Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma.

Background: Type 2 endotype asthma is driven by IL-4 and IL-13 signaling via IL-4Ra, which is highly expressed on airway epithelium, airway smooth muscle, and immunocytes in the respiratory mucosa, suggesting potential advantages of an inhalable antagonist. Lipocalin 1 (Lcn1), a 16 kDa protein abundant in human periciliary fluid, has a robust drug-like structure well suited to protein engineering, but it has never been used to make an inhaled Anticalin protein therapeutic.

Objectives: We sought to reengineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile.

SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity.

SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SOT101 among other immune cells specifically stimulates natural killer (NK) cells and memory CD8 T cells with no significant expansion or activation of the regulatory T cell compartment. In this study, we showed that SOT101 induced expression of cytotoxic receptors NKp30, DNAM-1 and NKG2D on human NK cells.

Tumor-Localized Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody-Anticalin Fusion PRS-343.

Purpose: 4-1BB (CD137) is a key costimulatory immunoreceptor and promising therapeutic target in cancer. To overcome limitations of current 4-1BB-targeting antibodies, we have developed PRS-343, a 4-1BB/HER2 bispecific molecule. PRS-343 is designed to facilitate T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation.

Incidence, location and classification of glenoid labrum meniscoid folds.

Introduction: The purpose of the present study was to arthroscopically investigate the incidence and location of labral meniscoid folds of the shoulder joint, as well as to classify them into types and detect any possible correlation with gender, side and age of patients.

Materials And Methods: The shoulder joint of 59 patients who underwent arthroscopic surgery for different reasons was examined for meniscoid folds. We classified all meniscoid folds into slim or thick and large or small.

Therapeutic antibodies to human L1CAM: functional characterization and application in a mouse model for ovarian carcinoma.

Recent work has identified L1CAM (CD171) as a novel marker for human carcinoma progression. Functionally, L1CAM promotes tumor cell invasion and motility, augments tumor growth in nude mice, and facilitates experimental tumor metastasis. These functional features qualify L1 as an interesting target molecule for tumor therapy.

Efficacy of oncolytic herpesvirus NV1020 can be enhanced by combination with chemotherapeutics in colon carcinoma cells.

NV1020, an oncolytic herpes simplex virus type 1, can destroy colon cancer cells by selectively replicating within these cells, while sparing normal cells. NV1020 is currently under investigation in a clinical phase I/II trial as an agent for the treatment of colon cancer liver metastases, in combination with conventional chemotherapeutic agents such as 5-fluorouracil (5-FU), SN38 (the active metabolite of irinotecan), and oxaliplatin. To study the synergy of NV1020 and chemotherapy, cytotoxicity and viral replication were evaluated in vitro by treating various human and murine colon carcinoma cell lines, using a colorimetric viability assay, a clonogenic assay, and a plaque-forming assay.

Gilbert's disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype.

Gilbert's disease leads to intermittent non-hemolytic hyperbilirubinemia by a reduction of hepatic bilirubin glucuronidation associated with the presence of the UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism. It is considered benign because it does not result in hepatocellular damage. However, pharmacogenetic analyses have linked UGT1A1*28 to drug toxicity and cancer predisposition.

Electromechanical delay of the knee extensor muscles is not altered after harvesting the patellar tendon as a graft for ACL reconstruction: implications for sports performance.

Although the scar tissue, which heals the donor site defect, has different elasticity from the neighbouring patellar tissue, it remains unclear if this scar tissue can lead to the changes of the electromechanical delay (EMD) of the knee extensor muscles. If such changes do exist, they can possibly affect both the utilization of the stored energy in the series elastic component, as well as the optimal performance of the knee joint movement. The purpose of this study was to investigate the influence of harvesting the patellar tendon during anterior cruciate ligament (ACL) reconstruction and the associated patellar tendon scar tissue development on the EMD of the rectus femoris (RF) and vastus medialis (VM) muscles.

Posterior tibial subluxation and short-term arthritis resulting from failed posterior cruciate ligament reconstruction.

Posterior tibial subluxations because of combined or isolated posterior cruciate ligament (PCL) injuries require detailed evaluation. PCL reconstructions are difficult procedures because of the low rate of such injuries and the complex anatomy of the ligament. We report on 2 cases of failed PCL reconstruction because of malpositioned femoral tunnels.

The diagnostic dilemma created by osteoid osteoma that presents as knee pain.

Purpose: Osteoid osteoma is a rare benign bone lesion with a high incidence in adolescents and young people. The objective of our study was to illustrate the difficulties in diagnosis of osteoid osteoma in patients presenting with atypical knee pain.

Type Of Study: Retrospective case series.

Simultaneous ligation of CD5 and CD28 with monoclonal antibodies restores impaired immunostimulatory function in human renal cell carcinoma.

Tumor cells, including renal cell carcinoma (RCC) cells, do not effectively stimulate T lymphocyte responses against specific antigens presented on their surface. Reasons for this low immunogenicity may include low or absent expression of MHC class I and/or class II molecules, as well as accessory and costimulatory molecules. We used tumor cell pretreatment with cytokines, together with monoclonal antibodies (mAbs) directed at receptors for costimulatory molecules, to render RCC cells immunostimulatory.

The presence of proprioceptive mechanoreceptors in the remnants of the ruptured ACL as a possible source of re-innervation of the ACL autograft.

This study investigated the presence of neural mechanoreceptors in the remnants of the ruptured ACL as a possible source of reinnervation of the ACL autologous graft. The remainder of the torn ACL was selected for further histological investigation from 17 patients during ACL reconstruction 3 months to 3.5 years after injury.

Alterations of the extensor apparatus after anterior cruciate ligament reconstruction using the medial third of the patellar tendon.

Purpose: The objective of this study was the ultrasound evaluation of the donor defect of the patellar tendon (PT) and the radiologic evaluation of the patella after harvesting of the medial third as a bone-patella tendon-bone (BPTB) graft for anterior cruciate ligament (ACL) reconstruction.

Type Of Study: This was a cohort study.

Methods: In 45 patients who had ACL reconstruction, the extensor apparatus of the donor side was studied using ultrasound cross-sections and radiographs (anteroposterior, lateral, and a tangential view of the patella) 3 to 70 months postoperatively.

Patellar fractures associated with medial-third bone-patellar tendon-bone autograft ACL reconstruction.

Patella fractures following anterior cruciate ligament (ACL) reconstruction are a recognized but rarely reported complication. To our knowledge, 24 reports of patella fractures after ACL reconstruction using the central-third patella-tendon autograft have been reported in the literature. Patellar fractures associated with the use of the medial-third bone-patellar tendon-bone autograft have not been reported.

Posterior cruciate ligament architecture: evaluation under microsurgical dissection.

Purpose: Our objective was to verify the fiber anatomy of the posterior cruciate ligament (PCL) and to measure the main dimensions and the femoral and tibial attachment site distances of the ligament after microsurgical dissection. We hypothesized that PCL anatomy is more complex than the 2 traditionally characterized bands.

Type Of Study: This is a purely anatomic description of microdissections of the PCL, focused on the fine anatomy of the ligament.

Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation.

Allogeneic human histocompatibility leukocyte antigen (HLA)-matched tumor cell lines that have been made immunogenic by the transfer of genes encoding for costimulatory molecules such as CD80 are considered to be potential vaccines for the induction of systemic immune reactions in cancer patients. We used a human HLA-A2.1+ CD80-transfected breast carcinoma cell line (KS-CD80) and investigated in vitro the efficiency at which antigen (Ag)-specific responses were induced following the stimulation of allogeneic HLA-A2.

Interleukin-12 requires initial CD80-mediated T-cell activation to support immune responses toward human breast and ovarian carcinoma.

One possible reason for the poor immunogenicity of tumors is the induction of peripheral tolerance by tumor cells that fail to deliver costimulatory signals. Furthermore, T cells stimulated with wild-type tumor cells often fail to secrete cytokines. The present study has been undertaken to identify cytokines that cooperate with CD80 in T-cell activation in vitro toward human breast and ovarian carcinoma cell lines.

T cell activation by monoclonal antibodies bound to tumor cells by a cell surface displayed single-chain antibody.

Tumor cells often lack the costimulatory molecules necessary for T cell activation. However, the transformation of cells with more than one stimulatory molecule is a difficult procedure. We therefore developed a retroviral vector for the expression of a cell membrane anchored single-chain antibody fragment (scFv) directed against the hapten 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one (phOx).

Nerve and vessel injuries during high tibial osteotomy combined with distal fibular osteotomy: a clinically relevant anatomic study.

Based on our clinical experience and an anatomical study, we examined the conditions under which injury to the popliteal artery, tibial nerve or peroneal nerve and its branches may occur during high tibial osteotomy. In 250 high tibial osteotomies performed in our department, we observed the following intraoperative complications. (1) The popliteal artery was severed in 1 patient and repaired by the same surgical team using a microsurgical technique.

Difficulties and early results of the endoscopic carpal tunnel release using the modified Chow technique.

In reporting on the preliminary results of our series of 76 patients, this paper aims to identify potentially complicating aspects of endoscopic carpal tunnel release (ECTR) using the two-portal Chow technique, and to recommended solutions, based on our early experience, which enhance the ease and safety of this minimally invasive technique. Of the first 24 patients, 16 cases required conversion to an open procedure. Based on these initial cases, we developed certain modifications of the Chow technique which precluded any need for open conversion in the 60 remaining cases.

Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.

Colorectal cancer is considered a non-immunogenic malignany. One strategy to augment the immunogenicity of such tumours is represented by the expression of costimulatory molecules by gene transfer. Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro.

Strong immunogenic potential of a B7 retroviral expression vector: generation of HLA-B7-restricted CTL response against selectable marker genes.

The stimulation of a specific immune response is an attractive goal in cancer therapy. Gene transfer of co-stimulatory molecules and/or cytokine genes into tumor cells and the injection of these genetically modified cells leads to tumor rejection by syngeneic hosts and the induction of tumor immunity. However, the development of host immune response could be either due to the introduced immunomodulatory genes or due to vector components.

Anterior cruciate ligament reconstruction with the press-fit technique. 2-5 years followed-up of 42 patients.

42 patients underwent anterior cruciate ligament (ACL) reconstruction with the press-fit technique. The ACL was reconstructed with a bone-tendon-bone graft from the medial third of the patellar tendon. The graft was stabilized without screws in the femur and tibia by press-fit.