Higher levels of adiponectin in American than in Japanese men despite obesity

Levels of adiponectin are inversely associated with obesity levels. We examined the levels of adiponectin in American (n = 98) and Japanese (n = 92) men aged 40 to 49 years. Contrary to our expectations, the American men had higher levels of adiponectin than the Japanese men (13.3 +/- 5.8 vs 7.3 +/- 4.2 (microg/mL) despite higher levels of obesity. Smaller areas of visceral adipose tissue in American than in Japanese men may have resulted in the higher levels of adiponectin.     

The determinants of plasma plasminogen activator inhibitor-1 levels differ for American and Japanese men aged 40-49

BACKGROUND: Elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels were associated with higher incidence of type II diabetes. Elucidating the determinants of PAI-1 in various ethnicities may help to understand the susceptibility to developing diabetes. The aim of our study was to compare PAI-1 levels between Americans and the Japanese in the post-war generation and to elucidate the determinants of the PAI-1 levels. METHODS: We conducted a cross-sectional study on a total of 198 men aged 40-49 in the US (Body mass index (BMI): 27.0+/-3.3 kg/m(2)) and Japan (BMI: 23.3+/-3.1 kg/m(2)). Examination included physique measurement (BMI and waist girth), blood analysis (lipid profiles, glucose, insulin, C-reactive protein, and PAI-1), and life-style assessment by self-administered questionnaires. RESULTS: PAI-1 levels were significantly lower in American than in Japanese men, even after adjustment for age, waist girth, cigarette smoking, habitual alcohol drinking, and other factors. In the Americans, waist girth, insulin, and cigarette smoking were significantly associated with PAI-1 levels, while waist girth and triglycerides were significantly associated with PAI-1 levels in the Japanese. CONCLUSIONS: PAI-1 levels were significantly lower in American than in Japanese men and the determinants of PAI-1 levels differ for American and Japanese men aged 40-49.     

Antibody-based tumor vascular theranostics targeting endosialin/TEM1 in a new mouse tumor vascular model

Tumor endothelial marker 1 (TEM1, endosialin) is a tumor vascular marker with significant diagnostic and therapeutic potential. However, in vivo small animal models to test affinity reagents specifically targeted to human (h)TEM1 are limited. We describe a new mouse tumor model where tumor vascular endothelial cells express hTEM1 protein. Methods: Immortalized murine endothelial cells MS1 were engineered to express hTEM1 and firefly luciferase and were inoculated in nude mice either alone, to form hemangioma-like endothelial grafts, or admixed with ID8 ovarian tumor cells, to form chimeric endothelial-tumor cell grafts. MORAb-004, a monoclonal humanized IgG₁ antibody specifically recognizing human TEM1 was evaluated for targeted theranostic applications, i.e., for its ability to affect vascular grafts expressing hTEM1 as well as being a tool for molecular positron emission tomography (PET) imaging. Results: Naked MORAb-004 treatment of mice bearing angioma grafts or chimeric endothelial-tumor grafts significantly suppressed the ability of hTEM1-positive endothelial cells, but not control endothelial cells, to form grafts and dramatically suppressed local angiogenesis. In addition, highly efficient radioiodination of MORAb-004 did not impair its affinity for hTEM1, and [¹²⁴I]-MORAb-004-PET enabled non-invasive visualization of tumors enriched with hTEM1-positive, but not hTEM1 negative vasculature with high degree of specificity and sensitivity. Conclusion: The development of a new robust endothelial graft model expressing human tumor vascular proteins will help accelerate the development of novel theranostics targeting the tumor vasculature, which exhibit affinity specifically to human targets but not their murine counterparts. Our results also demonstrate the theranostic potential of MORAb-004 as PET imaging tracer and naked antibody therapy for TEM1-positive tumor.     

The NFκB inhibitor,SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype

The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.     

Scanning electron microscope observations on the monogenean parasite <Emphasis Type="BoldItalic">Paraquadriacanthus nasalis</Emphasis> from the nasal cavities of the freshwater fish <Emphasis Type="BoldItalic">Clarias gariepinus</Emphasis> in Egypt with a note on some surface features of its microhabitat

Surface features of the monogenean Paraquadriacanthus nasalis Ergens, 1988 (quoted by Kritsky, 1990) inhabiting the nasal cavities of the freshwater fish Clarias gariepinus were studied for the first time using scanning electron microscopy. The anterior adhesive areas possess two slit-like openings. Many small openings were detected on the tegument covering the anterior-most region of the head. Some considerably large openings were also found in the median region between the two slit-like openings of the adhesive sacs. A transverse slit-like mouth opening with two lip-like structures was detected on the ventral surface of the body. Three types of presumed sensory structures were found associated with the tegument of the anterior adhesive area and anterior region of the body. These are surface ciliary sensilla, dome-shaped structures, and many spherical structures. The possible functions of these presumed sensory structures were discussed. The tegument covering the anterior adhesive area lacks microvilli, while the tegument covering the haptor is associated with microvilli. The haptoral sclerites were found in two different positions. Some surface features of the nasal cavities of C. gariepinus (microhabitat of P. nasalis) were also studied using scanning electron microscopy. Many lamellae-like and spine-like structures were recognized. The epithelium lining in some regions of the nasal cavities has small and large openings and covered with mucus. The possible roles of some haptoral sclerites in the attachment of the parasite to the host tissues were discussed.     

Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC- and ctDNA-based liquid biopsies is envisioned.     

The clinical presentation caused by truncating CHD8 variants

Variants in the chromodomain helicase DNA-binding protein 8 (CHD8) have been associated with intellectual disability (ID), autism spectrum disorders (ASDs) and overgrowth and CHD8 is one of the causative genes for OGID (overgrowth and ID). We investigated 25 individuals with CHD8 protein truncating variants (PTVs), including 10 previously unreported patients and found a male to female ratio of 2.7:1 (19:7) and a pattern of common features: macrocephaly (62.5%), tall stature (47%), developmental delay and/or intellectual disability (81%), ASDs (84%), sleep difficulties (50%), gastrointestinal problems (40%), and distinct facial features. Most of the individuals in this cohort had moderate-to-severe ID, some had regression of speech (37%), seizures (27%) and hypotonia (27%) and two individuals were non-ambulant. Our study shows that haploinsufficiency of CHD8 is associated with a distinctive OGID syndrome with pronounced autistic traits and supports a sex-dependent penetrance of CHD8 PTVs in humans.