Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc(Min/+) mice

The transmembrane glycoprotein CD98 regulates integrin signaling that in turn controls cell proliferation and survival. CD98 expression is upregulated in various carcinomas, including colorectal cancer. Recently, by generating gain- and loss-of-function mouse models featuring genetic manipulation of CD98 expression specifically in intestinal epithelial cells (IECs), we have explored the crucial role of CD98 in the regulation of intestinal homeostasis and inflammation-associated tumorigenesis. In the present study, we investigated the contribution of CD98 to intestinal tumorigenesis in Apc(Min/+) mice and the underlying mechanism of action. Mice featuring IEC-specific CD98 overexpression (Tg animals) were crossed with Apc(Min/+) mice, and the characteristics of intestinal adenoma formation were assessed. Compared with Apc(Min/+) mice, Tg/Apc(Min/+) animals exhibited increases in both intestinal tumor incidence and tumor size; these parameters correlated with enhanced proliferation and decreased apoptosis of IECs. IEC-specific CD98 overexpression resulted in increased synthesis of the oncogenic proteins c-myc and cyclin-D1 in Apc(Min/+) mice, independently of the Wnt-APC-β-catenin pathway, suggesting the implication of CD98 overexpression-mediated Erk activation. IEC-specific CD98 overexpression enhanced the production of proinflammatory cytokines and chemokines that are crucial for tumorigenesis. We validated our results in mice exhibiting IEC-specific CD98 downregulation (CD98(flox/+)VillinCre animals). IEC-specific CD98 downregulation efficiently attenuated tumor incidence and growth in Apc(Min/+) mice. The reduction of intestinal tumorigenesis upon IEC-specific CD98 downregulation was caused by the attenuation of IEC proliferation and cytokine/chemokine production. In conclusion, we show that CD98 exerts an oncogenic activity in terms of intestinal tumorigenesis, via an ability to regulate tumor growth and survival.     

Contralateral recurrence of a malignant solitary fibrous tumor of the pleura

We present an unusual case of a contralateral recurrence of malignant solitary fibrous tumor of the pleura (SFTP) nine years after a complete resection. Recurrence of malignant SFTP has already been described, but is usually localized. In our case the patient underwent surgical resection for a malignant SFTP of the left upper lobe in 2000. Nine years later computed tomography (CT)-scans showed lesions that were suspicious of tumor recurrence in the right lung. Thoracoscopy, wedge-resections and pathological findings revealed four nodules of a malignant SFTP of the right middle and lower lobe, histopathologically identical to the tumor, which had been resected nine years ago. A coincidental mucinous bronchioloalveolar carcinoma of the left lower lobe was resected by thoracotomy. To our knowledge this is the first report of contralateral recurrence of a malignant SFTP years after complete resection in the literature. The possibility of a new primary tumor on the right with local metastasis could not be excluded in the clinical and histopathological examinations. Therefore, contralateral recurrence of malignant SFTP should be considered in the postoperative follow-up even years after complete resection.     

Kidney transplantation and infection in childhood

Infectious risk is more important in the transplanted child than in adult because children are less often immunised against pathogens ant more exposed than adults to numerous infectious agents (virus but also bacteria including pneumococcus). The application of the standard immunisation schedule must be a permanent concern of transplantation (Tx) teams. Some vaccines that are not planned in the standard immunization schedule are particularly advised for the child and his family circle, as well as for caregivers. Immunisation response must be evaluated by a serological follow-up before Tx, in particular during the pre-Tx diagnostic work-up, then regularly after Tx. The more frequent absence of immunisation against Epstein Barr Virus (EBV) in children explains the increased frequency of post-transplant lymphoproliferative disorder at the pediatric age.     

New considerations on the management of osteoporosis in Central and Eastern Europe (CEE): summary of the ��3rd Summit on Osteoporosis��CEE��, November 2009, Budapest, Hungary

Introduction

In November 2009, the ??3rd Summit on Osteoporosis??Central and Eastern Europe (CEE)?? was held in Budapest, Hungary. The conference aimed to tackle issues regarding osteoporosis management in CEE identified during the second CEE summit in 2008 and to agree on approaches that allow most efficient and cost-effective diagnosis and therapy of osteoporosis in CEE countries in the future.

Discussion

The following topics were covered: past year experience from FRAX? implementation into local diagnostic algorithms; causes of secondary osteoporosis as a FRAX? risk factor; bone turnover markers to estimate bone loss, fracture risk, or monitor therapies; role of quantitative ultrasound in osteoporosis management; compliance and economical aspects of osteoporosis; and osteoporosis and genetics. Consensus and recommendations developed on these topics are summarised in the present progress report.

Conclusion

Lectures on up-to-date data of topical interest, the distinct regional provenances of the participants, a special focus on practical aspects, intense mutual exchange of individual experiences, strong interest in cross-border cooperations, as well as the readiness to learn from each other considerably contributed to the establishment of these recommendations. The ??4th Summit on Osteoporosis??CEE?? held in Prague, Czech Republic, in December 2010 will reveal whether these recommendations prove of value when implemented in the clinical routine or whether further improvements are still required.     

Perinatal nutritional programming of health and metabolic adult disease

Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases.The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on the type of alteration (nutritional,psychological,endocrine disruptors,etc.),its intensity and duration,species,sex and the time during which it is applied.Perinatal stress,via disturbances of both hy-pothalamo-pituitary-adrenal (HPA) axis and sympathoadrenal-system (SAS),as well as brain-adipose axis and pancreas alterations could play a crucial role.Interestingly,it has been demonstrated that perinatal insults may be transmitted transgenerationally,suggesting that these long-term consequences may be inherited via epigenetic mechanisms.Finally,since the placenta has been demonstrated to be sensitive to perinatal nutritional manipulations,the identification of placental markers may thus represent an important new avenue to identify the more susceptible babies prone to developing meta-bolic diseases.     

Depressive symptoms predict long-term mortality after liver transplantation

Objective

Depressive symptoms are common after liver transplantation (LT). We studied whether depressive symptoms affect long-term survival after LT.

Methods

In a prospective cohort study, 134 liver transplant patients were assessed for depressive symptoms using the Beck Depression Inventory—short form (BDI), focusing on the 3 months post-LT score and on the score change from the waiting list period. They were followed up for long-term survival. The median duration of the follow-up period was 43 months post-LT. None of the 134 patients was lost to follow-up for survival.

Results

A total of 33.6% of the LT patients had mild to moderate depressive symptoms 3 months post-LT. Eighteen (13.4%) patients died during the follow-up. Using Cox proportional hazards analysis, depressive symptoms were significantly associated with mortality (hazard ratio [HR] 1.22, 95% confidence interval (CI) 1.07-1.40, P<.003), one more point in the BDI score being associated with a 17% increase in mortality risk. Other predictive factors of mortality were older age and hepatitis C virus with recurrence 3 months post-LT. Similarly, an increase in depressive symptoms between the waiting list and 3 months post-LT periods predicted mortality (HR 1.18, 95% CI 1.01-1.38, P=.03), especially for patients without depressive symptoms on waiting list (HR 1.56, 95% CI 1.16-2.12, P=.004).

Conclusion

Depressive symptoms after LT and an increase in depressive symptoms between the waiting list and post-LT are associated with an increased risk of long-term mortality. Interventions that could reduce depressive symptoms could potentially decrease long-term mortality after LT.