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Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms

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… Moreover, autologous MSCs that expressed Herpes simplex virus thymidine kinase (HSV-TK) enzyme were utilized to treat human advanced gastrointestinal cancer (EudraCT number 2012-003741-15). HSV-TK converts ganciclovir from monophosphorylate to triphosphate form with a more potent cytotoxic effect. …

Targeted and epigenetic therapies for acute myeloid leukemia treatment.

This article provides a comprehensive overview of targeted and epigenetic therapies for acute myeloid leukemia (AML), highlighting their role in advancing treatment strategies. Recognizing that AML arises from complex genetic and epigenetic alterations, a deeper understanding of its pathogenesis has paved the way for precision medicine. The article reviews key targeted therapies, including IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3 alterations, BCL2 inhibitors (e.g., venetoclax) impacting apoptosis, and emerging M

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… The therapeutic transgenes’ repertoire in targeting malignant cells spans genes encoding cytotoxic, pro-apoptotic, antiproliferative proteins alongside conventional suicide genes like the herpes simplex virus thymidine kinase gene. …

Болезни Увечье с возрастом в экспериментальной модели множественного склероза: роль иммунозенсии.

Начавшийся множественный склероз (MS) у пожилых людей соотносится с более высоким риском развития первичных прогрессивных MS, ускорения перехода к вторичным прогрессивным MS и увеличения накопления инвалидности. Это явление может быть связано с возрастными изменениями в иммунной системе: с возрастом иммунная система проходит процесс, называемый иммунной сенсацией, который характеризуется снижением функции как врожденной, так и адаптивной иммунной реакции. Такое снижение может привести к снижению способности контролировать воспаление и восстанавливать поврежденные ткани. Кроме того, пожилые люд

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… At the same time, 1 μCi of [ 3 H]‐thymidine (NET027Z001MC; PerkinElmer, Waltham, MA, USA) was added to each well. Splenocyte cultures were maintained under the same conditions for an additional 18 h (Calvo‐Barreiro et al.  2020 ). …

Cancer Therapy-Induced Encephalitis.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as im

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… phosphatase, age > 60, neurological comorbidity | Frequently self-limiting 5-Fluorouracil | Acute encephalopathy | Rare | | Low dihydropyridine dehydrogenase | None Cerebellar dysfunction plus facultative additional CNS symptoms | Rare | | Allopurinol increase, N-Phosphonoacetyl- aspartate (PALA) thymidine …

Molecular Delivery of Cytotoxic Agents via Integrin Activation.

Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugate

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… It is a fluorinated pyrimidine antimetabolite, which irreversibly inhibits the enzyme thymidylate synthase and prevents cell proliferation by reducing the thymidine formation required for DNA synthesis [ 54 ]. …

Current cancer therapies and their influence on glucose control.

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT

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… Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase in 5-fluorouracil formation from tegafur in human liver. Clin Cancer Res . 2001;7:675–681. 77. Yucel H, Warmerdam LV. Capecitabine-induced pancreatitis. …

The roles of curcumin in regulating the tumor immunosuppressive microenvironment.

Cancer is a harmful threat to human health. In addition to surgery, a variety of anticancer drugs are increasingly used in cancer therapy; however, despite the developments in multimodality treatment, the morbidity and mortality of patients with cancer patients are on the increase. The tumor-specific immunosuppressive microenvironment serves an important function in tumor tolerance and escape from immune surveillance leading to tumor progression. Therefore, identifying new drugs or foods that can enhance the tumor immune response is critical to develop improved cancer prevention methods and tr

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… Another synthetic nanomaterial, chitosan nanoparticles loaded with demethoxycurcumin in combination with cisplatin, downregulates the expression levels of thymidine phosphorylase required for DNA self-repairing pyrimidine salvage pathways and induces apoptosis in non-small cell lung cancer (NSCLC) cell …

A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies.

Adult T-cell leukemia-lymphoma (ATL), a rare and aggressive T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1), is associated with a poor prognosis. Evidence-based standard treatment options are lacking and outcomes are generally unsatisfactory, particularly for patients with relapsed or refractory disease. Continued research is contributing to changing treatment landscape as a number of existing and investigational agents are evaluated. We describe the epidemiology of HTLV-1 and ATL, discuss the biology behind the disease, review current treatment practices and guidel

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… This inhibition results in the depletion of thymidine and other biologic molecules [ 64 ]. The PROPEL study was a phase 2 study of pralatrexate in patients with R/R PTCL (however, the study population included only one patient with ATL) [ 65 ]. …

Current and emerging therapeutic options in adrenocortical cancer treatment.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p'DDD (ortho-, para'-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment f

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… The systemic administration of antisense oligonucleotides would represent an interesting approach for ACC therapy; moreover, an in vitro study demonstrated that a suicide vector, in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the CYP11B1 promoter with a P450scc enhancer …

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

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… Tolerability and Pharmacodynamics of Intravenous Administration of IDOV-SAFE in Patients With Advanced Malignant Solid Tumors Who Have Failed in Standard Treatment. 5/6/2024 No NCT0309 5 Pexa-Vec No TSA RCC Pexa-Vec I/II A Phase 1b/2a Dose-escalation and Safety/Efficacy Evaluation Study of Pexa-Vec (Thymidine … Pharmacodynamics of Intravenous Administration of IDOV-SAFE in Patients With Advanced Malignant Solid Tumors Who Have Failed in Standard Treatment. | 5/6/2024 | No | NCT0309 5 | Pexa-Vec | No TSA | RCC | Pexa-Vec | I/II | A Phase 1b/2a Dose-escalation and Safety/Efficacy Evaluation Study of Pexa-Vec (Thymidine …

In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

Perspectives on the Risk-Stratified Treatment of Multiple Myeloma.

The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article d

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… Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma . Blood 1993 ; 81 : 3382 – 7 . 8507875 69. Fernández de Larrea C , Kyle R , Rosiñol L , Paiva B , Engelhardt M , Usmani S , . …

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

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… In this regard, the primary target of the deoxynucleoside analogues is the DNA polymerases involved in DNA replication. 12 , 13 , 21 Although there are five kinase enzymes in human cells phosphorylating deoxynucleoside analogues (eg deoxycytidine and deoxyguanosine kinase, thymidine kinase 1/2, and 5 …

Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces sign

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… with their mechanistic action and their comparison in terms of efficacy SAP, stress-activated protein; SOD, superoxide dismutase; ERK, extracellular signal-regulated kinases; JNK, c-Jun amino-terminal kinases; G-CSF, granulocyte-colony stimulating factor; CCAAT, cytosine-cytosine-adenine-adenosine-thymidine …

Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types

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… It has also been found to contain nucleosides such as cystidine, adenosine, thymidine, guanosine, inosine, and uridine, as well as nucleotides such as guanine, adenine, hypoxanthine, thymine, and uracil [ 57 ]. …

CAR-T: What Is Next?

The year 2017 was marked by the Food and Drug Administration (FDA) approval of the first two chimeric antigen receptor-T (CAR-T) therapies. The approved indications were for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia (ALL) that is refractory or in a second or later relapse. Since then, extensive research activities have been ongoing globally on different hematologic and solid tumors to assess the safety and efficacy of CAR-T therapy for these diseases. Limitations to CAR

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… There are several validated suicide genes, two of which are among the most studied in the clinical setting: herpes-simplex-thymidine-kinase (HSV-TK) and inducible-caspase-9 (iCasp9). …

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.

Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantati

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… Nonetheless, this prodrug can also be deglycosylated in the active form by microbial thymidine or uridine phosphorylases, resulting in premature intestinal activation and toxicity [ 28 ]. …

Aptamers: Potential Diagnostic and Therapeutic Agents for Blood Diseases.

Aptamers are RNA/DNA oligonucleotide molecules that specifically bind to a targeted complementary molecule. As potential recognition elements with promising diagnostic and therapeutic applications, aptamers, such as monoclonal antibodies, could provide many treatment and diagnostic options for blood diseases. Aptamers present several superior features over antibodies, including a simple in vitro selection and production, ease of modification and conjugation, high stability, and low immunogenicity. Emerging as promising alternatives to antibodies, aptamers could overcome the present limitations

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… Hemophilia | Phase 1; first-in-human and proof-of-mechanism study in hemophilia patients, ClinicalTrials.gov, # NCT01191372 (terminated) | [ 65 , 66 , 67 , 68 , 69 ] P-selectin, cell adhesion molecule | Anti-P-selectin aptamers: ARC5690 and ARC5694 | ARC5690: -33-mer oligonucleotide- a 3′-inverted 2′-deoxy-thymidine—a …

Internalized Functional DNA Aptamers as Alternative Cancer Therapies.

Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular sig

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… | AS1411 | NOX-A12 | Macugen/Pegaptanib Aptamer type | Unmodified guanosine rich DNA | RNA Spiegelmer | PEGylated RNA with 2′-F and 2′-OMe modifications Generation method | Chemically synthesized consisting entirely of deoxyguanosine and thymidine. | SELEX is carried out against a mirror-image target …

Clinical uses of GM-CSF, a critical appraisal and update.

The role of granulocyte-macrophage-colony-stimulating factor (GM-CSF) in the supportive care of cancer patients has been evaluated with promising results. More recently, GM-CSF has been added to regimens for the mobilization of hematopoietic progenitor cells. An expanding role for GM-CSF in regulating immune responses has been recognized based upon its activity on the development and maturation of antigen presenting cells and its capability for skewing the immune system toward Th1-type responses. GM-CSF has been shown to preferentially enhance both the numbers and activity of type 1 dendritic

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… Cells were exposed to mitogens or control for 72 hours, and then thymidine incorporation was measured. …