genotherapy

Gene therapy represents a significant potential to revolutionize the field of hematology with applications in correcting genetic mutations, generating cell lines and animal models, and improving the feasibility and efficacy of cancer immunotherapy. Compared to different genetic engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9) emerged as an effective and versatile genetic editor with the ability to precisely modify the genome. The applications of genetic engineering in various hematological disorders have shown encouraging results...

Until now, strategies used to treat cancer are imperfect, and this generates the need to search for better and safer solutions. The biggest issue is the lack of selective interaction with neoplastic cells, which is associated with occurrence of side effects and significantly reduces the effectiveness of therapies. The use of nanoparticles in cancer can counteract these problems. One of the most promising nanoparticles is magnetite. Implementation of this nanoparticle can improve various treatment methods such as hyperthermia, targeted drug delivery, cancer genotherapy, and protein therapy...

Prostate cancer (PC) is the most frequent male cancer in the Western world. Progression to Castration Resistant Prostate Cancer (CRPC) is a known consequence of androgen withdrawal therapy, making CRPC an end-stage disease. Combination of cytotoxic drugs and hormonal therapy/or genotherapy is a recognized modality for the treatment of advanced PC. However, this strategy is limited by poor bio-accessibility of the chemotherapy to tumor sites, resulting in an increased rate of collateral toxicity and incidence of multidrug resistance (MDR)...

Suitable carriers are crucial to RNAi applications for cancer genotherapy and T-cell immunotherapy. In this research, we selected two extensively-investigated biocompatible inorganic nanoparticle carriers, i.e., layered double hydroxide (LDH) and lipid-coated calcium phosphate (LCP) and then compared their efficacy for siRNA delivery in T cells, in order to understand which carrier is more efficient in delivering functional programmed cell death protein 1 siRNA (PD-1 siRNA) to suspended T lymphocytes. Both LDH and LCP nanoparticles quickly delivered gene segment to mouse T cell lines (EL4), while the LCP nanoparticles exhibited more cellular uptake and higher PD-1 gene silence efficiency...

AIMS: To develop an approach for the effective treatment of ovarian tumor, prevention of metastases and limitation of side effects. MATERIALS & METHODS: In order to combine chemotherapy with genotherapy, we constructed a nanoscale-based tumor-targeted system containing two anticancer drugs, two antisense oligonucleotides (suppressors of cellular resistance) and a ligand specific to receptors overexpressed in cancer cells. The system was tested in a mouse metastatic xenograft model using tumor isolates from patients with ovarian carcinoma...

BACKGROUND AND PURPOSE: The aim of the study was to estimate the usefulness of the antineoplastic vaccination in treatment of malignant brain tumors. According to medical knowledge there is no cure for this kind of tumors. MATERIAL AND METHODS: Between 2001 and 2005, ten patients suffering from malignant glial tumors were treated. There were 5 male and 5 female individuals, aged from 17 to 76 (mean age: 40.8 years). The histopathological examination showed 4 cases of glioblastoma and 6 cases of anaplastic astrocytoma...

Neuronal injury may have one of the following three sequelae: death of the neurone, persistent atrophy or recovery. The ability of mature neurones to recover is dependent to a not inconsiderable degree on neurotrophins, on the basis of which consideration the following objective of genotherapy in craniocerebral injury (CCI) is formulated: achievement of therapeutically useful levels of expression of neutrophins by employment of genetical methodological approaches. The next prerequisite for institution of genotherapy in CCI is a proved dependance of CCI sequelae on individual genetic features, on APO E-genotype in particular, which fact suggests to us that specific correction is within the bounds of possibility...

For a solid tumor to become life-threatening, an adequate blood supply has to be established. Although neovascularization has dire consequences for the host, it furnishes a common route through which tumors may be accessed and eradicated by drugs. The fact that a tumor's vasculature is relatively more permeable than that of healthy host tissue means selective delivery of drugs may be achieved. The role played by the cells making up the tumor vascular bed, vascular endothelial cells (VECs), has to be evaluated closely in attempts to design ways for enhancing drug delivery to solid tumors via the vasculature...

Moleculo-genetic pathways of development and progression of prostate cancer have been studied. In the norm, paracrine regulation of the glandular secretory epithelium are predominant due to the influence of hormonal and protein factors of the stroma. The altered prostatic epithelium becomes independent from the stroma and androgens and, consequently, prone to metastasizing, following activation of protooncogenes (growth factor genes), inactivation of gene-suppressors, hyperexpression of certain growth factors and apoptosis inhibitor Bcl-2, and inactivation of androgen receptor...

The cells constituting a solid tumour may vary considerably due to biological disparities, but for a solid tumour to pose as a threat to its host, an adequate blood supply has to be established. Although neovascularisation may have dire consequences for the host, it provides a common route by which tumours in general may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue means that selective delivery of drugs may be achieved. A closer examination of the role played by the cells making up the tumour vascular bed, vascular endothelial cells (VECs), is required to facilitate design of ways for enhancing drug delivery to solid tumours via the vascular route...

The article deals with modern methods, viz. PCR, molecular display and genotherapy, which permit the new approach to the solution of problems connected with the identification of infective agents, the study of the mechanisms of the pathogenesis of infectious diseases and their treatment. In this article concrete examples, clearly demonstrating how each of the above-mentioned technologies makes it possible to broaden the circle of problems solved in infectious pathology of man, are presented.

Based on the previous experiments with the N17 mutant of CDC42, it has been speculated, but not proved as yet, that CDC42 is required for Ras-induced malignant transformation of fibroblasts. However, since this inhibitor could sequester many GDP-dissociation stimulators (GDSs), such as DBL, OST and Tiam-1 which activate not only CDC42, but also Rho or Rac, in fact it is not a specific inhibitor that inactivates only CDC42. Thus, we have taken the minimum CDC42-binding domain (residues 504 - 545, called ACK42) of the Tyr-kinase ACK-1 that binds only CDC42 in the GTP-bound form, and thereby blocking the interactions of CDC42-GTP with its downstream effectors such as ACKs, PAKs and N-WASP...

The need for genotherapy to refocus its attention on to laboratory evaluation of better methods rather than proceeding to the clinic with semi-apt tools for genetic transfer has been highlighted in clinical study reports documented to date. Quintessential for tumour genotherapy is the ability to target abnormal cells, hence reducing exposure of normal cells to genetic material whilst maximizing gene dosage to tumour cells. This becomes increasingly important as genotherapy establishes itself in the clinic alongside the older modes of treatment...

Technical advances in molecular genetics have succeeded in elucidating the molecular basis of many hereditary diseases. The characterization of these abnormalities is currently giving rise to the concept of pharmacological treatment or, if possible, organ replacement (bone marrow grafting or liver transplantation). Genotherapy aims at replacing a single deficient gene by a functional gene introduced into an autologous, and therefore unrejectable, tissue. The haematopoietic stem cells are excellent targets for gene transfer, since the procurement, ex vivo, manipulation and reimplantation of these cells are easily performed...