lactoferrin and Neoplasm-Metastasis

In experimental studies, bovine lactoferrin (bLF) has been found to significantly inhibit colon, esophagus, lung, and bladder carcinogenesis in rats when administered orally in the post-initiation stage. Furthermore, concomitant administration with carcinogens resulted in inhibition of colon carcinogenesis, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2), which is preferentially induced by carcinogenic heterocyclic amines. Enhancement of the activities of their phase II counterparts, such as glutathione S-transferase might have also played a critical role in post-initiation suppression in a study of tongue carcinogenesis. Anti-metastatic effects were moreover detected when bLF was given intragastrically to mice bearing highly metastatic colon carcinoma 26 cells (Co 26Lu), with apparent enhancing influence on local and systemic immunity. Marked increase in the number of cytotoxic T and NK cells in the mucosal layer of the small intestine and peripheral blood cells was thus found, this in turn enhancing the production of Interleukin 18 (IL-18) and caspase-1 in the epithelial cells of the small intestine, with possible consequent induction of interferon (IFN)-gamma positive cells. Furthermore, bLF has been found to exert anti-hepatitis C virus (HCV) activity in a preliminary clinical trial in patients with chronic active hepatitis due to this virus, a main causative factor in hepatocellular carcinoma development in Japanese. More extensive clinical trials are now underway in the National Cancer Center Hospital and other institutes to further explore the preventive potential against colon carcinogenesis.

Topics: Animals; Antiviral Agents; Clinical Trials as Topic; Colonic Neoplasms; Hepatitis C, Chronic; Humans; Immunity, Mucosal; Lactoferrin; Lung Neoplasms; Neoplasm Metastasis; Neoplasms; Pilot Projects

We evaluated safety and activity of talactoferrin, a novel immunomodulatory protein in a phase IB trial of patients with refractory solid tumors.. Thirty-six patients with metastatic cancer who had progressed on, or were ineligible for, standard chemotherapy received single-agent oral talactoferrin. Following dose-escalation, with no DLTs , patients were randomized to 4.5 or 9 g/day talactoferrin.. Talactoferrin was well tolerated with apparent anti-cancer activity, particularly in NSCLC and RCC. One patient had a PR (RECIST) and 17 patients (47%) had stable disease (50% disease control rate). Median PFS in the twelve NSCLC and seven RCC patients was 4.2 and 7.3 months, respectively. There was no apparent difference in anti-tumor activity or adverse events between talactoferrin doses.. Oral talactoferrin was well tolerated. Although evaluated in a small number of patients, talactoferrin appeared to have anti-cancer activity, particularly in NSCLC and RCC and should be evaluated further.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Cell Proliferation; Demography; Female; Humans; Kidney Neoplasms; Lactoferrin; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Tomography, X-Ray Computed

Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron-binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine-activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types. The purpose of the current study was to evaluate the activity and safety of TLF in patients with refractory metastatic renal cell carcinoma (RCC).. Forty-four adult patients with progressive advanced or metastatic RCC who had failed prior systemic therapy received oral talactoferrin at a dose of 1.5 g twice daily on a 12-week-on 2-week-off schedule. Patients were evaluated for progression-free survival at 14 weeks, overall response rate, and progression-free and overall survival.. TLF was well tolerated. No significant hematologic, hepatic, or renal toxicities were reported. The study met its predefined target with a 14-week progression-free survival rate of 59%. The response rate was 4.5%. The mMedian progression-free survival was 6.4 months and the median overall survival was 21.1 months.. TLF is a well-tolerated new agent that has demonstrated preliminary signs of clinical activity. Given the lack of toxicity, the lack of rapid disease progression in this cohort, and the preclinical data on immune activation, a randomized study assessing its effects on disease progression in patients with metastatic RCC is rational.

Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Kidney Neoplasms; Lactoferrin; Male; Middle Aged; Neoplasm Metastasis; Recombinant Proteins; Survival Analysis

Lactoferrin, an innate immunity molecule, is involved in anti-inflammatory, anti-microbial, and anti-tumor activities. We previously reported that lactoferrin is downregulated in specimens of nasopharyngeal carcinoma and negatively associated with tumor progression and metastasis of patients with nasopharyngeal carcinoma. However, the relationship between lactoferrin and the pro-metastatic microenvironment has not been reported yet. Here, by using the lactoferrin knockout mouse, we found that lactoferrin deficiency facilitated melanoma cells metastasizing to lungs, through recruiting myeloid-derived suppressor cells (MDSCs) in the lungs. Mechanistic studies showed that in the lung microenvironment of the lactoferrin knockout mice, the TLR9 signaling was the most repressed signaling. Lactoferrin can induce MDSCs differentiation and apoptosis, as well as upregulate TLR9 expression. TLR9 agonist or lactoferrin treatment can rescue this phenotype in the tumor metastasis mouse model. Our results suggest a protective role of lactoferrin in cancer metastasis, along with a deficiency in certain components of the innate immune system, may lead to a pro-metastatic tumor microenvironment.

Topics: Animals; Apoptosis; Cell Differentiation; Cell Line, Tumor; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Immunity, Innate; Lactoferrin; Lung; Melanoma, Experimental; Mice; Mice, Knockout; Myeloid-Derived Suppressor Cells; Neoplasm Metastasis; Signal Transduction; Toll-Like Receptor 9; Tumor Microenvironment

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

Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors for which identification and validation of biological markers may improve clinical management. The fraction of low-molecular-weight (LMW) circulating proteins and fragments of proteins is a rich source of new potential biomarkers. To identify circulating biomarkers useful for STS early diagnosis and prognosis, we analyzed 53 high-grade STS sera using hydrogel core-shell nanoparticles that selectively entrap LMW proteins by size exclusion and affinity chromatography, protect them from degradation and amplify their concentration for mass spectrometry detection. Twenty-two analytes mostly involved in inflammatory and immunological response, showed a progressive increase from benign to malignant STS with a relative difference in abundance, more than 50% when compared to healthy control. 16 of these were higher in metastatic compared to non-metastatic tumors. Cox's regression analysis revealed a statistical significant association between the abundance of lactotransferrin (LTF) and complement factor H-related 5 (CFHR5) and risk of metastasis. In particular, CFHR5 was associated with the risk of metastasis. The role of circulating proteins involved in metastatic progression will be crucial for a better understanding of STS biology and patient management.

Topics: Biomarkers, Tumor; Blood Proteins; Complement System Proteins; Early Diagnosis; Humans; Lactoferrin; Nanoparticles; Neoplasm Metastasis; Prognosis; Sarcoma; Tandem Mass Spectrometry

Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers; however, its roles in oral squamous cell carcinoma (OSCC), one of malignant head and neck carcinomas, has not been explored.. Here, the expression of LTF in OSCC tissues and TCA8113 cells was detected with RT-PCR, qPCR, and IHC. And the correlation between LTF expression and OSCC metastasis was assessed. MS-PCR was performed to reveal the methylation status in promoter regions of LTF both in OSCC tissue samples and cells. The influences of 5-Aza-Cdc treatment to the methylation status and expression levels of LTF were also analyzed. At last, the functions of LTF in OSCC progression were demonstrated by MTT analysis, clone formation assay, and cell cycle analysis in TCA8113 cells with forced ectopic expression of LTF.. LTF showed a low or null expression pattern in OSCC tissues and cells, at least partially, due to the hypermethylated status in promoter regions for 5-Aza-Cdc, a methyltransferase inhibitor, could restore the expression of LTF in TCA8113 cells. And the expression level of LTF exhibited a negative correlation with OSCC metastasis.. Re-expression of LTF inhibited the growth, proliferation, as well as cell cycle progression of TCA8113 cells. In conclusion, hypermethylation contributes much to LTF inactivation in OSCC. And LTF can partially reverse the malignant phenotypes of OSCC cells and may be served as a potential target for diagnosis and therapy of OSCC in future.

Topics: Base Sequence; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; DNA Methylation; Gene Silencing; Genes, Tumor Suppressor; Head and Neck Neoplasms; Humans; Immunohistochemistry; Lactoferrin; Molecular Sequence Data; Mouth Neoplasms; Neoplasm Metastasis; Polymerase Chain Reaction; Promoter Regions, Genetic; Squamous Cell Carcinoma of Head and Neck

Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of β-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity.

Topics: Antineoplastic Agents; Cell Death; Cell Line, Tumor; Cell Membrane Permeability; Humans; Lactoferrin; Melanocytes; Melanoma; Models, Molecular; Neoplasm Metastasis; Peptide Fragments; Phosphatidylserines; Protein Structure, Secondary

Lactoferrins exhibit antitumoral activities either as a secretory lactoferrin or an intracellular delta-lactoferrin isoform. These activities involve processes such as regulation of the cell cycle and apoptosis. While lactoferrin has been shown to exert its function by activating different transduction pathways, delta-lactoferrin has been proven to act as a transcription factor. Like many tumor suppressors, these two proteins are under-expressed in several types of cancer, particularly in breast cancer.. In order to compare the differential effects of the re-introduction of lactoferrin isoforms in breast cancer cells we chose the cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line stably expressing delta-lactoferrin. We also treated these cells with fresh purified human breast lactoferrin. We performed two quantitative proteomic studies in parallel using SILAC coupled to mass spectrometry in order to compare the effects of different doses of the two lactoferrin isoforms. The proteome of untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231 cells were compared. Overall, around 5300 proteins were identified and quantified using the in-house developed MFPaQ software. Among these, expression was increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin expressing cells and 190 proteins in lactoferrin treated cells. At the same time, about 200 and 40 proteins were found to be downregulated (0-0.7-fold) in response to delta-lactoferrin and lactoferrin, respectively.. Re-introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly leads to modifications of protein profiles involved in processes such as proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation and mRNA quality control. Moreover, this study identified new target genes of delta-lactoferrin transcriptional activity such as SelH, GTF2F2 and UBE2E1.

Topics: Alternative Splicing; Breast Neoplasms; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Isotope Labeling; Lactoferrin; Neoplasm Metastasis; Promoter Regions, Genetic; Protein Binding; Protein Isoforms; Proteome; Proteomics; Recombinant Proteins; Reproducibility of Results; Response Elements; Selenoproteins; Transcription Factors; Transcription Factors, TFII; Ubiquitin-Conjugating Enzymes

This report provides the first proteomic analysis of normal ovine lymph. By establishing the fact that lymph is more than an ultrafiltrate of blood plasma, it documents that the lymph proteome contains an array of proteins that differentiates it from plasma. The protein chip technology, surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS), two-dimensional gel electrophoresis (2-D PAGE) and MS, were employed to examine the protein expression profiles of ovine lymph. Using a weak cation exchange chip surface to assay lymph and plasma samples by SELDI-TOF-MS showed that the analysis of peak maps from lymph contained three protein peaks that were found only in lymph, while analysis of peak maps from plasma samples showed that five protein peaks were found only in plasma. Lymph and plasma samples showed eight peaks that were common to both. There were also more ions present in plasma than in lymph, which is consistent with the 2-D PAGE analysis. MS analysis of a large number of protein spots from 2-D PAGE gels of lymph produced MS/MS sequences for 18 proteins that were identified by searching against a comprehensive protein sequence database. As in plasma, large protein spots of albumin dominated the protein pattern in lymph. Other major proteins identified in 2-D PAGE gels of lymph included, fibrinogen alpha- and beta-chains, immunoglobulin G (IgG) heavy chain, serotransferrin precursor, lactoferrin, and apolipoprotein A-1. Two proteins that were identified and were differentially expressed in lymph were glial fibrillary astrocyte acidic protein and neutrophil cytosol factor-1. By bringing the technologies of proteomics to bear on the analysis of lymph, it is possible to detect proteins in lymph that are quantitatively and qualitatively differentially expressed from those of plasma.

Topics: Animals; Apolipoprotein A-I; Biomarkers, Tumor; Cattle; Databases as Topic; Electrophoresis, Gel, Two-Dimensional; Glial Fibrillary Acidic Protein; Humans; Hydrogen-Ion Concentration; Isoelectric Focusing; Lactoferrin; Lymph; Mass Spectrometry; NADPH Oxidases; Neoplasm Metastasis; Neoplasms; Peptides; Phosphoproteins; Proteome; Proteomics; Sheep; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transferrin

Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity.. Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration.. Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion.. These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

Topics: Aged; Angiogenesis Inhibitors; Antigens, CD; Biomarkers, Tumor; CD24 Antigen; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Indoles; Lactoferrin; Leukocytes, Mononuclear; Male; Matrix Metalloproteinase 9; Membrane Glycoproteins; Middle Aged; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Protein-Tyrosine Kinases; Pyrroles; Reverse Transcriptase Polymerase Chain Reaction

Bovine lactoferrin (bLF), a milk protein known to have bacteriostatic properties was examined for its preventive effects on colon and other organ carcinogenesis and experimental metastasis. (Experiment 1) The influence on colon carcinogenesis was investigated in male rats treated with azoxymethane (AOM), then received 2 or 0.2% bLF for 36 weeks. Significant reduction in the incidence (27% and 46% of the control, respectively) and number of adenocarcinomas of the large intestine was observed. (Experiment 2) In BALB/c mice bearing subcutaneous (s.c.) implants of colon carcinoma 26 (Co 26Lu). bLF demonstrated significant inhibition of spontaneous lung metastasis (approximately 43% of the control). Number of cytotoxic asialoGM1+ and CD8+ cells in white blood cells increased (171% and 122% of control, respectively) after treatment. Results of those experiments indicate that bLF remarkably prevents colon carcinogenesis and lung metastasis of colon carcinoma cells, possibly due to increasing cytotoxic cells in the peripheral blood.

Topics: Animals; Azoxymethane; Cattle; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Coculture Techniques; Colonic Neoplasms; G(M1) Ganglioside; Lactoferrin; Leukocytes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Rats; Rats, Inbred F344; Tumor Cells, Cultured

The effect of a bovine milk protein, lactoferrin (bLf), and a pepsin-generated peptide of bLf, lactoferricin (Lfcin-B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, was examined in experimental and spontaneous metastasis models using syngeneic mice. The subcutaneous (s.c.) administration of bovine apo-lactoferrin (apo-bLf) and Lfcin-B 1 day after tumor inoculation significantly inhibited liver and spleen metastasis of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells, whereas human apo-lactoferrin (apo-hLf) and bovine holo-lactoferrin (holo-Lf) at the dose of 1 mg/mouse did not. Furthermore, both apo-bLf and Lfcin-B, but not apo-hLf and holo-bLf, inhibited the number of tumor-induced blood vessels and suppressed tumor growth on day 8 after tumor inoculations in an in vivo model. However, in a long-term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo-bLf significantly suppressed the growth of B16-BL6 cells throughout the examination period, but Lfcin-B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis model, multiple administration of both apo-bLf and Lfcin-B significantly inhibited lung metastasis of B16-BL6 cells, however it was only apo-bLf that exhibited the inhibitory effect of tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. The results suggest that apo-bLf and Lfcin-B inhibit tumor metastasis through different mechanisms, and that the inhibitory activity of bLf on tumor metastasis may be related to the property of iron (Fe3+)-saturation.

Topics: Animals; Antineoplastic Agents; Cattle; Humans; Lactoferrin; Lymphoma; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic

The antitumor effects of the multifunctional iron-binding glycoprotein, lactoferrin (Lf), were investigated. Lf inhibited growth in mice of transplantable solid tumors induced by v-ras transformed fibroblasts and a methylcholanthrene-induced fibrosarcoma. Lf also substantially reduced lung colonization (experimental metastasis) by B16-F10 melanoma cells in syngeneic mice. Iron-saturated and apo-Lf exhibited comparable levels of tumor inhibition and antimetastatic activity. Transferrin, a related iron-binding protein, had no effect on lung colonization. In the B16-F10 system, elimination of natural killer cell activity by pretreatment of mice with anti-asialo GM1 antibody abrogated the effects of Lf, whereas inhibition of macrophage function with silica did not. The results demonstrate a novel activity for Lf and suggest a potentially important role for this molecule in the primary defense against tumorigenesis.

Topics: 3T3 Cells; Animals; Cell Division; Female; Fibroma; Humans; Lactoferrin; Methylcholanthrene; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Tumor Cells, Cultured

A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 10(5) plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relationship to other clinical parameters. We also found immunoreactivity in 20/41 (49%) cases of ductal carcinoma in situ. Expression was not observed in any breast or gastric cell line examined. Thus lactoferrin appears to be down regulated in some forms of cancer. The presence of lactoferrin could be a contraindication for effective endocrine therapy.

Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Cell Line; Cloning, Molecular; DNA, Neoplasm; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gene Expression; Gene Library; Humans; Immunoenzyme Techniques; Lactoferrin; Menopause; Middle Aged; Milk, Human; Neoplasm Metastasis

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

Oestrogen receptor content, lactoferrin, hexokinase, and glucose-6-phosphate dehydrogenase levels were measured in cytosol from 25 primary breast cancers and 3 fibroadenomas. Both hexokinase and glucose-6-phosphate dehydrogenase activity were higher in malignant tissue as compared to benign breast lesions. Oestrogen receptor concentration and lactoferrin content failed to predict the development of metastatic disease, while glucose-6-phosphate dehydrogenase activity was significantly higher in cytosol from those tumours which subsequently metastasized compared to those which remained localized.

Topics: Adenofibroma; Adult; Aged; Breast Neoplasms; Female; Glucosephosphate Dehydrogenase; Hexokinase; Humans; Lactoferrin; Middle Aged; Neoplasm Metastasis; Prognosis; Receptors, Estrogen

Activity was seen in the breasts of a patient with galactorrhea 72 h after intravenous injection of Ga-67 citrate. Differential protein separation of breast secretion, extracted from the breast, revealed that the Ga-67 was contained primarily in the lactoferrin-rich protein fraction. Additional studies on partially purified lactoferrin revealed that lactoferrin binds Ga-67 more avidly than does transferrin. Since lactoferrin is present in high concentration non only in human colostrum and milk, but also in neutrophilic leukocytes, bone marrow, spleen, colon, tears, and in genital, salivary, and nasopharyngeal secretions, binding of Ga-67 to lactoferrin may explain the localization of Ga-67 in certain normal tissues and inflammatory lesions.

Topics: Adult; Female; Galactorrhea; Gallium Radioisotopes; Humans; Lactation Disorders; Lactoferrin; Lactoglobulins; Leukemia, Myeloid, Acute; Neoplasm Metastasis; Pregnancy; Protein Binding; Radionuclide Imaging; Spinal Cord Neoplasms