Serosal Cells Research Articles

Elevated carbohydrate antigen 125 (CA125) is associated with incident heart failure and mortality in acute coronary syndrome.

Carbohydrate antigen 125 (CA125), a mucin produced by serosal cells in response to mechanical and inflammatory stimuli, has emerged as an important biomarker to guide risk stratification in heart failure (HF). The prognostic value of CA125 in acute coronary syndrome (ACS) patients is less explored. In a cohort of 524 ACS patients (73% males, mean age 67±12years), we assessed the associations between CA125 and the risk for HF and death during a median follow-up period of 27.3months for incident HF and 39.5months for mortality. Plasma CA125 was measured within 24h after admission in the entire cohort and after 6weeks in a subgroup of 115 elderly patients (>75years of age). We also assessed the relationships between baseline CA125 and echocardiographic parameters of cardiac structure and function at 1year post-ACS in this subgroup. Baseline CA125 was associated with incident HF in the entire cohort in a Cox proportional hazards model adjusted for age, sex, cardiovascular (CV) risk factors (diabetes, smoking, hypertension, previous HF, previous ACS and previous stroke), renal function and revascularization {hazard ratio [HR] 1.46 [95% confidence interval (CI) 1.10-1.93] per 1-standard deviation [SD] CA125 increase; P=0.009}. In the detailed follow-up subgroup, elevated baseline CA125 predicted subsequent deterioration of left ventricular (LV) ejection fraction (LVEF), defined as a >5% absolute LVEF decrease in patients with LVEF≥50% at discharge [odds ratio (OR) 3.31 (95% CI 1.15-9.54) per 1-SD baseline CA125 increase; P=0.027]. We also found significant correlations between high baseline CA125 and larger LV volumes (LV end-diastolic volume index, Spearman's r=0.329, P<0.001; LV end-systolic volume index, r=0.391, P<0.001) and left atrial volume index (r=0.320, P<0.001) at 1year post-ACS, indicative of adverse cardiac remodelling. Elevated baseline and follow-up CA125 were associated with increased mortality, independently of age and sex [HR 1.37 (95% CI 1.09-1.71), P=0.006, per 1-SD baseline CA125; HR 1.98 (95% CI 1.06-3.67), P=0.031, per increasing 6week CA125 tertile]. The relationship between 6week CA125 and incident mortality remained significant in the fully adjusted model [HR 2.23 (95% CI 1.15-4.35) per increasing CA125 tertile; P=0.018]. We report independent associations between elevated CA125, LV dysfunction, cardiac remodelling, incident HF and mortality post-ACS. Our results warrant further evaluation of CA125 as a potential biomarker for risk stratification and management of ACS patients, both at the time of the acute coronary event and during follow-up.

Characterization of the serosal cells surrounding Cotesia kariyai larvae and their role in host immunosuppression

About half of the serosal cells (Scs) of Cotesia kariyai (Ck) eggs are released as teratocytes into the host body cavity after hatching, and another half remain attached to the larval epidermis until the 1st instar larvae of Ck ecdysis to 2nd instars. To investigate the role of the serosal cells surrounding Ck 1st instar larvae (1st Scs) in immune avoidance, Ck 1st instar larvae with and without Scs removed using dispase were transplanted into Mythimna separata larvae (MsLrv), respectively. As a result, Ck 1st instar larvae surrounded by Scs were less susceptible to the MsL encapsulation than Ck 1st instar larvae without the Scs, suggesting that the Scs are involved in suppressing the encapsulation of the MsL. Furthermore, when the granular cells and plasmatocytes of the MsL involved in the encapsulation were incubated in a medium supplemented with proteins extracted from 1st Scs, the plasmatocytes failed to adhere to glass slides, and did not spread their filopodium and lamellipodium. These findings suggest that 1st Scs express proteins that inhibit filopodium and lamellipodium spreading to prevent the MsL plasmatocytes from adhering to Ck larvae.

A minimal promoter region of Kit gene recapitulates mast cell differentiation in development, aging and inflammation

To follow mast cells (MCs) distribution during aging and inflammation, we characterized two transgenic mouse models in which the EGFP expression is controlled by 9 kb or 12 kb of Kit gene promoter, defined as p18 and p70, respectively. We detected EGFP-positive cells in the serosal surfaces of the peritoneum, pleuras and pericardium, mucosal cavities, and connective tissue of almost all organs including gonads of p70, but not of p18 mice. By FACS and immunofluorescence for FcεR1, Kit and β7-integrin, we found that these EGFP positive cells were MCs. In non-inflammatory conditions, a higher percentage of EGFP positive cells was found in juvenile with respect to adult serosal surfaces, but no differences between males and females at both developmental ages. We found, however, a striking difference in developing gonads, with low numbers of EGFP positive cells in fetal ovaries compared to age matched testes. Under inflammatory conditions caused by high fat diet (HFD), mice showed an increase in serosal EGFP positve cells. Altogether our results identify a regulatory region of the Kit gene, activated in MCs and that directing EGFP expression, can be employed to trace this immune cell type throughout the organism and in different animal conditions.

Oral metastasis of pleural sarcomatoid mesothelioma, a rare aggressive variant of mesothelioma and a diagnostic challenge

<h3>Introduction</h3> Malignant mesothelioma is a rare neoplasm that most commonly develops after exposure to asbestos and arises from the serosal cells of the pleura or rarely peritoneum. Various histological subtypes have been recog- nized: epithelioid, sarcomatoid, biphasic-epithelioid, and biphasic-sarcomatoid, with the sarcomatoid variant being a less common, but more aggressive variant. Numerous genetic alterations have been identified in the development and progression of malignant mesothelioma, most notably mutations in tumor suppressor genes, <i>neurofibromatosis type 2 (NF2), BRCA1-associated protein-1 (BAP1),</i>and <i>cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF)</i>. Mesothelioma metastasis to the oral cavity is infrequent, with only nineteen cases reported in the literature. Soft tissue involvement of the oral cavity has been reported in the tongue, followed by the mandibu- lar gingiva, and alveolar mucosa. Prognosis for malignant mesothelioma is poor as it is typically unresponsive to conventional chemotherapeutic agents. New targeted therapies are currently in ongoing clinical trials. <h3>Case Findings</h3> An 81-year-old male, undergoing treatment for malignant pleural mesothelioma and with a history of asbestos exposure, presented for evaluation of a raised, necrotic mass on the left posterior mandibular buccal and lingual gingiva. Panoramic radiograph revealed extensive bone loss. The histopathology was that of a sarco- matoid neoplasm. Immunohistochemistry demonstrated positive staining for WT1, cyclin D1, and P53, supporting the diagnosis of metastatic malignant mesothelioma, sarcomatoid variant. Other stains that help to define mesothe- lioma such as CK5/6, calretinin, and D2-40 were negative. Despite equivocal immunostaining results, the diagnosis was further supported by comprehensive genomic analysis with identification of mutated <i>NF2</i>and <i>BAP1</i>tumor sup- pressor genes. <h3>Conclusion</h3> The diagnosis of malignant pleural mesothelioma relies on morphology supplemented with immuno- histochemistry. The diagnosis is challenging, especially so for the sarcomatoid variant, with immunohistochemical staining profiles often being inconsistent. The current case demonstrates the utility of comprehensive genomic analysis in firmly establishing the diagnosis.

Mesothelioma.

Mesothelioma arises from the surface serosal cells lining the pleural, peritoneal, and pericardial cavities. It has three variants including: epithelioid, sarcomatous/desmoplastic, and biphasic types. Mesothelioma cells, predominantly of the epithelioid type, can shed into effusions as sheets, clusters/ morulae, papillae, or single cells. The challenges to cytologic diagnosis of mesothelioma are two-fold: 1. distinguishing mesothelial cells from metastatic malignant (most commonly carcinoma) cells; 2. distinguishing reactive mesothelial from mesothelioma cells. Immunocytochemistry is a helpful aid to cytologic evaluation for the former. The distinction of reactive mesothelial cells from mesothelioma can be more difficult, as there is considerable overlap in their appearances in effusion specimens. Recently developed ancillary molecular and genetic tests are proving to be useful in confirming the diagnosis of malignant mesothelioma in cytology specimens.

Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities

The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NM on ILCs and other components of the serosal immune system are scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NM may lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NM on the serosal immune system.

Assembly, Release, and Transport of Airway Mucins in Pigs and Humans.

The respiratory system is protected from inhaled particles and microbes by the mucociliary system. This system differs between animal species, where pigs and humans have numerous submucosal glands. The polymer-forming mucin, MUC5B, is packed in a highly organized way in granules of the mucus-secreting cells in the glands. Upon secretion, the packed MUC5B is flushed out by a chloride- and bicarbonate-rich fluid from the cystic fibrosis transmembrane conductance regulator-expressing serosal cells located at the most distal part of the gland. The bicarbonate raises the pH and removes calcium from the N terminus of MUC5B, allowing the mucin to be pulled out into a linear polymer. Thousands of such polymers gather in bundles in the submucosal gland duct, and these bundles appear at the opening of the glands. They are moved by the beating cilia, and sweep over the airway surface and are patchily coated with the MUC5AC mucin from the surface goblet cells. The movement of these bundles is controlled by the MUC5AC mucin attachment/detachment to the goblet cells. Thus, higher animals with submucosal glands and large diameters of the proximal airways are efficiently cleaned by the thick mucus bundles sweeping the airway surface and moving particles and bacteria toward the larynx.

Development and ultrastructure of the thickened serosa and serosal cuticle formed beneath the embryo in the stonefly Scopura montana Maruyama, 1987 (Insecta, Plecoptera, Scopuridae)

We aimed to describe the development and ultrastructure of the thickened serosa and serosal cuticle formed beneath the embryo of Plecoptera, using Scopura montana of Scopuridae as a euholognathan representative. Using transmission electron microscopy, we found that the egg membranes were composed of a thick exochorion, a thicker endochorion consisting of two sublayers, and an extremely thin vitelline membrane. The egg membrane construction represents a groundplan feature of the euholognathan egg membranes. The serosa converges beneath the embryo to form a thickened serosa, comprising cells in a radial arrangement, in association with the formation of the amnioserosal fold. The thickened serosa then deposits the thickened serosal cuticle, consisting of four layers differing in fine structure and electron density. After achieving its secretory function, the thickened serosa then disintegrates, and the liberated serosal cells float for a short period in the peripheral region of the egg inside. Collectively, our findings should provide the basis for further characterization of the serosal structures concerned, but we were unable to corroborate previous studies assigning the thickened serosa and serosal cuticle in Plecoptera to the water absorption function.

Histopathology and enhanced detection of tumor invasion of peritoneal membranes.

Tumor invasion of the peritoneal membrane may have an adverse prognostic significance, but its histopathologic features can be diagnostically difficult to recognize. We observed that local peritoneal injury associated with tumor invasion is characterized by activation and proliferation of serosal stromal cells that express cytokeratin, a characteristic property of injured serosal membranes that may have diagnostic utility. To explore this, we examined 120 primary tumors of the gastrointestinal tract and pancreaticobiliary system using cytokeratin and elastic stains to assess for tumor invasion of peritoneal membranes. Peritoneal invasion by tumor was associated with retraction, splaying, and destruction of the elastic lamina and proliferation of keratin-expressing stromal cells of serosal membranes. All 82 peritoneal invasive tumors were characterized by neoplastic cells that invaded the elastic lamina and the serosal connective tissue with neoplastic cells that abutted or were surrounded by keratin-positive stromal cells, whereas all 38 tumors limited to the subserosa showed none of these features. The diagnosis of tumor invasion of peritoneal membranes is enhanced by the combined use of cytokeratin and elastic stains, which in turn would enable better histopathologic correlation with patient treatment and outcome.

Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.

Malignant mesothelioma (MM) is an asbestos-related malignancy arising from surface serosal cells of pleural and peritoneal cavities. Somatic mutations of BRCA1 associated protein-1 (BAP1) gene were recently found in MM as well as in uveal melanoma and kidney cancer among the Caucasian and Japanese people. However, frequency of mutations varies among the reported studies, which might be due to presence of undetected gross rearrangements of BAP1 gene that might escape detection by sequencing strategy. We investigated the presence and frequency of gross genomic rearrangements in the BAP1 gene by multiplex ligation-dependent probe amplification (MLPA) in 17 Japanese cases of MM tumors. We found five tumors with partial deletion of BAP1 gene; each tumors displayed partial deletion of exons 1-4 (MM39), exons 1-5 (MM48), exons 11-17 (MM57), exons 1-15 (MM19) and exons 1-16 (MM21). Two tumors (MM34, MM14) had biallelic deletion and four tumors (MM29, MM35, MM45 and MM56) had monoallelic deletion of entire BAP1 gene. Therefore, MLPA analysis revealed large gene rearrangements of BAP1 gene in 65% of MM (11/17). Unusually high frequency of large deletions indicates that the 3p21 chromosomal region surrounding BAP1 gene is structurally unstable. MLPA was useful in characterizing both monoallelic and biallelic deletion of BAP1 gene precisely at exon level.

Embryonic development of a collembolan, Tomocerus cuspidatus Börner, 1909: With special reference to the development and developmental potential of serosa (Hexapoda: Collembola, Tomoceridae)

The embryogenesis of a collembolan, Tomocerus cuspidatus, was examined and described, with special reference to the development of serosa and its developmental potential. As a result of cleavage, which starts with holoblastic cleavage and changes to the superficial type, the blastoderm forms. At the center of the dorsal side of the egg, the primary dorsal organ develops. The mesoderm is segregated beneath the entire blastoderm, excluding the primary dorsal organ. The mesoderm then migrates to the presumptive embryonic area, and the embryonic and extra-embryonic areas differentiate. The area lined with mesoderm is the embryo, and that devoid of it is the serosa. Owing to blastokinesis completion, the extra-embryonic area or the serosa is highly stretched, and the serosal cells are often found to undergo mitosis. The serosa possesses the ability to differentiate into the body wall. It was confirmed, in contrast to the previous understanding, that the serosal cells do not degenerate, but participate in the formation of the body wall or definitive dorsal closure. Integrating this newly obtained information and other embryological evidence, the basal splitting of Hexapoda was phylogenetically discussed and reconstructed, and a phylogeny formulated as “Ellipura (= Protura + Collembola) + Cercophora (= Diplura and Ectognatha)” was proposed.

Ancient expansion of the hox cluster in lepidoptera generated four homeobox genes implicated in extra-embryonic tissue formation.

Gene duplications within the conserved Hox cluster are rare in animal evolution, but in Lepidoptera an array of divergent Hox-related genes (Shx genes) has been reported between pb and zen. Here, we use genome sequencing of five lepidopteran species (Polygonia c-album, Pararge aegeria, Callimorpha dominula, Cameraria ohridella, Hepialus sylvina) plus a caddisfly outgroup (Glyphotaelius pellucidus) to trace the evolution of the lepidopteran Shx genes. We demonstrate that Shx genes originated by tandem duplication of zen early in the evolution of large clade Ditrysia; Shx are not found in a caddisfly and a member of the basally diverging Hepialidae (swift moths). Four distinct Shx genes were generated early in ditrysian evolution, and were stably retained in all descendent Lepidoptera except the silkmoth which has additional duplications. Despite extensive sequence divergence, molecular modelling indicates that all four Shx genes have the potential to encode stable homeodomains. The four Shx genes have distinct spatiotemporal expression patterns in early development of the Speckled Wood butterfly (Pararge aegeria), with ShxC demarcating the future sites of extraembryonic tissue formation via strikingly localised maternal RNA in the oocyte. All four genes are also expressed in presumptive serosal cells, prior to the onset of zen expression. Lepidopteran Shx genes represent an unusual example of Hox cluster expansion and integration of novel genes into ancient developmental regulatory networks.

159. Modulation of mucosal immunity by the enteric nervous system

Nowhere is the balance between protective inflammation against pathogens and tolerance towards innocuous substances more challenging than at the intestinal. Apart from containing the largest lymphoid organ in the body, the intestine is seen as “a second brain”, with as many neurons as the spinal cord. Our preliminary characterization shows antigen-presenting cells (APCs) in close proximity to neuronal processes in the intestine. These processes extend towards myenteric plexi, where they are contact a previously unappreciated population of APCs. These cells quickly responds to inflammatory stimuli from mucosal pathogens, before bacteria is detected deeper in the intestine. This data suggests that intestinal neurons convey inflammatory signals received at the mucosal surface, preparing the intestinal tissue for a response. We then characterized the behavior and movement of intestinal APCs using intravital multiphoton using fluorescent reporters for enteric neurons and cells of the immune system, in the serosa in steady state, and following non-invasive bacterial challenge in the mucosa. While APCs in the mucosa move in steady state this is not true for serosal APCs. Nonetheless, following challenge in the mucosa, serosal APCs extend dendrites within minutes. This signaling is prevented by pretreatment with tetrodotoxin. Longitudinal signaling is seen between mucosal APCs to serosal cells in a distant (>5 cm) segment. We believe this represents a short loop for controlling and synchronizing responses along the intestine during pathogenic challenge.

Role of new radiation techniques in the treatment of pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from the surface serosal cells of the pleural cavity. Surgery remains the main therapeutic standard in the treatment of MPM with the goal of complete gross cytoreduction of the tumor. Because MPM is a diffuse disease affecting the entire mesothelial lining of the hemithorax, surgery alone can rarely achieve adequate tumor-free resection margins. The surgical choices are pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP). Radiotherapy (RT) is usually applied postoperatively with the aim to improve local control. However, the efficacy of RT is limited by the large volume of the target to be irradiated (tumor and pleural cavity) and the radiosensitivity of the nearby organs (heart, liver, lung, spinal cord, and esophagus). These factors have historically limited the effective radiation doses that can be given to the patient. There is no role for radical RT alone, but the role of RT as part of multimodality therapy is discussed. After EPP adjuvant RT to the entire hemithorax can reduce the recurrence rate and is well tolerated if strict limits to the dose to contralateral lung are applied: the V20 and V5 (the percent volume of the lung receiving more than 20Gy and 5Gy of radiation) correlate with increased lung toxicity. The use of modern sophisticated techniques allows good target coverage, more conformal high dose delivery, and clinically relevant normal tissue sparing.

Appearance of differentiated cells derived from polar body nuclei in the silkworm, Bombyx mori

In Bombyx mori, polar body nuclei are observed until 9 h after egg lying, however, the fate of polar body nuclei remains unclear. To examine the fate of polar body nuclei, we employed a mutation of serosal cell pigmentation, pink-eyed white egg (pe). The heterozygous pe/+pe females produced black serosal cells in white eggs, while pe/pe females did not produce black serosal cells in white eggs. These results suggest that the appearance of black serosal cells in white eggs depends on the genotype (pe/+pe) of the mother. Because the polar body nuclei had +pe genes in the white eggs laid by a pe/+pe female, polar body nuclei participate in development and differentiate into functional cell (serosal cells). Analyses of serosal cells pigmentation indicated that ~30% of the eggs contained polar-body-nucleus-derived cells. These results demonstrate that polar-body-nucleus-derived cells appeared at a high frequency under natural conditions. Approximately 80% of polar-body-nucleus-derived cells appeared near the anterior pole and the dorsal side, which is opposite to where embryogenesis occurs. The number of cells derived from the polar body nuclei was very low. Approximately 26% of these eggs contained only one black serosal cell. PCR-based analysis revealed that the polar-body-nucleus-derived cells disappeared in late embryonic stages (stage 25). Overall, polar-body-nuclei-derived cells were unlikely to contribute to embryos.

Abstract 3082: TGF-β synergistically stimulates malignant mesothelioma growth with defects in the Hippo pathway by inducing CTGF expression

Abstract Malignant mesothelioma (MM) arises from the serosal cells of the pleural, peritoneal and pericardial cavities with poor prognosis because of its frequent diagnosis in advanced stages. The primary cause of this disease has often been linked to asbestos exposure, and the number of patients worldwide is expected to peak in the next two decades. There is no known curative therapy for MM and further understanding in molecular mechanism is needed to identify new candidates for targeted treatment. We found that the TGF-β pathway is associated with oncogenic mutations and loss of the tumor suppressor NF2, and induces pro-oncogenic biological activities. Loss of NF2 is one of the genetic lesions which have been related to the growth of human MM. The NF2 gene is responsible for neurofibromatosis type II syndrome and encodes Merlin which negatively regulates YAP function. Nearly 75% MM cases have inactivating mutations in the NF2 gene or in downstream signaling molecules of Hippo signaling cascade. We examined a functional interaction between the Hippo and TGF-β pathways and found that endothelin-1 and connective tissue growth factor (CTGF) are the only proteins affected by these two pathways in MM cells. The CTGF promoter contains both a YAP/TEAD-binding site and a consensus Smad-binding site adjacent to each other. The expression of CTGF induced by TGF-β in MM cell lines was greatly affected by the existence of YAP, by its binding with Smad3, forming a complex on CTGF promoter lesion. Knocking down CTGF expression in MM cells prolonged the survival of mice, and a significant association was seen between CTGF expression and extracellular matrix deposition in MM xenografts and in patient tissue specimens. This study elucidates a novel molecular mechanism induced by the TGF-β pathway, which may be applicable to malignancies with defective NF2 and of mesenchymal origin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3082. doi:1538-7445.AM2012-3082

Factors that Impact Susceptibility to Fiber-Induced Health Effects

Asbestos and related fibers are associated with a number of adverse health effects, including malignant mesothelioma (MM), an aggressive cancer that generally develops in the surface serosal cells of the pleural, pericardial, and peritoneal cavities. Although approximately 80% of individuals with MM are exposed to asbestos, fewer than 5% of asbestos workers develop MM. In addition to asbestos, other mineralogical, environmental, genetic, and possibly viral factors might contribute to MM susceptibility. Given this complex etiology of MM, understanding susceptibility to MM needs to be a priority for investigators in order to reduce exposure of those most at risk to known environmental carcinogens. In this review, the current body of literature related to fiber-associated disease susceptibility including age, sex, nutrition, genetics, asbestos, and other mineral exposure is addressed with a focus on MM, and critical areas for further study are recommended.

CA125—A Test with a Change of Heart

CA125 is well known as a tumour marker for ovarian cancer. Like all tumour markers it is not specific for a specific tumour and may be elevated in benign disease. Even in ovarian cancer it seems that CA125 is derived from mesothelial production rather than from the cancer cells. CA125 is a natural product of serosal epithelial cells and present in most serosal fluids whether malignant or benign. Benign causes of CA125 elevation include liver cirrhosis, peritoneal infection, abdominal surgery or the congestion of cardiac failure. Elevated CA125 levels are found in ascitic, pleural or pericardial fluid of patients with cardiac failure and the serum levels correlate with the clinical staging of cardiac failure. Whilst CA125 levels might be useful for diagnosis of cardiac failure, it has an equally impressive ability for defining prognosis in that condition, especially when combined with measuring natriuretic peptides. The CA125 assay is not standardised and different methods, such as new CA125II assays, often give differing results. Furthermore, as CA125 levels fall at the menopause, and may rise in the elderly, reference limits appropriate for age and gender need to be refined in order for CA125 to fulfil any of its potential as a marker of cardiac failure in these age groups.

Biological Agents Involved in Malignant Mesothelioma: Relevance as Biomarkers or Therapeutic Targets

Malignant mesothelioma (MM) is a rare, highly aggressive tumor that arises from the surface serosal cells (pleural, peritoneal and pericardial cavities). Epidemiological and clinical data show that there is an association between asbestos exposure and MM development, even if the exact mechanism whereby asbestos induces MM is unknown. The continuing identification and elucidation of the molecular defects involved in mesothelioma pathogenesis and progression should lead to better disease control and greater therapeutic options in the near future. Goal of this article is to summarize the most recent advances in molecular pathogenesis of mesothelioma with particular emphasis on genes that could be considered as biomarkers or therapeutic targets and discuss possible clinical implications of these findings.

Epithelial reorganization events during late extraembryonic development in a hemimetabolous insect

As extra-embryonic tissues, the amnion and serosa are not considered to contribute materially to the insect embryo, yet they must execute an array of morphogenetic movements before they are dispensable. In hemimetabolous insects, these movements have been known for over a century, but they have remained virtually unexamined. This study addresses late extraembryonic morphogenesis in the milkweed bug, Oncopeltus fasciatus. Cell shape changes and apoptosis profiles are used to characterize the membranes as they undergo a large repertoire of final reorganizational events that reposition the embryo (katatrepsis), and eliminate the membranes themselves in an ordered fashion (dorsal closure). A number of key features were identified. First, amnion–serosa “fusion” involves localized apoptosis in the amnion and the formation of a supracellular actin purse string at the amnion–serosa border. During katatrepsis, a ‘focus’ of serosal cells undergoes precocious columnarization and may serve as an anchor for contraction. Lastly, dorsal closure involves novel modifications of the amnion and embryonic flank that are without counterpart during the well-known process of dorsal closure in the fruit fly Drosophila melanogaster. These data also address the long-standing question of the final fate of the amnion: it undergoes apoptosis during dorsal closure and thus is likely to be solely extraembryonic.