Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm.

BACKGROUND: We investigated the roles of p120 catenin, Cdc42, Rac1, and RhoA GTPases in regulating migration of presomitic mesoderm cells in zebrafish embryos. p120 catenin has dual roles: It binds the intracellular and juxtamembrane region of cadherins to stabilize cadherin-mediated adhesion with the aid of RhoA GTPase, and it activates Cdc42 GTPase and Rac1 GTPase in the cytosol to initiate cell motility. RESULTS: During gastrulation of zebrafish embryos, knockdown of the synthesis of zygotic p120 catenin δ1 mRNAs with a splice-site morpholino caused lateral widening and anterior-posterior shortening of the presomitic mesoderm and somites and a shortened anterior-posterior axis. These phenotypes indicate a cell-migration effect. Co-injection of low amounts of wild-type Cdc42 or wild-type Rac1 or dominant-negative RhoA mRNAs, but not constitutively-active Cdc42 mRNA, rescued these p120 catenin δ1-depleted embryos. CONCLUSIONS: These downstream small GTPases require appropriate spatiotemporal stimulation or cycling of GTP to guide mesodermal cell migration. A delicate balance of Rho GTPases and p120 catenin underlies normal development.

Sociotropy, autonomy, and masculinity/femininity: implications for vulnerability to depression.

To explore the magnitude of overlap between sociotropy and autonomy with sex-role orientation, relations of Beck's Sociotropy-Autonomy Scale with 6 measures of sex-role orientation were examined using a convenience sample of 153 undergraduate students. The sample included 95 women and 58 men whose mean age was 20.4 yr. A principal axis factor analysis yielded two dear factors, one masculine and one feminine. Sociotropy related strongly to the feminine factor, and Autonomy related strongly to the masculine factor. The mean score for women was significantly higher than that for men on Sociotropy, but the mean difference on Autonomy was not statistically significant. These findings suggest there may be some definitional overlap between vulnerability to depression and sex-role orientation.

Show Us the Data: The Critical Role Health Information Plays in Health System Transformation.

Truly transforming the healthcare delivery and payment system turns on the ability to engage in the interoperable electronic exchange of patient health information across and beyond the care continuum. Achieving transformation requires a legal framework that supports information sharing with appropriate privacy and security protections and a trusted governance structure.

Existing Medicaid beneficiaries left off the Affordable Care Act's prevention bandwagon.

The recent health reform law promotes access to preventive care through new insurance coverage requirements. Most private insurance plans, Medicare, and Medicaid expansion programs are required to cover US Preventive Services Task Force A- and B-rated services without cost sharing. However, because the Affordable Care Act treats newly eligible and existing Medicaid beneficiaries differently, all adult Medicaid beneficiaries within a state might not be eligible for the same preventive services. This study reviewed Medicaid programs across the country and found that most states do not cover all of these recommended services as preventive measures for adults. As a result, existing adult Medicaid beneficiaries might not have coverage of the same important preventive services that most other insured people have. In addition, aspects of how preventive services are defined in many states result in confusion about coverage parameters, potentially creating an additional access barrier for existing Medicaid beneficiaries.

Up-regulation of vascular endothelial growth factor-C by nicotine in cervical cancer cell lines.

PROBLEM: Smoking and infection with human papilloma virus (HPV) are major risk factors for cervical cancer. Our earlier work shows that nicotine enhances cellular proliferation of cervical cancer cell lines by up-regulating epidermal growth factor (EGF) and its receptor EGF-R, which leads to increased insulin-like growth factor II in vitro. We found that the vascular endothelial growth factor (VEGF)-C, one of the five isoforms of VEGF, may be specifically involved in lymphogenic metastasis of cervical cancer. This has prompted us to study if in vitro nicotine treatment will up-regulate VEGF-C alongside EGF-R levels, while down regulating the anti-proliferative transforming growth factor (TGF)-beta levels in HPV positive cervical cancer cell lines. METHOD OF STUDY: Cervical cancer cell lines CaSki, HeLa and ME-180, were cultured in serum free DMEM medium for 24-hr, and treated with 10 ng/mL nicotine in the medium supplemented with 10% fetal bovine serum. A group of untreated cells served as controls. The cells were cultured in chamber slides (for immunofluorescent antibody assay) as well as microtiter plate wells (for BrdU cell proliferation assay). The cellular levels of VEGF-C, TGF-beta, EGF-R and HPV-E6 (early protein 6) were measured by a semi-quantitative immunofluorescent antibody assay. The cell proliferation and immunofluorescent assay data were analyzed by a Student's t-test. RESULTS: Cell proliferation was significantly increased after nicotine treatment in all the cell lines. The VEGF-C levels were significantly increased, while TGF-beta levels were decreased by nicotine in all the cell lines (P < 0.00001). EGF-R levels were also significantly increased after nicotine treatment in HeLa and ME-180, while HPV-E6 levels remained unchanged in all three. CONCLUSIONS: Nicotine up regulates expression of cell proliferative VEGF-C and EGF-R, while down-regulating anti-proliferative TGF-beta. Our data suggest that nicotine in circulation and in cervical squamous epithelial cells may promote not only rapid tumor growth but its lympho-angiogenic spread (VEGF-C) as well. It appears that nicotine does not promote HPV spread in the cervical cancer cells.

Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected].

OBJECTIVES: An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected] VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3). MATERIAL AND METHODS: (a) Serum levels of IGF-II, IGF-BP3, VEGF-A [corrected] (VEGF(165)) and VEGF-C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75 persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III; 70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t test, chi-square analysis and linear regression analysis were used. RESULTS: (a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF-BP3 showed a significant decrease with advancing disease. Serum VEGF-A [corrected] levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF-C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF-C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF-C and IGF-II and a negative correlation between IGF-BP3 and VEGF-C (P < 0.0001). CONCLUSION: Serum IGF-II up-regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF-C up-regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF-BP3 and VEGF-A [corrected] appear to be common markers for all gynecological cancers.