Update on the Use of Nanocarriers and Drug Delivery Systems and Future Directions in Cervical Cancer.

Cervical cancer represents a major health problem among females due to its increased mortality rate. The conventional therapies are very aggressive and unsatisfactory when it comes to survival rate, especially in terminal stages, which requires the development of new treatment alternatives. With the use of nanotechnology, various chemotherapeutic drugs can be transported via nanocarriers directly to cervical cancerous cells, thus skipping the hepatic first-pass effect and decreasing the rate of chemotherapy side effects. This review comprises various drug delivery systems that were applied in cervical cancer, such as lipid-based nanocarriers, polymeric and dendrimeric nanoparticles, carbon-based nanoparticles, metallic nanoparticles, inorganic nanoparticles, micellar nanocarriers, and protein and polysaccharide nanoparticles. Nanoparticles have a great therapeutic potential by increasing the pharmacological activity, drug solubility, and bioavailability. Through their mechanisms, they highly increase the toxicity in the targeted cervical tumor cells or tissues by linking to specific ligands. In addition, a nondifferentiable model is proposed through holographic implementation in the dynamics of drug delivery dynamics. As any hologram functions as a deep learning process, the artificial intelligence can be proposed as a new analyzing method in cervical cancer.

Impact of the Liquid Crystal Order of Poly(azomethine-sulfone)s on the Semiconducting Properties.

Organic semiconductors are an attractive class of materials with large application in various fields, from optoelectronics to biomedicine. Usually, organic semiconductors have low electrical conductivity, and different routes towards improving said conductivity are being investigated. One such method is to increase their ordering degree, which not only improves electrical conduction but promotes cell growth, adhesion, and proliferation at the polymer-tissue interface. The current paper proposes a mathematical model for understanding the influence of the ordering state on the electrical properties of the organic semiconductors. To this end, a series of aromatic poly(azomethine)s were prepared as thin films in both amorphous and ordered states, and their supramolecular and electrical properties were analyzed by polarized light microscopy and surface type cells, respectively. Furthermore, the film surface characteristics were investigated by atomic force microscopy. It was established that the manufacture of thin films from mesophase state induced an electrical conductivity improvement of one order of magnitude. A mathematical model was developed in the framework of a multifractal theory of motion in its Schrodinger representation. The model used the order degree of the thin films as a fractality measure of the physical system's representation in the multifractal space. It proposed two types of conductivity, which manifest at different ranges of fractalization degrees. The mathematical predictions were found to be in line with the empirical data.

Basic aspects in selecting a suitable transgenic rodent model for Alzheimer's disease.

Due to Alzheimer's disease (AD) great aggressiveness, many worldwide health associations began to globalize research efforts in order to find a suitable treatment and to clarify once and for all its controversial aetiology. Moreover, the animal modelling research is one of the best tools to evaluate molecular mechanisms and to correlate them with clinical features and behaviours. However, in order to provide valuable scientific data correlated to low error sources, a rigorous algorithm of selecting the proper animal model for testing is required. An ideal animal model for AD research has probably not yet been developed, but by a careful selection of the existent models or even by developing new models suitable to research conditions, consistent progress in this area of research can be achieved. This paper aims to show and centralize some of the valuable information gathered along the past years of failure and success in Alzheimer's disease animal modelling, in order to provide a theoretical ground for new and innovative aspects in this rather new area of research.

BRCA1 5382insC founder mutation has not a significative recurrent presence in Northeastern Romanian cancer patients.

Developed two decades ago, oncogenetic medical practice mainly concern breast, ovarian and colorectal cancers, and is targeting the hereditary risk factor, the only one that shows positive predictive value justifying the molecular diagnosis. Screening for BRCA1 and BRCA2 gene mutations is standard practice today for hereditary breast and ovarian cancer (HBOC) families in developed countries, offering the possibility of medical follow-up. The gold standard for molecular diagnosis is Sanger sequencing of all exons and exon-intron boundaries, which is expensive and time consuming. More than 3000 BRCA sequence variants are reported in international databases, but in some populations or ethnic groups a few founder mutations showed to have a recurrent presence. This may be very useful in establishing a combined technical approach for mutation detection, including rapid and cheap pre-screening methods for most common mutations. The BRCA1 5382insC mutation has an Ashkenazi founder effect and is also the second most recurrent mutation in Eastern European populations, having been already identified in several Romanian HBOC patients. Here we present a complete screening of consecutive series of breast and ovarian cancer patients for the presence of BRCA1 5382insC. The presence of the mutation was investigated by allele specific multiplex-PCR on genomic DNA extracted from peripheral blood. No mutation carrier was identified among breast or ovarian cancer patients. Our findings suggest that BRCA1 5382insC may not have a strong recurrent effect in Romanian population comparing to neighboring countries. This may be particularly useful in establishing further pre-screening strategies.

Optimization of culture conditions for bone marrow stromal cells in RPMI-1640 medium.

UNLABELLED: Bone marrow mesenchymal stem cells are important for both research and clinical purpose. A number of culture methods for these cells are available on the market, many of them consisting of specialized growing media in combination with growth factors. Our goal was to optimize a less expensive culture method for bone marrow mesenchymal cells. MATERIAL AND METHODS: Eight samples of bone marrow aspirates from patients were used. Out these 8 samples 2 were from healthy people, 3 from chronic granulocytic leukemia patients, 2 from multiple myeloma patients and 2 from patients with myelodysplastic syndrome. Bone aspirates from healthy people were used to optimize the culture method and the rest were used for testing the optimized method. Two methods were tried: 1. Cell culture starting from whole bone marrow, 2) cell culture after bone marrow separation in density gradient with Histopaque. RESULTS: Cell culture starting from whole bone marrow gives better yields for mesenchymal stem cells than methods which include gradient density separation of mononuclear cells with Ficoll-Histopaque. CONCLUSIONS: We have optimised a less expensive cell culture method for bone marrow mesenchymal cells.

Validation of PCR-RFLP techniques for the evaluation of codon 72 of p53 and CYP1A1 gene's polymorphisms in relation with ovarian cancer in a Romanian population.

Epidemiological studies suggest that the onset and progression of ovarian cancer are associated with the presence of estrogens. CYP1A1 gene has two polymorphisms, which may affect the estrogens' metabolites and contribute to increased susceptibility to neoplastic transformation of ovarian cells. P53 is a tumor suppressor gene, which acts to preserve stability of human genome. Codon 72 polymorphism of p53 gene was correlated with susceptibility for ovarian cancer. The aim of our study was to validate the use of PCR-RFLP techniques for the evaluation of p53 codon 72 and CYP1A1 gene polymorphisms in relation with ovarian cancer in a Romanian population and to evaluate gene-environment interaction in this context. The case-control study included 42 subjects. The assessment of risk and protective factors was performed using a questionnaire. Polymorphisms of CYP1A1 and p53 genes were assessed using the validated PCR-RFLP techniques. The statistical analysis was performed using Epi Info 3.5.1 software. Frequency of Arg/Arg genotype of p53 gene was higher among cases (43%) compared with controls (33.3%), but the difference was not statistically significant (p=0.75). The presence of Ile/Val polymorphism of CYP1A1 gene was identified in 9.5% of the cases and the MspI polymorphism of CYP1A1 gene was not identified in our subjects. Validation of techniques consisted in the optimization of RFLP methods for p53 and CYP1A1 genes polymorphism analyzing that allowed highlighting the existence of codon 72 polymorphism of p53 gene and Ile/Val polymorphism of CYP1A1 gene in the population from this region.

Complete BRCA mutation screening in breast and ovarian cancer predisposition families from a North-Eastern Romanian population.

Breast cancer is the most common cancer in women worldwide, including Romania, where its incidence has increased significantly during the last decade. Ovarian cancer is the fourth leading cause of mortality by cancer in women. BRCA1 and BRCA2 are major cancer predisposition genes, responsible for a large percentage of hereditary breast and ovarian cancer (HBOC) families. We investigated 17 patients from unrelated HBOC families in north-eastern Romania, screening for mutations in BRCA1 and BRCA2 by mutation-specific PCR and by dideoxy sequencing. We identified four BRCA1 and two BRCA2 mutations in the 17 families. The overall mutation frequency was 41% (7/17; 5 BRCA1 and 2 BRCA2). Two mutations (BRCA1 c.2241dupC and BRCA2 c.8680C>T) were novel and not listed in the BIC database. Two recurrent BRCA1 mutations (c.5266dupC and c.181T>G), previously described among Ashkenazi Jewish and Eastern European populations, were also found. Two unclassified variants (UV) were found, one of which was novel (BRCA2 c.4589A>G). Medical follow-up for mutation carriers was implemented. Our study is the first molecular investigation of the role of the BRCA genes in breast and ovarian cancer in Romania.

Using MLPA for large genomic rearrangements detection in breast cancer predisposition genes.

UNLABELLED: Breast and ovarian cancer are common pathologies in women, with increasing incidences worldwide. In hereditary breast and ovarian cancer (HBOC) families, a large percentage of cases are attributable to hereditary factors compatibles with dominant autosomal transmission of a major tumour suppressor gene with incomplete penetrance. Screening for BRCA1 mutations is now standard practice for HBOC cases in western world, and permits medical follow-up and genetic counselling. Over 300 BRCA1 germinal mutations are stored in the Breast Cancer Information Core (BIC) mutation database. MATERIAL AND METHODS: Estimates in different countries range from 5 to 15% the BRCA1 related cases of hereditary breast cancer due to copy number changes of one or more exons of this gene. Exon deletions and amplifications will usually not be detected by sequence analysis of the complete BRCA1 gene, therefore MLPA screening is needed. RESULTS: Here we describe Multiplex Ligation-dependent Probe Amplification technique (MLPA) implementation for BRCA1 large genomic rearrangements. CONCLUSIONS: We did not detect any BRCA1 mutation by analysis of 15 HBOC recruited patients.

[Malignancy risk in some benign mammary lesions]. / Riscul malignizarii unor leziuni mamare benigne.

We analyzed retrospectively 821 patients operated on in our clinic for benign mammary lesions and for breast cancer. Histopathology identified in some cases associated benign and malign lesions. Atypical hyperplasia is considered significant risk factor for malignancy. Women in this category need close surveillance.

[Practical aspects in diagnosis and treatment of benign breast lesions]. / Elemente practice privind diagnosticul si tratamentul leziunilor mamare benigne.

We analyzed 444 patients operated on in our clinic. Triple test diagnosis is the modern trend. Surgical treatment is not justified in all cases. When needed, partial mastectomy is commonly used. Surgical principles must be respected for good cosmetic results. Histopathology only certifies the diagnostic.

[Reasons for conservative treatment in breast cancer]. / Argumentarea aplicarii tratamentului conservator în cancerul mamar.

We analyze 112 patients with breast conservative treatment operated in our clinic in the last 5 years. Breast preservation surgery represented 30.35% of all cases treated for breast cancer in this interval of time. In other 63 situations conservative treatment was attempted but finally given up due to justified motivations and decision for mastectomy was adopted as optimal. Rigorous selection of patients for conservative surgery was our care. Tumor size, excisional margins, nodal status were the main criteria. Correlation with breast volume, age, patient's opinion were also important. Preservation of breast in women interested and cosmetic results were the purposes of our attitude. Breast conserving therapy may be indicated only respecting the oncological principles and close surveillance of patients is obligatory.