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[Biological properties and sensitivity to induction therapy of differentiated cells expressing atypical immunophenotype in acute leukemia of children].

The atypical immunophenotype (expression of determinant from the another cell lines than line of origin) of acute leukaemia blast cells are … ) for CD determinants and MDR. The spontaneous proliferation of leukaemia cells was studied with 3H-Thymidine uptake after 3-days culture in vitro. The type of proliferation (autocrine, paracrine) was defined based on comparison of shorter (3-days) and longer (6-days) culture of leukaemia cells. The percentage of apoptotic leukaemia cells was analysed with …

CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.

BackgroundPatients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC).Patients and methodsThis single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and ir

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… Two agents have been approved by the US Food and Drug Administration (FDA) for the treatment of third-line and above metastatic CRC, namely trifluridine-tipiracil hydrochloride (Lonsurf®), a thymidine-based nucleoside analogue 3 and regorafenib (Stivarga®), a multikinase inhibitor. 4 The DNA mismatch …

EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some

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… In cellular assays, it was shown that panobinostat enhances histone acetylation and affects processes known to be regulated by histone acetylation status (gene expression of 21 kilodalton cyclin dependent kinase inhibitor (p21), TPRM, Hep27, thymidine kinase). …

Oncolytic viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics

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… Keri Streby (Nationwide Children’s Hospital, Columbus, OH) showed that cells infected with oHSV expressing NAT had increased 131 I-mIBG uptake and associated cytotoxicity. oHSV replication can be imaged by 18F FHBG-PET due to thymidine kinase (TK) expression (Darshini Kuruppu, Massachusetts General Hospital …

Keyword Index for Volume 100

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… review 436, 1852 tamoxifen 281, 1048 tamoxifen sensitivity 123 target 1002 targeted therapy 431, 623, 1330 TATI 1540 telangiectasia 1680 temozolomide 322, 1154, 1245, 1250 testicular cancer 1861 TGFBR1 1674 TGFBR1 * 6A 1674 Th17 1061 therapeutic antibodies 113 therapy 1731 Theratope 1746 thymidine …

Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are

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… kinase SBRT Pembrolizumab NSCLC Phase II 2017–2022 The Methodist Hospital Research Institute NCT 02,831,933 ADV/HSV-tk Herpes simplex virus thymidine kinase SBRT Nivolumab NSCLC Phase II 2017–2020 Eric Bernicker, MD Table 1 Completed and current clinical trials evaluating the applicability of Oncolytic … kinase | SBRT Pembrolizumab | NSCLC | Phase II | 2017–2022 | The Methodist Hospital Research Institute NCT 02,831,933 | ADV/HSV-tk | Herpes simplex virus | thymidine kinase | SBRT Nivolumab | NSCLC | Phase II | 2017–2020 | Eric Bernicker, MD Targeted antibodies for lung cancer Scientists have well …

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

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… Scheme 25 Prodrugs of 3-carboranyl thymidine analogues as antitumor agents. Non-secosteroidal vitamin D receptor (VDR) ligands are leading candidates in numerous biological applications. … Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors. Eur. J. Med. Chem. 2012;55:325–334. doi: 10.1016/j.ejmech.2012.07.033. 59. …

Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this r

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… Herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir is another safety switch that inhibits DNA synthesis through death-inducing signaling cascades and, therefore, induces CAR T-cell death ( Fig. 3 G ) . … Proteolysis-targeting chimera Switch-off CARs Hepatitis C virus Tumor-associated antigen Methotrexate Complement dependent cytotoxicity Antibody-dependent cell-mediated cytotoxicity Truncated epidermal growth factor receptor Inducible caspase 9 Immune Effector Cell Encephalopathy Herpes simplex virus thymidine …

Атипичные презентации Acolovir-Resistant Herpes Simplex Virus в иммунокомпромиссированных пациентах: Серия дел.

Инфекции, связанные с вирусом герпеса (HSV), у иммунокомпромиссированных пациентов могут иметь атипичные представления - от грануломатных до линейных эрозийных повреждений - и превращаться в рефракторную и стандартную терапию. Мы сообщаем three :: случаи некротизации категорической инфекции HSV у иммунокомпромиссированных пациентов с гематологическими малигнациями или предшествующими химиотерапиями, все из которых имеют нетипичные и рефракторные проявления заболевания. One дело касалось 53-year-old :: пациентка с реанимацией/рефрактом острой миэлоидной лейкемией (АМЛ), разработавшая некротизир

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… These unusual forms are often driven by antiviral resistance mechanisms, particularly thymidine kinase (TK) mutations and alterations in viral DNA polymerase, which reduce the efficacy of standard therapies like acyclovir. …

Canine Multicentric Lymphoma: Diagnostic, Treatment, and Prognostic Insights.

Lymphoma accounts for 24% of all documented canine neoplasms and 85% of hematological malignancies, while multicentric lymphoma corresponds to 84% of all canine lymphomas. Canine lymphomas of B-cell origin account for 60% to 80% of lymphomas. Similar to humans, the histologic grade, architecture, as well as immunophenotype determination, are crucial. These lesions are the most prevalent spontaneous tumors in dogs and this species may be a valuable animal model for the study of human non-Hodgkin's lymphoma. Therefore, it is important to investigate and assess therapeutic responses and to seek p

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… In CL, acute phase proteins, such as thymidine kinase 1 (TK1), monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP) and endostatin have been assessed [ 16 ]. … Serum Thymidine Kinase Activity in Dogs with Malignant Lymphoma: A Potent Marker for Prognosis and Monitoring the Disease J. Vet. Intern. Med. 2008 18 696 702 10.1111/j.1939-1676.2004.tb02608.x 15515587 95. Saellström S. Sharif H. Jagarlamudi K.K. Rönnberg H. Wang L. Eriksson S. …

Imaging for Plasma Cell Dyscrasias: What, When, and How?

Imaging plays a vital role in the diagnosis, response assessment, and follow-up of patients with plasma cell bone disease. The radiologic diagnostic paradigm has thus far evolved with developing technology and availability of better imaging platforms; however, the skewed availability of these imaging modalities in developed vis-à-vis the developing countries along with the lack of uniformity in reporting has led to a consensus on the imaging criteria for diagnosing and response assessment in plasma cell dyscrasia. Therefore, it is imperative for not only the radiologists but also the treating

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… role | Phase I trial—limited data 18F-Sodium fluoride (18F-NaF) | NaF: marker of osteoblastic activity | Poor sensitivity owing to the suppressed osteoblastic action in MM Poor specificity—uptake in any focus of bone reconstruction | Poor detection rate 18F-Fluorothymidine (18F-FLT) | Fluorothymidine: thymidine … High thymidine kinase activity in rapidly proliferating cells responsible for increased uptake | Inferior to FDG PET in the detection of lesions | Poor detection rate Radiologist-Initiated Suspicion Backache is a common complaint in the elderly and imaging is performed to detect the 5% of patients …

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting

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… In this study, transduced hPMSC, hPMSC-DF (herpes simplex virus truncated thymidine kinase and firefly luciferase), and hPMSC-DF + GCV (hPMSC-DF combined with ganciclovir) were administered in male Nu/Nu nude mice. … Cytosine deaminase converts 5-fluorocytosine into 5-FU, and herpes simplex virus thymidine kinase catalyzes ganciclovir, leading to a toxic form [ 42 ]; here, hAFSC were used as vehicles of these two suicide genes for breast cancer. …

Роль TP53 и FGFR2 в ходе лечения эндометического рака

Заболеваемость и смертность, вызываемые раком эндомеза, по-прежнему растут во всем мире. В последние годы была предложена новая система стратификации опухолей, основанная на статусе мутации POLE, TP53 и стабильности микроспутников. Цель этого исследования заключалась в анализе обширной группы по генам, которые потенциально могут быть связаны с геномомом эндомеального рака у польского населения. One hundred и three В исследование были зачислены белые пациентки с подтвержденным эндомеозным раком. Мы провели последовательность с использованием панели Hot Spot Illumin и стабильности микроспутников

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… Figure 1 A graphical presentation of molecular findings. ( A ) comparison the mutation types with an evident dominance of missense mutation. ( B ) We noted the single nucleotide polymorphism as a main molecular aberration. ( C ) The cytosine-thymidine shift was observed to be the most frequent. ( D ) …

High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease.

AimTo determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD).Methods50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was

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… Br J Dermatol 1996 134 780 3 10.1111/j.1365-2133.1996.tb06991.x 8733392 11 Aubin Cahn JY Ferrand C Angonin R Humbert P Tiberghien P Extensive vitiligo after ganciclovir treatment of GvHD in a patient who had received donor T cells expressing herpes simplex virus thymidine kinase. …

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome e

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… HDR-mediated knock-in mostly includes suicide genes, such as thymidine kinase, inserted into the tumor genome for achieving a therapeutic. … The fusion genes MAN2A1-FER found in hepatocellular carcinoma (HCC) and TMEM135-CCDC67 in prostate cancer (PC) offer the means of designing CRISPR/Cas9 therapies for the insertion of suicidal genes, such as the one for thymidine kinase ( TK ), that catalyzes the conversion of the harmless Ganciclovir …

The Emergence of Universal Immune Receptor T Cell Therapy for Cancer.

Chimeric antigen receptor (CAR) T cells have shown great success in the treatment of CD19+ hematological malignancies, leading to their recent approval by the FDA as a new cancer treatment modality. However, their broad use is limited since a CAR targets a single tumor associated antigen (TAA), which is not effective against tumors with heterogeneous TAA expression or emerging antigen loss variants. Further, stably engineered CAR T cells can continually and uncontrollably proliferate and activate in response to antigen, potentially causing fatal on-target off-tumor toxicity, cytokine release s

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… The first suicide switch system transferred the herpes simplex virus thymidine kinase (HSV-TK) gene into donor T cells. Upon administration of ganciclovir, the thymidine kinase of HSV-TK catalyzes the transformation of ganciclovir to the lethal triphosphate ganciclovir (GCV) ( 75 ). …

Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs.

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex(GM-CSF)]), is almost complete, wi

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… One of the first reports of an oncolytic virus being used for cancer therapy was in the early 1990s when Martuza et al 2 showed that a replication competent thymidine kinase negative herpes simplex virus (HSV)-1 mutant effectively prolonged survival of nude mice bearing intracranial glioma. … Initial extremely encouraging findings of the trial have been reported, with T-Vec demonstrating a statistically significant improvement in durable response rate. 20 Table 1 Oncolytic HSVs in clinical trials Abbreviations: HSV, herpes simplex virus; ICP, infected cell polypepetide; tk, thymidine kinase …

Keyword Index for Volume 90

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… 137 Cs- γ rays 48 [ 18 F]FETA 2232 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) 620 2D gel electrophoresis 1955 2D-DIGE 173 2-methoxyoestradiol 932 2-methoxyoestradiol- bis- sulphamate 932 2-nitroimidazole 2232 3 H-thymidine 48 3-hydroxy-3-methylglutaryl coenzyme A inhibitors …

Витамин D Дополняет медиацию, переходя к борьбе с воспламенением Цитокина при множественном склерозе.

ЦЕЛЬ: В этом исследовании мы провели оценку воздействия добавки витамина D (Vit-D) на профиль цитокина у недавно диагностировавшихся пациентов с множественным склерозом (MS) наркозависимости. Мы завербовали 16 :: пациенты с несчастными случаями 12 месяцев. Уровни сыворотки 25-hydroxy-Vit-D измерялись при наборе персонала и принятии последующих мер. Периферийные моноядерные клетки крови были изолированы от образцов крови и стимулировались митогеном в тканевой культуре для получения цитокина. Культурные супернататы были испытаны после 4 - дней после занятия культурой для уровней, обеспечивающих

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… The proliferation of PBMC was assessed by radiolabeled thymidine uptake. Culture supernatants were collected, centrifuged for 5 min at 5,000 g , and then stored at −80°C to estimate cytokine levels. …

Promotion of Bone Lesions Through the Myeloma Integrin α6-Mediated Osteolytic Signaling.

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients' quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study el

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… Thymidine Phosphorylase Exerts Complex Effects on Bone Resorption and Formation in Myeloma. Sci Transl Med (2016) 8(353):353ra113. 10.1126/scitranslmed.aad8949 4. Hynes RO. Integrins: Bidirectional, Allosteric Signaling Machines. Cell (2002) 110(6):673–87. 10.1016/S0092-8674(02)00971-6 5. …