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A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy.

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tum

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… Nowadays, cytotoxic payloads usually act as DNA-damaging agents or tubulin inhibitors, but novel potential drugs under investigation include inhibitors of B-cell lymphoma-extra large (Bcl-xL) anti-apoptotic protein, RNA and Niacinamide phosphate ribose transferase (NAMPT) inhibitors, and carmaphycins …

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor c

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… Olaparib is a United States Food and Drug Administration (FDA)-approved dual inhibitor of poly [ADP-ribose] polymerase 1 (PARP-1) and PARP-2 for the treatment of advanced ovarian and breast cancers. …

RNA метилтрансферазы METTL8 устанавливает m3C32 в митохондриальном tRNASThr/Ser (UCN) для оптимизации структуры trNA и митохондриального перевода.

Модифицированные нуклеотиды в tRNA являются важными определяющими факторами сворачивания, структуры и функции. Здесь мы идентифицируем METTL8 как митохондриальный белок и активный РНК метилтрансферазы, ответственный за установку m3C32 в митохондриале человека (mt-)tRNAThr и mt-tRNAser (UCN). METTL8 имеет перекрестные связи с антикодоновой стволовой петлей (ASL) многих мт-тРНК в клетках, в связи с чем возникает вопрос о том, каким образом достигается целевая специфичность метилирования. Расчленение элементов распознавания mt-tRNA выявило наличие U34G35 и t6A37/(ms2)i6A37, которые одновременно п

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… Introduction of specific base and ribose modifications into eukaryotic tRNAs is an important step during tRNA maturation, which can not only regulate their roles as amino acid adaptors during translation but also influence other extra-translational functions, such as the production of tRNA-derived small …

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

Clinical Posters From JADPRO Live 2024

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Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… Nucleotide Metabolism Cancer cell growth and proliferation depend on de novo nucleotide synthesis from intermediates in the TCA cycle, glucose-derived ribose sugars from the pentose phosphate pathway (PPP) and amino acids that generate purines and pyrimidine nucleotides. …

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeut

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… The poly (ADP-ribose) polymerase (PARP) enzyme acts as a highly sensitive sensor for DNA damage, which recruits DNA repair proteins to damage sites to facilitate efficient repair [ 185 ]. …

Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (Review).

In oncology, liquid biopsy is used in the detection of next-generation analytes, such as tumor cells, cell-free nucleic acids and exosomes in peripheral blood and other body fluids from cancer patients. It is considered one of the most advanced non-invasive diagnostic systems to enable clinically relevant actions and implement precision medicine. Medical actions include, but are not limited to, early diagnosis, staging, prognosis, anticipation (lead time) and the prediction of therapy responses, as well as follow-up. Historically, the applications of liquid biopsy in cancer have focused on cir

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… A second example was published by Goodall et al ( 159 ) on cfDNA to guide prostate cancer treatment with poly(ADP)-ribose polymerase (PARP) inhibition. …

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity. To address this gap, the international consensus-driven SPIRIT-DEFINE checklist was developed through a robust methodological framework for guideline development, with the aim to improve completeness and clarity in EPDF t

Influence of the Mediterranean Diet on Healthy Aging.

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologi

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… Oleuropein (one of the main phenolic components of green olive pulp) reduced Poly ADP-ribose polymerase (PARP)-1 activation, protecting neuronal cells from oxidative damage. …

Иммунотерапия Множественной миеломы: Текущий статус как пролог в будущее.

Площадь терапевтических мер по лечению множественной миеломы претерпела сейсмические изменения с начала нынешнего столетия. Это было обусловлено главным образом введением новых классов небольших молекул, таких, как протеазонные блокаторы (например, бортезомиб) и иммуноводители (например, линалидомид), а также иммунотерапевтическими агентами, начиная с anti-CD38 Моноклональная антитела Daratumumab 2015. В последнее время в арсенал лекарств, доступных для борьбы с этим злоумышленником, добавились и другие иммунотерапии. В их число входят продукты биконкретных теклистамб, талькетамаб и эльранатам

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… Its primary role appears to result from its cyclic ADP ribose hydrolase activity, the products of which are important regulators of intracellular calcium levels. …

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

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… Calpain 1 endorses permeabilization of lysosomal membranes and triggers the release of cathepsin B and deoxyribonuclease II to induce apoptosis by activating poly (ADP-ribose) polymerase (PARP) cleavage. …

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

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… Poly-ADP-Ribose Polymerase (PARP) Inhibition PARP is a protein involved in DNA repair. …

Митохондриальная передача метаболических перепрограмм и лекарственная устойчивость в метастазе костей: механизмы и терапевтические стратегии.

Кость это one из наиболее распространенных участков удаленного метастаза в твердых опухолях, в частности рак груди, рак простаты и рак легких. Метатические повреждения костей часто свидетельствуют о стойком сопротивлении многосистемной терапии, включая химиотерапию, целевую терапию, эндокринную терапию и ингибиторы иммунных контрольно-пропускных пунктов (ИПК). Накопляющиеся данные свидетельствуют о том, что метаболическая перепрограммирование в пределах костной микроокружающей среды способствует этому сопротивлению, однако механизмы в верхнем течении по-прежнему недостаточно понятны. В качеств

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… Poly(ADP-ribose) polymerase 1 (PARP1) enhances single-strand break repair capacity in a manner dependent on nicotinamide phosphoribosyltransferase (NAMPT) upregulation ( 160 ). …

Gut microbiota and microbial metabolites for osteoporosis.

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can

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… . | After FMT treatment, secondary bile acids and other metabolites (arabinose, ribose, and inosine) may help extend the healthy lifespan and longevity in prematurely aged mice. | Gavage twice a week for two weeks, and then once a week until death. | antibiotic cocktail with 1 g/L ampicillin, 0.5 g/L …

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of b

Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis.

The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a

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… , it can promote FasL mRNA expression and enhance the activity of p51, p21, and GADD45 signaling pathways. [ 156 ] Seo et al. found that quercetin induces caspase‐dependent extrinsic apoptosis upregulating the levels of cleaved caspase‐8 and cleaved caspase‐3, and inducing the cleavage of poly (ADP‐ribose …

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age

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… Tarantini S Yabluchanskiy A Csipo T Fulop G Kiss T Balasubramanian P DelFavero J Ahire C Ungvari A Nyul-Toth A Farkas E Benyo Z Toth A Csiszar A Ungvari Z Treatment with the poly(ADP-ribose) polymerase inhibitor PJ-34 improves cerebromicrovascular endothelial function, neurovascular coupling responses …