lactoferrin and Carcinoma

Most abdominal disorders present with a limited number of overlapping symptoms. Blood tests are not routinely available for use in diagnosis and so investigation tends to require complex imaging procedures or endoscopy and biopsy. These are invasive for the patient, may be associated with morbidity and mortality and have considerable resource implications. Biochemical tests on a single sample of faeces are therefore a valuable alternative. Measurement of faecal calprotectin has been shown to have a role in the diagnosis of inflammatory bowel disease and in its monitoring. Lactoferrin is also of benefit used in this way. Faecal elastase has been demonstrated to be of use in the diagnosis of pancreatic insufficiency. A number of faecal markers have been explored in colorectal cancer. Faecal occult blood testing is used for population screening, but the metabolomic marker tumour, M2-pyruvate kinase, has potential for use in both diagnosis and screening. DNA testing has advantages in colorectal cancer but the exact applications of such tests require further evaluation.

Topics: Biomarkers; Carcinoma; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Feces; Humans; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Mass Screening; Metabolome; Occult Blood; Pancreatic Elastase; Pancreatitis; Pyruvate Kinase; Sensitivity and Specificity

Lactoferrin (LF) is a member of the transferrin family, which is known for its immunomodulatory properties. LF has been widely used as an anticancer medication in various cancers including breast cancer.. The current study aimed to examine the molecular mechanisms underlying the therapeutic potential of recombinant human lactoferrin (rhLF), either alone or combined with epirubicin (EPI), in mice bearing solid Ehrlich carcinoma (SEC).. SEC-bearing female mice (n=40) were divided into 4 equal groups. Mice were given rhLF orally (100mg/kg/mouse) daily and/or EPI i.p (8mg/kg/mouse). The experiment lasted 14 days, after which samples were collected to measure IL-18 and phosphorylated c-Jun N-terminal kinase (p-JNK) by ELISA and p. Administration of rhLF, either alone or combined with EPI, markedly decreased the tumor volume and increased tumor inhibition rate as well as survival rate compared to either tumor control group or EPI-mono treated group. In addition, co-administration of rhLF and EPI increased the level of activated JNKs and expression of p. Recombinant human lactoferrin exhibited potential anticancer and immune-enhancing properties in mice with breast cancer. Co-treatment with rhLF and EPI proved to be a promising strategy in cancer treatment.

Topics: Animals; Breast Neoplasms; Carcinoma; Epirubicin; Female; Humans; Interleukin-18; Lactoferrin; Mice; Recombinant Proteins

It has been hypothesised that secretory carcinoma of the salivary gland (SCsg) might have a lactational-like differentiation. Therefore, we aimed to assess the immunoexpression of breast hormonal receptors and milk-related proteins in cases of SCsg and other salivary gland tumours with prominent secretory activity.. Immunohistochemistry against prolactin and growth hormone receptors, lactoferrin, human milk fat globule 1, MUC 1 and MUC4 was performed in twelve cases of SCsg and 47 other salivary gland tumours.. Most cases of SCsg were negative for prolactin and growth hormone receptors. All cases of SCsg showed enhanced membranous-cytoplasmic staining for human milk fat globule 1, a pattern seen in other tumour groups. Only SCsg showed widespread strong staining for lactoferrin, concomitantly in the cell compartment and secretion. The other positive tumour types exhibited restricted staining. MUC1 and MUC4 showed no distinct pattern of expression.. Although SCsg failed to demonstrate a complete lactational-like differentiation, lactoferrin showed a distinctive expression pattern in SCsg compared to other tumour types, which makes it a good marker to help in its differential diagnosis.

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Humans; Lactoferrin; Prolactin; Receptors, Somatotropin; Salivary Gland Neoplasms; Salivary Glands

Urothelial carcinoma of the bladder (UCB) is potentially life-threatening; therefore, we aimed to discover a novel urine biomarker for diagnosis and prognostication of UCB. This is a retrospective case-control study. Exploration of a new biomarker using urine from 20 UCB patients in the present study revealed that urinary level of lactoferrin (LF), a multifunctional glycoprotein released from neutrophils, was higher in 11 of 15 with invasive/high-grade UCB than 5 with non-invasive one, and 2 healthy adults. We therefore focused on LF and assessed the value of urine LF normalized by urine creatinine concentration (LF/Cr) using an enzyme-linked immunosorbent assay. Diagnostic performance of urine LF/Cr was examined using urine from 92 patients with primary (newly diagnosed) untreated UCB and 166 controls without UCB, including 62 patients with pyuria, and 104 subjects without pyuria consisting of 84 patients and 20 healthy adults. However, the diagnostic accuracies were accompanied by the risk of bias. In 92 primary UCB patients, both pyuria and tumor-infiltrating neutrophils (TINs) were independent predictors for urine LF/Cr. In contrast, TINs or urine LF/Cr were independent predictors for invasive histology, whereas pyuria was not. In terms of prognostication, urine LF/Cr and nodal metastasis were independent predictors of disease-specific survival in 22 patients with muscle-invasive bladder cancer, characterized by a high mortality rate, in the Cox proportional hazards model. In conclusion, urine LF/Cr linked to TINs was a predictor of both invasive histology and prognosis in UCB. Urine LF/Cr is a potential biomarker reflecting the degree of malignancy in UCB.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma; Case-Control Studies; Cell Proliferation; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lactoferrin; Male; Middle Aged; Neoplasm Metastasis; Neutrophils; Prognosis; Reference Standards; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium; Young Adult

In view of the promising applications of nanoparticles in drug delivery, this study highlights the fabrication of new bioactive green protein-polysaccharide nanocomplexes with significant antibacterial and antitumor efficacies. We preformulated the water-insoluble drugs Quercetin (Quer) and Resveratrol (Res) as water-soluble nanocrystals to facilitate their entrapment in the electrostatic lactoferrin-chondroitin (Lf-ChS) nanocomplex. Quer and Res were physically entrapped in the Lf-ChS nanomatrix with high encapsulation efficiencies (EE %) of 85.2 and 90.1% w/w for Quer and Res, respectively. The

Topics: Carcinoma; Drug Delivery Systems; Humans; Lactoferrin; Lung; Nanomedicine

Lactotransferrin (LTF), also known as lactoferrin, is a key component of innate immune defense. We previously reported that LTF was downregulated in nasopharyngeal carcinoma (NPC) and could suppress NPC cell proliferation. However, the relevance of the relationship between LTF expression and NPC clinical outcome has not been reported. This study aims to assess the possible correlations between LTF expression and clinical parameters and its potential prognostic predictive ability in the outcomes of patients with NPC. Complementary DNA (cDNA) microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC) results suggested that LTF expression was significantly downregulated in NPC tissues compared to non-NPC tissues. LTF was negatively correlated with lymph node metastasis (P = 0.042), T stage (P < 0.001), clinical tumor-node-metastasis (TNM) stage (P = 0.022), and EBV-encoded RNA 1 (EBER-1) expression (r = -.167, P = 0.016). A survival analysis of 108 patients with NPC revealed that positive expression of LTF could predict a good prognosis [disease-free survival (DFS): P = 0.043, overall survival (OS): P = 0.040]. Multivariable analysis revealed that LTF could independently predict prognosis (DFS: HR = 0.414, P = 0.003; OS: HR = 0.309, P = 0.005). These observations indicated that LTF is a potential prognostic factor of NPC.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma; Cell Proliferation; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Lactoferrin; Lymphatic Metastasis; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis

LTF (lactotransferrin, also known as lactoferrin) is a key component of innate immune defense. It has recently been found to have anti-tumor and anti-metastatic activity in different cancers. We previously reported LTF to be the most significantly downregulated gene in nasopharyngeal carcinoma (NPC) specimens relative to normal nasopharyngeal epithelial tissues, and it was also negatively associated with the progression and metastasis of NPC. However, the mechanism underlying this remains unclear. In the current study, we revealed that LTF can suppress 3-phosphoinositide-dependent protein kinase 1 expression via the mitogen-activated protein kinase/c-Jun pathway and thus repress AKT signaling. We also showed that LTF interacts with keratin 18 (K18) and so blocks the formation of the K18-14-3-3 complex, leading to downregulation of K18-mediated AKT activation. Thus, LTF suppresses AKT signaling by two separate mechanisms, leading to inhibition of NPC tumorigenesis. This is the first report on the tumor suppressive effects of LTF through repression of AKT signaling in NPC. It suggests that both LTF and AKT signaling merit further study in the field of NPC research.

Topics: 14-3-3 Proteins; Adult; Aged; Animals; Biomarkers, Tumor; Carcinoma; Cell Line, Tumor; Cell Proliferation; Exonucleases; Exoribonucleases; Female; Gene Expression; Humans; Lactoferrin; Male; Mice; Middle Aged; Mitogen-Activated Protein Kinases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Protein Binding; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Signal Transduction

Lactotransferrin (LTF) is a component of the nonspecific immune system, having antimicrobial properties against bacteria, fungi, and several viruses. The gene coding for LTF is polymorphic, with the occurrence of several common alleles in the general population. Our previous study found that LTF inhibited nasopharyngeal carcinoma (NPC) cell proliferation in vitro and in vivo. To better understand one possible mechanism of LTF-mediated antitumor activity in NPC cells, in the present study, we investigated the distribution of LTF gene polymorphisms (rs1126477, rs1126478, rs2073495, and rs9110) in NPC and revealed whether these polymorphisms were associated with LTF gene expression. It was found that rs2073495 and rs9110 were correlated significantly with NPC. The frequency of CC genotype was higher and GG or TT genotype was lower, in NPC patients compared with that in the control group (P < 0.05, χ(2) = 8.73 and 9.33, respectively). CC genotype is the risk factor for NPC. Haplotype analyses indicated that NPC patients had lower rate of 'A-G-G-T' haplotype (constructed with rs1126477, rs1126478, rs2073495, and rs9110) compared with controls (P = 4.12 × 10(-6) < 0.001, χ(2) = 21.25). The population with 'A-G-G-T' haplotype had 0.322-fold risk to be NPC. The expression of LTF gene was high in NPC tissues and control tissues with 'A-G-G-T' haplotype compared with these without its. These findings suggested that rs2073495 and rs9110 could play important roles in NPC physiological processes.

Topics: Blotting, Western; Carcinoma; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Lactoferrin; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors

Lactoferrin (LF) is a multifunctional glycoprotein that plays an important role in native immune defense against infections, including human herpetic viruses, such as cytomegalovirus and herpes simplex virus types 1 and 2. However, its anti-Epstein-Barr virus (EBV, a γ-herpesvirus) function has not been reported in the literature. EBV is widespread in all human populations and is believed to be linked to tumorigenesis, such as lymphomas and nasopharyngeal carcinoma (NPC). We previously reported that LF expressed a significantly lower level in NPC tissues and was a likely tumor suppressor. Since EBV infection is a major carcinogen of NPC development, we investigated the effect of LF on EBV infection and found that LF could protect human primary B lymphocytes and nasopharyngeal epithelial cells from EBV infection, but had no effect on EBV genome DNA replication. LF prevented EBV infection of primary B cells mediated by its direct binding to the EBV receptor (CD21) on the B-cell surface. Tissue array immunohistochemistry revealed that LF expression was significantly downregulated in NPC specimens, in which high EBV viral capsid antigen-IgA levels were observed. These data suggest that LF may inhibit EBV infection and that its downregulation could contribute to NPC development.

Topics: Antigens, Viral; B-Lymphocytes; Capsid Proteins; Carcinoma; Cell Line, Tumor; Cells, Cultured; DNA Replication; DNA, Viral; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunoglobulin A; Lactoferrin; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Virus Replication

The lactoferrin (LTF) gene, located at 3p21.3, behaves like a tumor suppressor gene in diverse tumors. To elucidate the exact role of LTF in NPC, we first detected its expression level in seven NPC cell lines by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed the mRNA level of LTF was nearly undetectable in all the seven NPC cell lines, while it could be detected in chronic nasopharyngitis tissues. Subsequently, we used methylation-specific PCR (MSP), microsatellite assay, PCR-single-strand conformation polymorphism (PCR-SSCP) and sequencing methods to examine the promoter methylation, loss of heterozygosity (LOH) and gene mutation of LTF in NPC cell lines respectively. Consequently, we found that 100% (7 of 7) of NPC cell lines were methylated in LTF promoter, only one cell line (14%, 1 of 7) had LOH and gene mutation of LTF, respectively, while LTF exhibited re-expression in all cell lines after 5-aza-dC treatment, indicating promoter methylation should be the key mechanism causing LTF downregulation in NPC cell lines. Furthermore, patched methylation assay confirmed that promoter methylation could down-regulate LTF gene expression in NPC cells. Finally, we investigated the function of LTF in NPC cell lines by gene transfection. Restoration of LTF expression in NPC cells resulted in blockage of cell cycle progression, significant inhibition of cell growth and a reduced colony-formation capacity in vitro and obviously weaker tumor formation potential in vivo. In conclusion, our data indicate LTF may participate in NPC carcinogenesis as a negative effector, that is, a tumor suppressor gene.

Topics: Animals; Base Sequence; Carcinoma; Cell Line, Tumor; Cell Proliferation; DNA Methylation; DNA Mutational Analysis; Female; G1 Phase; Humans; Lactoferrin; Loss of Heterozygosity; Male; Mice; Mice, Nude; Molecular Sequence Data; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Transplantation; Promoter Regions, Genetic; Recombinant Proteins; Transcription, Genetic; Tumor Burden

We have investigated Lf immunoexpression as well as its biological meaning in 71 formalin-fixed, paraffin-embedded surgical samples of endometrial carcinomas (EC); 64 EC were endometrioid type, whereas 7 were non-endometrioid carcinomas. Immunohistochemistry was performed by primary antibodies against Lactoferrin (Lf), estrogen receptor (ER), progesterone receptor (PR) and Ki-67 antigen. Quantification of Lf immunoreactivity was performed using an intensity-distribution (ID) score. Moreover, the AgNOR technique according to guidelines of the Committee on AgNOR Quantification was used to assess the proliferation rate (NORA). A variable expression of Lf was revealed in 43 cases (61%) of EC. Endometrioid type carcinoma showed a significant higher Lf ID-score than non-endometrioid type; in contrast, no relationships were demonstrated between Lf immunoexpression and histologic grade, stage, clinical course as well as proliferative activity of EC. Moreover, a significantly higher Lf ID-score was encountered in ER-positive carcinomas. Survival analysis in EC indicated the architectural, nuclear and combined histologic grades as well as the stage, PR, Ki-67 and NORA as significant parameters. The utilization of Lf as a prognostic marker, able to identify patients at different risk of death, or alternatively, its clinical application as therapeutic agent, must be considered with great caution.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Nuclear; Biomarkers, Tumor; Carcinoma; Cytoplasm; Endometrial Neoplasms; Female; Gonadal Steroid Hormones; Humans; Ki-67 Antigen; Lactoferrin; Middle Aged; Mitotic Index; Nuclear Proteins; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Risk

To investigate the roles of lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF), located at 3p21.3 within the common minimal deletion region, in the pathogenesis of nasopharyngeal carcinoma (NPC), we first detected its expression level in 33 primary NPC tissues and 15 chronic nasopharyngitis tissues. Absent expression or downregulation of LTF were observed in 76% (25 of 33) of primary NPC tissues. We further found that 25% (5 of 20) of NPC specimens had loss of heterozygosity (LOH) at the LTF locus. LTF mutation assessed by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing was noted in 30% (6 of 20) of primary NPC tissues. In addition, hyper-methylation of LTF promoter region was found in 63.6% (21 of 33) of primary NPC samples but not in chronic nasopharyngitis tissues. The LTF transcripts in NPC cell lines increased upon treatment with the demethylation compound, 5-aza-2-deoxycytidine. In conclusion, our data indicate that two-hit silencing of LTF through genetic and epigenetic changes may be a common and important event in the carcinogenesis of NPC.

Topics: Azacitidine; Base Sequence; Carcinoma; Cell Line, Tumor; Chromosomes, Human, Pair 3; CpG Islands; Decitabine; DNA Methylation; DNA Modification Methylases; DNA Mutational Analysis; Down-Regulation; Enzyme Inhibitors; Epigenesis, Genetic; Exons; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Lactoferrin; Loss of Heterozygosity; Male; Middle Aged; Molecular Sequence Data; Mutation; Nasopharyngeal Neoplasms; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Bovine lactoferricin (LfcinB) is a cationic, amphipathic peptide that is cytotoxic for human and rodent cancer cells. However, the mechanism by which LfcinB causes the death of cancer cells is not well understood. Here, we show that in vitro treatment with LfcinB rapidly induced apoptosis in several different human leukemia and carcinoma cell lines as determined by DNA fragmentation assays and phosphatidylserine headgroup inversion detected by Annexin V binding to the surface of cancer cells. Importantly, LfcinB treatment did not adversely affect the viability of untransformed human lymphocytes, fibroblasts, or endothelial cells. Studies with different LfcinB-derived peptide fragments revealed that the cytotoxic activity of LfcinB resided within the amino acid sequence FKCRRWQWRM. Treatment of Jurkat T leukemia cells with LfcinB resulted in the production of reactive oxygen species followed by caspase-2-induced dissipation of mitochondrial transmembrane potential and subsequent activation of caspase-9 and caspase-3. Selective inhibitors of caspase-2 (Z-VDVAD-FMK), caspase-9 (Z-LEHD-FMK), and caspase-3 (Z-DEVD-FMK) protected both leukemia and carcinoma cells from LfcinB-induced apoptosis. Conversely, a caspase-8 inhibitor (Z-IETD-FMK) had no effect, which argued against a role for caspase-8 and was consistent with the finding that death receptors were not involved in LfcinB-induced apoptosis. Furthermore, Jurkat T leukemia cells that overexpressed Bcl-2 were less sensitive to LfcinB-induced apoptosis, which was characterized by mitochondrial swelling and the release of cytochrome c from mitochondria into the cytosolic compartment. We conclude that LfcinB kills cancer cells by triggering the mitochondrial pathway of apoptosis at least in part through the generation of reactive oxygen species.

Topics: Animals; Annexin A5; Anti-Bacterial Agents; Antioxidants; Apoptosis; Carcinoma; Caspase 2; Caspase 3; Caspase 9; Caspases; Cattle; Cell Line, Tumor; Cell Survival; DNA Fragmentation; Dose-Response Relationship, Drug; Endothelial Cells; Enzyme Activation; Enzyme Inhibitors; Fibroblasts; Humans; Immunoblotting; Jurkat Cells; Lactoferrin; Leukemia; Lymphocytes; Membrane Potentials; Microscopy, Electron; Mitochondria; Oligopeptides; Phosphatidylserines; Reactive Oxygen Species; Tetrazolium Salts; Thiazoles; Time Factors

Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1-deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1(-/-) PMNs and in human PMNs blocked with anti-Mac-1 monoclonal Ab (mAb). Mac-1(-/-) PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1(-/-) and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1(-/-) PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1(-/-) PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis.

Topics: Animals; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Breast Neoplasms; Candida albicans; Carcinoma; CD18 Antigens; Cell Adhesion; Crosses, Genetic; Cytotoxicity, Immunologic; Exocytosis; Female; Glucuronidase; Humans; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Macrophage-1 Antigen; Membrane Fusion; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; NADPH Dehydrogenase; NADPH Oxidases; Neutrophils; Opsonin Proteins; Phagocytosis; Phosphoproteins; Protein Transport; Receptors, Fc; Respiratory Burst; Tumor Cells, Cultured

The effects of oral administration of bovine lactoferrin (bLF) and its hydrolysate on the lung colonization by colon 26 carcinoma were investigated. At doses of 100 or 300 mg/kg/day for seven successive days, bLFs demonstrated a significant inhibitory effect on experimental metastasis, which indicated effectiveness before and after tumor implantation. Oral administration of bLFs augmented CD4+, CD8+, and asialoGM1+ cells in the spleen and peripheral blood. Their cytotoxic activities against Yac-1 and colon 26 carcinoma were enhanced by bLF. In the small intestinal epithelium, CD4+ and CD8+ cells were markedly increased, and, simultaneously, enhanced production of interleukin-18 (IL-18) was confirmed in the intestinal epithelial cells. In this model, intravenous injection of murine IL-18 showed significant inhibition of the lung colonization by colon 26 carcinoma. These results suggested that inhibition of experimental metastasis by oral administration of bLF and pepsin hydrolysate of bLF might be due to enhanced cellular immunity, presumably mediated by enhanced IL-18 production in the intestinal epithelium.

Topics: Administration, Oral; Animals; Carcinoma; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Colonic Neoplasms; Fluorescent Antibody Technique; G(M1) Ganglioside; Humans; Immunity, Cellular; Interleukin-18; Intestinal Mucosa; Killer Cells, Natural; Lactoferrin; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Specific Pathogen-Free Organisms; Spleen; Tumor Cells, Cultured

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

The mouse lactoferrin gene responded to forskolin, 12-O-tetradecanoyl phorbol-13-acetate, and epidermal growth factor (EGF) stimulation via two adjacent enhancer elements, the cAMP response element (CRE) and EGF response element (EGFRE), collectively referred to as the mitogen response unit. In this report, we examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF-induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the chloramphenicol acetyltransferase (CAT) reporter construct whereas the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters [SV 40 and thymidine kinase (TK)]. Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. In transiently transfected cells, EGF and forskolin showed synergistic effects on the CAT reporter that contained both response elements. Mutation made at either element or insertion of extra nucleotides between the two elements severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells formed three complexes (A, B, and C) with the oligonucleotides containing both EGFRE and CRE in electrophoretic mobility shift assay. A new complex (E) was detected with the nuclear protein of EGF-treated cells. By oligonucleotide competition experiments, we demonstrated that the complex E was generated by protein bound to CRE. EGF-induced binding activity could be abolished by calf intestinal alkaline phosphatase but not by the protein synthesis inhibitor, cycloheximide. Therefore, binding of a preexisting phosphoprotein to the CRE region could be one of the requirements for EGF-induced mouse lactoferrin gene promoter activity.

Topics: Animals; Binding Sites; Carcinoma; Electrophoresis; Endometrial Neoplasms; Epidermal Growth Factor; ErbB Receptors; Female; Gene Expression Regulation; Humans; Lactoferrin; Mice; Nuclear Proteins; Promoter Regions, Genetic; Receptors, Cyclic AMP; Recombinant Proteins; TATA Box; Transfection; Tumor Cells, Cultured

The human neutrophil lactoferrin (Lf), a cationic iron-binding glycoprotein, has an inhibitor role on granulocyte macrophage colony-stimulating factor (GM-CSF) production via interleukin-1 (IL-1). The nuclear localization of Lf suggests that it may be involved in the transcriptional regulation of GM-CSF gene expression. To explore this possibility, the effect of Lf on GM-CSF gene expression was investigated in various cell lines and in primary cultures of fibroblasts. Down-regulation of GM-CSF mRNA level was observed in Lf-transfected embryonic fibroblasts induced to produce GM-CSF by IL-1 beta. In 5637 cell-line and in embryonic fibroblasts, co-transfection experiments, in which an Lf expression vector was used together with a vector carrying a reporter gene linked to the GM-CSF promoter, revealed that Lf reduces the activity of the GM-CSF promoter. This effect is marked in IL-1 beta-stimulated cells. These findings suggest that Lf plays a negative role in GM-CSF expression at the transcriptional level, perhaps through the mediation of IL-1 beta.

Topics: Carcinoma; Cells, Cultured; Depression, Chemical; Fibroblasts; Gene Expression Regulation; Genes, Reporter; Genetic Vectors; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; Lactoferrin; Lung; Lymphoma, Large B-Cell, Diffuse; Promoter Regions, Genetic; Recombinant Fusion Proteins; RNA, Messenger; T-Lymphocytes; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Lactoferrin was analysed with an ELISA in pleural effusions from 21 patients with malignant exudative effusions (15 carcinomas and 6 mesotheliomas), 12 patients with non-malignant exudative effusions of unknown aetiology, 11 patients with transudative effusions due to congestive heart failure, 12 patients with exudative effusions secondary to infection, and 2 patients with tuberculous effusions. Median pleural fluid lactoferrin was 133 micrograms/l (range 25-435) in carcinomas, 55 micrograms/l (23-185) in mesotheliomas, 198 micrograms/l (31-530) in non-malignant exudates, 68 micrograms/l (17-205) in transudates, 1815 micrograms/l (1380-2050) in infectious exudates and 107 micrograms/l (88-125) in tuberculosis. Due to a wide overlap between the various groups pleural fluid lactoferrin appears to be of limited value in the routine diagnostic evaluation of non-infectious pleural effusions, but seems to separate infectious exudates from non-infectious exudates.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Infections; Lactoferrin; Male; Mesothelioma; Middle Aged; Pleural Effusion; Pleural Effusion, Malignant

Estrogen exerts a variety of biological effects on human reproductive tissues. However, little is understood about the estrogenic effect on human endometrial cells in vitro. This study was designed to investigate estrogen action on c-myc and c-fos oncogenes and lactoferrin gene expression in human endometrial carcinoma RL95-2 cells. The results indicate that estrogen can induce c-myc oncogene expression in 4 h. Neither c-fos nor the lactoferrin messenger was detectable, nor could they be induced by estrogen. Transfection with human estrogen receptor expression vector to the RL95-2 cells does not restore the estrogen responsiveness. In addition to estrogen, epidermal growth factor (EGF) and tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) can also induce c-myc expression with no effect on c-fos or lactoferrin expression. Our data suggest that the c-myc oncogene in human endometrial carcinoma RL95-2 cells is the sensitive target gene for steroid hormone and growth factor action.

Topics: Carcinoma; Endometrial Neoplasms; Estrogens; Female; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, myc; Humans; Lactoferrin; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-myc; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured

In order to identify expression of RNA transcripts for a number of important tracheobronchial cell products and molecules, we developed simple reverse transcription-polymerase chain reaction (RT-PCR) assays. Assays included the RNA for two apomucins (MUC1 and MUC2), secretory component, secretory leukocyte inhibitor protein, lysozyme, lactoferrin, 15-lipoxygenase, and the cystic fibrosis transmembrane conductance regulator. We tested RNA of normal and neoplastic origin. Sources of normal tissue included human tracheal surface epithelial cells and tracheobronchial submucosal tissues, acutely isolated human tracheal surface epithelial and tracheobronchial gland acini, and confluent cultures of human tracheal epithelial and tracheobronchial gland cells. Sources of neoplastic tissue included cell lines of non-small cell carcinomas of the lung. RNA expression was correlated with protein expression as assessed by immunocytochemistry. Tracheal surface epithelial tissues, isolated cells and cultures, and tracheobronchial submucosal tissues expressed RNA transcripts for all of the RNA transcripts assayed. Isolated gland acini and cultured gland cells expressed all RNA transcripts except 15-lipoxygenase. Expression of RNA transcripts by non-small cell lung carcinomas was heterogeneous and not necessarily influenced by histopathologic type. In most instances, RNA expression predicted expression of immunocytochemically detectable protein. These RT-PCR assays are useful for characterizing the molecular phenotype of cell cultures derived from normal or neoplastic airway epithelium and for establishing the potential of cultured cells for functional studies.

Topics: Arachidonate 15-Lipoxygenase; Base Sequence; Carcinoma; Cells, Cultured; Cystic Fibrosis Transmembrane Conductance Regulator; DNA Primers; Epithelium; Gene Expression; Lactoferrin; Lung Neoplasms; Membrane Proteins; Molecular Sequence Data; Mucins; Muramidase; Phenotype; Polymerase Chain Reaction; Proteinase Inhibitory Proteins, Secretory; Proteins; RNA-Directed DNA Polymerase; RNA, Messenger; Secretory Component; Serine Proteinase Inhibitors; Trachea

Eight cases of acinic cell carcinoma of the salivary glands were histologically reclassified and their immunohistochemical expression and distribution for various tissue antigens were examined. The epithelial elements were divided into tubuloglandular components, microcystic patterns and solid nests. The authors' results indicated the following: 1) The duct luminal cells of tubuloglandular components have distinct epithelial features with cytokeratin (KL 1), alpha 1-antichymotrypsin (alpha 1-ACT), transferrin, lactoferrin, IgA, and carcinoembryonic antigen (CEA) positivity. 2) The cyst-lining cells of microcystic pattern expressed immunophenotypes similar to those of the duct luminal cells. 3) The acinic cells in solid nests had positive results for KL 1, alpha 1-antitrypsin (alpha 1-AT), transferrin, lactoferrin and vasoactive intestinal polypeptide (VIP). 4) The clear cells in solid areas had positive results for KL 1, alpha 1-AT, transferrin and VIP. Both the clear cells and the neoplastic acinic cells showed a rather similar pattern of immunoreactivity. Therefore, the clear cells may transform from the neoplastic acinic cells. 5) Secretory products in tubuloglandular and microcystic patterns had positive results for alpha 1-ACT, lactoferrin, IgA and CEA. 6) The basement membrane-like material between the neoplastic islands has distinct positivity for alpha 1-AT. The result suggests that alpha 1-AT is a useful marker of basement membrane-like material.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Biomarkers, Tumor; Carcinoma; Cytoplasm; Female; Ferritins; Humans; Immunoenzyme Techniques; Intermediate Filaments; Lactoferrin; Male; Middle Aged; Proteins; Reference Values; Salivary Gland Neoplasms; Transferrin

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

Immunohistochemical expression of 8 cases of mucoepidermoid carcinomas (G-I, 3 cases; G-II, 2 cases; and G-III, 3 cases) revealed marked heterogeneity of the proteins examined. Immunohistochemically detectable keratins (TK, KL1, and PKK1) were distributed in epidermoid cells, but were absent in mucous secreting cells. Strongly positive deposits of keratin proteins were detected in squamoid tumor cells in the G-I tumors. The tumor cells displayed positive staining for S-100 alpha, but did not stain with polyclonal S-100 antiserum or with monoclonal S-100 beta. The cells showing highest reactivity for S-100 protein were scattered in neoplastic foci and were probably Langerhans cells. Lactoferrin and lysozyme reactions were generally negative in tumor foci; but a positive reaction for lactoferrin was found in luminal tumor cells although rarely, and lysozyme staining was occasionally noted in histiocytes in the stroma. Amylase activity was usually absent in the tumor cells, with the exception of one case in which it was confined to the tumor cells. Mucoepidermoid carcinomas of various grades indicated marked heterogeneity in terms of various immunohistochemically detectable proteins.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amylases; Carcinoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Lactoglobulins; Male; Middle Aged; Muramidase; Periodic Acid-Schiff Reaction; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling

136 breast carcinomas were investigated immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr), human milk fat globule membrane antigen (HMFG-2), transferrin receptor (TrfR), Ki-67 and epidermal growth factor receptor (EGFR). The relationships of pathologic features and steroid receptor status previously shown to be of prognostic significance and the immunohistochemical parameters were examined. It was found that estrogen receptor (ER) was inverse related to TrfR, Ki-67 and EGFR whereas progesterone receptor (PgR) was inverse correlated to Ki-67 solely. Tumor grading revealed significant correlations between TrfR, Ki-67 and HMFG-2 (inverse correlation). Tumor diameter showed correlation between Ki-67 solely. Moreover there were significant relationships between lymphoid infiltration and TrfR, Ki-67 and HMFG-2 (inverse correlation). The comparison of the immunohistochemical parameters showed correlations between Ki-67 and TrfR, Ki-67 and HMFG-2 (inverse correlation) as well as HMFG-2 and ALA. Therefore it is suggested that functional and tumor kinetic properties determined by HMFG-2, Ki-67 and TrfR may be an additional indicator with prognostic significance. On the other hand immunoreactivities of ALA in conjunction with HMFG-2 possibly indicates a subpopulation of breast carcinomas that may have to be investigated further. Moreover these results showed that lymphoid infiltration was correlated with Ki-67 reactivity as well as TrfR expression.

Topics: Adenocarcinoma, Mucinous; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; ErbB Receptors; Female; Humans; Lactalbumin; Lactoferrin; Membrane Glycoproteins; Middle Aged; Mucin-1; Prognosis; Receptors, Estrogen; Receptors, Transferrin

Five cases of lipid-rich carcinomas of the breast were investigated ultrastructurally and immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr) and human milk fat globule membrane antigen (HMFG-2). Staining for ALA and Lfr showed intensive reaction on nearly all of the tumour cells whereas immunoreaction for HMFG-2 revealed positivity in single cells. All tumours were negative for steroid receptor content. Ultrastructurally the tumour cells showed numerous intracytoplasmic non-membrane bound lipid droplets which were often found within autophagocytic vacuoles. Neither rough endoplasmic reticulum nor Golgi complexes showed any sign of lipid synthesis. Extrusion of lipid droplets and extracellular lipid deposition was not observed. In conclusion, our findings do not justify the consideration of lipid-rich carcinoma of the breast as a clearly defined group of tumours with specific secretory activity. Therefore, the term lipid-rich carcinoma should be used in preference to lipid-secreting, unless there is evidence of active lipid secretion.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Lactalbumin; Lactoferrin; Lipids; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1

Forty-three cases of large cell anaplastic thyroid carcinoma were examined with various antisera. Four histological patterns were identified: spindle cell, giant cell, trabecular and squamous. In 38 cases the epithelial origin was demonstrated with various epithelial markers: 11 cases stained positively for thyroglobulin, 19 for T3 and/or T4, 35 for fat globule membrane antigens, 28 for keratin, 29 for lactoferrin, and one for calcitonin. Five cases were negative for all epithelial markers but could not be characterized further since, except for vimentin, they did not have mesenchymal markers. The immunohistochemical proof of the epithelial nature of anaplastic thyroid tumours is given by staining with anti-keratin and anti-fat globule membrane antigen. In addition the detection of lactoferrin seems useful, but not that of thyroglobulin which was present in only 4% of the spindle cell tumours and in 32-56% of the other histological types. Thirty carcinomas were positive for vimentin; the co-expression of vimentin and epithelial markers seems frequent in thyroid anaplastic carcinomas.

Topics: Aged; Aged, 80 and over; Animals; Calcitonin; Carcinoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Lectins; Male; Membrane Proteins; Middle Aged; Mucin-1; Peptides; Plant Lectins; Rabbits; Thyroglobulin; Thyroid Neoplasms; Thyronines; Tissue Polypeptide Antigen; Vimentin

Topics: Adenocarcinoma, Mucinous; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunoenzyme Techniques; Lactalbumin; Lactoferrin; Lactoglobulins; Membrane Proteins; Mucin-1; Neoplasm Invasiveness; Prognosis

A clonal neoplastic epithelial duct cell (HSGc) of human salivary gland origin has a fine structure similar to the intercalated duct cell and the capacity to express secretory component and lactoferrin. HSGc cells tend to form an occasional glandular arrangement in vitro and in vivo, and transplantation of cells into nude mice resulted in production of adenocarcinoma. By repeated single cell cloning, different types of clones could be isolated from HSGc. Cuboidal clones resemble the parent cell, but fail to form the glandular arrangement or express lactoferrin, suggesting a less differentiated type. Elongated clones have a fine structure similar to myoepithelial cells and carry myoepithelial markers such as S100 protein, actin, and myosin which are not detected in the HSGc and its cuboidal clones. These myoepithelial-like clones are able to express secretory component, lactoferrin, and lysozyme and to produce glycosaminoglycans, suggesting that they are a functionally active form of the neoplastic cell but different from the normal myoepithelial cell. Judging from their growth properties in vitro and in vivo, the myoepithelial-like clones are less malignant than HSGc or its cuboidal clones. Of four elongated clones, two did not produce tumors in athymic mice, while all of the cuboidal clones were tumorigenic. These findings suggest a possible conversion of the neoplastic duct cell to myoepithelial-like variants with low malignancy.

Topics: Actins; Adenocarcinoma; Antigens; Carcinoma; Cell Cycle; Cell Line; Cell Separation; Clone Cells; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Lactoferrin; Microscopy, Electron; Muramidase; Myosins; S100 Proteins; Salivary Gland Neoplasms; Secretory Component

Antisera of several secretory products of the salivary gland were used to investigate the histogenesis of acinic cell tumors and mixed salivary gland tumors for comparison. Amylase, lactoferrin, secretory piece, and proline-rich protein (PRP) immunoreactivity was detected in the majority of acinic cell tumors; staining was focal, except for PRP, which was diffuse. Lysozyme immunoreactivity was rare. There was discordance for immunoreactivity with several antisera in identifiable tumor lobules of half of the neoplasms. An antikeratin serum outlined microcystic and follicular areas but rarely solid foci. These findings support the contention that acinic cell tumors derive from a tubular type stem cell. Lactoferrin and secretory piece immunoreactivity was not common in mixed tumors and was confined to scattered ductal cells and luminal contents. Rare small foci of amylase and PRP immunoreactivity were found in two mixed tumors only.

Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Amylases; Carcinoma; Female; Humans; Immunochemistry; Keratins; Lactoferrin; Male; Middle Aged; Muramidase; Peptides; Proline-Rich Protein Domains; Salivary Gland Neoplasms; Staining and Labeling

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

Using immunoperoxidase procedures, the presence of lactoferrin was investigated in benign hypertrophy (40 cases), differentiated adenocarcinomas (20 cases) and undifferentiated carcinomas (10 cases) of the prostate. In benign hypertrophy, the glandular epithelium and the secretory product were consistently negative. Strong staining for lactoferrin was always observed in neoplastic cells of differentiated adenocarcinomas and in their endoluminal material; in contrast, a very slight positivity was noted in undifferentiated carcinomas. These findings are discussed in relation to the different degree of neoplastic glandular differentiation and functional activity of prostatic carcinomas.

Topics: Adenocarcinoma; Carcinoma; Histocytochemistry; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Male; Prostatic Hyperplasia; Prostatic Neoplasms

An immunoperoxidase staining technique was used for detecting three major iron binding proteins (ferritin, transferrin and lactoferrin) in 40 breast carcinoma cases and six benign breast proliferative lesions. Ferritin staining was detected mainly in connectival stroma and in histiocytes surrounding neoplastic cells. Few and faint ferritin positivities were also detected in neoplastic cells of 20 carcinoma cases. Transferrin was found inconsistently in myoepithelial cells surrounding normal ductules, or around neoplastic ducts of ductal in situ carcinoma. In eight carcinoma cases, transferrin staining was also positive in neoplastic cells. Lactoferrin was detected only in normal breast epithelial cells and in benign breast proliferative lesions. These immunohistochemical findings may suggest that raised serum ferritin concentrations in breast carcinoma patients might be attributed to stromal reaction rather than to tumour synthesis. Transferrin staining of neoplastic cells in these carcinoma cases appears to be very intriguing, particularly since transferrin is considered an obligate requirement for growing cells, and transferrin receptors have been demonstrated only in dividing cells. On the basis of the immunohistochemical data, lactoferrin might be used as a pointer to benign lesions.

Topics: Adenocarcinoma, Mucinous; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Female; Ferritins; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Transferrin

In a collection of parotid gland tumors the presence of different antigens was studied by immuno-histochemical methods. The series was composed of different tumors: adeno- and cystadenocarcinomas, adenoid-cystic carcinomas, salivary duct carcinomas, mucoepidermoid tumors, squamous cell carcinomas and anaplastic carcinomas. The following substances were studied: 1. Substances normally present in salivary glands like lysozyme and lactoferrin. 2. Oncofetal antigens: carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). 3. Different classes of intermediate-sized filaments: prekeratin and vimentin. The presence of lactoferrin and carcinoembryonic antigen could be demonstrated in the glandular differentiated tumors, whereas the squamous cell carcinomas, although CEA positive, were lactoferrin negative. The anaplastic carcinomas were negative for lactoferrin and CEA. Lysozyme and AFP could not be demonstrated in the tumors of our material. Mucoepidermoid tumors and squamous cell carcinomas were clearly positive for prekeratin filaments whereas the stromal part showed a vimentin filaments in the cytoplasm of fibroblasts. These antigens provide a useful tool to distinguish between the epithelial and mesenchymal tumors.

Topics: alpha-Fetoproteins; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Immunoenzyme Techniques; Lactoferrin; Muramidase; Parotid Neoplasms

Lactoferrin and lysozyme, parts of the non-specific defense system, were studied in normal and diseased parotid glands, using the immunohistochemical PAP-method. 31 normal and inflamed glands were investigated. The presence of lactoferrin and lysozyme was demonstrated in the acinar cells and some duct cells. The amount of these substances was increased in obstructive parotitis. The 52 carcinomas showed a distinct distribution pattern for lactoferrin (positive cases: adenocarcinomas 5 of 8; cystadenocarcinoma: 3 of 5; adenoid cystic carcinomas 2 of 4; salivary duct carcinomas 2 of 3). Some of the carcinomas in pleomorphic adenomas were positive for lactoferrin. Squamous cell carcinomas and anaplastic carcinomas were constantly negative. All carcinomas were negative for lysozyme. These observations are discussed with respect to their physiological and pathological significance.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Squamous Cell; Cystadenocarcinoma; Humans; Lactoferrin; Lactoglobulins; Muramidase; Parotid Neoplasms; Parotitis