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CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo.

BackgroundChemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood.ResultsWe found that three mainstream chemotherapeutic agents--carmustine (BCNU), cisplatin, and cytosine arabinoside (cytarabine), representing two DNA cross-linking agents and an antimetabolite, respectively--applied at clinically relevant exposure levels to cultured cells are more toxic for the p

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… Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats. J Neurooncol. 1995;24:229–240. doi: 10.1007/BF01052839. Jung KH, Chu K, Lee ST, Kim SJ, Sinn DI, Kim SU, Kim M, Roh JK. … Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: hemodynamic changes studied by double-tracer autoradiography. Neurosurgery. 1991;29:19–25. doi: 10.1097/00006123-199107000-00004. Kerbel RS, Kamen BA. …

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias.

Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95%

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… The immunoprecipitates were washed with 0.5 M NaCl-NET/IGEPAL CA-630 and analyzed by SDS-PAGE and autoradiography. The specificity of the autoantibodies was confirmed using human reference sera [ 25 ]. …

Inhibition of Heat Shock-Induced H3K9ac Reduction Sensitizes Cancer Cells to Hyperthermia.

Heat stress, clinically known as hyperthermia, is a promising adjunctive modality in cancer treatment. However, the efficacy of hyperthermia as a monotherapy is limited and the underlying mechanism remains poorly understood. Targeting histone modifications is an emerging strategy for cancer therapy, but little is known regarding the role of heat stress in altering these modifications. Here, we report that heat shock inhibits H3K9 acetylation (H3K9ac) via histone deacetylase 6 (HDAC6) regulation. Heat shock inhibits the interaction between HDAC6 and heat shock protein 90 (HSP90), enhances nucle

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… Finally, immunoreactive products were visualized using enhanced chemiluminescence reagents and autoradiography. CCK8 assay Cell viability was assessed by Cell Counting Kit-8 (Yeasen Biotechnology, Shanghai, China) according to the manufacturer's protocol. …

cAMP response element-binding protein activation in ligation preconditioning in neonatal brain.

Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal HI encephalopathy that allows for neuroprotection is to investigate the states of tolerance to HI. Twenty-four-hour carotid-artery ligation preconditioning established by delaying the onset of hypoxia for 24 hours after permanent unilateral carotid ligation rats markedly diminished the cerebral injury, however, the signaling mechanisms of this carotid-artery ligation preconditioning in neonatal rats remain unknown. Ligation of the carot

Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease.

Recent evidence suggest that the blockade of cannabinoid CB1 receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease (PD). In the present study, we have explored the motor effects of rimonabant, a selective antagonist of CB1 receptors, in a rat model of PD generated by an intracerebroventricular injection of 6-hydroxydopamine. Compared with rats subjected to unilateral injection of this toxin in the medial forebrain bundle, this model allows nigral dopaminergic neurons be symmetrically affected. Dose-response studies with 6-hydroxydopamine revealed that the a

Уровень амилиновой сыворотки у пациентов с множественным склерозом: перекрестное исследование сечения.

Амилин — это поджелудочный нейроэндокринный пестид, который связывает периферическое метаболическое регулирование с центральными гомеостатическими и нейродегенеративными путями. Однако его значение для подстрекательских и демиелионирующих процессов, лежащих в основе множественного склероза (МС), остается неясным. До настоящего времени роль амилина в РС не была расследована. В ходе этого исследования были исследованы уровни сыворотки амилина у пациентов с MS и их связь с состоянием болезни. Это межсекторальное тематическое исследование включало в себя 62 пациенты, встречающиеся 2017 Критерии Mc

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… These findings suggest that central amylin signaling, like leptin and insulin signaling, contributes to maintaining body weight homeostasis in adults. [ 8 , 10 ] Receptor autoradiography studies have demonstrated high-affinity amylin receptor binding sites in several CNS regions, particularly within …

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma.

Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, includ

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… High speed scintillation autoradiography . …

Noise overstimulation induces immediate early genes in the rat cochlea.

In mammals, exposure to intense noise produces a permanent hearing loss called permanent threshold shift (PTS), whereas a moderate noise produces only a temporary threshold shift (TTS). Little is known about the molecular responses to such high intensity noise exposures. In this study we used gene arrays to examine the early response to acoustic overstimulation in the rat cochlea. We compared cochlear RNA from noise-exposed rats with RNA from unexposed controls. The intense PTS noise induced several immediate early genes encoding both transcription factors (c-FOS, EGR1, NUR77/TR3) and cytokine

Differential effects of amylin and salmon calcitonin on neuropeptide gene expression in the lateral hypothalamic area and the arcuate nucleus of the rat.

The pancreatic peptide hormone amylin (AMY) and the AMY receptor agonist salmon calcitonin (sCT) reduce short-term food intake in rats primarily by activating neurons located in the circumventricular area postrema. In the present study we analyzed the involvement of (an)orexigenic neuropeptides expressed in the lateral hypothalamic area (LHA) and in the arcuate nucleus in mediating the AMY and sCT-induced suppression of food intake. By using semiquantitative in situ hybridization 120 min after intraperitoneal injection of AMY or sCT (50 microgram/kg), orexin mRNA levels were decreased in LHA b

Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells.

In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fat

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… Membranes were subjected to autoradiography, and quantitative densitometric analysis was performed with the Scion Image software package. 2.6. …

Actinium-225 targeted alpha particle therapy for prostate cancer.

Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (225Ac), a potent alpha-emitting radionuclide, may be incorporated into targeting vectors, causing robust and in some cases sustained antitumor responses. The development of radiolabeling techniques involving EDTA, DOTA, DOTPA, and Macropa chelators has laid the groundwork for advancements in this field. At the forefront of clinical trials with 225Ac in PCa are PSMA-targeted TAT agents, notably [225Ac]Ac-PSMA-617, [225Ac]Ac-PSMA-I&T and [225Ac]Ac-J591. Ongoing inve

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… This involves ex-vivo autoradiography of alpha particle decay events, generating a real-time dose-rate map that provides information about the spatial distribution of the radioactivity in the tissue 121 . …

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

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… screening Lost in Translation monoclonal antibodies minimal anticipated biological effect level no adverse effect level organic anion transporter organic cation transporter positron emission tomography proof of concept proof of pharmacology proof of therapeutic efficacy quantitative whole body autoradiography … Current methods for measuring cellular distribution of drugs and their metabolites rely on quantitative whole body autoradiography (QWBA), isolation of cell populations, homogenization of organs and matrix‐assisted laser desorption ionization MS imaging techniques. …

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

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… Visualization of immunoblots from cell culture was performed using Pierce ECL Western Blotting Substrate (#32106; ThermoFischer Scientific, Waltham, MA, USA); Blue Autoradiography and Western Blotting Film (# 1968-3810 ; USA Scientific, Ocala, FL, USA); and Agfa CP1000 Developer (Agfa, Mortsel, Belgium …

Highlights lecture EANM 2016: "Embracing molecular imaging and multi-modal imaging: a smart move for nuclear medicine towards personalized medicine".

The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights inclu

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… Tumour heterogeneity was demonstrated by immunohistochemistry and autoradiography. In addition to EGFR, another target set linked to major drug development programmes is the immune checkpoint PD-1 expressed on T cells, and its ligand PD-L1, expressed on tumour and antigen-presenting cells [ 4 ]. …

Микроглиапозитрон эмиссии томографии и прогресс в множестве склероза: таламус горит.

Усиливающаяся иммунная активность способствует нейродегенерации и прогрессированию в множестве склерозов. Это перспективное тематическое исследование направлено на изучение таламической плотности микроглии на 18kDa транслокаторном протеине PET у пациентов с множественным склерозом с использованием радиолиганда третьего поколения, 11C-ER176, и расследовать деятельность ассоциаций 11C-ER176 Поглощение ПЕТ с помощью изображений и клинических показателей развития в множестве склерозов. Пациенты с множественным склерозом (n = 50) и органов управления (n = 55) были зачислены и прошли 11C-ER176 ПЕТ и

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… progressive multiple sclerosis more specifically The current study has important novel observations, and using a third-generation TSPO radioligand 11 C-ER176 in MS is one of them. 11 C-PK11195 is the first radioligand developed for TSPO PET and to evaluate the specificity of 11 C-PK11195 to microglia, autoradiography …

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

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… Furthermore, ex vivo autoradiography showed that the tracer could detect and image the heterogeneity of the MMR expression throughout the TME, as its biodistribution patterns were heterogeneous at the tumor borders as well as in intra-tumoral hotspots [ 123 ]. … As with the many nanobody imaging agents targeting other markers, the binding specificity of MB cAbVcam1-5 to VCAM-1 was also verified using IHC, autoradiography, and in vivo experiments. …

Cardiac amyloidosis: Innovations in diagnosis and treatment.

Cardiac amyloidosis (CA) is a progressive, underdiagnosed condition caused by the deposition of misfolded proteins in the myocardium, forming amyloid fibrils that impair cardiac structure and function. This review highlights recent advances in the diagnosis and treatment of amyloid light-chain (AL) and transthyretin (ATTR) CA, which globally account for most cases of CA. Novel diagnostic tools, including artificial intelligence-enhanced analysis and advanced imaging modalities like positron emission tomography with amyloid-specific tracers, might improve detection rates and diagnostic accuracy

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… Park M-A, Padera RF, Belanger A, Dubey S, Hwang DH, Veeranna V et al. 18 F-Florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging 2015;8:e002954. 38. …

Роль окситоцина и Васопрессина в нейропсихиатрических расстройствах: терапевтический потенциал агонистов и антагонистов.

Окситоцин (OT) и вазопрессин (AVP) являются гипоталамическими нейропептидами, которые традиционно ассоциируются с их регулирующей ролью в размножении, гомеостазисе воды и социальном поведении. Интересно, что в последние годы эта роль расширилась и эти нейропептиды стали лечебными мишенями для различных нейропсихиатрических заболеваний, таких, как аутизм, зависимость, шизофрения, депрессия и тревожное расстройство. В связи с химическими и физическими характеристиками этих нейропептидов, включая короткий период полураспада, плохое проникновение через мозговые барьеры, беспорядочность для AVP и O

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… Then, when binding of V 1A R and OT-R was analyzed using autoradiography, the effects of isolation were brain area sex specific. For V 1A R binding, a significant sex effect in BNST, mPOA, and anterior hypothalamus (AH) was reported. …

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages. PSMB5 and LC3I/II protein levels were determined using Western blot, proteasome proteolytic activity (PPA) with spectrofluorometry, and ROS with flow cytometry. PSMB5 accumulation

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… The SuperSignal™ West Pico PLUS Chemiluminescent Substrate was used for antigen detection (Thermo Fisher Scientific, Waltham, MA, USA), and autoradiography films (Fujifilm Hellas, Athens, Greece) were used to develop the signal. 2.5. …

Light Chain Amyloidosis.

Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy. The specific treatment is chemotherapy targe

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… PN Moon JC Cardiovascular magnetic resonance for amyloidosis Heart Fail Rev 2015 20 2 133 144 https://doi.org/10.1007/s10741-014-9470-7 25549885 10.1007/s10741-014-9470-7 33 Park MA Padera RF Belanger A 18F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits: Autoradiography …