Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186.

Background: Despite clinical success with T cell engagers (TCEs) targeting hematological malignancies, achieving a safe and efficacious dose in patients with solid tumors remains challenging. Due to potency, low levels of target antigen expression on normal tissues may not be tolerated. To overcome this, we engineered a novel conditionally active TCE design called COBRA (nditional ispecific edirected ctivation).

TriTACs, a Novel Class of T-Cell-Engaging Protein Constructs Designed for the Treatment of Solid Tumors.

T cells have a unique capability to eliminate cancer cells and fight malignancies. Cancer cells have adopted multiple immune evasion mechanisms aimed at inhibiting T cells. Dramatically improved patient outcomes have been achieved with therapies genetically reprogramming T cells, blocking T-cell inhibition by cancer cells, or transiently connecting T cells with cancer cells for redirected lysis.

COBRA™: a highly potent conditionally active T cell engager engineered for the treatment of solid tumors.

Conditionally active COBRA™ (COnditional Bispecific Redirected Activation) T cell engagers are engineered to overcome the limitations of inherently active first-generation T cell engagers, which are unable to discern between tumor and healthy tissues. Designed to be administered as prodrugs, COBRAs target cell surface antigens upon administration, but engage T cells only after they are activated within the tumor microenvironment (TME). This allows COBRAs to be preferentially turned on in tumors while safely remaining inactive in healthy tissue.

Monoclonal antibody-mediated detection of CTX-M β-lactamases in Gram-negative bacteria.

Gram-negative bacteria (GNB) that express CTX-M β-lactamases have become a serious threat to the clinical management of GNB infections. While antibody-based platforms have been successfully used in research settings to study and detect other β-lactamases-including SHV, CMY, and TEM enzymes-there is currently a lack of antibody-based tools to detect the CTX-M enzymes. Here we describe the development of an anti-CTX-M sandwich ELISA based on a pair of monoclonal antibodies (mAbs)-mAb 6101-33 and mAb 6101-19-used as the capture and detection antibody, respectively.

A rapid, inexpensive and disposable point-of-care blood test for sickle cell disease using novel, highly specific monoclonal antibodies.

Sickle cell disease (SCD) is a significant healthcare burden worldwide, but most affected individuals reside in low-resource areas where access to diagnostic testing may be limited. We developed and validated a rapid, inexpensive, disposable diagnostic test, the HemoTypeSC , based on novel monoclonal antibodies (MAbs) that differentiate normal adult haemoglobin (Hb A), sickle haemoglobin (Hb S) and haemoglobin C (Hb C). In competitive enzyme-linked immunosorbent assays, each MAb bound only its target with <0·1% cross-reactivity.

The Asian Grocery Store-Based Cancer Education Program: Creating New Education Modules.

Operating since 1994, the UCSD Moores Cancer Center's Asian Grocery Store-Based Cancer Education Program (the Program) is a proven and sustainable strategy for disseminating cancer and poison control information to Asian and Pacific Islander (API) communities. This paper describes the process taken to identify health topics that can be readily addressed within the Program's infrastructure and reports results of the pilot testing of the educational module that was developed by following that process. The development of each new module is guided by the Health Belief Model and the Tipping Point Model.

The RpoE Stress Response Pathway Mediates Reduction of the Virulence of Enteropathogenic Escherichia coli by Zinc.

Zinc supplements are an effective clinical treatment for infantile diarrheal disease caused by enteric pathogens. Previous studies demonstrated that zinc acts on enteropathogenic Escherichia coli (EPEC) bacteria directly to suppress several virulence-related genes at a concentration that can be achieved by oral delivery of dietary zinc supplements. Our in vitro studies showed that a micromolar concentration of zinc induced the envelope stress response and suppressed virulence in EPEC, providing a possible mechanistic explanation for zinc's therapeutic action.

Convergent and divergent dislocation of the pediatric elbow: two case reports and comprehensive review of literature.

Convergent and divergent pediatric elbow dislocations are rare injuries. When properly diagnosed and treated without delay, both types of dislocations have a good prognosis. We describe a case of convergent elbow dislocation in a 16-year-old boy.

The Clinical Application of Kaplan's Cardinal Line as a Surface Marker for the Superficial Palmar Arch.

We feel the original description of Kaplan's cardinal line provides a more accurate reference point to the superficial palmar arterial arch. We sought to anatomically correlate the relationship of Kaplan's cardinal line to the superficial palmar arch. Sixty hands (30 cadavers) were dissected after Kaplan's original description was drawn on each hand.

Dorsal dislocation of the distal interphalangeal joint and volar dislocation of the metacarpophalangeal joint in the same finger: a case report.

Double dislocations of the finger interphalangeal and/or metacarpophalangeal joints are a rare entity. Sixty-four cases of distal and proximal interphalangeal joint double dislocations have been previously reported. Five cases of metacarpophalangeal and interphalangeal double dislocations of the thumb have also been reported.

Comparison of fixation methods for scaphoid nonunions: a biomechanical model.

The purpose of this study was to analyze the relative bio- mechanical stability of three types of internal ixation with cancellous bone graft in a cadaveric, scaphoid nonunion model. A scaphoid nonunion model was created by remov- ing a volar wedge of bone from the waist of the scaphoid in 18 fresh frozen human cadavers. Cancellous sawbone graft was inserted into the osteotomy site and three groups of six cadavers each were then internally ixed with a pair of parallel 0.

Fixation systems of greater trochanteric osteotomies: biomechanical and clinical outcomes.

The development of cerclage systems for fixation of greater trochanteric osteotomies has progressed from monofilament wires to multifilament cables to cable grip and cable plate systems. Cerclage wires and cables have various clinical indications, including fixation for fractures and for trochanteric osteotomy in hip arthroplasty. To achieve stable fixation and eventual union of the trochanteric osteotomy, the implant must counteract the destabilizing forces associated with pull of the peritrochanteric musculature.

A biomechanical comparison of the modified Mason-Allen stitch and massive cuff stitch in vitro.

Purpose: The suture-tendon interface is generally regarded as the weak link in rotator cuff fixation. High rates of failure in arthroscopic rotator cuff repair have led to a search for strong yet easy-to-perform suture configurations. The goal of this study was to compare the strength of 2 commonly used suture configurations, the modified Mason-Allen stitch and the massive cuff stitch, when suture-anchored into bone.

Loss of total arc of motion in collegiate baseball players.

Published studies on asymptomatic athletes show an increase in external rotation and decrease in internal rotation while maintaining the total arc of motion of the glenohumeral joint. The purpose of this study was to determine whether overhand athletes with shoulder pain maintained their total arc of motion. Sixty-seven college-level baseball players were examined.

A meta-analysis of the literature on distal radius fractures: review of 615 articles.

A structured meta-analysis of the available literature was performed to evaluate the outcome of the treatment of displaced intra-articular fractures of the distal radius. A comprehensive search of Medline using the key words "radius" and "fracture" revealed over 4,000 articles. After limiting the search to clinical trials in English and excluding pediatric and geriatric age groups as well as biomechanical and animal studies, 615 abstracts were identified in the period from 1976 to May 1998.

Elbow fracture-dislocations: the role of hinged external fixation.

Fracture-dislocations of the elbow remain a complex problem in orthopaedics. The myriad of treatment protocols and methodologies focuses on precise articular alignment and restoration of the skeletal architecture. The goal is to re-establish function as quickly as possible so as to allow rehabilitation involving the full range of motion.