21 results about "PTEN" patented technology

Methods are provided for detecting gene deletions and driver mutations using tumor-specific methylation patterns from cell-free DNA and tissue biopsies. The methods exploit the mutual exclusivity between tumor-specific methylation and homozygous gene deletion, enabling detection through absence of expected methylation signals. Applications include detection of MTAP, PTEN, and RB1 deletions, as well as prediction of EGFR single nucleotide (SNV) and small (up to 50 base pair) insertions and deletions (indel) driver mutations, enabling identification of patients eligible for targeted therapies.

Provided herein are engineered or modified cell lines in which the expression of at least one of ADM2, AURKA, BCL2, CCND1, CHD1, CREB3L3, RIGI / DDX58, ECSIT, EHHADH, ERBB2, FAS, FBXW7, FGFR3, FOXL2, GATA1, HDAC5, HOXA5, HSP90B1, IL6, ITGA2B, KAT5, LAS1L, LIF, NFKB1, NFKB2, NFKB1A, NFE2L2, NGEF, NME1, NR3C1, POLN, PPAR-A, PTEN, RELB, RPA1, RXRA, SMAD4, SS18, TCF7, TGM2, THEM6, TNFAIP3, TP63, TRPC1, DBH, ITGAM, HHEX, TXNIP, ASNS, PLEKH02, CDKN1A, C5orf64, COL20A1, GJB3, ISYNA1, PARD6G-AS1, ACTA1, ACTC1, ADCY10, ADCY4, ADORA2A, ALKBH5, ATP1A4, ATP1B2, ATP2B2, BAIAP3, BAZ1B, BTK, CBL, CCNA1, CD14, CLTC, COPS3, CRHR2, CXADR, DAPK1, DCTN5, DYNLRB1, EME2, EXOC3L1, EYA3, EYA4, FANCA, FEN1, GAK, GCGR, GHSR, GSK3B, H2BC5, H4C7, H4C8, HAP1, HCAR1, INO80, KCNB1, LAT2, LIN7C, MAP1B, MBD4, MYH11, MYH15, MYH3, MYH7B, NAPA, NKD2, NLRP5, NPM2, NR4A3, NFRKB, PAXIP1, PIAS1, PIAS4, POLE, POLE3, POLD1, POLH, PPP4R2, PTGER3, RAB25, RAB40C, RAB44, RAD9A, REV1, RIF1, RNF111, RNF168, RNF4, RPA4, RTEL1, SCRIB, SNRNP70, SPHK1, STX3, SYT1, SYT2, SYT5, SYTL1, SYNJ2, TERF2, TNFSF10, TNPO2, TOP3A, TRIM25, TRIM72, TXLNA, UBA7, UNC5A, VAV3, VPS18, WASL, XRN2, and YY1 is altered as compared to a control cell line. Also provided are methods of producing recombinant AAV particles in said engineered or modified cell lines.

This invention relates to the field of ovarian tissue in vitro culture technology, and discloses a formulation for activating and increasing follicles and its application. The formulation consists of a PI3K / Akt / mTOR pathway activator and / or a PTEN inhibitor SF1670. The PI3K / Akt / mTOR pathway activator is a 5-15 μM statin, and the PTEN inhibitor is a 20-50 μM SF1670. Using this formulation can achieve the follicle activation and increase effect of existing technologies, contributing to the development and selection of in vitro follicle activators in clinical practice. Furthermore, the use of this formulation opens up a new technological application area for statins.

The application discloses biomarkers, kits and application thereof for breast cancer detection. Specifically disclosed are application of biomarkers and / or substances for detecting the biomarkers in breast cancer gene detection, wherein the biomarkers include 13 gene mutation sites, namely AKT1, EGFR, ERBB2, ERBB3, ESR1, FBXW7, KRAS, MTOR, PDGFRA, PIK3CA, PTEN, SF3B1 and TP53. The application also discloses a breast cancer gene mutation detection method, which covers 173 mutation sites of 13 genes, reduces the number of detection reactions by designing a primer panel, realizes simultaneous coverage of more gene mutation sites by using fewer primers, and completes library construction through one round of PCR amplification, is short in operation time, and is high in sensitivity and can reach 0.2%.

The present invention is based, in part, on cancer vaccine compositions that comprise PTEN- and p53-deficient cancer cells with activated TGFβ-Smad / p63 signaling pathway, and methods for using same to prevent and / or treat cancer.

The present application relates to a rabbit polyclonal antibody targeting human PI3K beta tyrosine phosphorylation at position 962, and a preparation method and application thereof. The present application first identifies that PI3K beta protein Y962 site is phosphorylated and modified and the phosphorylation modification of the site significantly affects the function of PI3K beta protein in PTEN knockout cells through mass spectrometry combined with a series of molecular biology experiments, so an antigen peptide containing Y962 site phosphorylation is synthesized, an immunogen is obtained by coupling a carrier protein hole hemocyanin, a Japanese white rabbit is immunized six times combined with an adjuvant, and a PI3K beta Y962 site specific phosphorylation antibody is obtained after purification and identification. The present application can specifically detect the PI3K beta Y962 site phosphorylation level in cells and tissue samples, and provides an important tool for studying the role and mechanism of PI3K beta phosphorylation in tumors.

The invention provides a plasmid tool for simulating Kras random evolution and application thereof, and the plasmid tool comprises at least two guide RNA expression cassettes driven by a first promoter, which respectively target a Pten gene and a Trp53 gene; the pilot editing guide RNA expression box is driven by a second promoter, targets the 12th codon of the Kras gene, and comprises a repair template sequence for editing the codon into G12D; the fusion protein expression cassette is driven by a third promoter and comprises SpCas9 protein and MMLV reverse transcriptase; and at least one eukaryotic selection marker gene expression cassette. The invention also discloses a method for constructing a simulated Kras random evolution model by adopting the plasmid tool, and application of the plasmid tool in screening targeted drugs aiming at KRAS mutation tumors. The plasmid tool provided by the invention can realize cell multi-gene locus editing, construct a Kras locus random evolution model and simulate a Kras random evolution process in ovarian cancer.

The application belongs to the field of biological medicine, and particularly relates to a group of gene mutations and application thereof in diagnosis of pancreaticobiliary duct cancer. Specifically, the application provides a group of gene mutations for detecting pancreaticobiliary duct cancer, wherein the gene mutations include one or more of AKT1, KRAS, APC, NRAS, ARID1A, PIK3CA, AXIN1, PPP2R1A, BAP1, PTEN, BRAF, SMAD4, CDKN2A, TERT, TP53, EGFR, FBXW7, FGFR2, HRAS, IDH1 and IDH2.

Inventors have firstly demonstrated that the transcriptomic signature of PTENpc- / - LSCmed cells is enriched in human MSPC signature, associated to metastases and ADT resistance. Using scRNAseq specifically with sorted PTENpc- / - LSCmed cells, they identified three distinct LSCmed clusters and showed that castration favors the emergence of the most stem-like LSCmed subpopulation by cell plasticity. In the latter, they identified the transcription factor FOSL1 / AP-1 and the kinase PIM1 as relevant therapeutic targets, and they showed that combined inhibition using JQ1, a BET / AP-1 inhibitor, and CX-6258, a pan-PIM kinase inhibitor, efficiently prevents PTENpc / - LSCmed cell growth in organoids. These findings were confirmed in the human prostate HPV10 cell line here identified as a robust model of Club / Hillock cells. Combined drug delivery to castrated PTEN-null mice induced a significant prostate weight decrease associated with the reduction of histopathological phenotypes and dramatically altered organoid-formation capacity of LSCmed cells sorted from these tumors. Accordingly, the drug combination significantly delayed tumor growth of MSPC-like human PC-3 cells subcutaneously injected into castrated immunodeficient mice. Altogether, this work shows a new therapeutic potential of combined FOSL1 and PIM1 targeting to prevent, or at least delay, the growth of MSPC-like cells. Accordingly, the invention relates to i) an inhibitor of FOSL1 and ii) an inhibitor of PIM1, as a combined preparation for use in the treatment of prostate cancer in a subject in need thereof.

This invention discloses the use of LAPTM5 in the preparation of drugs regulating renal tubular epithelial-mesenchymal transition (EMT). Through bioinformatics analysis and multi-level experimental verification, this invention found that LAPTM5 is significantly upregulated in an aging kidney model and is positively correlated with renal aging and the severity of fibrosis. Mechanistic studies show that LAPTM5 interacts with the deubiquitinating enzyme USP10 and promotes its lysosomal degradation, weakening the deubiquitination effect of USP10 on PTEN. This leads to proteasomal degradation of PTEN via the K48-linked polyubiquitination pathway, thereby relieving PTEN's inhibition of the PI3K / AKT / mTOR signaling pathway, inhibiting autophagy activity, promoting renal tubular epithelial-mesenchymal transition, and accelerating the process of renal fibrosis. At the cellular level, PTEN overexpression can rescue LAPTM5-induced EMT; in animal models, the PTEN agonist matrine significantly improves D-galactose-induced renal fibrosis in aging mice and protects renal function by restoring autophagy.

The invention relates to the technical field of medicines, and particularly discloses a pharmaceutical composition based on an IRF7-PTEN signal axis and application of the pharmaceutical composition in spinal cord injury. According to the application, a plurality of spinal cord injury single cell sequencing data sets are integrated, and the interferon regulatory factor 7, namely IRF7, is screened and verified to be a key hub gene for regulating and controlling apoptosis of astrocytes. Knock-down IRF7 significantly inhibits astrocyte apoptosis induced by etoposide, and rotation IRF7 can reverse the effect. In mechanism, the IRF7 promotes cell apoptosis by negatively regulating a PTEN pathway, and the PTEN inhibitor SF1670 can block the IRF7 overexpression mediated apoptosis promoting effect. On the basis, the invention provides a pharmaceutical composition taking the signal axis as a target spot, and the active ingredient of the pharmaceutical composition can be an IRF7 inhibitor or a PTEN inhibitor; the invention also discloses application of the inhibitor in preparation of drugs for treating spinal cord injury. The application provides a new target spot and an effective intervention strategy for treatment of spinal cord injury.

The application belongs to the field of proteomics research, and discloses application of a reagent in preparation of a product for detecting or treating IgG4-RD. Six PD-L1 related DEPs (RPS6KB1, NFATC1, CD3E, PTEN, PTPN6 and JAK2 proteins) can be used as biomarkers for patient stratification and identification of individuals with high risk of severe disease progression or fibrosis sequelae, secondly, activation of the PD-1 / PD-L1 pathway suggests that immune checkpoint regulation may be a new treatment method for IgG4-RD, thirdly, significant enrichment of metabolic pathways indicates that IgG4-RD is a metabolic disorder disease, which provides a way for targeted immunometabolism. Finally, drug repositioning research highlights resveratrol and sorafenib as candidate therapeutic drugs, and the potential combination of these drugs provides a new method for rebalancing immune activation and inhibition in IgG4-RD.

The application provides a peptide lipid nanoparticle, a preparation method, an application and a cancer combined treatment drug combination, and belongs to the technical field of biological medicines.The application proposes a novel synergistic anti-tumor strategy based on the combination of a peptide lipid nanoparticle and a low-dose mTOR inhibitor, synergistically inhibits a PI3K / AKT / mTOR signal pathway, co-applies the peptide lipid nanoparticle loaded with p53 circular RNA and the mTOR inhibitor to cancer cells, restores p53 function, reactivates PTEN, blocks the feedback activation of PI3K / AKT, and directly inhibits mTOR by the mTOR inhibitor, thereby producing a persistent cascade double blocking. Moreover, p53 inhibits the evirolimus-induced pro-survival autophagy, converts it into a stress-induced process, and realizes the double inhibition and persistent blocking of the PI3K / AKT / mTOR pathway.

The application discloses a zinc finger protein ZFP gene and application thereof, and identifies the interaction protein ZFP of BmPGRP2 through yeast two-hybrid screening; the ZFP directly combines with the GACATAGATATT sequence on the PTEN promoter as a transcription factor, and inhibits the transcription of PTEN; the expression amount of PTEN can be significantly increased by knocking out the ZFP, and the proliferation of BmNPV is inhibited. Therefore, the ZFP is a negative regulation factor of PTEN, has important value in the research and application of the silkworm antiviral molecular breeding, and the antiviral ability of the silkworm can be improved by knocking out the gene through gene editing.

The invention discloses a probe set for evaluating whole-body tumor load of small cell lung cancer and application of the probe set, the probe set comprises a plurality of oligonucleotide probes for specifically capturing mutation regions of SCLC related genes in a targeted mode, and the genes are selected from TP53, RB1, CREBBP, EGFR, PTEN, PIK3CA, LRP1B and NOTCH1; and the probe set is capable of covering at least 94.9% of at least one mutation existing in an SCLC patient sample. The invention relates to the technical field of biotechnology and molecular diagnosis, and has the beneficial effects that based on a clinical queue, the probe group incorporates high-frequency mutant genes of SCLC, can be superposed with personalized probes for use, and is used for ctDNA detection of SCLC patients and evaluation of whole-body tumor load. The SCLC cancer species specific probe group provided by the invention plays a role in monitoring tumor evolution and new mutation, can overcome the space-time heterogeneity of tumors to a certain extent, and also can improve the capture efficiency at the same time.

This invention provides a protein chip for early warning of liver cancer and its application. The protein chip includes an antigen set; the antigen set includes antigens; the antibodies corresponding to the antigens are at least one of 61 selected from GNA11, GNAS, IDH1, MSH2, NPM1, PAX5, PTCH1, PTEN, SRSF2, Survivin, CAST, PAIP1, PRKCZ, RAD23A, RUNX1T1, SARS, TP53, APEX2, RCSD1, and AIF1; the protein chip is used for early warning assessment of liver cancer, and the early warning assessment steps include: collecting serum from the target population, using the protein chip to detect the serum to obtain detection data, and then determining whether they belong to a low-risk, medium-risk, or high-risk population based on a risk warning model; the protein chip systematically detects tumor-related autoantibody risk factor signals using high-throughput technology for early warning detection of liver cancer.

The invention discloses a gene marker combination for predicting the curative effect of abiraterone in metastatic castration resistant prostate cancer (mCRPC). The gene marker combination comprises 16 genes, namely HDAC2, TP53, GEN1, FOXA1, ATR, MUTYH, SPOP, BRCA2, ATM, PALB2, RB1, CDK12, BARD1, PTEN, NCOR2 and MLH1. The invention further discloses an mCRPC abiraterone curative effect prediction model based on the marker combination and a construction method of the mCRPC abiraterone curative effect prediction model. According to the method, mCRPC gene markers highly related to abiraterone treatment response are screened based on detection data of related genes of prostate cancer in combination with clinical abiraterone treatment effect results, and an abiraterone treatment effect prediction model is constructed based on the markers, so that personalized prediction of the treatment effect of an mCRPC patient using abiraterone treatment is realized, and the treatment effect of the patient is improved. And an effective reference can be provided for accurate medication.

In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2α axis of the UPR adaptive response. Agents that disrupt PERK-eIF2α pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.

Provided herein are engineered or modified cell lines in which the expression of at least one of ADM2, AURKA, BCL2, CCND1, CHD1, CREB3L3, RIGI / DDX58, ECSIT, EHHADH, ERBB2, FAS, FBXW7, FGFR3, FOXL2, GATA1, HDAC5, HOXA5, HSP90B1, IL6, ITGA2B, KAT5, LAS1L, LIF, NFKB1, NFKB2, NFKB1A, NFE2L2, NGEF, NME1, NR3C1, POLN, PPAR-A, PTEN, RELB, RPA1, RXRA, SMAD4, SS18, TCF7, TGM2, THEM6, TNFAIP3, TP63, TRPC1, DBH, ITGAM, HHEX, TXNIP, ASNS, PLEKH02, CDKN1A, C5orf64, COL20A1, GJB3, ISYNA1, PARD6G-AS1, ACTA1, ACTC1, ADCY10, ADCY4, ADORA2A, ALKBH5, ATP1A4, ATP1B2, ATP2B2, BAIAP3, BAZ1B, BTK, CBL, CCNA1, CD14, CLTC, COPS3, CRHR2, CXADR, DAPK1, DCTN5, DYNLRB1, EME2, EXOC3L1, EYA3, EYA4, FANCA, FEN1, GAK, GCGR, GHSR, GSK3B, H2BC5, H4C7, H4C8, HAP1, HCAR1, INO80, KCNB1, LAT2, LIN7C, MAP1B, MBD4, MYH11, MYH15, MYH3, MYH7B, NAPA, NKD2, NLRP5, NPM2, NR4A3, NFRKB, PAXIP1, PIAS1, PIAS4, POLE, POLE3, POLD1, POLH, PPP4R2, PTGER3, RAB25, RAB40C, RAB44, RAD9A, REV1, RIF1, RNF111, RNF168, RNF4, RPA4, RTEL1, SCRIB, SNRNP70, SPHK1, STX3, SYT1, SYT2, SYT5, SYTL1, SYNJ2, TERF2, TNFSF10, TNPO2, TOP3A, TRIM25, TRIM72, TXLNA, UBA7, UNC5A, VAV3, VPS18, WASL, XRN2, and YY1 is altered as compared to a control cell line. Also provided are methods of producing recombinant AAV particles in said engineered or modified cell lines.

The application discloses a method for rapidly establishing an ovarian cancer model based on SauriCas9, and particularly discloses a recombinant plasmid for knocking out Pten and Trp53 genes, which comprises an EPI vector system; the recombinant plasmid takes an ori element as a replication start site, and sequentially comprises sgRNA sequences for targeting Trp53 genes and Pten controlled by a double U6 promoter, a CAG promoter, a SauriCas9 nuclease expression unit, a fluorescent protein expression element, a resistance gene, and an orip element and an EBNA1 protein expression element. The application further discloses a method for rapidly establishing an ovarian cancer model based on SauriCas9, and an ovarian cancer cell model obtained by construction. The ovarian cancer cell model is constructed by adopting the method, the period from cell editing to animal tumorigenesis is shortened, the stability and immune integrity of the genetic background of the model are ensured, and large-scale drug screening and high-throughput experiments are facilitated.

This invention discloses an in vitro candidate screening method based on the LAPTM5 / USP10 / PTEN pathway. This method is based on the mechanism by which LAPTM5 weakens PTEN stability by promoting lysosomal degradation of USP10, thereby activating the PI3K / AKT / mTOR pathway, inhibiting autophagy, and promoting epithelial-mesenchymal transition. The screening method includes: establishing senescence-induced or LAPTM5-overexpressing cell models; after candidate treatment, detecting multi-level indicators such as LAPTM5 / USP10 / PTEN expression and modification, PI3K / AKT / mTOR phosphorylation, autophagy markers LC3 and p62, EMT markers, cell morphology, and migration ability; and comprehensively evaluating and ranking candidates based on their regulatory effects on each indicator. The screening system integrates data acquisition, processing, analysis, evaluation, storage, and visualization output modules to automate the screening process. This invention establishes a candidate screening platform based on a clear molecular mechanism, a comprehensive indicator system, and quantifiable evaluation, which can be used to screen candidates from compound libraries or natural products that have regulatory effects on the aforementioned signaling axis, and provides a technical basis for subsequent research.