54 results about "Prostate carcinoma" patented technology

The present disclosure relates to the field of nuclear imaging and therapy, and more specifically to high purity copper radiotracer compositions useful in imaging, such as positron emission tomography (PET) and single-photon emission computerized tomography (SPECT), and therapy. More specifically, the present disclosure relates to novel compositions useful in imaging and treatment of conditions such as prostate cancer, somatostatin receptor-expressing tumors, like neuroendocrine tumor, epithelial tumors, as well as to methods wherein such compositions are prepared.

The present disclosure relates to the field of nuclear imaging and therapy, and more particularly, to high purity copper radiotracer compositions that can be used in imaging (e.g., positron emission tomography (PET) and single photon emission computed tomography (SPECT)) and therapy. More specifically, the present disclosure relates to novel compositions useful for imaging and treating conditions (e.g., prostate cancer, somatostatin receptor expressing tumors, such as neuroendocrine tumors, epithelial tumors), and methods of making such compositions.

Provided are methods and compositions for enhancing radiotherapy in various cancers by administering dopamine receptor (DRD2)‐binding phenylpiperazine derivatives such as brexpiprazole, cariprazine, pipamperone, and perospirone. In vitro studies show that combining these agents with ionizing radiation (e.g., 5 Gy) significantly reduces cancer cell survival, suppresses metastatic and stemness markers (e.g., CD44, MMP‑2, Snail, Nanog), and promotes apoptosis. Fractionated or single‐fraction radiation regimens can be paired with DRD2 antagonists to lower treatment‐resistant phenotypes, decrease the likelihood of recurrence, and potentially reduce necessary radiation dosages. The approach applies to breast, prostate, lung, pancreatic, and brain cancers, among others. Depending on tumor characteristics, additional chemotherapeutic or immunotherapeutic agents may further improve outcomes.

The application provides a novel diagnostic marker for neuroendocrine prostate cancer and application thereof, and relates to the technical field of genetic engineering. The novel diagnostic marker is PCSK1N and / or C4orf48. The application overcomes the defects of the prior art, verifies the high expression of PCSK1N and / or C4orf48 in neuroendocrine prostate cancer, and based on this, the PCSK1N and / or C4orf48 can be used as a novel diagnostic marker for neuroendocrine prostate cancer.

The invention discloses a chiral 6-NH2 uracil compound as well as a preparation method and application thereof, and belongs to the technical field of chemical synthesis. The invention provides a method for constructing C-N axial chiral 6-NH2 uracil and a corresponding amide compound thereof through asymmetric organic catalysis, under the catalysis of chiral phosphoric acid, racemization 6-NH2 uracil and azlactone are used as reaction substrates, and 6-amide uracil with optical activity is obtained by utilizing a kinetic resolution strategy. And the 6-NH2 uracil compound with optical activity is recovered. According to the method, chiral uracil is constructed by using an asymmetric catalysis strategy for the first time, and the method has the characteristics of convenience in operation, cheap and easily available raw materials, and high yield and enantioselectivity. The C-N axial chiral uracil shows excellent anti-tumor cell activity, and especially has excellent biological activity on colon cancer, cervical cancer, multiple myeloma, prostate cancer cells and the like.

The invention belongs to the technical field of biomedical detection and tumor molecular diagnosis, particularly relates to a plasma exosome metabolite, and further discloses a method for screening a prostatic malignant tumor biomarker based on plasma ultracentrifugation combined with liquid mass spectrometry metabonomics, and application of the method to preparation of the prostatic cancer biomarker. According to the method, the UC method for extracting the exosome and the LC-MS metabonomics analysis technology are organically combined, the high-efficiency advantage of UC in exosome purification can be fully played, precise detection and quantitative analysis of trace metabolites in the exosome can be achieved by means of an LC-MS platform, and then a characteristic metabonomics spectrogram is constructed.

This invention provides a peptide targeting the degradation of P300, a drug for the prevention and treatment of prostate cancer, a preparation method, and its applications, belonging to the field of protein peptide drug technology. The amino acid sequence of the peptide targeting the degradation of P300 is shown in SEQ ID NO: 1, and its binding constant to P300 protein is 78.3 nM, indicating a strong binding ability to P300 protein. Delivery of the peptide targeting the degradation of P300 to prostate cancer cells can significantly inhibit the proliferation of prostate cancer cells. Simultaneously, the peptide also has the ability to degrade P300. Compared with existing targeted drugs, the peptide drug conjugated with selenium nanoparticles of this invention provides a treatment strategy for drug-resistant and advanced castration-resistant prostate cancer, especially addressing the practical problem of a lack of therapeutic drugs for neuroendocrine prostate cancer.

The invention belongs to the field of chemical medicines, and particularly relates to a combined medicine for preventing and / or treating neuroendocrine prostate cancer, application of the combined medicine and a medicine composition. The combined medicine disclosed by the invention is prepared from the fluphenazine and the illliseme-copper chloride; wherein the fluoroperphenazine can be used for treating neuroendocrine prostate cancer (NEPC) by improving the oxygen consumption of NEPC cells and reducing the glycolytic ability of the NEPC cells; the invention relates to a pharmaceutical composition for treating prostatic cancer with NEPC phenotype, in particular to a pharmaceutical composition for treating prostatic cancer with NEPC phenotype, and ilisimus-copper chloride has no obvious killing effect on prostatic cancer cells with NEPC phenotype, but after fluphenazine and ilisimus-copper chloride are combined for use, the pharmaceutical composition has obvious treatment effect on prostatic cancer with NEPC phenotype, and shows synergistic interaction. The invention opens up a new direction for treating the neuroendocrine prostate cancer, and has a wide application prospect.

The present application belongs to the field of chemical medicine, and particularly relates to a combined drug for preventing and / or treating neuroendocrine prostate cancer, use thereof and a pharmaceutical composition. The combined drug of the present application is fluphenazine and ilesidomosine-copper chloride; wherein fluphenazine can be used for treating neuroendocrine prostate cancer (NEPC) by increasing the oxygen consumption of NEPC cells and reducing the glycolytic capacity of NEPC cells; and ilesidomosine-copper chloride has no obvious killing effect on prostate cancer cell lines with NEPC phenotype, but when fluphenazine is combined with ilesidomosine-copper chloride, the combination has a significant therapeutic effect on prostate cancer with NEPC phenotype, and shows synergistic effect. The present application opens up a new direction for treating neuroendocrine prostate cancer, and has a broad application prospect.

The invention relates to application of HNRNPA3 in treatment and prognosis evaluation of prostate cancer. Through deep research, the HNRNPA3 is determined to be a key target spot for prognosis judgment and treatment of the neuroendocrine prostate cancer, can be used for treatment, auxiliary diagnosis and prognosis evaluation of the neuroendocrine prostate cancer, and meanwhile, improves the understanding of the pathogenesis of the neuroendocrine prostate cancer to a new height; the neuroendocrine prostate cancer pathogenesis content is greatly enriched, a sufficient scientific basis and theoretical basis are provided for searching new prostate cancer diagnosis, prognosis judgment and treatment molecular targets and developing new targeted drugs, and important social value and scientific significance are achieved.

The invention relates to a pharmaceutical composition of an extract of Agarophyton chilensis, with antiproliferative effect in prostate cancer, comprising(a) 0.1 to 90% of an oleoresin of Agarophyton chilensis, with the following major components: palmitic acid, arachidonic acid, oleic acid, stearic acid, meristic acid, linoleic acid; and(b) 10 to 99.9% excipients and formulation aids for different pharmaceutical forms.And its use to prepare a drug for the treatment or prevention of prostate cancer and other hyperproliferative states of prostate tissue cells.

The application discloses a kind of 1,5-diaryl-1,2,4-triazole compounds or pharmaceutically acceptable salt represented by structural formula I, II or pharmaceutical composition containing such compounds.The application also discloses the application of the compound or pharmaceutically acceptable salt in the preparation of drugs for treating various malignant tumors and related diseases of tumor metastasis.The compound represented by formula I, II of the application can inhibit the proliferation, invasion and infiltration of tumor cells such as gastric cancer cells, breast cancer cells, prostate cancer cells, colon cancer cells, liver cancer cells, non-small cell lung cancer cells and bladder cancer cells in a concentration gradient-dependent manner, has the characteristics of high efficiency and low toxicity, and has a wide application prospect in the biological medicine industry.

The invention belongs to the field of organic synthesis and medicinal chemistry, and particularly relates to a synthesis method of a 12-bromine-5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound and an anti-tumor application of the 12-bromine-5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound. Through efficient and simple one-pot bromination reaction, selective functionalization of a C12 site is realized, and the first brominated derivative based on a naphtho-indolizine phenothiazine skeleton is constructed. In-vitro anti-tumor activity research shows that the target compound shows broad-spectrum anti-tumor activity: the target compound has remarkable inhibitory activity (IC50 values are respectively 1.52 mu M, 3.14 mu M and 4.19 mu M) on cervical cancer Hela, lung adenocarcinoma A549 and prostatic cancer PC-3 cells, and the activity is improved by 3.5-16.5 times compared with that of a clinical drug cis-platinum. Preliminary toxicity evaluation shows that the toxicity to normal human umbilical vein endothelial cells (HUVEC) is lower than that of tumor cells, and good selectivity is achieved. The invention provides an important lead compound for developing novel anti-cancer drugs.

The invention relates to the technical field of prostate cancer treatment, in particular to an individualized precise treatment method for advanced prostate cancer, which comprises the following steps: S1, performing biopsy, namely pathological and immunohistochemical detection, on CRPC patients, and performing next-generation sequencing, namely sequencing of oncogene exon mutation sites; s2, determining whether the converted immunophenotype is a CRPC-Adeno adenocarcinoma type or a CRPC-NEPC neuroendocrine type, and respectively determining whether gene mutation exists or not; s3, carrying out standard treatment if no gene mutation exists, matching a corresponding targeted drug if gene mutation exists, and giving an individualized targeted drug scheme; s4, constructing a miniPDX model, namely a function prediction model for accurate treatment of CRPC prostate cancer, and efficiently modeling and rapidly testing drug efficacy through capsule implantation; s5, mainly recording the PFS, and secondarily recording the relationship between the OS and different drug resistance mechanisms and the OS of the patient. The detection technology is simple and convenient, the clinical application popularity is relatively high, the miniPDX model can be used for efficiently modeling and rapidly testing the drug efficacy, and the application value of the miniPDX model in personalized cancer treatment is powerfully enhanced.

The invention discloses a dual-mode immune structure based on a titanium carbide SERS substrate and rare earth doped sodium fluoride nanoparticles and a preparation method and application thereof.The dual-mode immune structure comprises a titanium carbide / molybdenum disulfide composite immune substrate and NaYF4: Yb and Er immune probes, the NaYF4: Yb and Er comprise 78% of Y, 20% of Yb and 2% of Er, and the preparation method comprises the following steps that (S10) titanium carbide powder is prepared through an acid etching method; (S20) preparing a titanium carbide / molybdenum disulfide composite immune substrate; and (S30) preparing a NaYF4: Yb, Er immune probe. The dual-mode immune structure is suitable for detecting prostatic cancer, has high efficiency, high accuracy and high sensitivity in detection, and is suitable for clinical popularization and application.

This invention discloses a PSMA-targeted zwitterionic functionalized gold nanostar composite and its applications. The invention uses hyperbranched polyethyleneimine (PEI.NH2) as a carrier, and sequentially modifies its surface with diethylenetriaminepentaacetic acid dianhydride (DTPA), succinimide ester-polyethylene glycol-PSMA targeting ligand NHS-PEG-ACUPA, succinimide ester-polyethylene glycol-thiol NHS-PEG-SH, and fluorescein isothiocyanate (FI). The composite is further modified by chelating gadolinium ions (Gd) with diethylenetriaminepentaacetic acid dianhydride. 3+ Finally, functionalized polyethyleneimine was linked to alkoxyphenylsulfonamide-modified gold nanostars APAS-Au NSs via gold-sulfur bonds. The resulting gold nanostar complex can achieve efficient enrichment in prostate cancer cells and has CT / MR dual-modal imaging and photothermal therapy functions.

Provided herein are methods for treating autophagy dependent cancers. In particular, provided herein are methods for treating neuroendocrine prostate cancer (NEPC), pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (PNETs), pancreatic neuroendocrine carcinomas (NECs), colorectal cancer (CRC), and non-small cell lung cancer (NSCLC) comprising administering a therapeutic agent, e.g., ESK981, that inhibits PIKfyve and, optionally, a RAS inhibitor.

This invention discloses a CD33-blocking humanized antibody and its uses. The CD33-blocking humanized antibody comprises a heavy chain and a light chain; the heavy chain includes a variable region, the amino acid sequence of which is shown in SEQ ID NO. 20; the light chain includes a variable region, the amino acid sequence of which is shown in SEQ ID NO. 21. This invention also discloses a method for preparing the CD33-blocking humanized antibody, obtained by humanizing a rabbit CD33 antibody. Furthermore, it discloses the application of the CD33-blocking humanized antibody in the preparation of drugs for inhibiting liver metastasis of neuroendocrine prostate cancer and small cell lung cancer. The CD33-blocking humanized antibody of this invention exhibits high affinity and high specificity for CD33, and demonstrates excellent therapeutic and inhibitory effects on liver metastasis of neuroendocrine prostate cancer and small cell lung cancer.

The invention relates to a novel GSPT1 degradation agent and application thereof. Specifically, the present disclosure relates to compounds of formula I, stereoisomers, hydrates, solvates or pharmaceutically acceptable salts thereof; a pharmaceutical composition for the treatment of uncontrolled cell proliferation diseases comprising the compound; and methods of treating uncontrolled cell proliferation diseases by administering the compounds to a mammal. The compound disclosed by the invention shows high selectivity and continuous degradation activity to GSPT1, excellent pH stability and low cytotoxicity to normal cells, so that the compound has an excellent anti-cancer effect and a high therapeutic index. In addition, the compound of the present invention can exhibit excellent anticancer activity against cancers having neuroendocrine phenotypes, such as small cell lung cancer (SCLC), pulmonary neuroendocrine cancer (NEC), neuroendocrine prostate cancer (NEPC), and the like.

Heterocyclic compounds, their stereoisomers and their pharmaceutically acceptable salts are useful in the treatment of many types of cancers, such as cancers of the breast, prostate, pancreatic, gastric, lung, colon, rectum, esophagus cancer, duodenum, tongue, pharynx, liver, kidney, bile duct, uterine body, cervix, ovaries, urinary bladder, and skin. Other cancers to be treated include brain tumor, neurinoma, clear cell carcinoma, non-small cell lung cancer, small cell lung cancer, hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bone tumor, vascular fibroma, glioblastoma, Neuroblastoma, sarcoma, neuroendocrine tumors, retinoblastoma, penile cancer, pediatric solid cancer, renal cell carcinoma, lymphoma, myeloma, leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, cutaneous T-cell lymphoma (CTCL), multiple myeloma (MM), myeloproliferative neoplasms (MPN), Myelodysplastic syndrome (MDS), polycythemia vera (PV), essential thrombocythemia, essential thrombocytosis (ET), and myelofibrosis (MF), and also including their metastases.

The invention belongs to the technical field of biomedical detection and tumor molecular diagnosis, particularly relates to a plasma exosome metabolite, and further discloses a method for separating and purifying a plasma exosome based on exclusion chromatography and screening a prostatic malignant tumor biomarker in combination with liquid mass spectrometry metabonomics. The invention also discloses application of the compound in preparation of a prostatic cancer biomarker. According to the method, the SEC method for extracting the exosome and the LC-MS metabonomics analysis technology are organically combined, so that the high-efficiency advantage of the SEC in exosome purification can be fully played, accurate detection and quantitative analysis of trace metabolites in the exosome can be realized by virtue of an LC-MS platform, and then a characteristic metabonomics spectrogram is constructed.

The invention relates to novel crystalline solid forms of the chemical compound N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Compound 1), and solvates thereof, including hydrates, that are useful for the treatment of cancer. Also disclosed are pharmaceutical compositions comprising the crystalline solid forms and processes for making the crystalline solid forms, as well as methods of using them for the treatment of cancer, particularly thyroid cancer, prostate cancer, hepatocellular cancer, renal cancer, and non-small cell lung carcinoma. The crystalline solid forms can be used to make the L-malate salt of cabozantinib.

The application belongs to the technical field of biological medicine, and particularly relates to a dipicolinate ester derivative and application thereof. The dipicolinate ester derivative has broad-spectrum antitumor activity, can significantly inhibit the proliferation activity of lung cancer cells, pancreatic cancer cells and prostate cancer cells, and has more excellent inhibitory activity on lung cancer cells, and can significantly inhibit the growth of mouse subcutaneous small cell lung cancer transplanted tumors. In addition, the dipicolinate ester derivative has no toxic effect on normal cells of the body, can be applied to preparation of anticancer drugs, and has broad application prospects in the aspect of anticancer.

Compounds of formula (I), pharmaceutical compositions thereof, and kits thereof, are disclosed wherein A1 is C(O) or CHRz1 with Rz1 being OH, amine, imine, halogen, (C1-C5)alkoxy, OC(O)(C1-C5)alkyl, or OSO2-amine; A2 is CH2 or O; R1 is hydrogen, (C1-C5)alkyl optionally substituted with one or more Z substituents, (C1-C5)alkoxy optionally substituted with one or more Z substituents, (C2-C5)alkenyl optionally substituted with one or more Z substituents, (C2-C5)alkynyl optionally substituted with one or more Z substituents, (C3-C8)cycloalkyl, aryl, or heteroaryl; Z is halogen, OH, (C1-C5)alkyl, (C1-C5)haloalkyl, (C1-C5)alkoxy, (C1-C5)haloalkoxy, or amine; R2 is a heterocyclic aromatic ring having 5, 6 or 7 members having at least one N, S and / or O; R3 is a (C1-C5)alkyl substituted with one or more Br, Br76; I, I123, I124, or I131; m is an integer from 0 to 2; n is an integer from 0 to 2; and p is an integer from 0 to 5. Compounds of Formula I are inhibitors of 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and are for use in the treatment or prevention of steroid hormone dependent disease, such as breast cancer, lung cancer, prostate carcinoma, ovarian cancer, uterine cancer, endometrial cancer and endometrial hyperplasia.

The invention provides a neuroendocrine prostate cancer biomarker and application thereof, and relates to the technical field of prostate cancer diagnostic markers. The biomarkers of the neuroendocrine prostate cancer are ASCL1 and WDFY4; the biomarker can be applied to preparation of a prostatic cancer risk assessment kit and a prostatic cancer risk assessment chip, and through single-cell RNA sequencing analysis, copy number variation assessment by InferCNV, pseudo-time analysis and a BayesPrism method, NEPC prognosis characteristics are further researched, a program for distinguishing is determined, clinical prognosis of a patient is assessed, and the like. The invention overcomes the defects in the prior art, reveals the heterogeneity of prostate cancer cells and the key transcription program thereof, successfully verifies the novel biomarker of NEPC, and provides a solid foundation for early prediction and clinical prognosis management of NEPC.

The present invention belongs to the technical field of radiopharmaceutical chemistry and nuclear medicine diagnosis and treatment. Disclosed are a compound for dual targeting of a tumor cell, a preparation method therefor and the use thereof. The compound for dual targeting of a tumor cell has general formulas as represented by formula (I) and formula (II), wherein L1 and L3 are linking groups between a chelator and a PSMA-targeting structure; L2 and L4 are linking groups between the chelator and Peptide1; the Peptide1 and Peptide2 are polypeptide molecules having an SSTR2 targeting property, such as JR11, LM3, LM4, TATE, TOC and NOC; and Chelator1 and Chelator2 are chelators or chelating structures. In the present invention, a PSMA-targeting group and an SSTR2-targeting group are simultaneously linked to a metal chelator (HBED-CC, DOTAGA, DOTA(GA)2, etc.) for the first time for labeling a radioactive metal nuclide such as 68Ga, 18F-AlF, 177Lu, 90Y, 44Sc, 225Ac, 212Pb and 213Bi. The dual targeting function on PSMA and SSTR2 is beneficial to improving the lesion detection rate of neuroendocrine prostate cancer, and achieving more accurate tumor staging and disease prognosis, and is expected to be used for radionuclide targeted therapy.

A technetium [99mTc] injection preparation and a preparation method therefor and the use thereof. The preparation comprises component A and component B which are physically isolated from each other, wherein the component A comprises an active ingredient capable of being combined with a compound providing technetium [99mTc] to form a technetium [99mTc] drug, and the component B comprises a solvent capable of dissolving the technetium [99mTc] drug. The technetium [99mTc] injection preparation is suitable for single-photon emission computed tomography (SPECT) / CT imaging of prostate-specific membrane antigen (PSMA) positive lesions in prostate cancer patients.

Provided are a purine compound and the use thereof. The purine compound has a structure as represented by formula I, and the definition of each substituent is as described in the description and the claims. By means of specifically targeting ZMYND8 and inhibiting the activity thereof, the compound inhibits the transdifferentiation of prostate cancer to neuroendocrine tumors and the growth of prostate cancer, and can also inhibit the growth and progression of small cell lung cancer.

Compositions and treatment methods for cancer, such as enzalutamide resistant cancers, using one or more alternatives to daclatasvir (DCV). DCV has been shown to inhibit the Tribbles homolog 2 (TRIB2) pseudokinase encoded in humans by the TRIB2 gene, but more potent compounds are described herein that bind and inhibit the TRIB2 pseudokinase with greater affinity. TRIB2 is a target for several types of very aggressive cancers, such as castration resistant prostate cancer (CRPC), small cell lung cancer (SCLC), pancreatic neuroendocrine cancer (PNEC), triple negative breast cancer (TNBC), sarcomatoid kidney cancer, and melanoma.

The invention relates to an application of a circ0106416 inhibitor in diagnosis and treatment of prostatic cancer. The neuroendocrine related circRNA-circ0106416 is obtained by constructing a neuroendocrine prostate cancer cell line and carrying out whole transcriptome sequencing screening, and the biological function of the neuroendocrine related circRNA-circ0106416 is verified. Further, through a series of in-vivo and in-vitro functional experiments, knock-down of circ0106416 can reduce neuroendocrine marker expression, inhibit cell proliferation and clone formation ability, reduce subcutaneous tumor growth speed and volume, and reduce subcutaneous tumor final weight. In addition, the invention also defines that the expression level of circ0106416 has obvious influence on the treatment effect of ARSII, and when the expression of circ0106416 is inhibited to reduce the level of circ0106416 in cells, the sensitivity of PCa to the treatment of ARSIs can be effectively improved. Therefore, circ0106416 can be determined to be an important molecule for promoting neuroendocrine conversion of prostate cancer, and is a key therapeutic target of NEPC.