Liliana Vauthay

Novel invasive orthotopic bladder cancer model with high cathepsin B activity resembling human bladder cancer.

PURPOSE We developed and characterized an orthotopic invasive bladder tumor model. MATERIAL AND METHODS The MB49-I invasive bladder tumor cell line was obtained after 13 consecutive in vivo passages of primary tumor obtained by subcutaneous inoculation of MB49 bladder tumor cells in C57Bl/6J male mice. RESULTS MB49-I tumor local invasiveness, tumor weight and spontaneous metastatic capacity were higher than in MB49 tumors. In MB49-I bladder tumors increased vimentin was observed, suggesting epithelial mesenchymal transition. In vitro the MB49-I cell line showed higher invasive properties associated with an increase in cathepsin B, metalloproteinase 9 and urokinase-type plasminogen activator proteolytic activities. Orthotopic bladder tumors induced by electrocautery of the bladder wall and subsequent instillation of MB49 and MB49-I bladder cancer cells generated superficial and invasive bladder tumors, respectively. CONCLUSIONS The new murine bladder model described resembles human bladder disease, making it a useful tool for studying the molecular mechanisms of tumor progression and metastasis, and assaying antimetastatic and anti-invasive agents.

Gastroschisis is a defect of the umbilical ring: evidence from morphological evaluation of stillborn fetuses.

BACKGROUND Gastroschisis (GS) is usually described as an abdominal wall defect, to the right of a normally inserted umbilical cord, without membraneous covering of the extruded organs. However, precise anatomical descriptions are lacking in the literature. Our aims were to provide evidence that allows reconsideration of its current definition, as well as an explanation for prenatal death, based on detailed observation of stillborn fetuses with GS and a review of the literature. METHODS Prenatal studies, clinical examinations, and histological findings of five stillborn fetuses with isolated GS are described and photographic evidence is provided. RESULTS In all five cases, the umbilical cord was only attached to the left side of the umbilical ring, while the right side remained uncovered, allowing evisceration of abdominal organs. Histological evidence of mucoid-like tissue at the free border of the ring suggests that at that site the cord was initially inserted and later detached. Characteristics of the umbilical ring, bowel dilatation, and autopsy findings of acute asphyxia strongly support compression of umbilical vessels as the cause of fetal death. CONCLUSIONS Based on these findings, on the lack of evidence in the literature demonstrating full-thickness abdominal wall separating the defect from the umbilical cord, and on a critical review of the proposed mechanisms favoring the hypothesis of a defect separate from the umbilical ring, we propose that GS represents a failure in the normal attachment between umbilical cord and umbilical ring. The consistent clinical course of fetuses with prenatal demise suggests careful targeted monitoring during late gestation.

Mast cells in female mouse lymph nodes

This study was designed to examine the possible role of sex steroid hormones on mast cells localized in uterus draining lymph nodes (UDLN) in mice. Young virgin estrous animals had more mast cells than diestrous animals in both the UDLN and popliteal lymph nodes (PLN). In retired breeders there were no differences in mast cell numbers of estrous and diestrous animals. There were no differences in mast cell numbers among weanling and older animals in diestrous in the UDLN but, in the PLN, mature animals in either diestrous or estrous had more mast cells than the PLN of weanlings. In mature animals, ovariectomy did not alter mast cell number in either node. However, ovariectomy of weanlings increased mast cell numbers in the PLN but not in the UDLN. These results suggest that the UDLN behaves as a nonclassical target organ for the endocrine system, with mast cell number variations related to gonadal steroid levels.

Acephaly: Further Evidence for Disruption but Not for Amniotic Bands

Complete absence of the fetal head in singleton pregnancies is a very rare defect; to our knowledge there are only 7 reported cases. Decapitation by amniotic bands has been considered as the most probable cause. However, in none of the described cases except one were amniotic bands, constriction rings, or other related findings observed, raising the possibility that mechanisms other than amputation by amniotic bands are involved. We present a further case of acephaly and discuss the role of amniotic bands and alternative mechanisms of decapitation and a possible sequence of events leading to acephaly.

Renal enlargement in the fetus and newborn with Congenital diaphragmatic hernia : A refuted hypothesis

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) is one of the most frequent causes of neonatal death because of lung hypoplasia (LH). The literature mentions a relationship between renal and pulmonary development, with higher kidney weight in presence of LH. The aims of this study were to evaluate the relationship between lung and kidney weight and to test the hypothesis of renal enlargement in fetuses and newborns with CDH. METHODS Body weight (BW), combined kidney weight (KW), and lung weight (LW) of 52 CDH cases were established; 52 morphologically normal fetuses or newborns, matched by BW, served as a control population. Comparisons were done by covariance analysis, and a P value of less than .05 was considered as significant. RESULTS Excluding renal abnormalities, adjusted mean kidney weights were 22.0 g (+/-1.8 SE) in CDH cases and 20.5 g (+/-1.5 SE) in controls (F = 1.05; P = .308). KW to BW ratio was lower in CDH cases than in controls (P = .023). LW was significantly lower in CDH cases than in controls. CONCLUSIONS No significant difference between KW of CDH cases and controls could be observed. The current study provides enough evidence to reject the hypothesis of renal enlargement in cases of LH and CDH.

Tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas is associated with the degree of tumor progression.

Purpose: To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the “morphologically normal tissues” adjacent to them is associated with the degree of tumor progression. Methods: Tumor and “normal tissues” were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and “normal tissues” and we investigated the existence of correlations between: (a) PA production in the tumor and “normal tissues”, (b) different components of the PA system, and (c) PA system and the degree of tumor progression. Results: (1) Total PA activity, u-PA activity and PAI-1 expression are significantly higher in tumor than in “normal tissues”, whereas t-PA activity does not differ between them. (2) Total PA activity mainly correlates with u-PA activity in tumor tissues and similarly with u-PA and t-PA activities in “normal tissues”. (3) There is a significant association between t-PA activity in tumor and “normal tissues” and the degree of tumor progression. Conclusions: “Morphologically normal tissues” adjacent to carcinomas present abnormal t-PA activity that is associated with the degree of tumor progression. Assaying of this activity could be useful as a predictive parameter.

Estrual cycle periodicity in hormone-independent tumor-bearing mice

SummaryThe periodicity of the estrual cycle in mice was studied by vaginal cytology during the growth of a hormone-independent mammary adenocarcinoma. A direct relationship between age progression and lengthening of estrual cycle was observed in control mice but not in tumor-bearing mice of the same age. These results suggest that hormone regulation of the estrual cycle may be affected in tumor-bearing hosts.