Theranostic Nanoparticles and Their Spectrum in Cancer

Nanoparticles offer a lot of advantageous backgrounds for many applications due to their physical, chemical and biological properties. Their different composition (metals, lipids, polymers, peptides) and shapes (spheres, rods, pyramids, flowers and so on) are influenced by the synthesis methods and functionalization procedures. However, in the medical field, researchers focus on the biocompatibility and biodegradability of the nanoparticles in their attempts for a targeted therapy in which the nanocarriers need to bypass certain biological barriers. Moreover, the increased interest in molecular imaging has brought nanoparticles in the spotlight for their applications in two distinct directions: therapy and diagnosis. Furthermore, recent advances in nanoparticle designs have introduced novel nano-objects suitable as both detection and delivery systems at the same time, thus providing theranostic applications

The role of Skp2 and its substrate CDKN1B (p27) in colorectal cancer

Colorectal cancer is one of the most frequent cancers worldwide, having the fourth mortality rate among cancers in both sexes. Numerous studies are investigating the signaling pathways and different factors involved in the development and progression of colorectal cancer. It has recently been shown that the S-phase kinase-associated protein 2 (Skp2) overexpression plays an important role in the pathogenesis of colorectal cancer. We review the role of Skp2 and its ubiquitin-proteasome pathway in colorectal cancer. The F-box protein Skp2, a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex, has been shown to regulate cellular proliferation, cancer progression and metastasis by targeting several cell cycle regulators for ubiquitination and subsequent 26S proteasome degradation. The best known protein substrate of the Skp2 is the cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27Kip1. Overexpression of Skp2 and loss of CDKN1B (p27) was strongly associated with aggressive tumor behavior and poor clinical outcome in a variety of cancers, including colorectal cancer. An efficient interaction between Skp2 and CDKN1B (p27) requires the presence of an essential activator of the SCF-Skp2 complex, the cyclin-dependent kinase subunit 1 (Cks1) cofactor. Alterations in the Skp2, Cks1 and CDKN1B (p27) expression have major effects on colorectal carcinogenesis and may serve as an important and independent prognostic marker. Furthermore, we highlight that Skp2 may be a promising therapeutic target for colorectal cancer, and development of Skp2 inhibitors would have a great impact on colorectal cancer therapy.</jats:p

Noncoding RNAs in Lung Cancer Angiogenesis

Lung cancer is the major death-related cancer in both men and women, due to late diagnostic and limited treatment efficacy. The angiogenic process that is responsible for the support of tumor progression and metastasis represents one of the main hallmarks of cancer. The role of VEGF signaling in angiogenesis is well‐established, and we summarize the role of semaphorins and their related receptors or hypoxia‐related factors role as prone of tumor microenvironment in angiogenic mechanisms. Newly, noncoding RNA transcripts (ncRNA) were identified to have vital functions in miscellaneous biological processes, including lung cancer angiogenesis. Therefore, due to their capacity to regulate almost all molecular pathways related with altered key genes, including those involved in angiogenesis and its microenvironment, ncRNAs can serve as diagnosis and prognosis markers or therapeutic targets. We intend to summarize the latest progress in the field of ncRNAs in lung cancer and their relation with hypoxia‐related factors and angiogenic genes, with a particular focus on ncRNAs relation to semaphorins

Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

Ovarian cancer is composed of a complex system of cells best described by features such as clonal evolution, spatial and temporal genetic heterogeneity, and development of drug resistance, thus making it the most lethal gynecologic cancer. Seminal work on cancer as an evolutionary process has a long history; however, recent cost-effective large-scale molecular profiling has started to provide novel insights coupled with the development of mathematical algorithms. In the current review, we have systematically searched for articles that focused on the clonal evolution of ovarian cancer to offer the whole landscape of research that has been done and highlight future research avenues given its characteristic features and connections to evolutionary biology. Keywords: Clonal evolution; Ovarian cancer; Spatial heterogeneity; Survival; Temporal heterogeneit

Microarrays and NGS for Drug Discovery

Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options

Particularities of traditional and novel atherosclerotic risk factors in women with peripheral arterial disease in a Romanian Rehabilitation Hospital

Introduction. The increasing prevalence of peripheral arterial disease (PAD) among women is becoming a general healthcare issue, as this populational group is still underrepresented in clinical trials and registries addressing this disease. The aim of this research is to determine women peculiarities in both classical and novel atherosclerosis risk factors in patients admitted in a Romanian Rehabilitation Hospital. Material and methods. 83 consecutive female patients with a mean age of 68.48±10.39 years, symptomatic PAD and a pathological ankle-brachial index were included in the analysis. Data regarding the traditional and novel cardiovascular risk factors, both clinical, biological and paraclinical parameters were all registered. A subgroup of 40 subjects had novel inflammatory markers (hs-CRP, IL-6 and TNF-α) measured, which were compared in a case-control manner to those of 17 agematched healthy controls. Results. Traditional risk factors most prevalent in our overall cohort were hypertension (85%), smoking (44.57%) and diabetes mellitus (45.7%). Mean ankle-brachial index was 0.47±0.17. Novel inflammatory markers were significantly higher in women with symptomatic PAD compared to healthy controls: hs-CRP (p<0.0001), IL-6 (p=0.0053 and TNF-α (p=0.005). Multivariate statistical analysis found ankle-brachial index (ABI)- (p<0.0001), diastolic blood pressure (p=0.0272), obesity (p=0.0445), LDL-cholesterol (p=0.0018), HDL-cholesterol (p=0.0092) and serum creatinine (p<0.0001) to be independent predictors for a more advanced PAD. 59% of the patients exhibited critical limb ischemia on admission, while 60.24% had at least one major arterial occlusion on angiography. Percutaneous revascularization was the most employed treatment method, with 42% of subjects receiving PTA compared to 21.7% in the surgical arm. Conclusion. Women with PAD have specific clinical and biological characteristics that ultimately affect treatment modality, prescription of a rehabilitation program and outcome

Progresses towards safe and efficient gene therapy vectors

The emergence of genetic engineering at the beginning of the 1970′s opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients’ body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.This work is part of research grant No. 128/2014; PNII- PT-PCCA-2013-4-2166 “New strategies for improving life quality and survival in cancer patients: molecular and clinical studies of the tumor genome in deuterium-depleted water treatment augmentation - GenCanD”. Dr Calin is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in Dr. Calin’s laboratory is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01, the UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI (P50 CA093459), Aim at Melanoma Foundation and the Miriam and Jim Mulva research funds, the Brain SPORE (2P50CA127001), the Center for Radiation Oncology Research Project, the Center for Cancer Epigenetics Pilot project, a 2014 Knowledge GAP MDACC grant, a CLL Moonshot pilot project, the UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation and the Estate of C. G. Johnson, Jr,.http://www.impactjournals.com/oncotargetam2016Immunolog

PDGF beta targeting in cervical cancer cells suggest a fine-tuning of compensatory signalling pathways to sustain tumourigenic stimulation

Abstract The platelet-derived growth factor (PDGF) signalling pathway has been reported to play an important role in human cancers by modulating autocrine and paracrine processes such as tumour growth, metastasis and angiogenesis. Several clinical trials document the benefits of targeting this pathway; however, in cervical cancer the role of PDGF signalling in still unclear. In this study, we used siRNA against PDGF beta (PDGFBB) to investigate the cellular and molecular mechanisms of PDGFBB signalling in Ca Ski and HeLa cervical cancer cells. Our results show that PDGFBB inhibition in Ca Ski cells led to rapid alterations of the transcriptional pattern of 579 genes, genes that are known to have antagonistic roles in regulating tumour progression. Concomitantly, with the lack of significant effects on cervical cancer cells proliferation, apoptosis, migration or invasion, these findings suggests that cervical cancer cells shift between compensatory signalling pathways to maintain their behaviour. The observed autocrine effects were limited to cervical cancer cells ability to adhere to an endothelial cell (EC) monolayer. However, by inhibiting PDGFBB on cervical cells, we achieved reduced proliferation of ECs in co-culture settings and cellular aggregation in conditioned media. Because of lack of PDGF receptor expression on ECs, we believe that these effects are a result of indirect PDGFBB paracrine signalling mechanisms. Our results shed some light into the understanding of PDGFBB signalling mechanism in cervical cancer cells, which could be further exploited for the development of synergistic anti-tumour and anti-angiogenic therapeutic strategies