Neuro-regenerative behavior of adipose-derived stem cells in aligned collagen I hydrogels.

Peripheral nerve injuries persist as a major clinical issue facing the US population and can be caused by stretch, laceration, or crush injuries. Small nerve gaps are simple to treat, and the nerve stumps can be reattached with sutures. In longer nerve gaps, traditional treatment options consist of autografts, hollow nerve guidance conduits, and, more recently, manufactured fibrous scaffolds.

Preclinical Profile of BYON3521 Predicts an Effective and Safe MET Antibody-Drug Conjugate.

MET, the cell-surface receptor for the hepatocyte growth factor/scatter factor, which is widely overexpressed in various solid cancer types, is an attractive target for the development of antibody-based therapeutics. BYON3521 is a novel site-specifically conjugated duocarmycin-based antibody-drug conjugate (ADC), comprising a humanized cysteine-engineered IgG1 monoclonal antibody with low pmol/L binding affinity towards both human and cynomolgus MET. In vitro studies showed that BYON3521 internalizes efficiently upon MET binding and induces both target- and bystander-mediated cell killing.

The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985 Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers.

SYD985 is a HER2-targeting antibody-drug conjugate (ADC) based on trastuzumab and vc-seco-DUBA, a cleavable linker-duocarmycin payload. To evaluate the therapeutic potential of this new ADC, mechanistic in vitro studies and in vivo patient-derived xenograft (PDX) studies were conducted to compare SYD985 head-to-head with T-DM1 (Kadcyla), another trastuzumab-based ADC. SYD985 and T-DM1 had similar binding affinities to HER2 and showed similar internalization.

Preclinical profile of the HER2-targeting ADC SYD983/SYD985: introduction of a new duocarmycin-based linker-drug platform.

A linker-drug platform was built on the basis of a cleavable linker-duocarmycin payload for the development of new-generation antibody-drug conjugates (ADC). A leading ADC originating from that platform is SYD983, a HER2-targeting ADC based on trastuzumab. HER2-binding, antibody-dependent cell-mediated cytotoxicity and HER2-mediated internalization are similar for SYD983 as compared with trastuzumab.

N-[2-(Pyridin-2-yl)ethyl]-derivatives of methane-, benzene- and toluenesulfonamide: prospective ligands for metal coordination.

The molecular and supramolecular structures are reported of N-[2-(pyridin-2-yl)ethyl]methanesulfonamide, C8H12N2O2S, (I), N-[2-(pyridin-2-yl)ethyl]benzenesulfonamide, C13H14N2O2S, (II), and N-[2-(pyridin-2-yl)ethyl]toluenesulfonamide, C14H16N2O2S, (III). Although (II) and (III) are almost structurally identical, the N(amide)-C(ethyl)-C(ethyl)-C(pyridinyl) torsion angles for (I) and (II) are more closely comparable, with magnitudes of 175.37 (15)° for (I) and 169.

Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors.

CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells.

Asymmetric total synthesis of pyranicin.

The asymmetric total synthesis of pyranicin (1) is reported. The butenolide ring was constructed via an asymmetric alkylation/ring-closing metathesis strategy. The three stereocenters in the left-hand tetrahydropyran ring were installed by sequential chiral auxiliary-mediated aldol reactions.

Hypertension during pregnancy in South Australia, part 2: risk factors for adverse maternal and/or perinatal outcome - results of multivariable analysis.

Objective: To identify factors associated with adverse pregnancy outcomes among women with hypertension during pregnancy.

Design: A population-based retrospective multivariable analysis using the South Australian perinatal data collection.

Methods: Perinatal data on 70,386 singleton births in 1998-2001 were used in multivariable analyses on three groups: all women combined, all hypertensive women and women with pregnancy hypertension only, in order to identify independent risk factors for requirement for level II/III care, preterm birth, small for gestational age (SGA) birth and maternal length of stay greater than 7 days.

Hypertension during pregnancy in South Australia, part 1: pregnancy outcomes.

Background: There have been conflicting reports about pregnancy outcome in the hypertensive disorders of pregnancy. The present study was undertaken to examine outcomes using a population database.

Aims: To examine for differences in a range of pregnancy outcomes between three different groups of hypertensive women and normotensive women in South Australia.

Risk factors for hypertension during pregnancy in South Australia.

Objective: To identify risk factors for hypertension in pregnancy among South Australian women.

Design: A population-based retrospective analysis using the South Australian perinatal data collection for 1998-2001.

Methods: Three groups of women with hypertension (pre-existing hypertension, pregnancy hypertension, and superimposed pre-eclampsia) were compared with normotensive women using unconditional logistic regression analysis on 70,386 singleton births to identify sociodemographic and clinical risk factors for hypertension in pregnancy.

Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells.

The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) are assumed to be mainly caused by Vdelta2-Jalpha rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vdelta2-Jalpha rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B-ALL. A significant proportion (44%) of Vdelta2-Jalpha rearrangements in childhood precursor-B-ALL were oligoclonal.