, 12.8 ± 1.0, 18.1 ± 0.2, 10.2 ± 1.2 μM for KB, HeLa, MKN-28, and MCF-7, respectively.