Expression and Targeting of the Apoptosis Inhibitor, Survivin, in Human Melanoma

The newly described apoptosis inhibitor survivin is expressed in many human cancers and appears to play a critical part in both apoptosis regulation and cell cycle progression. Its potential role in malignant melanoma is unknown. In a panel of 30 malignant melanomas, survivin was strongly expressed in all cases (15 of 15) of metastatic malignant melanomas and 13 of 15 cases of invasive malignant melanomas by immunohistochemistry. In invasive malignant melanomas, survivin was also expressed in the in-situ component of the lesion. Survivin expression was found in all cases (11 of 11) of nevi, but not in melanocytes in sections of normal skin. The apoptosis inhibitor bcl-2 was expressed in 26 of 30 cases, but generally at lower levels than that of infiltrating lymphocytes. The mitotic index, as assessed by MIB-1 staining, was consistently higher in metastatic than invasive malignant melanomas. Assessment of apoptotic index by in situ end-labeling revealed extremely low rates of apoptosis in most malignant melanomas. Survivin expression by western blotting was detected in four human metastatic malignant melanoma cell lines but not in cultured normal human melanocytes. Transfection of both YUSAC-2 and LOX malignant melanoma cells with green fluorescence protein-conjugated survivin anti-sense or green fluorescence protein-conjugated survivin dominant negative mutant (Cys85Ala) resulted in increased apoptosis in the absence of other genotoxic stimuli. Two-color flow cytometry confirmed that YUSAC-2 cells transfected with survivin anti-sense expressed less endogenous survivin and exhibited an increased fraction of cells with sub-G1 DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of malignant melanomas, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or metastatic disease

Billie Boy

The Staunton Sisters sing live over Roanoke Country Radio station WDBJ. The musicians are the Georgia Wildcats

Australian university general practices : potential to reach out to vulnerable young people

There will be some 1.9 billion youth aged 15–24 globally by 2030.1 Youth can be a positive force for economic growth when they are provided with the knowledge and opportunities to thrive. However, for young people and particular those that are marginalised, health care access has been identified as a contributory factor to their vulnerability.2 Barriers include lack of knowledge of health services, inconvenient opening hours, cost, waiting times, unfriendly environments and lack of doctor confidence in dealing with young people.3 Best practice guidelines and proposals of alternate youth-centric models of healthcare are proposed. One group of healthcare services that has yet to be described in the literature are university associated general practices located on and close to university campuses. This group of general practices may already be providing improved access to health care for many young people and be uniquely positioned to reach out to the more vulnerable amongst them. As an initial step to better understand Australian university general practices we conducted a pilot study of Brisbane’s Queensland University of Technology (QUT) general practice. This descriptive work included a retrospective review of 12-months of age stratified encounter data (Ethics: 1500001132)