Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells

Introduction: There is a high expression of receptor tyrosine kinase like orphan receptor-1 (ROR-1), a tyrosine kinase receptor, in various tumor-cell types. ROR-1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR-1 is an attractive and promising therapeutic target. There are many therapeutic approaches that target ROR-1 and these include specific monoclonal antibodies (mAbs), modified T cells (CART cell), miRNAs and tyrosine kinase inhibitors (TKI).

Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.

Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1⁺ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment.     

Drug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's disease

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders, bringing about huge medical and social burden in the elderly worldwide. Many aspects of its pathogenesis have remained unclear and no effective treatment exists for it. Within the past 20 years, various mice models harboring AD-related human mutations have been produced. These models imitate diverse AD-related pathologies and have been used for basic and therapeutic investigations in AD. In this regard, there are a wide variety of preclinical trials of potential therapeutic modalities using AD mice models which are of paramount importance for future clinical trials and applications. This review summarizes more than 140 substances and treatment modalities being used in transgenic AD mice models from 2001 to 2011. We also discuss advantages and disadvantages of each model to be used in therapeutic development for AD.     

Assessing college students’ ego-identity status and their use of motivational regulation strategies

Using correlational analyses and structural equation modeling, this study tests three hypotheses: students’ reported use of motivational strategies is 1) correlated with their ego-identity status; 2) positively correlated with their reported use of learning strategies and negatively associated with their level of procrastination; and 3) related to their existing motivational beliefs and attitudes. Participants were American college students (N?=?113). The findings support all three hypotheses.

The study computed Pearson product moment correlations (listwise) among the ego identity and motivation measures; significant correlations ranged from 0.19 to 0.29. To test the hypothesized conceptual model, the study subjected the correlations to a confirmatory factor analysis. The five model varimax solution had excellent loadings on 16 variables; their standardized path coefficients were highly significant (p?df?=?161, p?=?0.0003; goodness of fit (GFI)?=?0.913; RMSEA?=?0.056).

The findings support the existence of a positive relationship between college students’ identity status and their use of motivational regulation strategies. They also suggest students’ use of motivational strategies is closely related to their use of cognitive and metacognitive strategies, but not to their level of academic procrastination. This article discusses practical applications for mental health providers and educators.     

Coincidence of celiac disease with nongastrointestinal tumors in children

The association of celiac disease (CD) with cancers of gastrointestinal origin has been noted. However, coincidence of CD with nongastrointestinal neoplasms is an unusual event. Here we present five children with concurrent CD and nongastrointestinal neoplasms. All of the patients had positive serologic results for anti-tTG antibodies. Histological investigation of intestinal mucosa showed inflammation (Marsh score = 2) in all the patients. Two of these patients represented with germ cell malignancies. One patient had Wilms' tumor. To our knowledge, these are the first reports of coincidence of these two cancers with CD in children. From the remaining two patients, one was diagnosed with acute lymphoblastic leukemia, and the other with astrocytoma. The diagnosis of malignancy preceded CD diagnosis in all the patients (mean ages of cancer and CD diagnosis of 1.8 and 5.4 years old, respectively). Whether malignancy can promote immune deregulation and predispose to CD is uncertain. On the other hand, undiagnosed celiac may be a risk factor for cancer. Our results suggest a potential association of CD with malignancy nature of CD, however, occurrence of CD may be influenced by various intrinsic and extrinsic factors. There are few reports noting CD as a paraneoplastic condition. Further investigations are necessitated to stablish such relationship.     

Severe scar problems following use of a locking barbed skin closure system in the foot

BackgroundBarbed sutures provide a novel technique for knotless wound closure. They have mainly been used in plastic and general surgery. There are no reports about its use in the foot.MethodsWe present a case series of 11 feet in 8 patients whose wounds were closed with barbed sutures. Ten had primary hallux valgus correction and one had a revision correction.ResultsNo problems were noted at 2-weeks follow-up. Four of the 11 cases required open suture excision due to an adverse reaction. Five were followed to delayed wound healing. Histology results from one scar showed a localised histiocytic reaction and superficial dermal abscess formation.ConclusionsWe feel the thin subcutaneous tissue of the foot, the amount of motion and pressure from the shoe causes the barbs to repeatedly irritate the soft tissue. Based on our short case series we cannot recommend the use of a barbed skin closure system in the foot.     

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.