70 results match your criteria: "Centre for Drug Development[Affiliation]"

May Measurement Month 2021: an analysis of blood pressure screening results from Hungary.

Eur Heart J Suppl

June 2024

Hungarian Society of Hypertension, Tetenyi str. 12-16, Budapest 1115, Hungary.

Elevated blood pressure (BP) is the most important risk factor for cardiovascular diseases (CVDs), which are still the leading cause of mortality in Hungary. Therefore, screening programmes identifying subjects with hypertension have an important role in CVD prevention. In 2017, the International Society of Hypertension initiated May Measurement Month (MMM) aimed at raising awareness of elevated BP.

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Background: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful.

Patients And Methods: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon.

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  • The study investigates how a novel CHK1 inhibitor, SRA737, affects cancer cell lines with different P53 gene statuses, focusing on non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines.
  • CHK1 is activated in response to DNA damage, allowing damaged cells to pause their cycle; inhibiting CHK1 aims to make these cells more susceptible to treatment by preventing this pause.
  • Results show that cancer cells with mutated P53 were more sensitive to SRA737, exhibiting increased DNA damage and reduced proliferation compared to wild-type cells, highlighting the importance of P53 status in cancer treatment response.
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  • - A Phase I trial tested the safety and tolerability of MOv18 IgE, a new type of chimeric IgE antibody, in cancer patients whose tumors express folate receptor-alpha, with a focus on minimizing allergic reactions.
  • - The study involved dose escalation from 70 μg to 12 mg, using skin prick and basophil activation tests to identify low-risk patients; the main side effect noted was temporary hives, with one case of anaphylaxis linked to pre-existing reactive basophils.
  • - Results indicate that MOv18 IgE therapy is tolerable and shows potential anti-tumor activity, evidenced by a positive response in a patient with ovarian cancer, suggesting that IgE-based
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  • Modern cancer therapies are targeting specific aspects of cancer for better effectiveness and tolerability, but many still face issues with side effects and overall tolerability.
  • The traditional maximum tolerated dose (MTD) model may no longer be suitable, prompting a move towards a more holistic approach for determining optimal dosing in early clinical trials.
  • The FDA's Project Optimus and international collaborations through Project Orbis are working on optimizing dose selection and improving patient access to new cancer therapies, emphasizing the need for reform in how early phase oncology trials are conducted.
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  • The study investigates AZD3965, a novel inhibitor of monocarboxylate transporter 1 (MCT1), intended to evaluate its safety and effectiveness in treating advanced cancers in patients with no standard treatment options.
  • During the trial's dose escalation, 40 patients were treated, with common side effects including mild fatigue and changes in retinal function; dose-limiting toxicities mainly occurred at higher doses.
  • The findings suggest that AZD3965 is generally well-tolerated at effective doses, establishing an optimal dosage of 10 mg twice daily for further testing in cancers with high MCT1 expression.
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  • HMBD-001 is a humanized IgG1 monoclonal antibody that targets HER3, a receptor commonly found on certain cancer cells.
  • A selective bioanalytical method using a bridging ELISA was created to accurately measure HMBD-001 levels in human serum without interference from HER3.
  • This assay is sensitive (with a lower limit of 250 ng/ml), has a wide range (250-7000 ng/ml), and is now being used in clinical trials to quantify HMBD-001.
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Male infertility and somatic health - insights into lipid damage as a mechanistic link.

Nat Rev Urol

December 2022

Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia.

Over the past decade, mounting evidence has shown an alarming association between male subfertility and poor somatic health, with substantial evidence supporting the increased incidence of oncological disease, cardiovascular disease, metabolic disorders and autoimmune diseases in men who have previously received a subfertility diagnosis. This paradigm is concerning, but might also provide a novel window for a crucial health reform in which the infertile phenotype could serve as an indication of potential pathological conditions. One of the major limiting factors in this association is the poor understanding of the molecular features that link infertility with comorbidities across the life course.

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Tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesised via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT), a promising radiation type for cancer, as this therapy does little damage to biological tissue. An unexpected decarbonylation/decarboxylation to five 2,3,4,5-tetrachlorobenzamides was observed and confirmed by X-ray crystallography studies, thus, giving access to a family of borylated 2,3,4,5-tetrachlorobenzamides. Biological evaluation showed the benzamide drugs to possess good to weak potencies (74.

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Simultaneous targeting of glycolysis and oxidative phosphorylation as a therapeutic strategy to treat diffuse large B-cell lymphoma.

Br J Cancer

September 2022

Cancer Research Horizons Therapeutic Innovation, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Background: We evaluated the therapeutic potential of combining the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 with the mitochondrial respiratory Complex I inhibitor IACS-010759, for the treatment of diffuse large B-cell lymphoma (DLBCL), a potential clinically actionable strategy to target tumour metabolism.

Methods: AZD3965 and IACS-010759 sensitivity were determined in DLBCL cell lines and tumour xenograft models. Lactate concentrations, oxygen consumption rate and metabolomics were examined as mechanistic endpoints.

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  • The study evaluates the effects of PI3Kδ inhibitor AMG319 in patients with head and neck cancer, showing that it reduces regulatory T cells while boosting the activity of tumor-fighting T cells.
  • However, the treatment resulted in significant immune-related adverse events (irAEs) in nearly half of the patients, raising concerns about systemic effects on T cells.
  • Mouse models suggest that altering dosing regimens could reduce these toxic effects while still effectively shrinking tumors, prompting further exploration of treatment strategies.
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Quantitative proteomic dataset of mouse caput epididymal epithelial cells exposed to acrylamide .

Data Brief

June 2022

Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.

This article reports the proteomic legacy of exposure to the xenobiotic, acrylamide, on the epithelial cell population of the proximal segments of the mouse epididymis. Specifically, adult male mice were administered acrylamide (25 mg/kg bw/day) or vehicle control for five consecutive days before dissection of the epididymis. Epididymal epithelial cells were isolated from the proximal (caput) epididymal segment and subjected to quantitative proteomic analysis using multiplexed tandem mass tag (TMT) labeling coupled to mass spectrometry.

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Article Synopsis
  • PFAS are chemicals found in many products and can harm the environment and male health because they stay in the body for a long time.
  • Studies show that PFAS exposure may lead to issues like infertility and other health problems in men, but more research is needed to understand the exact effects.
  • The review also looks at the ways PFAS can damage male reproductive health and suggests new methods to reduce the harmful effects of these chemicals.
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A more comprehensive understanding of how cells respond to drug intervention, the likely immediate signalling responses and how resistance may develop within different microenvironments will help inform treatment regimes. The nonreceptor tyrosine kinase SRC regulates many cellular signalling processes, and pharmacological inhibition has long been a target of cancer drug discovery projects. Here, we describe the in vitro and in vivo characterisation of the small-molecule SRC inhibitor AZD0424.

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Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation†.

Biol Reprod

March 2022

Priority Research Centre for Reproductive Science, Schools of Biomedical Science & Pharmacy and Environmental & Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.

The dormant population of ovarian primordial follicles is determined at birth and serves as the reservoir for future female fertility. Yet our understanding of the molecular, biochemical, and cellular processes underpinning primordial follicle activation remains limited. The survival of primordial follicles relies on the correct complement and morphology of granulosa cells, which provide signaling factors essential for oocyte and follicular survival.

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Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development.

Cell Rep

October 2021

Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address:

Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile, modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the reproductive toxicant acrylamide.

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Objectives: The primary objective is to evaluate the efficacy of camostat to prevent respiratory deterioration in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Secondary objectives include assessment of the ability of camostat to reduce the requirement for Coronavirus disease 2019 (COVID-19) related hospital admission and to reduce the requirement for supplementary oxygen and ventilation as treatment for SARS-CoV-2 infection, to evaluate overall mortality related to COVID-19 and to evaluate the efficacy of camostat by effect on clinical improvement. Research objectives include to assess change in COVID-19 symptom severity, to evaluate the ability of camostat to reduce viral load throughout duration of illness as well as translational research on host and viral genomics, serum antibody production, COVID-19 diagnostics, and validation of laboratory testing methods and biomarkers.

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The Impact of Aging on Macroautophagy in the Pre-ovulatory Mouse Oocyte.

Front Cell Dev Biol

June 2021

Priority Research Centre for Reproductive Science, Schools of Biomedical Science & Pharmacy and Environmental & Life Sciences, University of Newcastle, Callaghan, NSW, Australia.

Accompanying the precipitous age-related decline in human female fertility is an increase in the proportion of poor-quality oocytes within the ovary. The macroautophagy pathway, an essential protein degradation mechanism responsible for maintaining cell health, has not yet been thoroughly investigated in this phenomenon. The aim of this study was to characterize the macroautophagy pathway in an established mouse model of oocyte aging using in-depth image analysis-based methods and to determine mechanisms that account for the observed changes.

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May Measurement Month 2019: an analysis of blood pressure screening results from Hungary.

Eur Heart J Suppl

May 2021

Hungarian Society of Hypertension, Tetenyi str. 12-16, Budapest 1115, Hungary.

Cardiovascular diseases are not only the leading causes of mortality in Hungary but also the mortality rate is twice as high as the European Union average, so screening programmes identifying subjects with elevated blood pressure (BP) are of utmost importance. May Measurement Month (MMM) is an annual global initiative that began in 2017 aimed at raising awareness of high BP. Hungary joined the 3rd campaign of MMM in 2019 and an overview of the results are presented in this paper.

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Two alternative methods for the retrieval of somatic cell populations from the mouse ovary.

Mol Hum Reprod

May 2021

Priority Research Centre for Reproductive Science, Schools of Biomedical Science & Pharmacy and Environmental & Life Sciences, University of Newcastle, Callaghan, NSW, Australia.

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis, therefore, necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging.

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Spermatozoa transition to functional maturity as they are conveyed through the epididymis, a highly specialized region of the male excurrent duct system. Owing to their transcriptionally and translationally inert state, this transformation into fertilization competent cells is driven by complex mechanisms of intercellular communication with the secretory epithelium that delineates the epididymal tubule. Chief among these mechanisms are the release of extracellular vesicles (EV), which have been implicated in the exchange of varied macromolecular cargo with spermatozoa.

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A scoping review of the information provided by fertility smartphone applications.

Hum Fertil (Camb)

October 2022

Priority Research Centre for Reproductive Science, Schools of Biomedical Science & Pharmacy and Environmental & Life Sciences, University of Newcastle, Callaghan, Australia.

The growth of smartphone application use across areas of female reproductive health has led to increased interest into their functions and benefits. This scoping review aims to determine the nature and extent of the peer-reviewed literature presented on fertility-based apps, to identify the reliability of the information within the apps, and to determine the ability of this information to educate users. A systematic search of six databases was conducted in April 2020, returning a total of 21,158 records.

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Information on the morphology and histology of the male reproductive system of the Crocodylia species is necessary to determine the role of these tissues in the production of functional spermatozoa. Accordingly, in this study we examined the gross morphology and microanatomy of the testis and the male excurrent duct system through which spermatozoa pass before ejaculation. The data demonstrate that the reproductive system in male saltwater crocodiles comprises paired testes, which convey spermatozoa distally via the rete testis into an excurrent duct system comprising ductuli efferentes, ductuli epididymides, ductus epididymidis and ductus deferens.

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