Deprivation Treatments Research Articles

A hypothetical method for controlling highly glycolytic cancers and metastases

Most proliferating cancer cells and cancer-associated tumor stroma have an upregulated glucose energy demand in relation to normal cells. Cancer cells are further less metabolically flexible than normal cells. They can therefore not survive metabolic stress as well as normal cells can. Metabolic deprivation thus provides a potential therapeutic window.Unfortunately, current glucose blockers have toxicity problems. An alternative way to reduce a cancer patient’s blood glucose (BG), for a short-term period to very low levels, without the concomitant toxicity, is hypothesized in this paper.In vitro tests have shown that short-term BG deprivation to 2 mmol/L for 180 min is an effective cancer treatment. This level of hypoglycaemia can be maintained in vivo with a combination of very low-dose insulin and the suppression of the glucose counter-regulation system. Such suppression can be safely achieved by the infusion of somatostatin and a combination of both α and β-blockers.The proposed short-term in vivo method, was shown to be non-toxic and safe for non-cancer patients. The next step is to test the effect of the proposed method on cancer patients. It is also suggested to incorporate well-known, long-term BG deprivation treatments to achieve maximum effect.

Androgen deprivation and immunotherapy for the treatment of prostate cancer.

Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary treatment for recurrent prostate cancer is androgen deprivation, and this therapy is typically continued lifelong for patients with metastatic prostate cancer. Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where immune-based treatments for cancer are being increasingly explored. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect the use of approved immunotherapies, or those that are being developed for the treatment of prostate cancer. In this review, we provide a brief overview of the different types of androgen deprivation treatments used in the management of prostate cancer, discuss their effects on prostate tumors and the immune system and how they are being explored in combination with immunotherapy. Finally, we address some of the critical questions in the field that must be answered to identify the best approaches to combine androgen deprivation with immunotherapy for the treatment of prostate cancer.

Interaction with a bovine cortical bone in the Finnraccoon (Nyctereutes procyonoides ussuriensis)

Finnraccoons (Nyctereutes procyonoides ussuriensis) are farmed for their fur. The welfare of Finnraccoons in the current housing conditions has not been thorough documented. The aim of the present study is to measure the juvenile Finnraccoons’ interaction with a commonly used activity object, namely bovine cortical bone. The subjects of the study were 16 sister pairs of juvenile Finnraccoons (born in May) housed in commercial housing conditions. The behaviour of the Finnraccoons was recorded and the interaction with the bone was registered from video recordings in two time points; at the time when the deciduous teeth are being replaced with the permanent ones (September), and later in autumn (November). In order to evaluate how much the Finnraccoons value the access to the bone, the effect of two-weeks deprivation of the bone was recorded in half of the animals (8 pairs of Finnraccoons) in both time points. The duration and frequency of various types of interactions with the bone were continuously recorded for 15 mins from each hour of the day and statistically analysed by using Linear Mixed Model (SAS). The Finnraccoon pairs interacted with the bone a mean from 2 to 8% of time. The time (month) did not affect the interaction with the bone, but both the percentage of time and frequency of the interaction with the bone increased after the deprivation treatments (after returning the access to the bone) in the Finnraccoons deprived of the bone. Oral activities were the most frequent activities with the bone, but oral activity combined with the use of paws was the longest duration interaction with the bone. The interaction with the bone was not randomly distributed throughout the day, but was most intense in early morning. The present results show that the Finnraccoons interact regularly with a bovine cortical bone, and they do not lost interest towards the bone with time. The bone induces various behaviours and provides a long lasting, biologically and behaviourally relevant activity object in the Finnraccoon. Bone is a significant environmental enrichment in the Finnraccoon.

If and when: intrinsic differences and environmental stressors influence migration in brown trout (Salmo trutta).

Partial migration is a common phenomenon, yet the causes of individual differences in migratory propensity are not well understood. We examined factors that potentially influence timing of migration and migratory propensity in a wild population of juvenile brown trout (Salmo trutta) by combining experimental manipulations with passive integrated transponder telemetry. Individuals were subjected to one of six manipulations: three designed to mimic natural stressors (temperature increase, food deprivation, and chase by a simulated predator), an injection of exogenous cortisol designed to mimic an extreme physiological challenge, a sham injection, and a control group. By measuring length and mass of 923 individuals prior to manipulation and by monitoring tagged individuals as they left the stream months later, we assessed whether pre-existing differences influenced migratory tendency and timing of migration, and whether our manipulations affected growth, condition, and timing of migration. We found that pre-existing differences predicted migration, with smaller individuals and individuals in poor condition having a higher propensity to migrate. Exogenous cortisol manipulation had the largest negative effect on growth and condition, and resulted in an earlier migration date. Additionally, low-growth individuals within the temperature and food deprivation treatments migrated earlier. By demonstrating that both pre-existing differences in organism state and additional stressors can affect whether and when individuals migrate, we highlight the importance of understanding individual differences in partial migration. These effects may carry over to influence migration success and affect the evolutionary dynamics of sub-populations experiencing different levels of stress, which is particularly relevant in a changing world.

Diesel exhaust particles (DEP) pre-exposure contributes to the anti-oxidant response impairment in hCMEC/D3 during post-oxygen and glucose deprivation damage

Recently, air pollution has been identified as a significant modifiable risk factor to the increasing stroke burden. Diesel exhaust particles, characterized by high polycyclic aromatic hydrocarbons content, constitute an important component of outdoor air pollution and is known to cause oxidative stress, and could therefore contribute to and exacerbate the effects of ROS in post-ischemic injury.hCMEC/D3 cells have been submitted to 48h treatment with diesel exhaust particles (25μg/ml and 50μg/ml, DEP50) or alternatively to 3h of oxygen and glucose deprivation, followed by 1h of oxygen and glucose restoration. The combined treatment consisted in 48h of diesel exhaust particles (25μg/ml and 50μg/ml, DEP50) followed by 3h of oxygen and glucose deprivation and 1h of restoration. A panel of markers related to oxidative stress and inflammatory responses, such as transcription factors (Nrf2 and HIF-1α), anti-oxidant proteins (HO-1, SOD-1, Hsp70) and proteins potentially inducing further oxidative-stress or inflammation (Cyp1b1, iNOS, COX-2, TNF-α, IL-1α, IL-1β, IL-8, VEGF), have been examined.Data obtained showed that diesel exhaust particles and oxygen and glucose deprivation treatments alone elicited the antioxidants response, each by means of a different transcription factor, while the combined treatment led to a dysregulation of the antioxidant response during ischemic injury reperfusion.

A Bioengineering Approach to Myopia Control Tested in a Guinea Pig Model.

PurposeTo investigate the biocompatibility of an injectable hydrogel and its ability to control myopia progression in guinea pigs.MethodsThe study used a hydrogel synthesized from acrylated hyaluronic acid with a conjugated cell-binding peptide and enzymatically degradable crosslinker. Seven-day-old guinea pigs were first form deprived (FD) with diffusers for 1 week. One group was kept as an FD-only control; two groups received a sub-Tenon's capsule injection of either hydrogel or buffer (sham surgery) at the posterior pole of the eye. Form deprivation treatments were then continued for 3 additional weeks. Treatment effects were evaluated in terms of ocular axial length and refractive error. Safety was evaluated via intraocular pressure (IOP), visual acuity, flash electroretinograms (ERG), and histology.ResultsBoth hydrogel and sham surgery groups showed significantly reduced axial elongation and myopia progression compared to the FD-only group. For axial lengths, net changes in interocular difference (treated minus control) were 0.04 ± 0.06, 0.02 ± 0.09, and 0.24 ± 0.08 mm for hydrogel, sham, and FD-only groups, respectively (P = 0.0006). Intraocular pressures, visual acuities, and ERGs of treated eyes were not significantly different from contralateral controls. Extensive cell migration into the implants was evident. Both surgery groups showed noticeable Tenon's capsule thickening.ConclusionsSub-Tenon's capsule injections of both hydrogel and buffer inhibited myopia progression, with no adverse effects on ocular health. The latter unexpected effect warrants further investigation as a potential novel myopia control therapy. That the hydrogel implant supported significant cell infiltration offers further proof of its biocompatibility, with potential application as a tool for drug and cell delivery.

Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms.

Background: Prostate cancer (PCa) is a critical health burden, impacting the morbidity and mortality of millions of men around the world. Most of the patients with PCa have their disease at first sensitive to androgen deprivation treatments, but later they develop resistance to therapy and eventually die of metastatic castration-resistant prostate cancer (CRPC). Although the newly developed anti-androgen therapies are effectively alleviating symptoms and prolonging lives of patients, there are still no curable treatments for CRPC. Recently, statistical studies have shown that the chronic use of aspirin might be significantly associated with better outcomes in PCa patients. Through this review, we aim to identify the different proposed molecular mechanisms relating aspirin to the pathobiology of PCa neoplasms, with a major focus on basic research done in this context.Methods: Articles were retrieved via online database searching of PubMed and MEDLINE between 1946 and September 2016. Keywords and combinations related to PCa and aspirin were used to perform the search. s of the articles were studied by two independent reviewers and then data extraction was performed on the relevant articles that met our review objectives.Results: Aspirin, a non-steroidal anti-inflammatory drug (NSAID), affects the proliferation, apoptosis, resistance and metastasis of PCa cell lines, through both COX-dependent and COX-independent mechanisms. It also lowers levels of the PCa diagnostic marker prostate specific antigen (PSA), suggesting that clinicians need to at least be aware if their patients are using Aspirin chronically.Conclusion: This review strongly warrants further consideration of the signaling cascades activated by aspirin, which may lead to new knowledge that might be applied to improve diagnosis, prognosis and treatment of PCa.

Physiological basis of metabolic trade-offs between growth and performance among different strains of rainbow trout

Adaptive trade-offs define the trait combinations that differentiate taxa and allow coexistence along environmental gradients. To understand the physiological trade-offs associated with growth, we examined relationships among metabolic rate, digestive capacity, tissue energy content, and growth in juveniles of three strains of rainbow trout (Oncorhynchus mykiss) that differ in growth. Fish were reared under satiation, 1% of body mass per day, and complete food deprivation treatments to assess differences in performance and adaptive trade-offs along a gradient of resource availability. The fast-growing hatchery strain had higher standard metabolic rate (SMR), lower aerobic scope, and potentially lower maximum metabolic rates, suggesting that high growth trades off against a reduced capacity to do metabolic work. Trout with high growth rates also generally had larger gastrointestinal tracts, maximum food consumption, and growth efficiency. Results demonstrate (i) higher SMR of fast growers appears to be related to a greater investment in high-maintenance digestive tissue that supports rapid growth; (ii) growth appears to trade off against active metabolism; and (iii) selection on growth involves a suite of integrated physiological and anatomical traits that are affected by both genotype and environment (ration).

Abstract 4764: Development of a multigenic bioluminescence imaging system to detect prostate cancer cells and assess their response to therapy

Abstract BACKGROUND Currently, liquid biposies for imaging single cancer cell to provide personalised medicine is gaining importance. In the last years, molecular imaging techniques using transcriptional amplification systems have been developed but a system enabling both PCa cell detection and treatment response assessment is lacking. PCA3 RNA is a unique PCa biomarker that has been widely studied for PCa screening and detection while the PSA gene is another biomarker of high clinical significance as it gives an account of response to androgen deprivation treatments (ADT). In this study, we have developed and studied an imaging system based on the combined transcriptional activities of the PCA3 and PSA gene promoters for single PCa cell detection and ADT response assessment from patients body fluids. METHODS Adenoviruses (Ad) were constructed utilizing the ability of site-specific recombination of the Cre-Lox system. The PCA3 and PSA promoters were integrated into a single Ad backbone with one promoter driving the expression of CRE recombinase and the other driving the Two Step Transcriptional Amplification system and the Firefly luciferase gene (fl) to generate a new system that we named the Multigenic Integrative Transcriptional Amplification System (MP-ITSTA). PCa cells specificity and ADT response was tested by transient infection. To detect cells in body fluid, 22Rv1-GFP cells were spiked in urine or blood of healthy control, infected with MP-ITSTA after purification and single cell imaging was done using the LV200 bioluminescence microscope. RESULTS We show that the PCA3-TSTA driven fl expression is specific to PCa cells (22Rv1, LAPC4, PC3, DU145) giving 8.5-108.4 fold higher expression when compared to SW780 bladder cancer cells. Contrary to PCA3-TSTA, the PSA-TSTA activity is regulated by androgen treatment but is not prostate cancer-specific as it is active in AR responsive breast cancer cells (CAMA-1 and ZR-75). We show that MP-ITSTA reporter expression is dependent on the combined activation of two promoters (PCA3 and PSA promoter) in a DHT dependent manner. MP-ITSTA could therefore also give an account of responsiveness to bicalutamide or enzalutamide treatments PCa cells. The signal obtained by MP-ITSTA system is 2.3 and 1.6 times higher than PCA3-TSTA in 22Rv1 and LAPC4, respectively proving that MP-ITSTA has the ability to enhance the reporter gene expression from a weak but PCa specific PCA3 promoter. Finally, MP-ITSTA could specifically target spiked 22Rv1-mcherry cells isolated from urine while no signal was found in non-spiked samples. CONCLUSIONS MP-ITSTA therefore represents a prostate cancer specific and non-invasive tool to target with high accuracy PCa cells and to detect their response to ADT cell per cell from body fluids. Citation Format: Pallavi Jain, Bertrand Neveu, Yves Fradet, Frédéric Pouliot. Development of a multigenic bioluminescence imaging system to detect prostate cancer cells and assess their response to therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4764.

Pengaruh lama ketiadaan inang terhadap kapasitas reproduksi parasitoid Snellenius manilae Ashmead (Hymenoptera: Braconidae)

The objective of this research was to study the influence of host deprivation on the oviposition and physiological condition of Snellenius manilae Ashmead. The research was conducted at Laboratory of Bioecology of Parasitoid and Predator, Department of Plant Protection, Faculty of Agriculture, IPB. Ten parasitoids of the same age and cohort were used in this experiment. Deprivation of hosts were done for 1, 2, 3, 4, 5, 6 and 7 days at the beginning and toward the end of their life. All hosts were replaced every 24 hours. Result indicated that host deprivation affects the reproductive capacity of Snellenius manilae. Even though parasitoids were able to lay eggs even when they were deprived of hosts for seven consecutive days, the overall results of host deprivation experiment showed that the length and timing of deprivation period can affect reproductive capacity. Deprivation of hosts tends to increase the parasitism rate and the numbers of eggs laid upon their first encounter of hosts after the treatment. The difference is more pronounced on treatements that allowed parasitism to occur before the deprivation treatment. However, the overall results suggests that deprivation overall decrease the reproductive capacity of the parasitoid. The longevity of deprived individuals was also lengthened. Parasitoids that were given host before deprivation treatments tend to produced more eggs than those were not. These results showed that deprivation of hosts in the field may affect the effectiveness of parasitoids and the success of biological control.

Androgen Deprivation Therapy for Patients With Localized Prostate Cancer Treated With High-Dose-Rate Brachytherapy Boost

Purpose/Objective(s): To evaluate the effectiveness and tolerability of neo-adjuvant/concomitant/adjuvant androgen deprivation therapy (ADT) for patients treated with external beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost for localized prostate cancer. Our hypothesis was that ADT does not add to the efficacy of the combined treatments. Materials/Methods: This is a retrospective cohort study conducted in a Canadian academic oncology center. All patients treated at our institution with EBRT followed by 192Ir HDR brachytherapy boost for localized prostate cancer between 1998 and 2010 were included in the study. Data on patients’ age, disease severity at diagnosis, androgen deprivation and radiation treatments received and follow up were collected from the patients’ medical records. The primary outcome was biochemical recurrence-free survival (bRFS). The secondary outcomes were genitourinary and gastrointestinal toxicities. Biochemical recurrence was determined according to the Phoenix consensus definition. Survival curves were calculated with the Kaplan-Meier method and compared between the two groups (ADT versus no ADT) with a logrank test. Multivariate Cox regressions were also performed to take into account potentially confounding variables such as age, PSA at diagnosis, TNM stage, Gleason score, biologically effective dose and type and duration of ADT. Genitourinary toxicities were assessed with the IPSS tool and compared between groups with student t-tests. Gastrointestinal toxicities (diarrhea, tenesmus, rectal bleeding) were evaluated with a three points scale (0: never, 1: occasionally, 2: frequently) and compared between groups with chi-squared tests. Results: Six hundred thirty-eight patients were treated with EBRT and HDR brachytherapy boost. Of those, 186 received ADT and 452 received no ADT. Doses ranged from 40 to 45 Gy in 20 to 25 fractions for EBRT and from 15 to 20 Gy in 1 to 3 fractions for the boost. According to NCCN risk classification, 7.8% of patients were low risk, 81.8% were intermediate risk and 10.3% were high risk. Median follow-up was 53 months. There was no significant difference in bRFS between groups in univariate (HR: 0.83; 95% CI: 0.51-1.38; p Z 0.48) and in multivariate analyses (HR: 0.72; 95% CI: 0.42-1.26; p Z 0.20). bRFS at 7 years was 86% in the ADT group and 92% in the no-ADT group (p Z 0.48). We observed no significant difference between groups in mean global IPSS scores at 3 months (ADT: 11.17 vs. no-ADT: 10.4; pZ 0.49) and at 12 months (ADT: 9.64 vs. no-ADT: 10.75; p Z 0.28) post-radiation therapy as well as in gastrointestinal toxicities at 3 and 12 months. Conclusions: For patients with a localized prostate cancer treated with EBRT combined with HDR brachytherapy boost, the addition of ADT does not seem to yield to a significant increased in bRFS neither to be associated with increased genitourinary and gastrointestinal toxicities. Author Disclosure: S. Magnan: None. P. Despres: None. W. Foster: None. A. Martin: None. E. Vigneault: None.

Postimplant Multiparametric MRI-Based Dosimetry After Permanent Iodine Seed Prostate Brachytherapy: The Impact of the Dose Delivered to the Dominant Intraprostatic Lesion on Prostate-Specific Antigen Bounce

Purpose/Objective(s): To evaluate the effectiveness and tolerability of neo-adjuvant/concomitant/adjuvant androgen deprivation therapy (ADT) for patients treated with external beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost for localized prostate cancer. Our hypothesis was that ADT does not add to the efficacy of the combined treatments. Materials/Methods: This is a retrospective cohort study conducted in a Canadian academic oncology center. All patients treated at our institution with EBRT followed by 192Ir HDR brachytherapy boost for localized prostate cancer between 1998 and 2010 were included in the study. Data on patients’ age, disease severity at diagnosis, androgen deprivation and radiation treatments received and follow up were collected from the patients’ medical records. The primary outcome was biochemical recurrence-free survival (bRFS). The secondary outcomes were genitourinary and gastrointestinal toxicities. Biochemical recurrence was determined according to the Phoenix consensus definition. Survival curves were calculated with the Kaplan-Meier method and compared between the two groups (ADT versus no ADT) with a logrank test. Multivariate Cox regressions were also performed to take into account potentially confounding variables such as age, PSA at diagnosis, TNM stage, Gleason score, biologically effective dose and type and duration of ADT. Genitourinary toxicities were assessed with the IPSS tool and compared between groups with student t-tests. Gastrointestinal toxicities (diarrhea, tenesmus, rectal bleeding) were evaluated with a three points scale (0: never, 1: occasionally, 2: frequently) and compared between groups with chi-squared tests. Results: Six hundred thirty-eight patients were treated with EBRT and HDR brachytherapy boost. Of those, 186 received ADT and 452 received no ADT. Doses ranged from 40 to 45 Gy in 20 to 25 fractions for EBRT and from 15 to 20 Gy in 1 to 3 fractions for the boost. According to NCCN risk classification, 7.8% of patients were low risk, 81.8% were intermediate risk and 10.3% were high risk. Median follow-up was 53 months. There was no significant difference in bRFS between groups in univariate (HR: 0.83; 95% CI: 0.51-1.38; p Z 0.48) and in multivariate analyses (HR: 0.72; 95% CI: 0.42-1.26; p Z 0.20). bRFS at 7 years was 86% in the ADT group and 92% in the no-ADT group (p Z 0.48). We observed no significant difference between groups in mean global IPSS scores at 3 months (ADT: 11.17 vs. no-ADT: 10.4; pZ 0.49) and at 12 months (ADT: 9.64 vs. no-ADT: 10.75; p Z 0.28) post-radiation therapy as well as in gastrointestinal toxicities at 3 and 12 months. Conclusions: For patients with a localized prostate cancer treated with EBRT combined with HDR brachytherapy boost, the addition of ADT does not seem to yield to a significant increased in bRFS neither to be associated with increased genitourinary and gastrointestinal toxicities. Author Disclosure: S. Magnan: None. P. Despres: None. W. Foster: None. A. Martin: None. E. Vigneault: None.

Mapping QTLs for potassium-deficiency tolerance at the seedling stage in wheat (Triticum aestivum L.)

Potassium (K) deficiency is a major factor limiting crop development and yield. In this study, 20 traits were investigated at the seedling stage using a doubled-haploid population subjected to normal K and K deprivation treatments. Evaluation of phenotypes expressed under the two K supply conditions revealed that K deprivation was able to decrease values of ten measured traits, whereas values of the other ten traits increased. A total of 65 QTLs were detected across all 21 chromosomes, except for chromosomes 2B, 5A, and 7B. Individual QTLs in the two K supply treatments explained between 5.35 and 39.64 % of the phenotypic variation. Nine QTL clusters (C1–C9) involving 34 QTLs under the different K supply treatments were mapped to chromosomes 1A, 1B, 1D, 3B, 4A, 5B, 6A, and 7B. Our results are helpful for understanding the genetic basis of K deficiency in wheat, and provide useful information for genetic improvement of K deficiency in wheat by marker-assisted selection.

A national analysis of the outcome of major head and neck cancer surgery: implications for surgeon-level data publication.

To undertake a national outcomes analysis following major head and neck cancer surgery in order to identify risk factors for complications and in-hospital mortality, as well as areas whose closer examination and formal benchmarking in the context of local and national quality assurance audits may lead to improved results for this condition. An analysis using Hospital Episode Statistics data. All units undertaking major head and neck cancer surgery in England. Cancer sites, co-morbidities, social deprivation, surgical and non-surgical treatments, complications, and in-hospital mortality were recorded. Regression analysis was used for casemix adjustment and for identifying independent predictors of complications and mortality. Funnel plots were used for data visualisation. We identified 10,589 major head and neck cancer operations performed in England between 2006 and 2011. There were 7312 males, and mean age at surgery was 63 ± 13 years. Oral cavity (42%) and the larynx (28%) were the commonest cancer sites. At least one complication occurred in 33.1% of patients, and there were 322 (3.05%) in-hospital deaths. Variables associated with in-hospital mortality were trust volume, age, co-morbidities, performing emergency major surgery and performing a tracheostomy or reconstructive surgery. Occurrence of major medical complications including pulmonary infections (7%), major acute cardiovascular events (4.7%) and acute renal failure (0.6%) also increased mortality risk. The analysis identified units that were outside of crude and risk-adjusted 99.8% limits of confidence for complications and mortality. Mortality following head and neck cancer surgery shows significant national variation and is associated with fixed risk factors like age and co-morbidities, but also with modifiable risk factors like performing major surgery during an emergency admission, tracheostomy, reconstructive surgery and medical complications. We propose that the quality of tracheostomy care, reconstructive surgery, emergency major surgery rate, and occurrence and treatment of major medical complications should be closely examined and formally benchmarked as part of loco-regional and national quality improvement audits.

Identification of a truncated form of methionine sulfoxide reductase a expressed in mouse embryonic stem cells

BackgroundMethionine Sulfoxide Reductase A (MsrA), an enzyme in the Msr gene family, is important in the cellular anti-oxidative stress defense mechanism. It acts by reducing the oxidized methionine sulfoxide in proteins back to sulfide and by reducing the cellular level of reactive oxygen species. MsrA, the only enzyme in the Msr gene family that can reduce the S-form epimers of methionine sulfoxide, has been located in different cellular compartments including mitochondria, cytosol and nuclei of various cell lines.MethodsIn the present study, we have isolated a truncated form of the MsrA transcript from cultured mouse embryonic stem cells and performed eGFP fusion protein expression, confocal microscopy and real time RT-PCR studies.ResultsResults show a different expression response of this truncated transcript to oxygen deprivation and reoxygenation treatments in stem cells, compared to the longer full length form. In addition, a different subcellular localization pattern was noted with most of the eGFP fusion protein detected in the cytosol.ConclusionOne possibility for the existence of a truncated form of the MsrA transcripts could be that with a smaller protein size, yet retaining a GCWFG action site, this protein might have easier access to oxidize methionine residues on proteins than the longer form of the MsrA protein, thus having an evolutionary selection advantage. This research opens the door for further study on the role and function of the truncated MsrA embryonic mouse stem cells.

No evidence for general condition‐dependence of structural plumage colour in blue tits: an experiment

Condition-dependence is a central but contentious tenet of evolutionary theories on the maintenance of ornamental traits, and this is particularly true for structural plumage colour. By providing diets of different nutritional quality to moulting male and female blue tits, we experimentally manipulated general condition within the natural range, avoiding deprivation or stressful treatments. We measured reflectance of the structural-coloured UV/blue crown, a sexually selected trait in males, and the white cheek, a nonpigmented structural colour, directly after moult and again during the following spring mating season. We employed a variety of colour indices, based on spectral shape and avian visual models but, despite significant variation in condition and coloration, found no evidence for condition-dependence of UV/blue or white plumage colour during either season. These and previously published results suggest that structural colour might be sensitive to stress, rather than reduced body condition, during moult.

FOOD MAKES YOU A TARGET: DISENTANGLING GENETIC, PHYSIOLOGICAL, AND BEHAVIORAL EFFECTS DETERMINING SUSCEPTIBILITY TO INFECTION

Genetics, physiology, and behavior are all expected to influence the susceptibility of hosts to parasites. Furthermore, interactions between genetic and other factors are suggested to contribute to the maintenance of genetic polymorphism in resistance when the relative susceptibility of host genotypes is context dependent. We used a maternal sibship design and long- and short-term food deprivation treatments to test the role of family-level genetic variation, body condition, physiological state, and foraging behavior on the susceptibility of Lymnaea stagnalis snails to infection by a trematode parasite that uses chemical cues to locate its hosts. In experimental exposures, we found that snails in the long-term food deprivation treatment contracted fewer parasites than snails that were continuously well-fed, possibly because well-fed snails grew larger and attracted more transmission stages. When we kept the long-term feeding rates the same, but manipulated the physiological state and foraging behavior of the snails with short-term food deprivation treatment, we found that snails that were fed before the exposure contracted more parasites than snails that were fed during the exposure. This suggests that direct physiological effects of food processing, but not foraging behavior, predisposed snails to infection. Feeding treatments also affected the family-level variation in snail susceptibility, suggesting that the relative susceptibility of host genotypes was context dependent.

236 GROWTH INHIBITORY EFFECTS OF ENIGMOL, (2-AMINO-3,5-DIHYDROXYOCTADECANE[2S,3S,5S]), ON ANDROGEN-DEPENDENT AND ANDROGEN-INDEPENDENT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2010236 GROWTH INHIBITORY EFFECTS OF ENIGMOL, (2-AMINO-3,5-DIHYDROXYOCTADECANE[2S,3S,5S]), ON ANDROGEN-DEPENDENT AND ANDROGEN-INDEPENDENT PROSTATE CANCER Suzanne Mays, Harsha Ramaraju, Anatoliy Bushnev, Dennis Liotta, Alfred Merrill, and John Petros Suzanne MaysSuzanne Mays Atlanta, GA More articles by this author , Harsha RamarajuHarsha Ramaraju Ann Arbor, MI More articles by this author , Anatoliy BushnevAnatoliy Bushnev Atlanta, GA More articles by this author , Dennis LiottaDennis Liotta Atlanta, GA More articles by this author , Alfred MerrillAlfred Merrill Atlanta, GA More articles by this author , and John PetrosJohn Petros Atlanta, GA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.294AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Enigmol (2-amino-3,5-dihydroxyoctadecane[2S,3S,5S]) is a rationally designed analog of sphingosine (So) that has demonstrated anti-cancer activity. Because Enigmol lacks a hydroxyl group on carbon 1, it is not phosphorylated to a mitogenic 1-phosphate version. Here, two large-scale nude mouse xenograft studies were used to compare Enigmol's efficacy to that of conventional prostate cancer therapies: androgen deprivation for androgen-sensitive prostate cancer and docetaxel for androgen-independent prostate cancer. METHODS Tumors were established in nude mice by subcutaneous injection of LNCaP or PC-3 cells. In the androgen-sensitive (LNCaP) model, mice were treated with either (i) vehicle gavage + sham operation (ii) vehicle gavage + castration, (iii) Enigmol gavage + sham operation, or (iv) Enigmol gavage + castration (n=10-12 per group). In the androgen-independent (PC-3) study, mice received one of four treatment regimens (n=14-15 per group): (i) vehicle gavage + vehicle IP, (ii) vehicle gavage + docetaxel IP (iii) Enigmol gavage + vehicle IP, or (iv) Enigmol gavage + docetaxel IP. Enigmol dosage was 10mg/kg/day in both studies. Tumor sizes were measured over time. RESULTS In both models, Enigmol treatment resulted in significantly slower tumor growth rate than controls (P <0.05). In LNCaP model, tumor growth was inhibited by 59% in animals treated with Enigmol compared to controls and was equally effective as androgen-deprivation alone after 22 days of treatment (P<0.03). In the PC-3 model, tumor growth was inhibited by 59% after 12 days of treatment of Enigmol compared to controls (P=0.00003) and was not statistically different from docetaxel treatment alone. There was support for an additive effect in both models: growth of LNCaP tumors treated with both Enigmol and castration and of PC-3 tumors treated with both Enigmol and docetaxel was inhibited by 70% and 79%, respectively, compared to untreated controls (P<0.0003). No signs of toxicity were observed. CONCLUSIONS Enigmol was as least as effective as androgen deprivation or docetaxel treatments alone; furthermore, combining Enigmol treatment with standard therapies appeared to show additive effects. Enigmol is a promising new oral drug for both androgen sensitive and androgen independent prostate cancer that was effective and non-toxic in these preclinical trials. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e92 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Suzanne Mays Atlanta, GA More articles by this author Harsha Ramaraju Ann Arbor, MI More articles by this author Anatoliy Bushnev Atlanta, GA More articles by this author Dennis Liotta Atlanta, GA More articles by this author Alfred Merrill Atlanta, GA More articles by this author John Petros Atlanta, GA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Sham rehydration contributes to increased Fos staining in the hindbrain after water deprivation in the rat

This experiment tested the role of the oropharyngeal and gastric afferents on Fos staining in the hindbrain of dehydrated and rehydrated rats instrumented with gastric fistulae. Rats were divided into control (CON) or 48 hour water deprivation (WD) treatments. WD rats were further subdivided to include 3 rehydration treatments: 2 hour rehydration with fistulae closed (RHC), fistulae open (RHO), or rehydration with isotonic saline (RHS). An open fistula facilitates sham rehydration while closed fistulae allow for complete ingestion; WD and RHS rats also had open fistulae. WD increased osmolality and only RHC treatment reduced osmolality (CON: 296±2 WD: 307±2 RHC: 278±2 RHO: 305±1 RHS: 308±3). Hindbrains were processed for fos and the nucleus of the solitary tract (NTS) for each rat was examined. Water deprivation modestly increased Fos in the NTS (CON: 7±2; WD: 15±3). Rehydration significantly increased Fos staining in both RHO (37±6) and RHC (35±6) rats compared to CON and WD rats. In RHS rats, Fos staining was only slightly elevated compared to WD rats (23±4) and significantly less than RHC and RHO rats. Fos staining in the NTS associated with rehydration appears to be mediated by visceral afferents activated during sham rehydration and possibly independent of the solute concentration of the solution ingested. Supported by NIH R01 HL62579.

Neuroprotective effects of 5-S-GAD against oxidative stress-induced apoptosis in RGC-5 cells

N-β-Alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from the flesh fly, has been described as having multipotential biological activities toward various tissues. In a previous paper, we reported a novel neuroprotective action of 5-S-GAD on rat retinal ganglion cell apoptosis induced by optic nerve injury and intraocular N-methyl- d-aspartate treatment in vivo. In the present study, we further investigated the protective mechanism of this small peptide against other types of apoptosis in cultured cells of the established rat retinal ganglion cell line RGC-5. Hydrogen peroxide and serum deprivation treatments induced intracellular reactive oxygen species levels and lipid peroxidation, revealed by 4-hydroxy-2-nonenal production, in RGC-5 cells within 9–12 h. The treatments also induced cell death accompanied by nuclear condensation, DNA laddering and increases in apoptotic Bax and caspase-3 proteins in RGC-5 cells within 12–24 h. 5-S-GAD at 25–50 μM clearly suppressed the cell death and apoptotic features induced by these treatments. 5-S-GAD restored the nuclear condensation, DNA laddering and increases in apoptotic proteins. Furthermore, 5-S-GAD directly activated anti-apoptotic phospho-Akt and Bcl-2 proteins in RGC-5 cells. 5-S-GAD also quenched the reactive oxygen species production and inhibited the lipid peroxidation induced by oxidative stress. Therefore, 5-S-GAD may complementarily protect RGC-5 cells against apoptosis through dual actions as a radical scavenger and an inducer of anti-apoptotic phospho-Akt and Bcl-2. Taken together, 5-S-GAD is a high-potential tool for rescuing the retinal ganglion cell apoptosis induced by a variety of glaucomatous conditions.