Medicine & Health

Publication Search Results

Now showing 1 - 10 of 4261
  • (2008) Wani, Erick; Mooney-Somers, Julie; Akee, Angie; Maher, Lisa
    Journal Article
    The Indigenous Resiliency Participatory Action Research (IR PAR) project is one of four components of a collaborative project being conducted by Townsville Aboriginal and Islander Health Service, Derbarl Yerrigan Aboriginal Health Service, Perth, the Aboriginal Medical Service, Redfern and the National Centre in HIV Epidemiology and Clinical Research, UNSW. This part of the project uses a participatory action research framework to bring young Aboriginal and Torres Strait Islander people, staff from Aboriginal community controlled health services (ACCHS), and university researchers together to develop and conduct research on what keeps young people protected against blood borne viruses (BBV) and sexually transmitted infections (STI). This paper focuses on the research process, describing how we developed the IR PAR project in Townsville, reflecting on the challenges and celebrating the strengths we have encountered working together.

  • (2008) Webster, Lucy R.; Lee, Shu-Fen; Ringland, Clare; Morey, Adrienne L.; Hanby, Andrew M.; Morgan, Graeme; Byth, Karen; Mote, Patricia A.; Provan, Pamela J.; Ellis, Ian O.; Green, Andrew R.; Lamoury, Gillian; Ravdin, Peter; Clarke, Christine L.; Ward, Robyn L.; Balleine, Rosemary L.; Hawkins, Nicholas
    Journal Article
    Purpose: Identification of biologically and clinically distinct breast cancer subtypes could improve prognostic assessment of primary tumors. The characteristics of ‘molecular’ breast cancer subtypes suggest that routinely assessed histopathologic feature

  • (2009) Packham, Deborah; Ward, Robyn L; Lin, Vita Ap; Hawkins, Nicholas J; Hitchins, Megan P
    Journal Article
    Abstract: Activating mutations of the BRAF and KRAS genes cause constitutive stimulation of an important cell-signaling pathway promoting tumorigenesis, and are increasingly recognized as determinants of response to targeted cancer therapies. The V600E mutation accounts for most of the BRAF mutations in cancer, and KRAS mutations are predominantly encoded by nucleotide substitutions within codons 12 and 13. We designed novel pyrosequencing assays for the detection of the common ‘‘hotspot’’ mutations in these genes, which demonstrated analytical sensitivities of Z10% in titrations of mutant cell AQ1 lines. The KRAS pyrosequencing assay has the ability to simultaneously identify all potential nucleotide changes within the mutation cluster at codons 12 and 13, with a sequence output in the sense direction to facilitate results interpretation. These assays were used to determine the mutation status in a prospective series of 1198 sporadic colorectal cancers. The BRAF V600E mutation was detected in 13.2% of the colorectal cancers. The frequency of KRAS mutations in our cohort was 32.4%, with G>A transitions at position 2 of codons 12 and 13 being most prevalent. Both assays proved highly sensitive and specific when applied to clinical specimens, and were applicable to both fresh-frozen and formalin-fixed paraffin-embedded archival tissues. These assays would serve as a suitable platform for large-scale mutation detection in cancer specimens where the facility for pyrosequencing is available.

  • (2007) Hitchins, Megan P.; Lin, Vita Ap; Buckle, Andrew; Cheong, Kayfong; Halani, Nimita; Ku, Su; Kwok, Chau-To; Packham, Deborah; Suter, Catherine M.; Meagher, Alan; Stirzaker, Clare; Clark, Susan; Hawkins, Nicholas; Ward, Robyn L.
    Journal Article
    Biallelic promoter methylation and transcriptional silencing of the MLH1 gene occurs in the majority of sporadic colorectal cancers exhibiting microsatellite instability due to defective DNA mismatch repair. Long-range epigenetic silencing of contiguous genes has been found on chromosome 2q14 in colorectal cancer. We hypothesized that epigenetic silencing of MLH1 could occur on a regional scale affecting additional genes within 3p22, rather than as a focal event. We studied the levels of CpG island methylation and expression of multiple contiguous genes across a 4 Mb segment of 3p22 including MLH1 in microsatellite-unstable and -stable cancers, and their paired normal colonic mucosa. We found concordant CpG island hypermethylation, H3-K9 dimethylation and transcriptional silencing of MLH1 and multiple flanking genes spanning up to 2.4 Mb in microsatellite-unstable colorectal cancers. This region was interspersed with unmethylated genes, which were also transcriptionally repressed. Expression of both methylated and unmethylated genes was reactivated by methyltransferase and histone deacetylase inhibitors in a microsatellite-unstable colorectal carcinoma cell line. Two genes at the telomeric end of the region were also hypermethylated in microsatellite-stable cancers, adenomas, and at low levels in normal colonic mucosa from older individuals. Thus, the cluster of genes flanking MLH1 that was specifically methylated in the microsatellite-unstable group of cancers extended across 1.1 Mb. Our results show that coordinate epigenetic silencing extends across a large chromosomal region encompassing MLH1 in microsatellite-unstable colorectal cancers. Simultaneous epigenetic silencing of this cluster of 3p22 genes may contribute to the development or progression of this type of cancer.

  • (2007) Hitchins, Megan P.; Wong, Justin J.L.; Suthers, Graeme; Suter, Catherine M.; Martin, David I.K.; Hawkins, Nicholas; Ward, Robyn L.
    Journal Article
    Persons who have hypermethylation of one allele of MLH1 in somatic cells throughout the body (a germ-line epimutation) have a predisposition for the development of cancer in a pattern typical of hereditary nonpolyposis colorectal cancer. By studying the f

  • (2007) Hettiaratchi, A.; Hawkins, Nicholas; McKenzie, G.; Ward, Robyn L.; Hunt, J.E.; Wakefield, D.; Di Girolamo, N.
    Journal Article
    Matrix metalloproteinase (MMP) overexpression has been implicated in the pathogenesis of colorectal carcinoma (CRC). Accumulating evidence suggests that MMP promoter single nucleotide polymorphisms ( SNPs) effecting gene transcription are associated with

  • (2006) Colebatch, A.; Hitchins, M.; Williams, R.; Hawkins, Nicholas; Meagher, A.; Ward, Robyn L.
    Journal Article


  • (2006) Hitchins, Megan; Suter, C; Wong, Jenny; Cheong, Kay; Hawkins, Nicholas; Leggett, B; Scott, R; Spigelman, Allan; Tomlinson, Ian; Martin, David; Ward, Robyn
    Journal Article

  • (2005) Ward, Robyn; Turner, Jennifer; Williams, Rachel; Pekarsky, B; Packham, Deborah; Velickovic, M; Meagher, Alan; O'Connor, Terence; Hawkins, Nicholas
    Journal Article
    This study prospectively examines the accuracy of immunohistochemical staining in the identification of mismatch repair defective (MMRD) colorectal cancer in routine clinical practice. The potential impact of this information on decisions regarding adjuva