Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70–80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.     

Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clinicopathologic study of 25 patients and 26 tumors

BACKGROUND: To determine the effects of anatomic site on the presentation and diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) and on the treatment and outcomes of the patients, the authors initiated a study of these tumors at different sites. An earlier report described MPNSTs of the buttock and lower extremity, and the current series analyzes those presenting at intrathoracic (IT) and subdiaphragmatic (SD) paraspinal sites. METHODS: The authors reviewed data on patients with paraspinal MPNSTs who were seen at Memorial Hospital during the period 1960-1995 and for whom histologic slides were available. Various clinicopathologic parameters and their effects on patient outcomes were examined. RESULTS: Twenty-five patients with 26 tumors were evaluated. Seven tumors were IT and 19 were SD; 60% of the patients had neurofibromatosis type 1 (NF1). Most patients presented with pain, and a diagnostic delay (of 3 months to 2 years) was often noted. Mean tumor sizes for SD and IT tumors were 14.3 cm and 6.6 cm, respectively. Most MPNSTs were composed of spindle cells in fascicles. Twenty-seven percent exhibited divergent differentiation. Twenty-four tumors were high grade, and a low grade component was identified in 8 tumors. Surgical resection was attempted for 23 tumors (88%), but complete resection was achieved in only 6 cases (23%). Eighty percent of the patients died of their tumors, 2-year and 5-year survival rates were 35% and 16%, and median survival was 8.5 months. Significant prognostic factors were tumor size <5 cm, the presence of a low grade component, and complete tumor resection. CONCLUSIONS: Paraspinal MPNSTs have more aggressive behavior than peripherally located tumors, mainly because of the difficulty encountered in resecting them completely. Prognoses of patients with MPNST at this site appear to be affected by resection status, tumor size, and tumor grade.     

Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia

In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. An expansion of cells with lesions on one copy of chromosome 2 was evident in 20-25% of treated mice at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hypermutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer.     

Demonstration of protein-protein interaction specificity by NMR chemical shift mapping

Chemical shift mapping is becoming a popular method for studying protein-protein interactions in solution. The technique is used to identify putative sites of interaction on a protein surface by detecting chemical shift perturbations in simple (1H, 15N)-HSQC NMR spectra of a uniformly labeled protein as a function of added (unlabeled) target protein. The high concentrations required for these experiments raise questions concerning the possibility for non-specific interactions being detected, thereby compromising the information obtained. We demonstrate here that the simple chemical shift mapping approach faithfully reproduces the known functional specificities among pairs of closely related proteins from the phosphoenolpyruvate:sugar phosphotransferase systems of Escherichia coli and Bacillus subtilis.     

Laser-assisted preparation of single cells from stained histological slides for gene analysis

Individual cells are prepared from histological tissue sections of routinely formalin-fixed and paraffin-embedded tissues using an ultraviolet laser micromanipulator. This technology, in combination with polymerase chain reaction (PCR)-based gene analysis, will enable researchers to routinely detect a variety of nucleic acid abnormalities underlying cancer, infection, and genetic disease with previously unknown sensitivity: at the single cell level. The utility of this technique is demonstrated by PCR amplification and sequencing of the E-cadherin gene, which codes for a homophilic cell-to-cell adhesion molecule, in early gastric carcinomas of the diffuse type of Lauren's classification. The main characteristics of the laser-assisted microdissection technique are high precision without contamination and easy application. The assignment of individual gene sequences to single cells will now provide a direct link between molecular biology on the one hand and histology and pathology on the other.     

Effects of lupin oil on carp lipids during chilling 1. Changes in lipid class composition

The effect of lupin (Lupinus termis) oil on the muscle lipids of carp (Cyprinus carpio) during chilling was studied. During chilling, total lipids decreased whereas triglycerides remained almost constant. Neither the behavior of total lipids nor that of triglycerides during chilling was affected by the composition of the dietary lipids. The proportions of ?free”? fatty acids increased and the proportions of phospholipids decreased during chilling. These changes were markedly affected by the composition of the diet.     

Influences of the chemical defects on the crystal thickness and their melting of isothermally crystallized isotactic polypropylene

Ziegler-Natta and Metallocene Catalysis isotactic polypropylene with different chemical defects were isothermally crystallized at various crystallization temperatures. The crystal thickness and their corresponding melting behavior were studied using small angle X-ray scattering, atomic force microscopy, optical microscopy, and differential scanning calorimetry. The equilibrium melt temperature of the samples was calculated from the Hofmann-Weeks extrapolation for the supercooling. Two lamellar populations were distinctly observed in all cases during the crystallization process. Relatively thicker and stable lamellar crystals which melt at higher temperatures were observed with lowering the supercooling and found catalysis dependence in these crystals. During melting, no significant recrystallization of the samples has been detected for higher crystallization temperature where recrystallization processes enhance the lamellae thickness. The melting of the crystals has found strong dependence with the crystallization temperatures, the catalysis process and the nature of the defects present in the isotactic polypropylene. The increase of the crystal lamellae thickness and their melting temperature might be presumably related with the chain folding mechanism as well as the stability of the crystals formed during the isothermal crystallization process. A combined plot of SAXS and DSC results is demonstrated for the equilibrium melting temperature followed by critical analysis of the results.     

Experimental investigation on the stability of bride girder against tsunami forces

Bridges are the most useful part in the transportation network. Any disruption of the bridge structures may hamper the whole transportation system. In the last recent tsunamis, numerous number of bridges were structurally damaged by the tsunami waves. Lack of proper provisions of tsunami forces in the design guidelines also contributes to the augmentations of the damage level. Therefore, proper evaluation of the tsunami forces on the bridge girder should be introduced in the design promptly. In this study, laboratory experiments were carried out to reveal the damage mechanism of the bridge girder by assessing the exerted tsunami forces. Both broken and unbroken waves were considered for the analysis. The results showed that measured forces were larger for broken waves than those of unbroken waves. Maximum force of the broken waves was 4.59 times as large as the hydrostatic pressure. Also, waves reached the peak value more rapidly for larger wave heights than those of smaller ones. Additionally, a girder that is placed at a higher position is much vulnerable to tsunami hazard.