Heat shock proteins and cancer: The FoxM1 connection.

Heat shock proteins (Hsp) and FoxM1 have significant roles in carcinogenesis. According to their relative molecular weight, Hsps are divided into Hsp110, Hsp90, Hsp70, Hsp60, Hsp40, and small Hsps. Hsp70 can play essential functions in cancer initiation and is overexpressed in several human cancers. Hsp70, in combination with cochaperones HIP and HOP, refolds partially denatured proteins and acts as a cochaperone for Hsp90. Also, Hsp70, in combination with BAG3, regulates the FoxM1 signaling pathway. FoxM1 protein is a transcription factor of the Forkhead family that is overexpressed in most human cancers and is involved in many cancers' development features, including proliferation, migration, invasion, angiogenesis, metastasis, and resistance to apoptosis. This review discusses the Hsp70, Hsp90, and FoxM1 structure and function, the known Hsp70 cochaperones, and Hsp70, Hsp90, and FoxM1 inhibitors.

Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

OBJECTIVE: Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. METHODS: This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. RESULTS: In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. CONCLUSION: According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1.

Intakes of Vegetables and Fruits are Negatively Correlated with Risk of Stroke in Iran.

BACKGROUND: Stroke is a leading cause of death. Current therapeutic strategies have been unsuccessful. Several studies have reported benefits on reducing stroke risk and improving the poststroke associated functional declines in patients who ate foods rich in fruits and vegetables. Their potential protective effects may be due to their antioxidants, calcium, potassium, riboflavine, peridoxin, riboflavin contents. Folic acid, peridoxin, and riboflavin are all cofactors in hyperhomocysteinemia as a stroke risk factor.Studies suggest that oxidative stress plays important roles in pathogenesis of ischemic cerebral injury and higher intake of antioxidants has been associated with a lower stroke risk. The aim of this study was to examine if the dietary intake of vegetables and fruits in patients with stroke were comparatively worse than those in patients without stroke. METHODS: In this case control study, 93 stroke patients admitted to Alzahra hospital were matched for age and sex with 60 patients who were not affected with acute cerebrovascular diseases and did not have a history of stroke. Dietary intake was assessed with a validated food frequency questionnaire.Food intakes were compared between two groups and with recommended value. RESULTS: Mean daily intake of vegetable and fruits was more in male with stroke than male without stroke as well as calorie intake from vegetables and fruit was higher in male with stroke.Mean daily intake of vegetable and fruits were lower in women with stroke than women without stroke as well as calorie intake from vegetables and fruit was lower in women with stroke. CONCLUSIONS: Our findings suggest that increased vegetable and fruits intake may be associated with decreased risk of stroke.