lactoferrin and Precancerous-Conditions

The present study was carried out to examine the chemopreventive effects of 5-fluorouracil (5-FU) and lactoferrin (LF) on goldfish intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). DMH was given to fish by intraperitoneal injection in a dosage of 15 mg/kg body weight once a week for 6 weeks. Eight weeks after the initial DMH injection, fish were randomly divided into 2 groups, control and LF-treated groups. Control fish fed a commercial diet. LF- treated fish fed a commercial diet with bovine lactoferrin (oral administration at 200 mg/kg body weight/day). Ten weeks after the initial DMH injection, each was divided into 2 groups, saline- and 5-FU- treated groups. Physiological saline for freshwater fish (0.75% NaCl solution) in the saline-treated fish and 5-FU dissolved in 0.75% NaCl solution in the 5-FU-treated (75 mg/kg body weight) fish were injected intramuscularly three times every other day, respectively. The mean number of precancer cell foci (PCF) per intestine was 2.7 in DMH treated fish. PCF showed broader distribution in the entire intestine derived from DMH-treated fish. LF-only-treatment has no effect on the number of PCF. Mean number of PCF in 5-FU-only-treated fish decreased in comparison with that of the saline-treated control group, though no statistically significant reduction in PCF was found. But if 5-FU treatment was added to LF pretreatment, a statistically significant reduction in the number of PCF was observed. Pretreatment with LF for 2 weeks also reduced the deleterious side effects of 5-FU.

Topics: 1,2-Dimethylhydrazine; Animals; Anti-Infective Agents; Antimetabolites, Antineoplastic; Blood Cell Count; Fluorouracil; Goldfish; Intestinal Neoplasms; Lactoferrin; Precancerous Conditions

We have established a medium-term colorectal carcinogenesis rat model initiated with 1,2-dimethylhydrazine (DMH) followed by dextran sodium sulfate (DSS) treatment, featuring induction of neoplastic lesions within 10 weeks. In the present study, we examined its ability to detect modification of colon lesion development with 10- or 20-week experimental periods. F344 male rats were given three subcutaneous injections of DMH (40 mg/kg b.w.) in a week followed by free access to drinking water containing 1% DSS for a week. One week after this regimen, basal diet alone, basal diet containing 0.04% nimesulide or 2% lactoferrin as known inhibitors, 0.3% deoxycholic acid (DCA) as a promoter or 1.5% 1-hydroxyanthraquinone (1-HA) as a carcinogen were supplied. At week 10, the incidence and multiplicity of combined adenomas and adenocarcinomas were significantly (P < 0.05 or 0.01) decreased by nimesulide and lactoferrin, and values for adenomas were significantly (P < 0.01) increased in the 1-HA group. There was no clear change in the DCA group. At week 20, multiplicity and volume of the tumors were significantly (P < 0.01 or 0.05) decreased by nimesulide, but no effect was now evident with lactoferrin. Multiplicity and volume of tumors were significantly (P < 0.01) increased in 1-HA group and a similar tendency was apparent (P = 0.08) with DCA. It is concluded that this system offers a useful tool for detection of colorectal carcinogenesis modifiers within 10-20 weeks, pending further studies for verification employing other model chemicals.

Topics: 1,2-Dimethylhydrazine; Animals; Anthraquinones; Carcinogenicity Tests; Colorectal Neoplasms; Deoxycholic Acid; Dextran Sulfate; Lactoferrin; Male; Precancerous Conditions; Rats; Rats, Inbred F344

Lactoferrin was studied in 50 patients with laryngeal precancer: chronic hyperplastic laryngitis (n=28), leukoplakia (n=22). Lactoferrin was measured before the treatment, 10-12 days and 12 months after the treatment. Blood serum concentration of lactoferrin was significantly increased before the treatment. By the authors, it was due to inflammation in laryngeal tissues. Conservative treatment of patients with chronic hyperplastic laryngitis resulted in a considerable reduction in this protein concentration. Surgical removal of leukoplakias stimulated laryngeal inflammation and raised lactoferrin concentration in blood serum. One year after the examination, those patients who had neither exacerbation of chronic hyperplastic laryngitis no recurrent leukoplakia exhibited serum lactoferrin in concentrations close to the baseline but still higher than in healthy individuals. This is explained by chronicity of inflammation in laryngeal tissues. These findings can be used in diagnosis and prognosis of the disease course in patients with laryngeal precancer.

Topics: Adult; Humans; Lactoferrin; Laryngeal Neoplasms; Leukoplakia, Oral; Male; Precancerous Conditions

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.

Topics: 4-Nitroquinoline-1-oxide; Animals; Body Weight; Carcinogens; Cattle; Epithelium; Glutathione Transferase; Immunohistochemistry; Lactoferrin; Liver; Male; Mucous Membrane; NAD(P)H Dehydrogenase (Quinone); Organ Size; Ornithine Decarboxylase; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Quinolones; Rats; Rats, Inbred F344; Tongue; Tongue Neoplasms

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Topics: Animals; Azoxymethane; Carcinogens; Cattle; Colon; Colonic Neoplasms; Lactoferrin; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred F344

The influence of concomitant administration of bovine lactoferrin (bLF) on induction of aberrant crypt foci (ACF) by azoxymethane was investigated in male F344 rats. Two percent bLF and 3% Bifidobacterium longum (B. longum), as a positive control, significantly decreased the numbers of ACF as well as the total numbers of aberrant crypts reproducibly in three independent studies (2% bLF, P < 0.01; 3% B. longum, P < 0.05). Most importantly large size foci composed of four or more crypts were always significantly decreased by 2% bLF (P < 0.05). Additional investigation of the natural killer activity of spleen cells demonstrated enhancement by bLF (P < 0.01) and B. longum (P < 0.01) in line with the levels of influence on foci induction, indicating a possible role for elevated immune cytotoxicity in the observed inhibition.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Bifidobacterium; Carcinogens; Chemoprevention; Colonic Neoplasms; Drug Administration Schedule; Killer Cells, Natural; Lactoferrin; Male; Neoplasm Staging; Precancerous Conditions; Rats; Rats, Inbred F344

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Breast; Breast Diseases; Breast Neoplasms; Cell Transformation, Neoplastic; Epitopes; Female; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Membrane Glycoproteins; Mucin-1; Neoplasm Invasiveness; Neoplasm Metastasis; Precancerous Conditions

In gastric carcinomas, including 20 cases of intestinal type and 10 cases of diffuse type, in adenomas with mild to severe dysplasia (20 cases), and in hyperplastic polyps (10 cases), the presence of lactoferrin was investigated by immunohistochemistry. Incomplete or complete intestinal metaplasia or both and normal gastric mucosa were also tested. Preoperative hematocrit and serum iron levels (18 patients) were recorded. An evident reactivity for lactoferrin was encountered in intestinal type carcinomas, adenomas, and incomplete intestinal metaplasia, whereas diffuse-type carcinomas, hyperplastic polyps, and complete intestinal metaplasia were always unstained; mucous neck cells of the antrum and body were also positive for lactoferrin. The results are discussed in relation to the increased requirement of iron by neoplastic cells, although in gastric carcinomas serum iron levels appear to be unrelated to the immunohistochemical presence of lactoferrin.

Topics: Adenoma; Carcinoma; Humans; Immunohistochemistry; Lactoferrin; Lactoglobulins; Precancerous Conditions; Stomach Neoplasms