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Tumour heterogeneity

Armelle Dufresne, Mehdi Brahmi, Marie Karanian, Jean-Yves Blay
Sarcomas are a heterogeneous group of malignancies that arise from cells of a mesenchymal origin. Surgery forms the mainstay of the treatment of most patients with localized sarcoma and might be followed or preceded by chemotherapy and/or radiotherapy. In the metastatic setting, systemic treatments tend to improve survival and control symptoms. However, the adverse events and sometimes disappointing outcomes associated with these empirical approaches to treatment indicate a need for new approaches. The advent of next-generation sequencing (NGS) has enabled more targeted treatment of many malignancies based on the presence of specific alterations...
April 17, 2018: Nature Reviews. Clinical Oncology
Bo Wang, Jing Li, Xi Cheng, Qiao Zhou, Jingxu Yang, Menghuan Zhang, Haifeng Chen, Jing Li
Identifying deleterious mutations remains a challenge in cancer genome sequencing projects, reflecting the vast number of candidate mutations per tumour and the existence of interpatient heterogeneity. Based on a 3D protein interaction network profiled via large-scale cross-linking mass spectrometry, we propose a weighted average formula involving the combination of three types of information into a 'meta-score'. We assume that a single amino acid polymorphism (SAP) may have a deleterious effect if the mutation rarely occurs naturally during evolution, if it inhibits binding between a pair of interacting proteins when located at their interface, or if it plays an important role in a protein interaction (PPI) network...
April 16, 2018: Scientific Reports
Simon Chang-Hao Tsao, Jing Wang, Yuling Wang, Andreas Behren, Jonathan Cebon, Matt Trau
Real-time monitoring of cancer cells' phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as "cell signature"), without the need for isolating individual CTCs...
April 16, 2018: Nature Communications
Viktor H Koelzer, Aline Gisler, Jonathan C Hanhart, Johannes Griss, Stephan N Wagner, Niels Willi, Gieri Cathomas, Melanie Sachs, Werner Kempf, Daniela S Thommen, Kirsten D Mertz
AIMS: Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD-L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardized digital protocol for the assessment of PD-L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists...
April 16, 2018: Histopathology
V Grégoire
The ultimate goal of any radiotherapy is to eradicate the disease without inflicting damage on the normal tissues surrounding the tumours, which could be responsible for late treatment morbidity. To achieve this objective, the first step is to precisely select and delineate the target volumes to which a given dose will be prescribed. This step requires the use of multi-modal images from clinical examination to anatomical and molecular images. Imaging examination will be used not only to delineate the boundaries of the tumour volume, but also to assess tumour heterogeneity and, possibly, to guide a heterogeneous dose prescription (i...
January 1, 2018: Annals of the ICRP
Laura Mincarelli, Ashleigh Lister, James Lipscombe, Iain C Macaulay
Cells are a fundamental unit of life, and the ability to study the phenotypes and behaviours of individual cells is crucial to understanding the workings of complex biological systems. Cell phenotypes (epigenomic, transcriptomic, proteomic and metabolomic) exhibit dramatic heterogeneity between and within the different cell types and states underlying cellular functional diversity. Cell genotypes can also display heterogeneity throughout an organism, in the form of somatic genetic variation - most notably in the emergence and evolution of tumours...
April 12, 2018: Proteomics
Sarah Shields, Emer Conroy, Tony O'Grady, Alo McGoldrick, Kate Connor, Mark P Ward, Zivile Useckaite, Eugene Dempsey, Rebecca Reilly, Yue Fan, Anthony Chubb, David Gomez Matallanas, Elaine W Kay, Darran O'Connor, Amanda McCann, William M Gallagher, Judith A Coppinger
Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by absence of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC patients can exhibit poor prognosis and high recurrence stages despite early response to chemotherapy treatment. In this study, we identified a pro-survival signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in a subset of TNBC cell lines and tumour tissues...
March 20, 2018: Oncotarget
Kai Pun Wong, Julian Shun Tsang, Brian Hung-Hin Lang
Pancreatic neuroendocrine tumours (PNETs) are rare. They are generally accepted to be slow-growing and have an indolent course. These tumours can be non-functioning or functioning, consisting of a biochemically heterogeneous group of tumours including insulinomas, gastrinomas, carcinoids and glucagonomas. Although surgery remains the mainstay of treatment, controversy still exists especially for non-functioning tumours <2 cm in size. Whether these should be resected or undergo intensive surveillance remains unclear...
February 2018: Gland Surgery
Bartosz Czapski, Szymon Baluszek, Christel Herold-Mende, Bozena Kaminska
Glioblastoma (GBM) is the most common and most aggressive type of primary brain tumour in adults. It represents 54% of all gliomas and 16% of all brain tumours (Ostrom et al. 2016). Despite surgery and treatment with radiotherapy plus an oral alkylating agent, temozolomide (TMZ), tumours invariably recur, and the patient survival is an average of ~14-16 months. In this review we summarise the current understanding of multiple factors that may affect survival of patients with GBMs. In particular, we discuss recent advancements in surgery and detection of genomic-based markers with prognostic values, such as IDH1/2 mutations, MGMT gene promoter methylation, and TERT gene promoter alterations...
March 2018: Contemporary Oncology Współczesna Onkologia
Sergiusz Nawrocki
Treatment based on molecular profiling of tumor is advertised however there are very limited clinical data supporting this approach so far. Only one, relatively small, randomized clinical trial (SHIVA) have not met its primary endpoint - prolongation of PFS. Some other unpublished series were reported during ASCO 2017 and are discussed in this review. There are many issues to be resolved before the tumor profiling will enter the clinical practice with significant benefit for patients, eg. spatial and temporal heterogeneity of tumor cells in individual patient, wide access to targeted therapies, toxicity of combined targeted therapies...
March 2018: Contemporary Oncology Współczesna Onkologia
Kamonwon Cattapan, Wiwatana Tanomkiat, Sarayut L Geater, Nantaka Kiranantawat
INTRODUCTION: Pleural procedures are performed to prove the diagnosis of pleural effusion. This study was to assess the incidence and outcome of pleural procedure-related tumour seeding in lung cancer with malignant pleural effusion, and to review the characteristics of the implanted tumours on computed tomography (CT) images. METHODS: From January 2008 to December 2010, 165 patients with the diagnosis of lung cancer with malignant pleural effusion, who underwent at least one pleural procedure and had follow-up CT, were included...
April 6, 2018: Journal of Medical Imaging and Radiation Oncology
Omar Abdel-Rahman, Zeinab Elsayed, Hesham Elhalawani
BACKGROUND: Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and ampullary carcinomas. Surgery remains the optimal modality of therapy leading to long-term survival for people diagnosed with resectable biliary tract carcinomas. Unfortunately, most people with biliary tract carcinomas are diagnosed with either unresectable locally-advanced or metastatic disease, and they are only suitable for palliative chemotherapy or supportive care...
April 6, 2018: Cochrane Database of Systematic Reviews
Athanasios Fountas, Shu Teng Chai, John Ayuk, Neil Gittoes, Swarupsinh Chavda, Niki Karavitaki
Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve...
2018: Endocrinology, Diabetes & Metabolism Case Reports
Giuseppe Badalamenti, Carlo Messina, Ida De Luca, Emmanuela Musso, Alessandra Casarin, Lorena Incorvaia
Soft tissue sarcomas (STSs) represent a rare and heterogeneous group of solid tumours derived from mesenchymal progenitors and account for 1% of all adult malignancies. Although in the last decade anthracycline-based chemotherapy single agent or in combinations has been able to improve clinical benefits, prognosis is still poor and STSs represent an important unmet medical need. Continuous advances in cancer genetics and genomics have contributed to change management paradigms of STSs as it occurred for other solid tumours...
April 4, 2018: La Radiologia Medica
Erik Engwall, Lars Glimelius, Elin Hynning
Non-&#13; small cell lung cancer (NSCLC) is a tumour type thought to be well-suited for&#13; proton radiotherapy. However, the lung region poses many problems related to organ&#13; motion and can for actively scanned beams induce severe interplay effects. In this study we investigate four mitigating rescanning techniques: (1) volumetric rescanning, (2) layered rescanning, (3) breath-sampled (BS) layered rescanning, and (4) continuous breath-sampled (CBS) layered rescanning. The breath-sampled methods will spread the layer rescans over a full breathing cycle, resulting in an improved averaging effect at the expense of longer treatment times...
April 4, 2018: Physics in Medicine and Biology
Chih-Hsing Hung, Fang-Ming Chen, Yi-Ching Lin, Mei-Lan Tsai, Shih-Ling Wang, Yen-Chun Chen, Yi-Ting Chen, Ming-Feng Hou
BACKGROUND: Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. METHODS: Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited...
April 3, 2018: BMC Cancer
E Biasibetti, J Giorcelli, F Deideri, P Bianco, M T Capucchio, M Volante
Bovine adrenal gland tumours are considered relatively common, although scarce data are available about their real incidence, pathological characterization, classification criteria and immunohistochemical profile. This study describes the morphological and immunophenotypical characteristics of 35 dairy cattle adrenal gland tumors from Northern Italy and compare them with human pathology. Macroscopical, histological, histochemical and immunohistochemical investigations were performed. Microscopically proliferative lesions were classified as focal hyperplasia (8/35), primary cortical tumors (15/35) , primary medullary tumors (12/35)...
December 2017: Polish Journal of Veterinary Sciences
Jon Zabaleta, Tomohiko Iida, Pierre E Falcoz, Samer Salah, José R Jarabo, Arlene M Correa, Maria G Zampino, Takashi Matsui, Sukki Cho, Francesco Ardissone, Kazuhiro Watanabe, Michel Gonzalez, Pascal Gervaz, Jose I Emparanza, Víctor Abraira
OBJECTIVES: To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. METHODS: We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014...
March 21, 2018: European Journal of Surgical Oncology
Elizabeth Rourke, Gilda Digman, Eric Gourley, Dharam Kaushik
A 39-year-old man presented with a 2-day history of worsening constant, dull diffuse lower abdominal pain with associated constipation and known history of left undescended testicle. He was evaluated at an outside hospital where a non-contrasted CT scan revealed a 20 cm well-circumscribed soft tissue mass within the pelvis.He was referred and further imaging revealed a 12 cm heterogeneous mass with foci of air that appeared to be contiguous with the left spermatic cord. This constellation of findings could represent torsion of undescended left testicle with infarction or underlying malignancy...
March 28, 2018: BMJ Case Reports
Michail Sideris, Ana Nora Donaldson, John Hanrahan, Matthew Grunwald, Savvas Papagrigoriadis
BACKGROUND/AIM: Several studies report outcomes of Transanal Endoscopic Microsurgery (TEMS) surgery in combination with radiotherapy, however the combination of those treatments is provided mostly on an adhoc individual basis and the role of radiotherapy remains unclear. The aim of this study was to identify the effect of neo-adjuvant or adjuvant radiotherapy in the oncological outcomes of rectal cancer treated surgically with TEMS. MATERIALS AND METHODS: We performed a systematic review of the literature on MEDLINE and Pubmed databases...
April 2018: Anticancer Research
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