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Oxidized Lipids in Persistent Pain States.

Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; f

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… , immunoblotting analysis | PPARγ | ( Liu et al., 2005 ; Hiesinger et al., 2019 ) pulmonary murine microvascular endothelial cells | no | PI3K/Akt pathway activation, proliferation, migration | In vitro | stimulation with EETs/DHETs and quantification with NICI/GC/MS, proliferation assay with [ 3 H]thymidine … enzyme immunoassay, Western Blot, TNFα stimulation | PPARγ | ( Node et al., 1999 ) DRG neurons, pulmonary murine microvascular endothelial cells | | p38 MAPK, ERK pathway | In vitro, in vivo angiogenesis | stimulation with EETs/DHETs and quantification with NICI/GC/MS, proliferation assay with [ 3 H]thymidine …

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cf

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… It is worth noting that Mueller et al. used nucleosomal DNA, specifically thymidine kinase, in their study involving 25 patients, and, similar to our results regarding the baseline cfDNA concentration, their outcomes did not reach statistical significance. …

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs

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… Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma. Anticancer Res. 2007;27:2605–11. 86. Krzyzanowska MK, Tannock IF, Lockwood G, Knox J, Moore M, Bjarnason GA. …

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

Диметил фумарат отменяет гепатоцеллюлярный карциномный рост, подавляя ось Nrf2/Bcl-xL и повышая эффективность сорафениба.

Гепатоклеточная карцинома (ГК) характеризуется плохим прогнозом и остается одной из основных причин смертности от рака во всем мире. Усовершенствованный КЦУК регулируется несколькими методами лечения первой линии, включая ингибиторы тиросина киназы (TKI) и иммунную терапию (mAb-PD-1 и mAb-VEGF). Вместе с тем эффективность лечения КЦХВ зачастую недолговечна. Недавние исследования показали, что активация траектории Nrf2-Bcl-xL способствует плохому прогнозу у группы пациентов с КЦХВ. Здесь мы обнаружили, что диметилфумарат (DMF), лекарство, используемое для лечения псориаза и множественного склер

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… Edu staining assay Ethynyl-2-deoxyuridine incorporation assay was used to determine cell proliferation of huh7 in vitro. 5-Ethynyl-2′-deoxyuridine (EdU), an analog of thymidine, is incorporated into dividing cells during DNA synthesis (Beyotime, Shanghai, China). …

Antibody-Based Immunotherapeutic Strategies for the Treatment of Hematological Malignancies.

As the most common type of cancer in the world, hematological malignancies (HM) account for 10% of all annual cancer deaths and have attracted more attention. Conventional treatments, such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT), could relieve patients suffering HM. However, serious side effects and high costs bring patients both physical complaints and mental pressure. Recently, compared with conventional therapeutic strategies for HM patients, antibody-based immunotherapies, including cancer vaccines, oncolytic virus therapies, monoclonal antibody tr

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… Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer. Blood. 2006;107(12):4954–4960. doi: 10.1182/blood-2005-09-3883. 13. Jitschin R., Braun M., Büttner M., et al. …

Cell therapy for brain tumors: The first 60 years.

Primary brain tumors remain among the most lethal cancers, but immunotherapy holds immense potential to overcome limitations of current standard treatment modalities. Since the late 1960s, early-phase clinical trials have iteratively tested cellular immunotherapies for the treatment of brain tumors. Six decades ago, in the earliest studies, brain tumor patients were treated with infusions of nonspecific leukocytes, peripheral blood mononuclear cells (PBMCs), and bone marrow cells. These earliest studies demonstrated safety and occasional durable antitumor responses, particularly when cell ther

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… specific); EphA2, EPH receptor A2; GD2, disialoganglioside; HER2, human epidermal growth factor receptor 2; IL13Rα2, IL-13 receptor subunit alpha 2; CLTX, chlorotoxin; Costim, costimulatory domain of CAR; GR, glucocorticoid receptor; HyTK, hygromycin phosphotransferase gene/herpes simplex virus type 1 thymidine … specific); EphA2, EPH receptor A2; GD2, disialoganglioside; HER2, human epidermal growth factor receptor 2; IL13Rα2, IL-13 receptor subunit alpha 2; CLTX, chlorotoxin; Costim, costimulatory domain of CAR; GR, glucocorticoid receptor; HyTK, hygromycin phosphotransferase gene/herpes simplex virus type 1 thymidine …

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

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… For this purpose, VV strains are attenuated by several passages to render them replication defective; VV can also serve as an oncolytic vector to kill tumour cells by deleting or modifying the thymidine kinase (TK) locus of the VV genome, thus creating replication-competent VV strains [ 147 , 150 ]. … Construction of recombinant vaccinia virus: cloning into the thymidine kinase locus. Methods Mol Biol. 2004;269:31–40. 151. Parviainen S, Ahonen M, Diaconu I, Kipar A, Siurala M, Vaha-Koskela M, Kanerva A, Cerullo V, Hemminki A. GMCSF-armed vaccinia virus induces an antitumor immune response. …

Роль врожденных иммунных клеток в множественном склерозе.

Множественный склероз (MS) — хроническое аутоиммунное, воспалительное и нейродегенеративное заболевание, затрагивающее центральную нервную систему (КНС). MS ассоциируется со сложным взаимодействием между нейродегенеративными и воспалительными процессами, в основном связанными с патогенными Т и В клетками. Однако все большее количество доклинических и клинических данных свидетельствует о том, что врожденный иммунитет играет ключевую роль в поощрении и развитии НР. В этой связи в настоящее время изучаются доклинические и клинические исследования, ориентированные на различные врожденные иммунные

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… First attempt to dissect the role of microglia in EAE came with a study by Heppner et al. where, by using a CD11b-HSVTK transgenic mice, all CD11b+ cells, including macrophages and microglia, express the herpes simplex thymidine kinase and after ganciclovir administration, it blocks cell activation, …

Cell-based medicinal products approved in the European Union: current evidence and perspectives.

Advanced Therapy Medicinal Products (ATMPs) are innovative clinical treatments exploiting the pharmacological, immunological, or metabolic properties of cells and/or gene(s) with the aim to restore, correct, or modify a biological function in the recipient. ATMPs are heterogeneous medicinal products, developed mainly as individualized and patient-specific treatments, and represent new opportunities for diseases characterized by a high-unmet medical need, including rare, genetic and neurodegenerative disorders, haematological malignancies, cancer, autoimmune, inflammatory and orthopaedic condit

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… with Provenge, with a 22.5% reduction in the risk of death compared with control Zalmoxis (nalotimagene carmaleucel) | Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor and the herpes simplex I virus thymidine …

Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients.

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occas

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… DNA–Protein Cross-Linking Sequencing for Genome-Wide Mapping of Thymidine Glycol J. Am. Chem. Soc. 2022 144 454 462 10.1021/jacs.1c10490 34978433 PMC8755629 46. Stock W. Diouf B. Crews K.R. Pei D. Cheng C. Laumann K. Mandrekar S.J. Luger S. Advani A. Stone R.M. …

m6A reader hnRNPA2B1 drives multiple myeloma osteolytic bone disease.

Rationale: Bone destruction is a hallmark of multiple myeloma (MM) and affects more than 80% of patients. Although previous works revealed the roles of N6-methyladenosine (m6A) reader hnRNPA2B1 in the development of tumors, whether hnRNPA2B1 regulates bone destruction in MM is still unknown. Methods: Alizarin red S staining, TRAP staining, ELISA and quantitative real-time PCR assays were used to evaluate osteogenesis and osteoclastogenesis in vitro. X ray and bone histomorphometric analysis were preformed to identify bone resorption and bone formation in vivo. Exosome isolation and characteriz

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… Additional data are available upon reasonable request to the corresponding author. 1 Palumbo A Anderson K Multiple myeloma N Engl J Med 2011 364 1046 60 21410373 10.1056/NEJMra1011442 2 Liu H Liu Z Du J He J Lin P Amini B Thymidine phosphorylase exerts complex effects on bone resorption and formation …

Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer.

Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110

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… Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin's lymphoma. Tumour Biol. 2003;24:53–60. doi: 10.1159/000070661. 20. Allard B, Pommey S, Smyth MJ, Stagg J. …

Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and

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… For instance, deletion of thymidine kinase (TK) gene in HSV restricts replication to rapidly dividing tumor cells while sparing normal cells ( 89 ). In T-VEC, deletions of γ34.5 and α47 gene combined with insertion of GM-CSF gene, enhances tumor selectivity and immune activation ( 55 ). … This results in thymidine nucleotide depletion, leading to DNA synthesis arrest, replication stress, and cell death. …

Вирус Эпштейн-Барр BALF0/1 подрывает пути кавеолина и ERAD, чтобы охватить комплексы рецепторов клеток B для разложения.

Вирус Эпштейн-Барр (ЭБВ) устанавливает стойкую инфекцию, вызывает инфекционный мононуклеоз, является одним из основных пусковых факторов множественного склероза и способствует возникновению множественных раковых заболеваний. Тем не менее, знания о том, как вирус реконструирует клетки В для поддержки литического воспроизведения, остаются неполными. Ранее мы обнаружили, что EBV литическое воспроизведение приводит к избирательному истощению комплексов рецепторов клеток В (КРВ), состоящих из иммуноглобулина, а также цепочек сигнализации CD79A и CD79B. Здесь мы использовали протеомные и биохимическ

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… To establish CRISPR-edited cells, single guide RNAs (sgRNAs) were separately expressed to target BALF0/1 or instead as a control to target the EBV early lytic gene BXLF1, which encodes the viral thymidine kinase that is dispensable for EBV replication ( 27 , 28 ). …

Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening.

Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the γ-Secretase and thereby affect several different γ-Secretase substra

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… Notch reporter assay HEK293T cells were transiently transfected using Turbofect (Fermentas, Italy) with a firefly luciferase reporter plasmid carrying a multimerized 6xCSL (CBF1-RBP-J) Notch responsive element [ 33 ] and a plasmid carrying the Renilla luciferase under the control of thymidine kinase …

Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing.

BackgroundPulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension.Methods and resultsAfter developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats

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… B, PASMCs were transfected with 3.2 kb or 0.6 kb bcl‐x promoter‐controlled firefly luciferase with renilla luciferase controlled by thymidine kinase (TK) promoter as a control. Luciferase activities were monitored by dual luciferase system. …

Biological response modifiers and infectious diseases: actual and potential therapeutic agents.

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against vi

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… Replication of human immunodeficiency virus in monocytes: granulocytes/macrophage colony-stimulating factor (GM-CSF) potentiates viral production yet enhances the antiviral effect mediated by 3′azido-2′-3′-dideoxythymidine (AZT) and other dideoxynucleoside congeners of thymidine. …

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

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… To work properly, capecitabine requires high levels of thymidine phosphorylase (TP), a key enzyme that allows its conversion into 5-FU within the tumor. … Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression. Oncotarget. 2016;7:7715–7731. doi: 10.18632/oncotarget.6802. 84. …

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

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… Resistance to acyclovir is a rare event and mainly caused by reduced activity or mutations of viral thymidine kinase resulting in reduced activation of acyclovir in infected cells [ 143 , 144 ]. … Novel resistance-associated mutations of thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 and type 2. Antivir Ther. 2011;16(8):1297–1308. doi: 10.3851/IMP1870. 144. McLaren C, Sibrack CD, Barry DW. …