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Quadruplet therapy for newly diagnosed myeloma: comparative analysis of sequential cohorts with triplet therapy lenalidomide, bortezomib and dexamethasone (RVd) versus daratumamab with RVD (DRVd) in transplant-eligible patients.

Lenalidomide, bortezomib, and dexamethasone (RVd) have previously been established as standard-of-care induction therapy for newly diagnosed multiple myeloma (NDMM). More recently, randomized phase 3 data have demonstrated the benefit of the addition of daratumumab (Dara-RVd) to the RVd backbone in terms of improved both depth of response and long-term survival benefit as measured by progression-free survival (PFS). Our group has previously published on a historical cohort of 1000 NDMM patients uniformly treated with RVd induction with impressive both PFS and overall survival. Here, we present

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… Genetic risk-stratification was done in accordance with the IMWG definition and defined by the presence of deletion (17p), translocation (4;14), and (14;16) by either fluorescence in-situ hybridization (FISH) on CD138 selected cells or by metaphase cytogenetics. …

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma.

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 m

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… Median (Range) | 64.5 (41.0–88.0) | 64.0 (41.0–88.0) Gender: Male | 25 (52.1%) | 24 (53.3%) ECOG performance score 0 | 25 (52.1%) | 23 (51.1%) 1 | 19 (39.6%) | 18 (40.0%) 2 | 4 (8.3%) | 4 (8.9%) mSMART risk Standard risk | 34 (70.8%) | 31 (68.9%) High or intermediate | 14 (29.2%) | 14 (31.1%) Abnormal metaphase …

TEAD4 regulates trophectoderm differentiation upstream of CDX2 in a GATA3-independent manner in the human preimplantation embryo.

STUDY QUESTION: What is the role of transcriptional-enhanced associate (TEA) domain family member 4 (TEAD4) in trophectoderm (TE) differenti … ead4-targeted group to develop beyond implantation stages. Following the mouse investigation, human metaphase-II (MII) oocytes obtained by IVM were microinjected with gRNA-Cas9 during ICSI (n = 74) to target TEAD4 or used as media-control (n = 33). The editing efficiency was successfully assessed in n = 25 TEAD4-targeted human embryos. Finally, immunofluore …

miR-21 regulates osteogenic and adipogenic differentiation of BMSCs by targeting PTEN.

ObjectiveTo explore the effects and mechanism of miR-21 on the osteogenic/adipogenic differentiation of mouse BMSCs.MethodsThe bilateral ovaries of C57BL/6J mice (n=24) were removed to construct an osteoporosis model. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-21, osteogenic/adipogenic genes, and PTEN. ALP and ARS and ORO staining were used to detect the formation of calcium nodules and lipid droplets in BMSCs. Western blot was used to detect the expression of PTEN.ResultsmiR-21 was significantly down-regulated in osteoporotic mice. The

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… OPN is a marker of osteoblast metaphase differentiation and a regulatory gene of matrix mineralization, which can promote hydroxyapatite formation, osteoblast mineralization and bone formation[ 29 ]. …

Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview.

Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. However, due to a very low number of patients, their impact on the progn

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… molecular pathogenesis of MDS, offering great advances in diagnosis, gauging patient prognosis and treatment response 1 .With modern developments in diagnostic techniques, genetic abnormalities such as point mutations and copy-number abnormalities can be detected in a large number of MDS patients 3 .Metaphase …

Разработка и утверждение прогнозной номограммы венерического хромбоэмболизма для пациентов с множественными миеломами: одноцентральное кохортное исследование в Китае.

Цели: Венозный тромбоэмболизм (VTE) представляет собой значительное осложнение у пациентов с множественной миеломой (MM), которое отрицательно сказывается на заболеваемости, смертности и результатах лечения. Цель этого исследования состояла в том, чтобы разработать и подтвердить прогнозную номограмму для оценки риска VTE у пациентов, страдающих расстройствами питания, с использованием клинопатологических факторов. Методы: клинические данные, включая 25 Была собрана информация о потенциальных факторах риска. Для выявления независимых факторов риска для VTE был проведен унифицированный и многова

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… Abnormal metaphase cytogenetics predicts venous thromboembolism in myeloma: Derivation and validation of the PRISM score. Blood. 2022;140:2443–2450. doi: 10.1182/blood.2022015727. 11. Han H.J., Kim M., Lee J., Suh H.S. …

Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achiev

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… Maintenance therapy with thalidomide improves survival in patients with multiple myeloma Blood 2006 108 3289 3294 16873668 10.1182/blood-2006-05-022962 28 Barlogie B Pineda-Roman M van Rhee F Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase …

The combination therapy with venetoclax in therapeutic strategy of acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is characterized by the malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood, and extramedullary sites. Leukemic cells can develop drug resistance both before and after treatment, complicating disease management. Combination therapy with Venetoclax has been shown to enhance the efficacy of standard anti-leukemia drugs. Therefore, this study aims to review combination treatment strategies as potential therapeutic alternatives, drawing on evidence from previous published literature. METHODS: This narrativ

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… Its primary mechanism involves inhibition of microtubule polymerization, leading to metaphase arrest and induction of apoptosis [ 61 , 62 ]. …

NEAT1 lncRNA overexpression results in short-term progression and poor treatment outcome in childhood B-ALL.

Childhood acute lymphoblastic leukaemia (chALL) remains the most prevalent malignancy in children and adolescents. Improving risk stratification and providing personalized prognosis and treatment remain major clinical challenges. Herein, we analysed the clinical utility of NEAT1 lncRNA for the prognosis and prediction of treatment outcome of childhood B-cell precursor ALL (chB-ALL). NEAT1_1 isoform was quantified in bone marrow samples of chB-ALL patients at diagnosis (n = 160) and at the end of induction (n = 108) of ALL-BFM protocol, and in age-matched healthy children (n = 68). Relapse and

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… The standard G‐banding technique was employed for metaphase chromosome analysis, and classification was performed according to the International System for Cytogenetic Nomenclature (ISCN). …

Predicting new drug indications for prostate cancer: The integration of an in silico proteochemometric network pharmacology platform with patient-derived primary prostate cells.

BackgroundDrug repurposing enables the discovery of potential cancer treatments using publically available data from over 4000 published Food and Drug Administration approved and experimental drugs. However, the ability to effectively evaluate the drug's efficacy remains a challenge. Impediments to broad applicability include inaccuracies in many of the computational drug-target algorithms and a lack of clinically relevant biologic modeling systems to validate the computational data for subsequent translation.MethodsWe have integrated our computational proteochemometric systems network pharmac

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… specimens were processed via protease dissociation as previously described. 11 , 18 Primary cultures were established at Georgetown University using the CR method, and drug senstivity experiments were performed in conditioned media (CM) as previously described. 19 Genetic profiles, obtained by performing metaphase …

Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis.

This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22-4.88] (P < 0.00

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… Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities Blood 2008 112 8 3115 3121 10.1182/blood-2008-03-145235 2-s2.0-54049148621 18492953 PMC2569166 26 Barlogie B. Tricot G. Anaissie E. …

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

IntroductionPesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.MethodsAnalyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for

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… . | ( 71 ) Permethrin | Peripheral blood mononuclear cells | The pesticide at low concentrations induces aberrations in the KMT2A and IGH genes, detected in the interphase and metaphase phases. | ( 49 ) Thiamethoxam | Adenocarcinoma cells (H295R) | Exposure to neonicotinoid pesticides could increase … Furthermore, permethrin exposure induced numerical aberrations frequently observed in the metaphase phase ( 49 ). Other results from in vitro and in vivo exposure to pesticides evaluated in the present review are shown in Tables 5 , 6 . …

Guidelines on the diagnosis and management of multiple myeloma treatment: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associação Médica Brasileira - 2012.

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… Cytogenetics [karyotyping in metaphase and fluorescent in situ hybridization (FISH)]; 9. Evaluation of x-rays of the skeleton, including the spine, pelvis, skull, femur and humerus, with magnetic resonance imaging in specific situations; 10. … Between 20 and 50% of patients with MM have numeric or structural chromosomal changes identified by cytogenetics (metaphases or FISH) ( 12 ) (B). …

Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mecha

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… Vinca alkaloids cause apoptosis of cancer cells by binding to the β-tubulin subunit of microtubules and to the spindle proteins in the S phase of the cell cycle, inhibiting microtubule formation, which results in mitotic arrest of the cancer cells in metaphase ( Himes, 1991 ; Downing, 2000 ). … The disruption of mitotic spindle formation results in the mitotic arrest of cancer cells at metaphase and subsequent cell death. …

Статинское воздействие после многократного диагностирования миеломы и риск полной смертности, венозного тромбоэмболизма, патологических переломов и острых повреждений почек: ретроспективное когортное исследование.

Множественная миелома (ММ) сопряжена со значительным риском венозного тромбоэмболизма (VTE), патологических переломов, острых повреждений почек (AKI) и смерти. Статины обладают антивоспалительными, иммунодуляционными и антитромботическими свойствами, которые могут уменьшить эти осложнения, однако их связи с рядом ключевых результатов MM не оценивались одновременно в одной реальной группе. ЦЕЛИ: Оценить связь между воздействием последиагностической статистики и 5-year Смертельная смертность, VTE, патологические переломы и AKI в MM. МЕТОДЫ: Мы провели ретроспективное когортное исследование в сет

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… Abnormal metaphase cytogenetics predicts venous thromboembolism in myeloma: derivation and validation of the PRISM score. Blood 2022;140:2443–50. [30] Shi R, Mei Z, Zhang Z, et al. Effects of statins on relative risk of fractures for older adults: an updated systematic review with meta-analysis. …

Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time?

Therapy-related myeloid neoplasms (t-MN), including myelodysplastic neoplasms (t-MDS) and acute myeloid leukemia (t-AML), have emerged as significant late complications after CAR T cell therapy. We retrospectively analyzed 539 patients with B cell lymphoma treated with CD19 directed CAR T cell therapy across four French centers. Cumulative incidences of t-MN was estimated with relapse or death treated as competing risk. Univariate and propensity score matching (PSM) analyses were conducted to assess risk factors with age and the number of prior treatments as covariates. After a median follow-u

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… t-AML and t-MDS analysis Cytogenetics including standard metaphase karyotyping and fluorescent in situ hybridization were performed locally in each center. Cytogenetic risk was stratified by current European LeukemiaNet (ELN) guidelines [ 25 ]. …

Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance.

Triplet combinations containing a proteasome inhibitor are a standard of care in newly diagnosed multiple myeloma (NDMM). We examined the long-term efficacy and safety of the all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd), followed by single-agent ixazomib maintenance in NDMM patients. Of 65 enrolled patients, 53 received ixazomib 4 mg (days 1, 8, and 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, and 22) for up to twelve 28-day induction cycles. Twenty-three patients discontinued induction for stem cell transplantation (SCT). In

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… patients, those who did not receive SCT, and those who proceeded to maintenance ISS International Staging System, MM multiple myeloma, SCT stem cell transplantation a High-risk cytogenetic abnormalities included: del 17/17p, t(4;14), and/or t(14;16) detected by fluorescence in situ hybridization or metaphase …

Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare disease that arises from skeletal muscle mainly affects children and adolescents. Patients with RMS have diverse symptoms and prognosis based on tumor sizes, tumor anatomical locations, histological subtypes of the tumors and genetic testing of paired-box-forkhead box O1 (PAX-FOXO1) fusion gene. The 4 subtypes of RMS include embryonal RMS (eRMS), alveolar RMS (aRMS), spindle cell/sclerosing RMS (scRMS) and pleomorphic RMS (pRMS). Treatment for RMS patients remains challenging due to its heterogeneous nature. Thus, a combinatory approach is likely to warrant bet

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… Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and thus interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. …

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials.

We aimed to quantitatively synthesize data from randomized controlled trials (RCTs) concerning maintenance for multiple myeloma (MM). We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA) to determine adequacy of sample size for overall and subgroup meta-analyses. We per

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… Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 112 3115–3121. 10.1182/blood-2008-03-145235 Begg C. B., Berlin J. A. (1989). Publication bias and dissemination of clinical research. J. Natl. …

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients w

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… , CD7, CD19, CD10 and CD20 and lineage non-specific antigens HLA-DR, CD34 and CD56 were used to characterize the phenotypes of the leukemia cells as previously described. 9 Cytogenetic study BM cells were harvested directly or after 1–3 days of unstimulated culture as described previously. 10 The metaphase …