68 results about "Cisplatin resistance" patented technology

The invention discloses a tetravalent platinum complex with a bioactive group and a preparation method of the tetravalent platinum complex. The tetravalent platinum complex is a platinum (IV) complex and has the structure shown in the formula II (please see the formula in the description), wherein in the formula II, Y is OH or Cl, and Bio represents the bioactive group. The platinum (IV) complex is prepared according to the equation in the formula III (please see the formula in the description), wherein in the formula III, Y is OH or Cl, Bio-OH represents a compound with bioactivity, TBTU represents a coupling agent O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, TEA represents a catalyst triethylamine, DMF represents solvent N,N-dimethyl formamide, and DMSO represents solvent dimethylsulfoxide. Cis-platinum is adopted for the bottom face of an octahedron, a small-molecular targeted or medicine active group is introduced to one axial position, a hydroxyl group or helium atom is introduced into another axial position, and the anti-tumor tetravalent platinum complex overcoming cisplatin resistance is provided, so the high-efficiency and low-toxin platinum (IV) complex is obtained.

The invention provides a compound having anticancer activity, which is obtained by cooperation of Norabieta cantharidin and platinum (IV) and modification of a piperazine derivative. The compound is characterized in that a Norabieta cantharidin piperazine derivative ligand is introduced, thereby cytotoxicity of a platinum (IV) compound is reduced, and high antineoplastic activity is provided. The result of the cytotoxicity experiments shows that the provided platinum (IV) compound has less destruction to normal mice fibroblast L929, but has good killing effect to cancer cells such as human breast cancer MCF-7 cell, human cervical carcinoma HeLa cell and human lung adenocarcinoma A549 cell, so that the compound having anticancer activity is capable of reducing the system toxicity and having equal anticancer activity with cisplatin. The compound having anticancer activity has good killing effect by aiming at cisplatin resistance human lung adenocarcinoma A549/DDP cell. Therefore, the toxicity is reduced, the cisplatin resistance can be reversed, and anticancer effect of the platinum medicines can be increased.

The invention provides an anti-tumor tetravalent platinum complex with an anti-drug resistance function and a preparation method thereof. The structural formula of the compound is shown as a formula Ior a formula II, and the compound is one of the following structures: the compound has excellent cytotoxic activity to tumor cells, especially to cisplatin-resistant tumor cells, and shows excellenttumor inhibition effect and relatively low toxicity in vivo.

The disclosure relates to a method for culture of a cis-platinum drug-resistant lung cancer organoid. The method comprises the following steps: mixing cis-platinum drug-resistant lung cancer tissue cells with the medium and matrix gel to obtain a to-be-cultured substance, wherein the medium contains matrix metalloproteinase-10, and the concentration of the matrix metalloproteinase-10 is 50-200nM based on the medium; and carrying out culture amplification on the to-be-cultured substance to obtain the cis-platinum drug-resistant lung cancer organoid. According to the culture method for the cis-platinum drug-resistant lung cancer organoid provided by the invention, since the employed medium contains the matrix metalloproteinase-10 with specific concentration, and the matrix metalloproteinase-10 with the specific concentration can promote in-vitro growth of the cis-platinum drug-resistant lung cancer organoid, the success rate of the culture is high when the method provided by the disclosure is used for the culture of the cis-platinum drug-resistant lung cancer organoid.

Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.

The invention discloses application of long-chain non-coding RNA and an inhibitor of the long-chain non-coding RNA in prevention and treatment of breast cancer, a full-length sequence of the long-chain non-coding RNA LINC01778V2 is cloned for the first time, and the long-chain non-coding RNA LINC01778V2 is differentially expressed in cis-platinum drug-resistant breast cancer and cis-platinum sensitive breast cancer. Therefore, by detecting the LINC01778V2, the diagnosis of the cis-platinum drug resistance of the breast cancer can be realized. Meanwhile, the LINC01778V2 corresponding expression inhibitor can inhibit proliferation of breast cancer tumor cells, promote apoptosis of the breast cancer tumor cells, kill the tumor cells and reverse cisplatin resistance of cisplatin-resistant triple negative breast cancer. The invention also discloses application of the corresponding inhibitor in prevention and treatment of the triple negative breast cancer with cis-platinum resistance.

The invention discloses a human gastric cancer cell line with 5-fluorouracil resistance and an establishing method and application thereof. The human gastric cancer cell line is preserved in China Center for Type Culture Collection and has a preservation number of CCTCC NO:2013154. The human gastric cancer cell line has the advantages of stable characters, stable multiple passages, high tumor formation rate, short incubation period and good uniformity, and provides a novel experimental material closer to the biological characteristics of clinical tumor for the study of gastric carcinoma. The human gastric cancer cell line has tumorigenicity; the generated tumor has 5-fluorouracil resistance and can be used to analyze the in vitro and in vivo drug sensitivity and resistance correlation, and then establish in vitro and in vivo two related drug screening platforms; and the is cell line is ideal for basic research of gastric cancer and clinical early stage application.

The invention discloses an indium complex taking APT as a ligand and having a potential leaving group as well as a synthesis method and application of the indium complex. The synthesis method comprises the following steps: dissolving 2-acetylpyridine in a mixed solution of methanol and acetonitrile, adding aminothiourea, uniformly mixing the mixture, dropwise adding acetic acid, uniformly mixing the mixture, refluxing the mixed solution, performing vacuum concentration to obtain a concentrate, extracting the concentrate with ethyl acetate, washing a product with saturated sodium bicarbonate and water in order after the extraction step, and carrying out silica gel column chromatography separation to obtain a ligand; adding the ligand obtained in the step 1) and INCl3 into a closed reactionkettle, dropwise adding a mixed solution of methanol and ethanol for dissolving, sealing the reaction kettle after dissolving, and standing the reaction kettle in a vacuum drying oven at 65-80 DEG C for 72 hours to obtain the indium complex. The complex shows good inhibition activity on a cisplatin drug-resistant strain, new data is provided for application of the novel metal-based complex to drug-resistant tumor cell strains, and the synthesis method is simple to operate and convenient to implement.

The invention discloses three ursolic acid piperazine dithioformic acid-pyridine ruthenium complexes as well as a preparation method and application thereof. The preparation method of the ursolic acidpiperazine dithioformic acid-pyridine ruthenium complexes comprises the steps: respectively putting ligand ursolic acid piperazine dithioformic acid sodium and tris(2,2'-dipyridyl)ruthenium dichloride, tris(1,10-phenanthroline)ruthenium dichloride or tris(4,7-diphenyl-1,10-phenanthroline)ruthenium dichloride into a first organic solvent for coordination reaction, and thus obtaining a corresponding target crude product. Tests of the applicant show that the complexes have extremely remarkable inhibitory activity on certain tumor cell strains, the inhibitory activity is greatly higher than thatof parent nucleus and cis-platinum of the complexes, meanwhile, the inhibitory activity of the complexes on cis-platinum drug-resistant strain cells is remarkably superior to that of cis-platinum, andthe complexes are expected to be used for preparing anti-tumor drugs.

Disclosed is a cisplatin-resistance marker for determining whether ovarian tumor cells of interest are resistant to cisplatin.

The cisplatin-resistance marker of the present invention includes a polynucleotide having any one of the base sequences of SEQ ID NOs. 1 to 11 and can be used in a detection method involving the following steps (1) to (3) to determine whether ovarian tumor cells of interest are resistant to cisplatin:

• • (1) hybridizing RNA prepared from a biological sample from a subject, or a complementary polynucleotide transcribed from the RNA, with the cisplatin-resistance marker;
  • (2) quantifying the RNA from the biological sample, or the complementary polynucleotide transcribed from the RNA, that has hybridized with the cisplatin-resistance marker, using the cisplatin-resistance marker as an index; and
  • (3) determining whether the biological sample is a cisplatin-resistant ovarian tumor based on the results of the quantification.

The invention belongs to the field of anti-cervical cancer drugs, and particularly relates to application of T-LAK cell-originated protein kinase (TOPK) serving as a cisplatin resistance therapy target for cervical cancer. In the prior art, a relationship between the TOPK and cervical cancer proliferation and cisplatin resistance is not yet studied. In order to clarify the mechanism of cisplatin resistance of cervical cancer patients, and provide a better therapeutic drug for the cervical cancer patients, the invention conducts a series of researches on the influences of TOPK on cervical cancer proliferation and cisplatin resistance. Results show that the TOPK is highly expressed in tissue of the cervical cancer patients, the TOPK promotes proliferation of cervical cancer cells, and overexpression of the TOPK promotes cisplatin resistance of the cervical cancer cells. A further study shows that a TOPK specific inhibitor OTS514 significantly inhibits proliferation of the cervical cancercells in vivo and in vitro, and the TOPK inhibitor OTS514 and cisplatin are combined and applied to therapy of the cervical cancer, and the therapy effect is superior to a pure cisplatin cisplatin therapy effect.

The invention discloses a human gastric cancer cell line with cisplatin resistance and an establishing method and application thereof. The human gastric cancer cell line is preserved in China Center for Type Culture Collection, and has a preservation number of CCTCC NO:C2013152. The human gastric cancer cell line has the advantages of stable characters, stable multiple passages, high tumor formation rate, short incubation period and good uniformity, and provides a novel experimental material closer to the biological characteristics of clinical tumor for the study of gastric carcinoma. The human gastric cancer cell line has tumorigenicity, and the generated tumor has cisplatin resistance; compared with the passage parental tumor, the generated tumor can be used to analyze the in vitro and in vivo drug sensitivity and resistance correlation, and then establish in vitro and in vivo two related drug screening platforms; and the is cell line is ideal for basic research of gastric cancer and clinical early stage application.

The invention discloses miR-517a-3p related to cisplatin resistance of tumor cells and an application of the miR-517a-3p. The invention also discloses a kit for detecting the drug resistance degree oftumor cells to cisplatin. According to the miR-517a-3p, by establishing an SK-OV-3/DDP drug-resistant cell strain, it is found that miR-517a-3p can be used as a marker of drug resistance of tumor cells; the miR-517a-3p plays a certain role in the drug resistance of the SK-OV-3/DDP cells to the DDP, and the drug resistance of the SK-OV-3/DDP cells to the DDP can be reversed by down-regulating themiR-517a-3p; in addition, the proliferation speed of ovarian cancer SK-OV-3/DDP cells can be inhibited, and meanwhile, the cloning formation capability of the ovarian cancer SK-OV-3/DDP cells is alsoinhibited. The miR-517a-3p is advantaged in that a scientific basis is provided for searching a new molecular treatment target, guiding clinical medication and more effectively resisting cisplatin resistance.

The invention discloses an application of a class of alkaloids in reversing cisplatin resistance of lung cancer. Cisplatin (DDP) is the first-line chemotherapy drug after lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compounds TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, and TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, in which TC-1, and TD-1 not onlycan reverse drug resistance, but also enhance the sensitivity of lung cancer cells to cisplatin. A compound TB-4 does not have this effect.

The invention discloses an alkaloid compound for preventing and treating cisplatin resistance of lung cancer patients. Cisplatin (DDP) is the first-line chemotherapy drug after lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compound TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, in which TC-1, TD-It not only reversed drug resistance, but also enhanced the sensitivity of lung cancer cells to cisplatin. Compound TB-It does not have this effect.