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Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinical

Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function.

Estrogens exert their physiological and pathophysiological effects via cellular receptors, named ERα, ERβ, and G-protein coupled estrogen receptor (GPER). Estrogen-regulated physiology is tightly controlled by factors that regulate estrogen bioavailability and receptor sensitivity, while disruption of these control mechanisms can result in loss of reproductive function, cancer, cardiovascular and neurodegenerative disease, obesity, insulin resistance, endometriosis, and systemic lupus erythematosus. Restoration of estrogen physiology by modulating estrogen bioavailability or receptor activity

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.

Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various

Use of Cannabis and Cannabinoids for Treatment of Cancer.

The endocannabinoid system (ECS) is an ancient homeostasis mechanism operating from embryonic stages to adulthood. It controls the growth and development of many cells and cell lineages. Dysregulation of the components of the ECS may result in uncontrolled proliferation, adhesion, invasion, inhibition of apoptosis and increased vascularization, leading to the development of various malignancies. Cancer is the disease of uncontrolled cell division. In this review, we will discuss whether the changes to the ECS are a cause or a consequence of malignization and whether different tissues react dif

Targeting the DNA Damage Response for Cancer Therapy.

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucid

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… NHEJ does not demand homology at the broken ends and is an error-prone repair method that can occur at various stages of the cell cycle but is prevalent during the G1 phase. …

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-

Efficacy and Safety of Daratumumab, Pomalidomide, and Dexamethasone (DPd) Compared to Daratumumab, Bortezomib, and Dexamethasone (DVd) in Daratumumab-Naïve Relapsed Multiple Myeloma.

Daratumumab-based combinations with pomalidomide/dexamethasone (DPd), or bortezomib/dexamethasone (DVd), have shown activity in relapsed/refractory multiple myeloma (RRMM) patients. However, no direct comparisons of safety or efficacy of the two regimens have been published to date. We conducted a retrospective study to compare the safety and efficacy of DPd and DVd in daratumumab-naïve RRMM patients. We included 140 daratumumab-naïve patients who had received DPd or DVd for RRMM. Overall, the DPd group had a greater number of patients who had high-risk disease characteristics. Although respon

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers.

Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present sig

Структурный анализ процесса сбора света с помощью антенн, содержащих родопсины в морской архееи Асгарда.

Акватические бактериальные редопсиновые протонные насосы собирают световую энергию для фотогетертрофного роста и, как известно, содержат гидроксилированные каротеи, расширяющие волны используемого света, но они не характеризуются морской археей. Здесь, комбинируя морскую хромофорную экстракт с очищенными архейскими родопсинами, выявленными в морских метагеномах, мы показываем передачу легкой энергии из различных гидроксилоидных каротеоидных в геймдаллархаэ (HeimdallRs) из некультурных морских планктонных членов «Candidatus Cariarachaeceae» (Candidatus Asgardarchaeota). Эти светообрабатывающие

Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma.

The immune system is strongly linked to the maintenance of healthy bone. Inflammatory cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as osteoclast differentiation modulators and as such, must be carefully monitored and regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone diseases are tied to IL-6 overexpression, including rheumatoid arthritis, osteop

Эффективность бортезомиба в сочетании с гипер-CVAD у взрослых с рецидивом острой лимфоболической лейкемии или положительными измеримыми остаточными заболеваниями; воздействие бортезомиба в лейкемии.

Несмотря на прогресс, достигнутый в лечении острой лимфоболической лейкемии (ОЛЛ), рецидив остается наиболее серьезной проблемой в деле улучшения прогнозирования. Оценка измеримых остаточных заболеваний (MRD) может спрогнозировать рецидив костного мозга на основе позитивности MRD. Поскольку доступ к инновационным методам лечения по-прежнему ограничен из-за высоких затрат, химиотерапия является широко используемым вариантом лечения. Об эффективности сочетания бортезомби и Hyper-CVAD сообщалось у пациентов с множественной миеломой; однако его эффективность еще не была подтверждена у пациентов, и

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… Notably, bortezomib has been reported to halt the cell cycle, arresting cells in the G1 phase and inducing apoptosis in leukemia cell lines (MOLT-4) [ 12 ]. …

Individual Trade-Offs Between Possible Benefits and Risks of Cancer Treatments: Results from a Stated Preference Study with Patients with Multiple Myeloma.

BACKGROUND: The objectives of this study were to elicit the preferences of patients with multiple myeloma regarding the possible benefits and risks of cancer treatments and to illustrate how such data may be used to estimate patients' acceptance of new treatments. PATIENTS AND METHODS: Patients with multiple myeloma from the cancer charity Myeloma UK were invited to participate in an online survey based on multicriteria decision analysis and swing weighting to elicit individual stated preferences for the following attributes: (a) 1-year progression-free survival (PFS, ranging from 50% to 90%)

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… Consequently, the downregulation of miR-190a-3p upregulates its target gene, PTEN, ultimately leading to cell cycle arrest at the G1 phase. 60 Similarly, in non-small cell lung cancer (NSCLC), Triptolide targets and inhibits miR-21, thereby alleviating its suppression of PTEN. … Under simulated tumor microenvironment conditions, TPL/NPs significantly lowered the IC 50 against MDA-MB-231 cells (4.96–9.5 μg/mL) compared to free Triptolide (28.02–31.94 μg/mL), induced higher apoptosis rates, and arrested the cell cycle at the G0/ G1 phase. …

SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.

Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein

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… Together with other PTMs, SUMOylation is involved in the regulation of pRB activity during the cell cycle. pRB is SUMOylated during the early G1 phase. … SUMOylation of Rb Enhances its Binding with CDK2 and Phosphorylation at Early G1 Phase. Cell Cycle 15 (13), 1724–1732. 10.1080/15384101.2016.1182267 Moschos S. J., Jukic D. M., Athanassiou C., Bhargava R., Dacic S., Wang X., et al. (2010). …

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigeneti

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

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… For example, elevated levels of Zinc Finger E-Box-Binding Homeobox 2 (ZEB2) enhance the proportion of colorectal CSCs in the G0/G1 phase, contributing to resistance against platinum-based treatments [ 55 ]. …

Воздействие остаточных клональных плазменных клеток в фазе S во время аутологической трансплантации стволовых клеток на клинические результаты.

Автологическая трансплантация стволовых клеток (ASCT) является ключевой терапевтической стратегией для многих пациентов, у которых диагностируется миелома (ММ), однако ранние рецидивы после трансплантации остаются серьезной клинической проблемой. Испытание на распространение плазменных клеток (ПХПРО), в ходе которого определяется доля клональных плазменных клеток в костном мозге в фазе S-фазе (S-фаза %), представляет собой масштабируемую альтернативу измерению их скорости распространения по сравнению со старым индексом плазменных клеток (PCLI). Воздействие S-фазы в остаточных клональных плазме

Поэтапное сокращение сотрудничества между людьми.

Сотрудничество между людьми носит динамичный характер и зачастую сокращается даже при наличии благоприятных условий conditions1-4. Многие из существующих теорий объясняют уменьшение масштабов сотрудничества с точки зрения стратегического поведения или обучения, сформулированного как свидетельство рационального поведения или продвижения в направлении rationality5-9. Здесь мы показываем, что одним из ключевых источников долгосрочного спада являются отклонения от рационального поведения, которые систематически меняются с течением времени. Мы анализируем естественную социальную дилемму на местах,

Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

UnlabelledThis study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa) to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb) to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day) and intravenous cetuximab (400 mg/m(2) followed by weekly 250 mg/m(2)) in 28-day c