Increased NFκ-B Activity in HCT116 Colorectal Cancer Cell Line Harboring TLR4 Asp299Gly Variant

Toll-Like Receptor 4 (TLR4), considered one of the most important TLR, recognizes lipopolysaccharide of gram-negative bacteria. Recognition of ligands by TLRs induces signaling pathways resulting in activation of transcriptional factors such as NF-κB which are involved in the expression of inflammatory cytokines and chemokines. To prevent an inappropriate immune response, a complex network of molecules negatively regulates TLRs and their associated signaling pathways. Two cosegregating single nucleotide polymorphisms of the human TLR4 gene, namely Asp299Gly and Thr399Ile, have been associated with hyporesponsiveness to inhaled LPS. The purpose of this study was to determine the impact of TLR4 gene variant on NF-κB activity in colorectal cancer cell line. HCT116 cells were transfected with wild-type and mutants Flag-CMV1-TLR4 expression vectors. Western blot analysis was performed to evaluate selected molecules involved in TLR4 signaling. NF-κB activity was assessed by dualluciferase reporter assay and cytokine profiles were evaluated by ELISA and Cytometric Bead Array method. Results showed that the activity of pNF-κB was higher in cells harboring TLR4 D299G compared to the other cells. However, the activity of pAKT, pERK1 and pIRAK was higher in wild-type. The results of cytokine measurements showed about four fold higher level of IL-8 in cells with wild-type TLR4. This study suggest that TLR4 Asp299Gly gene variant has an impact on TLR4 signaling and potentially on intestinal homeostasis due to impaired control signals at the epithelial cell level which may lead to chronic intestinal inflammation and interrupted intestinal homeostasis and may eventually lead to colorectal cancer. Copyright© 2012, Iranian Journal of Allergy, Asthma and Immunology. All rights reserved

Effect of gold nanoparticles on prostate dose distribution under Ir-192 internal and 18 MV external radiotherapy procedures using gel dosimetry and monte carlo method

Background: Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. Objective: The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. Method: A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. Results: The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15 and 8 higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 and 7 due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. Conclusion: There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices. © 2015 Shiraz University of Medical Sciences. All Rights Reserved

Effect of tissue inhomogeneities on dosimetric accuracy of conformal radiotherapy of prostate cancer using Monte Carlo simulation

Background and purpose: The human body is composed of various inhomogenous tissues with a variety of physical and radiological properties. These inhomogeneities could change isodose distributions, increase the probability of geometric errors, and eventually lead to missing of the target irradiation or incorrect isodose coverage in conformal radiation therapy (CRT) due to the uncertainties resulted from the effect of such inhomogeneties on isodose curves. In this study, the effect of inhomogeneities on dosimetric accuracy of the CRT of prostate was investigated using Monte Carlo simulation method. Materials and methods: An anthropomorphic pelvis phantom was used in two modes representing a homogeneous and heterogeneous phantom. Three dimensional (3D) CRT planning composed of five fields were performed on the CT images of the phantoms using the CorPLAN treatment planning system (TPS) of a 2100C/D Varian linac. Delivery of 3DCRT was also simulated by EGSnrc Monte Carlo code for the same conditions used in the CorPLAN TPS. The dose distributions resulted from the MC simulations were compared with those of the CorPLAN TPS for both of the phantoms based on the �dose difference (DD) percentages� and �distance to agreement (DTA)� parameters. Results: Findings indicated that the heterogeneity leads to an overdose estimation at the target location up to 2.8 and 4.4 for the 6 and 18 MV energies, respectively by the CorPLAN TPS compared with the MC simulation data. The average DD and DTA for the homogeneous phantom were 2.7-3.4mm and 1.6-2.3 mm while for the inhomogeneous phantom they were 5.5-3.7 mm and 6.0-2.5 mm at the 6 and 18 MV energies, respectively. Conclusion: Our results indicates that the accuracy of the dosimetry parameters estimated by the CorPLAN TPS at 18 MV is more than that of 6 MV energy. But, the heterogeneity deteriorates more the accuracy level of such dosimetry parameters estimated by this commercial TPS at 18 MV energy. � 2016, Mazandaran University of Medical Sciences. All rights reserved

Estimation of dosimetric parameters based on K nr and K ncsf correction factors for small field radiation therapy at 6 and 18 MV linac energies using monte carlo simulation methods

Background: Estimating dosimetric parameters for small fields under non-reference conditions leads to significant errors if done based on conventional protocols used for large fields in reference conditions. Hence, further correction factors have been introduced to take into account the influence of spectral quality changes when various detectors are used in non-reference conditions at different depths and field sizes. Objective: Determining correction factors (K NR and K NCSF ) recommended recently for small field dosimetry formalism by American Association of Physicists in Medicine (AAPM) for different detectors at 6 and 18 MV photon beams. Methods: EGSnrc Monte Carlo code was used to calculate the doses measured with different detectors located in a slab phantom and the recommended K NR and K NCSF correction factors for various circular small field sizes ranging from 5-30 mm diameters. K NR and K NCSF correction factors were determined for different active detectors (a pinpoint chamber, EDP-20 and EDP-10 diodes) in a homogeneous phantom irradiated to 6 and 18 MV photon beams of a Varian linac (2100C/D). Results: K NR correction factor estimated for the highest small circular field size of 30 mm diameter for the pinpoint chamber, EDP-20 and EDP-10 diodes were 0.993, 1.020 and 1.054; and 0.992, 1.054 and 1.005 for the 6 and 18 MV beams, respectively. The K NCSF correction factor estimated for the lowest circular field size of 5 mm for the pinpoint chamber, EDP-20 and EDP-10 diodes were 0.994, 1.023, and 1.040; and 1.000, 1.014, and 1.022 for the 6 and 18 MV photon beams, respectively. Conclusion: Comparing the results obtained for the detectors used in this study reveals that the unshielded diodes (EDP-20 and EDP-10) can confidently be recommended for small field dosimetry as their correction factors (K NR and K NCSF ) was close to 1.0 for all small field sizes investigated and are mainly independent from the electron beam spot size. © 2019, Shiraz University of Medical Sciences. All rights reserved

Target dose enhancement factor alterations related to interaction between the photon beam energy and gold nanoparticles� size in external radiotherapy: Using Monte Carlo method

Introduction: To study the effects of various sizes of gold nanoparticles (GNPs) on the target tissue dose enhancement factor at the time of external radiotherapy with various photon beam energies ranged from kilovolts (kVs) to Megavolts (MVs) by using Monte Carlo (MC) method. Materials and Methods: MCNPX code was used for simulating the interaction of photon beams with various levels of energy with water solution including various sizes of GNPs at a presumptive region including a tumor. Initially, a water phantom including GNPs, which consisted a tumor with a size of 1�1�1 cm3 was simulated. The phantom was irradiated with various external monoenergetic photon beam ranged from kVs to MVs. The macroscopic dose enhancement factor (DEF) of the tumor due to the presence of various sizes of GNPs (15, 50, and 100 nm) at a concentration of 7 mg/g was calculated. Results: The tumor (target) DEF at the presence of the GNPs was obtained within the range of 1.69 to 2.66 kV and 1.08 to 1.10 MV photon beam. The highest DEF was found at 50 kV photon beam. The target DEF was increased with the increase in GNPs size. Conclusion: The calculated target DEFs at the presence of GNPs for photon beam energies in kV were similar to the previous studies. For the photon beam energies in MV, after a decrease at the interface of two regions of pure water and solution including the GNPs, DEF the tumor was increased and with 2 and 6 MV energies reached to its maximum at the depths 6.2 and 6.5 cm, respectively. © 2015, Semnan University of Medical Sciences. All rights reserved

Determination of correction factors for small field radiotherapy using 6 and 18MV energies of a linac

Background and purpose: Estimating dosimetric parameters for small fields at non-reference conditions lead to significant errors if they are done based on the conventional protocols used for large fields and reference conditions. The aim of this study was to determine and compare small fields correction factors (KNR and KNCSF) based on a novel protocol by using different types of detecors.Materials and methods: Specific circular cones were constructed and attached to a medical linac head to produce small field sizes down to 30 and 5mm diameters. Then, the KNR and KNCSF correction factors based on a recent protocol (TG155), proposed for small field dosimetry formalism, were determined for different active detectors (a pinpoint chamber, EDP20 and EDP10 diodes) in a homogeneous and a nonhomogeneous phantom at the above fields when irradiated to 6 and 18 MV beams of a Varian linac.Results: The KNR correction factors for the circle field of 30mm estimated for the pinpoint chamber, EDP20 and EDP10 diodes were 0.993, 1.020 and 1.054 at 6 MV; and 0.992, 1.054 and 1.005 at 18 MV, respectively. The KNCSF correction factor for the 5mm circle field estimated for the pinpoint chamber, EDP20 and EDP10 diodes were 0.994, 1.023 and 1.040 at 6MV; and 1.000, 1.014 and 1.022 at 18MV, respectively.Conclusion: Our results indicated that implementing the correction factors estimated for the small fields based on the new proposed dosimetry protocol increases the dosimetric precision and accuracy of such fields in radiotherapy practices. Also, considering the perturbations happening between the boundaries of non-homogeneous area could increase the accuracy of the dosimetry procedures in such conditions. � 2015, J Mazandaran Univ Med Sci. All rights reserved

Clear-cell carcinoma originating from cesarean section scar: two case reports

Background: Clear-cell carcinoma arising from the surgical cesarean section scar is very infrequent. The present study reports two patients with clear-cell carcinoma arising from an abdominal wall scar 20 and 23 years after their last cesarean section. Case presentation: Both Iranian patients had prior cesarean sections nearly 20 years earlier. Patients 1 and 2 had transverse and vertical abdominal incisions, respectively. The initial clinical presentation was a huge lower abdominal mass at the site of the previous cesarean section scar. Both patients underwent abdominal wall mass biopsy. The histological analysis revealed the presence of malignancy. Both patients underwent full-thickness resection of the abdominal wall mass. All surgical margins were tumor-free; however, patient 1 had a very narrow tumor-free margin near the pubic symphysis. As the imaging report of patient 2 revealed the presence of a pelvic mass, the exploration of the intraperitoneal space, simple total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and the excision of enlarged pelvic lymph nodes were performed during the surgery. Six cycles of paclitaxel and carboplatin every 3 weeks as adjuvant chemotherapy was administered for both patients after the surgery. One of the patients had disease recurrence 5 months after the termination of chemotherapy, and the other is still disease-free. These two patients had similar pathology and received a similar initial adjuvant treatment; however, they were different in terms of the direction of tumor spread, tumor distance from the pubic symphysis, status of tumor margins, and surgical procedures. Conclusions: We encountered distinct prognoses in the clear-cell carcinoma of cesarean section scars presented herein. The researchers can recommend complete surgical excision of the abdominal wall mass with wide tumor-free margins, exploration of the abdominopelvic space, TAH, and BSO during the first surgery. © 2021, The Author(s)

Bone mineral density in Iranian adolescents and young adults with β-thalassemia major

The authors investigated the prevalence of low bone mass in patients from Tehran, Iran, with β-thalassemia major (n = 203), aged 10-20 years, and the potential risk factors for osteoporosis in this patient population. Prevalence of osteoporosis was 50.7 in lumbar spine, 10.8 in femur, and 7.9 in both regions with no significant difference between the two genders. The following factors were associated with low BMD: height for age and weight for age below 3rd percentile, delayed puberty or hypogonadism, age when Desferal (for iron chelation) was started, duration of Desferal therapy, and serum zinc. Low serum copper and 25(OH)D were not associated with low BMD. Copyright © Informa Healthcare USA, Inc

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters