Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas

Neuropilins (NRP) are cell surface receptors for VEGF and SEMA3 family members. The role of NRP in neurons and endothelial cells has been investigated, but the expression and role of NRP in epithelial cells is much less clear. Herein, the expression and localization of neuropilin 1 (NRP1) was investigated in human and mouse skin and squamous cell carcinomas (SCC). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did colocalize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or EGF-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity

Factors Determining Outcome After Surgery for Chronic Groin Pain Following a Lichtenstein Hernia Repair

Some patients develop chronic groin pain after a Lichtenstein hernia repair. Previous studies have demonstrated beneficial effects of removal of entrapped inguinal nerves or a meshectomy in patients with chronic pain after open inguinal hernia mesh repair. Factors determining success following this remedial surgery are unknown. The aim of the study was to identify potential patient- or surgery-related factors predicting the surgical efficacy for inguinodynia following Lichtenstein repair.Consecutive adult patients with a history of persistent pain following Lichtenstein repair who underwent remedial surgery were analysed using univariate analysis. Significant confounders (p <0.05) were combined in a multivariate logistic regression model using a backward stepwise regression method.A total of 136 groin pain operations were available for analysis. Factors contributing to success were removal of a meshoma (OR 4.66) or a neuroma (OR 5.60) and the use of spinal anaesthesia (OR 4.38). In contrast, female gender (OR 0.30) and preoperative opioid use (OR 0.38) were significantly associated with a less favourable outcome. Using a multivariate analysis model, surgery under spinal anaesthesia (OR 4.04), preoperative use of opioids (OR 0.37), and meshoma removal (OR 5.31) greatly determined surgical outcome.Pain reduction after remedial surgery for chronic groin pain after Lichtenstein repair is more successful if surgery is performed under spinal anaesthesia compared to general anaesthesia. Removal of a meshoma must be considered as success rates are optimized following these measures. Patients using opioids preoperatively have less favourable outcomes

Size consistent multireference single and double excitation configuration interaction calculations. The multireference coupled electron-pair approximation

A new size-consistent extension to the multireference CI method is described. The method termed multireference CEPA (MRCEPA) is akin to a multireference CEPA(0) approach, though nonlinear terms do receive sep. attention. We show the performance of the approach in some model systems, as well as in an application to calcn. of ground and excited pp* states of ethylene. [on SciFinder (R)

Recall bias in pain scores evaluating abdominal wall and groin pain surgery

PURPOSE: To determine whether levels of pre-operative pain as recalled by a patient in the post-operative phase are possibly overestimated or underestimated compared to prospectively scored pain levels. If so, a subsequent misclassification may induce recall bias that may lead to an erroneous effect outcome. METHODS: Data of seven retrospective cohort studies on surgery for chronic abdominal wall and groin pain using three different pain scores were systematically analyzed. First, it was assessed whether retrospectively acquired pre-operative pain levels, as scored by the patient in the post-operative phase, differed from prospectively obtained pre-operative pain scores. Second, it was determined if errors associated with retrospectively obtained pain scores potentially lead to a misclassification of treatment outcome. Third, a meta-analysis established whether recall misclassifications, if present, affected overall study conclusions. RESULTS: Pain data of 313 patients undergoing remedial surgery were evaluated. The overall prevalence of misclassification due to a recall error was 13.7%. Patients not benefitting from surgery ('failures') judged their pre-operative pain level as more severe than it actually was. In contrast, patients who were pain free after remedial surgery ('successes') underestimated pre-operative pain scores. Recall misclassifications were significantly more present in failures than in successful patients (odds ratio 2.4 [95% CI 1.2-4.8]). CONCLUSION: One in seven patients undergoing remedial groin surgery is misclassified on the basis of retrospectively obtained pre-operative pain scores (success instead of failure, or vice versa). Misclassifications are relatively more present in failures after surgery. Therefore, the effect size of a therapy erroneously depends on its success rate

Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature

Crucial to designing angiostatic and vascular targeting agents is the identification of target molecules. Because angiogenesis is not limited to pathologic conditions, careful evaluation of putative therapeutic targets is warranted to prevent adverse effects associated with impaired physiologic angiogenesis. To identify tumor-specific angiogenesis markers, we compared transcriptional profiles of angiogenic endothelial cells isolated from malignant and nonmalignant tissues with those of resting endothelial cells. We identified 17 genes that showed specific overexpression in tumor endothelium but not in angiogenic endothelium of normal tissues, creating a therapeutic window for tumor vasculature-specific targeting. Antibody targeting of 4 cell-surface-expressed or secreted products (vimentin, CD59, HMGB1, IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. Our results demonstrate the usefulness of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy