207 results about "Decreased telomerase activity" patented technology

The present invention provides a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample. The method involves isolating a circulating tumor cell (CTC), for example, a viable CTC, from a sample using a parylene microfilter device comprising a membrane filter having or consisting of a parylene substrate, which has an array of holes with a predetermined shape and size; and detecting and quantifying telomerase activity in blood circulating tumor cells. The invention further provides methods of using cells live-captured in various applications.

The present invention provides methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells. In particular, the present invention includes a debulking step that uses a microfabricated filters for filtering fluid samples and the enriched rare cells can be used in a downstream process such as identifies, characterizes or even grown in culture or used in other ways. The invention also include a method of determining the aggressiveness of the tumor or of the number or proportion of cancer cells in the enriched sample by detecting the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression after enrichment of rare cells. This invention further provides an efficient and rapid method to specifically remove red blood cells as well as white blood cells from a biological sample containing at least one of each of red blood cells and white blood cells, resulting in the enrichment of rare target cells including circulating tumor cells (CTC), stromal cells, mesenchymal cells, endothelial cells, fetal cells, stem cells, non-hematopoietic cells etc from a blood sample. The method is based upon combination of immuno-microparticles (antibody coated microparticles) and density-based separation. The final enriched target cells can be subjected to a variety of analysis and manipulations, such as flowcytometry, PCR, immunofluorescence, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched rare cells, and therapeutic use of enriched rare cells. In addition, depleted plasma protein and white blood cells can be optionally recovered, and subjected to other analysis such as inflammation studies, gene expression profiling, etc.

Compounds and compositions for the transient expression of exogenous telomerase activity in a cell are provided. The compounds and compositions, which relate to a ribonucleic acid coding for a telomerase reverse transcriptase, are useful in the extension of telomeres in cells needing such treatment. Such cells include, for example, cells that contain shortened telomeres and cells from subjects that may benefit from telomere extension, for example subjects that suffer from, or are at risk of suffering from, age-related or other illnesses. Also provided are methods of extending telomeres through the administration of the provided compounds and compositions to animal cells, either in vitro or in vivo, and kits including the compounds or compositions and instructions for use.

Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Compounds and compositions for the transient expression of exogenous telomerase activity in a cell are provided. The compounds and compositions, which relate to a ribonucleic acid coding for a telomerase reverse transcriptase, are useful in the extension of telomeres in cells needing such treatment. Such cells include, for example, cells that contain shortened telomeres and cells from subjects that may benefit from telomere extension, for example subjects that suffer from, or are at risk of suffering from, age-related or other illnesses. Also provided are methods of extending telomeres through the administration of the provided compounds and compositions to animal cells, either in vitro or in vivo, and kits including the compounds or compositions and instructions for use.

Methods are disclosed for generating HLA homozygous parthenogenetic human stem cell (hpSC-Hhom) lines from both HLA homozygous and HLA heterozygous donors. These hpSC-Hhom lines demonstrate typical human embryonic stem cell morphology, expressing appropriate stem cell markers and possessing high levels of alkaline phosphatase and telomerase activity. Additionally, injection of these cell lines into immunodeficient animals leads to teratoma formation. Furthermore, in the case of HLA heterozygous donors, the hpSC-Hhom lines inherit the haplotype from only one of the donor's parents. SNP data analysis suggests that hpSC-Hhom lines derived from HLA heterozygous oocyte donors are homozygous throughout the genome as assessed by single-nucleotide polymorphism (SNP) analysis. The protocol as disclosed minimizes the use of animal-derived components, which makes the stem cells more practical for clinical application.

The invention provides methods and compositions for inhibiting telomerase activity and treatment of telomerase mediated conditions or diseases. The methods, compounds, and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents, surgery, or radiation in the treatment of conditions or diseases mediated by telomerase activity, such as in the treatment of cancer.

A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of a proteasome inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the proteasome inhibitor alone or the telomerase inhibitor alone. Preferably, efficacy is supraadditive or synergistic in nature relative to the combined effects of the individual agents, with minimal exacerbation of side effects.

The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L ("activator-antisense complex") which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

The invention discloses a colorectal cancer biomarker, relating to application of interferon-induced transmembrane protein 1 in inhibition of endogenous retrovirus in colorectal cancer. The hESCs of IFITM1-KO is constructed by using CRISPR / Cas9 technology so as to study the functions of IFITM1. Studies find that the IFITM1-deleted human embryonic stem cell (hESCs) is identical with IFITM1-WT in the aspects of cell proliferation, cell pluripotency, telomere length, telomerase activity and the like. The expression of human endogenous retrovirus in hESCs of IFITM1-KO increases, and expression in para-carcinoma tissue is higher than that in colorectal carcinoma tissue. ChIP-qPCR detection finds that the enrichment of H3K9me3 in hESCs of IFITM1-KO is reduced at the HERVs site. Data shows that the expression level of IFITM1 in hESCs and colorectal carcinoma is in negative correlation to HERVs expression, and the IFITM1 can inhibit the expression of HERVs by regulating epigenetic inheritance.

Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

The invention discloses a method for quantitatively detecting telomerase activity based on a nano pore channel and electrochemical sensing.The method comprises the following steps that firstly, a telomerase recognition sequence is connected to the inner wall of a porous anodic alumina template or a polyethylene terephthalate film to serve as a primer; secondly, telomerase amplifies the primer to form a G-rich sequence; a G-quadruplex is formed in the presence of potassium ions; electrochemical detection is conducted on the current produced through indicating molecules of the nano pore channel by utilizing an electrochemical workstation.The method does not need complex material preparation and DNA probe marking, and can avoid the defects of high detection cost, complicated operation and poor reproducibility caused by the complex material preparation and DNA probe marking and has the advantages of being low in cost, quick, simple, convenient, high in sensitivity and good in accuracy.

The invention discloses a double-stranded spire tetrahedral DNA nano-structural probe (STTS) as well as a preparation method and an application of the STTS in electrochemical detection of the activity of a telomerase. The STTS comprises a single-stranded probe STTS-A, a single-stranded probe B, a single-stranded probe C, a single-stranded probe D and a single-stranded probe SC-DNA. The invention also discloses a method for electrochemical detection of the activity of the telomerase by virtue of the STTS and the application of the STTS in electrochemical detection of the activity of the telomerase. By adopting the method for electrochemical detection of the activity of the telomerase, the signal to noise ratio of detected signals is more than twice higher than that of the detected signals detected the ordinary TSP (Test Sphere Probe) detection, the sensitivity is high, the specificity is strong and the application range is wide.

The present invention provides a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample. The method involves isolating a circulating tumor cell (CTC), for example, a viable CTC, from a sample using a parylene microfilter device comprising a membrane filter having or consisting of a parylene substrate, which has an array of holes with a predetermined shape and size; and detecting and quantifying telomerase activity in blood circulating tumor cells. The invention further provides methods of using cells live-captured in various applications.

The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical, including topical, and nutraceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient, such as, for example, HIV infection, various degenerative diseases, and acute or chronic skin aliments. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and proliferation of stem cells.

The invention provides methods and compositions for modulating the activity of therapeutic agents for the treatment of a cancer by administering one or more agents that (either alone or in combination) induces telomere damage and inhibits telomerase activity in the cancer cell. The method initially uses, e.g., a telomere damage-inducing agent such as paclitaxel, and a telomerase inhibitory agent such as AZT. The invention also provides methods for identifying other agents with telomere damage-inducing activity and / or telomerase inhibitory activity (as well as and compositions having such activity), for use in the treatment of cancer.

The present invention discloses a telomerase activity detection kit and a detection method thereof. According to the kit, a ternary linking structure probe is adopted to recognize a telomerase product, and a ternary linking structure triggered DNA molecule machine and a base stacking triggered DNA molecule machine are combined to achieve isothermal cascade nucleic acid amplification to convert a reverse transcription event of the telomerase in a tumor cell extract into a significantly-enlarged fluorescence detection signal so as to precisely determine telomerase activity in a trace amount of tumor cells and achieve detection on tumor cell telomerase activity inhibition by chemical drugs.

The invention discloses a 9-amino oxidized isoaporphine-platinum (II) complex, a synthetic method and an application thereof. The 9-amino oxidized isoaporphine-platinum (II) complex is prepared with 9-amino oxidized isoaporphine and dichloro bis(dimethyl sulfoxide)platinum (II) as raw materials through a coordination reaction in a polar solvent. A research result shows that the inhibition effect of the complex on telomerase reaches 56.97% and is improved significantly than those of a 1-aza-benzanthrone platinum (II) complex and 6-hydroxy oxidized isoaporphine-platinum (II) complex. The complex has significant inhibition effect on the activity of the telomerase and has excellent selectivity and significant in-vitro antitumor activity on various human tumor cell strains and a normal liver cell strain. The structure formula of the complex is represented as the formula (I).

The invention discloses a detection method for activity of telomerase. The method comprises the following steps: step 1, extracting telomerase in to-be-detected cells by using the CHAPS method; step 2, subjecting a captured substrate and the to-be-detected telomerase to extension and subjecting an extension product and a reporter label solution to a hybridization reaction, wherein the captured substrate is prepared by connecting a telomerase substrate to the surface of a gold shell-coated ferriferrous oxide nanoparticle, and the reporter label solution is prepared by connecting a telomere complementary sequence and a Raman molecule to the surface of a spherical gold nanoparticle; and step 3, observing the color of a hybridization reaction product by using colourimetry or carrying out dual signal path detection by using SERS technology so as to obtain SERS signals. According to the invention, colourimetry and SERS technology are integrated into a same telomerase activity detection system, colourimetry is used to realize rapid qualitative analysis of a sample, then the SERS technology is used to realize accurate quantitative analysis of the sample, and combination of the two methods enables rapid high-sensitivity telomerase activity detection to be realized.

The present invention relates generally to the field of diagnostic and prognostic assays such as diagnostic assays for conditions associated with telomerase activity. More particularly, the present invention provides an assay for measuring telomerase activity as an indicator of cancer, an inflammatory disorder and / or a condition involving embryogenesis and / or requiring stem cell proliferation and agents and kits useful for same. Automated and partially automated assays permitting high throughput screening also form part of the present invention. The subject invention further contemplates methods of treatment using agents identified by the subject assay or where treatment protocols are monitored by the assay.

Disclosed is lentinus edodes fermented pure protein with anti-tumor activity as well as an extracting method and a preparation thereof. The protein is obtained through fermentation, salting-out, dialysis, drying and column chromatography of mycelia of lentinus edodes C91-3; the protein is light brown or earthy yellow powder which can be dissolved in water and has specific fragrance, the pH value of aqueous solution is 5.0 to 8.0, the molecular weight is 1 KD to 90 KD, and the protein contains 18 types of amino acids and various proteins. The experiment proves that in the anti-tumor experiment in vitro, the tumor restraining rate of the lentinus edodes fermented pure protein LFP91-3-A to H22 and S180 in 72 hours can achieve 59.93 percent and 80.13 percent; lentinus edodes fermented pure protein LFP91-3-A has an inducing effect on H22 cell telomerase of which the activity is obviously restrained and apoptotic. The tumor restraining rate of lentinus edodes fermented pure protein LFP91-3-B to S180 can achieve 76.7 percent; the experiment proves that the strain fermented pure protein has relatively strong effect of directly killing tumor cells. The lentinus edodes fermented pure protein has no toxic side effect through animal acute toxicity experiments and long-term toxicity experiments.

The present invention embraces compounds selected for interacting with the T-pocket of telomerase and use thereof for modulating the activity of telomerase and preventing or treating diseases or conditions associated with telomerase.

The present invention relates generally to the field of diagnostic and prognostic assays such as diagnostic assays for conditions associated with telomerase activity. More particularly, the present invention provides an assay for measuring telomerase activity as an indicator of cancer, an inflammatory disorder and / or a condition involving embryogenesis and / or requiring stem cell proliferation and agents and kits useful for same. Automated and partially automated assays permitting high throughput screening also form part of the present invention. The subject invention further contemplates methods of treatment using agents identified by the subject assay or where treatment protocols are monitored by the assay.

The invention relates to a high-efficiency rapid bladder cancer urinalysis kit and a urinary cell active preservative fluid, which belong to the field of biomedicine. The high-efficiency rapid bladder cancer urinalysis kit contains the urinary cell active preservative fluid and a specific fluorescence labeled primer for detecting the activity of telomerase. The kit can perform detection of the activity of the telomerase on cells taken from urine further to efficiently and accurately detect whether a patient suffers from diseases related to the activity of the telomerase such as bladder cancer; the urinary preservative fluid in the kit is a key factor; the activity of the telomerase of an early cancer patient has lower expression level, the activity of the telomerase is difficult to detect in a small amount of tested cells, and the urinary preservative fluid can ensure that collected urinary cells preserve good activity so as to provide adequate time for acquiring adequate active cells; and the high-efficiency rapid bladder cancer urinalysis kit and the urinary cell active preservative fluid provide a feasible way for accurately detecting early bladder cancer and non-invasively monitoring the bladder cancer.

The invention discloses an electrochemical sensor for detecting telomerase activity and a method for manufacturing the electrochemical sensor. The method for manufacturing the electrochemical sensor mainly includes procedures of sequentially adsorbing DNA (deoxyribonucleic acid) strands S1 of thionine, Au@SiO<2> and G-rich structures in the surfaces of molybdenum disulfide nano-sheets and adding Hemin into the molybdenum disulfide nano-sheets to form MoS<2>-Thi-Au@Si<O>2 / DNAzyme nano-composite materials; modifying TS (telomerase substrate) precursors on the surfaces of gold electrodes, extending the DNA strands by the aid of telomerase to form DAN strands S2, screwing the DNA strands S2 and the DNA strands S1 complementarily, and ultimately detecting the intensity of electrochemical signals of catalytic hydrogen peroxide oxidation ABTS to directly detect the telomerase activity. The electrochemical sensor and the method have the advantages that the electrochemical sensor manufactured by the aid of the method is simple in operation and high in sensitivity and stability and has an important significance on detecting cancerous cells.

The invention relates to a method for detecting telomerase activity with a colorimetric method based on strand displacement reaction. According to the method, in the presence of active telomerase, hybridization is performed on a prolonging product of a substrate with assistant DNA so as to release a plurality of triggering DNAs, the triggering DNAs can trigger hairpin DNA probes H1 and H2 to have self-assembled strand displacement reaction, then G-4 chains are respectively formed at two tail ends of H1:H2, hemin reacts with the G-4 chains, thus G-4 chain DNA enzyme with catalytic activity can be formed, a TMB-H2O2 system is catalyzed to have reaction, the color of a solution is changed into blue from colorless, and the solution can be oxidized into yellow if acid is added; due to addition of active telomerase, the color of the solution can be changed, visible detection on telomerase activity can be achieved, meanwhile an ultraviolet absorption spectrum of the solution can be tested, and the telomerase activity can be more accurately and sensitively tested.

The invention provides an AETCA (anchored-extension and telomeric complements amplification) detection reagent kit for telomerase and a detection method. The reagent kit comprises an anchored PCR (polymerase chain reaction) tube, a probe BT (SEQ ID No.2), PCR primer, denaturing lysis buffer, extension hybridization buffer, PCR buffer and washing buffer, wherein telomerase primer ATS (SEQ ID No.1) are fixed in the anchored PCR tube. By utilizing a part of probe sequence (the probe BT) complementary with a telomere repetitive sequence as a template, the probe is combined on the telomere repetitive sequence synthesized by the telomerase in a multicopy manner, and accordingly, amplification of the probe BT can be kept in efficient fixed length though the length of the telomere repetitive sequence is not constant, and the defects of the TRAP (tartrate resistant acid phosphatase) method are overcome. The detection method is convenient and easy to operate, sensitivity and specificity of activity detection of the telomerase can be improved, and the detection method is applicable to detection of various sources including cells or tissues of clinical samples such as sputum.

The invention discloses a method for detecting telomerase activity. The method comprises the following steps: performing constant temperature incubation an aggregation-induced emission compound with positive groups, telomerase primers, dNTPs, an RNA enzyme inhibitor and a to-be-detected sample in a telomerase amplification buffer at the temperature of 23-37 DEG C so that the telomerase primers in a reaction system generate a telomerase extension reaction, and inactivating the reaction system at the temperature of 80-100 DEG C to stop the extension reaction. As a DNA molecule phosphoric acid skeleton carries negative charges, with the extension of telomerase primer sequences, the amount of aggregation-induced emission compounds capable of being bonded on each chain can be increased, the fluorescence effect of a reaction solution can be enhanced, and the telomerase activity of the to-be-detected sample can be detected by detecting the fluorescence intensity of the reaction solution. According to the invention, specific detection on the telomerase activity can be realized.