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Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of cotton (Gossypium hirsutum L.), was first used as a male contraceptive agent. Due to its diverse biological properties, including antifertility, antiviral, antioxidant, antibacterial, antimalarial, and most notably antitumor activities, gossypol has been the subject of numerous studies. Nevertheless, no systematic review has

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… A thymidine incorporation assay and doubling time (DT) measurement was used to investigate the effects of (±)-gossypol on the proliferation of human prostate cancer PC-3 cells. (±)-Gossypol decreased DNA synthesis and cyclin D1 mRNA, prolonged DTs, and increased TGF-β1 mRNA expression in PC-3 cells. …

Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.

Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER

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… Polyphenon E, which suppresses prostate cancer growth through ER stress, was identified to induce the mutant frequency in thymidine kinase locus and damage the myocardial fiber of Big Blue transgenic mouse when administered at a dosage of 2000 mg/kg for 28 days [ 177 ]. …

Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normal

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… Inhibition of human immunodeficiency virus type 1 activity in vitro by a new self-stabilized oligonucleotide with guanosine-thymidine quadruplex motifs. J. Virol. 2002;76(6):3015–22. doi: 10.1128/JVI.76.6.3015-3022.2002. 115. Matsukura M, et al. …

Целевые стратегии лечения рака цвета кожи: изучение использования аптемеров и золотых нанопчастей.

Рак цвета кожи (КЗК) является второй ведущей причиной смертности от рака и является причиной ~10% из всех случаев рака. По оценкам, во всем мире случаи, связанные с КПР 1.9 million и 930,000 смертями в 2022. Несмотря на расширение доступа к обследованиям и лечению в рамках КПР, ожидается, что показатели смертности резко возрастут в районах с низким уровнем ресурсов, что подчеркивает настоятельную необходимость принятия новаторских мер по лечению в рамках КПР. Текущая химиотерапия создает проблемы, такие, как плохая биодоступность, резистентность к многочисленным лекарствам и негативные побочны

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… Capping the 3′ end with inverted thymidine has also been utilized in pegaptanib derivatives resulting in ARC1779 and ARC1905, which prevented nuclease degradation [ 125 , 173 ]. …

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a hematological malignancy of undetermined etiology, possibly linked to chromosomal structural alterations, genetic mutations, presentation and carcinogenicity of variant antigens on cell surface, and the generation of pro-inflammatory microenvironment in the bone marrow. Current drugs are unable to cure this disease, and therefore, decreasing the survival and proliferation of malignant cells to delay disease progression and extend the survival time of patients becomes the primary approach to management. In recent years, the immune system has received increasi

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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(1):53–60. doi: 10.1159/000070661. 85. …

Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

T cells equipped with chimeric antigen receptors (CAR T cells) have recently provided promising advances as a novel immunotherapeutic approach for cancer treatment. CAR T cell therapy has shown stunning results especially in B-cell malignancies; however, it has shown less success against solid tumors, which is more supposed to be related to the specific characteristics of the tumor microenvironment. In this review, we discuss the structure of the CAR, current clinical advantages from finished and ongoing trials, adverse effects, challenges and controversies, new engineering methods of CAR, and

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… The example of off-switch is the administration of Herpes Simplex Virus thymidine kinase (HSV-TK) or inducible caspase-9 (iCasp-9) as self-destruction genes, which could be activated by injection of ganciclovir and FK506 binding protein, respectively. …

Cobalamin deficiency, hyperhomocysteinemia, and dementia.

IntroductionAlthough consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1) Which patients should be tested? (2) What test should be ordered? (3) How are inferences made from such testing? (4) In addition to serum B12, should other tests be ordered? (5) Is B12 deficiency compatible with dementia of the Alzheimer's type? (6) What is to be expected from treatment? (7) How is B12 deficiency treated?MethodsOn January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hype

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… Although the test is not fully understood and probably more complex than a simple explanation, 369 if incubated bone marrow cells or peripheral blood lymphocytes have sufficient folate and cobalamin, nonradioactive deoxyuridine is believed to suppress the thymidylate synthetase conversion of radioactive thymidine … into thymidylate, which is a normal response, but if cells have insufficient folate or cobalamin, nonradioactive deoxyuridine does not suppress the thymidylate synthetase conversion of radioactive thymidine into thymidylate, which is an abnormal response. …

Материалы Международного общества по картированию раковых заболеваний (ИСИС) 18th Ежегодный учебный курс: Ментон, Франция. 7-9 октябрь 2018

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… F-18 fluorocholine (FCH), which traces cell membrane production, looks promising but F-18 fluoro-L-thymidine (FLT) has limited capacity for assessment of the marrow due to high uptake in normal proliferating marrow. … Two PET tracers have especially been studied to explore MF, 18F-Fluorodeoxyglucose (18F-FDG) and 18F-Fluoro-L-thymidine (18F-FLT). 18F-FDG PET in myelofibrosis In 30 patients assessed with FDG PET before stem cell transplantation (SCT), Derlin et al. analyzed the distribution of FDG uptake in bone …

Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review.

Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023

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… It is a prodrug of fluorouracil, which is enzymatically converted to 5-fluorouracil (5-FU) in tumor tissue through the activation pathway of thymidine phosphorylase, and thus, it is able to block DNA synthesis, inducing cell death [ 30 ]. …

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into

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… a level of activity consistent with impaired subunit association of a dimeric enzyme ( Sumi et al., 2002 ). 3.4.6 DPYD The protein Dihydropyrimidine Dehydrogenase (DYPD) encoded by the DPYD gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine …

Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.

γδ T cells are among the first line of defense in the immune system, playing a crucial role in bridging innate and adaptive immunity. Although γδ T cells are crucial for tumor immune surveillance, the complete mechanism by which γδ T cell receptors identify molecular targets in target cells remains unknown. Target cells can produce phosphoantigens (PAgs) via the mevalonate pathway or the methylerythritol phosphate pathway. The BTN3A1-BTN2A1 complex undergoes conformational changes in its extracellular domains upon binding to PAgs, leading to Vγ9Vδ2 T cell recognition. However, the structural b

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… TUBag4 was identified as 5′-triphosphoryl thymidine, with the γ-phosphate group replaced by a low-molecular-weight moiety. TUBag4 stimulates the expansion of peripheral blood Vγ9Vδ2 T cells, supporting the hypothesis that γδ T-cell activation is related to non-peptide ligands [ 9 ]. …

CAR-T cell therapy in Multiple Myeloma: current status and future challenges.

The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the pote

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… For example, expression of the endothelial growth factor receptor (EGFR) enables used of EGFR inhibitors, and herpesvirus thymidine kinase confers sensitivity to ganciclovir [ 116 , 117 ]. …

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"

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… For the analysis of the RNA, cells are secluded with nanobeads that release within the droplet oligonucleotides composed by a stretch of thymidines to capture the mRNA and specific barcodes to recognize mRNA released from the cell within the droplet. …

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… folate cofactor, N5‐10‐methylenetetrahydrofolate, and 5‐fluoro‐2′‐deoxyuridine monophosphate bind to thymidylate synthase to form a covalently bound ternary complex; this binding prevents the formation of thymidylate from 2′‐deoxyuridylate; since thymidylate is a prerequisite for the production of thymidine …

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making dia

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… Moreover, various phase I/II trials have used ADV vectors that encoded the suicide gene HSV thymidine kinase (Ad. …

Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge.

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C a

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… Fluorine-18-Labeled thymidine positron emission tomography (FLT-PET) as an index of cell proliferation after pharmacological ascorbate-based therapy. Radiat. Res. 185 31 – 38 . 10.1667/RR14203.1 26720803 PMC4720529 Cimmino L. Dolgalev I. Wang Y. Yoshimi A. Martin G. H. Wang J. ( 2017 ). …

Hematopoietic Tumors

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… . | 65 , 88 , 89 , 90 Circulating enzyme markers | | X | Levels of both glutathione-S-transferase and thymidine kinase have been reported to predict outcome, but results need confirmation. | 259 , 260 Serum VEGF levels | | X | Small study suggests that pretreatment levels are predictive of remission … Males may have a higher incidence of the T-cell phenotype, which may account for the poorer prognosis. 60 Other reported potential biomarkers of the prognosis include circulating levels of glutathione-S-transferase, thymidine kinase, and vascular endothelial growth factor (VEGF). 261 , 262 , 263 One …

Эгоистические нейрофармацевтики: открытие кровеносного барьера для лечения следующего поколения.

Блокирование мозга крови (ББД) представляет собой огромную проблему в нейрофармакологии, ограничивая доставку терапевтических агентов в мозг. Экзосомы, нанокарьеры природы, стали многообещающим решением из-за их биосовместимости, низкой иммуногенности и врожденной способности пересекать ББД. Тщательное изучение анатомии и физиологии ББД свидетельствует о сложности доставки неврологических наркотиков и подчеркивает ограниченность традиционных методов. В настоящем обзоре изучается потенциал нейрофармацевтики с экзосомной силой, при этом особое внимание уделяется их структурным и функциональным с

Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of lif

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when a

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… Biochanin-A in a LNCaP cell line induced apoptosis incorporated by 3H-thymidine with increased DNA fragmentation, low p21, and cyclin B expression. Animal study with LNCaP xenografts, biochanin-A subsided the prostate cancer load and size of the tumour ( Rice et al. , 2002 ). …