Hyacinth bean (Lablab purpureus [Linn.] Sweet) possesses excellent characteristics for field production, but the response of this plant to drought stress has not been described at the molecular level. Suppression subtraction hybridization (SSH) is an effective way to exploit key factors for plant responses to drought stress that are involved in transcriptional and metabolic activities. In this study, forward and reverse SSH libraries were generated from root tissues of the drought-tolerant hyacinth bean genotype MEIDOU 2012 under water–stress conditions. A total of 1,287 unigenes (94 contigs and 1,193 singletons) were derived from sequence alignment and cluster assembly of 1400 ESTs, and 80.6% of those hit against NCBI non-redundant (nr) database with E value <1E−06. BLASTX analysis revealed that the majority top matches were proteins form Glycine max (L.) Merrill. (61.5%). According to a gene ontology (GO) functional classification, 816 functionally annotated unigenes were assigned to the biological process category (74.1%), and 83.9% of them classified into molecular function and 69.2% involved in cellular component. A total of 168 sequences were further annotated with 207 Enzyme Commission (EC) codes and mapped to 83 different KEGG pathways. Seventeen functionally relevant genes were found to be overrepresented under drought stress using enrichment analysis. Differential expression of unigenes were confirmed by quantitative real-time PCR assays, and their transcript profiles generally divided into three patterns, depending on the expression peaked levels after 6, 8 or 10 days dehydration, which indicated that these genes are functionally associated in the drought-stress response.

Acute myeloid leukemia (AML) with inversion of chromosome 3 is characterized by overexpression of EVI1 and carries a dismal prognosis. Arsenic-containing compounds have been described to be efficacious in malignancies overexpressing EVI1. Here, we describe a case of AML with inv(3)(q21q26.2) treated with the organic arsenical darinaparsin. Using a “personalized medicine approach,” two different arsenicals were screened for anti-leukemic effect against the patient’s cells ex vivo. The most promising compound, darinaparsin, was selected for in vivo treatment. Clinical effect was almost immediate, with a normalization of temperature, a stabilization of white blood cell (WBC) counts and an increased quality of life. Longitudinal monitoring of patient response and resistance incorporating significant correlative studies on patient-derived blood samples over the two cycles of darinaparsin given to this patient allowed us to evaluate potential mechanisms of response and resistance. The anti-leukemic effects of darinaparsin correlated with inhibition of the alternative NF-κB pathway and production of the inflammatory cytokine IL-8. Emergence of resistance was suspected during treatment cycle 2 and supported by xenograft studies in nude mice. Darinaparsin resistance correlated with an attenuation of the effect of treatment on the alternative NF-κB pathway. The results from this patient indicate that darinaparsin may be a good treatment option for inv(3) AML and that inhibition of the alternative NF-κB pathway may be predictive of response. Longitudinal monitoring of disease response as well as several correlative parameters allowed for the generation of novel correlations and predictors of response to experimental therapy in a heavily pretreated patient.

DNA double-strand breaks (DSBs) are among the most lethal lesions associated with genome stability, which, when destabilized, predisposes organs to cancers. DSBs are primarily fixed either with little fidelity by non-homologous end joining (NHEJ) repair or with high fidelity by homology-directed repair (HDR). The phosphorylated form of H2AX on serine 139 (γ-H2AX) is a marker of DSBs. In this study, we explored if the protein phosphatase PP6 is involved in DSB repair by depletion of its expression in human cancer cell lines, and determined PP6 expression in human breast cancer tissues by immunohistochemistry staining. We found that bacterially produced PP6c (the catalytic subunit of PP6)-containing heterotrimeric combinations exhibit phosphatase activity against γ-H2AX in the in vitro phosphatase assays. Depletion of PP6c or PP6R2 led to persistent high levels of γ-H2AX after DNA damage and a defective HDR. Chromatin immunoprecipitation assays demonstrated that PP6c was recruited to the region adjacent to the DSB sites. Expression of PP6c, PP6R2 and PP6R3 in human breast tumors was significantly lower than those in benign breast diseases. Taken together, our results suggest that γ-H2AX is a physiological substrate of PP6 and PP6 is required for HDR and its expression may harbor a protective role during the development of breast cancer.

In the last 15 years, chemotherapy-based therapeutic regimens for the treatment of osteosarcoma have failed to demonstrate improved survival rates. Novel approaches, including targeted therapy and antiangiogenic therapy, may provide new methods for the treatment of osteosarcoma, one of the most deadly malignant diseases. In the present study, the therapeutic efficacy of an endogenous angiogenesis inhibitor, endostatin, was tested in combination with the chemotherapeutic agent, adriamycin. BALB/c mice, aged 4-6 weeks were fed animal chow and had access to water ad libitum. The mice were divided into groups and injected with tumor cells. Immunohistochemical staining was performed to identify the microvessel density. The TUNEL technique was also used to determine the apoptotic index. The combination of endostatin and adriamycin produced marked synergistic antitumor activity in a mouse osteosarcoma model. These findings provide new guidelines for designing future clinical trials and for the application of currently available clinical drugs (endostatin has been approved for clinical use) in the treatment of osteosarcoma.

Objective

To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer.

Methods

A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were available for these patients.

Results

Luminal A (ER+ and/or PR+, HER2-) had a favorable disease-free survival (DFS) and overall survival (OS) compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2+ (ER-, PR-, HER2+) had the worst DFS (hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017) and luminal B (ER+ and/or PR+, HER2+) had the worst OS (HR=2.27, 95% CI 1.50 to 3.45, P<0.001); among the patients with lymph node negative disease, triple-negative (ER-, PR-, HER2-) had the worst DFS (HR=2.21, 95% CI 1.43 to 3.41, P<0.001), whereas no significant difference in DFS between HER2+ and luminal B or luminal A was observed.

Conclusion

As compared with luminal A, luminal B and HER2+ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.