Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance,Epidemiology, and End Results (SEER) Study of 14,228 Patients

Introduction

Left untreated, malignant pleural mesothelioma (MPM) is associated with uniformly poor prognosis. Better survival has been reported with surgery-based multimodality therapy, but to date, no trial has demonstrated survival benefit of surgery over other therapies. We evaluated whether cancer-directed surgery influenced survival independently from other predictors in a large population-based dataset.

Methods

The SEER database was explored from 1973 to 2009 to identify all cases of pathologically-proven MPM. Age, sex, race, year of diagnosis, histology stage, cancer-directed surgery, radiation, and vital status were analyzed. The association between prognostic factors and survival was estimated using Cox regression and propensity matched analysis.

Results

There were 14,228 patients with pathologic diagnosis of MPM. On multivariable analysis, female gender, younger age, early stage, and treatment with surgery were independent predictors of longer survival. In comparison to no treatment, surgery alone was associated with significant improvement in survival [adjusted hazard ratio (adj HR) 0.64 (0.61–0.67)], but not radiation [adj HR 1.15 (1.08–1.23)]. Surgery and radiation combined had similar survival as surgery alone [adj HR 0.69 (0.64–0.76)]. Results were similar when cases diagnosed between 1973 and 1999 were compared to cases diagnosed between 2000 and 2009.

Conclusions

Despite developments in surgical and radiation techniques, the prognosis for MPM patients has not improved over the past 4 decades. Cancer-directed surgery is independently associated with better survival, suggesting that multimodal surgery-based therapy can benefit these patients. Further research in adjuvant treatment is necessary to improve prognosis in this challenging disease.     

Importance of FADD signaling in serum deprivation- and hypoxia-induced cardiomyocyte apoptosis

Although cardiomyocyte (CM) apoptosis has been well described in both in vitro and in vivo models of ischemic heart disease, the intracellular pathways leading to CM death have not been fully characterized. To define the role of death receptor signaling in CM apoptosis, we constructed recombinant adenoviral vectors carrying wild-type (wt) or dominant negative (dn) forms of the death receptor adaptor protein FADD (Fas-associated death domain protein) and used these vectors to transduce rat neonatal CMs in models of hypoxia- and serum deprivation (SD)-induced apoptosis. The combination of SD and hypoxia induced rapid activation of caspase-3 and -8 as well as DNA fragmentation, reaching a plateau within 4-8 h. Adenoviral expression of FADD-dn inhibited caspase-8 activation as well as hypoxia/SD-induced apoptosis at 24 h in an moi (multiplicity of infection)-dependent manner. In contrast, adenoviral expression of FADD-wt increased apoptosis and caspase-3 activity in CMs under both normoxic and hypoxic conditions. Surprisingly, FADD-dn, as well as the specific caspase-8 inhibitor benzyloxycarbonyl-IETD-fluoromethylketone also inhibited the activation of caspase-9 and -3 in CMs subjected to hypoxia/SD. These data suggest a primary role for FADD/caspase-8 signaling that is necessary and sufficient for apoptosis of CMs subjected to hypoxia/SD.     

Homage to the red queen. I. Coevolution of predators and their victims

In this paper we develop a model to describe the coevolution of a two-species predator-victim ecosystem. Evolution among the predators acts to displace the predators' zero growth isocline, J, to the left, whereas victim evolution has the opposite effect. More important, we show that for many such systems, there is a value of J, J1, at which the rate of predator evolution exactly equals the rate of victim evolution. This value of J turns out to be a coevolutionary steady state (CSS) which is stable to perturbations. It is suggested that this analysis permits qualitative understanding of why certain real world predator-prey systems oscillate, whereas others do not.     

Cross-ethnic variation in dental, sensory and perceptual traits: a nonmetric multibivariate derivation of distances for ethnic groups and traits

The central concern of this paper is to illustrate how four apparently unrelated classes of variables — dental, perceptual, ethnic origin, and other — can be comprehended within a single parsimonious space, even though some of the measures were qualitative, others quantitative. Thirty-five hundred Israeli villagers of varied ethnic origin were examined on several aspects of oral epidemiology, a battery of tests relating to estimation of number, and miscellaneous traits, including eye colour, tasting PTC, tongue rolling, etc. Significant differences between the six Jewish groups — Yemen, Cochin, Kurdistan, Libya, Berber, and Djerba — were found in the scores of most variables. By the use of the Smallest Space Analysis, distances were established between the different ethnic groups which took into account the complex interrelations in each of 3,500 individual subjects of all 45 categories of 16 variables. A three-dimensional model of the interrelations between the ethnic groups and the trait categories was constructed from the 45 sets of coordinates which resulted from the iterative computer procedure. The ethnic group pairs at greatest distance from each other were found to be Kurdistan:Cochin, then Kurdistan:Djerba, followed by Djerba:Yemen. It is suggested that multivariate analyses of the type presented here, and including interrelations between genetic markers, anthropometric and behavioral variables, would deepen our understanding of the present structure and possible backgrounds of populations of diverse origins.     

Dentition of Bedouin in Israel. II. Morphology

Plaster casts of the dentition of 137 Bedouin, mostly members of the Abu Rabiya tribe in the Negev desert, were subjected to odontometric and morphologic analysis. They show a marked sexual dimorphism, very strongly developed maxillary and mandibular first molars and much reduced second molars. They exhibit the characteristics of middle-eastern populations with a rather weak expression of the shovel trait, upper premolars with relatively short BL diameters, a high prevalence of Carabelli's complex on the first maxillary molar and virtually complete absence of the protostylid. In general, the Bedouin have larger teeth than three other ethnic groups living in Israel whose dentitions have been recently investigated. Further similarities and differences are discussed.     

Hydrolysis of [Leu]enkephalin by chick brain in vitro.

Using high-performance liquid chromatography with electrochemical detection to measure substrate disappearance and metabolite accumulation following addition of [Leu]enkephalin to samples prepared from chick brain in vitro, the following were found: 1. [Leu]enkephalin hydrolysis by whole forebrain homogenates is almost solely attributable to aminopeptidase MII activity. 2. [Leu]enkephalin hydrolysis by whole forebrain P2 membrane fractions is attributable to both aminopeptidase MII and dipeptidyl carboxypeptidase activity. 3. Differences are apparent in both [Leu]enkephalin disappearance and Tyr-Gly-Gly accumulation in P2 membrane fractions, but not in homogenate fractions, prepared from several regions of the chick brain.