Growth regulation and co-stimulation of human colorectal cancer cell lines by insulin-like growth factor I, II and transforming growth factor alpha.

We have tested growth factor responsiveness of a panel of eight human colorectal carcinoma cell lines. Insulin-like growth factors I and II (IGF-I and IGF-II) stimulated growth of five lines (HT-29, LS411N, LS513, SW480, WiDr). At 30 ng ml-1 both factors enhanced growth up to 3-fold. They induced half-maximal stimulation at 1.9-6.51 ng ml-1. Even after delayed addition IGF-I and II significantly enhanced growth in a short-term proliferation assay. They exerted maximal effects under limiting serum conditions (0.5% FCS) and at low cell density (1.25-5 x 10(4) ml-1). Using these conditions transforming growth factor alpha (TGF alpha) enhanced proliferation of all IGF-responsive cell lines, except SW480. 1.11-3.31 ng ml-1 were required to obtain a half-maximal response. With 10-20 ng ml-1 maximal stimulation occurred at plateau values different from those for IGF-I/II. Proliferation of all cell lines responsive to both IGF-I and TGF alpha was further enhanced by combining both factors, resulting a synergistic response of LS513, while the effects on HT-29, LS411N and WiDr were additive. With HT-29 and LS411N a 24 h exposure to TGF alpha was sufficient to obtain a full response in the co-stimulatory assay. Our results illustrate the importance of IGF-I/II and TGF alpha as stimulators of growth of colorectal carcinomas

Postoperative chylous ascites after radical gastrectomy. A case report

Postoperative chylous ascites is a classical but uncommon complication following extensive retroperitoneal or near the root of the mesentery dissection with an incidence ranging from 1.2 to 3%. Only 6 cases of chylous ascites have been described after ulcer surgery with troncal vagotomy associated with pyloroplasty and only 1 after gastrectomy. We report the second case of chylous ascites after a D2 distal gastrectomy. A 56-year-old female underwent a D2 distal gastrectomy and gastro-duodenostomy with omentectomy for a prepyloric T1N0M0 moderately differentiated adenocarcinoma. The patient was treated conservatively by both of parenteral nutrition and a fat free diet. By the end of 2(nd) postoperative week, the effusion became serous again and the output gradually ceased. The drain could be removed on the 20(th) postoperative day. Normal enteral nutrition was resumed, no recurrence of chylous ascites occurred. This conservative treatment proved to be effective as it as already be reported with resolution in almost 60% of the patients and remains the first choice optio

Le cancer colo-rectal hereditaire: a propos d'une observation familiale. [Hereditary colorectal cancer: observations of a family study]

Described in Switzerland in the early '60, the major features of hereditary non-polyposis colon cancer syndrome (HNPCCS) were established 20 years ago by H. T. Lynch. HNPCCS accounts for at least 60% of the colon cancer etiology. Cancer family syndrome is defined by the presence of extracolonic primary tumors in addition to colon cancer. Both syndromes are transmitted by an autosomic dominant pattern. None of the known biomarkers are specific and/or sensitive enough to rely on their predictive values of patient's risks. A typical Swiss family was investigated on the basis of the cancer-prone family history. 21% of the family members observed over 5 generations presented one or more (30% of the cases) colo-rectal neoplasms at the age of 50. 55% of the tumors were right sided. Histologically, half of the tumors were mucinous. 30% of metachronous cancer appeared within 10 years. Polyps (1-3) and flat adenomas were associated to the lesion in 57%. Extra-colonic tumors appeared in 18% of family members and in half of the colon cancer patients. The sites of these tumors were the urinary tract, ovary, small bowel, breast and stomach. Two fibroblast strains of affected individuals were established. No increased tetraploidy was noted. Preliminary results suggest that this two strains are rather sensitive to ionising radiation. Often neglected, family history of colon cancer remains the major diagnostic and decision-making tool of a such syndrome. It will necessitate special treatment of affected subjects and early screening of the relatives.(ABSTRACT TRUNCATED AT 250 WORDS

Epidermal growth factor responsiveness of a new human neuroblastoma cell line

A human neuroblastoma cell line, CA-2E, has been established from a bone-marrow aspirate of a 16-month-old boy with progressive disease. The karyotype and antigen phenotype of the cells correspond to those of a neuroblastoma. This cell line grows well in liquid cultures supplemented with 5% fetal calf serum; conversely, colony formation in semi-solid medium by cells from early passages is dependent upon exogenous EGF. With time in continuous culture, the cloning efficiency in the absence of EGF increases, but the line remains sensitive to EGF, as evidenced by an enhancement of the number and size of colonies. A relative dependence upon EGF in liquid cultures has also been clearly demonstrated by limiting the concentration of serum. Long-term (over 2 weeks) treatment with EGF results in a decreased rate of proliferation, a decreased proportion of clonogenic cells, and the appearance of flat, epithelial-type cells. In some experiments, EGF also has a remarkable effect in inducing neurite outgrowth and process branching. Our results suggest that EGF may have both proliferation- and differentiation-inducing effects on this neuroblastoma cell line. We have also shown that EGF induces increased proliferation in 7 out of 8 other human neuroblastoma cell lines. Functional response of neuroblastoma cells to EGF appears to be a general phenomenon which may be related to a block in the normal maturation pathway of the neural crest cells from which this tumor originates

Interactions of interferon-alpha 2a with 5'-deoxy-5-fluorouridine in colorectal cancer cells in vitro

The biological activity of 5'-deoxy-5-fluorouridine (5'-dFUrd) depends upon intracellular enzymatic cleavage by pyrimidine phosphorylase to form 5-fluorouracil (5-FU). Interferon-alpha 2a (IFN-alpha) effect was analysed alone and combined with 5-FU or 5'-dFUrd, on proliferation inhibition of eight human colorectal cancer cell lines. The toxicity of 5-FU was enhanced by IFN-alpha in only one line (SW-480). In contrast, interactive enhancement of IFN-alpha was observed with 5'-dFUrd in five lines (WiDr, HT-29, 513, SW-480 and Co-115). In each of the lines showing potentiation by IFN/5'dFUrd but not by IFN/5-FU, cytoplasmic pyrimidine phosphorylase activity was increased after 5 days' incubation with IFN-alpha in a dose-dependent manner. Two lines (LISP-1 and SW-620) showed no potentiation of either 5-FU or 5'-dFUrd toxicity by IFN-alpha, and no change in pyrimidine phosphorylase activity. Potentiation of 5'-dFUrd effect by IFN-alpha may thus be explained by an enhancement of its conversion to 5-FU through stimulation of pyrimidine phosphorylase activity