141 results about "Microsatellite Stable" patented technology

Disclosed are compounds of formula (I) useful as Werner helicase (WRN) inhibitors, a pharmaceutical composition comprising same, and the use thereof in the prevention or treatment of cancers characterized by microsatellite instability-high (MSI-H) or defective mismatch repair (dMMR).

The present disclosure is directed to compounds of Formula I: wherein Z1, Z2, R1, R2, R3, and R4 are described herein, which are spirocyclic compounds for inhibiting Werner Syndrome dsDNA helicase (WRN) and methods of treating disease using these compounds. This disclosure further provides compounds and their use for the treatment of cancers characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), including colorectal, gastric, endometrial and ovarian cancer.

The invention provides a method of treating a colorectal carcinoma with a combination of an anti-LAG-3 antibody and an anti-PD-1 or anti-PD-L1 antibody. In some aspects, the combination comprises 480 mg of each antibody such as, for example, 480 mg of an anti-LAG-3 antibody (e.g, relatlimab) and 480 mg of an anti-PD-1 antibody (e.g, nivolumab). In some aspects, the colorectal carcinoma is unresectable, advanced, or metastatic, including, for example, microsatellite stable or high microsatellite instable colorectal carcinoma.

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 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 belongs to the technical field of biological medicine, and discloses a cancer risk prediction and personalized vaccine preparation system and method based on single sample DNA sequencing, and the system comprises: a, a microsampling module; b, a multi-omics analysis engine; the engine synchronously executes the following operations: identifying a cfDNA terminal motif mode through a convolutional neural network; the presentation probability of the HLA-II type molecules is predicted on the basis of a Transform architecture; quantifying tumor mutation load (TMB) and microsatellite instability (MSI); c, a vaccine synthesis device; the device comprises: a programmable microfluidic mRNA synthesis chip; a self-assembly unit of lipid nanoparticles (LNP); and d, a closed-loop feedback system: monitoring the IFN-gamma through a wearable device to dynamically adjust the vaccine dosage. According to the invention, the early canceration detection rate can be improved, the antigen prediction accuracy is improved, the timeliness demand of early cancer intervention is met, and the adverse reaction rate is reduced.

Disclosed herein are methods of treating an individual having a cancer, of treating or identifying an individual having cancer for a treatment, or stratifying individuals having a cancer for a treatment based on a tumor mutational burden (TMB) score or a TMB score and a microsatellite instability assessment.

The invention discloses a microsatellite instability detection method and device based on a next-generation sequencing technology, and belongs to the technical field of biological detection. The method comprises the following steps: selecting MSI sites, and carrying out capture probe design and / or amplicon primer design based on any combination of the sites; selecting a plurality of samples, and calculating the missing fragment proportion and the normal fragment proportion of each sample at each MSI site; selecting a plurality of samples which are judged to be in an MSI-L or MSS state by a PCR method as baseline samples, and setting different depth levels for each baseline sample to construct a baseline; carrying out MSI state detection; selecting a sample of which the MSI state is MSI-H, and judging whether the sample is an abnormal sample or not through a Spearman rank correlation coefficient; and if yes, adjusting the base line and re-judging the MSI state. The method has high stability and high accuracy, does not need a control sample, and can be simultaneously applied to microsatellite instability detection of hybridization capture and amplicon sequencing data.

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 discloses a microsatellite instability detection system based on colorectal pathological images, wherein the image acquisition module is used to acquire the colorectal pathological images of the detected user; the tumor tissue detection module is used to cut the image into a plurality of image blocks and detect whether each image block is a tumor image; the microsatellite instability detection module uses a microsatellite instability classification model to identify whether each tumor image belongs to high microsatellite instability; when training the tumor tissue detection model, the pre-training weight is used for initialization, the top classifier and the auxiliary classifier are trained at a first training rate, and the parameters of other layers of the tumor tissue detection model are frozen at the same time until the tumor tissue detection model converges, all the parameters of the tumor tissue detection model are unfrozen, and the tumor tissue detection model is fitted at a second training rate. The invention is reliable, widely usable and cost-effective.

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.

The invention discloses a microsatellite instability detection method independent of contrast and reference baselines, and relates to the technical field of microsatellite instability detection.The microsatellite instability detection method comprises the following steps that the cancer type of a sample to be detected is known, site screening is conducted according to samples of the same cancer type, and the sample to be detected is obtained; obtaining a difference site set suitable for microsatellite instability detection; screening a constant stable site set which is always stable in the cancer type sample and meets a certain detection rate requirement; sequencing the difference site set and the constant stable site set of the to-be-detected sample, and extracting the repetition frequency distribution of each site; collecting microsatellite frequency distribution of the constant stable site set to construct a reference dictionary, and extracting data in the reference dictionary from the difference site set according to repetitive units of the difference site set to perform Pearson correlation analysis; and obtaining the instability score of the current sample to realize sample instability detection. According to the invention, the problems of high detection cost and low accuracy caused by limitation of negative sample collection and inaccurate site screening are solved.

The present invention relates to the use of antibodies against Thomsen-Friedenreich (TF) as reagents for in vitro diagnosis of microsatellite instability (MSI). Another aspect of the present invention relates to a method for in vitro diagnosis of MSI, which comprises using a composition of antibodies against TF antigen and measuring the expression of TF antigen in a tissue sample. The present invention also relates to a kit comprising the above-mentioned composition, which is used to detect MSI by implementing the method of the present invention. By sensitively and specifically detecting MSI in patients with gastric cancer, colorectal cancer and cancer of other tissues based on a single marker, the use, composition, method and kit of the present invention can be advantageously used to significantly promote the identification of MSI in clinical situations, thereby being used for diagnosis, prognosis or prediction of response to immunotherapy.

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.

The present application discloses a multiplex PCR detection kit based on colorectal cancer microsatellite instability sites, the kit comprising a primer set and a PCR premix; the primer set comprises a primer for detecting at least one of the sites BAT‑25, BAT‑26, NR‑21, NR‑22, NR‑27, HSP110, BAT‑52, and BAT‑56, the primer containing two inosines (I) and a stem-loop structure (SEQ ID NO.25) to simultaneously detect different states of MSI Del and Ins; when the kit uses MSI detection to determine the microsatellite instability of group colorectal cancer for 8 combined sites and the corresponding target coverage segments, capillary electrophoresis detection and ordinary PCR and digital PCR detection can be performed simultaneously, so that the gradient between the test result values ​​is more refined, and the MSI state is accurately defined as high, low, or stable; while saving the cost of reagents and materials, the test cycle is saved, the detection of the extreme cycle is achieved, the clinical multi-sample detection needs are met, and the kit has the characteristics of high sensitivity, specificity and repeatability.

The invention discloses a microsatellite stable colorectal cancer combination therapy based on a PCSK9 inhibitor, and belongs to the technical field of cancer treatment. The medicine for treating the microsatellite stable colorectal cancer comprises a PCSK9 inhibitor and a composition, and the composition comprises a PD-1 antibody and / or 5-fluorouracil. The invention provides a combination therapy of a PCSK9 blocking antibody combined with chemotherapy and immunotherapy. The combination therapy comprises a combination of a PCSK9 inhibitor, a PD-1 antibody and 5-FU for treatment of microsatellite stable colorectal cancer. The combination therapy can significantly enhance the sensitivity of the microsatellite stable colorectal cancer to 5-FU chemotherapy.

The invention discloses a multiplex PCR (Polymerase Chain Reaction) detection kit based on microsatellite instability sites of endometrial cancer. The kit comprises a primer group and a premixed solution, the primer group comprises a primer for detecting at least one of a site BAT-25, a site BAT-26, a site NR-24, a site MONO-27, a site CAT-25, a site BAT-59 and a site BAT-60, and the primer contains two inosine (I) and a stem-loop structure (SEQ ID NO.22) so as to simultaneously detect different states of MSI Del and Ins; according to the kit, when MSI detection is used for carrying out microsatellite instability judgment on endometrial cancer on seven combination sites and corresponding target coverage sections, capillary electrophoresis detection and common PCR (Polymerase Chain Reaction) and digital PCR detection can be carried out at the same time, so that the gradient among detection result numerical values is more refined, and the MSI state is accurately defined as high, low or stable; the kit has the advantages that reagent material cost is saved, detection period is shortened, detection in an extreme period is achieved, clinical multi-sample detection requirements are met, and the kit has the advantages of high sensitivity, specificity and repeatability.

The present invention provides a WRN inhibitor for use in the treatment of cancer, in particular microsatellite instability-high (MSI- H) or mismatch repair deficient (dMMR) cancer, wherein the treatment further comprises administration of: A. an ionising radiation-based therapy selected from: i) external beam radiation, ii) brachytherapy and Hi) a radiopharmaceutical, or B. carboplatin and paclitaxel; The WRN inhibitor is a compound of formula (1g) or compound C : Formula (C).

The present invention provides a biomarker group for detecting human microsatellite instability, the biomarker group including at least two of markers 1 to 22, and use thereof. Msl, which detects human populations using the biomarker group, has high detection accuracy, a versatile detection platform, and low detection costs.

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.