Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression

<p>Abstract</p> <p>Background</p> <p>The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.</p> <p>Methods</p> <p>We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.</p> <p>Results</p> <p>All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.</p> <p>Conclusion</p> <p>This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.</p

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored

Melanoma Patients with Positive Sentinel Nodes Who Did Not Undergo Completion Lymphadenectomy: A Multi-Institutional Study

Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45875/1/10434_2006_Article_10237.pd

The life of James Dwight Dana, scientific explorer, mineralogist, geologist, zoologist, professor in Yale University,

The United States exploring expedition, 1838-1842: p. 45-151.Bibliography: p. 385-394.Mode of access: Internet

University problems in the United States,

The Johns Hopkins university in its beginning.--The utility of universities.--The characteristics of a university.--The Sheffield scientific school of Yale university, New Haven.--The University of California in its infancy.--Knowledge and charity.--Modern progress in medicine.--University libraries.--The Teachers' college of Columbia university.--Washington and Lee university.--Higher education in the United States.--The proposals for a national university in Washington.Mode of access: Internet

The launching of a university, and other papers; a sheaf of remembrances,

Partly reprinted from pamphlets and from various periodicals.The Johns Hopkins University: I. Reminiscenses of thirty years in Baltimore (1875-1905) II. Johns Hopkins and the trustees of his choice. III. Fundamental principles. IV. The original faculty. V. Some noteworthy teachers. VI. Incidents of the early years. VII. Publications. VIII. The Johns Hopkins Medical School. IX. Resignation; after twenty-five years' service.--Addresses on various occasions, historical and educational. X. Remembrances; looking backwards over fifty years. XI. The relations of Yale to science and letters (1701-1901) XII. Books and politics. XIII. California revisited. XIV. Research; a speech at Chicago. XV. The dawn of a university in the Western Reserve. XVI. Hand-craft and rede-craft. XVII. De juventute. XVIII. Greek art in a manufacturing town. XIX. A study in black and white. XX. Civil service reform. XXI. Education in philanthropy. XXII. Colonel John Eager Howard, one of the worthies of Baltimore.Mode of access: Internet

Addresses at the inauguration of Daniel C. Gilman, as president of the Johns Hopkins University, Baltimore, February 22, 1876.

Inaugural address of Gilman, p. 17-64.Mode of access: Internet

Gilman, Daniel C.. -- 1884-1901

Funding for digitization provided by the National Historical Publications and Records Commission

Gilman, Daniel C.. -- 1884-1901

Funding for digitization provided by the National Historical Publications and Records Commission