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Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals.

In order to investigate the possibility of whether or not the lymphocytes of patients with Alzheimer's Disease (AD) are in an activated state, blood mononuclear cells from 45 AD patients and 45 healthy age matched controls were immunophenotyped by measuring the expression of CD3, CD4, CD7, CD8, CD25, CD28, CD56 and HLA-DR by flow cytometry. Circulating and in-vitro-produced cytokines were also measured by ELISA tests. CD7 and CD8 were significantly decreased in AD patients (48.3% and 18.2%, respectively) when compared to healthy subjects (63.2% and 28.3%, respectively). A significant increase

Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.

Background and aimOncolytic virotherapy is a novel therapeutic paradigm in oncology that uses viruses to selectively replicate within cancer cells, causing targeted tumor cell destruction with minimal toxicity to healthy tissues. With the rapid growth of oncolytic virotherapy and the accumulation of clinical studies on this subject, the present review aims to provide a comprehensive evaluation of current achievements in cancer treatments involving oncolytic viruses (OVs).Main textNumerous clinical trials have been conducted to assess the therapeutic efficacy and safety of OVs across a variety

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… Investigators employed a mutant strain of HSV-1 engineered with a targeted deletion of the gene encoding thymidine kinase. … kinase) has been replaced with an HSV-tk | Healthy volunteer | I | Systemic Injection | Completed | NCT07302945 hV01 | hV01 is a recombinant vaccinia virus with deletions of the viral thymidine kinase and viral growth factor genes and insertion of the human IL-21 gene | Advanced solid tumors | NA | …

Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review.

Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have

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… Thymidine phosphorylase in cancer; enemy or friend? Cancer Microenviron 9 2016 33 43 26298314 10.1007/s12307-015-0173-y PMC4842186 27 Shimaoka S. Matsushita S. Nitanda T. … The role of thymidine phosphorylase expression in the invasiveness of gastric carcinoma Cancer 88 2000 2220 2227 10820342 28 Kawahara A. Hattori S. Akiba J. …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy. Gene Ther. 2001;8:946‐953. 10.1038/sj.gt.3301489 117. Zhang JF, Wei F, Wang HP, et al. … Inhibition of melanoma growth by adenoviral‐mediated HSV thymidine kinase gene transfer in vivo. J Invest Dermatol. 1995;104(3):313‐317. 10.1111/1523-1747.ep12664614 120. Man J, Millican J, Mulvey A, Gebski V, Hui R. …

Role of LFB3 in cell-specific cAMP induction of the urokinase-type plasminogen activator gene.

In previous work we suggested that a kidney-specific transcription factor LFB3 cooperates with cAMP-response element (CRE)-binding proteins within a cAMP regulatory unit comprised of three protein-binding domains and located 3.4 kilobase pairs upstream of the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells (Menoud, P.-A., Matthies, R., Hofsteenge, J., and Nagamine, Y. (1993) Nucleic Acids Res. 21, 1845-1852). The two domains contain a CRE-like sequence, and the third domain is recognized by LFB3. The absolute requirement of LFB3 as well as the cooperation among the three domai

Keyword Index for Volume 104

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… survivorship 927 systematic review 1196 systemic lupus 1478 TACE 138 TAGLN2 808 tamoxifen 899, 1558 targeted therapy 399, 464, 1256, 1686 taxanes 316 temozolomide 1816, 1854 temsirolimus 643 testosterone 1452 tetraspanin 496 tetraspanin 8 155 tetraspanin CD151 1611 TFII-I 1349 TGFBR1 735 Thiothymidine 1869 thymidine … kinase 332 thymidine phosphorylase 1185 thymidine phosphorylase inhibitor 1185 thymidylate synthase 1594 thyroid atrophy 241 thyroid neoplasms 181 TIMP3 138 Tip-1 324 tissue factor 1401 tissue micro-arrays 693 TKI-258 75 toll-like receptor 2 460 tongue cancer 1890 toxicity 756, 1365 TRAIL 281, 1278 …

Данные о дисфункции мозга в крови и синтезе иммуноглобулина CSF в расстройстве регрессии синдрома Дауна.

ЦЕЛИ: Данное исследование было направлено на оценку протеомических, метаболомических и иммунных сигнатур в цереброспинной жидкости лиц с нарушением регрессии синдрома Дауна (DDRD). МЕТОДЫ: Было проведено перспективное исследование по контролю за конкретными случаями, сравнивающее протеомные, метаболомные и иммунные профили у отдельных лиц с ДСРД. Образцы были получены из биорепозитории затронутых лиц по сравнению с клиническими данными и ранее были получены результаты нейродиагностических исследований. Лица с ДСРД сравнивались с лицами с установленными нейро-воспалительными заболеваниями (напр

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… In contrast, the DSRD group showed many significant changes not observed in the neuroinflammatory controls, such as elevation of thymidine, butanoyl‐l‐carnitine, and nicotinamide (Fig.  2B , Fig.  S2A ). … For example, thymidine levels were significantly elevated in the CSF of DSRD cases, but not elevated in the CSF of neuroinflammatory controls or plasma samples of DS (Fig.  2B,C ). …

Keyword Index for Volume 88

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… 1339 Taxol 973 TCF 1932 telomere length 593 temozolomide 175 tenascin 996 testicular biopsy 828 testicular cancer 36 testicular germ-cell tumours 878 testicular intraepithelial neoplasia 828 testicular neoplasms 828 testis 843 TGF- β 1 1615 TGF β 420, 1424 thalidomide 822 therapy 478 thymidine … kinase 1963 thymidine phosphorylase 957 thymidine phosphorylase inhibitor 957 thyroid cancer 1358 thyroid carcinoma 1223 TIL 320 time course 1510 time-lapse microscopy 1310 TIMP-1 1248, 1605 tissue exposure 782 tissue microarray 231, 1417 TNF- α 314 tobacco 1702 tocopherol 1381 tomudex …

Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer.

BackgroundViscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.MethodsFour day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 microg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyze

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… After 4 days of co-culture, the cells were pulsed overnight with 0.5 μCi (0.037 MBq) of ( 3 H)thymidine to quantify T-cell proliferation. … After 48 hrs of co-culture, the cells were pulsed overnight with 0.5 μCi (0.037 MBq) of ( 3 H)thymidine to quantify T-cell proliferation (Panel A, filled bars). …

Circulating biosignatures in multiple myeloma and their role in multidrug resistance.

A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic

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… Markers of cellular change Thymidine kinase (TK) is a phospho-transferase involved in the DNA salvage pathway and specifically catalyses phosphorylation of deoxythymidine. Serum levels of thymidine kinase (TK) are an indirect measure of plasma cell proliferation [ 17 , 88 ]. … Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V Trial. 18. Bryant C, Suen H, Brown R, Yang S, Favaloro J, Aklilu E, Joshua DE. …

Final report on the safety assessment of octoxynol-1, octoxynol-3, octoxynol-5, octoxynol-6, octoxynol-7, octoxynol-8, octoxynol-9, octoxynol-10, octoxynol-11, octoxynol-12, octoxynol-13, octoxynol-16, octoxynol-20, octoxynol-25, octoxynol-30, octoxynol-33, octoxynol-40, octoxynol-70, octoxynol-9 carboxylic acid, octoxynol-20 carboxylic acid, potassium octoxynol-12 phosphate, sodium octoxynol-2 ethane sulfonate, sodium octoxynol-2 sulfate, sodium octoxynol-6 sulfate, and sodium octoxynol-9 sulfate.

Octoxynols are ethoxylated alkylphenols in which the size of the molecule is related to the number of moles of ethylene oxide used in synthe … ase mutation assay, malignant transformation assay, DNA alkaline unwinding test, and mouse lymphoma thymidine kinase locus forward mutation assay. Ethoxylated alkylphenols are generally considered to be estrogenic in that they mimic the effects of estradiol. Dermal exposure at three dose levels of rats to Octoxynol-9 failed to induce any malformations by ca …

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

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… Thymidine phosphorylase Thymidine phosphorylase (TYMP) is an enzyme involved in pyrimidine nucleotide metabolism and was recently reported to be identical to platelet-derived endothelial cell growth factor (PD-ECGF). PD-ECGF has angiogenic activity in vitro and in vivo [ 79 ]. … Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer. 1996;73:884–888. doi: 10.1038/bjc.1996.177. 82. …

Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G₂ delay and mitotic defects.

The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G₂/M and an associated decrease in expression of particular genes required for passage through G₂ and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G₂ del

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… To characterise this arrest further and study potential defects in DNA replication, cells were synchronised by double thymidine block and released into medium containing 100 nM panobinostat or excipient control. At 0 h, cells are synchronised at the G 1 /S boundary ( figure 1A ). … Cell cycle synchronisation 2 mM thymidine was added to 50% confluent cells, which were incubated for 15 h. Cells were then reseeded at 2 × 10 6 cells/10 cm plate and left to recover for 12 h. 2 mM thymidine was added again and the cells were incubated for 14 h. …

Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be

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… Houghton JA Tillman DM Harwood FG , Ratio of 2’-deoxyadenosine-5’-triphosphate/thymidine-5’-triphosphate influences the commitment of human colon carcinoma cells to thymineless death . Clin Cancer Res 1995 ; 1 : 723 - 30 . 9816038 76. … Wang L Munch PB Herrström SA Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates . FEBS Lett 1999 ; 443 : 170 - 4 . 9989599 10.1016/s0014-5793(98)01711-6 96. …

RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in cancers, although its oncogenic mechanism has not been well characterized. Phosphorylated level of RSK (T573) was increased in acute myeloid leukemia (AML) patients and associated with poor survival. To examine the role of RSK in AML, we analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in AML cell lines and patient AML cells. Characterization of mitotic phases showed that the metaphase/an

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… Figure 3 Metaphase arrest by the treatment of BI-D1870. ( A ) HL60 cells were synchronized at metaphase using a thymidine plus nocodazole block. One hour before release, cells were treated with BI-D1870 (5 μM). … For analysis of metaphase-to-anaphase transition, HL-60 cells were synchronized at metaphase using a modified thymidine plus nocodazole block [ 53 ]. HL-60 cells were treated with 1.5 mM thymidine (Sigma, St. Louis, MO, USA) for 16 h, washed with PBS and released in fresh media for 3 h. …

Oridonin, a diterpenoid purified from Rabdosia rubescens, inhibits the proliferation of cells from lymphoid malignancies in association with blockade of the NF-kappa B signal pathways.

This study found that oridonin, a natural diterpenoid purified from Rabdosia rubescens, inhibited growth of multiple myeloma (MM; U266, RPMI8226), acute lymphoblastic T-cell leukemia (Jurkat), and adult T-cell leukemia (MT-1) cells with an effective dose that inhibited 50% of target cells (ED50) ranging from 0.75 to 2.7 microg/mL. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining showed that oridonin caused apoptosis of MT-1 cells in a time-dependent manner. We explored effects of oridonin on antiapoptotic Bcl-2 family members and found that it down-regulated levels

Interleukin-7 signaling in human B cell precursor acute lymphoblastic leukemia cells and murine BAF3 cells involves activation of STAT1 and STAT5 mediated via the interleukin-7 receptor alpha chain.

Interleukin-7 (IL-7) stimulates the proliferation of normal and leukemic B and T cell precursors and T lymphocytes. Activation of the JAK/STAT pathway has been implicated in IL-7R signaling. We investigated which STAT complexes are formed upon stimulation of B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells with IL-7. Gel retardation assays with STAT-binding oligonucleotides showed that IL-7 induces the formation of two major STAT complexes in BCP-ALL cells. Supershifts with anti-STAT antibodies identified these as STAT1 and STAT5 complexes. This pattern of STAT activation was seen

Recurrent Respiratory Papillomatosis (RRP)-Juvenile Onset.

In this article, we describe the treatment of long standing juvenile-onset recurrent respiratory papillomatosis (JORRP) with eventual transformation to carcinoma in a patient who lived to the age of 73. Treatment modalities consisted of bronchoscopy and local excision initially. Later, YAG and CO2 laser debulking were used. Radiotherapy, chemotherapy with carboplatin (300 mg/m2) and 5-FU (600 mg/m2), oral methotrexate (5-7.5 mg/week), pegylated Interferon, indole-3-carbamide, and intralesional cidofovir were also utilized in the treatment of this patient. Except for methotrexate, each of the t

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… Acyclovir, a purine analogue, is preferentially activated by thymidine kinases encoded by herpes viruses and is then incorporated into viral DNA causing strand breakage. … Although the papillomavirus does not preferentially activate thymidine kinase, there have been clinical responses to acyclovir in patients with RRP. The current hypothesis is that a co-infection with herpes virus may exist. …

CAR-T Cell Therapy: Managing Side Effects and Overcoming Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy is an innovative and promising approach to treat cancer. Clinical trials have demonstrated remarkable results, providing hope for patients who have exhausted more traditional therapies. However, this new therapy is not without challenges, as significant side effects have been associated with it. Cytokine release syndrome (CRS) is a widely recognized and consequential side effect of CAR-T cell therapy. Neurological toxicity is another potential side effect that can cause confusion and seizures in some patients. Hematologic toxicities, such as ane

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… Additionally, applying such strategies provides an effective solution to these challenges.[ 67 ] HSV-TK There has been some research exploring the use of Herpes simplex virus thymidine kinase (HSV-TK) in conjunction with CAR-T cell therapy. … Curability of tumors bearing herpes thymidine kinase genes transfered by retroviral vectors. J Natl Cancer Inst. 1990;82:297–300. doi: 10.1093/jnci/82.4.297. 71. Sangro B, Mazzolini G, Ruiz M, Ruiz J, Quiroga J, Herrero I, et al. …