INTRODUCTION:Metastatic brain tumours remain an intractable clinical problem despite notable advances in the treatment of the primary cancers. It is estimated that 30-40% of breast and lung cancer patients will develop brain metastases. Typically, brain lesions are not diagnosed until patients exhibit neurological symptoms because there are currently no tests that can predict which patients will be afflicted. Brain metastases are resistant to current chemotherapies, and despite surgical resection and radiotherapy, the prognosis for these patients remains very poor with an average survival of only 6-9 months. Cancer is ultimately a genetic disease, involving patient genetics and aberrant tumour genomics; therefore the pursuit of an explanation for why or how brain metastases occur requires investigation of the associated somatic mutations. In this article, we review the current literature surrounding the molecular and genome-based mechanistic evidence to indicate driver oncogenes that hold potential biomarkers for risk, or therapeutic targets for treatment of brain metastases.CONCLUSION:Patients afflicted with metastatic brain tumours are in dire need of more effective therapies, and clinicians need predictive laboratory tests to identify patients at risk of developing metastatic brain tumours. The as yet unrealized comprehensive analysis of metastatic brain tumour genomics is necessary to meet these needs. Moreover, without improved understanding of the genomic aberrations that drive metastatic brain tumours, development of biomarkers and molecularly targeted therapies will remain stalled and patient outcomes will continue to be dismal.
Introduction Gastrointestinal stromal tumours (GISTs) represent a major fraction of gastrointestinal sarcomas, frequently showing c-kit exon 11 mutations and associated with a good response to imatinib mesylate. Secondary resistance to imatinib has also been reported during therapy; therefore, clinicians need non-invasive tools for early assessment of treatment response due to traditional morphologic criteria [X-rays and computerized tomography (CT)] being unsuccessful. We report upon a patient with GIST with exon 11 mutation showing excellent response to imatinib mesylate, only a few days after initiation of the therapy and persisting for 18 months of follow-up. Here we also provide a short review of the recent literature on this topic. Conclusion There is evidence that F-FDG PET and PET/CT could be used to optimally monitor c-kit inhibitor therapy in GISTs, detecting early responders, non-responders and secondary resistance, there by allowing better patient management. Introduction Gastrointestinal stromal tumours (GISTs) are rare malignancies even though they represent the most relevant part of the gastrointestinal (GI) tract sarcomas. In most cases, GISTs are localized in the stomach and small intestine, followed by the colon and rectum1. GISTs are derived from Cajal cells in myenteric plexus; they are frequently marked by the expression of the c-kit tyrosine kinase receptor1. C-kit is a tyrosine kinase and is normally activated as a ligand by stem cell factor; a mutation of the c-kit proto-oncogene activates the tyrosine kinase in the absence of physiologic stimulation, there by leading to unrestrained cell proliferation2. The majority of GISTs (75%–80%) shows gain-of-function mutations of transmembrane receptor c-kit, which causes continuous activation of cell proliferation. The most common is the exon 11 mutation3. Genetic mutation analysis allows investigation of the relationship between the mutations occurred and response to drugs, such as imatinib mesylate. Imatinib mesylate is a tyrosine kinase inhibitor of tumour growth, and it has been demonstrated to be effective in GIST treatment. It is currently the first-line drug in advanced GISTs4. Recent studies3,5 show that 85% patients with c-kit exon 11 mutation respond to imatinib mesylate; nevertheless, it has been reported that resistance to this drug may occur during therapy6. This phenomenon needs to be disclosed as early as possible to change the therapeutic strategy, improve the clinical outcome and reduce the cost of ineffective therapies. In this regard, the response evaluation criteria in solid tumours (RECIST) criteria which relates to morphological examinations, mainly contrastenhanced computed tomography (CT), are unsatisfactory in assessment of GISTs response because changes in tumour size may be minimal at an early post-therapy evaluation or the lesion could be even larger because of intra-tumoural necrosis or haemorrhage7,8. There is recent evidence that a functional imaging modality such as 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) or a hybrid imaging modality such as PET/ CT could achieve this goal9–11. This paper reports the case of a GIST patient treated with imatinib mesylate and showing an excellent response as documented by 18F-FDG PET/CT only a few days after initiation of the therapy and persisting for 18 months of follow-up. We also reviewed the relevant literature pertaining to the response monitoring tools in GISTs. Discussion In April 2008, a 54-year-old male patient underwent surgery for GIST T2N0M0 with mutation of exon 11. In August 2010, a controlled CT revealed bone and liver GIST metastasis that was proven at biopsy. Therapy with imatinib mesylate was scheduled. Before initiating therapy, the patient underwent baseline 18F-FDG PET/CT and repeated an early PET/CT examination 10 days after initiation of the therapy. Subsequent PET/CT controls during imatinib mesylate therapy * Corresponding author Email: domenico.rubello@libero.it † Current address: Nuclear Medicine and Radiology Unit, Morgagni-Pierantoni Hospital, Forli, Italy 1 Department of Nuclear Medicine, Medical Physics, Radiology, Neuroradiology, PET/ CT Centre, ‘Santa Maria della Misericordia’ Hospital, Via Tre Martiri 140, 45100 Rovigo, Italy 2 Department of Medical Physics, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy 3 Department of Oncology, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy Em er gi ng T ec hn ol og ie s
Introduction Primary and recurrent venous thromboembolism–persists as a source of major morbidity and mortality. Although frequent in general population, the incidence of venous thromboembolism among oncologic patients is roughly higher, and expected to keep rising not only due to prevalence of cancer and the ageing of occidental population, but also due to an enhanced detection of incidental thrombosis during follow-up and the thrombogenecity of some chemotherapeutic regimens. Because of the potential life-threatening nature of venous thromboembolism, oncologic patients might benefit from thromboprophylaxis. Therefore, in the last years, efforts have been made to help clinicians in the prevention and management of thrombotic events in cancer patients. In this way, some biomarkers have been used to create stratification risk scores, joined with clinical characteristics, and in this review we pursue to demonstrate the main thrombotic risk biomarkers related to cancer. Conclusion The widely used Khorana risk assessment model has been expanded by adding sP-selectin and D-dimer. Other biomarkers showing some improvement in thrombotic risk assessment as factor VIII (with a dose-related increased risk), elevated peak thrombin (defined as thrombin values = 611 nM), tissue factor or C-reactive protein have yielded promising results. However, the absence of widespread clinical availability of tests measuring these biomarkers, the lack of standardisation and their cost make their implementation in daily practice difficult.
While most naturally occurring DNA and RNA adopt the now quite familiar double-helix structure, certain sequences can under the appropriate conditions adopt a three-stranded, triple-helical structure. Both intramolecular and intermolecular triplexes have been described. Evidence for the existence of triplex structures in vivo is limited, although cellular proteins have been identified that avidly and specifically interact with such species. The postulated roles of triplexes and the proteins that interact with them in cancer and their potential utility as diagnostic markers are discussed in this review.
