lactoferrin and Adenoma

Lung cancer is one of the most common cancers in the world, and the incidence of lung cancer is increasing. Risk analysis of environmental chemicals on lung carcinogenesis is particularly important. Detection of chemopreventive agents of lung carcinogenesis is also important to reduce our risk of lung cancer. For that purpose, it is necessary to establish reliable in vivo animal models of lung carcinogenesis. The A/J mouse is a mouse strain sensitive to lung carcinogens, and also develops spontaneous lung tumors without any chemical treatment. We have demonstrated that a treatment of 4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone (NNK), a tobacco specific nitrosamine, or 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (MeIQx), a heterocyclic amine, induced lung tumors in the female A/J mouse in 16 and 32 weeks. The lung tumors developed in the A/J mouse are histopathologically classified as adenocarcinomas, adenomas, and alveolar cell hyperplasias. Some of these types of lung cancer are similar to those of human lung cancer. We also investigated the chemopreventive effects of bovine LF (bLF) on different phases of NNK-induced lung tumorigenesis in A/J mice. The A/J mouse is very useful mouse strain as a reliable in vivo model, which can be used for risk analysis of lung carcinogenesis.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinogens; Cattle; Disease Models, Animal; Female; Humans; Lactoferrin; Lung Neoplasms; Male; Mice; Mice, Inbred A; Mice, Inbred ICR; Nitrosamines; Risk Assessment

We investigated the effects of bovine LF (bLF) on different phases of NNK-induced lung tumorigenesis in A/J mice. Mice were orally administered 0.02, 0.2 and 2% bLF during the initiation phase, and 2% bLF during the whole tumorigenesis phase or post-initiation phase. Administered bLF during the post-initiation phase showed significant reduction of macroscopical lung nodules, and immunohistochemically decreased expression levels of cell proliferation marker and increased expression levels of apoptosis marker in lung proliferative lesions. bLF might inhibit NNK-induced mouse lung tumorigenesis, only when given limited to the post-initiation phase, through modification of cell proliferation and/or apoptosis.

Topics: Adenoma; Animals; Body Weight; Caspase 3; Cattle; Dietary Supplements; Female; Hyperplasia; Lactoferrin; Lung; Lung Neoplasms; Mice; Mice, Inbred A; Nitrosamines; Organ Size; Proliferating Cell Nuclear Antigen

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Ceruloplasmin; Gene Expression Regulation; Humans; Immunohistochemistry; Lactoferrin; Reproducibility of Results; Secretory Component; Sensitivity and Specificity; Thyroid Diseases; Thyroid Neoplasms

The expression of lactoferrin (LF), ceruloplasmin (CP) and secretory component (SC) in various thyroid diseases was investigated using an immunohistochemical method. LF is an iron-binding protein overexpressed in certain human adenocarcinomas. CP is implicated in carcinogenesis and SC is part of the local immune defense system. Sections of 15 follicular adenomas, 5 follicular carcinomas (FC), 16 papillary carcinomas (PC), 15 goitres and 2 cases of lymphocytic thyroiditis were re-examined and investigated immunohistologically by a streptavidin-biotin method. A positive immunostain reaction for CP and LF was observed in all cases of PC and FC. A positive immunostain reaction for SC was observed in 13/16 cases of PC and 4/5 cases of FC. A negative immunostain reaction for CP, LF and SC was observed in medullary cancers, in follicular adenomas and in the cases with goitre. We conclude that the immunostain expression of LF, CP and SC is a valuable diagnostic aid in the differential diagnosis between benign and malignant thyroid tumors. The expression of SC indicates the presence of a local immunodefensive system.

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Ceruloplasmin; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lactoferrin; Secretory Component; Thyroid Diseases; Thyroid Neoplasms

A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.

Topics: Adenoma; Animals; Anticarcinogenic Agents; Body Weight; Carcinogens; Carcinoma; Cattle; Dose-Response Relationship, Drug; Esophageal Neoplasms; Incidence; Lactoferrin; Lung Neoplasms; Male; Organ Size; Papilloma; Rats; Rats, Inbred F344; Survival Rate

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF 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 both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Azoxymethane; Carcinoma; Cattle; Colonic Neoplasms; Incidence; Intestinal Neoplasms; Intestine, Large; Intestine, Small; Lactoferrin; Male; Rats; Rats, Inbred F344

Fifty-nine thyroid tumors were re-examined and studied using immunohistochemistry to detect the presence of ceruloplasmin (CP), lactoferrin (LF), thyroglobulin, thyrocalcitonin, carcinoembryonic antigen and ferritin. In an attempt to study the contribution of the immunodetection of CP and LF in the diagnosis of malignant versus benign tumors, specially in follicular tumors, we compared our results of immunodetection with those of Tuccari and Barresi, and carried out our own studies on the usefulness of these immunolabelling. Concerning CP and LF staining, we have found the following data: 1) little (in contrast to Tuccari and Barresi) or no staining in normal thyroid and benign adenomas; 2) diffuse and intense staining in papillary and follicular carcinomas (as noted by the previous authors); 3) diffuse and weak staining for medullary carcinomas (in contrast to Tuccari and Barresi who found none). Our findings suggest that a diffuse and intense cytoplasmic staining with CP and LF concerning more than one third of all cells is a criterion of malignancy, whereas a weak paranuclear staining of a few cells is more in favor of a benign process.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Ceruloplasmin; Humans; Immunohistochemistry; Lactoferrin; Neoplasm Proteins; Retrospective Studies; Sensitivity and Specificity; Thyroid Neoplasms

Immunohistochemical identification of keratin proteins (TK, KL1 and PKK1), vimentin, myosin, S-100 protein (using polyclonal antiserum) and S-100 alpha and beta subunits, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), lactoferrin, and lysozyme was made in myoepitheliomas, myoepithelial adenomas, and clear cell adenomas of salivary gland origin. Myoepithelioma cells were divided into two types: plasmacytoid cells, which showed great heterogeneity in terms of keratins and S-100 alpha and beta proteins and a lack of GFAP, NSE, lactoferrin, and lysozyme in most the cells, and fibrous and dendritic tumor cells, which displayed variable staining for keratin and S-100 alpha and beta proteins. Myoepithelial adenomas were composed of small-, intermediate-, and large-sized spindle cells that showed irregular positive reactions for keratins and S-100 alpha and beta. Immunohistochemical deposition of S-100 protein was restricted strongly to the dendritic cells present in hyalinous and myxomatous areas. Clear cell adenomas revealed uniformly slight staining of keratins and S-100 proteins, and negative staining or rarely positivity for GFAP, NSE, lactoferrin, and lysozyme. When the immunohistochemical deposition of these proteins was compared between normal glands and myoepithelial tumors, heterogeneity of expression of keratins, S-100 proteins, GFAP, and NSE was notable in the tumors. Progenitor cells of several kinds of myoepithelioma were suggested to be intercalated reserve cells, which are thought to be the same cell that gives rise to pleomorphic adenoma of salivary glands.

Topics: Adenoma; Cytoskeletal Proteins; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Lactoferrin; Lactoglobulins; Lysosomes; Myoepithelioma; Myosins; Phosphopyruvate Hydratase; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Immunohistochemical identification of lysozyme and lactoferrin was made in salivary pleomorphic adenomas (147 cases) and the staining patterns were evaluated with respect to the histological features and histogenesis. In normal salivary glands, the intercalated duct cells gave positive staining for lysozyme in major glands, and serous acinar cells, demilune cells, and interlobular duct cells were positive in minor glands. Lactoferrin staining was irregularly positive in serous cells and ductal epithelium. In pleomorphic adenomas, the reaction for lysozyme was positive in 14% (21/147) of the cases, and was confined to luminal cells of tubulo-ductal structures. Lactoferrin in pleomorphic adenomas was distributed in luminal tumor cells (51%; 75/147), in outer tumor cells (3%; 4/147), and in both luminal and outer tumor cells (5%; 7/147) in tubulo-ductal structures; it was also detected in plasmacytoid myoepithelial cells (5%, 8/147). However, modified myoepithelial cells and other types of neoplastic myoepithelial participants were negative for lactoferrin staining. The occurrence of both lysozyme and lactoferrin in salivary pleomorphic adenomas suggests their participation in the local defense mechanism in the tumor.

Topics: Adenoma; Humans; Immunohistochemistry; Lactoferrin; Lactoglobulins; Muramidase; Salivary Gland Neoplasms

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

By immunohistochemistry, the presence of lactoferrin was investigated in follicular adenomas (10 cases) and carcinomas of the thyroid gland (23 cases). Normal thyroid tissue was also tested as control. Follicular adenomas showed a consistent negativity, whereas follicular and papillary carcinomas exhibited various degrees of positivity for lactoferrin. Incorporated organoid structures observed in anaplastic carcinomas were strongly stained; the spindle cell parts of these cancers were always negative for this iron-binding protein. Medullary carcinomas were also unstained. These findings are discussed in relation to the distribution pattern of thyroglobulin. The authors emphasize the possibility that lactoferrin may be useful in clarifying some diagnostic problems in neoplastic thyroid pathology.

Topics: Adenoma; Carcinoma; Cytoplasm; Histocytochemistry; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Thyroglobulin; Thyroid Neoplasms