Rho/ROCK signaling and caveolin-1 (Cav1) are implicated in tumor cell migration and metastasis; however, the underlying molecular mechanisms remain poorly defined. Cav1 was found here to be an ...independent predictor of decreased survival in breast and rectal cancer and significantly associated with the presence of distant metastasis for colon cancer patients. Rho/ROCK signaling promotes tumor cell migration by regulating focal adhesion (FA) dynamics through tyrosine (Y14) phosphorylation of Cav1. Phosphorylated Cav1 is localized to protrusive domains of tumor cells and Cav1 tyrosine phosphorylation is dependent on Src kinase and Rho/ROCK signaling. Increased levels of phosphorylated Cav1 were associated with elevated GTP-RhoA levels in metastatic tumor cells of various tissue origins. Stable expression and knockdown studies of Cav1 in tumor cells showed that phosphorylated Cav1 expression stimulates Rho activation, stabilizes FAK association with FAs, and promotes cell migration and invasion in a ROCK-dependent and Src-dependent manner. Tyrosine-phosphorylated Cav1, therefore, functions as an effector of Rho/ROCK signaling in the regulation of FA turnover and, thereby, tumor cell migration and invasion. These studies define a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors.
Introduction Diagnostic delays for breast problems is a current concern in British Columbia and diagnostic pathways for breast cancer are currently under review. Breast centres have been introduced ...in Europe and reported to facilitate diagnosis and treatment. Guidelines for breast centers are outlined by the European Society for Mastology (EUSOMA). A Rapid Access Breast Clinic (RABC) was developed at our hospital applying the concept of triple evaluation for all patients and navigation between clinicians and radiologists. We hypothesize that the Rapid Access Breast Clinic will decrease wait times to diagnosis and minimize duplication of services compared to usual care. Methods A retrospective review was undertaken looking at diagnostic wait times and the number of diagnostic centres involved for consecutive patients seen by breast surgeons with diagnostic workups performed either in the traditional system (TS) or the RABC. Only patients presenting with a new breast problem were included in the study. Results Patients seen at the RABC had a decreased time to surgical consultation (33 vs 86 days, p<0.0001) for both malignant (36 vs 59 days, p=0.0007) and benign diagnoses (31 vs 95 days, p<0.0001). Furthermore, 13% of the patients referred to the surgeon in the TS without a diagnosis were eventually diagnosed with a malignancy and waited a mean of 84 days for initial surgical assessment. Of the patients seen at the RABC, 5% required investigation at more than one institution compared to 39% patients seen in the TS (p<0.0001). Cancer patients had a shorter time from presentation to surgery in the RABC (64 vs 92 days, p=0.009). Conclusion The establishment of the RABC has significantly reduced the time to surgical consultation, time to breast cancer surgery, and duplication of investigations for patients with benign and malignant breast complaints. It is feasible to introduce a EUSOMA-based breast clinic in the Canadian Health Care System and improvements in diagnostic wait times are seen. We recommend the expansion of coordinated care to other sites.
Abstract Background To evaluate the expression pattern and prognostic significance of the type 1 growth factor receptor (T1GFR) family in colon carcinoma. Methods Tissue microarrays were constructed ...using 127 tumor samples and 47 metastatic lymph nodes and T1GFR family expression was determined by immunohistochemistry. Univariate and multivariate analyses examined clinicopathologic variables for prognostic significance, and the correlation between primary and lymph node expression was determined by Spearman correlation. Results Overexpression of HER-1, HER-2, HER-3, and HER-4 in tumor samples was 32%, 1%, 12%, and 37%, respectively, and 30%, 0%, 11%, and 24% in nodal samples, respectively. On multivariate analysis, positive margins, lymphatic invasion, and HER-3 expression were significant predictors of survival outcome. There was significant correlation between tumor and regional lymph node expression for the T1GFR family members. Tumor HER-3 expression was associated with lymphatic invasion and distant recurrence. Conclusions Tumor HER-3 expression has prognostic utility in individuals with colon carcinoma. Correlation between tumor and lymph node expression of T1GFR family members suggests that tumor receptor status may guide targeted therapy selection.
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