We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

A report of two cases

Blood vessels promote tumour growth, and both blood and lymphatic vessels facilitate tumour metastasis by serving as conduits for the transport of tumour cells to new sites. Angiogenesis and lymphangiogenesis are regulated by integrins, which are members of a family of cell surface receptors whose ligands are extracellular matrix proteins and immunoglobulin superfamily molecules. Select integrins promote endothelial cell migration and survival during angiogenesis and lymphangiogenesis, whereas other integrins promote pro-angiogenic macrophage trafficking to tumours. Several integrin-targeted therapeutic agents are currently in clinical trials for cancer therapy. Here, we review the evidence implicating integrins as a family of fundamental regulators of angiogenesis and lymphangiogenesis.

Integrins in angiogenesis and lymphangiogenesis

Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence-based or expert recommendations for the diagnosis and ...

/pdf/efns-guidelines-on-the-clinical-management-of-amyotrophic-23ryvnse4m.pdf

EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS) : revised report of an EFNS task force

https://www.returninghope.com/pdf/Cytotherapy_2008.pdf

Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up

Summary Background Determining the most advantageous size of liposuction cannula and injection needles in terms of adipocyte viability could help to increase fat graft survival. When recurrent injections are necessary, storing fat tissue which is harvested during the first operation could be a practical solution if it is stored at an appropriate temperature providing the highest amount of viable fat cells. Methods Fat tissue was removed from the abdomen of 10 consecutive female patients by 6-, 4- and 2-mm-diameter liposuction cannulas. Fat tissue harvested with the 6mm cannula was injected through 14, 16 and 20g needles and collected in separate tubes. An additional three tubes of fat samples were prepared from fat tissue obtained with the 6mm cannula to be stored at +4, −20 and −80°C for 2 weeks. Viability of the fat grafts was evaluated by fat cell isolation with collagenase digestion and staining with supravital dye and counting adipocytes with a haemocytometer. Results The viability of fat grafts harvested with the 6mm cannula was higher than grafts obtained with smaller cannulas. The viability of fat grafts injected through 14, 16 and 20g needles were similar to each other. The viability of fat grafts stored at +4°C was similar to fresh tissue whereas freezing fat grafts caused significant loss of viable adipocytes compared to fresh tissue. Conclusions The use of larger liposuction cannulas for fat tissue harvesting provides more viable fat grafts. A temperature of +4°C could be proposed as an effective and easily available way of storing fat grafts for at least 2 weeks.

The effects of the size of liposuction cannula on adipocyte survival and the optimum temperature for fat graft storage: an experimental study.

Summary

Background Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production.



Objectives  To investigate the possible role of leptin in psoriasis pathogenesis.



Methods  Forty-three patients with psoriasis, 10 diseased and 10 healthy controls with normal body mass index were included. Serum fasting leptin levels of the study group were examined by enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression of both patients and controls were investigated by immunohistochemistry.



Results  Serum leptin levels, tissue leptin and leptin receptor expression were significantly higher in patients with severe psoriasis than patients with mild–moderate psoriasis and controls (P < 0·05). Serum leptin levels showed a positive correlation with Psoriasis Area and Severity Index and involved body surface area in patients with psoriasis. In addition, serum leptin levels, tissue leptin and leptin receptor expression showed a positive correlation with disease duration in patients with psoriasis (P < 0·01, r = 0·979; P < 0·01, r = 0·691; P < 0·01, r = 0·428, respectively).



Conclusions  We assume that leptin might serve as a marker of severity in psoriasis and also may be a pathogenetic cofactor contributing to chronicity of the disease. Consequently, its role in obesity and cardiovascular disease in patients with psoriasis deserves to be studied. In addition, drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis.

Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morphology.

Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary glioblastomas. As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient’s treatment. However, H&E staining alone does not determine the IDH mutational status of a tumour. Deep learning methods applied to MRI data have been demonstrated to be a useful tool in IDH status prediction, however the effectiveness of deep learning on H&E slides in the clinical setting has not been investigated so far. Furthermore, the performance of deep learning methods in medical imaging has been practically limited by small sample sizes currently available. Here we propose a data augmentation method based on the Generative Adversarial Networks (GAN) deep learning methodology, to improve the prediction performance of IDH mutational status using H&E slides. The H&E slides were acquired from 266 grade II-IV glioma patients from a mixture of public and private databases, including 130 IDH-wildtype and 136 IDH-mutant patients. A baseline deep learning model without data augmentation achieved an accuracy of 0.794 (AUC = 0.920). With GAN-based data augmentation, the accuracy of the IDH mutational status prediction was improved to 0.853 (AUC = 0.927) when the 3,000 GAN generated training samples were added to the original training set (24,000 samples). By integrating also patients’ age into the model, the accuracy improved further to 0.882 (AUC = 0.931). Our findings show that deep learning methodology, enhanced by GAN data augmentation, can support physicians in gliomas’ IDH status prediction.

/pdf/isocitrate-dehydrogenase-idh-status-prediction-in-nxqsd6jl84.pdf

Aydin Sav

Papers

Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up

The effects of the size of liposuction cannula on adipocyte survival and the optimum temperature for fat graft storage: an experimental study.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis.

Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morphology.

Isocitrate dehydrogenase (IDH) status prediction in histopathology images of gliomas using deep learning.