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Bispecific antibody treatment of multiple myeloma: latest updates from the 2022 ASH annual meeting.

BackgroundEffective novel therapies for multiple myeloma (MM) patients who are unresponsive to conventional treatments (triple-class refractory) are an urgent need. Bispecific antibodies (BsAbs) offer a promising new approach to stimulate T cells and induce tumor cell death by targeting molecules on the surface of malignant plasma cells and CD3 on the surface of T cells.ObjectivesAddressing the issue of improving the prognosis of triple-class refractory MM patients has become a significant clinical challenge.DesignThis is a brief report.MethodsThis article summarizes the latest updates of BsAb

Roles of circadian clocks in cancer pathogenesis and treatment.

Circadian clocks are ubiquitous timing mechanisms that generate approximately 24-h rhythms in cellular and bodily functions across nearly all living species. These internal clock systems enable living organisms to anticipate and respond to daily changes in their environment in a timely manner, optimizing temporal physiology and behaviors. Dysregulation of circadian rhythms by genetic and environmental risk factors increases susceptibility to multiple diseases, particularly cancers. A growing number of studies have revealed dynamic crosstalk between circadian clocks and cancer pathways, providi

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… Daily rhythms in the tumor-specific cell cycle can be targeted by various cell cycle-specific anticancer drugs, including those that target the G1 phase (seliciclib), G–S phase transition (palbociclib), S phase (5-FU), and M phase (docetaxel). … Along these lines, preclinical and clinical cancer studies reporting on the chronoutility of cell cycle phase-specific drugs, such as cisplatin or 5-fluorouracil (5-FU) (S phase-specific), docetaxel (M phase-specific), and seliciclib (G1 phase-specific), showed that their maximal efficacy and minimal …

Study of Cinobufagin as a Promising Anticancer Agent in Uveal Melanoma Through Intrinsic Apoptosis Pathway.

Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apopt

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… As shown in Figure 2A , after treatment with cinobufagin for 24 h in OCM1 cells, the percentage of cells in G1 phase significantly increased ( Figure 2B ). Correspondingly, the percentages of S and G2/M phase cells decreased ( Figure 2C ). … The percentages of cells in the (B) G1 phase and (C) S + G2/M phase were quantified. The results are displayed as the mean ± SEM of three independent experiments [* P < 0.05, compared to OCM1 cells incubated with DMSO control]. …

Small compound 6-O-angeloylplenolin induces mitotic arrest and exhibits therapeutic potentials in multiple myeloma.

BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/principal findingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal

Anti-carcinogenic and Anti-bacterial Properties of Selected Spices: Implications in Oral Health.

"Let food be thy medicine and medicine be thy food", as said by the father of medicine, Hippocrates in 431 B.C. Nature has provided us with a variety of treatment modalities in the form of food. For the first 5,000 years of civilization, humans relied on herbs and foods for medicine. Only in the past 60 years have we forgotten our medicinal "roots" in favor of patented medicines. While pharmaceutical ingredients have their value, we should not overlook the well-documented, non-toxic and inexpensive healing properties of food. As an individual we consume food several times a day without a compl

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… Curcumin is responsible for cessation of proliferation of MF by arresting the cell cycle at G0/G1 phase and increasing apoptosis [ 9 ] through a decrease in Bcl-2/Bax ratio [ 10 ]. Ginger inhibits NFκB signaling pathway and thus represses COX-2 expressions [ 5 ]. … Thus honey acts on cancer cell line by inducing cell-growth arrest by cell cycle blockage at the sub-G1 phase [ 33 ]. Previous studies showed that water soluble derivative of honey i.e. propolis and its associated phenolic compounds had antimetastatic effects [ 30 33 34 ]. …

Doxorubicin- and Trastuzumab-Modified Gold Nanoparticles as Potential Multimodal Agents for Targeted Therapy of HER2+ Cancers.

Recently, targeted nanoparticles (NPs) have attracted much attention in cancer treatment due to their high potential as carriers for drug delivery. In this article, we present a novel bioconjugate (DOX-AuNPs-Tmab) consisting of gold nanoparticles (AuNPs, 30 nm) attached to chemotherapeutic agent doxorubicin (DOX) and a monoclonal antibody, trastuzumab (Tmab), which exhibited specific binding to HER2 receptors. The size and shape of synthesized AuNPs, as well as their surface modification, were analyzed by the TEM (transmission electron microscopy) and DLS (dynamic light scattering) methods. Bi

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… After 48 h, an increase in the G0/G1 phase was observed, and subsequently, cells started to accumulate in the S phase up to the next measurement point (72 h). … Overall, taking into account G2/M and S cell cycle arrest, and the reduction in the G1 phase, our results were in good agreement with the induction of apoptosis after treatment due to DNA damage. …

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview.

Over the past years, the identification of genetic alterations in oncogenic drivers in non-small cell lung cancer (NSCLC) has significantly and favorably transformed the outcome of patients who can benefit from targeted therapies such as tyrosine kinase inhibitors. Among these genetic alterations, anaplastic lymphoma kinase (ALK) rearrangements were discovered in 2007 and are present in 3-5% of patients with NSCLC. In addition, radiotherapy remains one of the cornerstones of NSCLC treatment. Moreover, improvements in the field of radiotherapy with the use of hypofractionated or ablative stereo

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… Cancer cells are more radiosensitive in the late G1 phase than the G2-M phase of the cell cycle [ 54 ]. The radiation resistance increases during the S phase and is maximal at the end of the S phase. Radioresistance in the S phase is related to elevated levels of DNA synthesis and repair enzymes. … Cell cycle blockade in the G1 phase of the cell cycle allows time for DNA damage recognition and repair, whereas during G2-M phases of the cell cycle, there is less time for adequate repair, explaining increased radiosensitivity. …

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

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… Monoterpenes inhibits or modulates the expression and function of cyclin D1 and CDK4 ( 101 ), thus preventing the phosphorylation of retinoblastoma protein (Rb) and the subsequent release of E2F transcription factors from Rb, thereby promoting G1 phase arrest. … Studies assessing the effects of EOs on cellular metabolism have demonstrated EOs’ capacity to induce cellular growth arrest through G1 phase ( 106 ). …

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.

Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are commo

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… These conflicting results can be explained in the elegant work of Wu and colleagues: using early- and late-passage mesenchymal stem cells, they found IR exposure resulted in a decreasing trend in arresting both early- and late-passage MSCs in the G0/G1 phase up to 72 h post IR, and a substantial accumulation … Given that more late-passage MSCs were in the G0/G1 phase, the error-prone NHEJ can be the major DNA repair mechanism for late-passage MSCs, which may result in more genomic alterations 87 . …

The role of Rhizoma Paridis saponins on anti-cancer: The potential mechanism and molecular targets.

Cancer is a disease characterized by uncontrolled cell proliferation, leading to excessive growth and invasion that can spread to other parts of the body. Traditional Chinese medicine has made new advancements in the treatment of cancer, providing new perspectives and directions for cancer treatment. Rhizoma Paridis is a widely used Chinese herbal medicine with documented anti-cancer effects dating back to ancient times. Modern research has shown that Rhizoma Paridis saponins (RPS) have various pharmacological activities. RPS can inhibit cancer in multiple ways, such as suppressing tumor growt

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… Studies have shown that p21 can inhibit cell cycle progression at the G1 phase by binding to CDK2/4 and cyclin proteins resulting in inhibiting their activity, thereby suppressing the growth of gefitinib-resistant cells. … Gracillin inhibits the growth of human leukemia HL60 cells and causes cell cycle arrest in the G1 phase. Cells were treated with gracillin resulted in a notable increase in malondialdehyde (MDA) and a dose-dependent reduction in superoxide dismutase (SOD). …

CAR T-Cell Terrapy Opveiled: Навигация за пределы ССЗ и ИКАНС для решения проблем, связанных с отсроченными последствиями, и оптимизации стратегий управления.

Цимерическая антигенная рецепторная (КАР) T-клетологическая терапия положила начало эпохе преобразований в регулировании рецидивов/отсутствий гематологической гематологии. Кульминацией интенсивных испытаний второго этапа, направленных на борьбу с повторной/охотничьей лимфомой, включая различные подтипы, такие, как диффузная большая лимфома B-клеток, фолликулярная лимфома и лимфома мантичной клетки, а также многочисленные миелома и острая лимфоболическая лейкемия B-клеток, стало одобрение различных продуктов CAR-T-клеток для этих конкретных указаний Администрацией по вопросам продовольствия и н

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

Всеобъемлющая оценка взаимодействия капсикум генотипа-окружающей среды с использованием моделей Biplot AMMI и GПЭ в различных поэтапных средах трансплантации.

Генотип х взаимодействие с окружающей средой (ГЭИ) создает серьезную проблему для выявления стабильных, высокоурожайных капсикум генотипов при неоднородных агроклиматических условиях. В настоящем исследовании дается оценка 96 Генотипы различных капсикум (Capsicum annuum L.) four поэтапная трансплантация среды в течение 2022 и 2023 в северо-западных Гималаях для разборки ГЭИ в целях получения фруктовой урожайности и ее составных характеристик. Совокупный анализ разницы показал, что она весьма значительна (p) ≤ 0.01) воздействие генотипа, окружающей среды и ГЭИ на все признаки, что свидетельству

Эволюция антиCD20 Лечения множественных склерозов: оптимизация характеристик и функций антител.

Истощение клеток B с помощью целевых агентов CD20 обычно используется для лечения множественных склерозов (MS), других аутоиммунных заболеваний и некоторых гематологов. Первоначальный очевидный успех с ритуксимабом в использовании MS и нейромиелитной оптики стимулировал развитие антиCD20 моноклональной антителной (mAb) терапии oprelizumab, atumumab и ublituximab, а также антиCD19 mAb inebilizumab. Хотя каждая из них является эффективной в плане целеопределения и истощения элементов В, структурные различия превращаются в различные механизмы действий, влияющие на поддержание истощения и безопасн

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

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… The findings reveal that panobinostat diminishes the viability of cervical cancer cells in a dose- and time-dependent manner, leading to cell cycle arrest in the G0/G1 phase in HeLa cells and in the G2/M phase in SiHa cells. … The administration of this inhibitor resulted in a notable decrease in cell proliferation, followed by cell cycle arrest in the G0/G1 phase, and substantial induction of tumor apoptosis. …

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resi

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… The G0/G1 phase of the cell cycle is an important period for cell volume growth and preparation for DNA replication and synthesis. NEAT1 can affect the chemoresistance of cancer cells by regulating the GO/G1 phase of the cell cycle. … NEAT1 in osteosarcoma (OS) cells can also enhance the resistance of OS cells to cisplatin by promoting the G0/G1 phase of the cell cycle [ 66 ]. …

Синергистические механизмы традиционной китайской медицины и протеиновых ингибаторов в многократной терапии миеломы: всеобъемлющий обзор.

Множественная миелома (ММ) — клональная плазменная порча клеток, характеризующаяся инфильтрацией костного мозга, производством моноклонального иммуноглобулина и многосистемным повреждением. Протеозные ингибиторы (ИП), такие, как бортезомиб, карфилзомиб и иксазомиб, значительно улучшили без прогрессии и общее выживание пациентов с ОМ. Однако резистентность к лекарственным препаратам и неблагоприятные последствия, включая периферическую нейропатию и кардиотоксичность, по-прежнему являются основными ограничениями для долгосрочного контроля за заболеваниями. Цель настоящего обзора заключается в вс

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effec

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting.

With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63r

A Phase II Trial of a Histone Deacetylase Inhibitor Panobinostat in Patients With Low-Grade Neuroendocrine Tumors.

Lessons learnedPancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials.Progression-free survival is more clinically relevant as the primary endpoint (rather than response rate) in phase II trials for low-grade neuroendocrine tumors.BackgroundThe most common subtypes of neuroendocrine tumors (NETs) are pancreatic islet cell tumors and carcinoids, which represent only 2% of all gastrointestinal malignancies. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in various malignancies. In NET