Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members

Background: mRNA levels of members of the Vascular Endothelial Growth Factor family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated as tissue-based markers of colon cancer. These studies, which used specimens obtained by surgical resection or colonoscopic biopsy, yielded contradictory results. We studied the effect of the sampling method on the marker accuracy of VEGF family members. Methods: Comparative RT-qPCR analysis was performed on healthy colon and colon carcinoma samples obtained by biopsy (n = 38) or resection (n = 39) to measure mRNA expression levels of individual VEGF family members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2 (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as markers for cellular stress and hypoxia. Results: Expression levels of COX2, 5-LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples of hypoxic cellular stress and a concurrent increment of basal expression levels of VEGF family members. This increment abolished differential expression of VEGF-B and VEGF-C in matched carcinoma resection samples and created a surgery-induced underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in carcinoma samples regardless of the sampling method. Conclusions: Sampling-induced hypoxia in resection samples but not in biopsy samples affects the marker-reliability of VEGF family members. Therefore, biopsy samples provide a more accurate report on VEGF family mRNA levels. Furthermore, this limited expression analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive mRNA-markers for molecular diagnosis of colon cancer

Molecular imaging of tumor-associated angiogenesis using a novel magnetic resonance imaging contrast agent targeting αvβ3 integrin

The recent introduction of biological anticancer therapy has renewed the interest in functional imaging of tumor-associated angiogenesis (TAA) as a tool to monitor early therapy response. The present study evaluated imaging of TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe targeting alpha(v)beta(3) integrin. HT29 human colorectal cancers were grown in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE sequence up to 110 min after injection of P1227 or gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA). Specificity was assessed by using P1227 1 h after intravenous administration of the alpha(v)beta(3) inhibitor cilengitide. Regions of interest were drawn encompassing the tumor rim and normal muscle. Imaging data were compared with microvessel density and alpha(v)beta(3) expression. Using P1227, specific enhancement of the angiogenic tumor rim, but not of normal muscle, was observed, whereas Gd-DOTA enhanced tumor and normal muscle. After administering cilengitide, enhancement with P1227, but not with DOTA, was significantly suppressed during the first 20 min. When using P1227, a significant correlation was observed between normalized enhancement of the tumor rim and immunohistochemical alpha(v)beta(3) integrin expression. Molecular MRI using a small monogadolinated tracer targeting alpha(v)beta(3) integrin and moderate magnetic field strength holds promise in assessing colorectal TAA

Use of a national identification database to determine the lifetime prognosis in cattle with necrotic laryngitis and the predictive value of venous pCO2

Background: Necrotic laryngitis, caused by Fusobacterium necrophorum, frequently requires surgical intervention (laryngostomy) in the chronic stage. Hypothesis/Objectives: To determine survival until slaughter of cattle surgically treated for necrotic laryngitis and to identify predictors of mortality. Animals: A total of 221 cattle diagnosed with necrotic laryngitis by laryngoscopy and surgically treated Methods: Retrospective cohort study. Clinical records were matched with the national cattle identification, registration, and movement database. Information on possible predictors including clinical examination, biochemistry, and surgery was collected. A multivariable Cox proportional hazard model was used to identify predictors of mortality. Results: The overall survival rate was 65.2% and 58.6% of the animals with a completed life cycle could be slaughtered. Animals <6 months old experienced significantly higher mortality risk (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1-3.5). The venous partial pressure of carbon dioxide (pCO(2); HR, 2.4; 95% CI, 1.4-4.2) at a 64.5 mm Hg cut-off was most significantly associated with mortality. Sensitivity and specificity of the final model consisting of age and pCO(2) were 49.1 and 86.4%, respectively. Instead of pCO(2), total carbon dioxide (TCO2) could also be used, with similar diagnostic accuracy. Conclusions and Clinical Relevance: The lifetime prognosis for chronic necrotic laryngitis in cattle with surgical intervention appears fair. Age, venous pCO(2) and TCO2 are easily accessible predictors of survival to support owners and veterinarians in their decision process of whether or not to operate and to identify high risk animals that require more intensive follow-up

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model.Journal Articleinfo:eu-repo/semantics/publishe

Case Report: Convalescent Plasma, a Targeted Therapy for Patients with CVID and Severe COVID-19

The disease course of COVID-19 in patients with immunodeficiencies is unclear, as well as the optimal therapeutic strategy. We report a case of a 37-year old male with common variable immunodeficiency disorder and a severe SARS-CoV-2 infection. After administration of convalescent plasma, the patient’s condition improved rapidly. Despite clinical recovery, viral RNA remained detectable up to 60 days after onset of symptoms. We propose that convalescent plasma might be considered as a treatment option in patients with CVID and severe COVID-19. In addition, in patients with immunodeficiencies, a different clinical course is possible, with prolonged viral shedding