Medicine and Health Sciences Commons^™

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

A Diagnostic Autoantibody Signature For Primary Cutaneous Melanoma, Pauline Zaenker, Johnny Lo, Robert L. Pearce, Phillip Cantwell, Lester Cowell, Mark Lee, Christopher Quirk, Henry Law, Elin S. Gray, Mel R. Ziman Dr

Research outputs 2014 to 2021

Melanoma is an aggressive form of skin cancer that is curable by surgical excision in the majority of cases, if detected at an early stage. To improve early stage melanoma detection, the development of a highly sensitive diagnostic test is of utmost importance. Here we aimed to identify antibodies to a panel of tumour associated antigens that can differentiate primary melanoma patients and healthy individuals. A total of 245 sera from primary melanoma patients and healthy volunteers were screened against a high-throughput microarray platform containing 1627 functional proteins. Following rigorous statistical analysis, we identified a combination of 10 autoantibody biomarkers …

Clinical Application Of Circulating Tumor Cells And Circulating Tumor Dna In Uveal Melanoma, Aaron Beasley, Timothy Isaacs, Muhammad K. Khattak, James B. Freeman, Richard Allcock, Fred K. Chen, Michelle R. Pereira, Kyle Yau, Jaqueline Bentel, Tersia Vermeulen, Leslie Calapre, Michael Millward, Melanie R. Ziman, Elin S. Gray

Research outputs 2014 to 2021

Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).

Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein β (S100β). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLCβ4, and CYSLTR2 …

Sensitive Droplet Digital Pcr Method For Detection Of Tert Promoter Mutations In Cell Free Dna From Patients With Metastatic Melanoma, Ashleigh C. Mcevoy, Leslie Calapre, Michelle Pereira, Tindaro M. Giardina, Cleo Robinson, Muhammad A. Khattak, Tarek M. Meniawy, Antonia L. Pritchard, Nicholas K. Hayward, Benhur Amanuel, Michael J. Millward, Mel R. Ziman Dr, Elin S. Gray

Research outputs 2014 to 2021

Background:

Currently mainly BRAF mutant circulating tumor DNA (ctDNA) is utilized to monitor patients with melanoma. TERT promoter mutations are common in various cancers and found in up to 70 % of melanomas, including half of BRAF wildtype cases. Therefore, a sensitive method for detection of TERT promoter mutations would increase the number of patients that could be monitored through ctDNA analysis.

Methods:

A droplet digital PCR (ddPCR) assay was designed for the concurrent detection of chr5:1,295,228 C > T and chr5:1,295,250 C > T TERT promoter mutations. The assay was validated using 39 melanoma cell lines and 22 matched plasma and …

Serum Peptidome Profiling For The Diagnosis Of Colorectal Cancer: Discovery And Validation In Two Independent Cohorts, Hao Wang, Chenghua Luo, Shengtao Zhu, Honghong Fang, Qing Gao, Siqi Ge, Haixia Qu, Qingwei Ma, Hongwei Ren, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were …

The Specialist Breast Care Nurse's Role In The Indentification And Minimisation Of Distress In A Members' Only, Breast Cancer Focused Online Support Community, Cynthia Witney, Joyce M. Hendricks Phd, Vicki C. Cope Ms

Research outputs 2014 to 2021

Objectives: To show how a specialist breast care nurse (SBCN) can use the distress thermometer to determine an online community member’s distress level and then use the information in their posts and blogs to identify the cause(s) and deal with them appropriately. To highlight the use of a structured written emotional expression (SWEE) format online, as a way of minimising distress. Method: A survey of online community members together with analysis of the content of members’ posts and blogs to determine whether their distress thermometer score had decreased since the SBCN had been online to deal with member distress. Results: …

Serum Concentrations Of The Biomarkers Ca125, Ca15-3, Ca72-4, Tpsa And Papp-A In Natural And Stimulated Ovarian Cycles, Melissa J. Stemp, Peter Roberts, Allison Mcclements, Vincent Chapple, Jay Natalwala, Michael L. Black, Phillip L. Matson

Research outputs 2014 to 2021

Objective: Biomarkers associated with cancer screening (CA125, CA15-3, CA72-4, total prostate specific antigen [tPSA]) and the monitoring of pregnancy (pregnancy associated plasma protein-A [PAPP-A]) were measured during natural and stimulated ovarian cycles in disease-free non-pregnant women to determine if they could reflect normal events relating to ovulation and/or endometrial changes. Methods: A total of 73 blood samples (10 women) collected throughout the natural menstrual cycle, and 64 blood samples (11 women) taken during stimulated ovarian cycles, were analysed on the Roche Cobas e411 automated analyser. Results: Detectable levels of tPSA were measured in at least one point in the cycle …