Objective To investigate the combined inhibition effect and the potential mechanism of rapamycin (mammalian target of rapamycin inhibitor) and PD98059 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor) on mouse colorectal cancer (CRC). Methods S-ICR mice were subcutaneously injected with 20 mg/kg of 1,2-dimethylhydrazine dihydrochloride in the nape for 20 weeks to induce CRC. From the 16th week, the mice were treated with alone or combined injection with 0.25 mg/kg rapamycin and 2.5 mg/kg PD98059. The drugs were administered for 8 weeks. Subsequently, the animals were sacrificed and dissected, the tumor sizes were measured, and the tumors were harvested for pathological assay. Furthermore, the phosphorylation of mTOR, p70S6K, and 4E-BPl proteins was detected by using immunohistoehemistry. Results The mice treated with rapamycin (44. 44 %) or PD 98059 (either alone (38.89%) or combination treatment (6.67%) were significantly less likely to develop cancer compared with mice receiving none of them (77.78%, P<0. 05). The average size of tumors was (6.15±2. 192), (8.85±3. 983), (2.917±0. 191), (16.36±6.855) mm3 respectively (P<0.05).The anti-cancer effect of the combination treatment was substantially significant. The proteins of phospho-mTOR, phospho-p70s6K and phospho-4E-BPl were significantly down-regulated after treatments (all P values < ,0.05). Conclusions Combined treatment was more effective than single-drug treatments of rapamycin or PD98059 alone for the prevention and treatment of mouse CRC. The mTOR signal pathway might be involved in the inhibitory mechanism.

OBJECTIVETo detect the expression of pan-neuronal marker protein gene product (PGP)9.5 and its clinicopathologic significance in breast cancer.

METHODSThe expression of PGP9.5 was examined by immunohistochemistry EnVision method in 196 cases during 2007 to 2011, including 20 normal tissues, 14 cases of fibroadenoma, 18 cases of ductal carcinoma in situ (DCIS) and 144 cases of invasive ductal carcinoma (IDC) of the breast. The relationship between PGP9.5 expression and clinicopathologic characteristics of IDC was assessed.

RESULTSPGP9.5 expression was localized in the stroma of all normal breast tissues, but there was no expression observed in all fibroadenomas and DCIS. Overall, the expression rate of PGP9.5 in IDC was 61.8% (89/144). PGP9.5 expression increased from grade 1 tumors (29.4%, 10/34) to grade 2-3 tumors (71.8%, 79/110; P = 0.000). In addition, patients with less than 3 years disease-free survival tended to show higher PGP9.5 expression (64.8%, 35/54), compared to patients with equal to and/or more than 3 years disease-free survival (46.7%, 42/90; P = 0.035). However, there was no correlation between PGP9.5 expression and tumor size, tumor stage, lymph metastasis, hormone receptor expression.

CONCLUSIONPGP9.5 expression is correlated with tumor grade and prognosis in IDC of the breast.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Disease-Free Survival ; Female ; Fibroadenoma ; metabolism ; pathology ; Humans ; Middle Aged ; Neoplasm Grading ; Ubiquitin Thiolesterase ; metabolism