Τρίτη 2 Αυγούστου 2016

Primary Soft Tissue Lymphomas: Description of Seven Cases and Review of the Literature

Abstract

The present study describes a series of primary soft tissue lymphomas, including immunohistochemical characterization by tissue microarray and cytogenetic profiling. Formalin-fixed, paraffin-embedded tissue samples were collected from patients who underwent soft tissue biopsy. Cases were selected according to the definition of primary soft tissue lymphoma as a lymphoid malignancy arising in soft tissues without evidence of other nodal or extranodal localization for a period of at least 6 months. Our series comprised seven patients with a mean age of 72 years. There were three diffuse large B-cell lymphomas (DLBCLs); one B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma; one DLBCL derived from follicular lymphoma; one ALK-negative anaplastic large cell lymphoma; and one follicular lymphoma. Immunohistochemical and molecular profiles were consistent with the histological diagnoses. The present study contributes to our knowledge about uncommon presentation of lymphoid neoplasms and confirms previously published clinical-pathological data. We present, for the first time, the complete immunohistochemical profile and molecular cytogenetic studies of these lymphoid neoplasms. A rare case of a primary soft tissue ALK-negative anaplastic large cell lymphoma is described in detail.



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Exercise Promotion in Geriatric Oncology

Abstract

Evidence of the benefits of exercise for people with cancer from diagnosis through survivorship is growing. However, most cancers occur in older adults and little exercise advice is available for making specific recommendations for older adults with cancer. Individualized exercise prescriptions are safe, feasible, and beneficial for the geriatric oncology population. Oncology providers must be equipped to discuss the short- and long-term benefits of exercise and assist older patients in obtaining appropriate exercise prescriptions. This review provides detailed information about professionals and their roles as it relates to functional assessment, intervention, and evaluation of the geriatric oncology population. This review addresses the importance of functional status assessment and appropriate referrals to other oncology professionals.



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Immune Checkpoint Blockade: A New Era for Non-Small Cell Lung Cancer

Abstract

Despite better understanding of it's molecular biology, non-small cell lung cancer (NSCLC) remains a challenging disease to treat. Unfortunately, treatment options are still very limited and prognosis for advanced disease is poor. Immune surveillance plays a crucial role in a host's defence against tumour cells, and this is particular relevant for lung cancer due to it's high somatic mutational load, which increases the chances for the immune system to recognize cancer cells as 'non-self'. Novel immunotherapies are emerging as an effective treatment for this disease. In this review, we present the data on immune checkpoint inhibitors for NSCLC, describing their mechanism of action, data efficacy from recent clinical trials, and strategies to select patients more likely to benefit from these agents.



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Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer

Abstract

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR539, miR-572 and miR-185) was found to be prognostic [p = 1.28E−07, HR 8.4 (95 % CI: 3.81–18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.



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Exhaled Breath Condensate as a Source of Biomarkers for Lung Carcinomas. A Focus on Genetic and Epigenetic Markers – A Mini-Review

Abstract

Lung carcinoma is one of the most common causes of cancer-related mortality worldwide. It is an aggressive tumor, often diagnosed at an advanced stage when treatment options are limited. Currently, the importance of detection and assessment of various genetic alterations in cancer is recognized as they can serve as very helpful markers in early diagnosis and follow-up of treatment regimens. Recently, several therapeutically important genetic markers have been identified. One major problem is that tumor tissue specimens used to assay these genetic biomarkers are not always available, especially in the early stages of the disease. Therefore, exhaled breath condensates (EBC) could represent a good non-invasive source to allow the evaluation of these important genetic markers; these could help in the diagnosis, follow-up of the disease and/or assessment of treatment efficacy. The key aims of this review are firstly to describe the origin and constituents of EBC, as well as the different methodological procedures used in studying EBC biomarkers, and secondly, to document genetic and epigenetic markers that have been analyzed in EBC from lung cancer patients and to estimate their diagnostic and prognostic value. This article is protected by copyright. All rights reserved.



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Cancers, Vol. 8, Pages 73: Developmental Drift and the Role of Wnt Signaling in Aging

Population aging is a public health problem affecting the majority of the developed world. As populations age, the incidence of degenerative diseases increases exponentially, leading to large increases in public spending on healthcare. Here we summarize recent findings on the developmental drift theory of aging, and the links that have been established between aging and the Wnt signaling pathways. We focus on insights derived from model organisms connecting the evolutionary basis of aging and the link to developmental programming.

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Δευτέρα 1 Αυγούστου 2016

Therapeutic RANKL inhibition reduces cancer stem cells

RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remains unknown. RANKL and its receptor RANK are downstream effectors of the progesterone signaling pathway. However, RANK expression is enriched in hormone receptor negative adenocarcinomas suggesting additional roles for RANK signaling beyond its hormone-dependent function. Here, to explore the role of RANK signaling once tumors have developed we use the mouse mammary tumor virus- Polyoma Middle T (MMTV-PyMT) which mimics RANK and RANKL expression patterns seen in human breast adenocarcinomas. Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes lactogenic differentiation of tumor cells. Moreover, RANK signaling in tumor cells negatively regulates the Ap2 transcription factors, and enhances the Wnt agonist Rspo1 and the Sca1- population, enriched in tumor initiating cells. Additionally, we found that expression of TFAP2B and the RANK inhibitor, OPG, in human breast cancer correlate and are associated with relapse free tumors. These results support the use of RANKL inhibitors to reduce recurrence and metastasis in breast cancer patients based on its ability to induce tumor cell differentiation.

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