Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival. MATERIALS AND METHODS: A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). RESULTS: The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery

Rapport préliminaire sur les activités de la mission archéologique franco-syrienne dans la micro-région d'Al-Rawda (Shamiyeh) : quatrième et cinquième campagnes (2005 et 2006)

This preliminary report presents the results of two campaigns of excavation and survey in 2005and 2006 on the site of AI-Rawda (West-Central Syria) and in the micro-region of 100 km2 around it. Thesite is a pre-planned circular new town. It was founded around 2400 BCE, in the steppe zone and was inhabitedonly during EB IV, until the end of the 3rd millennium. The work of 2005 and 2006 involved furtherextensive excavation of a sanctuary consisting of two temples and a temenos togeiher with aIl associatedinstallations (including a betyl in situ). The eastem gate of the town was excavated and four lines of defencehave been identified. A stratigraphie sounding in the southwest clarifies the origin of the town. In the necropolisassociated with the site, the excavation of a collective pit burial is presented. Intensive survey wascontinued outside the ancient town, with particular attention to sites that were occupied at the same time asAI-Rawda, to burials, which have been classified by type, and to installations that can be linked to agricultureor pastoralism. This work was supplemented by archaeobotanical, archaeozoological and geo-archaeologicalresearch, as weIl as a study of the environment.Ce rapport préliminaire présente les résultats de deux campagnes de fouilles et de prospection conduites en 2005 et 2006 sur le site d’Al-Rawda (Syrie du centre-ouest) et dans la microrégion de 100 km2 qui l’entoure. Le site, une ville neuve circulaire au plan d’urbanisme préconçu fondé vers 2500 av. J.-C., se trouve en zone steppique. Il n’est habité que durant le Bronze ancien IV, jusqu’à la fin du 3e millénaire.Les travaux en 2005 et 2006 ont porté sur la poursuite du dégagement extensif d’un sanctuaire qui regroupe deux temples et un temenos, avec l’ensemble des installations qu’ils contiennent (dont un bétyle in situ). À l’est, a été mise au jour la porte orientale de la ville tandis que quatre lignes de défense ont été identifiées. Un sondage stratigraphique au sud-ouest éclaire l’origine de la ville. Dans la nécropole associée au site, la fouille d’une tombe en puits collective est présentée.Parallèlement, la prospection intensive autour de la ville antique a été poursuivie en mettant l’accent sur les sites d’habitat contemporains d’Al-Rawda, les tombes caractérisées par type et les aménagements qui peuvent être liés à une mise en valeur agricole du territoire et au pastoralisme. Ces travaux ont été complétés par des études archéobotanique, archéozoologique, géoarchéologique et par une étude des milieux

PolyADP-Ribosylation Is Required for Pronuclear Fusion during Postfertilization in Mice

BACKGROUND: During fertilization, pronuclear envelope breakdown (PNEB) is followed by the mingling of male and female genomes. Dynamic chromatin and protein rearrangements require posttranslational modification (PTM) for the postfertilization development. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of poly(ADP-ribose) polymerase activity (PARylation) by either PJ-34 or 5-AIQ resulted in developmental arrest of fertilized embryos at the PNEB. PARylation inhibition affects spindle bundle formation and phosphorylation of Erk molecules of metaphase II (MII) unfertilized oocytes. We found a frequent appearance of multiple pronuclei (PN) in the PARylation-inhibited embryos, suggesting defective polymerization of tubulins. Attenuated phosphorylation of lamin A/C by PARylation was detected in the PARylation-inhibited embryos at PNEB. This was associated with sustained localization of heterodomain protein 1 (HP1) at the PN of the one-cell embryos arrested by PARylation inhibition. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that PARylation is required for pronuclear fusion during postfertilization processes. These data further suggest that PARylation regulates protein dynamics essential for the beginning of mouse zygotic development. PARylation and its involving signal-pathways may represent potential targets as contraceptives

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Applications of Remote Sensing Techniques to Update the Forest Inventory Data Base in British Columbia

The Inventory Branch of the Ministry of Forests is required to develop, compile and maintain the inventory of forests and range resources on all crown lands in the Province, including the management of the data base, the annual update of resource maps and associated data files, the collection of growth and yield statistics, the estimation of decay, waste and breakage, and the continuous monitoring of forest depletion. The Branch is also charged with assessing the actual potential effects of changing patterns of land use and any resulting shifts: in environmental values. This paper describes the applications of remote sensing and satellite image analysis techniques to monitor the forest and range resources Over 94.8 million hectares. The monitoring involves the acquisition and processing of conventional aerial photography, supplementary large scale 70 mm photography, LANDSAT imagery and airbourne multispectral scanner data. Prime interest is the forest land base, consisting of 52.1 million hectares, and the changes which occur in it continuously For example, the approximately\u27 200 000 hectares that are being harvested annually must be located by the end of each year, mapped and entered into the data base. This dynamic data base was developed during the past 10 years with remote sensing techniques and is now worth around $100 million. In 1978, the Branch acquired an Interactive Graphics Design System (I.G.D.S.) for computerized mapping. Currently, the 7000 forest cover maps are being digitized with the aid of I.G.D.S. and the corresponding inventory data attributes are set up on flexible data management systems. Highlights of the paper and results of operational applications of remote sensing are illustrated at the conference through a slide presentation