The Journal of pathology
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The Journal of pathology · Jan 2014
ReviewPathology is a necessary and informative tool in oncology clinical trials.
Clinical trials are essential for the improvement of cancer care. The complexity of modern cancer care and research require careful design, for which input from all disciplines is necessary. ⋯ In the current review all these aspects are discussed, with examples from colorectal cancer trials. We describe critical issues in biomarker evaluation and development and emphasize the importance of the role of the pathologist in quality control of cancer treatment.
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The Journal of pathology · Jan 2014
ReviewUsing the molecular classification of glioblastoma to inform personalized treatment.
Glioblastoma is the most common and most aggressive diffuse glioma, associated with short survival and uniformly fatal outcome, irrespective of treatment. It is characterized by morphological, genetic and gene-expression heterogeneity. The current standard of treatment is maximal surgical resection, followed by radiation, with concurrent and adjuvant chemotherapy. ⋯ Following recurrence, glioblastoma is quickly fatal in the majority of cases. Recent genetic molecular advances have contributed to a better understanding of glioblastoma pathophysiology and disease stratification. In this paper we review basic glioblastoma pathophysiology, with emphasis on clinically relevant genetic molecular alterations and potential targets for further drug development.
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The Journal of pathology · Jan 2014
ReviewImplications of intratumour heterogeneity for treatment stratification.
Despite advances in the diagnosis and treatment of cancer, the majority of advanced metastatic solid tumours remain incurable. Differential gene expression, somatic mutational status, tumour-specific genetic signatures and micro-environmental selection pressures within individual tumours have implications for the success of predictive assays to guide therapeutic intervention. ⋯ We highlight areas of research that could be improved in order to better stratify patient treatment. We also discuss the predictive potential of patient-derived models of tumour response, including xenograft and cell line-based systems within the context of intratumour heterogeneity.
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The discovery of the first major breast cancer susceptibility gene, BRCA1, occurred almost 20 years ago. BRCA1, together with BRCA2 remain the most important discoveries in human cancer genetics. Identification of highly penetrant mutations in these two tumour suppressor genes has had broad implications for women at risk and their families, for health professionals caring for these persons and for basic researchers. The BRCA proteins have many critical functions, the most notable of which, from a clinical perspective, is repair of double-strand DNA breaks.
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The Journal of pathology · Jan 2013
ReviewThe myofibroblast matrix: implications for tissue repair and fibrosis.
Myofibroblasts, and the extracellular matrix (ECM) in which they reside, are critical components of wound healing and fibrosis. The ECM, traditionally viewed as the structural elements within which cells reside, is actually a functional tissue whose components possess not only scaffolding characteristics, but also growth factor, mitogenic, and other bioactive properties. Although it has been suggested that tissue fibrosis simply reflects an 'exuberant' wound-healing response, examination of the ECM and the roles of myofibroblasts during fibrogenesis instead suggest that the organism may be attempting to recapitulate developmental programmes designed to regenerate functional tissue. ⋯ In the setting of wound healing (or physiological fibrosis), this occurs in a highly regulated and exquisitely choreographed fashion which results in cessation of haemorrhage, restoration of barrier integrity, and re-establishment of tissue function. However, pathological tissue fibrosis, which oftentimes causes organ dysfunction and significant morbidity or mortality, likely results from dysregulation of normal wound-healing processes or abnormalities of the process itself. This review will focus on the myofibroblast ECM and its role in both physiological and pathological fibrosis, and will discuss the potential for therapeutically targeting ECM proteins for treatment of fibrotic disorders.