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Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis.

Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was signific

Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.

Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpureosquamulosus Høil (G. pps) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28-35 ppm G. pps extract inhibited cell proliferation by ~46-79%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5-8-fol

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation.

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cel

Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

The Role of NLRP3, a Star of Excellence in Myeloproliferative Neoplasms.

Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is the most widely investigated inflammasome member whose overactivation can be a driver of several carcinomas. It is activated in response to different signals and plays an important role in metabolic disorders and inflammatory and autoimmune diseases. NLRP3 belongs to the pattern recognition receptors (PRRs) family, expressed in numerous immune cells, and it plays its primary function in myeloid cells. NLRP3 has a crucial role in myeloproliferative neoplasms (MPNs), considered to be the diseases best studied in the inflammasome

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM‑1 human myelodysplastic syndrome cell line.

Although certain combination therapies comprising arsenic trioxide (As2O3) with other agents exist for the treatment of several types of human cancer, few As2O3 combination therapies are clinically effective for myelodysplastic syndromes (MDS). Triptolide (TL) may be an effective therapeutic agent for the treatment of MDS. However, to date, there is no combination therapy for MDS with As2O3 and TL. Therefore, the aim of the present study was to investigate this combination therapy on the apoptosis of MDS SKM‑1 cells. The MDS SKM‑1 cells were treated with As2O3, TL or the two in combination at

1'-Acetoxyeugenol Acetate Isolated from Thai Ginger Induces Apoptosis in Human Ovarian Cancer Cells by ROS Production via NADPH Oxidase.

The rhizomes of Alpinia galanga (Thai ginger) have been used extensively as a spice in Southeast Asian and Arabian cuisines and reported to possess a wide range of biological properties, such as antioxidant, antimicrobial, and antibacterial. However, the specific molecular and cellular mechanisms underlying the anti-tumor effects induced by Thai ginger and its corresponding active compounds have been poorly characterized. We found that upon EtOH extraction, Thai ginger extract exhibits cytotoxic activity (IC50 < 10 μg/mL) and triggers cell death via caspase-dependent apoptosis in human ovarian

Bortezomib-induced neurotoxicity in human neurons is the consequence of nicotinamide adenine dinucleotide depletion.

The proteosome inhibitor bortezomib has revolutionized the treatment of multiple hematologic malignancies, but in many cases, its efficacy is limited by a dose-dependent peripheral neuropathy. We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory neurons provide a model system for the study of bortezomib-induced peripheral neuropathy, with promising implications for furthering the mechanistic understanding of and developing treatments for preventing axonal damage. Human neurons in tissue culture displayed distal-to-proximal neurite degeneration when exposed

pIL6-TRAIL-engineered umbilical cord mesenchymal/stromal stem cells are highly cytotoxic for myeloma cells both in vitro and in vivo.

BackgroundMesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors. However, apoptosis is not selective for cancer cells since specific TRAIL receptors are also ex

Mechanisms of IFNalpha-1a-Induced Apoptosis in a Laryngeal Cancer Cell Line.

BACKGROUND Interferon alpha (IFNalpha) exerts its anti-proliferative effect on many human cancers. Among the 13 subtypes of human IFNalpha, IFNalpha-1 subtype has 2 variants, named IFNalpha-1a and IFNalpha-1b, that differ from each other in only 1 amino acid, at residue 114. However, the mechanism by which IFNalpha-1a mediates growth inhibition is still unclear. MATERIAL AND METHODS Human laryngeal carcinoma HEp2 cells were treated with IFNalpha-1a by either transient transfection or exogenous delivery. Western blot and RT-PCR analysis were carried out to assess apoptotic pathways active in IF

Совпадение в полном тексте источника
… The hallmark of ER stress-mediated apoptosis is the activation of caspase 12 in mice or the activation of caspase 4 in humans, which can subsequently induce the cleavage of caspase 3/7 [ 17 , 18 ]. … -12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta Nature 2000 403 98 103 10638761 10.1038/47513 19 Kanehisa M Furumichi M Tanabe M KEGG: New perspectives on genomes, pathways, diseases and drugs Nucleic Acids Res 2017 45 D353 61 27899662 10.1093/nar/gkw1092 PMC5210567 …

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

Существенный потенциал борьбы с миломой вливания зеленого чая и его компонента дигидромиритина.

Множественная миелома (ММ) — фатальная гематологическая порча, характеризующаяся перерастанием моноклонных плазменных клеток. Хотя зеленый чай имеет хорошо задокументированные антивизорные свойства, его специфические последствия для MM по-прежнему плохо характеризуются. Цель этого исследования состояла в изучении антимиеломной активности вливаний четырех репрезентативных зеленых чая и выявлении их эффективных компонентов. Мы обнаружили, что апоптоз клеток MM был вызван зелеными чайными вливаниями в зависимости от концентрации, при этом вливание чая в Билуочун продемонстрировало самую мощную эф

Caspase-Dependent HMGB1 Release from Macrophages Participates in Peripheral Neuropathy Caused by Bortezomib, a Proteasome-Inhibiting Chemotherapeutic Agent, in Mice.

Given the role of macrophage-derived high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, we analyzed the role of HMGB1 and macrophages in the CIPN caused by bortezomib, a proteasome-inhibiting chemotherapeutic agent used for the treatment of multiple myeloma. Repeated administration of bortezomib caused CIPN accompanied by early-stage macrophage accumulation in the dorsal root ganglion. This CIPN was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin alfa capable of accelerating thrombin-dependent degradation of HMGB1, anta

Идентификация NLRP3PYD Homo-Oligomerization Inhibitors с антивоспалительной активностью.

Инфламасомы представляют собой многопротеиновые комплексы, которые представляют собой важнейшие элементы подстрекательской реакции. Регулирование дискриминированного комплекса NLRP3 инфламасома связано с патогенезом таких заболеваний, как множественный склероз, тип 2 сахарный диабет, болезнь Альцгеймера и рак. Несмотря на наличие молекулярных ингибиторов, специфичных для различных компонентов воспламенительных комплексов, в настоящее время ни о каких ингибиторах не сообщается конкретно для NLRP3PYD гомо-олигомеризации. В настоящем исследовании мы описываем идентификацию QM380 и QM381 в качеств

Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines.

Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional

Thalidomide attenuates radiation-induced apoptosis and pro-inflammatory cytokine secretion in oral epithelial cells by promoting LZTS3 expression.

Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors. The presence of oral mucosal rupture and ulcerative lesions, which are the defining features of this condition, can significantly affect the quality of life of patients. Additionally, it can interfere with tumor therapy and contribute to an unfavorable prognosis. Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development. Moreover, thalidomide (THD) has been r

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway.

Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathway