Colette O'Sullivan

Immunological and structural features of the protein core of human polymorphic epithelial mucin

The protein core of high mol. wt polymorphic epithelial mucin (PEM--approximately 400 kDa glycoprotein) which is associated with breast carcinomas, consists of a repeating 20 amino acid peptide motif [Gendler et al. (1988) J. biol. Chem. 263, 12,820-12,823]. Monoclonal antibodies C595 (anti-urinary mucin) and NCRC-11 (anti-breast carcinoma cells), and other antibodies against human milk fat globule membranes, were found to recognize determinants present within this 20 amino acid peptide. A model of the peptide was developed based on hydropathicity and structure prediction calculations and these indicated that the repeated structure is dominated by a hydrophilic domain of seven amino acids, extending into two flanking beta turns. NMR analysis of the 20 amino acid peptide was undertaken to probe the secondary structure. Epitope mapping experiments involving solid phase synthesis of overlapping heptapeptides in the repeat unit identified the minimum structures for antibody binding as Arg-Pro-Ala-Pro and Arg-Pro-Ala for the C595 and NCRC-11 antibodies, respectively. These determinants were found within the predicted hydrophilic turn region domain of the peptide. The epitopes for six other PEM-reactive monoclonal antibodies were also determined to reside within the predicted hydrophilic turn domain. This evidence is in accord with the disposition of this region of the PEM peptide core being at the exterior of the glycoprotein where it would be accessible to antibody recognition and binding events.

Tests to assist in the staging of cutaneous squamous cell carcinoma: a generic protocol

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine the diagnostic accuracy of sentinel lymph node biopsy (SLNB) for the detection of nodal metastases (in the investigated nodal basin) for the staging of cutaneous squamous cell cancer (cSCC). To determine the diagnostic accuracy of imaging tests, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, alone or in combination, for the detection of any metastasis for the staging of cutaneous squamous cell cancer. To determine the diagnostic accuracy of imaging tests for the detection of nodal metastases in the staging of cutaneous squamous cell cancer. To determine the diagnostic accuracy of imaging tests for the detection of distant metastases in the staging of cutaneous squamous cell cancer. We will estimate these separately for those undergoing primary staging and those who have experienced a disease recurrence. Sources of heterogeneity We will consider a range of potential sources of heterogeneity for investigation in each individual test review. These may vary between reviews but may include the following. i. Population characteristics • Primary tumour site (head and neck, trunk, limb, and other) • Primary staging versus mixed or unclear populations (i.e. including staging of recurrent disease) 1 Tests to assist in the staging of cutaneous squamous cell carcinoma: a generic protocol (Protocol) Copyright

Tests to assist in the staging of cutaneous melanoma: A generic protocol

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine the diagnostic accuracy of SLNB for the detection of nodal metastases (in the investigated nodal basin) for the staging of cutaneous invasive melanoma. To determine the diagnostic accuracy of imaging tests for the detection of any metastasis in the primary staging of cutaneous invasive melanoma (i.e. staging at presentation). To determine the diagnostic accuracy of imaging tests for the detection of any metastasis in the staging of recurrence in cutaneous invasive melanoma (i.e. re-staging prompted by findings on routine follow-up). To determine the diagnostic accuracy of imaging tests for the detection of nodal metastases in the staging of cutaneous invasive melanoma. To determine the diagnostic accuracy of imaging tests for the detection of distant metastases in the staging of cutaneous invasive melanoma. These will be estimated separately for those undergoing primary staging and those who have experienced a disease recurrence. Investigation of sources of heterogeneity We will consider a range of potential sources of heterogeneity for investigation in each individual test review. These may vary between reviews but may include the following. 1 Tests to assist in the staging of cutaneous melanoma: a generic protocol (Protocol) Copyright