Search

Nickel‐ and palladium‐catalyzed insertion copolymerization of ethylene and acrylate comonomers for synthesis of ethylene‐acrylates copolymers have attracted much academic and industrial interests and remained highly challenging. This review provides an overview of the developments in nickel‐ and palladium‐catalyzed insertion copolymerization of ethylene and acrylate comonomers. Mechanistic interpretation of metal‐catalyzed insertion copolymerization of ethylene and acrylate comonomers is described. Late transition metal catalysts are divided to nickel‐based and palladium‐based catalysts with different chelate ligands. The effects of catalyst structure on copolymerization performance and copolymer microstructure are comprehensively discussed. This review aims to promote the design and development of nickel and palladium catalysts for ethylene/acrylate copolymerizations and synthesis of ethylene‐acrylates copolymers.

The alternating copolymers of carbon monoxide (CO) and vinyl arene monomers, namely aromatic polyketones, are a family of attractive engineering plastic. In the catalytic synthesis of this kind of polymeric materials, [N,N] bidentate palladium catalysts represent the most successful catalytic systems. In this review, we introduce the present status of polyketone synthesis, with a focus on the aromatic polyketones made from vinyl arene and CO. We also address the palladium‐catalyzed CO/vinyl arene alternating copolymerization mechanism. A variety of [N,N] bidentate palladium catalysts bearing 2,2′‐bipyridine, 1,10‐phenanthroline, α‐diimine, and pyridine‐imine ligands are surveyed for CO/vinyl arene copolymerization. The effects of vinyl arene monomer, counteranion, and solvent on copolymerization are also discussed. The copolymerization stereochemistry including chain end‐control and enantiomorphic site control mechanisms is introduced. This review aims to promote the design of [N,N] bidentate palladium catalysts for CO/vinyl arene copolymerization for the development of high‐performance aromatic polyketones.

Objective: To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs.Methods: IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients’ serum was re-analyzed for altered expression of the miRNAs by qRT-PCR.Results: TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p; P< 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p; P< 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly (P< 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture (P< 0.05).Conclusions: The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms.Trial registration number: ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry)

Due to the lack of a delivery system that actively targets hypertrophic scar fibroblasts (HSFs), it is difficult to concentrate the effects of drugs on hypertrophic scars (HSs). We recently discovered that the HSF membrane has a homologous targeting effect and developed an active targeted drug delivery system for the local treatment of HSs. A diphenyl carbonate cross-linked cyclodextrin metal organic framework (CDF) containing more than 26% (w/w) quercetin (QUE) was coated with a HSF membrane (QUE@HSF/CDF) and then dispersed in Bletilla striatapolysaccharide (BSP)-fabricated dissolvable microneedles (BSP-MNs-QUE@HSF/CDF) for local administration. This biomimetic nanodrug delivery system improved efficacy on HSs by regulating Wnt/β-catenin and JAK2/STAT3 pathways and reducing the expression of collagens I and III in HS, and this performance was superior to those of systems without HSF functionalization or the assistance of microneedles. Additionally, we found that BSP has synergistic effects and the microneedles have higher mechanical strength and better physical stability than microneedles made of hyaluronic acid. This currently designed drug delivery strategy integrating biomimetic nanoparticles and dissolvable microneedles is promising for applications in the fields of skin disease treatment and cosmetics.

Introduction: The chronic neuropathic pain associated with postherpetic neuralgia (PHN) can last for several months or even many years, seriously affecting the affected person’s work, sleep, mood, and daily life activities. In generaly, current treatments for PHN are at best limited and unsatisfactory, and adverse reactions are common, especially in elderly patients. Electroacupuncture (EA) is widely used clinically to manage painful diseases, but there remains a lack of evidence to support the effectiveness of EA on PHN. This study is designed to assess the efficacy and safety of EA on PHN, and to provide evidence-based medical evidence for EA treatment of PHN. Methods: This multicenter, prospective, randomized controlled trial will recruit 448 patients with PHN at seven clinical centers. Multicenter stratified variable block randomization will be used, and the eligible patients will be randomly allocated in a ratio of 1:1 to the EA group or sham EA group. The EA group will receive 4 weeks of EA treatment, given as 30-min treatment sessions, once daily, 5 times per week, for a total of 20 treatments; the sham EA group will receive sham EA treatment under the same conditions. Planned Outcomes: The primary outcome measure is the 11-point Numeric Rating Scale pain score at week 4. The secondary outcome measures, including mechanical pain threshold, pain area of PHN, average number of pain episodes, the short-form McGill Pain Questionnaire 2, Zoster Brief Pain Inventory, the Depression, Anxiety, and Positive Outlook Scale, Patient Global Impression of Change, safety of EA, and use of concomitant medications, among others. The primary analysis of the outcomes will be the mixed-effect model with repeated measurement between groups on an intent-to-treat population. Trial Registration: Clinicaltrials.gov identifier: NCT04560361. Registered 23 September 2020 (https://clinicaltrials.gov/ct2/show/NCT04560361?term=NCT04560361&draw=2&rank=1).

There is a need for novel therapies for relapsed or refractory multiple myeloma, and B-cell maturation antigen (BCMA) is a validated target. Teclistamab is a bispecific antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. The aim of the MajesTEC-1 study was to evaluate the safety, tolerability, and preliminary efficacy of teclistamab in patients with relapsed or refractory multiple myeloma.

•Better clinical responses to teclistamab correlate with a more functional initial immune T-cell repertoire in the periphery and tumor site.•More durable responses to teclistamab associate with lower Tregs and lower expression of inhibitory receptors on T cells at baseline.

•Teclistamab provides clinically meaningful responses in patients with RRMM with prior anti-BCMA treatment.•The safety profile of teclistamab was similar in patients with and without prior exposure to anti-BCMA therapy.

The calcium-sensitive receptor (CaSR) plays a role in several biological processes. However, its role in intestinal motility remains unclear. In this study, we aimed to determine the effect of electro-acupuncture (EA) at Shangjuxu (ST37) on CaSR in colonic dysplasia mice, and to explore the possible mechanism of EA regulating colonic movement. The mice were injected with nicardipine or hexamethonium bromide to induce colonic dysplasia. Intestinal transit function was assessed by twelve hours fecal granules and fecal water content percentage, while colonic slow wave was assessed by multi-channel physiological signal acquisition system, immunofluorescence and laser confocal microscopy were used to examine CaSR expression in the gastrointestinal (GI) tract of the mice. We found that the number of fecal particles, the frequency and amplitude of colonic slow wave were disrupted after nicardipine or hexamethonium bromide injection. In addition, CaSR expression in control group was mainly distributed in intestinal epithelial cells, and the morphological structure of mucosal layer was regular. Compared with control group, the structure of mucosal layer in nicardipine group and hexamethonium bromide group were all disorderly, the expression and fluorescence intensity of CaSR in nicardipine group were visible, but in hexamethonium bromide group were weakened. After EA intervention, these disorders were ameliorated, which suggested that EA at ST37 could therefore regulate colonic motility disorders via the involvement of CaSR.

To evaluate the effect and safety of acupuncture for the treatment of irritable bowel syndrome (IBS) through comparisons with those of polyethylene glycol (PEG) 4000 and pinaverium bromide.

Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.

ABSTRACTEpithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST. The morphological alterations were observed with a microscopy. The protein and mRNA expressions were determined by Western blotting and real-time PCR. The protein localization was detected with immunofluorescence. The adhesion, migration, and invasion were determined by Matrigel, wound-healing, and Transwell assays. TGF-β1 treatment induced spindle-shaped alterations of cells, upregulation of N-cadherin, Vimentin, NF-κB p65, and downregulation of E-cadherin. Dysregulated membrane expression and mRNA expression of E-cadherin and N-cadherin were observed after TGF-β1 treatment. TGF-β1 increased abilities of migration and invasion and triggered the nuclear translocation of NF-κB p65. These alterations were dramatically inhibited by OST. Furthermore, PDTC, a NF-κB inhibitor, showed similar effects. In addition, TGF-β1-induced expression of Snail was significantly inhibited by OST and silenced Snail partially reversed TGF-β1-induced EMT biomarkers without affecting NF-κB p-65. In conclusion, OST inhibited TGF-β1-induced EMT, adhesion, migration, and invasion through inactivation of NF-κB-Snail pathways in A549 cells. This study provides novel molecular mechanisms for the anti-metastatic effect of OST.

CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m2 and twice-weekly 1.3 mg/m2 bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ≥1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00298766.

CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m2and twice-weekly 1.3 mg/m2bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ≥1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.govas #NCT00298766.

Introduction:Teclistamab (JNJ-64007957) is a T-cell redirecting, bispecific IgG4 antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells. Teclistamab is under investigation in MajesTEC-1, an ongoing phase 1/2 study in patients (pts) with heavily pretreated relapsed/refractory multiple myeloma (RRMM). Results from the phase 1 study (parts 1 and 2; NCT03145181) indicated that teclistamab is well tolerated at the recommended phase 2 dose (RP2D) and has encouraging efficacy, with an overall response rate (ORR) of 65% and very good partial response or better (≥VGPR) rate of 58% in 40 pts after a median of 6.1 mo of follow-up. Here we report for the first time initial data from the phase 2 portion of MajesTEC-1 (part 3; NCT04557098) and updated results for phase 1 pts treated at the RP2D.

Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria. Usmani: Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; EdoPharma: Consultancy; GSK: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; Abbvie: Consultancy; Amgen: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding. Garfall: Amgen: Honoraria; Tmunity Therapeutics: Research Funding; Novartis: Research Funding; GSK: Honoraria; Janssen: Honoraria, Research Funding. van de Donk: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy; Roche: Consultancy; Novartis /bayer/servier: Consultancy. Nahi: XNK Therapeutics AB: Consultancy. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Oriol: GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Nooka: GlaxoSmithKline: Consultancy, Other: Travel expenses; Bristol-Myers Squibb: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Adaptive technologies: Consultancy; Karyopharm Therapeutics: Consultancy. Martin: Amgen: Research Funding; Sanofi: Research Funding; Janssen: Research Funding; GlaxoSmithKline: Consultancy; Oncopeptides: Consultancy. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Chari: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Consultancy, Research Funding; Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Novartis: Consultancy, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Karlin: Abbvie: Honoraria; Amgen: Honoraria, Other: travel support and advisory board ; GSK: Honoraria, Other: member of advisory board; Janssen: Honoraria, Other: member of advisory board, travel support; Takeda: Honoraria, Other: member of advisory board; Celgene-BMS: Honoraria, Other: member of advisory board; Sanofi: Honoraria; oncopeptide: Honoraria. Mateos: Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Oncopeptides: Honoraria. Bahlis: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Genentech: Consultancy; Sanofi: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Popat: Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Abbvie, Takeda, Janssen, and Celgene: Consultancy; Janssen and BMS: Other: travel expenses. Besemer: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Sidana: Allogene: Research Funding; Janssen: Consultancy, Research Funding; Magenta Therapeutics: Consultancy, Research Funding; BMS: Consultancy. Pei: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Trancucci: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Verona: Janssen: Current Employment. Girgis: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Olyslager: Janssen: Current Employment. Jaffe: Janssen: Current Employment. Uhlar: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Stephenson: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Van Rampelbergh: Janssen: Current Employment. Banerjee: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Goldberg: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Kobos: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Krishnan: MAGENTA: Consultancy; BMS: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau; JANSSEN: Consultancy, Research Funding; City of Hope Cancer Center: Current Employment; REGENERON: Consultancy; SANOFI: Consultancy; GSK: Consultancy; Amgen: Speakers Bureau.

The commonly used two-sample tests of equal area-under-the-curve (AUC), where AUC is based on the linear trapezoidal rule, may have poor properties when observations are missing, even if they are missing completely at random (MCAR). We propose two tests: one that has good properties when data are MCAR and another that has good properties when the data are missing at random (MAR), provided that the pattern of missingness is monotonic. In addition, we discuss other non-parametric tests of hypotheses that are similar, but not identical, to the hypothesis of equal AUCs, but that often have better statistical properties than do AUC tests and may be more scientifically appropriate for many settings.

BackgroundMatrix metalloproteinase-9 (MMP-9) can degrade collagen IV (the main structural ingredient of basilar membrane), and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 (TIMP-1) can bind with MMP-9 to form 1:1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis.ObjectiveTo analyze the relationship of MMP-9 and TIMP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor (MPNST).DesignAn observational comparative experiment.SettingHeze Medical College.ParticipantsFifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor (10 cases of nerve sheath tumor and 10 cases of neurofibromatosis) and the normal peripheral nerves (by-products of some surgeries) of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co., Ltd.MethodsThe documented paraffin blocks were again prepared to sections of 5 μm. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed.Main outcome measuresRelationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis.Results▪ Expressions of MMP-9 and TIMP-1 in three tissues: MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor (P < 0.05), while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor (P < 0.05). ▪ Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST: The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2–3 was significantly higher than that in the MPNST patients of grade 1 (P < 0.05), while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 (P < 0.05). The metastatic rate was positively correlated with MMP-9 expression (r = 1.696, P < 0.05), but negatively correlated with TIMP-1 expression (r = –2.125, P < 0.05).ConclusionMMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and prognosis of MPNST.

Garfall: Tmunity: Consultancy, Other: Personal fees, Research Funding; Kite Pharma: Other: Personal fees; Amgen: Research Funding; Novartis: Research Funding; GSK: Consultancy; Janssen: Consultancy, Research Funding; Surface Oncology: Consultancy. Usmani:Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; SkylineDX: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Mateos:Adaptive: Consultancy; Amgen: Consultancy; GlaxoSmithKline: Consultancy; Pharmamar: Consultancy; Janssen: Consultancy; Celgene: Consultancy; EDOMundipharma: Consultancy; AbbVie: Consultancy; Takeda: Consultancy. van de Donk:Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Ferrer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Oriol Rocafiguera:Amgen: Consultancy, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chari:Seattle Genetics: Consultancy, Research Funding; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Array BioPharma: Honoraria; The Binding Site: Honoraria; Sanofi Genzyme: Consultancy; Adaptive Biotechnology: Honoraria; Novartis: Honoraria; Takeda: Consultancy, Research Funding; Antengene: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Secura Bio: Consultancy; Glaxo Smith Kline: Consultancy; Oncopeptides: Consultancy. Bhutani:Prothena: Other: Clinical Trial Funding to Institute; Janssen: Other: Clinical Trial Funding to Institute; Takeda: Other: Clinical trial funding to institute, Speakers Bureau; Amgen: Speakers Bureau; BMS: Other: Clinical trial funding to institute, Speakers Bureau; Sanofi Genzyme: Consultancy; MedImmune: Other: Clinical Trial Funding to Institute. Pei:J&J: Current Employment, Current equity holder in publicly-traded company. Verona:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Girgis:Johnson & Johnson: Current Employment, Current equity holder in private company. Stephenson:Johnson & Johnson: Current Employment, Current equity holder in private company. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Banerjee:Janssen: Current Employment. Krishnan:BMS/Celgene: Consultancy, Other: Stock BMS, Speakers Bureau; Janssen: Consultancy; Takeda: Speakers Bureau; Z Predicta: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Sanofi: Consultancy; Sutro: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy.

Background:MM inevitably relapses and becomes refractory to treatment, representing a patient (pt) population with unmet needs. Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing MM cells. Previously presented results from an ongoing study of teclistamab in RRMM (NCT03145181) included a 67% objective response rate [ORR] for the 270 µg/kg dose administered intravenously (iv) (Usmani et al, ASCO 2020 Oral Presentation #100). Here we present updated results and newly available data for subcutaneous (sc) administration.

Moreau: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Zweegman:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Perrot:Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria. Facon:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Leleu:Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria. Belhadj:Amgen: Honoraria; Celgene: Honoraria, Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work; Takeda: Honoraria; Janssen: Honoraria. Karlin:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Levin:Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Educational grant ; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Educational grant . Minnema:Servier: Honoraria; Amgen: Honoraria; Celgene Corporation: Honoraria, Research Funding; Gilead: Honoraria; Jansen Cilag: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SkylineDx: Research Funding. Pei:Janssen: Employment, Equity Ownership. de Boer:Janssen: Employment, Equity Ownership. Vermeulen:Janssen R&D, LLC: Employment, Equity Ownership. Kampfenkel:Janssen: Employment, Equity Ownership.Bortezomib/thalidomide/dexamethasone (VTd) + autologous stem cell transplantation (ASCT) is standard of care in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. The phase 3 CASSIOPEIA trial evaluated the efficacy and safety of adding daratumumab to VTd (D-VTd) before and after ASCT. Although daratumumab is approved as monotherapy and in combination with standard-of-care regimens for the treatment of MM, D-VTd has not yet been approved. This presentation/paper includes information/discussion of D-VTd in the CASSIOPET companion study to CASSIOPEIA.

Supplemental Digital Content is available in the text

Belch: Janssen-Cilag: Consultancy. Pei:Janssen Research and Development: Employment; Johnson & Johnson: Other: Stock Ownership. Yang:Janssen Research and Development: Employment. Robak:Janssen: Consultancy, Research Funding; MorphoSys AG: Consultancy, Honoraria, Research Funding. Rooney:Janssen Research and Development: Employment; Johnson & Johnson: Other: Stock Ownership. Cakana:Janssen Research and Development: Employment. van de Velde:Millennium Pharmaceuticals, Inc.: Employment; Johnson & Johnson: Equity Ownership.

Introduction

Robak: Janssen Research & Development: Consultancy, Research Funding. Off Label Use: The proteasome inhibitor bortezomib is approved in the US for the treatment of multiple myeloma and for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. In the present study, bortezomib is being investigated in combination with immunochemotherapy for previously untreated patients with mantle cell lymphoma, an indication for which it is currently not approved.. Siritanaratkul:Novartis: Research Funding; Roche: Research Funding; Janssen: Research Funding. Mayer:Janssen Research & Development: Research Funding; Roche: Research Funding; GlaxoSmithKline: Research Funding; Celgene: Research Funding. Pei:Janssen: Employment. Rooney:Johnson & Johnson: Equity Ownership; Janssen: Employment. van de Velde:Johnson & Johnson: Equity Ownership; Janssen: Employment. Cavalli:Roche: Research Funding; Takeda: Consultancy; Pfizer: Research Funding; Mundipharma: Research Funding; Novartis: Consultancy.

Drach: Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Off Label Use: The proteasome inhibitor bortezomib is approved in the US for the treatment of multiple myeloma and for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. In the present study, bortezomib is being investigated in combination with immunochemotherapy for previously untreated patients with mantle cell lymphoma, an indication for which it is currently not approved.. Belch:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Farber:Alexion: Equity Ownership, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau; Janssen/Pharmacyclics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Leukemia Lymphoma Society NJ Chapter: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosly:Amgen: Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zaucha:Roche: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria. Robak:Janssen Research & Development: Consultancy, Research Funding. Pei:Janssen: Employment. Rooney:Janssen: Employment; Johnson & Johnson: Equity Ownership. van de Velde:Janssen: Employment; Johnson & Johnson: Equity Ownership. Cavalli:Mundipharma: Research Funding; Pfizer: Research Funding; Roche: Research Funding; Takeda: Consultancy; Novartis: Consultancy.

Ogura: Janssen: Research Funding; Takeda: Research Funding; Chugai: Research Funding; Celgene: Research Funding; Symbio: Research Funding; Kyowahakko-Kirin: Research Funding; Pfizer: Research Funding; GlaxoSmithKline: Research Funding. Off Label Use: The proteasome inhibitor bortezomib is approved in the US for the treatment of multiple myeloma and for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. In the present study, bortezomib is being investigated in combination with immunochemotherapy for previously untreated patients with mantle cell lymphoma, an indication for which it is currently not approved.. Pei:Janssen: Employment. Rooney:Janssen: Employment; Johnson & Johnson: Equity Ownership. van de Velde:Janssen: Employment; Johnson & Johnson: Equity Ownership. Cavalli:Novartis: Consultancy; Takeda: Consultancy; Roche: Research Funding; Pfizer: Research Funding; Mundipharma: Research Funding.

Background:

Background:

Background:

The commonly used two-sample tests of equal area-under-the-curve (AUC), where AUC is based on the linear trapezoidal rule, may have poor properties when observations are missing, even if they are missing completely at random (MCAR). We propose two tests: one that has good properties when data are MCAR and another that has good properties when the data are missing at random (MAR), provided that the pattern of missingness is monotonic. In addition, we discuss other non-parametric tests of hypotheses that are similar, but not identical, to the hypothesis of equal AUCs, but that often have better statistical properties than do AUC tests and may be more scientifically appropriate for many settings.