Flank Region Research Articles

Effects of multiscale phase-mixing and interior conductance in the lunar-like pickup ion plasma wake. First results from 3-D hybrid kinetic modeling

The study of multiscale pickup ion phase-mixing in the lunar plasma wake with a hybrid model is the main subject of our investigation in this paper. Photoionization and charge exchange of protons with the lunar exosphere are the ionization processes included in our model. The computational model includes the self-consistent dynamics of the light (H+ or H2+ and He+), and heavy (Na+) pickup ions. The electrons are considered as a fluid. The lunar interior is considered as a weakly conducting body. In this paper we considered for the first time the cumulative effect of heavy neutrals in the lunar exosphere (e.g., Al, Ar), an effect which was simulated with one species of Na+ but with a tenfold increase in total production rates. We find that various species produce various types of plasma tail in the lunar plasma wake. Specifically, Na+ and He+ pickup ions form a cycloid-like tail, whereas the H+ or H2+ pickup ions form a tail with a high density core and saw-like periodic structures in the flank region. The length of these structures varies from 1.5RM to 3.3RM depending on the value of gyroradius for H+ or H2+ pickup ions. The light pickup ions produce more symmetrical jump in the density and magnetic field at the Mach cone which is mainly controlled by the conductivity of the interior, an effect previously unappreciated. Although other pickup ion species had little effect on the nature of the interaction of the Moon with the solar wind, the global structure of the lunar tail in these simulations appeared quite different when the H2+ production rate was high.

High Intensity Focused Ultrasound (HIFU) Heating Improves Perfusion and Antimicrobial Efficacy in Mouse Staphylococcus Abscess

Chronic wounds typically require long-duration treatment with a combination of antibiotics administered systemically. This incurs adverse side effects and can require aversive surgical treatments and limb amputations. To improve non-invasive antimicrobial therapy, the objective of this study was to investigate antimicrobial chemotherapy combined with high-intensity focused ultrasound (HIFU) heating (HT). A Staphylococcus aureus abscess (80 ± 30 mm3) was generated in the mouse flank region. Once the average temperature (~42 °C–46 °C) in the abscess was reached with HIFU-HT, a broad-spectrum antimicrobial (ciprofloxacin, 10 mg/kg) and perfusion marker (Evans blue dye, 40 mg/kg wt) were administered intravenously via the tail vein. Four hours later, mean abscess perfusion and colony-forming units (CFUs) per gram of abscess were determined. HIFU-HT increased abscess perfusion by ~2.5-fold (4 ± 0.6 µg/mL Evans blue) compared with control (1.5 ± 0.7 µg/mL), and improved antimicrobial efficacy to decrease percentage average survival of S. aureus by ~20% (46 ± 7 CFUs/g of abscess) versus that seen with ciprofloxacin alone (61 ± 4 CFU/g). Our in vivo data suggest that HIFU-HT can improve antimicrobial treatment responses against deep-seated bacteria in abscess wounds via enhanced perfusion.

AB164. 54. A novel treatment for chronic disease: minimal invasive surgery for Morel-Lavallee lesions

Background: Morel-Lavallee lesion (MLL) is a post-traumatic, closed, degloving soft tissue injury secondary to shearing or tangential forces. A dead space is created between the subcutaneous tissue and the underlying fascia that fills with heamolymphocel and liquefied fat. The common anatomical sites for these lesions are greater trochanter, flank, buttocks and lumbo-dorsal region. The patient presents with variable clinical features, ranging from a painful, fluctuant soft tissue swelling to abscess formation or skin necrosis with associated fever and malaise, following history of trauma such as motor vehicle accident or a fall. MRI is the investigation of choice and the treatment approaches initially involves conservative management with antimicrobial cover. But in case of failure of conservative management, open drainage and extensive debridement of devitalized tissues as well as skin grafting is required due to significant skin loss. This not only has severe morbidity but also can result in fatal complications. Therefore, the need to develop an alternative treatment methodology is urgently necessitated.

Long Noncoding RNA-Associated Transcriptomic Changes in Resiliency or Susceptibility to Depression and Response to Antidepressant Treatment.

BackgroundRecent emergence of long noncoding RNAs in regulating gene expression and thereby modulating physiological functions in brain has manifested their possible role in psychiatric disorders. In this study, the roles of long noncoding RNAs in susceptibility and resiliency to develop stress-induced depression and their response to antidepressant treatment were examined.MethodsMicroarray-based transcriptome-wide changes in long noncoding RNAs were determined in hippocampus of male Holtzman rats who showed susceptibility (learned helplessness) or resiliency (nonlearned helplessness) to develop depression. Changes in long noncoding RNA expression were also ascertained after subchronic administration of fluoxetine to learned helplessness rats. Bioinformatic and target prediction analyses (cis- and trans-acting) and qPCR-based assays were performed to decipher the functional role of altered long noncoding RNAs.ResultsGroup-wise comparison showed an overrepresented class of long noncoding RNAs that were uniquely associated with nonlearned helplessness or learned helplessness behavior. Chromosomal mapping within the 5-kbp flank region of the top 20 dysregulated long noncoding RNAs in the learned helplessness group showed several target genes that were regulated through cis- or trans-actions, including Zbtb20 and Zfp385b from zinc finger binding protein family. Genomic context of differentially expressed long noncoding RNAs showed an overall blunted response in the learned helplessness group regardless of the long noncoding RNA classes analyzed. Gene ontology exhibited the functional clustering for anatomical structure development, cellular architecture modulation, protein metabolism, and cellular communications. Fluoxetine treatment reversed learned helplessness-induced changes in many long noncoding RNAs and target genes.ConclusionsThe involvement of specific classes of long noncoding RNAs with distinctive roles in modulating target gene expression could confer the role of long noncoding RNAs in resiliency or susceptibility to develop depression with a reciprocal response to antidepressant treatment.

Turbulence and Heating in the Flank and Wake Regions of a Coronal Mass Ejection

As a coronal mass ejection (CME) passes, the flank and wake regions are typically strongly disturbed. Various instruments, including the Large Angle and Spectroscopic Coronagraph (LASCO), the Atmospheric Imaging Assembly (AIA), and the Coronal Multi-channel Polarimeter (CoMP), observed a CME close to the east limb on 26 October 2013. A hot ( ${\approx}\,10~\mbox{MK}$ ) rising blob was detected on the east limb, with an initial ejection flow speed of ${\approx}\, 330~\mbox{km}\,\mbox{s}^{-1}$ . The magnetic structures on both sides and in the wake of the CME were strongly distorted, showing initiation of turbulent motions with Doppler-shift oscillations enhanced from ${\approx}\, \pm 3~\mbox{km}\,\mbox{s}^{-1}$ to ${\approx}\, \pm 15~\mbox{km}\,\mbox{s}^{-1}$ and effective thermal velocities from ${\approx}\,30~\mbox{km}\,\mbox{s}^{-1}$ to ${\approx}\,60~\mbox{km}\,\mbox{s}^{-1}$ , according to the CoMP observations at the Fe xiii line. The CoMP Doppler-shift maps suggest that the turbulence behaved differently at various heights; it showed clear wave-like torsional oscillations at lower altitudes, which are interpreted as the antiphase oscillation of an alternating red/blue Doppler shift across the strands at the flank. The turbulence seems to appear differently in the channels of different temperatures. Its turnover time was ${\approx}\,1000$ seconds for the Fe 171 A channel, while it was ${\approx}\,500$ seconds for the Fe 193 A channel. Mainly horizontal swaying rotations were observed in the Fe 171 A channel, while more vertical vortices were seen in the Fe 193 A channel. The differential-emission-measure profiles in the flank and wake regions have two components that evolve differently: the cool component decreased over time, evidently indicating a drop-out of cool materials due to ejection, while the hot component increased dramatically, probably because of the heating process, which is suspected to be a result of magnetic reconnection and turbulence dissipation. These results suggest a new turbulence-heating scenario of the solar corona and solar wind.

Clinico-pathological alterations in geriatric dogs

The present study was conducted to evaluate the gross and microscopic changes in the tissues of dogs dying due to geriatric conditions. During the study period, 15 old dogs were taken into consideration as geriatric dogs during clinical presentation and died at different times. History and clinical findings along with haemato-biochemical alterations were studied in all the 15 cases. Systemic postmortem examination of 7 geriatric dogs was conducted and detailed gross lesion in different organ were recorded. Anemia, anemia associated with dirofilariasis, jaundice, hepatitis, nephritis and chronic enteritis were major cause of death during old age. Important gross changes included pale skeletal muscle, enlarged spleen, cardiac dilatation, necrotic liver, nephritic kidney, thickened intestinal wall etc. Significant histopathological findings related to old age were evidenced like glomerular sclerosis, glomerular atrophy in kidney, bile duct hyperplasia and centrilobular necrosis in liver, depletion of the splenic pulp and thickened epidermis of skin at flank region.

Abstract A200: CBT-502 (TQB2450), a novel anti-PD-L1 antibody, demonstrates favorable activity in MC-38/H-11 murine colon and A375 human melanoma animal models

Abstract Background: CBT-502 (TQB2450) is a novel humanized IgG1 antibody against programmed cell death-ligand 1(PD-L1) developed by CBT Pharmaceuticals, Inc. CBT-502 shows significant sequence divergence in CDRs from other anti-PD-L1 antibodies in the market today, including atezolizumab, durvalumab, and avelumab. Several human cancer cells express high levels of PD-L1. PD-L1 binds to its receptor, PD-1, on activated T cells, and CD80, on dendritic cells and monocytes and inhibits cytotoxic T cells. Therapeutic blockade of PD-L1 reduces the growth of tumors in the presence of immune cells. In vitro, CBT-502 demonstrated binding affinity to human PD-L1 by SPR of 0.25 nM and cyno-PD-L1 of 0.24 nM. In cell based assay, CBT-502 effectively blocked the interaction of hPD-1 and hPD-L1 (IC50 47.97 pM) and blocked binding of PD-L1 with CD80 (IC50 1.09 nM). CBT-502 strongly activates T cells as measured by IFN-gamma production in a mixed lymphocyte reaction assay. Pharmacokinetic data in cynomologus monkeys showed a linear dose-dependent relationship. No adverse clinical or histopathologic findings were observed in toxicology screen (NOAEL=200 mg/kg). CBT-502 showed no Fc receptor affinity including FcgRIa, FcgRIIa-167His/Arg, FcgRIIIa-176Phe/Val, FcRn SPR and C1Q. In vivo antitumor activity was evaluated in two mouse models, A375 (melanoma) and MC-38/H-11 (colon), reported herein. Methods: Fifty C57BL/6 mice were intraperitoneally (IP) inoculated with 1x105 MC-38/H-11 cells, and the mice were randomly divided into five groups on Day 2 (D0) following inoculation. The test article group was intraperitoneally injected (IP) with 1.5, 5 and 15 mg/kg once every other day (Q2D) x 11 times while the positive control group (atezolizumab) was administered IP with 15 mg/kg, and the negative control group (human IgG) was injected with same volume at 15 mg/kg. Similarly, A375 human melanoma cells (5 x 106) were implanted subcutaneously in the flank region of highly immune-deficient mouse model (NCG mouse, n=36). The mouse immune system was replaced with human PBMC. Only mice with high CD45 ratio are included in the study. CBT-502 was dosed IP at 5 and 10 mg/kg once weekly (qw) and three times weekly (tiw), whereas atezolizumab was dosed 10 mg/kg (tiw). Results: In the MC-38/H-11 model, CBT-502 relative to atezolizumab demonstrated comparable tumor growth inhibition (TGI) rates, 91.7% vs. 93.8% in the 15 mg/kg dose group. CBT-502 showed potent in vivo antitumor activity in a dose-dependent manner in the A375 model. TGI % at 10 mg/kg tiw was 53.5% and 59.4% for CBT-502 and atezolizumab, respectively. There was no obvious loss of body weight (BW) with CBT-502 administration, although a slight reduction in BW was observed with atezolizumab 10 mg/kg tiw. Conclusions: CBT-502 preclinical pharmacodynamics and toxicology studies demonstrated pharmacologic activity and is well tolerated at effective doses with a wide margin of safety. In vivo efficacy and safety data in the A375 model compared favorably to atezolizumab, with the MC38 model confirming activity of CBT-502. With these encouraging nonclinical data, CBT Pharmaceuticals and China partner CTTQ plan to develop and evaluate CBT-502 in multiple solid tumors, anticipated in 2018. Citation Format: Zhao Wei, Ling Yang, Yingchun Li, Jiansheng Lu, Xiquan Zhang, Xin Tian, Jiping Zha, Ziyong Sun, Junzhuan Qiu, Zhun Wang, Mamatha Reddy, Gavin S. Choy, Sanjeev Redkar. CBT-502 (TQB2450), a novel anti-PD-L1 antibody, demonstrates favorable activity in MC-38/H-11 murine colon and A375 human melanoma animal models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A200.

PRIMARY RENAL SQUAMOUS CELL CARCINOMA IN A NON-FUNCTIONING KIDNEY WITH NEPHROLITHIASIS: A CASE REPORT

Primary squamous cell carcinoma (SCC) of renal pelvis is a rare neoplasm. A 50-year-old female presented with a history of chronic dull aching pain in left flank region and burning micturition for 8 months. Workup showed multiple calculi in non-functioning, hydronephrotic left kidney. Histopathological examination of nephrectomy specimen revealed SCC of renal pelvis; although, there was no obvious growth. The case report highlights the fact that SCC should be suspected in a patient with renal mass in a non-functioning kidney following long-standing nephrolithiasis.

EFFECTS OF BLINDFOLD AND TAIL BEND OF EGYPTIAN WATER BUFFALO ON BEHAVIOURAL REACTIVITY AND PHYSIOLOGICAL RESPONSES TO PAIN INDUCTION

Buffaloes are an important economic source for milk and meat production and for work and draught power in Egypt. Improving management practices applied to water buffalo may not only improve their welfare but has also an economic benefit. This experiment was carried out to determine the effect of blindfold and tail bending during restraint for veterinary treatment of Egyptian buffaloes on their behavioural reactivity and physiological responses to stress. Forty-eight Egyptian water buffalo bulls, naïve to the testing situation, were arbitrarily assigned to either blindfold (visual restriction) (BF), tail bending (physical control) (TT) or control (CT) (no visual restriction or physical control) treatment during restraint. Animals were entered the squeeze chute and the sides of the chute were adjusted to make contact with the animal body so that preventing unsteady movements, and were subjected to a 3day (day 1, 2 and 3) testing trials (injection stress) of three minutes each (1 m pre injection induction phase, 1 m injection induction phase and 1 m post injection induction phase). Heart rate (HR) was recorded using a stethoscope as soon as the animal was positioned in the squeeze chute and the respiratory rate (RR) was determined through counting the movement of flank region, and various reactivity-indicating behaviours were collected onto check sheet. Average HR decreased in both TT and BF bulls during and after stress (P= 0.001) but the reduction in HR was greater in BF bulls (67.25±3.41 and 55.00±1.08, respectively) in day 3 after stress (P= 0.001). Similarly, average RR decreased in both TT and BF bulls (P= 0.001) during and after stress but the reduction was greater in BF bulls during stress (25.38±0.53 and 19.92±0.33, respectively). Blindfolding and tail bending buffalo bulls decreased average frequency of their behavioural indicators of reactivity including: chest chute forcing prestress (P=0.01), during and post stress (P=0.001); head move (P=0.001); kicking prestress (P=0.05) during stress (P=0.001) and post stress (P=0.05); struggling move prestress, during stress (P=0.001) and post stress (P=0.05). The reduction was greater in BF bulls in case of chest chute prestress (0.08±0.05 and 0.50±0.16, respectively), struggling move during (0.33±0.02 and 0.75±0.04, respectively) and post stress (0.13±0.06 and 0.29±0.08, respectively). Taken together, both tail bend and blindfold water buffaloes decreased behavioural and physiological indicators of stress but BF appeared more beneficial and may therefore be recommended to reduce stress accompanying routine veterinary examination of buffaloes

Studies on reconstruction of large skin defects following mammary tumor excision in dogs

Aim:The main objective of the study was to describe the use of skin fold advancement flaps (SFAFs) and other reconstructive techniques for closure of large skin defects following mammary tumor excision in dogs.Materials and Methods:Twelve dogs underwent reconstruction of large ventral skin defects following mammary tumor excision with wide margins. Skin fold flaps (flank fold flap and elbow fold flap) were elevated from the flank and elbow region, respectively, and transposed and sutured onto the large ventral skin defect following mastectomy in all the dogs. In addition to the skin fold flaps, other reconstructive techniques such as undermining, walking sutures, and tension-relieving suture techniques were followed during surgery in the closure of large skin defects without skin tension and compromising limb mobility. The skin flap viability was assessed subjectively by gross observation of the flap such as color, temperature, capillary perfusion, and cosmetic appearance, and scoring (1-4) was done. Tissue samples were collected from a surgical site on days 3, 6, and 12 post-operatively for histopathological evaluation and healing status of the skin flap.Results:All the surgical wounds healed primarily, without any major complications and the skin flap remained healthy throughout the healing process post-operatively. Distal flap necrosis was noticed in one case and necrosis of skin flap between two suture lines was noticed in another case in which the necrotized distal portion healed by secondary intention after 7 days. The mean survival of subdermal plexus flap in the above cases was 98% which was a subjective evaluation based on surface area of the skin defect measured by Image’ J software and the flap dimensions. The average healing of skin flap in days was 14.91±0.86.Conclusion:The SFAFs along with other reconstructive techniques help in the reconstruction of large ventral skin defects following mastectomy in dogs without much compromising limb mobility.

Spontaneous hemothorax caused by ruptured multiple mycotic aortic aneurysms: a case report and literature review

BackgroundMycotic aortic aneurysm (MAA) is a rare clinical entity with an incidence of 1-3%, but it is a life-threatening infection of aorta characterized by dilatation of aorta with false lumen. Multiple MAAs have been reported rarely with an incidence of 0.03% and associated with a high mortality rate of 80% if ruptured.Case presentationA hypertensive and diabetic 78-year-old man visited our emergency department complaining intermittent dull and tingled pain over the left flank region for 1 week. Chest X-ray showed left pleural effusion and hemothorax was confirmed by thoracocentesis. Computed tomography (CT) of chest demonstrated multiple thoracic aortic aneurysms and the pathological findings disclosed the diagnosis of multiple MAAs. He was discharged under an uneventful condition post-surgical aortic repair with adequate intravenous antibiotics for 4 weeks.ConclusionsCT scan may make a definite diagnosis of multiple MAAs and management with surgical debridement, aortic repair and full-course antibiotics for Gram-positive coccus and/or Gram-negative bacillus is recommended.

Skin measurements in relation to milking traits in Murrah buffaloes

There was significant effect of skin thickness on daily milk yield, milking time and milk flow rate in Murrah buffaloes. The daily milk yield was negatively correlated with skin fold thickness in these animals and significant correlations were found with skin fold thickness of flank (–0.334) and udder (–0.264) regions. The milk let down time was not affected; whereas milking time was significantly affected based on daily milk yield and milk flow rate. The milk flow rate was significantly higher for animals with thin and moderately thick skin of different body regions except abdomen (29.27±0.70 g/sec). No significant variation was seen in fat percentage based on skin thickness, except in chest region which was negatively correlated (–0.398).

MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using Physicochemical Properties and HMM profiles

Motivation. Intrinsically Disordered Proteins (IDPs) lack stable tertiary structure and they actively participate in performing various biological functions. These IDPs expose short binding regions called Molecular Recognition Features (MoRFs) that permit interaction with structured protein regions. Upon interaction they undergo a disorder-to-order transition as a result of which their functionality arises. Predicting these MoRFs in disordered protein sequences is a challenging task.Method. In this study, we present MoRFpred-plus, an improved predictor over our previous proposed predictor to identify MoRFs in disordered protein sequences. Two separate independent propensity scores are computed via incorporating physicochemical properties and HMM profiles, these scores are combined to predict final MoRF propensity score for a given residue. The first score reflects the characteristics of a query residue to be part of MoRF region based on the composition and similarity of assumed MoRF and flank regions. The second score reflects the characteristics of a query residue to be part of MoRF region based on the properties of flanks associated around the given residue in the query protein sequence. The propensity scores are processed and common averaging is applied to generate the final prediction score of MoRFpred-plus.Results. Performance of the proposed predictor is compared with available MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected training and test sets used to evaluate the mentioned predictors, the proposed predictor outperforms these predictors and generates lower false positive rate. In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as it can be used as input to other computational tools.Availability.https://github.com/roneshsharma/MoRFpred-plus/wiki/MoRFpred-plus:-Download

Origin of Radio Enhancements in Type II Bursts in the Outer Corona

We study interplanetary (IP) solar radio type II bursts from 2011 – 2014 in order to determine the cause of the intense enhancements in their radio emission. Type II bursts are known to be due to propagating shocks that are often associated with fast halo-type coronal mass ejections (CMEs). We analysed the radio spectral data and the white-light coronagraph data from 16 selected events to obtain directions and heights for the propagating CMEs and the type II bursts. CMEs preceding the selected events were included in the analysis to verify whether CME interaction was possible. As a result, we were able to classify the events into five different groups. 1) Events where the heights of the CMEs and type II bursts are consistent, indicating that the shock is located at the leading front of the CME. The radio enhancements are superposed on the type II lanes, and they are probably formed when the shock meets remnant material from earlier CMEs, but the shock continues to propagate at the same speed. 2) Events where the type II heights agree with the CME leading front and an earlier CME is located at a height that suggests interaction. The radio enhancements and frequency jumps could be due to the merging process of the CMEs. 3) Events where the type II heights are significantly lower than the CME heights almost from the start. Interaction with close-by streamers is probably the cause for the enhanced radio emission, which is located at the CME flank region. 4) Events where the radio enhancements are located within wide-band type II bursts and the causes for the radio enhancements are not clear. 5) Events where the radio enhancements are associated with later-accelerated particles (electron beams, observed as type III bursts) that stop at the type II burst emission lane, and no other obvious reason for the enhancement can be identified. Most of the events (38%) were due to shock–streamer interaction, while one quarter of the events was due to possible CME–CME interaction. The drift rates, bandwidth characteristics, or cross-correlations of various characteristics did not reveal any clear association with particular category types. The chosen atmospheric density model causes the largest uncertainties in the derived radio heights, although in some cases, the emission bandwidths also lead to relatively large error margins. Our conclusion is that the enhanced radio emission associated with CMEs and propagating shocks can have different origins, depending on their overall configuration and the associated processes.

Successful Conservative Management of Spontaneous Unilateral Adrenal Hemorrhage in Pregnancy

ABSTRACT Spontaneous adrenal hemorrhage (SAH) in the absence of trauma or adrenal tumor is a rare condition. Its incidence has been reported from 0.14 to 1.1% and it usually involves the right adrenal gland. During pregnancy, unilateral SAH has been reported very rarely. We describe a case who presented to us with pregnancy-induced hypertension and pain in right flank region for 1 day and diagnosed as a case of spontaneous right adrenal hemorrhage and managed conservatively. How to cite this article Mishra VV, Goyal P, Choudhary S, Aggarwal R, Roy P. Successful Conservative Management of Spontaneous Unilateral Adrenal Hemorrhage in Pregnancy. J South Asian Feder Obst Gynae 2017;9(3):287-288.

Abstract 5191: A combination of Stat3 inhibitor and radiation for the treatment of malignant pleural mesothelioma

Abstract Background: Trimodality therapy, including surgery, is the treatment for patients with malignant pleural mesothelioma (MPM). However, the 5-year survival rate remains less than 40%. To improve the survival rate, we investigated Stat3 as a potential therapeutic target for MPM. Methods:Cell viability was assessed using Cell Counting Kit-8 (CCK-8: WST-8 Dojindo). MPM cells (NCI-H28, NCI-H226, NCI-H2052, NCI-H2452, MSTO-211H) were seeded into 96-well plates. After treatment with a Stat3 inhibitor (BBI-608 : napabucasin), Cell Counting Kit-8 solution was added to each well and absorbance was measured using a microplate reader. The level of phosphorylated Stat3 (p-Stat3) in cell lysates was measured by ELISA. ROS level in cells was measured by FACS analysis. In the in vivo study, H226 cells were injected subcutaneously in the flank region of nude mice randomly assigned to four treatment groups (5 mice/group)—(1) treatment with vehicle control, (2) treatment with Stat3 inhibitor, (3) radiation therapy (RT), and (4) Stat3 inhibitor and RT. Tumor size was measured twice/week. Results: Napabucasin decreased the viability of MPM cells (epithelioid, sarcoma, biphasic) in a dose-dependent manner. p-Stat3 levels decreased by 90% after treatment with 10 μM napabucasin in H226 cells. Napabucasin treatment induced more ROS production in MPM cells than did Pemetrexed. Moreover, combinatorial treatment with napabucasin and radiation (2 Gy, 5 Gy) induced more ROS production than did RT alone. In the mouse model, treatment with napabucasin alone significantly suppressed tumor growth (p < 0.05), but napabucasin and RT completely suppressed tumor growth. Conclusion:We showed that napabucasin inhibited proliferation of the MPM cells (epithelial, biphasic, sarcomatoid) and demonstrated that combination therapy with napabucasin and radiation completely suppressed tumor growth in a mouse model. Treatment with the napabucasin alone and the combination of napabucasin and RT induced high ROS production in MPM cells. Collectively, the combination of Stat3 inhibitor with Radiation Therapy (START) is a promising approach for the treatment of MPM.TheA combination of of Stat3 inhibitor and radiation with for the treatment of malignant pleural mesothelioma Citation Format: Seiji Matsumoto, Hiroshi Doi, Akihiro Fukuda, Tohoru Nakamichi, Ayumi Kuroda, Masaki Hashimoto, Teruhisa Takuwa, Nobuyuki Kondo, Seiki Hasegawa. A combination of Stat3 inhibitor and radiation for the treatment of malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5191. doi:10.1158/1538-7445.AM2017-5191

Core and Surface Temperature Modification During Road Transport and Physical Exercise in Horse After Acupuncture Needle Stimulation

In this study, the effect of acupuncture on skin temperature (TSKIN), including six body regions (neck, shoulder, ribs, flank, internal thigh, and back), rectal temperature (TRECTAL), serum levels of total proteins, hematocrit, magnesium, calcium (Ca), phosphorus, and chloride was evaluated in five Thoroughbred horses. Horses competed in two official races. For each race, animals were transported from their stables to the racetrack. Horses transported and competed in the first race represent the control group. Two weeks later, the same horses competed in the second race. Before road transport, they were treated with acupuncture. From animals, the TSKIN, TRECTAL, and blood samples were collected at rest; after unloaded, 30 minutes after unloaded, at rest in the transit box, at the end of the race, and 30 minutes after the race. A significant effect of transport and exercise was found on all studied parameters (P < .01), except for Ca and TSKIN of neck (P > .05), in both groups. Transported and exercised horses subjected to acupuncture treatment showed statistically significant higher values of TRECTAL and TSKIN of flank (P < .01). Thoroughbred horses display a classic hemodynamic response to transport and exercise; acupuncture affects body temperature and skin temperature of flank region in both transported and exercised horses suggesting a controlling effect of acupuncture on thermoregulatory function, probably, by decreasing the activities of sympathetic function and manifested as vasodilatation, arterial blood flow, and skin microcirculation increase.

MP83-04 SUPPRESSION OF HUMAN PROSTATE CANCER (CAP) BY ADOPTIVE TRANSFER OF PATIENT-DERIVED PSMA-SPECIFIC, TGF-ß-INSENSITIVE CD8+ T CELLS

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II1 Apr 2017MP83-04 SUPPRESSION OF HUMAN PROSTATE CANCER (CAP) BY ADOPTIVE TRANSFER OF PATIENT-DERIVED PSMA-SPECIFIC, TGF-ß-INSENSITIVE CD8+ T CELLS Qiang Zhang, Timothy Kuzel, Brian Helfand, Ximing J Yang, Weijun Qin, Chung Lee, Benebito Carneiro, and Francis J Giles Qiang ZhangQiang Zhang More articles by this author , Timothy KuzelTimothy Kuzel More articles by this author , Brian HelfandBrian Helfand More articles by this author , Ximing J YangXiming J Yang More articles by this author , Weijun QinWeijun Qin More articles by this author , Chung LeeChung Lee More articles by this author , Benebito CarneiroBenebito Carneiro More articles by this author , and Francis J GilesFrancis J Giles More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2572AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has previously been shown that tumor-derived TGF-β related potent immunosuppression and lack of tumor killing specificity promote CaP progression. Here we report a new immunotherapeutic approach using adoptive transfer of patient-derived PSMA-specific, TGF-β-insensitive human CD8+ T cells to inhibit solid xenograft CaP. METHODS Peripheral blood CD8+ T cells were collected from metastatic castration resistant CaP patient by leukapheresis and cultured in the FDA approved Cell Processing Work Station (CPWS, Panasonic) with CD-3 Biotin/CD28/Anti-Biotin Beads (Bead: Cell 1:2) and IL-2 (100units/ml). We developed a TβRIIDN-TK-IRES-PZ1 chimeric T cell receptor retroviral construct using an anti-PSMA IgTCR(ζ) gene (PZ1) and a dominant negative TGF-β type II receptor (TβRIIDN) that could induce CD8+ T cells to be PSMA reactive and insensitive to TGF-β. PC-3 cells (PSMA negative; ATCC) or PSMA positive PC-3-PSMA cells (Cleveland Clinic) were used for target cells. Subcutaneous injection of PC-3 and PC-3-PSMA cells (2x105 cells/each, infected with HSV1-tk-GFP-luciferase reporter) into the left and right flank region respectively in each of 48 immunodeficient RAG-1 mice was performed. One week later, the animals were randomly assigned to one of three adoptive transfer groups (16 mice /each group, 2x106 CD8+ T cells/each mice): Group 1: CD8+ T cells infected with TβRIIDN-TK-IRES-PZ1 (71.1% positive); Group 2: Naive CD8+ T cells; Group 3: No treatment group. Tumor growth was monitored by IVIS luciferase imaging. The animals were provided 2 weekly adoptive transfer treatments and sacrificed after 3 weeks. The size and the weight of the tumor were recorded, and the infiltration of CD8+ T cells and apoptosis was evaluated by immunofluorescence staining and TUNEL. RESULTS In Group 1, the average tumor weight and volume was significantly lower in the PC3-PSMA tumor (0.413g and 514.2mm3) compared to the PC3 tumor (2.75 g and 3165.2 mm3); (~3-6×, P<0.05). There was no difference between the PC3 tumor (2.36g and 2768.5mm3 ) compared to PC3-PSMA tumor (2.45g and 2411.99 mm3) in Group 2 or Group 3. H&E staining showed large amount of nuclear fusion, fragmentation and necrosis were found in PC3-PSMA tumors in Group 1 compared to Group 2 and 3. In Group 1, tumor apoptosis (72.5/1,000 µm2) and CD8+ T cell infiltration (45.5/1,000 µm2 ) in PC3-PSMA tumor parenchyma was significantly higher compared to PC3 tumor (6.7/1,000 µm2 and 3.1/1,000 µm2 respectively). There was no significant apoptosis or CD8+ T cells infiltration observed in either PC3 and PC3-PSMA tumor in Group 2 and Group 3. CONCLUSIONS Our approach combines TGF-β insensitive with PSMA selectivity that significantly enhance the specificity and tumor killing ability of patient CD8+ T cells, and simultaneously suppress the tumor derived TGF-βinduced immunosuppression. Therefore, this construct may offer a novel therapeutic intervention for both primary CaP treatment as well as for recurrence after prostatectomy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1107 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Qiang Zhang More articles by this author Timothy Kuzel More articles by this author Brian Helfand More articles by this author Ximing J Yang More articles by this author Weijun Qin More articles by this author Chung Lee More articles by this author Benebito Carneiro More articles by this author Francis J Giles More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abdominoplasty in prune belly syndrome: Modifications in Monfort technique to address variable patterns of abdominal wall weakness

Abdominoplasty is an important component of the management of children with prune belly syndrome (PBS). While there are features of the abdominal defect in PBS which are common to all patients, there will be differences unique to each patient that should be taken into consideration in surgical planning. Specifically, we have come to realize that although the Monfort procedure assumes a symmetric pattern of abdominal wall laxity, this symmetry is rarely present. The aim of this report is to describe our modifications and review our outcomes for the Monfort procedure which more completely address correction of the abdominal wall laxity including both common and uncommon features while positioning the umbilicus to a more anatomically correct position (Figure). Sixteen male patients with PBS and one female pseudoprune belly syndrome patient, aged 2-9 years, were treated at our institution between 2003 and 2014. Modifications incorporated into the abdominoplasty procedure for PBS applied to this study group included: 1) use of diagnostic laparoscopy to define the topography of the abdominal wall defect, 2) initial midline rather than elliptical skin incision to defer retailoring of the skin coverage until the final step of the procedure, 3) varying the width of the central plate to correct side to side asymmetry in redundancy, 4) plication of the central plate to reduce vertical redundancy and reposition the umbilicus, and 5) plication of focal areas of fascial weakness, most often in the flank region. All patients have improved abdominal wall contour with a more uniform correction of areas of weakness at a mean follow-up of 5.5 years (range 18 months-11.5 years). All patients and parents indicate that they are very satisfied with the outcome of their procedures without any revisions being performed. This study is descriptive in nature and retrospective, with the patient population treated in a relatively uniform fashion that does not allow direct comparison with other techniques. The modified Monfort procedure recognizes the pattern of abdominal muscular deficiency unique to each patient and incorporates this information into the surgical design.

An imaging target TGF-β1 for hepatocellular carcinoma in mice.

The TGF-β1 antibody was obtained from Bioss Inc. The Huh-7 cell line (Liver Cancer Institute, Zhongshan Hospital, Fudan University) is a HCC cell line with high metastatic potential. Each mouse was subcutaneously injected with 5×106/0.1mL Huh-7 cells in the right upper flank region for the establishment of a subcutaneous xenograft model. The Iodogen method was used to label TGF-β1 antibody with 125I. In this experiment, 100μL of 125I- TGF-β1 antibody solution, which contained approximately 18,5MBq of 125I-liraglutide, was injected into the tail veins of each of three nude mice with Huh-7 HCC. Micro SPET/CT imaging was performed for each mouse using a nano SPET/CT. The average percentage of injected dose per gram of tissue (ID%) was 1,3% and 2,4%. The tumor was strongly positive for TGF-β1. This pilot study provides an experimental basis for further exploration of the feasibility of TGF-β1 receptor as a target in HCC imaging and in other cancers.