A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

Extracellular vesicles (EVs), such as exosomes or oncosomes, often carry oncogenic molecules derived from tumor cells. In addition, accumulating evidence indicates that tumor cells can eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing drug resistance phenotype is often coupled with cellular dedifferentiation and transformation in cells undergoing epithelial-mesenchymal transition (EMT), and the adoption of a cancer stem cell phenotype. The release of EVs is also involved in immunosuppression. Herein, we address different aspects by which EVs modulate the tumor microenvironment to become resistant to anticancer and antibody-based drugs, as well as the concept of the resistance-associated secretory phenotype (RASP)

National Cultures and Capital Structure: Evidence from the Emerging Markets

This paper identifies the combinations between Hofstede’s six cultural aspects and four selected firm-specific factors, which have a significant impact on the choice of capital structure, in 15,821 listed companies from 34 countries in the emerging market, for the period 2012 – 2014. Thirty seven independent variables and one dependent variable have been tested using regression analysis. It has been concluded that the combinations that have a significant impact on the choice of capital structure (leverage) in the emerging markets were [Cultural – Firm-specific]: Power distance – cash flows, cost of debt Individualism – cash flows, cost of debt Masculinity – interest coverage ratio, cost of debt Uncertainty avoidance – cash flows, cost of debt Long-term orientation – intangibility, cash flows, cost of debt Indulgence – intangibility, cash flows, interest coverage rati

Biochemical Evaluation of some Natural Feed Additives against Dexamethasone-induced Metabolic Alterations in Rabbits

Glucocorticoid therapy is limited by numerous metabolic adverse effects associated with long term exposure to excess doses. Therefore, the present study aims to determine the possible protective effects of date palm and/or Saccharomyces cerevisiae probiotics on dexamethasone-induced metabolic changes in rabbits. 25 healthy male white New Zealand rabbits were grouped into group 1 (control), group 2 (2 mg/kg bw/day dexamethasone I/M), group 3 (0.5 g/kg/day date palm flesh+2 mg/kg bw/day dexamethasone I/M), group 4 (1g/kg/day S. cerevisiae probiotic + 2 mg/kg bw/day dexamethasone I/M), group 5 (date palm flesh + S. cerevisiae probiotic + dexamethasone at the aforementioned doses). Dexamethasone injection resulted in marked increases (p≤0.05) in hepatic MDA concentration and catalase activity, as well as significant decreases in hepatic GSH concentration and body weight gain. The serum levels of glucose, lipid profile (TG, cholesterol, VLDL, LDL/HDL risk ratio), and liver function biomarkers (serum total proteins, albumin, ALT, ALP) showed significant variations (P≤0.05) between control and dexamethasone treated group. The ameliorative effect of date palm fruit and/or probiotics (S. cerevisiae) was markedly indicated by restoration of these tested parameters to near normalcy. Therefore, the co-treatment with date or S. cerevisiae could be considered of great interest as potential feed additives for reduction of the adverse metabolic effects induced by dexamethasone in rabbits

Lignocellulosic Biomasses from Agricultural Wastes Improved the Quality and Physicochemical Properties of Frying Oils

In this work, the effects of using natural lignocellulosic-based adsorbents from sugarcane bagasse (SC), cornstalk piths (CP), and corn cob (CC) on the physicochemical properties and quality of fried oils were studied. The properties of lignocellulosic biomasses were examined using X-ray diffraction (XRD), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). Moreover, the changes in the physicochemical properties of fresh, fried oils (for 4, 8, 12, 16 and 20 h) and adsorbents-treated oils were examined. The XRD results revealed that SC and CP biomasses have more amorphous regions than CC biomass, which had the highest crystallinity percentage. The results also showed that lignocellulosic biomasses enhanced the quality of the used oils. SC was the most effective biomass to enhance the properties of the used sunflower oil. For instance, the acid value of oil samples fried for 20 h reduced from 0.63 ± 0.02 to 0.51 ± 0.02 mg KOH/g oil after SC biomass treatment. For the peroxide value, the SC biomass treatment reduced it from 9.45 ± 0.56 (fried oil for 20 h) to 6.91 ± 0.12 meq O2/kg. Similarly, SC biomass adsorbent reduced the p-Anisidine Value (p-AV) of the used oil (20 h) from 98.45 ± 6.31 to 77.92 ± 3.65. Moreover, SC adsorbents slightly improved the lightness of the used oils (20 h). In conclusion, natural lignocellulosic biomasses, particularly SC, could be utilized as natural adsorbents to improve the oil quality. The results obtained from this study could help in developing sustainable methods to regenerate used oils using natural and cheap adsorbents

Assessment of patient safety culture perception among healthcare workers in intensive care units of Alexandria Main University Hospital, Egypt

Background: Patient safety culture (PSC) is a vital feature to assess the ability of any healthcare setting in addressing and reducing patients harm. This study attempted to assess the PSC in Intensive Care Units (ICUs) at Alexandria Main University Hospital (AMUH) from the point of view of physicians and nurses. Methods: A cross-sectional study was implemented in two ICUs at AMUH over period of six months. Seventy-two participants were interviewed using the Hospital Patient Safety Scale, customized by the Agency for Healthcare Research and Quality (AHRQ). Results: The average positive response to individual items in the patient safety scale ranged from 2.7% to 79.2%. The “Teamwork within Units” dimension had the utmost average percentage positive score (63.5%) amongst all participants, on the other hand, the “Non-Punitive Response to Errors” dimension had the lowest one (12.0%). Less than half (45.8%) of the interviewed participants rated patient’s safety at the hospital as accepted. Conclusions: PSC is friable in targeted ICUs, much of work is needed to raise the responsiveness of health care givers regarding this issue. Executives and supervisors need to encourage the practices of PS through a blame free culture

Completeness and Readability of Health Information in Hospitals Records – North Kordofan State-Sudan 2015

Documentation of patients` information in the hospital registry is crucial for efficient quality of care. The objective was to assess the completeness and readability of patients` information in the inpatients files of internal medicine and pediatric departments. A descriptive audit study carried out in four hospitals in North Kordofan State. A total of 549 and 555 inpatients` files were reviewed from the internal medicine and pediatric departments respectively. A structured review checklist was used for the audit.  Data was managed by SPSS version 20. Comprehensiveness proportions were calculated manually. Chi square test at 95% CL was used for comparison. Complete and readable full names of patients were shown in 6.2% and 34.2% of internal medicine and pediatric files respectively. Patients` full contact address was complete and readable in 11.3% and 4.5% respectively. Only 0.5% of pediatric files had recorded age. Completeness of basic information in inpatients` files was significantly different in favor to the internal medicine department, P- value=0.01. Documentation of clinical assessment items was complete in internal medicine files (65.6%) and pediatric files (62.5%). Pediatric files had complete readable vaccination history (55.7%), complete readable perinatal, natal and postnatal history (40%) and complete readable milestones history(29.9%). The summary discharge pages had comprehensiveness scores, 13% and 18.7% in internal medicine and pediatric files respectively, P-value 0.01. Date of discharge was adequately complete in 74.1% and 77.5% of the internal medicine and pediatric files respectively. Information in hospital inpatients` files was not complete.Two thirds of inpatients` files were complete and readable for clinical assessment items. The childhood developmental history was under-documented. The summary discharge pages were not completely documented except the date of discharge.  A reform plan and computerization of the data base is recommended.

Antiparkinson Drug Benztropine Suppresses Tumor Growth, Circulating Tumor Cells, and Metastasis by Acting on SLC6A3/DAT and Reducing STAT3

Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-kappa B, and beta-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors

Anticancer effects of punicalagin and 5-fluorouracil on laryngeal squamous cell carcinoma: an <i>in vitro</i> study

The purpose of this study was to assess the apoptotic effects of punicalagin alone and in combination with 5-fluorouracil (5-FU) on laryngeal squamous cell carcinoma (Hep-2) cell line. Hep-2 cells were cultured and divided into four groups: Group 1 received no therapy and served as control, Group 2 received 5-FU only, Group 3 received punicalagin only, and Group 4 received a combination of 5-FU and punicalagin. After 48 hours of incubation, cellular changes were examined under an inverted microscope. The methyl thiazolyl tetrazolium assay, caspase-3 gene level, and vascular endothelial growth factor (VEGF) level were assessed. The control group showed the highest mean value of cancer cell proliferation rate (1.595±0.58), followed by the punicalagin group (1.263±0.447), then the 5-FU group (0.827±0.256), while the combination group showed the lowest proliferation rate (0.253±0.111). The combination group showed the highest mean value of caspase-3 concentration (3.177±0.736), followed by the 5-FU group (1.830±0.646), and punicalagin group (0.741±0.302), while the control group showed the lowest mean value (0.359±0.117). Regarding VEGF levels, the control group had a statistically significant higher mean value, followed by the punicalagin and 5-FU groups, and finally, the combination group which showed the lowest value. Punicalagin exerts an anticancer effect through anti-proliferative action and induction of apoptosis on Hep-2 cell line. Combining punicalagin with 5-FU potentiates its anti-proliferative, apoptotic, and anti-angiogenic actions. It, further, helps in mitigating the putative side effects of 5-FU by reducing the dose required for its therapeutic effects

A Role of Therapy that Targets Immune Checkpoint Proteins for the Treatment of Melanoma Brain Metastasis, Liver, Breast, Pancreatic Cancer and Pancreatic Adenocarcinoma

Checkpoint inhibitors are a type of immune therapy used to treat different types of cancers. These drugs block different checkpoint proteins, for example, CTLA-4, PD-1, and PD-L1 inhibitors. They block proteins that stop the immune system from attacking the cancer cells.  Checkpoints are also described as a type of monoclonal antibody that antagonizes binding between B7 to CTLA-4 and PD-L1 to PD-1.  Immune checkpoint inhibitors are used to treat BARCA mutated triple-negative breast cancer (TNBCS) in patients who do not respond to chemotherapy, and also in the treatment of highly mutated and solid tumors such as brain tumors, liver, and pancreatic cancers. Immune checkpoint inhibitors exhibit an effect on solid tumors by suppressing CTLA-4, PD-1, and PDL-1. Anti-PD-1 is less toxic than anti-CTLA-4. For melanoma Brain metastasis immune checkpoint therapy is more effective and Combination therapy has great efficacy and less toxicity which improves overall survival rather than individual therapy liver cancer as hepatocellular carcinoma and cholangiocarcinoma used treatment with Genetics based therapy while using alternative immune checkpoint ligands, co-inhibitory (eg. LAG-3) or decreased t-cell infiltration causing therapy failure. Clinical studies for pancreatic cancer have not been completed yet and treating PDA needs more research as immune checkpoint inhibitors is a new treatment against  PDA. A new potent class of nivolumab, pembrolizumab, and ipilimumab have been FDA approved. For mutated tumors, Combination therapy between checkpoint inhibitors and chemotherapy has great efficacy and improves the city of life and overall survival, rather than individual therapy when using radiation or chemotherapy alone