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Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have con

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… The dual role of thymidine phosphorylase in cancer development and chemotherapy. Medicinal Research Reviews. 2009;29(6):903–953. doi: 10.1002/med.20159. 60. Liekens S., Bronckaers A., Pérez-Pérez M.-J., Balzarini J. … Targeting platelet-derived endothelial cell growth factor/thymidine phosphorylase for cancer therapy. Biochemical Pharmacology. 2007;74(11):1555–1567. doi: 10.1016/j.bcp.2007.05.008. 61. Wang L., Huang X., Chen Y., Jin X., Li Q., Yi T. N. …

Palbociclib as an Antitumor Drug: A License to Kill.

Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discus

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… The results revealed a suppression of the serum thymidine kinase activity (83% of the patients exhibited a level below the detection limit on the 15th day of the therapy cycle). Higher serum thymidine kinase activity was associated with shorter progression-free survival [ 44 ]. … Bagegni et al. [ 48 ] previously reported the reduction of the serum thymidine kinase activity after palbociclib treatment as a result of the NeoPalAna clinical trial ( Table 3 ). …

A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses.

Oncolytic viruses (OVs) are gaining traction as advanced tools in cancer therapy. They are distinguished by their ability to destroy malignant cells while sparing normal tissue specifically. In addition to their direct tumor-lysing properties, an essential benefit of oncolytic virus therapy is its capacity to activate both the innate and adaptive immune systems. To enhance these therapeutic actions, many OVs have been genetically engineered to encode immune-modulating factors that reestablish or strengthen antitumor immune responses. Recent studies show that combining OVs with other forms of i

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… Targeting specificity of VV is strongly influenced by the thymidine kinase (TK) gene, which is essential for viral replication and is commonly upregulated in cancer cells but expressed at low levels in normal cells. … HSV-1 TK differs from the human version in that it phosphorylates thymidine analogs to produce monophosphates, which are then sequentially phosphorylated by cellular kinases to form triphosphates. …

Keyword Index for Volume 103

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… /uracil 1343 telomerase activity and pathways 1255 temozolomide 29, 498, 820, 827, 1588 temsirolimus 649 testicular cancer 1269, 1467 testicular germ cell tumour 18 TGF β 1716 Th17 1245 therapeutic response 486 therapeutic target 1671 therapy 196, 239, 1479 therapy toxicity 820 thymic carcinoma 196 thymidine … phosphorylase (TP) 845, 1680 thymidine synthase (TS) 354, 845, 1680 thymoma 6, 196 time-dependent variable 727 tissue microarray 961, 1710 TNFSF10 256 tobacco use 1093 tosedostat 1362 toxicity 581, 772, 1548 TP53 362 TRAIL 642, 1380, 1692, 1783 transcriptional regulation 275 transgenic mice 1297 trans-signalling …

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes.

Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials eva

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… Further studies using recombinant vaccinia virus armed with GM-CSF gene, the lacZ under the control of viral promoter p7.5. and viral thymidine kinase gene deletion (JX-594, pexastimogene devacirepvec, Pexa-Vec) has demonstrated limiting replication in cells with high intrinsic thymidine kinase activity … The thymidine kinase (TK) gene of the herpes simplex virus HSV-1 is often cloned into the genome of oncolytic viruses (24 studies). …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

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… The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Lond) 1978;81:267–77. doi: 10.1017/s0022172400025109. https://doi.org/10.1017/S0022172400025109 . 10. Jamieson AT, Gentry GA, Subak-Sharpe JH. … Induction of both thymidine and deoxycytidine kinase activity by herpes viruses. J Gen Virol. 1974;24:465–80. doi: 10.1099/0022-1317-24-3-465. https://doi.org/10.1099/0022-1317-24-3-465 . 11. Whitley RJ, Roizman B. Herpes simplex virus infections. …

Anti-carcinogenic and Anti-bacterial Properties of Selected Spices: Implications in Oral Health.

"Let food be thy medicine and medicine be thy food", as said by the father of medicine, Hippocrates in 431 B.C. Nature has provided us with a variety of treatment modalities in the form of food. For the first 5,000 years of civilization, humans relied on herbs and foods for medicine. Only in the past 60 years have we forgotten our medicinal "roots" in favor of patented medicines. While pharmaceutical ingredients have their value, we should not overlook the well-documented, non-toxic and inexpensive healing properties of food. As an individual we consume food several times a day without a compl

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… oxidative damage and its inhibition of nitric oxide in lipopolysaccharide-stimulated RAW 264.7 macrophages J Med Food 2010 13 137 141 20136447 10.1089/jmf.2008.0154 39 Koch C Reichling J Kehm R Sharaf MM Zentgraf H Schneele J Schnitzler P Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive … and thymidine-kinase-negative herpesviruses J Pharm Pharmacol 2008 60 1545 1550 18957177 10.1211/jpp/60.11.0017 40 Zoe C 7 ways to be free eliminate bad breath naturally [Internet] 2010 9 11 cited 2015 January 14 Available from: http://goarticles.com/article/7-Ways-To-Be-Free-Eliminate-Bad-Breath-Naturally …

Emerging Therapies for Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and

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… A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene Ther. 2010;17:837–843. doi: 10.1038/cgt.2010.40. 52. Nakai H., Fuess S., Storm T.A., Muramatsu S., Nara Y., Kay M.A. … Suicide gene therapy for hepatocellular carcinoma cells by survivin promoter-driven expression of the herpes simplex virus thymidine kinase gene. Oncol. Rep. 2013;29:1435–1440. doi: 10.3892/or.2013.2248. 76. …

The treatment of multiple myeloma--an important MRC trial.

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… Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V trial. 84 2 6 1993 238 241 Br J Haematol 8398824 10.1111/j.1365-2141.1993.tb03058.x Buckner C. D. Fefer A. Bensinger W. I. Storb R. Durie B. G. Appelbaum F. R. Petersen F. B. Weiden P. … Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. 81 12 15 6 1993 3382 3387 Blood 8507875 Grogan T. M. Spier C. M. Salmon S. E. Matzner M. Rybski J. Weinstein R. S. Scheper R. J. Dalton W. S. …

Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding variou

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… Suicide Gene Switch To date, two suicide genes have been integrated into CAR-T cells and tested in the clinic: the gene coding for herpes simplex virus thymidine kinase (HSV-TK) and the gene coding for inducible caspase-9 (iCasp9). … Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: Fifteen years of application Curr. Gene Ther. 2003 3 13 26 10.2174/1566523033347426 12553532 27. Ciceri F. Bonini C. Marktel S. Zappone E. Servida P. Bernardi M. Pescarollo A. Bondanza A. …

A year in pharmacology: new drugs approved by the US food and drug administration in 2025.

The US Food and Drug Administration approved 45 new drugs and 4 new cellular and gene therapy products in 2025, that is, a total of 49 new medical therapies. Oncology, hematology/immunotherapy, and cardiovascular/respiratory drugs remain most frequent. Among oncology drugs, there is a trend for targeting ever smaller subtypes of malignancies and/or rarer malignancies. Trends over the past 6 years include steady levels of first-in-indication (about 10%), first-in-class (about 38%), and next-in-class (about 51%) approvals. Along with a large share of approvals in orphan indications (> 50%), fast

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… A combination of pyrimidine nucleosides, doxecitine and doxribtimine , has been approved for the treatment of thymidine kinase 2 deficiency in adults and pediatric patients with symptom onset at or before 12 years of age. … N Engl J Med 392:1569–1581. 10.1056/NEJMoa2411664 Chow E, Miller L, Clearman A, Arnold P, Koenig MK, Russo SN (2025) Doxecitine and doxribtimine treatment in an adult patient with thymidine kinase 2 deficiency. …

Trial watch: Oncolytic viruses for cancer therapy.

Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several diffe

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… Strategies that have been undertaken in this sense include the integration into the viral genome of sequences coding for: (1) enzymes that can transform a non-toxic pro-drug into a lethal cytotoxic chemical, such as the thymidine kinase (TK) of herpes simplex viruses (HSVs), converting ganciclovir into … kinase Cancer Res 1999 59 410 3 9927055 34 Tseng JC Zanzonico PB Levin B Finn R Larson SM Meruelo D Tumor-specific in vivo transfection with HSV-1 thymidine kinase gene using a Sindbis viral vector as a basis for prodrug ganciclovir activation and PET J Nucl Med 2006 47 1136 43 16818948 35 Foloppe …

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials.

Until very recently, the major use, for gene therapy, specifically of linear or circular DNA, such as plasmids, was as ancillary products for viral vectors' production or as a genetic template for mRNA production. Thanks to targeted and more efficient physical or chemical delivery techniques and to the refinement of their structure, non-viral plasmid DNA are now under intensive consideration as pharmaceutical drugs. Plasmids traditionally carry an antibiotic resistance gene for providing the selection pressure necessary for maintenance in a bacterial host. Nearly a dozen different antibiotic-f

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… The thymidine auxotrophy brought about by the lethal amber mutation can be overcome by adding thymidine in the bacterial growth medium to maintain the non-transformed strain. … Inside the bacterial cells, thymidine is converted into dTMP via an alternative metabolic pathway involving the thymidine kinase enzyme. …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

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… Cytidine nucleotides and thymidine nucleotides can be derived from UMP [ 56 ]. … The activation of thymidine nucleoside analogs depends on cytosolic TK1. In colorectal cancer cells, silencing of TK1 renders cells resistant to trifluridine while preserving their susceptibility to 5‐FU [ 268 ]. …

Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.

The transforming properties of oncogenes are derived from gain-of-function mutations, shifting cell signaling from highly regulated homeostatic to an uncontrolled oncogenic state, with the contribution of the inactivating mutations in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional and target-directed therapy. On the other hand, this scenario fulfills two requirements for oncolytic virus infection in tumor cells: inactivation of tumor suppressors and presence of oncoproteins, also the requirements to engage malignancy. Several of these oncogenes have a negative i

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… Therefore, important modifications were performed in order to make this virus safe for clinical use: (a) deletion of thymidine kinase (TK), a protein involved in DNA synthesis and repair, 103 where expression of its cellular homolog is correlated with malignancy; 104 (b) deletion of ICP 34.5 gene, which … A marker for malignant cells Adv Exp Med Biol 1998 431 455 460 9598110 104 Alegre MM Robison RA O’Neill KL Thymidine kinase 1 upregulation is an early event in breast tumor formation J Oncol 2012 2012 575647 22778736 10.1155/2012/575647 PMC3388419 105 Liu BL Robinson M Han ZQ ICP34.5 deleted herpes …

Paediatric intestinal pseudo-obstruction: a scoping review.

Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a

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… 2 Causes of PIPO identified [ 2 , 8 – 11 , 14 , 42 , 45 , 46 , 48 – 50 ] ACTG2 , actin gamma 2, smooth muscle; FLNA, filamin; L1CAM , L1 cell adhesion molecule; LMOD1 , Leiomodin 2; POLG , polymerase DNA gamma; RAD21 , cohesion complex component; SGOL1 , shugoshin-like 1; SOX10 , SRY-BOX 10; TYMP , thymidine … Of note, mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a well-described autosomal recessive condition resulting from mutations in the thymidine phosphorylase gene, leading to impaired intestinal motility and also involving other organs [ 45 , 47 ]. …

Prospects for repurposing CNS drugs for cancer treatment.

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drug

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… Moreover, it initiated Wnt and Raf/MEK/ERK pathway. 67 In the event of HCC, the activation of caspase-3, ROS, and autophagy were introduced by Valproate/Doxorubicin combination. 68 Breast cancer A study has shown that Valproate can increase thymidine phosphorylase levels in breast cancer cells leading … Terranova-Barberio M Roca MS Zotti AI Leone A Bruzzese F Vitagliano C Valproic acid potentiates the anticancer activity of capecitabine <i>in vitro</i> and <i>in vivo</i> in breast cancer models via induction of thymidine phosphorylase expression . …

Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A.

Recently, attention has been focused on the role of aldosterone in the pathophysiology of hypertension and cardiovascular disease. Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. However, the molecular mechanisms of the effects of aldosterone in signal transduction and the cell-cycle progression of mesangial cells are not well known. For determining the signaling pathway of aldosterone in cultured mesangial cells, the effects of aldosterone on the mitogen-activated protein kinase 1/2 (MAPK1/2) pathway and the promot

Small compound 6-O-angeloylplenolin induces mitotic arrest and exhibits therapeutic potentials in multiple myeloma.

BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/principal findingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal

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… Analysis of cell cycle MM cells were synchronized to G1/S boundary by a double-thymidine block. … Briefly, cells were treated with 2 mM thymidine (Sigma-Aldrich) for 16 h, released into fresh medium for 9 h and subjected again to thymidine for another 16 h and then exposed to 6-OAP for indicated time points. …

Oral presentations

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… Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors. 60 22 15 11 2000 6298 6302 Cancer Res 11103787 Carragher N. O. Fincham V. J. Riley D. Frame M. C. …