60 results about "Microsatellite Stable" patented technology

The invention belongs to the technical field of biological medicines, and discloses a traditional Chinese medicine composition for treating microsatellite stability (MSS) type tumors by a sensitization immune checkpoint inhibitor. The traditional Chinese medicine composition provided by the invention comprises radix scutellariae, rhizoma zingiberis, Chinese herbaceous peony, liquorice root and Chinese date, can increase CD8 + T cell infiltration, promote the CD8 + T cell to secrete cytokines and improve the immunosuppression of MSS type tumors, and further breaks through the conventional range of anti-tumor treatment of immune examination inhibitors; meanwhile, the traditional Chinese medicine composition can also improve adverse reaction of gastrointestinal tracts caused by tumor treatment by an immune examination inhibitor, and the life quality of patients is improved.

The invention discloses application of a TEAD1 palmitoylation inhibitor VT103 in preparation of a PD-1 immune checkpoint antibody sensitization drug, and belongs to the technical field of tumor immunotherapy. It is confirmed for the first time that TEAD palmitoylation inhibition can overcome immunotherapy drug resistance of MSS tumors by regulating and controlling the state of the microsatellite, a brand new action target is provided for clinical development of immune checkpoint inhibitor sensitizing drugs, microsatellite instability is induced firstly, then immunotherapy is carried out in a combined mode, and therefore the treatment effect is improved.

The invention discloses a microsatellite instability detection method based on single-sample high-throughput sequencing for microsatellite site micro-offset, and relates to the technical field of bioinformatics, and the microsatellite instability detection method comprises the following steps: processing a sequencing sequence of a to-be-detected sample obtained by a high-throughput sequencing technology to obtain a comparison file; according to the method, selection and quality control of microsatellite sites are strictly controlled, a microsatellite instability detection method based on single-tumor sample high-throughput sequencing can be used for analyzing the repetition times of candidate microsatellite site repetition units without depending on a control sample, and meanwhile, the method has very good sensitivity to a sample with relatively large offset, so that the accuracy of the microsatellite instability detection is greatly improved. The method can also be applied to other cancer species with MSI characteristics, and can adapt to detection requirements of different cancer species by adjusting candidate microsatellite loci no matter whether a micro-migration condition exists or not, provide visualization, assist in seeing the degree of microsatellite migration, facilitate manual recheck and reduce misjudgment.

Methods for evaluating microsatellite instability (MSI) analyze nucleic acid sequence reads corresponding to a plurality of marker regions for MSI. The marker regions may include long homopolymers and / or short tandem repeats (STRs). For a target homopolymer, a histogram of homopolymer signal values is calculated based on flow space signal measurements for the homopolymer region in the sequence reads. A score per marker based on features of the histogram of homopolymer signal values is determined for each marker region corresponding to the target homopolymers. For a target STR, the method includes calculating a histogram of repeat lengths for sequence reads corresponding to the marker region of the target STR. A score per STR marker is calculated based on features of the histogram of repeat lengths. A plurality of per marker scores may be combined to form a total MSI score for the sample.

The present application provides a mouse model for studying microsatellite stable and unstable intestinal cancer. Specifically, the present application provides the use of a hybrid mouse in a reagent or kit for preparing a mouse model animal for constructing MSS type intestinal cancer and MSI-H type intestinal cancer, wherein the mouse is a F1 generation of C57BL / 6 x BALB / c. The mouse model of the present application provides the same genetic background for MSS type intestinal cancer cells and MSI-H type intestinal cancer cells, making the research of MSS type intestinal cancer and MSI-H type intestinal cancer more scientific.

The invention provides a microsatellite site stability detection method and an electronic device thereof. The microsatellite locus stability detection method comprises the following steps: S1) utilizing high-throughput targeted sequencing data of a sample to be detected to obtain feature data in a preset microsatellite locus set, the feature data at least comprising length variation of a short tandem repeat sequence and structural variation occurring at a microsatellite locus; according to the microsatellite stability detection method and device, the problem that in the prior art, a method for detecting microsatellite instability has limitation can be solved, and the microsatellite stability detection method and device are suitable for the field of tumor detection.

The invention relates to the technical field of medicines, and provides application of L-histidine as a PD-1 antibody for treating a microsatellite stable colon cancer sensitizer. According to the technical scheme, the problem that in the related technology, the PD-1 antibody drug is poor in microsatellite stable colon cancer treatment effect is solved.

This invention describes systems, primers, kits, and methods for detecting microsatellite instabilities in biological samples. Signal data is received from a capillary electrophoresis genetic analysis instrument, wherein the signal data is determined based on the fluorescence of fragments comprising nucleic acid sequences amplified from the biological sample by polymerase chain reaction (PCR). The nucleic acid sequences correspond to multiple different microsatellite loci and are obtained using multiple PCR primers configured to side-join the multiple microsatellite loci of the biological sample. When the PCR primers are combined with the biological sample and subjected to PCR amplification, fluorescently labeled DNA fragments comprising the multiple microsatellite loci are generated. The microsatellite instabilities of the biological sample are classified using the fluorescence data obtained from the multiple fluorescently labeled microsatellite loci.

The invention relates to the technical field of biomedical detection, in particular to a multi-dimensional tumor marker joint detection device and a using method thereof.The device comprises a sample processing module, a sequencing module, a marker extraction module, a feature fusion and detection module and a result output module, and 6 types of markers such as chromosome copy variation, microsatellite instability and the like are extracted respectively. The method comprises the following steps: collecting a body fluid sample to extract cfDNA, directly constructing a library without special treatment, obtaining effective data through whole genome sequencing, synchronously extracting six types of markers through each module of the device, optimizing an algorithm to adapt to low-depth data, inputting an integrated learning model to output a risk score, and finally outputting related information by a result output module. The method does not need special experimental treatment, realizes low-cost and high-accuracy joint detection, and meets the clinical large-scale screening requirements.

Techniques for identifying a microsatellite instability (MSI) status of a sample are described. An example method includes identifying sequence read data indicating sequences of DNA fragments of a sample obtained from a subject with cancer and determining, based on the sequence read data, endpoint positions of the DNA fragments with respect to a reference genome. Input features are determined based on the endpoint positions of the DNA fragments with respect to the reference genome. Using a classifier, and based on the input features, an MSI status (e.g., MSI-High, MSI-Low, MSI-Stable, etc.) of a sample is determined.

Provided herein are methods for determining the microsatellite instability status of samples. In one aspect, the methods include quantifying a number of different repeat lengths present at each of a plurality of microsatellite loci from sequence information to generate a site score for each of the plurality of the microsatellite loci. The methods also include comparing the site score of a given microsatellite locus to a site specific trained threshold for the given microsatellite locus for each of the plurality of the microsatellite loci and calling the given microsatellite locus as being unstable when the site score of the given microsatellite locus exceeds the site specific trained threshold for the given microsatellite locus to generate a microsatellite instability score, which includes a number of unstable microsatellite loci from the plurality of the microsatellite loci.

The present application relates to a microsatellite site screening method capable of screening a microsatellite site with lower polymorphism. The present application also relates to a microsatellite instability detection method using a microsatellite site obtained by the microsatellite site screening method.

This application relates to the field of tumor grading and detection, specifically to the use of gene combinations in the manufacture of products for grading and detecting homologous recombination deficiency, tumor mutation burden, and microsatellite instability in human tumors. The gene combination consists of gene set A and gene fragment set B. The gene combination is obtained through specific pairwise clustering analysis from actual high-throughput sequencing data, and the data obtained from real-world data has higher reliability and certainty, enabling accurate grading and prediction of pan-cancer homologous recombination deficiency, tumor mutation burden, and microsatellite instability.

The problem to be solved by the present invention is to provide more and better options for treating any solid tumor with high frequency microsatellite instability (high frequency MSI or MSI-H) alterations, cervical cancer, endometrial cancer, lung cancer, brain cancer and breast cancer.SOLUTION: The present invention relates to multispecific antibodies comprising an antigen binding site that binds an extracellular part of CD137 and an antigen binding site that binds an extracellular part of a second membrane protem for use in a method of treatment of cancers in a subject in need thereof. The invention further relates to such multispecific antibodies, as well as methods and other aspects related thereto.SELECTED DRAWING: None

This invention discloses a method for inducing B-CD4 + Freeze-dried tumor tissue with T-cell interaction, its preparation method, and its applications. This study aims to address the lack of effective treatments for postoperative recurrence of microsatellite stable (MSS) solid tumors, the easy degradation and inactivation of traditional autologous whole antigen vaccines, insufficient presentation efficiency, and the limitation of only activating classical CD8. + The core bottleneck of the T cell pathway. This invention utilizes vacuum freeze-drying technology to prepare porous, degradable freeze-dried tumor tissue (LT) from clinically derived or artificially cultured tumor tissue. This process fully preserves the tumor's complete antigen spectrum, tumor-specific antigens, and the immunogenicity of related antigens. It allows for highly efficient antigen presentation via dendritic cells, specifically inducing B cells and CD4+. + T-cell interaction mediates non-classical anti-tumor immunity that does not rely on traditional cytotoxic immune cells, significantly inhibiting the growth of residual lesions after solid tumor surgery. It has both broad-spectrum anti-cancer effects and excellent biosafety, and is especially suitable for postoperative adjuvant immunotherapy for MSS-type colorectal cancer.

The invention discloses application of morusin O in preparation of a sensitizer of an immune checkpoint inhibitor, and relates to the technical field of biological medicines. The invention also discloses a pharmaceutical composition for treating microsatellite stable tumors and a method for screening a small molecule compound for inducing a microsatellite instability state. The morusin O is used for reducing the expression level of the mismatch repair protein and promoting the tumor to be converted into a microsatellite instability state, so that the sensitivity of the MSS type tumor to immunotherapy is enhanced, and a new treatment strategy is provided for development of MSS tumor drugs.

Methods and compositions for detecting genetic instability using digital amplification assays. The methods may be performed in a set of isolated volumes and generally may involve competitive hybridization of a competitor and a probe / primer with a normal allele and one or more mutant alleles of a microsatellite locus. The competitor may be configured to compete similarly with, or to outcompete, the primer / probe for hybridization with the normal allele. The primer / probe may be configured to outcompete the competitor for hybridization with various mutant alleles of the locus that alter the length of the repetitive sequence by different amounts. Isolated volumes in which the primer / probe outcompetes the competitor may be enumerated, and represent one or more of the mutant alleles. The methods may enable diagnosing microsatellite instability and treating a subject based on the diagnosis.

The application provides a microsatellite site stability detection method and an electronic device thereof. The microsatellite site stability detection method comprises the following steps: S1, obtaining characteristic data in a preset microsatellite site set by using high-throughput targeted sequencing data of a to-be-detected sample, wherein the characteristic data at least comprises the following: length variation of a short tandem repeat sequence and structural variation occurring at the microsatellite site; S2, establishing a prediction model by using the characteristic data; and S3, outputting a microsatellite stability result of the to-be-detected sample by using the prediction model. The method can solve the limitation problem of the microsatellite instability detection method in the prior art and is suitable for the tumor detection field.

The present application provides a method for identifying microsatellite instability using a primer combination, the method comprising the steps of: (1) setting a plurality of MSI target sequences; (2) for a plurality of gene reads including one or more sequences among the plurality of MSI target sequences, forming a primer combination group for each gene read having the same start point and end point; (3) for each MSI target sequence included in the primer combination group, identifying whether gene deletion is present; and (4) for the MSI target sequence in which the presence of gene deletion has been identified, determining whether "False shortening" or "True shortening" is present through comparisons in the primer combination group.

Methods and systems for detecting MSI are provided. Also provided are methods for enriching human genomic DNA for microsatellite loci. Additionally, an oligonucleotide array for detecting MSI is provided. In some embodiments, the method for detecting MSI comprises detecting sequencing reads from a sample for a plurality of microsatellite loci; determining a metric for repeat length distribution (RLD) for each microsatellite locus; comparing the metric to a threshold value for the microsatellite locus; quantifying the number of microsatellite loci having an RLD metric exceeding the threshold value; and comparing the number of microsatellite loci having an RLD metric exceeding the threshold value to a microsatellite instability (MSI) proportion threshold.

A gene signature for evaluating likely sensitivity of a cancer cell to treatment with inhibitors of Werner syndrome RecQ helicase (WRN) is provided. For cancer cells that have microsatellite instability (MSI) and / or mismatch repair deficiency (dMMR), sensitivity to treatment with a WRN inhibitor is likely if the cancer cell has a loss of function mutation in at least two of KMT2D, ARID1A or RAD50, or if the cancer cell has a loss of function mutation in ARID1A only, without loss of function mutations in KMT2D and RAD50. Cancer cells that are MSI and / or dMMR in which both ARID1A and at least one of KMT2D and RAD50 are wild type or have only missense mutations are unlikely to be sensitive to treatment with WRN inhibitors.

The application discloses a spiro derivative as a WRN helicase inhibitor and application thereof. The spiro derivative has better WRN helicase inhibiting activity, can be used for inhibiting the growth of microsatellite instability (MSI) tumor cells by inhibiting WRN to cause high levels of DNA double-strand breaks (DSB) in the MSI cells, can be used for preventing and / or treating related cancers, especially colorectal cancer, gastric cancer, ovarian cancer and endometrial tumor, can fill the gap of specific MSI typing cancer targeting drugs, and has very good application prospect and value in the medical field.

Methods for evaluating microsatellite instability (MSI) analyze nucleic acid sequence reads corresponding to a plurality of marker regions for MSI. The marker regions may include long homopolymers and / or short tandem repeats (STRs). For a target homopolymer, a histogram of homopolymer signal values is calculated based on flow space signal measurements for the homopolymer region in the sequence reads. A score per marker based on features of the histogram of homopolymer signal values is determined for each marker region corresponding to the target homopolymers. For a target STR, the method includes calculating a histogram of repeat lengths for sequence reads corresponding to the marker region of the target STR. A score per STR marker is calculated based on features of the histogram of repeat lengths. A plurality of per marker scores may be combined to form a total MSI score for the sample.

Disclosed herein are compounds of Formula (I) that induce selective cell death in tumor cells having microsatellite instability (MSI), and thus these compounds are useful for treating cancer, including cancer characterized by MSI and / or defective DNA mismatch repair system (dMMR). In addition, also disclosed are pharmaceutical compositions comprising such compounds, methods of using such compounds, and methods of making such compounds. (I)

The present invention concerns the field of cancer and methods for early detection of cancerous lesions. Specifically, the invention relates to a method for early detection of cancerous lesions through the analysis of microsatellite instability in the genome of an individual from a liquid biopsy.

The invention relates to microsatellite instability detection in cell-free DNA. Provided herein are methods for determining a microsatellite instability state of a sample. In one aspect, the method includes quantifying the number of different repetitive sequence lengths present at each of the more than one microsatellite loci according to sequence information to produce a locus score for each of the more than one microsatellite loci. The method further includes, for each of the more than one microsatellite locus, comparing the locus score for the given microsatellite locus to a locus-specific training threshold for the given microsatellite locus, and identifying the given microsatellite locus as unstable to produce a microsatellite instability score when the locus score for the given microsatellite locus exceeds a locus-specific training threshold for the given microsatellite locus, the microsatellite instability score includes a number of unstable microsatellite loci from more than one microsatellite locus.

The invention discloses a microsatellite instability detection marker combination screening method based on an NGS technology and application, and belongs to the technical field of gene detection.The method comprises the steps that firstly, MSS normal samples serve as the basis, high-consistency samples are screened through a sliding window algorithm to construct a coverage baseline, MSI-H tumor sample signals are corrected in combination with tumor purity, and the coverage baseline is obtained; calculating a false positive control threshold and a detection rate threshold by adopting binomial distribution and dichotomy, and screening out a specific MSI-H marker; a two-dimensional baseline model is constructed by utilizing an MSS negative tissue sample, an MSIscore / MSSscore scoring system and a dynamic judgment threshold are included, and a standardized detection process of coverage calculation-effective site screening-signal scoring-state judgment is formed. The method solves the problems that a traditional method is poor in site universality, rigid in threshold value and insufficient in low-purity sample adaptability, is widely applied to MSI detection of colorectal cancer, endometrial cancer and other tumors, is suitable for clinical low-tumor-content sample scenes, and has high accuracy, high stability and good clinical applicability.

This disclosure relates to methods and compositions for treating cancer (e.g., cancers containing MSI-H cells) by: targeting WRN for degradation (in the presence or absence of a WRN inhibitor); promoting WRN association with chromatin (in the presence or absence of a WRN inhibitor); and / or promoting WRN localization from the nucleolus to foci on the chromatin.

The invention discloses a gastric cancer microsatellite instability state diagnosis model. The model comprises an instance segmentation module which is used for generating a segmentation mask for a hematoxylin eosin dyed image so as to generate an instance image block of a target pixel in a tissue related area; the feature extraction module is used for extracting initial features by utilizing a plurality of selected optimal pre-training models according to the input blocks; the dynamic weight distribution module is used for evaluating the importance of the plurality of optimal pre-training models on the primary features output by the same image and generating a fusion weight; the feature fusion module is used for fusing the primary features extracted by the plurality of optimal pre-training models into an advanced feature vector in combination with the fusion weight; the attention score calculation module is used for calculating attention scores of the high-level feature vectors of the different image blocks of the same image, and the multi-instance classifier is used for diagnosing the MSI state according to the high-level feature vectors of the image blocks which are ranked before M. Through the system, the instability state of the microsatellite can be accurately diagnosed.

Provided herein are methods for determining the microsatellite instability status of samples. In one aspect, the methods include quantifying a number of different repeat lengths present at each of a plurality of microsatellite loci from sequence information to generate a site score for each of the plurality of the microsatellite loci. The methods also include comparing the site score of a given microsatellite locus to a site specific trained threshold for the given microsatellite locus for each of the plurality of the microsatellite loci and calling the given microsatellite locus as being unstable when the site score of the given microsatellite locus exceeds the site specific trained threshold for the given microsatellite locus to generate a microsatellite instability score, which includes a number of unstable microsatellite loci from the plurality of the microsatellite loci.