E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.     

The middle mesenteric artery

Angiography was performed in a 70-year-old man because of a recurrence of massive hemochezia. The angiogram demonstrated a third mesenteric artery, arising from the aorta between the superior and inferior mesenteric arteries and supplying the splenic flexure. Although many variations of colonic arterial supply have been described, those involving vessels originating from the aorta separate from the celiac, superior mesenteric, or inferior mesenteric arteries are extremely rate.     

Neurofibromatosis of atypical presentation

Neurofibromatosis (NF) is considered to be a heterogeneous neuroectodermal disease clinically defined by the presence of neurofibromas, multiple café-au-lait spots, intertriginous freckles and Lisch nodules. Mosaicism explains atypical presentations of the disease. Early mutations, before tissue differentiation, give rise to generalized disease. We report an atypical presentation of neurofibromatosis with an unusual distribution of neurofibromas, a peculiar, clinically and pathologically, neurofibroma on the trunk and the association with an ovarian serous cystoadenofibroma.     

Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced colorectal cancer: Taiwan experience

Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.      

Comparative aspects of oxytocin in baboon (Papio hamadryus anubis) and human corpora lutea

In spite of the importance of the corpus luteum in human reproduction,little is known about its formation after ovulation and duringregression in the absence of conception. This is largely dueto constraints on the availability of normal human tissue: thereforean appropriate model which could be studied and provide informationapplicable to the human was sought. The baboon (Papio), a non-humanprimate, has been determined to be one such model. Thus, inthe past several years our studies have examined the role ofluteal peptides in corpus luteum function, and, when possible,we have attempted to examine corpora lutea from the human andbaboon in parallel. Although a milk-ejection factor was recognizedto be present in luteal tissue in 1910 (Ott and Scott, Proc.Soc. Exp. Biol. Med., Vol. 8, p 49), the role of oxytocin inluteal physiology has not been easy to ascertain. This is inpart due to the methodologies employed to assess its role. Ourstudies summarized below suggest that oxytocin does not directlyaffect luteal steroidogenesis, but that it may play a role incell to cell communication involving the expression of the gapjunction proteins, the connexins. In view of the fact that oxytocin,its receptor, gap junctions and associated proteins are notunique to the human and non-human primates, the model of lutealdevelopment and demise proposed may be applicable to most species.