myelin-basic-protein and Breast-Neoplasms

A double-blind pilot study of 130 female patients was carried out to determine the feasibility and significance of the EM test in the early diagnosis of carcinoma of the female genital organs and breast. Early stages of cervical carcinoma (carcinoma in situ) as well as fibroid adenoma, mastopathy and breast tumors were tested and compared with the results of their manifest forms. Positive results were recorded in 87.5% of the cases of middle-grade to severe epithelial dysplasia (Papanicolaou III and IV) (n = 10) and in 90% of the cases of carcinoma in situ (n = 16). A positive result in 90% of the cases of carcinoma in situ (n = 16). A positive result in 90% of the cases of genital carcinoma was also recorded. In the case of fibroid adenoma (n = 10) and breast tumor (Prechtel I and II) (n = 16), negative results were recorded in 80.8%, whereas in the manifest forms of carcinoma of the breast a positive result of over 95% was shown. As a result of this pilot study, it can be seen that immunological in vitro screening has clinical significance in the early diagnosis of tumors as well as for confirmation of their manifest forms.

Topics: Animals; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Erythrocytes; Female; Humans; Immunoelectrophoresis; In Vitro Techniques; Lymphocytes; Lymphokines; Myelin Basic Protein; Precancerous Conditions; Sheep; Time Factors; Uterine Cervical Neoplasms

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Endoplasmic Reticulum Chaperone BiP; Female; Humans; Mice; Mice, Nude; Myelin Basic Protein; Nanoparticles; Paclitaxel; Peptide Fragments; Prodrugs

The significance of neurospecific proteins in the diagnosis of neurotoxicity in patients with breast, lung, testicular, and ovarian cancer treated by taxane and cisplatin drugs was evaluated. The most pronounced increase in the content of these proteins and titers of autoantibodies to these proteins was observed in patients with clinical manifestations of neurotoxicity induced by cytostatics. A strong correlation was found between the concentration of myelin basic protein and cumulative dose of the drug (R=0.922; p<0.0001). These data suggest that myelin basic protein and gliofibrillar acid protein can be used as markers in the diagnosis and monitoring of antitumor drug neurotoxicity.

Topics: Antineoplastic Agents; Autoantibodies; Breast Neoplasms; Cisplatin; Dose-Response Relationship, Drug; Female; Glial Fibrillary Acidic Protein; Humans; Lung Neoplasms; Male; Myelin Basic Protein; Neurons; Ovarian Neoplasms; Testicular Neoplasms; Time Factors

In vitro cell-mediated immunity was assayed by leukocyte adherence inhibition (LAI) to determine the extent of autosensitization to myelin basic protein (MBP). Leukocytes from 123 cancer patients, 16 patients freed of cancer, 135 patients with benign disease, and 26 patients with destruction of nervous parenchyma were tested. Most patients with cancer reacted to MBP: 92%, 93%, 82%, 78%, 75% and 62% for pancreatic, colonic, esophageal, lung, ovarian and breast. Few patients with benign diseases reacted to MBP. Patients with multiple sclerosis (MS) were sensitized to MBP, but patients with other nervous tissue injury did not react to MBP. Cancer patients did not remain sensitized to MBP once they were freed of their cancer. The LAI assay is a straightforward method of measuring cellular autosensitivity to MBP. In the population of patients tested, autosensitivity to MBP was confined, except for MS, principally to cancer patients.

Topics: Autoantigens; Breast Neoplasms; Dose-Response Relationship, Immunologic; Humans; Immunologic Techniques; Intestinal Polyps; Leukocyte Adherence Inhibition Test; Multiple Sclerosis; Myelin Basic Protein; Neoplasms; Pancreatic Neoplasms; Pancreatitis

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Topics: Adolescent; Adult; Aged; Brain Diseases; Breast Neoplasms; Cerebrospinal Fluid Proteins; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Meningeal Neoplasms; Middle Aged; Myelin Basic Protein

Phytohaemagglutinin (PHA), a well-known mitogen, and encephalitogenic factor (EF) are recognized by lymphocytes of patients with different malignant diseases as non-specific antigens. Utilizing these two antigens, the SCM (structuredness of the cytoplasmatic matrix) test offers a means of discrimination between malignant and non-malignant diseases. The SCM test can also be used as a specificity test since lymphocytes from donors with a given malignant disease react exclusively with the tumour-associated antigen (TAA) of that disease. Results from 73 donors (15 healthy patients, 38 patients with different types of malignant disorders and 20 patients with autoimmune diseases) indicate the predictive value of the test. First, the non-specific test was applied in order to establish whether the patients suffered from an active malignant disease. The lymphocytes of those patients which were found to suffer from an active malignant disorder were then exposed to different types of tumour tissues. Twenty-five out of the 38 patients with malignant disorders were found by the SCM test to have an active disease. The lymphocytes of 24 out of these 25 patients showed a positive reaction when exposed to tumour tissue of the same type of cancer of which they were found to suffer by other clinical tests, and displayed no reaction with any other tumour tissues for which they were tested. One patient, with an inconclusive value of the SCM test, showed no reaction with any type of tumour to which he was exposed. The remaining 13 patients, who were diagnosed by the test as non-cancerous, did not show any clinical evidence of malignancy at the time of the test, after their tumours had been excised. Eighteen out of 20 patients with autoimmune diseases showed negative results when tested by the general test and by the various specificity tests.

Topics: Antigens, Neoplasm; Breast Neoplasms; Colonic Neoplasms; Epitopes; Fluorescence Polarization; Humans; Lymphocyte Activation; Lymphocytes; Myelin Basic Protein; Neoplasms; Phytohemagglutinins

27 female patients with breast cancer and 23 with benign breast diseases have been investigated with the MEM-test. Antigens used in these experiments were human encephalitogenic protein (HEP) and 3M KC1 tissue extracts from carcinomas of breast and kidney. Preoperative examination of the patients showed an accuracy of the test of 89% (breast cancer extract) and 86% (HEP) respectively. The control persons gave less than 9% false positive tests. The results obtained with the extract from kidney cancer demonstrate the organ specificity (3% positive responses). Follow-up studies were carried out with cancer patients. We found, beginning with a delay, a strong decrease of reactivity 5 to 8 weeks after surgical treatment and later again increased reactivity in some patients. We suppose a relation between this restoration of MEM-reactivity and development of recurrent cancer whereby follow-up studies can get some clinical importance. The investigation of frequency distribution of MEM values obtained shows a division into low values of about 0% and high values of about 10% mobility inhibition without overlapping. The reasons are discussed regarding the levels of the patient and the test principle.

Topics: Antigens, Neoplasm; Breast Neoplasms; Cell Migration Inhibition; Electrophoresis; Female; Humans; Macrophage Activation; Macrophages; Mastectomy; Myelin Basic Protein; Neoplasm Recurrence, Local

A subpopulation of T lymphocytes sensitized to human myelin basic protein in peripheral blood of patients with multiple sclerosis, central nervous system (CNS) tumors, and cerebrovascular accidents was demonstrated by the antigen-stimulated, rosette-forming T-cell assay. A significant increase in the percent of active rosette-forming T cells was detected after in vitro exposure of peripheral blood lymphocytes to human myelin basic protein but not to histones. In contrast, peripheral blood lymphocytes from healthy controls and from patients with benign and malignant breast diseases were unresponsive to stimulation by either antigen. These results demonstrate a functionally active T-lymphocyte subpopulation sensitized to myelin basic protein in patients with multiple sclerosis and in patients with certain other CNS diseases.

Topics: Adult; Aged; Breast Diseases; Breast Neoplasms; Central Nervous System Diseases; Cerebrovascular Disorders; Histones; Humans; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Rosette Formation; T-Lymphocytes

Leukocyte migration tests under agarose (Clausen technique) were performed in 28 patients tentatively diagnosed as having any malignancy with the use of a 3 M KCl-extract panel prepared from bronchogenic, gastric, colonic, renal, and mammary carcinoma, corresponding normal tissues, carcinoembryonic antigen (CEA), and human encephalitogenic protein (HEP). 17 out of 22 proven carcinoma patients showed sensitization by reaction with optimal concentrated KCl-extract of cancer from the same organ type as their own tumor. In some cases positive reactions could be observed also with normal tissue antigen (NTA) of tumor organ type (7/22) or with an additional carcinoma extract of organ type differing from patients own primary tumor (8/22). Gastrointestinal carcinomas, especially, showed sensitization to CEA (7/12) contrary to nongastrointestinal carcinomas (1/10). With HEP no positive reactivity could be found (0/10). With the use of tumor antigen panel (5 antigens) only few positive reactions (MI less than 0.80 or greater than 1.20) could be observed in 6 patients with nonmalignant diseases (1/30 tests) and 8 healthy blood donors (1/40 tests). A widespread individual screening program using tissue antigens for patients suspected of malignancies could give a pattern of reactivities and improve the recognition of cell-mediated sensitization against tumor tissues.

Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoembryonic Antigen; Cell Migration Inhibition; Colonic Neoplasms; Epitopes; Female; Humans; Immunity, Cellular; Kidney Neoplasms; Leukocytes; Lung Neoplasms; Male; Middle Aged; Myelin Basic Protein; Neoplasms; Sepharose; Stomach Neoplasms