Biomedical subjects

E Malecka-Panas

Publications and source records attributed to E Malecka-Panas.

9 recordsLinked to original sources

PubMed2002

Elevated plasma gastrin, CEA, and CA 19-9 levels decrease after colorectal cancer resection.

BACKGROUND AND AIMS: Gastrin stimulates mucosal growth of much of the gastrointestinal tract and has also been implicated in promoting growth of colonic tumors, but its role in colorectal carcinogenesis remains controversial. This study determined fasting serum gastrin levels before and after surgery for colorectal cancer (CRC) and the relationship to the clinical stage of the disease to investigate it possible prognostic role. PATIENTS AND METHODS: Fasting radioimmunoassay gastrin, CA 19-9, and CEA levels were measured before and after surgery for CRC. Helicobacter pylori status was also assessed since it causes significant hypergastrinemia. RESULTS: Mean fasting plasma gastrin level was significantly higher in CRC patients than in controls before surgery but not 59 days after surgery. Mean CEA and CA 19-9 levels were significantly higher in patients with CRC before surgery than after tumor resection. There was a significant positive correlation between the plasma gastrin, CEA, and CA 19-9 levels and the CRC stage (Dukes' classification). CONCLUSION: The significance of gastrin as a marker for diagnosis or prognostic purposes in colorectal cancer needs to be further examined.

Aged↗

PubMed2000

In vitro genotoxicity of ethanol and acetaldehyde in human lymphocytes and the gastrointestinal tract mucosa cells.

The influence of ethanol and acetaldehyde on DNA in human lymphocytes, gastric mucosa (GM) and colonic mucosa (CM) was investigated by using the comet assay. All kinds of cells were exposed to ethanol and acetaldehyde in two regimens: the cells were incubated with either chemical and analysed or they were exposed first to ethanol, washed and then exposed to acetaldehyde and analysed. Lymphocytes were exposed to ethanol at final concentrations of 30 mM and acetaldehyde at 3 mM. GM cells were incubated with ethanol at 1 M and acetaldehyde at 100 mM. CM cells were exposed to ethanol at 10 mM and acetaldehyde at 100 mM. In combined exposure, the cells were subsequently exposed to ethanol and acetaldehyde at all combination of the concentrations of the agents. Ethanol caused DNA strand breaks, which were repaired during 4 hr, except when this agent was applied in GM cells at a concentration of 1 M. A dose-dependent decrease in the tail moment of all types of acetaldehyde-treated cells was observed. Similar results were obtained when a recognized DNA crosslinking agent, formaldehyde, was used. These results suggest that acetaldehyde may form crosslinks with DNA. These crosslinks were poorly repaired. CM cells showed the highest sensitivity of all cell types to ethanol than lymphocytes and GM cells. There were no differences in the sensitivity to acetaldehyde of all the cell types. Our results clearly indicate that ethanol and acetaldehyde can contribute to cancers of the digestive tract.

Acetaldehyde↗

PubMed1997

Differential responsiveness of proximal and distal colonic mucosa to gastrin.

In vivo and in vitro experiments were performed to examine the responsiveness of the proximal and distal colonic mucosa to the growth-promoting action of gastrin. Infusion (osmotic minipump) of gastrin G-17-I (250 ng/kg/h) for 5 days to 4-month-old male Fischer-344 rats resulted in a significant (90-150%) increase in proliferative activity (as assessed by BrdU or PCNA immunoreactivity) in the distal colonic mucosa. In contrast, gastrin caused no apparent change in proliferative activity in the proximal colon. Because tyrosine kinases (Tyr-ks) are thought to be critically involved in regulating the trophic action of gastrin, responsiveness of isolated colonocytes from both segments of the colon to gastrin (1 x 10(-9) M) was also examined. Exposure of isolated colonocytes from the distal, but not from the proximal, colon to gastrin for 2 min resulted in a significant (73%) stimulation in Tyr-k activity. This was also accompanied by a marked rise in phosphorylation of at least six membrane proteins with M, of 55, 60, 70, 94, and 170 kDa. Tyr-k activity induced by gastrin in colonocytes from the distal colon was inhibited by tyrphostin (3.2 microM) but not by staurosporine (20 nM). In colonocytes from the distal colon, gastrin also stimulated phospholipase C (PLC) activity, which could also be inhibited by tyrphostin, but not by staurosporine. We conclude that mucosa of the distal, but not the proximal, colon responds to the trophic action of gastrin. Tyr-ks are thought to be involved in the regulation of this process.

Animals↗

PubMed1996

Azoxymethane enhances ligand-induced activation of EGF receptor tyrosine kinase in the colonic mucosa of rats.

Recent observations suggest that transforming growth factor alpha (TGF-alpha), which binds to the epidermal growth factor (EGF) receptor (EGFR), may induce neoplastic growth of the colonic mucosa through an autocrine mechanism. To assess the functional role of TGF-alpha in colonic carcinogenesis the present investigation examines the changes in TGF-alpha-and EGF-induced activation of intrinsic tyrosine kinase (Tyr-k) activity of EGFR in the colonic mucosa of rats after administration of the colonic carcinogen azoxymethane (AOM; 20 mg/kg body wt). Five days after a single injection of AOM to 4- to 5-month old rats proliferative activity (as assessed by 5-bromo-2'-deoxyuridine immunoreactivity) in the colonic mucosa was increased by approximately 700% over the corresponding saline-injected controls. This was accompanied by: (i) a marked rise in autophosphorylation of a number of mucosal proteins, including one with a M(r) of 170 kDa, a molecular mass that corresponds to EGFR; (ii) a 110-130% increase in basal EGFR Tyr-k activity. Despite this rise in basal EGFR Tyr-k activity, exposure of isolated colonocytes or detergent-solubilized colonic mucosa from AOM-treated animals to either 1 x 10(-8) M TGF-alpha or EGF caused a further 90-160% increase in EGFR Tyr-k activity over the corresponding basal levels. In contrast, bombesin produced no apparent change in EGFR Tyr-k activity. We conclude that increased ligand-induced activation of EGFR Tyr-k may be an important event for development of the hyperproliferative state associated with induction of colorectal neoplasia.

Animals↗

PubMed1996

Increased activation of EGF-receptor tyrosine kinase by EGF and TGF-alpha in the colonic mucosa of aged rats.

Freshly isolated colonocytes as well as detergent-solubilized colonic mucosa and lectin purified receptor-enriched mucosal preparations were utilized to compare ligand-induced activation of EGF-receptor (EGF-R) tyrosine kinase (Tyr-k) activity between young (4 months) and aged (24 months) rats. In all three mucosal preparations, EGF and TGF-alpha produced a significantly greater stimulation in EGF-R Tyr-k activity in aged than in young rats, when compared with the corresponding basal levels. This was observed in spite of a significantly higher basal EGF-R Tyr-k activity in the colonic mucosa of aged rats than in young animals. Neither in young nor in aged rats did bombesin cause any significant change in EGF-R Tyr-k activity in the colonic mucosa. In aged rats, TGF-alpha also caused a stimulation in tyrosine phosphorylation of EGF-R and autophosphorylation of the 165 kDa band (a molecular mass that corresponds to EGF-R) and several other mucosal proteins (M, 120, 110, 70, 60, 55 and 50 kDa). We suggest that mitogenic activation of EGF-R Tyr-k may be an important event for the development of hyperproliferative state in the colonic mucosa of aged rats.

Aging↗

PubMed1995

Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity.

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.

3T3 Cells↗

PubMedDate not supplied

Differential activation of total and EGF receptor (EGF-R) tyrosine kinase (tyr-k) in the rectal mucosa in patients with adenomatous polyps, ulcerative colitis and colon cancer.

BACKGROUND/AIMS: Tyrosine kinase and a number of growth factors, especially EGF and TGF-alpha are known to stimulate proliferation in much of the gastrointestinal tract, including colon. In humans increased colonic mucosal proliferative activity has been observed in numerous premalignant lesions including adenomatous polyps and ulcerative colitis. The aim of the present study was to determine the differences of proliferative patterns in patients with adenomatous polyps, ulcerative colitis and colonic adenocarcinoma as reflected by rectal mucosa tyrosine kinase, EGF receptor tyrosine kinase and PCNA and to evaluate the role of tyr-k in colonic mucosal cell proliferation during carcinogenic process. MATERIALS AND METHODS: The study population comprised 40 patients, aged 17-74 years (mean 57), in which 10 patients had adenomatous polyps, 10-ulcerative colitis in remission phase, 10- colon adenocarcinoma and 10 healthy controls. After informed consent 6-8 rectal mucosal biopsy specimen were obtained at 10 cm from the anal verge at the beginning of the colonoscopy examination and at least 10 cm away from any macroscopic mucosal changes. RESULTS: Mean PCNA labeling indices in patients with colon adenocarcinoma, adenomatous polyps, ulcerative colitis ulcerosa and healthy controls were respectively: 27.6% +/- 5.75; 12.18% +/- 6.76; 10.9% +/- 5.34 and 1.5% +/- 0.97. PCNA labeling index in rectal mucosa of patients with adenomatous polyps, ulcerative colitis and colon cancer was significantly higher (p < 0.01) than in the control group. An upward expansion of the proliferative compartment was also observed in patients with premalignant and malignant colon conditions as regards to the control group. Total tyrosine kinase activity in the rectal mucosa of patients with polyps was elevated by 219%, with ulcerative colitis by 224% and with colorectal carcinoma by 600% as regards to the control group. EGF receptor tyrosine kinase was increased in colonic mucosa by 35.2% in patients with adenomatous polyps, by 40.6% in patients with ulcerative colitis and by 123% in patients with colon cancer. CONCLUSIONS: Increased values of this enzyme in the above mentioned group of patients may suggest that tyrosine phosphorylation represents an early sign of colonic mucosa susceptibility for cancer development. We conclude, that overall an EGF receptor-associated tyrosine kinase plays an important role in the development of hyperproliferative state of the colonic mucosa and colon carcinogenesis.

Adenocarcinoma↗

PubMedDate not supplied

Enhanced ligand-induced activation of EGF-receptor and overall tyrosine kinase and phospholipase C in colonocytes isolated from azoxymethane-treated rats.

BACKGROUND/AIMS: In order to evaluate the role of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in colorectal cancer, the present investigation examines changes in EGF and TGF-alpha-mediated activation of overall and EGF receptor (EGF-R) associated tyrosine kinase activity in isolated rat colonocytes after administration of the colonic carcinogen azoxymethane. METHODOLOGY: Five days after a single injection of azoxymethane (20 mg/kg) or saline solution to 3-4 month old Fischer-344 rats, colonocytes were isolated, exposed for 2 minutes to 1 x 10(8) M EGF and TGF-alpha, and assessed for overall and EGF-R associated tyrosine kinase and phospholipase C activity. RESULTS: In colonocytes isolated from control animals, incubation with EGF and TGF-alpha resulted in a small (21-35%) increase in overall tyr-k. However, a marked (113-127%) rise of this enzyme occurred in colonocytes from AOM-treated rats, when compared with the corresponding basal levels. These differences were even more pronounced in colonocytes isolated from the distal part of the colon, as regards to the proximal part. In addition, EGF and TGF-alpha activated EGF-R tyr-k by 40-60% in controls and by 84-85% in AOM-treated animals. Incubation of colonocytes with these growth factors also stimulated PLC activity (in controls by 120-150% and in AOM injected rats by 204-271%) when compared with corresponding basal values. CONCLUSIONS: We conclude that AOM enhances the responsiveness of colonocytes to EGF and TGF-alpha, which may be one of the mechanisms involved in colorectal carcinogenesis.

Animals↗

PubMedDate not supplied

Pancreatic fluid collections: diagnostic and therapeutic implications of percutaneous drainage guided by ultrasound.

BACKGROUND/AIMS: The aim of the present study is to assess the usefulness of biochemical and bacteriological analysis of the pancreatic fluid obtained at percutaneous drainage of pancreatic pseudocysts and abscesses guided by ultrasound. METHODOLOGY: The study population was comprised of 65 patients, aged 21-79 years: 18 with abscesses and 47 with pseudocysts. In all cases the etiological factor of pancreatic fluid collections was acute pancreatitis. Microbiological (both of aerobic and anaerobic flora), biochemical (including alpha 2-macroglobulin) and cytological analysis of aspirated fluid was performed. Duration of percutaneous drainage in pseudocysts was 10-40 days (mean 18 +/- 12) and in abscesses 21-56 days (mean 32 +/- 19). RESULTS: Complete resolution of pancreatic fluid collections was obtained in 54 (83%) patients, among them in 40 (85.1%) with pseudocysts and in 14 (77.7%) with abscesses, which was confirmed in follow-up ultrasound and/or computed tomography one year after the catheter was removed. Mild complications of this procedure observed in 17 (26.1%) patients were managed without catheter removal. A variety of organisms were cultured from pancreatic fluid, E. coli being the most prevalent. Enterobacter cloacae, staphylococcus aureus, staphylococcus epidermidis, peptococcus saccharolyticus, propionibacterium acnes and bacteroides fragilis were also isolated. Cytologic analysis of the aspirate revealed no atypical cells. The level of alpha 2-macroglobulin in the pancreatic fluid was significantly higher (p < 0.05) in patients with successful pancreatic drainage as compared to the remaining group. CONCLUSION: Percutaneous drainage represents a safe therapeutic method that also provides additional criteria for the management of patients with pancreatic cystic lesions.

Abscess↗