Insights on possible interplay between epithelial-mesenchymal transition and T-type voltage gated calcium channels genes in metastatic breast carcinoma.

Breast cancer (BC) is the most common life-threatening malignancy amongst women with high incidence worldwide. In Egypt, it is the most known malignancy amongst females. Epithelial-mesenchymal transition (EMT) participates in breast tumors' invasiveness, and metastasis, but the process is poorly understood. The involvement of voltage-gated calcium channels signaling in EMT has not yet been fully explored. Therefore, the aim of this study was to investigate the possible role of T-type calcium channels in metastasis and EMT among breast cancer patients. The study was carried out on 48 female breast cancer patients who were divided into two groups; metastatic and non-metastatic. qRT-PCR was employed to measure the expression of EMT marker genes (N- cadherin, E-cadherin, Snail, Vimentin and T-type VGCCs genes (CACNA1G, CACNA1H, and CACNA1I). The results of the present study revealed differential expression of the EMT marker genes in blood and tissue of non-metastatic and metastatic breast cancer patients, with a clear tendency for the mesenchymal markers to be significantly elevated in metastatic patients as well as malignant tissues taken from non-metastatic patients as compared to their paired tumor adjacent normal (TAN) tissue. Both CACNA1H and CACNA1I (T-type VGCCs oncogenes) were significantly elevated in blood of metastatic patients when compared to non-metastatic ones. In contrast, CACNA1G (tumor suppressor) exhibited a significant decrease in metastatic patients. The strong correlation between the expression of T-type VGCCs and mesenchymal marker genes in metastatic breast cancer patients casts light on the role of T-type VGCCs in metastasis and their involved in tumor invasiveness.

Design, synthesis, and antitumor activity of PLGA nanoparticles incorporating a discovered benzimidazole derivative as EZH2 inhibitor.

PURPOSE: Targeting enhancer of zeste homolog 2 (EZH2) can represent a hopeful strategy for oncotherapy. Also, the use of PLGA-based nanoparticles as a novel and rate-controlling carrier system was of our concern. METHODS: Benzimidazole derivatives were synthesized, and their structures were clarified. In vitro antitumor activity was evaluated. Then, a modeling study was performed to investigate the ability of the most active compounds to recognize EZH2 active sites. Compound 30 (Drug) was selected to conduct pre-formulation studies and then it was incorporated into polymeric PLGA nanoparticles (NPs). NPs were then fully characterized to select an optimized formula (NP4) that subjected to further evaluation regarding antitumor activity and protein expression levels of EZH2 and EpCAM. RESULTS: The results showed the antitumor activity of some synthesized derivatives. Docking outcomes demonstrated that Compound 30 was able to identify EZH2 active sites. NP4 exhibited promising findings and proved to keep the antitumor activity of Compound 30. HEPG-2 was the most sensitive for both Drug and NP4. Protein analysis indicated that Drug and NP4 had targeted EZH2 and the downstream signaling pathway leading to the decline of EpCAM expression. CONCLUSIONS: Targeting EZH2 by Compound 30 has potential use in the treatment of cancer especially hepatocellular carcinoma.

Association of matrix metalloproteinases 3 and 9 single nucleotide polymorphisms with breast cancer risk: A case-control study.

Two single nucleotide polymorphisms (SNPs) of matrix metalloproteinase (MMPs) 3 and 9 are functionally implicated in the progression of various types of cancer, including breast cancer (BC). However, the roles of these SNPs remain controversial. In addition, they also vary between one population and another. Therefore, the present study aimed to investigate the possible association between MMP3-1171 5A/6A and MMP9-1562 CT SNPs and the risk of BC among Egyptians, and to elucidate the alteration of MMP3 and MMP9 gene expression in patients with BC. The present case-control study enrolled 162 patients with BC and 146 control subjects. Restriction fragment length polymorphism-PCR was performed for analysis of the selected SNPs, gene expression of MMP3 and MMP9 was also assessed in 50 patients and 50 control subjects by reverse transcription-quantitative PCR. The frequencies of 5A/6A genotype and 5A allele of MMP3 were significantly higher in patients with BC compared with in healthy subjects. On the other hand, the distributions of MMP9 genotypes and alleles were not significantly different among patients and healthy subjects. Compared with healthy subjects, the expression levels of the two genes were found to be upregulated in patients with BC. Therefore, the present study indicated that MMP3-1171 5A/6A SNP, not MMP9-1562 C>T SNP may be a risk factor for developing BC among Egyptian females.

Effect of pulsed electromagnetic field on nonspecific low back pain patients: a randomized controlled trial.

BACKGROUND: Further research on pulsed electromagnetic field (PEMF) effects on the different conditions of low back pain was warranted due to lack of studies in this area. OBJECTIVES: To investigate the effects of pulsed electromagnetic field therapy with 50Hz frequency, with low intensity of 20Gauss compared to conventional non-invasive treatment modalities in patients with chronic non-specific low back pain. METHODS: Design - A prospective, randomized, patient-blinded, controlled trial. Setting - The study was conducted at Outpatient Physiotherapy Clinic in Cairo, Egypt. The study was conducted between May 2015 and September 2016. Participants - Fifty participants with non-specific low back pain enrolled into experimental and control groups. Interventions - The experimental group received the Conventional physical therapy Protocol as well as magnetic field, while the control group received the same Conventional physical therapy and sham electromagnetic field. Both groups received 12 sessions over 4 weeks' period. Outcome measures - Primary outcome measures was pain intensity while the secondary outcome measures were disability and lumbar range of motion - ROM. There were no adverse events occurred during the study. RESULTS: Fifty participants with non-specific low back pain (control group n=25; experimental group n=25) were randomized. There were significant between-group differences in pain scores (mean difference - MD 1.52; 95%CI -0.34 to 3.35), function disability (MD 8.14; 95%CI 6.5 to 9.96), Range of Motion (ROM) of lumbar flexion (MD -1.27; 95%CI -1.09 to -1.45), ROM of lumbar extension (MD -1.1; 95%CI -0.97 to -1.23), ROM of lumbar right side bending (MD 8.2; 95%CI 6.56 to 9.84) and ROM of lumbar left side bending (MD 10.4; 95%CI 8.81 to 11.99) in favour of the experimental group. CONCLUSION: Adding pulsed electromagnetic field to Conventional physical therapy Protocol yields superior clinical improvement in pain, functional disability, and lumbar ROM in patients with non-specific low back pain than Conventional physical therapy alone.

A TRAINING PROGRAM FOR NURSING STAFF ON HEALTH HAZARDS OF CHEMICAL INSECTICIDES EXPOSURE IN A PRACTICAL FIELD.

UNLABELLED: An insecticide is an agent used against insects, ticks, mites and other animals affecting human welfare. Exposure to Insecticides is one of the most important occupational risks among staff worker in Military camp, veterinary medicine, industry and household as well as schools and hospitals. This study Aimed to improve nursing staff knowledge regarding adverse health effects of chemical insecticides exposure in a military field. SETTING: The study was conducted in one of the Main Military Hospital. RESEARCH DESIGN: was used a quasi-experimental research design to conduct this study. SUBJECT: all nursing staff who work in a Military Hospital (n=55) who accept to participate in the research study. RESULTS: A significant improvement in the Nurses' Total knowledge score was found in post-test as compared to that in pre-test. All nurses obtained a satisfactory level of knowledge after the 1st & 2nd post-tests; all of them evaluate the program in relation to trainees' exnectations as "excellent".

Safe Cosmetic Leg Lengthening for Short Stature: Long-term Outcomes.

It is well known that limb lengthening is performed to treat limb-length discrepancies resulting from congenital anomalies and developmental problems. However, few studies discuss lengthening for cosmetic purposes. The current authors conducted a prospective study with long-term follow-up. From July 2002 through June 2007, 133 patients requested that their height be increased. Fifty-two were approved to undergo limb-lengthening surgery. Two were lost to final follow-up, leaving 50 in the study group. For all patients, the Ilizarov ring external fixator was applied with a maximum-stability technique that achieved frame stability and allowed patients to ambulate with a walker from the first week postoperatively. The method requires close follow-up for early detection of problems. Physiotherapy improved ankle function and prevented plantar flexion deformity, which can occur during lengthening. Excellent final outcomes were achieved in all patients except one, who required additional surgery. The Ilizarov device is a safe tool for limb lengthening in individuals of short stature when applied with the authors' maximum stability technique. To the authors' knowledge, this is the first article on this topic to report long-term results (minimum 5-year follow-up for all patients). Many factors influence the outcome of lengthening surgery performed with Ilizarov devices: the material of the rings, the use of a hybrid technique combining pins and wires, the diameter and number of pins over each bone segment, the size of the rings around the limb, the surgical technique for pin insertion, and the use of hydroxyapatite-coated pins or regular stainless pins.