High PI3K expression is associated with CRC metastasis. PI3K inhibitor induced apoptosis in CRC cells and displayed strong cytotoxicity for highly metastatic cells. PI3K inhibition may be an effective treatment for CRC.

There is an unmet clinical need to identify biomarkers for breast cancer neoadjuvant chemotherapy. Here, using miRNA TaqMan Low-Density Arrays (TLDA), we analyzed the miRNA expression profile in pre-treatment needle aspiration tumor samples from patients who received taxane-anthracycline-based neoadjuvant chemotherapy. Although, in an unsupervised hierarchical cluster analysis, the total miRNA expression profile could not generate a tree with clear distinction between pathologic complete response (pCR) and non-pCR classes, we found that elevated expression of miR-125b and miR-141 was associated with non-pCR. In vitro experiments indicated that inhibition of miR-125b and miR-141 expression reduced cellular survival in response to taxane-anthracycline treatment. Furthermore, co-transfection with miR-125b and miR-141 mimics increased resistance of MCF7 and BT549 cells to taxane-anthracycline induced cytotoxicity. Pathway analyses indicated that many of the target proteins of miR-125b are involved in apoptotic pathways and cell cycle control. Together, we provide evidence that elevated miR-125b and 141 expression predicts a poor clinical responsiveness of taxane-anthracycline-based neoadjuvant chemotherapy.

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Caveolin-1 (Cav-1) expression in stromal carcinoma-associated fibroblasts (CAFs) has been associated with tumor progression and clinical outcome. This study was undertaken to assess its prognostic significance in invasive micropapillary carcinoma of the breast (IMPC), a tumor with abundant stromal CAFs and a high tendency for nodal metastasis and poor outcome. Cav-1 expression was studied by immunohistochemistry in a group of 86 cases of IMPC along with a control group of 105 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). Our results indicate that absence of Cav-1 expression in CAFs of IMPC is more common than in IDC-NOS (57 %, 49/86 vs. 36 %, 38/105). The absence of expression was associated with larger tumor size and higher lymph node stage (P < 0.05) of IMPC. Univariate analysis suggested absence of Cav-1 in CAFs to be a candidate independent predictor of reduced progression-free survival (PFS) (HR = 3.945, 95 % CI = 1.717-9.063, P = 0.001), which was confirmed by multivariable analysis (P = 0.018). In patients with IMPC spreading to local lymph nodes, loss of stromal Cav-1 predicted a fourfold increase in risk for shortened PFS. In contrast, no significant difference of tumor epithelial Cav-1 expression was found between IMPC and IDC-NOS, and the expression of tumor Cav-1 was not significantly associated with the prognosis of patients with IMPC. Absence of Cav-1 expression in CAFs is a strong prognostic factor for IMPC patients, and it may further subgroup the patients with lymph node metastasis to guide clinical management.

Background: There has been a considerable focus on the changes of functional connections between brain regions in patients with type 2 diabetes mellitus (T2DM) by previous resting-state functional magnetic resonance imaging (rs-fMRI) studies. However, little is known about the function of brain information integration between the two hemispheres of the brain. This study explores differences in interhemispheric coordination between T2DM patients and normal control (NC) subjects using the voxel-mirrored homotopic connectivity (VMHC) method. We also assess whether differences in VMHC were relevant to cognitive dysfunction in T2DM patients.Methods: Sixty-nine T2DM patients and 69 NC subjects were enrolled (matched for age, sex and education level). All participants underwent cognitive assessments. VMHC between brain regions was obtained by rs-fMRI analysis. Partial correlation analysis (after controlling for age, sex and education level) was used to explore the correlation between VMHC value and neuropsychological tests.Results: Compared with NC subjects, T2DM patients exhibited significantly lower VMHC in the medial orbitofrontal gyrus cortex (mOFC), anterior cingulate gyrus, inferior parietal lobe, superior and middle temporal gyrus (MTG), middle occipital gyrus, and superior occipital gyrus. Moreover, after applying Bonferroni correction, the Montreal Cognitive Assessment (MoCA) score and VMHC value for the MTG were significantly positively correlated in T2DM patients. In contrast, T2DM patients exhibited higher VMHC in the cerebellum posterior lobe and tonsil and inferior temporal gyrus than the NCs.Conclusions: Our study indicates that functional coordination between homotopic brain regions is generally impaired in T2DM patients. In brain regions with decreased VMHC in the default mode network (DMN), MTG impairment could serve as a critical node for T2DM-related cognitive dysfunction. Furthermore, the increased VMHC observed in the cerebellum and inferior temporal gyrus might indicate a functional coordination mechanism.