Fiducial markers in prostate cancer image-guided radiotherapy

Background: Image-guided radiotherapy (IGRT) is recommended to reduce the risk of geometrical miss when modern radiotherapy technologies with high grades of conformity are used. The purpose of this study was to evaluate the efficacy of fiducial markers (FMs) for electronic portal imaging in prostate cancer radiotherapy in term of evaluating the complications associated with FMs implantation, quantifying inter-fraction prostate motion, and determination of optimal planning target volume (PTV) margins. Methods: In this single institution, prospective, consecutive study, 27 patients underwent implantation of three-gold seed FMs into the prostate gland before prostate radiotherapy. Prior to computed tomography planning, all patients were asked to report any complication associated with FMs implantation that have experienced to date. Daily pre-treatment electronic portal images were captured, and prostate position errors were corrected if they were greater than 2 mm along three translational directions. Optimal PTV expansions were computed using van Herk formula PTV-margin= 2.5Z + 0.7a. Results: FMs implantation was successful with an acceptable toxicity profile in all patients. Without IGRT, margins of 5.4 mm, 5.8 mm and 5.5 mm, in vertical, longitudinal and lateral directions, respectively, are needed for a 95% confidence level of complete clinical target volume (CTV) coverage in each treatment session. The PTV margins of 3.0 mm, 3.3 mm and 4.0 mm in corresponding directions were calculated when FMs based electronic portal imaging was applied. Conclusion: FMs based electronic portal imaging is an effective tool for prostate cancer IGRT. © Iran University of Medical Sciences

Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.</p> <p>Methods</p> <p>We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.</p> <p>Discussion</p> <p>Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.</p

Insulin-like growth factor binding protein 3 chemosensitizes pancreatic ductal adenocarcinoma through its death receptor

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Gemcitabine and doxorubicin are commonly used as the chemotherapy agents, but most of PDAC tumors eventually acquired resistance to chemotherapy. Accumulating evidence indicates that Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role against tumor growth but its expression has commonly suppressed. The present study was designed to evaluate IGFBP-3 effects in chemotherapy sensitization of PDAC cells. Here, we report that the re-sensitization of chemoresistant PDAC cells was occurred by IGFBP-3 through recruitment of its death receptor (IGFBP-3R). Using gemcitabine, doxorubicin-resistant PDAC cell lines, we found that IGFBP-3 sensitized chemoresistant cells by activating apoptosis (as evaluated by Bax up-regulation, Bcl-2 down-regulation as well as Caspase-3 and Caspase 8 activation). IGFBP-3R was also found to have higher expression level in resistant AsPc-1 and MIA PaCa-2 cells in comparison to parental cells. IGFBP-3R was also highly expressed in PDAC tumor which exposed to chemotherapy in comparison to un-treated PDAC tumors. In addition, we confirmed our finding by using specific siRNA to knocking down of IGFBP-3R which prevents IGFBP-3 Chemosensitization. Taken together, the present study for the first time indicates the clinical relevance for combining IGFBP-3 with chemotherapy to reduce chemoresistance in PDAC

Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.

The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate

Effect of consumption of fatty acids, calcium, Vitamin D and boron with regular physical activity on bone mechanical properties and corresponding metabolic hormones in rats

223-231The consumption of fatty acids, nutrients, and regular physical activity, individually influence bone mechanical properties in rats. To investigate their effects in combination, male rats were divided into the seven groups: G1: regular food and drinking water; G2: same as Gr.1 + physical activity (Whole body vibration; WBV); G3: same as Gr.2 + Calcium, Vit. D, Boron; G4: same as Gr.3 + canola oil; G5: same as Gr.3 + sunflower oil; G6: same as Gr.3 + mix of sunflower oil and canola oil; and G7: same as Gr.3 + coconut oil; and treated for 8 weeks. Analysis between the control with the groups 2 and 3 revealed that vibration in the G2 increased the body weight (P= 0.04), with no other major difference in plasma and bone indices. Comparison between the control with the G4-G7 (the oil groups) revealed that the rats in the G5 had a lower body weight (15 % less) and a significant increase in plasma levels of Estradiol in the G7 was noted. In addition, levels of Testosterone in the G4 and G7, and Free Testosterone in the G7 had a remarkable increase. Similar trend was observed for plasma levels of Vit. D in the G4 and G5. The stiffness and the breaking strength of the femur in the G7, and the breaking strength of the lumbar in the G7 compared to the control and the G4 and G5 was significantly higher and tended to increase in comparison to the G6. Better and stronger measurements observed for coconut oil is warranted to further study its effect on biomechanical properties of bones

Recombinant production, purification and characterization of vessel dilator in E. coli

Vessel dilator is a 3.9-KDa potent anticancer peptide and a valuable candidate in the treatment of conditions such as congestive heart failure and acute renal failure amongst others. Here we report the recombinant production of vessel dilator in Escherichia coli. Three different synthetic ORF's dubbed VDI, VDII and VDIII, each encoding a trimmer of the vessel dilator peptide attached to a His tag sequence at their C- terminal, were synthesized and placed in pET21c expression vectors. The highest yield, following expression in E. coli BL21 (DE3), was recorded with VDII that carried the shortest fusion partner. Subsequent to the initial capture of the fusion protein by a Ni affinity column, the vessel dilator monomers were cleaved by trypsin treatment, and further purified to at least 90% homogeneity by anion exchange chromatography. De-novo sequencing and in vivo anticancer activity tests were used to verify the peptide sequence and its biological activity, respectively. The final yield was estimated to be approximately 15 mg of the purified vessel dilator per gram wet weight of the bacterial cells

The effect of the combination of Malva sylvestris L. and Althaea digitata Boiss. on prevention of acute radiation proctitis in patients with prostate cancer

The effect of a combination of Malva sylvestris and Althaea digitata flower powder in prevention of acute radiation proctitis was assessed in patients undergoing radiation therapy (RT) for prostate cancer. This double-blind randomized controlled study was conducted at three centers in Iran. Before starting RT, patients (N = 65) received a 4 g packet of flower powder or placebo to use 3 times a day as an infusion from the first day of RT and for five consecutive weeks including the three weeks of RT. They were visited by a physician 3 times during this period. Acute morbidity was classified according to the Radiation Therapy Oncology Group (RTOG) criteria. Severity of proctitis symptoms was assessed by Visual Analog Scale (VAS) with 10 points. Non-statistical significant differences were observed between the groups in relation to RTOG grade criteria (grade 0: drug 22.8 (N = 8), placebo 10 (N = 3), difference 12.8; grade 1: drug 65.8, placebo 64.4, difference 1.4; grade 2: drug 11.4 (N = 8), placebo 26.6 (N = 4), difference 15.2. (P =.059)) According to VAS, the most common complaint was anal burning and diarrhea in the flower powder group showing a significant decrease in these symptoms at the end of the study as compared to the placebo; flower powder (1.56 ± 1.07) vs placebo (3.82 ± 1.67) for burning (P <.05) and flower powder (1.06 ± 0.58) vs placebo (1.95 ± 0.79) for diarrhea (P =.046). The flower powder prevented anal discomfort and diarrhea induced by prostate radiotherapy, although there were no significant differences between the two groups in RTOG. No serious side effects were reported, so the combination could be suggested for patients who cannot tolerate symptoms of proctitis after further studies. © 2018 Elsevier Gmb

The effect of the combination of Malva sylvestris L. and Althaea digitata Boiss. on prevention of acute radiation proctitis in patients with prostate cancer

The effect of a combination of Malva sylvestris and Althaea digitata flower powder in prevention of acute radiation proctitis was assessed in patients undergoing radiation therapy (RT) for prostate cancer. This double-blind randomized controlled study was conducted at three centers in Iran. Before starting RT, patients (N = 65) received a 4 g packet of flower powder or placebo to use 3 times a day as an infusion from the first day of RT and for five consecutive weeks including the three weeks of RT. They were visited by a physician 3 times during this period. Acute morbidity was classified according to the Radiation Therapy Oncology Group (RTOG) criteria. Severity of proctitis symptoms was assessed by Visual Analog Scale (VAS) with 10 points. Non-statistical significant differences were observed between the groups in relation to RTOG grade criteria (grade 0: drug 22.8 (N = 8), placebo 10 (N = 3), difference 12.8; grade 1: drug 65.8, placebo 64.4, difference 1.4; grade 2: drug 11.4 (N = 8), placebo 26.6 (N = 4), difference 15.2. (P = .059)) According to VAS, the most common complaint was anal burning and diarrhea in the flower powder group showing a significant decrease in these symptoms at the end of the study as compared to the placebo; flower powder (1.56 ± 1.07) vs placebo (3.82 ± 1.67) for burning (P < .05) and flower powder (1.06 ± 0.58) vs placebo (1.95 ± 0.79) for diarrhea (P = .046). The flower powder prevented anal discomfort and diarrhea induced by prostate radiotherapy, although there were no significant differences between the two groups in RTOG. No serious side effects were reported, so the combination could be suggested for patients who cannot tolerate symptoms of proctitis after further studies. © 2018 Elsevier Gmb