Sodium valproate inhibits MDA-MB-231 breast cancer cell migration by upregulating NM23H1 expression.

Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.

Correction of Hyperglycemia in Diabetic Rats With the Use of Microencapsulated Young Market Pig Islets.

OBJECTIVE: The aim of this work was to investigate the transplantation efficacy of microencapsulated young market pig islets in a diabetic rat model. METHODS: Islets were isolated and purified from young market pigs obtained from a local slaughterhouse. The islets were encapsulated in barium alginate and subjected to a glucose-induced insulin release functional assay in culture. Microencapsulated islets were transplanted into diabetic Sprague-Dawley rats and removed after 30 days for histologic examination. RESULTS: The mean islet equivalent (IEQ) yield per gram of digested tissue was 3,125 ± 617 IEQ/g after isolation and 2,618 ± 917 IEQ/g after purification, respectively. Host rats' blood glucose concentrations normalized (from 22.3 ± 2.7 mmol/L to 5.1 ± 0.67 mmol/L) following encapsulated islet transplantation. After graft removal, hyperglycemia recurred in the rats, indicating that the grafts were responsible for maintaining euglycemia. Histology revealed viable islets in the capsules 30 days after graft removal. Immunolabeling of insulin verified that ß-cells within the capsules remained well granulated. No fibrosis or immune cells were found in histopathology. CONCLUSIONS: Barium alginate encapsulation of young market pig islets can normalize glucose regulation in diabetic rats without fibrosis or an immunologic response.

SmartArc-based volumetric modulated arc therapy can improve the middle ear, vestibule and cochlea sparing for locoregionally advanced nasopharyngeal carcinoma: a dosimetric comparison with step-and-shoot intensity-modulated radiotherapy.

OBJECTIVE: Radiation-induced sensorineural hearing loss is a common complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that significantly affects their quality of life. The goal of this study was to compare SmartArc-based volumetric modulated arc therapy (VMAT-S) with step-and-shoot intensity-modulated radiation therapy (IMRT) for patients with locoregionally advanced NPC with regard to the sparing effect on middle ear, vestibule and cochlea. METHODS: 20 patients with non-metastatic Stage III or IV NPC were selected to have planning with VMAT-S and IMRT [using Philips Pinnacle Planning System (Philips, Fitchburg, WI) for Varian accelerator] for dosimetric comparison. Mean middle ears, vestibule and cochlea doses for the two planning techniques were compared using a paired t-test. Target coverage and dose homogeneity were evaluated by calculating conformity index (CI) and homogeneity index (HI) values. RESULTS: VMAT-S had significantly improved homogeneity and conformity compared with IMRT. Mean HI of planning target volume of gross tumour volume (PGTV) was better with VMAT-S (1.05 ± 0.02) than IMRT (1.09 ± 0.03) (p < 0.001). Mean CI of PGTV is also better with VMAT-S (0.59 ± 0.12) than IMRT (0.54 ± 0.12) (p < 0.001). Mean doses to the left cochleas were 43.8 ± 3.6 and 47.8 ± 4.0 (p < 0.001) for VMAT-S and IMRT plans, respectively. Mean doses to the right cochleas were 42.7 ± 4.7 and 47.6 ± 5.4 (p < 0.001) for VMAT-S and IMRT plans, respectively. VMAT-S also significantly reduced the mean doses to middle ears (p < 0.001 for both) and vestibule (p < 0.001 for both). CONCLUSION: Our results indicate that VMAT-S provides better sparing of hearing apparatus in locoregionally advanced NPC. ADVANCES IN KNOWLEDGE: VMAT-S can improve the middle ear, vestibule and cochlea sparing in patients with locoregionally advanced NPC.