A physicochemical model of X-ray induced photodynamic therapy (X-PDT) with an emphasis on tissue oxygen concentration and oxygenation.

X-PDT is one of the novel cancer treatment approaches that uses high penetration X-ray radiation to activate photosensitizers (PSs) placed in deep seated tumors. After PS activation, some reactive oxygen species (ROS) like singlet oxygen (1O2) are produced that are very toxic for adjacent cells. Efficiency of X-PDT depends on 1O2 quantum yield as well as X-ray mortality rate. Despite many studies have been modeled X-PDT, little is known about the investigation of tissue oxygen content in treatment outcome. In the present study, we predicted X-PDT efficiency through a feedback of physiological parameters of tumor microenvironment includes tissue oxygen and oxygenation properties. The introduced physicochemical model of X-PDT estimates 1O2 production in a vascularized and non-vascularized tumor under different tissue oxygen levels to predict cell death probability in tumor and adjacent normal tissue. The results emphasized the importance of molecular oxygen and the presence of a vascular network in predicting X-PDT efficiency.

Modulating Survivin as a Radioresistant Factor, Caspase-3, and Apoptosis by Omega-3 Docosahexaenoic Acid Sensitizes Mutant-p53 Colorectal Cancer Cells to γ-Irradiation.

Mutant-p53 colorectal cancer (CRC) cells are often resistant to radiotherapy. Loss of suppressor activity of wt-p53 on survivin is responsible for the enhanced expression of survivin as a radioresistant factor in tumor cells. Yet, no survivin-modulating drug has been approved for clinical application in CRC. Thus, the search for safe compounds that modulate survivin expression and induce apoptosis irrespective of p53 status may potentiate the efficacy of radiotherapy in mutant-p53 CRC cells. Omega-3 docosahexaenoic acid (DHA) induces apoptosis in malignant cells without cytotoxicity in normal cells. However, little is known whether in vitro concentrations of DHA equal to the human plasma levels are able to modulate expression of survivin and sensitize mutant-p53 CRC cells to γ-irradiation. Radioresistant mutant-p53 HT-29 cells were pretreated with 50- and 100-µM DHA for 48-h before 2-, 4-, 6-, 8-, and 10-Gy of γ-irradiation. Thereafter, proliferation rates were measured after 6 d. HT-29 cells were also pretreated with 50- and 100-µM DHA for 4-h before 2- and 10-Gy of γ-irradiation after which, cell number, survivin expression, caspase-3 activation, apoptosis, and ED50 (γ-irradiation dose causing 50% growth inhibition) were evaluated. Pretreatment of HT-29 cells with 50- and 100-µM DHA for 48-h followed by 2- to 10-Gy of γ-irradiation induced a dose-dependent additive decrease in cell proliferation rate and ED50 values were decreased by 88%, 44%, 41%, and 27% for 500-, 1500-, 2500-, and 5000 cells per well pretreated with 100-µM DHA respectively. Pretreatment of 5 × 105 HT-29 cells per well with 100-µM DHA for 4-h followed by 2- or 10-Gy of irradiation resulted in 53% and 86% decreases in cell numbers, 2- and 5.1-fold activation in caspase-3 followed by 66% and 60% decreases in survivin mRNA levels respectively. DHA in combination with radiation increased total apoptotic rate 48-h post-treatment. DHA decreases survivin expression and induces caspase-3 activation irrespective of p53 status. Significant decreases in ED50 values at concentrations of DHA equal to human plasma levels, suggesting that DHA could be used as an attractive radiosensitizer agent in CRC patients with mutant-p53.

Helicobacter pylori Multidrug Resistance Due to Misuse of Antibiotics in Iran.

BACKGROUND: Helicobacter pylori might become highly resistant to antibiotics taken through the life time of patients. This study examined the change in antibiotic resistance of H. pylori by time. METHODS: Out of 985 dyspeptic patients who were referred to the endoscopy unit of Shariati hospital during 2010-2017, 218 patients with gastric biopsies positive for rapid urease test (RUT) and H. pylori culture were recruited in the study. H. pylori isolates were examined for resistance to 8 currently used antibiotics by the disc diffusion method. Results were compared with those from our three previous studies. The frequency of multidrug resistance (MDR) was also assessed. RESULTS: The highest resistance rate was to metronidazole (MTZ) (79.4%) followed by ofloxacin (OFX) (58.7%), ciprofloxacin (CIP) (46.8%), levofloxacin (LVX) (45%), tetracycline (TET) (38.5%), clarithromycin (CLR) (34.4%), amoxicillin (AMX) (27.1%) and furazolidone (FRZ) (23.9%). No significant difference was found between resistance of H. pylori isolates from male and female <40 and >40 years old and patients with gastritis and peptic ulcer. The highest rates of MDR were to MTZ+OFX (4.6%), MTZ+OFX+TET (2.8%), MTZ+OFX+CIP+LVX (6.4%) and MTZ+OFX+TET+ CIP+LVX (5%). CONCLUSION: Resistance to MTZ increased from 33%-55.6% in previous studies to 79.4% by time, to CLR increased from 1.4-7.3% to 34.4%, to TET increased from 0-38.1% to 38.5%, to AMX increased from 1.4%-7.3% to 27.1% and to FRZ increased from 0%-4.5% to 23.9%. Resistance to FQs was 45%-58.7%. Increase in H. pylori antibiotic resistance indicates antibiotic misuse. In Iran, with a considerable number of H. pylori- infected patients, antibiotic therapy should be saved for high risk patients and according to local antibiotic resistance patterns.

Simulation of tumor induced angiogenesis using an analytical adaptive modeling including dynamic sprouting and blood flow modeling.

In this paper, an adaptive model for tumor induced angiogenesis is developed that integrates generation and diffusion of a growth factor originated from hypoxic cells, adaptive sprouting from a parent vessel, blood flow and structural adaptation. The proposed adaptive sprout spacing model (ASS) determines position, time and number of sprouts which are activated from a parent vessel and also the developed vascular network is modified by a novel sprout branching prediction algorithm. This algorithm couples local vascular endothelial growth factor (VEGF) concentrations, stresses due to the blood flow and stochastic branching to the structural reactions of each vessel segment in response to mechanical and biochemical stimuli. The results provide predictions for the time-dependent development of the network structure, including the position and diameters of each segment and the resulting distributions of blood flow and VEGF. Considering time delays between sprout progressions and number of sprouts activated at different time durations provides information about micro-vessel density in the network. Resulting insights could be useful for motivating experimental investigations of vascular pattern in tumor induced angiogenesis and development of therapies targeting angiogenesis.

Evaluation of methods for H. pylori detection in PPI consumption using culture, rapid urease test and smear examination.

BACKGROUND: Culture, rapid urease test (RUT) and smear examination have been used as reliable methods for diagnosis of H. pylori infection. Accurate performance of these tests requires good quality biopsies with considerable number of bacterial cells. However, consumption of proton pump inhibitors (PPIs) affects growth and urease activity of H. pylori, leading to false negative results. In this study the efficacy of culture, RUT and smear examination was assessed and the effect of PPI consumption was evaluated. METHODS: Two antral biopsies from 530 dyspeptic patients with and without PPI consumption were used for RUT, culture and smear examination. Statistical analysis was used to determine the association between results of culture, RUT or smear examination and PPI consumption. Sensitivity and specificity of three tests were calculated by standard methods. RESULTS: H. pylori infection was detected in 40% of patients by culture, 48.3% by RUT and 21.1% by smear examination and the overall detection rate was 54%. A strong correlation was found between PPI consumption and negative results of culture and RUT (P<0.05) but not smear examination. The sensitivity of RUT was reduced as a result of PPI consumption. This reduction was more profound in 1-hr RUT (92.2% to 74.4%) compared with 24-hr RUT (93.9% to 81.6%). CONCLUSIONS: Prevalence of H. pylori was declined, compared with previous studies. This decrement could be due to false negative results of H. pylori diagnostic tests, among which culture and RUT are mostly affected by PPI. Accordingly, PPI consumption should be stopped before performance of endoscopy.