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Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants.

Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porok

Enhanced Antitumor Activity and Induction of Immunogenic Cell Death in NUT Carcinoma Cells by Combining Oncolytic Viruses with the Dual Inhibitor NEO2734.

NUT carcinoma (NC) is a rare exceptionally aggressive malignancy, defined by NUTM1 gene translocations, most commonly generating a BRD4::NUTM1 fusion that results in a poor prognosis and limited therapeutic options. Oncolytic virotherapy has emerged as a promising strategy for NC, and the dual bromodomain and extra-terminal domain (BET) and p300/CBP inhibitor NEO2734 has demonstrated potent antiproliferative activity. To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinan

Is the Scope of Costs Considered in Budget Impact Analyses for Anticancer Drugs Rational? A Systematic Review and Comparative Study.

Background: With the increasing disease burden of cancer worldwide, more and more anticancer drugs have been approved in many countries, and the results of budget impact analyses (BIAs) have become important evidence for related reimbursement decisions. Objectives: We systematically reviewed whether BIAs for anticancer drugs consider the scope of costs rationally and compared the results of different cost scopes to provide suggestions for future analyses and decision-making. Methods: Eligible BIAs published in PubMed, Embase, Web of Science, and the Cochrane Library from 2016 to 2021 were iden

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

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… By suppressing the telomerase and cyclin D levels in ER-positive cancers, retinoids can cause aging and cell cycle blockage. They also promote growth suppression in ER-negative cancers by upregulating the expression of retinoblastoma proteins p21 and p53. …

Artificial intelligence in drug discovery and development.

Artificial intelligence-integrated drug discovery and development has accelerated the growth of the pharmaceutical sector, leading to a revolutionary change in the pharma industry. Here, we discuss areas of integration, tools, and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them.

Evolving Paradigms in the Management of Multiple Myeloma: Novel Agents and Targeted Therapies.

Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone mar

:: разработка системы запретов на использование кинжалов на основе капсаицина для модуляции взаимодействия киназы A/PHB2 и митофагии в раковых клетках.

A/AURKA — киназа серена/трионина, часто перевоплощающаяся в рак. Недавние открытия указывают на подклеточные пулы АУРКА, в том числе в митохондрии. Там AURKA вызывает расчистку органеллой митофагией вместе с автоматическим посредником LC3 и его рецептором PHB2. Здесь мы показываем, что натуральный продукт капсаицин изменяет взаимодействие AURKA/PHB2. Мы синтезируем 16 Аналоговые аналоги капсаицина и передача энергии/флюоресценция Förster's Energy Transport/Fluorescence Life Time Imageing Microscope (FRET/FLIM) в клетках рака груди показывают, что соединения 12 и 13 :: расширение взаимодействия

Gambogic Acid as a Candidate for Cancer Therapy: A Review.

Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form mice

Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes.

Improved understanding as to the biology of multiple myeloma (MM) and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus

Targeting erythroid progenitor cell metabolism to enhance cancer immunotherapy.

While cancer immunotherapy has transformed clinical management for cancer patients, its low response rates remain a critical challenge to be addressed. Tumor immune evasion now extends beyond the tumor microenvironment (TME), as advanced tumors induce extramedullary hematopoiesis (EMH) in the spleen, leading to a substantial expansion of erythroid progenitor cells (EPCs) with potent immunosuppressive capacity. EPCs are typically transient populations in erythroid maturation and differentiation; however, under tumor burden, they undergo profound metabolic reprogramming that exacerbates their im

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

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… Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106:296–303. 10.1182/blood-2005-01-0034 16. Kaiser MF, Walker BA, Hockley SL, Begum DB, Wardell CP, Gonzalez D, et al. …

Role of nuclear factor-kappa B in feline injection site sarcoma.

BackgroundChronic inflammation has been implicated in sarcomagenesis. Among various factors, activation of nuclear factor-kappa B (NF-κB) signaling pathway has been documented being able to target genes associated with tumor progression and up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. Feline injection sites sarcomas (FISS) are malignant entities derived from the mesenchymal origin. The disease has been considered to be associated with vaccine adjuvant, aluminum, which serves as a stimulus continuously inducing overzealous inflammator

First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.

AZD5153, a reversible, bivalent inhibitor of the bromodomain and extraterminal family protein BRD4, has preclinical activity in multiple tumors. This first-in-human, phase I study investigated AZD5153 alone or with olaparib in patients with relapsed/refractory solid tumors or lymphoma. Adults with relapsed tumors intolerant of, or refractory to, prior therapies received escalating doses of oral AZD5153 once daily or twice daily continuously (21-day cycles), or AZD5153 once daily/twice daily continuously or intermittently plus olaparib 300 mg twice daily, until disease progression or unacceptab

Pancreatic cancer: chemotherapy and radiotherapy.

Pancreatic cancer in many cases appears in a non-curatively resectable stage when the diagnosis is made. Palliative treatment become an option in the patients with advanced stage. The present article reviewed chemotherapy and radiotherapy in various advanced stage of pancreatic cancer.

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bo

Сокращение ячеек не улучшает восстановления мышей при искусственном обезвоживании аутоиммунной энцефаломиэлитом (EAE).

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся демиэлированием на основе иммунных клеток и прогрессивным нейродегенерацией. В последнее время в хронических поражениях MS наблюдались чувствительные клетки (КЦ), что указывает на их возможное участие в прогрессии заболеваний. Вместе с тем роль СК и потенциальные терапевтические выгоды их сокращения с помощью сенолитной терапии еще предстоит определить в экспериментальной аутоиммунной энцефаломиелите (EAE), широко используемой доклинической модели MS. Здесь мы показываем, чт

Chemical Patterns of Proteasome Inhibitors: Lessons Learned from Two Decades of Drug Design.

Drug discovery now faces a new challenge, where the availability of experimental data is no longer the limiting step, and instead, making sense of the data has gained a new level of importance, propelled by the extensive incorporation of cheminformatics and bioinformatics methodologies into the drug discovery and development pipeline. These enable, for example, the inference of structure-activity relationships that can be useful in the discovery of new drug candidates. One of the therapeutic applications that could benefit from this type of data mining is proteasome inhibition, given that mult

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Despite the current available multiple therapeutic options, the prognosis for high-risk NB patients remains unsatisfactory and makes the disease a clear unmet medical need. Thus, more tailored therapeutic approaches are warranted to improve both the quality of life and the survival of the patients. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a key role in several diseases, including cancer. Preclinical and clinical studies in NB patients convergently indicate that MIF exerts pro-tumorige

Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer.

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-canc