Simon Fear

Bio: Simon Fear is an academic researcher from University of Liverpool. The author has contributed to research in topics: Cancer & Stromal cell. The author has an hindex of 3, co-authored 3 publications receiving 227 citations.

Localisation by in situ hybridisation of S100A4 (p9Ka) mRNA in primary human breast tumour specimens.

Abstract: Rodent S100A4 (p9Ka) induces a metastatic phenotype in benign rat mammary tumour cells and cooperates with the neu oncogene to produce metastatic tumours in a transgenic mouse model system. Human S100A4 possesses similar metastasis-inducing properties. S100A4 mRNA is now sought in human breast tumour-derived cell lines and tumour specimens. S100A4 mRNA is present in some cell lines derived from malignant breast cancers, but is not detectable in cells derived from benign breast tumours, In human tumour specimens, using in situ hybridisation, the mRNA for S100A4 is localised to the epithelial cells of carcinoma specimens, and in some normal breast specimens, to a stromal region surrounding the epithelial ducts, In carcinoma specimens, S100A4 mRNA is also found in the stromal region surrounding islands of cancer cells. For both the epithelial and stromal components, S100A4 mRNA is present at a higher level in carcinomas relative to benign breast tumour specimens. In general, there is a concordance between the S100A4 mRNA signal from the epithelial and stromal elements of the same carcinoma specimens. Using Northern blotting techniques, these results have been extended to a panel of 137 benign and malignant breast tumour specimens. The results show that S100A4 mRNA occurs in the more-malignant, rather than in the more-benign tumour specimens. Int. J, Cancer 86: 219-228, 2000. (C) 2000 Wiley-Liss, Inc.

Abstract 5246: Conceptualization of core clinico-molecular variables for registries enrolling patients diagnosed with a solid tumor and profiled with next-generation sequencing (NGS)

Abstract: In precision oncology, tailored treatment decisions are largely driven by genomic alterations in a patient’s tumor. To support epidemiological research, we initiated a registry that enrolls patients diagnosed with a solid tumor and profiled with NGS. Collecting and standardizing variables of interest across the patient journey is critical for data harmonization and understanding clinical relevance. We propose a framework for identifying core variables most critical for solid tumor-based, real-world data studies and registries in precision oncology. A patient representative and panel of experts in NGS, oncology, epidemiology, bioinformatics, molecular tumor boards, clinical coordination, and molecular pathology was assembled to compile a draft variables list. To reduce the burden of data collection and missingness, the variables were categorized by decreasing importance and reconciled with draft European Medicines Agency guidelines at the time of writing (final guidelines released October 26, 2021) on registry-based studies. If applicable, internationally harmonized coding dictionaries were used to standardize the variables. The variable list was created to: describe a patient’s cancer history and journey effectively; allow conduct of comparative effectiveness studies and comparisons with clinical trials; and represent key risk factors or important confounders for prognosis or statistical analysis adjustments. The draft list comprised ~500 variables and was reconciled to ~150; highest priority was given to patient information (e.g. consent, demographics, risk and prognostic factors, dates of cancer-related events), NGS test results (e.g. actionable alterations, genomic signatures), cancer details (e.g. disease ontology, staging, metastases), and therapy details/outcomes (e.g. treatment information, response, progression, death). Variables with moderate to lower priority comprised NGS (e.g. technical, quality criteria), familial cancer history, adherence to molecular tumor board recommendations, and primary cause of death. This list provides viable guidance for conducting research- and regulatory-grade real-world data-based precision oncology studies, and facilitating standardized data collection and thus pooling from various datasets. Citation Format: Rodrigo Dienstmann, Clare Turnbull, Allan Hackshaw, Jean-Yves Blay, Maud Kamal, Nicolas Servant, Jan Geissler, David Tamborero, Janick Weberpals, Simon Fear, Camille Perret, Laura Perez, Martina von Meyenn, Christophe Le Tourneau. Conceptualization of core clinico-molecular variables for registries enrolling patients diagnosed with a solid tumor and profiled with next-generation sequencing (NGS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5246.

A systematic review of the literature

Abstract: OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002

Group based training for self‐management strategies in people with type 2 diabetes mellitus

Abstract: Background It has been recognised that adoption of self-management skills by the person with diabetes is necessary in order to manage their diabetes. However, the most effective method for delivering education and teaching self-management skills is unclear. Objectives To assess the effects of group-based, patient-centred training on clinical, lifestyle and psychosocial outcomes in people with type 2 diabetes. Search methods Studies were obtained from computerised searches of multiple electronic bibliographic databases, supplemented by hand searches of reference lists of articles, conference proceedings and consultation with experts in the field. Selection criteria Randomised controlled and controlled clinical trials which evaluated group-based education programmes for adults with type 2 diabetes compared with routine treatment, waiting list control or no intervention. Studies were only included if the length of follow-up was six months or more and the intervention was at least one session with the minimum of six participants. Data collection and analysis Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed if there were enough homogeneous studies reporting an outcome at either four to six months, 12-14 months, or two years, otherwise the studies were summarised in a descriptive manner. Main results Fourteen publications describing 11 studies were included involving 1532 participants. The results of the meta-analyses in favour of group-based diabetes education programmes were reduced glycated haemoglobin at four to six months (1.4%; 95% confidence interval (CI) 0.8 to 1.9; P < 0.00001), at 12-14 months (0.8%; 95% CI 0.7 to 1.0; P < 0.00001) and two years (1.0%; 95% CI 0.5 to 1.4; P < 0.00001); reduced fasting blood glucose levels at 12 months (1.2 mmol/L; 95% CI 0.7 to 1.6; P < 0.00001); reduced body weight at 12-14 months (1.6 Kg; 95% CI 0.3 to 3.0; P = 0.02); improved diabetes knowledge at 12-14 months (SMD 1.0; 95% CI 0.7 to 1.2; P < 0.00001) and reduced systolic blood pressure at four to six months (5 mmHg: 95% CI 1 to 10; P = 0.01). There was also a reduced need for diabetes medication (odds ratio 11.8, 95% CI 5.2 to 26.9; P < 0.00001; RD = 0.2; NNT = 5). Therefore, for every five patients attending a group-based education programme we could expect one patient to reduce diabetes medication. Authors' conclusions Group-based training for self-management strategies in people with type 2 diabetes is effective by improving fasting blood glucose levels, glycated haemoglobin and diabetes knowledge and reducing systolic blood pressure levels, body weight and the requirement for diabetes medication.

S100 proteins in cancer

Abstract: In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca(2+) sensors and as extracellular factors. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.

A review of the S100 proteins in cancer

Abstract: Aim In the quest to reduce mortality and morbidity from cancer, there is continued effort to identify novel biomarkers to aid in the early detection and the accurate prediction of tumour behaviour. One group of proteins that is emerging as a potentially important group of markers in multiple tumour types is the S100 family. This review summarises the biological and clinical relevance of these proteins in relation to different tumour types. Methods A literature search was performed using the PubMed database and the reference lists of relevant articles. Single case studies were excluded and only reports with a clinical relevance from 1961 to 2007 were included. Results The search yielded over 1000 published articles and reports. Important reports and studies were reviewed, screened and tracked for further relevant publications. Only the most relevant publications are discussed with relation to individual members of the S100 family. Conclusion There is increasing evidence that altered expression of S100 family members is seen in many cancers including breast, lung, bladder, kidney, thyroid, gastric, prostate and oral cancers. S100 proteins are commonly up-regulated in tumours and this is often associated with tumour progression. In contrast S100A2, S100A11 and S100A9 have been documented as tumour suppressors in some cancers but as tumour promoters in others. This demonstrates the complexity of the family and variability of their functions. Although the precise roles of these proteins in cancer is still to be discovered many of the family are associated with promoting metastases through interactions with matrix metalloproteinases or by acting as chemoattractants. There is also evidence that some members can regulate transcription factors such as p53. S100B already has a role in a clinical setting in the diagnosis and therapeutic monitoring of malignant melanoma. As our understanding of this family develops it is likely that many more members will aid the diagnosis, monitoring and potential treatment of cancers in the future.