Search results for "heterogeneity"

PO-324 Detection of high-risk prostate cancer biomarkers by RNA sequencing and qPCR method

2018

Introduction New prognostic biomarkers for prostate cancer have the potential to overcome the clinical challenge of therapy decision and overtreatment. Present diagnostic and prognostic tests are still limited in specificity resulting in a large number of false positives and unnecessary biopsies. Furthermore, they do not enable a proper stratification between men with a high risk for an aggressive disease course requiring comprehensive therapy scheme after surgery and men with a low risk of disease recurrence cured after prostatectomy or eligible for active surveillance. In particular, patients with Gleason score 6 and 7 tumours (low and mid stage) are difficult to stratify for the appropri…

Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models

2018

Patient-derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach …

In the literature: April 2018

2018

The most important aim of precision medicine is the selection of the best treatment for each individual patient. To achieve this objective, the analysis of the molecular changes that can occur due to tumour heterogeneity or after anticancer treatment is fundamental. A dynamical study of the disease could lead to the identification of specific targets, which need to be inhibited at time of tumour progression. By using high-throughput sequencing, it is possible to identify a very limited number of somatic mutations that can be exploited for cancer treatment and drug development. However, the ability to predict response to targeted agents needs to be further improved. To do this, parallel stud…

Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

2015

Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…

215P Analysis of spatial heterogeneity of responses in metastatic sites with nivolumab in renal cell carcinoma

2020

Prognostic markers in low-grade papillary urothelial neoplasms of the urinary bladder: an update

2009

Abstract Papillary urothelial neoplasms of the urinary bladder comprise a heterogeneous spectrum of ‘continuous' lesions in which the assessment of an accurate histological grade and tumour stage is mandatory for the clinical management of patients. The 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) consensus classification and the 1999 WHO classification proposed new malignancy grading schemes, mainly based on morphometric studies for the replacement of the 1973 WHO grading system. In accordance with these novel grading systems, two major categories of papillary urothelial neoplasms were distinguished: low-grade and high-grade papillary urothelial …

Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.

2012

Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an e…

Growth in a time of external imbalances

2019

Abstract Globalization and financial integration have increased in the last three decades giving rise to cumulated large external imbalances. The question we address in this paper is whether economic growth can be affected by these external imbalances. We estimate an augmented growth equation with the external stock position of the countries measured by the net foreign asset position. Unlike previous literature, we use non-parametric methods that capture non-linearities and heterogeneity, and apply them to a sample that includes 106 developed and developing countries for the period 1983-2011. Contrary to the neoclassical theory, we find that improvements in the external position foster grow…

Clinical heterogeneity in infantile galactosialidosis

1987

A new case of infantile galactosialidosis is presented. The condition was diagnosed when the patient was 4 months of age and she died at 20 months. She exhibited some of the symptoms of classical infantile galactosialidosis but no corneal clouding, cherry-red macular spot or limitation of joint mobility. Sonographic examination showed large kidneys and thickened cardiac septa, two symptoms as yet undescribed in this disorder. Urinary oligosaccharide analysis gave grossly pathological results and subsequent fibroblast enzyme analysis showed a deficiency of alpha-neuraminidase and beta-galactosidase. The patient's clinical features are compared with the few cases so far described in the liter…

Fibroblast and Myofibroblast Participation in Malignant Fibrous Histiocytoma (MFH) of Bone

1989

Eight malignant fibrous histiocytomas (MFH) of bone were studied with immunohistochemistry and electron microscopy. Ultrastructurally, fibroblasts and myofibroblasts were the main tumor cells in four cases and abundant in two other cases; these cells showed immunohistochemical positivity to alpha 1-antitrypsin, vimentin and anti-muscle antigen (HHF 35). Moreover, histiocytic-like tumor cells were electron-microscopically detected in four cases, being the main tumor cell type in two of the cases; immunohistochemically these cells expressed positivity to alpha-1-antichymotrypsin (A1ACT), alpha-1-antitrypsin (A1AT) and vimentin. Present results confirm the cellular heterogeneity of MFH of bone…