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Криопрезентация против пересадки свежих стволовых клеток в автоматической трансплантации для множественной миеломы: воздействие на раннюю токсичность и пересадку.

ВВЕДЕНИЕ: Аутологическая трансплантация стволовых клеток (ASCT) по-прежнему является краеугольным камнем терапии для имеющих на это право пациентов с множественной миеломой. Криопирование гематополиетических трансплантаций обеспечивает логистическую гибкость, но может способствовать повышению токсичности, связанной с процедурой, и использованию ресурсов. Мы провели two- Фаза, неслучайное двухнациональное исследование в высших центрах Сантьяго, Чили, и Севилье, Испания, сравнивая криопрезентированные и некриопретрофированные трансплантаты у пациентов, проходящих ACCT. На ретроспективном этапе20

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… However, cryopreservation also introduces additional procedural complexity, costs, and exposure to cryoprotective agents, most commonly dimethyl sulfoxide (DMSO). 2 The biological and clinical consequences of graft cryopreservation remain incompletely understood. … For the cryopreserved (CRYO) cohort, products were formulated with 10% dimethyl sulfoxide (DMSO) as a cryoprotectant and stored in liquid nitrogen (≤−150 °C) until infusion. …

Selinexor, a selective inhibitor of nuclear export, shows anti-proliferative and anti-migratory effects on male germ cells in vitro.

BackgroundSelinexor (SLX), a selective inhibitor of nuclear export (SINE), has been shown to interfere with nuclear export mechanisms and to exert antitumor effects in a variety of cancer cell types. It is known to regulate multiple fundamental cellular processes, including the DNA damage response, cell proliferation, and stress signaling pathways. Nevertheless, its potential effects on reproductive cells remain inadequately characterized. The present study was aimed to investigate the cytotoxic, apoptotic, anti-proliferative and anti-migratory effects of SLX on GC1 (spermatogonia) and GC2 (sp

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… Following incubation, the medium was carefully removed, and the formazan crystals were dissolved in dimethyl sulfoxide (DMSO) (Sigma). Absorbance was measured at 570 nm using a microplate Multiskan GO spectrophotometer (Thermo Scientific). … Abbreviations Acute Myeloid Leukemia Dimethyl Sulfoxide European Medicines Agency Epithelial Mesenchymal Transition U.S. …

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, th

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… sulfoxide (DMSO). … Abbreviations China Food and Drug Administration Corepressor of RE1-silencing transcription factor Chemoradiation therapy Dimethyl sulfoxide DNA methyltransferase Epstein Barr virus Epidermal growth factor receptor Epithelial–mesenchymal transition Endoplasmic reticulum Esophageal squamous …

Механизм поглощения и токсичности антителного препарата BCMA в сочетании с полезной нагрузкой MMAF неантигенными функционирующими элементами.

Belantamab mafodotin, антитело-наркомания (ADC), продемонстрировал высокую эффективность в множестве миеломы. Он состоит из гуманизированного антиклектового антигена (BCMA) IgG1 моноклонального антитела, смешанного с монометил-ауристатином F (MMAF) с помощью манимидокапроилового связующего устройства. С помощью неизвестных механизмов поступили сообщения о связанных с окультизмом неблагоприятных явлениях, в частности о роговицах, в которых содержится АКЦ, в том числе белантамб мафодотин. В ходе этого исследования изучался механизм поглощения и цитотоксичности белантамбом мафодотином, содержащим

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… EIPA (in dimethyl sulfoxide stock, A3085) was prepared in culture medium for a final concentration of 0–50 μM. Following treatment, plates were incubated for 30 min at room temperature (RT) in the dark. … S6 HCEC and RPTEC were pre-treated with EIPA for 30 min or 3 h; p -values for the test of no change relative to baseline ADC, antibody–drug conjugate; CI, confidence interval; Ctrl, control; DMSO, dimethyl sulfoxide; EIPA, 5-(N-Ethyl-N-isopropyl)amiloride; h, hours; HCEC, human corneal epithelial cells …

Необычная реакция профилей белков HERV-W в множестве склерозов: потенциальные биомаркеры для развития заболеваний.

ВВЕДЕНИЕ: Протеины конверта syncytin-1 и fHERV-W из эндогенной ретровирусной семьи человека "W" (HERV-W) были определены в качестве потенциальных факторов риска при множественном склерозе (MS). Цель этого исследования заключается в оценке как юморальной, так и клеточной иммунной реакции на антигенные пептиды, получаемые из этих белков, в различных клинических формах и фазах МУ. МЕТОДЫ: Косвенный анализ иммуносорбента, связанного с ферментом (ELISA), использовался для измерения ответов на иммуноглобулин G (IgG) syncytin-1env 486-500 и fHERV-Wenv 486-504 Пептиды у пациентов с склерозом. Дискрими

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… The cell pellet was then resuspended in a mixture of 10% dimethyl sulfoxide (DMSO) and 1 ml of fetal bovine serum and stored temporarily at -80° in a MrFrostie container before being transferred to liquid nitrogen (-196°C). … CN, negative control; DMSO, Dimethyl sulfoxide; Sync, syncytin-1 env 486-500 ; pH-W, pHERV-W env 486-504 ; IFN-γ, interferon-gamma; GM-CSF, Granulocyte-macrophage colony-stimulating factor; TNF, tumor necrosis factor-alpha; IL, interleukin; HC, healthy control; RR-SMS, relapsing-remitting stable phase …

Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib.

One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulati

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… sulfoxide molecular biology polyvinylidene fluoride one-way analysis of variance alternative non-homologous end joining Introduction Multiple myeloma (MM) is a class of malignant plasma cell clonal proliferative diseases of the bone marrow. … Stroke-physiological saline solution (SPSS) and dimethyl sulfoxide (DMSO) were provided by Beyotime (Shanghai, CHN). BALB/c nude mice were obtained from Vital River Laboratories (Beijing, CHN). The 20S-PSM kit (SED321Hu 96T) was purchased from cloud-clone (Wuhan). …

Протекционный субъект PSMD1 является ключевой терапевтической целью в множестве миеломы.

Мы пришли к выводу, что PSMD1 - ключевой субъект протеиновой регуляционной частицы 19S - был чрезмерно экспрессирован и коррелировал с плохим прогнозом в множестве миеломы (ММ). Генетическое истощение PSMD1 снизило жизнеспособность раковых клеток, вызвало поликутилизированное накопление белка и способствовало апоптозу. Протеомический анализ показал активацию иммунных путей, что свидетельствует о потенциале иммунной модуляции. Нацеливание PSMD1 на незначительную поражающую РНК (SIRNA), доставляемую через липидные наночастицы (LNPs), уменьшило рост опухоли в линиях клеток MM и первичных проб пац

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… (C) H929 cells were treated with either 50nM LNP-SCT siRNA or LNP-PSMD1 siRNA for 24 hours, or with dimethyl sulfoxide (DMSO) (CT), or bortezomib (BTZ) at 1μM for 3 hours. … (C) H929 cells were treated with either 50nM LNP-SCT siRNA or LNP-PSMD1 siRNA for 24 hours, or with dimethyl sulfoxide (DMSO) (CT), or bortezomib (BTZ) at 1μM for 3 hours. …

Dual targeting of protein translation and nuclear protein export results in enhanced antimyeloma effects.

Selinexor (KPT-330) is a small molecule inhibitor of XPO1, which mediates the transport of tumor suppressor proteins, oncogene messenger RNAs, and other proteins involved in governing cell growthfrom the cell nucleus to the cytoplasm. It is overexpressed in many cancer types. Because eukaryotic translation initiator factor 4E (eIF4E) plays a critical role in protein translation in cancer cells in multiple myeloma (MM), we evaluated the effectiveness of combined inhibition of protein translation and nuclear export in MM. Selinexor, an inhibitor of nuclear protein export, dose-dependently decrea

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… sulfoxide at a final concentration of 1 mM. … Rocaglamide is an eIF4A inhibitor (selleckchem) and was dissolved in dimethyl sulfoxide at a final concentration of 1 mM. …

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

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… The dried extracts were tared to constant weight and dissolved in dimethyl sulfoxide (DMSO) to prepare 50,000 ppm (parts per million) stock solutions. Cell culture Cell lines used in this study included acute myeloid leukemia (AML), lymphoma and multiple myeloma. … Abbreviations acute myeloid leukemia annexin V cell counting kit-8 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester dimethyl sulfoxide Gymnopilus purpureosquamulosus inhibitory (50%) concentration internal transcribed spacer 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine …

CXCL12 in astrocytes contributes to bone cancer pain through CXCR4-mediated neuronal sensitization and glial activation in rat spinal cord.

BackgroundPrevious studies have demonstrated that chemokine CXCL12 and its receptor CXCR4 are critical for pain sensitization, but the mechanisms involved are not clear. In this study, we investigated the specific cellular mechanisms of CXCL12/CXCR4 chemokine signaling in the development and maintenance of bone cancer pain after tumor cell implantation (TCI).MethodsTCI in the tibial cavity of rats was used to establish a bone cancer pain model. Mechanical allodynia and thermal hyperalgesia were determined by measuring the paw withdrawal threshold and latency, respectively. The protein expressi

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… SP600125 were dissolved in dimethyl sulfoxide (DMSO) and diluted in NS (final concentration of DMSO: 1%). … Abbreviations aCSF: Artificial cerebrospinal fluid; ANOVA: Analysis of variance; BCP: Bone cancer pain; CGRP: Calcitonin gene-related peptide; CNS: Central nervous system; CXCL12: Chemokine CXC motif ligand 12; CXCR4: Chemokine CXC motif receptor 4; DMSO: Dimethyl sulfoxide; DRG: Dorsal root ganglion …

Considerations on the mechanism of action of artemisinin antimalarials: part 1--the 'carbon radical' and 'heme' hypotheses.

The isolation of artemisinin from the traditional medicinal herb qīng hāo (Artemisia annua), its characterization as a peroxide and preparat … o those conducted under highly reducing and eminently artificial conditions, usually in the solvent dimethyl sulfoxide (DMSO) that both forms well characterized complexes with heme-Fe(2+) and actually assists in driving single electron transfer processes. It is noted that alkylated products tend to form in high yields under the last conditions, and this aspect is re …

Усовершенствованная последовательность транскриптомов и искусственный интеллект/машинное обучение (AI/ML) в имитируемом псориазом воспалении кератиноцитов человека.

ВВЕДЕНИЕ: Несмотря на то, что модель Keratinocyte HaCAT использовалась в предыдущих исследованиях для изучения воздействия антипсориатических агентов, по-прежнему отсутствует полное понимание механизма имитируемого имимодом распространения и трансдукции сигналов в псориазных кератиноцитах. ЦЕЛИ: Данное исследование было направлено на изучение молекулярных механизмов и путей, связанных с воспалением, подобным псориазу, в результате IMQ в кератиноцитах человека. МАТЕРИАЛЫ И МЕТОДЫ: Клетки HACAT подвергались воздействию различных концентраций IMQ, чтобы вызвать воспаление, аналогичное тому, котор

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… The compounds 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO), and imiquimod (IMQ) were acquired from Sigma–Aldrich (Merck KGaA, Darmstadt, Germany). Fetal bovine serum (FBS) was obtained from Invitrogen (Carlsbad, CA, USA). 2.2. … List of Abbreviations Artificial intelligence Dulbecco’s Modified Eagle medium Dimethyl sulfoxide Fetal bovine serum Gene Set Enrichment Analysis Genome-wide association studies Human leukocyte antigen Interferon-gamma Interleukin Imiquimod Ingenuity Pathway Analysis Machine Learning Mechanism …

Low-dose peripheral blood stem cell graft after high-dose chemotherapy - an evaluation of hematopoietic reconstitution.

BackgroundHigh-dose (HD) chemotherapy followed by autologous blood stem-cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) patients. However, the collection of sufficient peripheral blood stem cell (PBSC) grafts can be challenging, and the question arises whether reinfusion of low-dose grafts will lead to a hematopoietic recovery.MethodsThe hematopoietic recovery of 148 MM patients who underwent HD melphalan chemotherapy and received PBSC transplants with varying CD34+ cells doses (3-4 × 106 [n = 86], 2-2.5 × 106 [n = 53], 6 [n = 9] per kg body weight [bw]) was ana

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… After storage, the PBSC products were centrifuged and diluted with autologous plasma or resuspension medium (Plasmalyte A, Baxter, Unterschleissheim, Germany or Composol PS, Fresenius Kabi, Bad Homburg, Germany) and CryoSure-D dimethyl sulfoxide (DMSO, WAK-Chemie Medical, Steinbach, Germany). … Abbreviations Autologous blood stem cell transplantation Body weight Cyclophosphamide, doxorubicin, dexamethasone Confidence interval complete remission Cryosure-D dimethyl sulfoxide Granulocyte-colony-stimulating factor High-dose Hazard ratio International Staging System Liter Leukapheresis …

HERV-W Env вызывает нейронный пироптоз с помощью NLRP3-CASP1-GSDMD Pathway в недавней Шизофрении.

HERVs (человеческие эндогенные ретровирусы) являются остатками древних внешних ретровирусов, которые интегрировались в геном человека, особенно в микробных клетках. Среди них белковый ген HERV-Wenv (Human Internal revoiruses W семейный белок), расположенный на хромосоме 7 и выраженный главным образом в плаценте человека, тесно связан с различными нейропсихиатрическими расстройствами, включая шизофрению, а также аутоиммунные заболевания и рак. Недавние исследования выявили аномальное выражение цитокина в качестве ключевого фактора в патофизиологии шизофрении. В частности, повышенные уровни сыво

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… Dimethyl fumarate (DMF) (MedChemExpress, HY-17363, Monmouth Junction, NJ, USA) at 5 μmol in dimethyl sulfoxide (DMSO). CY-09 (MedChemExpress, HY-103666, Monmouth Junction, NJ, USA) at 1 μmol in DMSO. ML385 (MedChemExpress, HY-100523, Monmouth Junction, NJ, USA) at 5 μmol in DMSO. …

History and Development of Autologous Stem Cell Transplantation for Acute Myeloid Leukemia.

This review describes the development of cryopreservation, the birth of autologous stem cell transplantation (ASCT) and its past and present use to consolidate adult patients with acute myelogenous leukemia (AML). It summarizes the first autografts in patients in relapse, the experience of autografting in complete remission (CR), using bone marrow unpurged or purged in vitro with cyclophosphamide-derivatives, and the important shift to peripheral blood stem cells. The review also discusses the results of recent studies in favor of the use of ASCT to consolidate good- and intermediate-risk pati

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… We used a freezing scheme ( Figure 1 ) in which BM suspended in tissue culture medium (M199) with a final 10% dimethyl sulfoxide (DMSO) concentration was refrigerated at a fixed cooling rate of −1°C/min [ 8 ] with permananent temperature recording to detect the release of the heat of fusion and supercool … sulfoxide Cryobiology 1970 7 136 40 10.1016/0011-2240(70)90010-6 5498351 [7] Schaefer UW Dicke KA Van Bekkum DW Recovery of hematopoiesis in lethally irradiated monkeys by frozen allogeneic bone marrow grafts Rev Eur Etud Clin Biol 1972 17 483 8 4630654 [8] Gorin NC Bull MI Herzig GP Graw RG Long …

B-Cell и T-Cell популяции в периферальной крови, связанные с лечением Ocrelizumab.

СПРАВОЧНАЯ ИНФОРМАЦИЯ/AIM: Ocrelizumab, a CD20-targeting Моноклональные антитела используются для лечения множественных склерозов. Цель этого исследования заключалась в изучении полезности периферийных поднаборов кровеносных клеток для прогнозирования реакции на орлезизумаб при повторном переносе множественных склерозов (RRMS). ПАТИЕНТЫ И МЕТОДЫ: Thirty-one пациенты, у которых IRMS устойчиво к первичным иммуномодуляционным агентам, были зачислены в учебные заведения, и были приняты последующие меры в отношении 12 Лечение при окролизумабском лечении за месяцы. За деятельностью, связанной с забо

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… Peripheral blood mononuclear cells were isolated using Ficoll density-gradient centrifugation, then aliquoted at a density of 1×10 6 per cryovial in freezing media (fetal bovine serum with 10% dimethyl sulfoxide) and stored in liquid nitrogen. …

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

BACKGROUND This study aimed to examine the effects of the sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of MDA-T32 human papillary thyroid carcinoma cells in vitro and in mouse tumor xenografts. MATERIAL AND METHODS Cell proliferation and viability of MDA-T32 human papillary thyroid carcinoma cells were determined by MTT assay, and cell migration was studied using a transwell assay. Fluorescence microscopy using acridine orange (AO) and ethidium bromide (EB) staining evaluated apoptosis. Transmission electron microscopy was used to study the effects of parthenolid

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… Then, the media was removed and the colored formazan product was solubilized by 200 μl of dimethyl sulfoxide (DMSO). The viability of the MDA-T32 human papillary thyroid carcinoma cells and the normal human thyrocytes was then determined by measuring absorbance at 570 nm. …

Tubulin binding potentially clears up Bortezomib and Carfilzomib differential neurotoxic effect.

Proteasome inhibitors (PIs) represent the gold standard in the treatment of multiple myeloma. Among PIs, Bortezomib (BTZ) is frequently used as first line therapy, but peripheral neuropathy (PN), occurring approximately in 50% of patients, impairs their life, representing a dose-limiting toxicity. Carfilzomib (CFZ), a second-generation PI, induces a significantly less severe PN. We investigated possible BTZ and CFZ off-targets able to explain their different neurotoxicity profiles. In order to identify the possible PIs off-targets we used the SPILLO-PBSS software that performs a structure-base

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… Himes RH Burton PR Gaito JM Dimethyl sulfoxide-induced self-assembly of tubulin lacking associated proteins J. Biol. Chem. 1977 252 6222 6228 10.1016/S0021-9258(17)40053-6 19469 23. Robinson J Engelborghs Y Tubulin polymerization in dimethyl sulfoxide J. Biol. …

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

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… Suberoylanilide hydroxamic acid (SAHA) was purchased from Cayman Chemical (San Diego, CA, USA) and was prepared in dimethyl sulfoxide (DMSO) at 10 mM concentration as a stock solution. The reagents were diluted in order to obtain the final concentration with respective culture medium. 4.2. … Abbreviations ANOVA | Analysis of variance BC | Breast cancer CBF1 | Centromere-binding protein 1 CDDP | Cisplatin CSL | CBF1/Su(H)/Lag-1 DCIs | Ductal carcinoma in situ DRRCs | Log-probit dose–response relationship curves Dll | Delta like ligand DMSO | Dimethyl sulfoxide DNA | Deoxyribonucleic acid …