Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity.

Background: Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins.

Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models.

The antibody-drug conjugate (ADC) MORAb-202, consisting of farletuzumab paired with a cathepsin B-cleavable linker and eribulin, targets folate receptor alpha (FRA), which is frequently overexpressed in various tumor types. MORAb-202 was highly cytotoxic to FRA-positive cells in vitro, with limited off-target killing of FRA-negative cells. Furthermore, MORAb-202 showed a clear in vitro bystander cytotoxic effect in coculture with FRA-positive/negative cells.

A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease.

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication.

Open-label Extension Phase of a Chronic Diabetic Foot Ulcer Multicenter, Controlled, Randomized Clinical Trial Using Cryopreserved Placental Membrane.

Objective: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved placental membrane; CPM; Osiris Therapeutics, Inc, Columbia, MD) multicenter, blinded, randomized, controlled clinical trial for chronic diabetic foot ulcers (DFUs) is reported.

Materials And Methods: Twenty-six patients in the standard wound care (SWC) arm whose DFUs did not close in the blinded phase chose to receive weekly applications of the CPM in an open-label extension phase.

Results: In the extension phase, 17 (65.

Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature.

Over-expression of endosialin/CD248 (herein referred to as CD248) has been associated with increased tumor microvasculature in various tissue origins which makes it an attractive anti-angiogenic target. In an effort to target CD248, we have generated a human CD248 knock-in mouse line and MORAb-004, the humanized version of the mouse anti-human CD248 antibody Fb5. Here, we report that MORAb-004 treatment significantly impacted syngeneic tumor growth and tumor metastasis in the human CD248 knock-in mice.

The efficacy and safety of Grafix(®) for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial.

In a randomised, controlled study, we compared the efficacy of Grafix(®) , a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase.

Child and family factors associated with teacher-reported behavior problems in young children of substance abusers.

Background: We examined child and family factors associated with teacher-reported behavior problems in 79 children of substance abusers (COSAs).

Method: Using regression models, we examined the impact of four family risk factors, cumulatively and individually, on children's behavior and explored children's engagement of adults as a protective factor.

Results: More than half (55%) of children had clinically elevated behavior problems.

Clathrate Ba8Au16P30: the "gold standard" for lattice thermal conductivity.

A novel clathrate phase, Ba8Au16P30, was synthesized from its elements. High-resolution powder X-ray diffraction and transmission electron microscopy were used to establish the crystal structure of the new compound. Ba8Au16P30 crystallizes in an orthorhombic superstructure of clathrate-I featuring a complete separation of gold and phosphorus atoms over different crystallographic positions, similar to the Cu-containing analogue, Ba8Cu16P30.

BaAu2P4: layered zintl polyphosphide with infinite ∞(1)(P–) chains.

Barium gold polyphosphide BaAu2P4 was synthesized from elements and structurally characterized by single crystal X-ray diffraction. BaAu2P4 crystallizes in a new structure type, in the orthorhombic space group Fddd (No. 70) with a = 6.

Abdominal apoplexy: two unusual cases of hemoperitoneum.

Abdominal apoplexy, or idiopathic spontaneous intraperitoneal hemorrhage, is a rare and often fatal condition resulting from a variety of disease processes affecting the arterial and venous abdominal vasculature. Preoperative and intraoperative diagnosis and treatment of abdominal apoplexy are challenging. The source of bleeding may remain elusive even after careful autopsy dissection given the absence of intravascular pressure.

Fenfluramine disrupts the mitral valve interstitial cell response to serotonin.

Serotonin (5HT) receptor signaling and 5HT-related agents, such as the anorexogen fenfluramine (Fen), have been associated with heart valve disease. We investigated the hypothesis that Fen may disrupt mitral valve interstitial cell (MVIC) homeostasis through its effects on mitogenesis and extracellular matrix biosynthesis. Normal and myxomatous mitral valves, both human and canine, were harvested, and primary MVIC cultures were established.

Biomechanical and biologic effects of meniscus stabilization using triglycidyl amine.

The susceptibility of meniscus allografts to enzymatic degradation may be reduced through tissue stabilization. We have previously reported on an epoxide-based crosslinker, triglycidyl amine (TGA), which can be used alone or with a bisphosphonate (MABP) to stabilize heterograft heart valves and reduce their pathologic calcification. Our objective was to evaluate the effects of TGA and TGA-MABP pretreatment on an orthopedic allograft involving meniscus crosslinking, degradation, calcification, and compressive properties.

Foxl1-Cre BAC transgenic mice: a new tool for gene ablation in the gastrointestinal mesenchyme.

The use of Cre-loxP technology for the purpose of cell type-specific gene ablation has revolutionized developmental biology and biomedicine. Several transgenic mouse lines have been developed for the analysis of gene function in the gastrointestinal tract, but in all of these the expression of Cre is limited to the epithelial cell layer. No Cre- expressing transgenic mouse lines ("Cre lines") exist for the deletion of loxP-flanked genes specifically in gut mesoderm.

Biological stability of polyurethane modified with covalent attachment of di-tert-butyl-phenol.

Polyurethane cardiovascular implants are subject to oxidation initiated surface degradation, which is mediated by monocyte-derived macrophages (MDM); this often leads to surface cracking and device failure. The present studies examined the hypothesis that covalently attaching antioxidant, di-tert-butylphenol (DBP), to the urethane nitrogens of a polyether polyurethane (PU) via bromo-alkylation reactions could prevent this problem. PU was configured with two dosages of DBP, 0.

Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate.

Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked heterograft materials, porcine aortic valves or bovine pericardium, have been widely used in cardiac surgery to treat heart valve disease. However, these bioprosthetic heart valves often fail in long-term clinical implants due to pathologic calcification of the bioprosthetic leaflets, and for stentless porcine aortic valve bioprostheses, bioprosthetic aortic wall calcification also typically occurs. Previous use of the epoxide-based crosslinker, triglycidyl amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior biocompatibility, mechanics, and calcification resistance for porcine aortic valve cusps (but not porcine aortic wall) and bovine pericardium, vs.

The initiation of liver development is dependent on Foxa transcription factors.

The specification of the vertebrate liver is thought to occur in a two-step process, beginning with the establishment of competence within the foregut endoderm for responding to organ-specific signals, followed by the induction of liver-specific genes. On the basis of expression and in vitro studies, it has been proposed that the Foxa transcription factors establish competence by opening compacted chromatin structures within liver-specific target genes. Here we show that Foxa1 and Foxa2 (forkhead box proteins A1 and A2) are required in concert for hepatic specification in mouse.

The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.

Mutations in the gene encoding hepatocyte nuclear factor-4alpha (HNF-4alpha) result in maturity-onset diabetes of the young (MODY). To determine the contribution of HNF-4alpha to the maintenance of glucose homeostasis by the beta cell in vivo, we derived a conditional knockout of HNF-4alpha using the Cre-loxP system. Surprisingly, deletion of HNF-4alpha in beta cells resulted in hyperinsulinemia in fasted and fed mice but paradoxically also in impaired glucose tolerance.

Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency.

Foxa1 is a member of the winged helix family of transcription factors and is expressed in the collecting ducts of the kidney. We investigated its potential contribution to renal physiology in Foxa1-deficient mice on a defined genetic background. Foxa1(-/-) mice are dehydrated and exhibit electrolyte imbalance as evidenced by elevated hematocrit and plasma urea levels, hypernatremia, and hyperkalemia.