Abstract: High affinity monoclonal antibodies for recognizing estrogen receptor (clone SP1) with immunohistochemistry and methods for creating such an antibody are disclosed. The lagomorph derived ER antibody provides a significant advantage over the currently available mouse ER antibodies in that there is no need for target retrieval when performing immunohistochemistry. Furthermore, the very low background when the lagomorph derived ER antibody is used in immunohistochemistry is also impressive. The immunohistochemistry comparative study with about fifty clinical specimens showed that the new ER (clone SP1) antibody had favorable results when compared to mouse monoclonal ER antibodies (clone 1D5). The lagomorph derived ER antibody may prove of great value in the assessment of ER status in human breast cancer. Humanized versions of the ER antibody may also provide therapeutic benefits.

Abstract: Methods, reagents, and kits are provided that permit flow cytometric determination of the phosphorylation status of retinoblastoma susceptibility gene protein (pRB) in individual cells. Methods are described that permit the hypophosphorylated, active, form of pRB to be measured either as an absolute quantity or as a proportion of total cellular pRB. Further described are methods that permit pRB phosphorylation status to be correlated with cell cycle phase and with protein components of the cell cycle. Screening of chemical compounds for antiproliferative and antineoplastic activity using the flow cytometric assays is demonstrated. Reagent kits that facilitate the subject methods are also provided.

Abstract: The present invention relates to a method for monitoring the effect of in vivo administration of Cathepsin S inhibitors by measuring accumulation of an intermediate degradation product of invariant chain (Ii), in particular the p10 Ii fragment, in blood of dosed subjects.

Abstract: New intracorporeal radiodense medicaments and certain medical uses and methods for use of such high energy phototherapeutic medicaments for treatment of human or animal tissue are described, wherein a primary active component of such medicaments is a halogenated xanthene or halogenated xanthene derivative. The halogenated xanthenes constitute a family of potent radiosensitizers that become photoactivated upon irradiation of the treatment site with ionizing radiation.

Abstract: Disclosed is a testing device and methods for the identification of an analyte of interest in a sample. In a preferred embodiment, the testing device includes a front panel having at least one sample application aperture; a rear panel having at least one solvent application aperture; a sample collection matrix disposed between the rear panel and the front panel, the sample collection matrix being in communication with the sample and solvent application apertures of the front and rear panels; and at least one insertable test strip containing a reagent enabling detection of the analyte of interest.

Abstract: There is provided an apparatus for screening pharmacological agents for agents which induce regression of cancer. The apparatus includes an evanescent sensing device, at least one sensor having affixed to its surface molecules of a first type, which have affinity for molecules of a biological receptor, the surface molecule and receptor molecule combination having the effect that, in vivo, the binding affects the rate of transcription of gene products, and a molecular tag wherein the molecular tag is bound to the sensor wherein the binding between molecules of the first type and molecules the biological receptor cause the tag to produce a alteration in signal recorded by the evanescent sensing device, the tag also being bound to molecules of a second type, the molecules of the second type having affinity for the receptor molecules.

Abstract: In vitro methods of determining whether or not an individual has metastasized colorectal cancer cells are disclosed. In vitro methods of determining whether or not tumor cells are colorectal in origin are disclosed. In vitro kits for practicing the methods of the invention and to reagents and compositions useful to practice the methods, for example as components in such in vitro kits of the invention are provided. Methods of and kits and compositions for analyzing tissue samples from the colon tissue to evaluate the extent of metastasis of colorectal tumor cells are disclosed.

Abstract: The vascular endothelial growth factor (VEGF) activity in a patient's bloodstream or other biological sample can serve as a diagnostic and prognostic index for cancer, diabetes, heart conditions, and other pathologies. Antibody-sandwich ELISA method and kits for VEGF as an antigen were developed to detect VEGF levels in biological samples from animal models and human patients and are used as a diagnostic/prognostic index.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly breast cancer, are disclosed. Illustrative compositions comprise one or more breast tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly breast cancer.

Abstract: The invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the invention method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers.

Abstract: The present invention is directed to the use of antibodies or binding portions thereof or probes which recognize an antigen of normal, benign, hyperplastic, and cancerous prostate epithelial cells or portions thereof. These antibodies or binding portions thereof or probes can be labeled and used for detection of such cells. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate cancer. Also disclosed is a hybridoma cell line which produces a monoclonal antibody recognizing antigens of normal, benign, hyperplastic, and cancerous prostate epithelial cells or portions thereof.

Abstract: Provided are methods, and assay kits, and compositions useful for generating an indicator of a disease condition selected from the group consisting of multiple sclerosis (MS), a pro-MS immune response, and a combination thereof. A method for assaying a sample of an individual for an indicator of the disease condition comprises contacting the sample with a combination of two or more affinity ligands, at least one of which comprises a detection reagent; measuring an amount of the detection reagent which is bound to the sample in determining a value of a marker in the sample; wherein a difference in the value of the marker determined in the sample, when compared to the reference value, comprises an indicator of the presence of the disease condition.

Abstract: A kit containing the reagents necessary for the qualitative or quantitative demonstration of epidermal growth factor receptor (EGFR) in formalin-fixed, paraffin-embedded tissue sections. A immunohistochemical staining procedure is employed which utilizes a primary monoclonal mouse antibody that selectively binds to EGFR. The primary antibodies bound to tissue antigens are detected using a peroxidase labeled polymer that is conjugated with secondary anti-mouse immunoglobulin antibodies. The enzymatic conversion of the subsequently applied chromogen results in formation of a visible reaction product at the site of the EGFR antigen. Following development of the chromogen, specimens may then be counterstained and coverslipped. Results are interpreted using a light microscope or other optical imaging device. The detection system is adapted for both manual and automated staining.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly ovarian cancer, are disclosed. Illustrative compositions comprise one or more ovarian tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly ovarian cancer.

Abstract: The present invention provides fusion proteins for the detection and treatment of neuroectodermal tumors. Previous work demonstrated that chlorotoxin is specific for glial-derived or meningioma-derived tumor cells. The current invention has extended the use of chlorotoxin-cytotoxin fusion proteins to treat the whole class neuroectodermal tumors such as gliomas, meningiomas, ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas, melanomas, PPNET's, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain. Also, diagnostic methods are provided for screening neoplastic neuroectodermal tumors.

Abstract: Compositions and methods for the detection and therapy of breast cancer are disclosed. The compounds provided include nucleotide sequences that are preferentially expressed in breast tumor tissue, as well as polypeptides encoded by such nucleotide sequences. Vaccines and pharmaceutical compositions comprising such compounds are also provided and may be used, for example, for the prevention and treatment of breast cancer. The polypeptides may also be used for the production of antibodies, which are useful for diagnosing and monitoring the progression of breast cancer in a patient.

Abstract: The present invention provides for pharmaceutical compositions comprising carvedilol for treatment of cancer. More particularly the invention relates to the use of carvedilol for treatment of cancers of the colon, ovary, breast, prostate, pancreas, lung, melanoma, glioblastoma, oral cancer and leukemias. Although not bound to any theory, the anticancer activity of carvedilol appears to be attributed to the inhibition of Epidermal Growth Factor and Platelet derived growth factor dependent proliferation of cancer cells. Further, carvedilol exerts anticancer effect by inhibition of the Protein kinase C (PKC) activity and that of the cyclooxygenase 2 enzyme. The invention also relates to the anticancer activity of the optically pure isomers S(−) and R(+) of carvedilol and the use of carvedilol and its isomers in pharmaceutical compositions for the treatment of cancer.

Abstract: The invention provides monoclonal antibodies that selectively bind to ectodermally- and endodermally-derived stem cells and methods for the diagnosis of a neoplasm in a subject by contacting a tissue sample from the subject with the antibodies. Also disclosed are methods for isolating such stem cells from a heterogeneous cell population by contacting the population with antibodies which selectively bind to stem cells.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as ovarian cancer, are disclosed. Compositions may comprise one or more ovarian carcinoma proteins, portions thereof, polynucleotides that encode such portions or antibodies or immune system cells specific for such proteins. Such compositions may be used, for example, for the prevention and treatment of diseases such as ovarian cancer. Polypeptides and polynucleotides as provided herein may further be used for the detection and monitoring of ovarian cancer.

Abstract: In vitro methods of determining whether or not an individual has metastasized colorectal cancer cells are disclosed. In vitro methods of determining whether or not tumor cells are colorectal in origin are disclosed. In vitro kits for practicing the methods of the invention and to reagents and compositions useful to practice the methods, for example as components in such in vitro kits of the invention are provided. Methods of and kits and compositions for analyzing tissue samples from the colon tissue to evaluate the extent of metastasis of colorectal tumor cells are disclosed.

Abstract: This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column.

Abstract: The present invention relates to methods of detecting carcinomas by measuring the level of a glycero compound, such as glycerol-3-phosphate, in a plasma, serum, or urine specimen from a patient. The method is particularly useful as a screening test for ovarian and breast carcinomas.

Abstract: A system of diagnostic test methods are provided for diagnosing whether a primary breast tumor from an individual human subject is a clinically metastatic tumor. These in-vitro diagnostic methods detect and utilize the presence or absence of a 55 kilodalton protein for the DNA or the RNA coding for an expressing this protein as a marker and indicator of tumor metastasis. The test methods thus can detect either the presence of the protein itself, or its unique DNA, or its singular RNA individually or collectively. Each method of detection provides a reliable indicator and marker by which to clinically diagnose and determine if a primary tumor within the breast of a living human subject is now or will soon likely be a metastatic tumor.

Abstract: Methods for detecting or diagnosing gynecological carcinomas in a patient are provided. One method The method, which involves assaying for the presence of lysophosphatidic acid in a plasma sample of the patient, is useful for detecting ovarian carcinoma, cervical carcinoma, endometrial carcinoma, and peritoneal carcinoma. In a preferred embodiment the method comprises: providing a blood specimen from the patient, obtaining a plasma sample for the blood specimen under conditions which minimize the release of lysophosphatidic acid from the platelets in the blood specimen into the plasma, extracting lipids from the plasma, and detecting the presence of lysophosphatidic acid in the lipid. Another method involves assaying for the presence of lysophosphatidyl inositol in a bodily fluid, preferably plasma, from the subject.

Abstract: Method of monitoring or diagnosing disease conditions, including disease of the prostate, that involve measuring a combination of tumor markers and at least one component of the IGF axis. The invention is exemplified with prostate cancer and benign prostatic hyperplasia, the tumor marker prostate specific antigen, and the insulin-like growth factors and their binding proteins.

Abstract: A prenatal screening method for Down's syndrome involves assaying for hyperglycosylated gonadotropin in biological test samples such as urine, plasma or serum obtained from pregnant women. Hyperglycosylated gonadotropin comprises a variant population of chorionic gonadotropin, chorionic gonadotropin-free &bgr;-subunit, &bgr;-core fragment, and/or free &agr;-subunit exhibiting differences in the carbohydrate content from what is observed in samples obtained from pregnant women carrying normal fetuses. Qualitative or quantitative observation of differences in the carbohydrate content of the hyperglycosylated gonadotropin population from corresponding control samples containing a normal gonadotropin population, or direct observation of the variant species seen in Down's syndrome, indicates that the woman's fetus has Down's syndrome. Typical screens involve carbohydrate analyses, immunoassays, or combinations of these methods.

Abstract: A method of distinguishing prostate cancer from benign prostatic hyperplasia (BPH) is provided. The mathematical combination or ratio of proPSA and BPSA serum or tissue markers may be used for distinguishing benign prostatic hyperplasia (BPH) from prostate cancer. It is the discovery of the present invention that BPSA is preferentially elevated in transition zone prostate tissue whereas pPSA is elevated in the peripheral zone of prostate tissue. A kit for aiding in distinguishing BPH from prostate cancer is also provided.

Abstract: The present invention relates to the assessment of ultraviolet radiation UV effects on sunscreen-treated and non-treated human skin using a more sensitive technique.

Abstract: This invention relates to substantially purified Retinoic Acid Receptor &egr; (RAR&egr;), having the amino acid sequence given in FIG. 1, and to the isolated nucleic acid encoding RAR&egr;. In addition, polypeptides comprising, and nucleic acids encoding, the DNA-binding and hormone-binding domain of the receptor are provided. Further, methods of detecting RAR&egr; and nucleic acids encoding RAR&egr; and its domains are provided.

Abstract: The present invention relates to methods of tyramide coating live cells for flow cytometry, using catalyzed reporter deposition and serial amplification staining. A catalyzed reporter deposition or an analyte dependent enzyme activation system is described for detecting and/or quantitating an analyte of interest on the surface of a cell by flow cytometry. Also described is a method for serial amplification staining by tyramide coating cells which possess an analyte of interest or a solid phase to which an analyte is bound.

Abstract: Methods of treating and imaging diseased tissue having the steps of administering a radiosensitizer agent proximate to or into the diseased tissue; and treating the diseased tissue with x-rays or other ionizing radiation so as to activate the radiosensitizer agent in the diseased tissue. Preferably, the radiosensitizer agent is a halogenated xanthene.

Abstract: The invention relates to the discovery that the concentration of free cysteine in mammalian tumor tissue is elevated compared with the concentration of free cysteine in non-tumor tissue of the same origin. Elevated levels of free cysteine is, in turn, correlated with resistance of tumors to antitumor therapy such as chemotherapy and radiation therapy. Therefore, the invention further relates to methods of detecting the presence of tumors in mammalian tissues, assessing the resistance of tumors to antitumor therapies as it relates to free cysteine concentration, and to the identification of compounds which affect free cysteine concentration in mammalian tissues.

Abstract: Non-invasive methods are provided for obtaining biological samples of mammary fluid or mammary fluid components by administering oxytocin to a patient to stimulate expression of mammary fluid. During or after mammary fluid expression, a biological sample is collected in the form of whole mammary fluid, whole cells or cellular components, other selected liquid or solid fractions of the mammary fluid, purified or bulk proteins, glycoproteins, peptides, nucleotides or other desired Constituents of mammary fluid. Methods and kits are also provided for determining the presence or amount of a breast disease marker in biological samples of mammary fluid or mammary fluid components obtained according to the above sample collection methods. Also provided within the invention are novel breast pump and breast pump adapter devices which incorporate a solid phase sample collection medium integrated within the breast pump or adapter or otherwise fluidly connected therewith.

Abstract: The invention relates to the identification of complexes of human leukocyte antigen molecules and tyrosinase derived peptides on the surfaces of abnormal cells. The diagnostic ramifications of this observation are the subject of the invention.

Abstract: This invention provides a kit and a method for detecting sucrose in physiological fluids and said method. The kit comprises: (a) a solid mixture comprising ATP, NAD, hexokinase, G-6-PDH, and a buffer; which, after reconstitution with water, results in a solution having a pH in the range from about 7 to about 8; and (b) a solid mixture comprising ATP, NAD, hexokinase, G-6-PDH, invertase, and a buffer; which, after reconstitution with water, results in a solution having a pH in the range from about 7 to about 8.

Abstract: The invention involves the recognition of a previously unidentified protein family which belongs to the human SCP family. The members of the family, such as SCP-2 and rat SCP-3 homolog, are markers for cell transformation. Also disclosed is the analysis of SCP proteins association with nuclear bodies. Diagnostic and therapeutic uses of these proteins and related molecules are taught.

Abstract: The alkane profile, comprising the alveolar gradients of n-alkanes in breath having 2 to 20 carbons, and the alveolar gradients of methylated C3-C20 alkanes, is determined for the diagnosis of disease in mammals, including humans.

Abstract: The present invention relates to a method of predicting the therapeutic response of a drug directed towards a cancer in a human patient using samples of blood cells taken from the patient at different times. The method comprises the steps of culturing cells from the samples in a suitable medium; adding a stimulator of proliferation and an immuno-modulating drug of the cells to the culture; and assaying the proliferation of the cells in the culture; comparing the assay of proliferation with a previously made analysis demonstrating correlation between the proliferation of the cells and parameters of the therapeutic response of the drug in the human patient.

Abstract: A new class of cellular receptors extensively homologous but not identical to coagulation factors V and VIII is identified. These new cell surface receptors are designated effector cell protease receptors (EPRs) and include EPR-1, which is shown to bind protease ligands. The DNA and amino acid residue sequences of the receptor are also described. The invention also discloses methods, sequences and vectors useful in the purification and synthesis of cellular receptors of the present invention. Antibody compositions capable of immunoreacting with the receptor or with polypeptides containing the identified amino acid residue sequences and related therapeutic and diagnostic protocols are also described, as are polypeptides, compositions and methods relating to the inhibition of T lymphocyte proliferation using the antibodies disclosed herein. The receptors are also demonstrated to bind coagulation factor Xa, which binding is inhibited by various disclosed monoclonal antibodies to the receptors.

Abstract: Nuclear matrix proteins (NMP) are useful markers in diagnosing and monitoring the stage of malignancy of a cell, and in treating cell proliferative disorders associated with the NMP.

Abstract: The present invention provides a process for the extraction of proteins from gastrointestinal tract samples taken from humans or other mammals wherein the sample is mixed with an excess amount of aqueous extraction medium comprising at least one dissociating, disaggregating and/or chelating agent, homogenised in a closed vessel, the solid and liquid materials of the dispersion are separated from each other and the clear liquid extract is recovered.

Abstract: Disclosed is a testing device and methods for the identification of an analyte of interest in a sample. In a preferred embodiment, the testing device includes a front panel having at least one sample application aperture; a rear panel having at least one solvent application aperture; a sample collection matrix disposed between the rear panel and the front panel, the sample collection matrix being in communication with the sample and solvent application apertures of the front and rear panels; and at least one insertable test strip containing a reagent enabling detection of the analyte of interest.

Abstract: The present invention relates to monoclonal antibodies that are specific for the protein thymidylate synthase, and hybridomas producing these monoclonal antibodies. The invention further relates to methods of detection and diagnostic kits to test for the presence of thymidylate synthase. The invention also relates to the use of the monoclonal antibodies in determining the presence of colon carcinoma cells.

Abstract: The present invention relates to DNA sequences from regions of copy number change on chromosome 20. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases.

Abstract: A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling tube. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to present only on cancer cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to present only on hematologic progenitor cells.

Abstract: Tumor cells, particularly carcinoma cells, are separated from peripheral blood by magnetic sorting. The tumor cells are magnetically labeled with antibodies directed to tissue specific antigens, preferably cytoplasmic proteins. Labeling for cytoplasmic antigens is accomplished first permeabilizing, then fixing the cells. The cells are separated on a magnetic matrix. The number of tumor cells in the enriched fraction is used to calculate the number of tumor cells present in a patient hematopoietic sample.

Abstract: Identification of defective ER and subclassifying ER+ breast cancers on the basis of the presence of defective ER is described as a tool potentially useful, as previously shown by the results of a pilot study, for predicting which among the ER+ tumors will respond and which will fail to repsond to hormonal modes of therapy. Improvements are introduced in the specimen sampling and ligand introduction steps of the immunohistochemical procedure which was developed for sub-classifying estrogen receptor-positive tumors of human breast cancers and other cancers of the estrogen target organs on the basis of the presence of defective estrogen receptors. Additionally, a new monoclonal antibody reagent which has potential use as a replacement for the polyclonal anti-ER antibody reagents is also described. The modified steps include the use of tumor imprints instead of cryosections; use of ligand coated slides instead of the original ligand layering step.

Abstract: The instant invention provides for the identification, diagnosis, monitoring, and treatment of invasive cells using the laminin 5 gamma-2 chain protein or nucleic acid sequence, or antibodies thereto.

Abstract: The invention disclosed herein relates to a method of monitoring bone metabolism comprising continuously collecting a sweat sample from a subject and assaying the sweat sample to determine the concentration of a marker of bone metabolism in the sample, wherein said marker is not pyridinoline or deoxypyridinoline.