44 results about "Tumor xenograft" patented technology

The invention relates to the field of human xenotransplantation model research, in particular to a method for establishing a human tumor xenotransplantation model cultured in vitro. The establishing method includes the following steps: (1) collecting a tumor tissue sample; (2) placing a tumor tissue in a culture solution; (3) completing the preparation for low-temperature transportation and treatment; (4) cutting the tumor tissue into grain size in a sterile operating table; (5) cleaning the tumor tissue and then placing the tumor tissue in a hole plate 48 for culture; (6) detecting tissue apoptosis by in situ end labeling method; (7) selecting immunocompromised NCG mice to perform anesthesia and skin treatment; (8) implanting the cultured tumor tissue into the renal capsule of the mice; (9) completing modeling after 3 months. According to the invention, tumor tissue blocks are selected for modeling for the xenotransplantation model, which is beneficial to preserving the histopathological and genetic characteristics of primary tumors; and moreover, the obtained tumor tissue are cultured in vitro, which is beneficial to tumor typing and clinical practice; the addition of PD 98059 and artificial matrix glue can greatly reduce tissue apoptosis, which is beneficial to improving the success rate of transplantation.

Development of a physiologically relevant 3D model system for cancer research and drug development represents quite a challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic tumor 3D microenvironment. The system has several unique advantages over other alternatives which include cell-matrix interaction sites provided by collagen derived peptides, a 3D construct suitable for reproducing the solid tumor microenvironment including multicellular tumor spheroids and metabolic gradients. In addition the controllable gel stiffness provides a wide range of mechanical restrictions; and compatibility with imaging based screening due to its transparent properties. In addition the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals with a high take rate. Overall, this unique 3D system could provide a platform to accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo, as well as for screening antineoplastic drugs and assessing the occurrence of drug resistance related to cancer cell stress.

Described herein is the use of phage display antibody engineering technology and synthetic peptide screening to identify SDl and SD2, human single-domain antibodies to mesothelin. SDl recognizes a conformational epitope at the C-terminal end (residues 539-588) of human mesothelin close to the cell surface. SD2 binds full-length mesothelin. To investigate SDl as a potential therapeutic agent, a recombinant human Fc (SDl-hFc) fusion protein was generated. The SDl-hFc protein exhibits strong complement-dependent cytotoxicity (CDC), in addition to antibody- dependent cellular cytotoxicity (ADCC), against mesothelin-expressing tumor cells. Furthermore, the SDl-hFc protein causes significant tumor growth inhibition of tumor xenografts in nude mice. SDl and SD2 are the first human single-domain antibodies targeting mesothelin-expressing tumors.

The invention relates to a circulating tumor cell mouse model and a construction method and application thereof. The method includes the following steps of 1, subcutaneous transplantation, wherein a primary tumor tissue sample is transplanted into the body of an immunodeficient mouse to construct a primary cancer heterotransplantation model PDX; 2, collection of circulating tumor cells, wherein the circulating tumor cells in peripheral blood in the primary cancer heterotransplantation model obtained in the step 1 are collected; 3, renal sac membrane transplantation, wherein the circulating tumor cells collected in the step 2 are transplanted into the renal sac membrane of the immunodeficient mouse, and then the circulating tumor cell mouse model is successfully constructed. According to the method, the mode of transplantation with two or more times of passages is adopted, the CTCs in the primary cancer heterotransplantation model are transplanted into the body of the immunodeficient mouse through renal sac membrane, and the circulating tumor cell mouse model is obtained; the circulating tumor cell mouse model can be applied to research on the in-vivo metastasis mechanism and proliferation condition of CTCs.

The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vitro and antitumor therapeutic efficacy in human tumor xenografts and could have little or no cross-resistance to either Taxol or Vinblastine. The results demonstrated that compounds disclosed herein possess potent antitumor therapeutic efficacy and are expected to have potential for clinical applications.

Liposomal compositions comprising peptide epoxyketone compounds are described, as well as methods of making and using such liposomal compositions. These liposomal compositions enhance the therapeutic window of peptide epoxyketone compounds by improving in vivo half-life relative to non-liposomal compositions comprising peptide epoxyketone compounds, providing desirable pharmacodynamic profiles, and providing anti-tumor activity in a human tumor xenograft model, greater than or equal to non-liposomal compositions comprising peptide epoxyketone compounds. Further, experiments performed in support of the present invention demonstrated improved tolerability of liposomal compositions comprising peptide epoxyketone compounds.

A method for screening a patient for angioinhibition resistance and treating said patient having a disease susceptible to treatment via an anti-angiogenic agent. The screening method includes an assay for identifying the presence of angioinhibition resistance in patients by collecting patient blood or serum and subjecting it to a Chick Chorioallantoic Membrane (CAM) angiogenesis assay configured for accepting a human tumor wherein the human tumor xenograft includes a vasculature system. The screening method and assay further includes steps that include using the CAM results for identifying the endogenous pro-angiogenic non-peptide hormone concentrations of the blood sample by calculating the vascular activity of the vasculature system of the human tumor xenograft in the presence of anti-angiogenic drugs and inducing in the patient, a state of subclinical hypothyroidism prior to commencing anti-angiogenic treatment.

The invention discloses two new compounds with anti-cancer effects of N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridinyloxy) phenyl]-thiourea and N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridinylthioxo) phenyl]-thiourea, and salt thereof. The invention further discloses preparation methods of the two new compounds and a pharmaceutical composition containing the compounds. Experimental studies show that the two new compounds can effectively inhibit the activity of Raf and VEGFR protein kinase, more widely inhibit growth of various types of human tumor cell lines and further induce apoptosis of tumor cells. Human tumor heterograft model investigation proves that the two new compounds are effective antineoplastic agents, can sharply inhibit growth of human liver cancer cells, lung cancer cells and intestinal cancer cells in vivo; and the anti-cancer effect of the compounds is much better than that of sorafenib tosylate.

The invention discloses a method for constructing a tumor xenograft model in mice immunized with gastric cancer based on an organ-like method, and an application thereof. The invention relates to a medical tumor animal model, based on an organ-like method. For the first time, the present invention employs a quasi-organ technique, that is, using a microcarrier as substrate. The composite human gastric cancer cell line SGC-7901 / MKN-45 is transplanted subcutaneously into C57BL / 6 mice to establish a tumor model of human gastric cancer with normal immune function. The tumor model constructed by this method has good tumorigenicity, and the tumorigenicity rate is up to 75%. The HE staining and the immunohistochemistry of the transplanted tumor accord with the characteristics of human gastric cancer. Compared with the existing immunodeficient mice transplanted tumor model, the model can better study and further clarify the mechanism of tumor occurrence and development in the normal immune system, and also provides a more valuable new animal model for the research and development of anticancer drugs. The invention is applied to the tumor model field.

The invention discloses an aporphine type alkaloid and a preparation method thereof. The compound is 8-acetamido-isocorydine, which is prepared through the nucleophilic substitution reactions between 8-amino-isocorydine, and the chemical structure formula of the compound is represented in the description. Through a Kunming white mouse tumor xenograft model, the results show that the provided alkaloid has a strong effect on inhibiting the tumor growth in body and has a good antitumor activity.

The invention discloses an in-vitro tissue preserving fluid as well as a preserving method and application thereof. The in-vitro tissue preserving fluid includes a penicillin-streptomycin solution, fetal calf serum and an improved L-15 culture medium. The obtained in-vitro tissue preserving fluid can provide nutrition for tumor tissues and has an antibacterial effect, the activity of the tumor tissues can be improved, the modeling success rate of clinical patient-derived tumor xenograft is further improved, in addition, tumor tissue samples can be preserved, a sample database can be established, secondary experiment needs are facilitated, and repeated material taking is reduced.

A tumor cell xenograft model in zebrafish, and methods of constructing and using the same. Primary cells dissociated from the tumor tissue of a patient are transplanted into zebrafish, so as to obtain a patient-derived tumor xenograft model. The tumor xenograft model retains the pathological features of human gastric cancer tissues in clinic, has higher clinical relevance, and can be used in the systematic research into the mechanisms underlying the proliferation, metastasis, spread and drug resistance of tumors, and to screen effective drugs for tumor treatments.

Liposomal compositions comprising peptide epoxyketone compounds are described, as well as methods of making and using such liposomal compositions. These liposomal compositions enhance the therapeutic window of peptide epoxyketone compounds by improving in vivo half-life relative to non-liposomal compositions comprising peptide epoxyketone compounds, providing desirable pharmacodynamic profiles, and providing anti-tumor activity in a human tumor xenograft model, greater than or equal to non-liposomal compositions comprising peptide epoxyketone compounds. Further, experiments performed in support of the present invention demonstrated improved tolerability of liposomal compositions comprising peptide epoxyketone compounds.

The present invention provides jervine or its pharmaceutically acceptable salt thereof as an active ingredient of antitumor drugs. This invention proves jervine strongly inhibits the hedgehog signal pathway and effectively inhibits the tumor growth using three human tumor xenograft models including lung cancer, pancreatic cancer and basal cell carcinoma in nude mice. Jervine has the potential to be a new antitumor agent.

The invention discloses a preparation method and application of transgenic zebra fish capable of specifically eliminating T cells. The preparation method comprises the following steps: introducing recombinant plasmids pTol2-lck-NTR-mVenus and Tol2 transposase mRNA into a wild zebra fish embryo together, and culturing to obtain the stably inherited transgenic zebra fish strain, wherein the stably inherited transgenic zebra fish line is a transgenic zebra fish capable of specifically eliminating T cells, and the recombinant plasmid pTol2-lck-NTR-mVenus carries a zebra fish lck gene promoter sequence and an escherichia coli NTR gene sequence. By utilizing the method, the transgenic zebrafish which specifically expresses the NTR gene in the T cell and can be stably inherited can be effectivelyprepared, in addition, under the action of metronidazole, few T cells of the transgenic zebra fish can be specifically removed, so that the transgenic zebra fish has immunologic function defects, andfurthermore, the transgenic zebra fish can provide an animal model for living body research on immune cell development, organ transplantation, tumor xenograft and related drug screening.

The present invention discloses a construction method of a human-derived tumor xenograft model. The construction method of the human-derived tumor xenograft model comprises the following steps: (1) taking fresh tumor tissues from clinical patients and storing the fresh tumor tissues in a preservation solution; (2) selecting immunodeficient mice for anesthesia; and placing the mice on right side lying positions and cutting skin on the back to peritoneum to expose the kidneys after disinfection; (3) cutting the tumor tissues in the preservation solution; (4) implanting the cut tumor tissues intokidney capsules of the mice, sending the kidneys back into the mice after successful inoculation, and suturing the wound; and (5) warming and recovering the mice and sending the mice back to cage boxes after the mice are awake. The construction method can promote formation of tumor microvessels. Compared with subcutaneous inoculation, tumor growth time is shorter, tumor formation is faster, tumorspecific growth rate is higher, the obtained tumor tissues are larger, modeling success rate of clinical patient-derived tumor xenograft is improved, the human-derived tumor xenograft model can be used to conduct sensitivity experiments on tumor chemotherapy drugs and in-vivo drug efficacy screening can be done in the shortest time.

The invention belongs to the technical field of chemical medicines, in particular to an anti-cancer drug medicine compound and the synthetic method. The invention relates to an anti-cancer medicine obtained by synthesizing a plurality of chemical raw materials in four steps. The chemical name is N-[4-chlorin-3-(trifluoromethyl) phenyl]-{[4-(N-methyl- carbamyl) (4-pyrimidine sulfur) phenyl] amido}-carboxamide, which is shown in the chemical structural formula. The product can effectively restrain the activity of Raf and VEGFR protein kinase, extensively control the growth of varied tumor cells, and further induce the apoptosis of tumor cells. In the study of tumor heterogeneity transplant model, the product has the huge potential of being developed into a new anti-liver cancer medicine.

The invention reasonably designs and prepares a polycarbonate polymer, namely, PMPC-Dns, modified through 2,4-dinitrobenzene sulfonyl so as to detect selenocysteine in living bodies. The compound can wrap fluorescent medicine doxorubicin (DOX) and selectively respond to Sec and a selenol compound without being interfered with by biological mercaptan, amine and alcohol. Formation of micelle, responses of Sec, cytotoxicity of probes and medicine release of the Sec responses are researched. The PMPC-Dns probes can be applied to imaging of endogenous Sec in cervical cancer tissue and hela cells under the physiological conditions, and the PMPC-Dns probes can conduct imaging and release medicine wrapped in the probes at the same time. The work opens up a road for understanding the effects of Sec in physiology and pathology systems and tumor xenograft model systems, and a method is provided for controlled releases of hydrophobicity molecules in target molecules in the biomedicine application.

The invention provides a construction method of a double patient-derived tumor xenograft model, and belongs to the technical field of biology. The construction method comprises the steps of S1, obtaining mononuclear cells, S2, preparing CD34+HSC cell sap of 5 * 10<5> cells / mL, S3, constructing an NSG mouse immune model, and S4, obtaining the double patient-derived tumor xenograft model. Accordingto the construction method of the double patient-derived tumor xenograft model, hCD34+ umbilical cord blood hematopoietic stem cells are adopted as an immune reconstruction blood source, the GvHD reaction is small, and the animal survival time is long; and for the standard for screening PDTX samples, the method has the advantages of being high in growth speed and uniform in growth size, and the characteristics of being basically consistent with clinical tumor histological characteristics are achieved.

NEO-201 is a humanized IgG1 monoclonal antibody (mAb) that is highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, breast,and uterine cancers, but the overwhelming majority of normal tissues are not recognized by this antibody. Functional assays revealed that NEO-201 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in combination with human peripheral blood mononuclear cells (PBMC) as an effector cell source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing mice revealed that NEO-201 preferentially accumulates in the tumor but not organ tissue. A single-dose toxicity study in non-human primates demonstrated safety and tolerability of NEO-201, as a transient decrease in circulating neutrophils was the only related adverse effect observed.

The invention belongs to the technical field of medical biology and particularly relates to a constructing method and application of a zebra fish NK / TCL tumor model. Through research, the invention successfully constructs an NK / TCL human tumor xenotransplantation model by taking zebra fish as a mode organism for the first time. The construction method has the advantages of simple and feasible experiment operation, short experiment period, extremely low consumption of tumor cells and high repeatability, and can be widely applied to the fields of molecular biology study, targeted drug screeningand the like.

The invention belongs to the field of medicines and discloses a novel application of Smurf1, in particular to a novel application of a Smurf1 gene, an expression product and a derivative or an inhibitor thereof in chemotherapy of colorectal cancer. The influence of high and low level of the Smurf1 gene and the expression product on chemotherapeutic drug sensitivity of colorectal cancer cells is detected through cell, tumor-bearing mice and a PDX model, a result shows that low-expression colorectal cancers of Smurf1 have higher sensitivity to chemotherapeutic drugs. Therefore, the invention provides an application of the Smurf1 gene as well as the expression product and the derivative thereof in preparation of a marker showing sensitivity of the tumor cells to the chemotherapeutic drugs. The invention also provides an application of the Smurf1 inhibitor in preparation of a sensitizer of the tumor cells to the chemotherapeutic drugs.

The invention provides a tumor cell heterogeneic transplantation zebrafish model, a construction method and application thereof. By implanting primary cells separated from a tumor tissue of a patientinto a zebrafish, the tumor heterogeneic transplantation model derived from the patient is obtained. According to the established tumor heterogeneic transplantation model, pathological characteristicsof human gastric cancer tissue in clinic are preserved, higher clinical correlation is achieved, the established tumor heterogeneic transplantation model can be used for systematically studying the mechanism of tumor proliferation, metastasis, diffusion and drug resistance, and tumor therapeutic drugs are effectively screened.

The invention discloses an alpha-helical polypeptide and application thereof. The amino acid sequence structure of the alpha-helical polypeptide is shown as the specifications. The invention further discloses the application of the alpha-helical polypeptide in preparing active medicine capable of inhibiting the growth of tumor stem cells. MDM2 / MDMX dual inhibitor polypeptide PDI sequences is adopted, with a formation method of alpha-helix by chiral induction and by experiments of fluorescence polarization detection, an immunoblotting analysis, a gene chip analysis, human-oriented tumor heterograft model and the like, it is proved that PhR can simulate the interaction of p53-MDM2 / MDMX through cell membrane penetration property and good binding affinity of the PhR and can reactivate an apoptosis pathway of the p53 and remove malignant CSC cells. The PhR is an efficient dual inhibitor active against both the MDM2 and the MDMX, can conduct chiral adjustment and control on molecular properties through polypeptide side chains, and inhibit the growth of tumor stem cells.

Inventors have generated two human anti-cath-D scFv fragments cloned in the human IgG1λ format (F1 and E2) that efficiently bind to human and mouse cath-D, even at the acidic pH of the TNBC microenvironment. F1 and E2 accumulated in TNBC MDAMB-231 tumor xenografts, inhibited tumor growth and improved mice survival without apparent toxicity. Using this xenograft model, they found that the Fc function of F1 was essential for maximal tumor inhibition. Inventors have shown that the anti-cath-D antibody F1 treatment prevented the recruitment of tumor-associated macrophages and myeloid-derived suppressor cells within the tumor, a specific effect associated with a less immunosuppressive tumor microenvironment. Moreover F1 inhibited tumor growth of TNBC patient-derived xenografts (PDXs). This preclinical proof-of-concept study validates the feasibility and efficacy of an immunomodulatory antibody-based strategy against cath-D to treat patients with TNBC. Accordingly, the present invention relates to an anti-cath-D antibody which inhibits the tumor recruitment of immunosuppressive tumor-associated macrophages M2 and myeloid-derived suppressor cells for use in the treatment of cancer.

An method of determining whether a gene of interest is necessary for a tumor cell to maintain its tumorigenicity is disclosed. The method is useful for validation of cancer therapeutic targets in vivo, using shRNAs and tumor xenografts. The inducible shRNA method operates an in vivo RNAi competition assay.

The present invention rationally designs and prepares a new 2,4-dinitrobenzenesulfonyl modified polycarbonate polymer-PMPC-Dns to detect selenocysteine ​​in a living body. The compound can encapsulate the fluorescent drug doxorubicin (DOX) and selectively respond to Sec and selenol compounds without interference from biothiols, amines, and alcohols. We investigated micelle formation, Sec-response, probe cytotoxicity, and Sec-responsive drug release. PMPC‑Dns micellar probes can be applied to imaging endogenous Sec in living cervical cancer tissues and HeLa cells under physiological conditions, and PMPC‑Dns micellar probes can simultaneously image and release drugs encapsulated in them. This work opens a way to understand the role of Sec in physiological, pathological systems, and tumor xenograft model systems, and also provides a method for the controlled release of hydrophobic molecules among target molecules for biomedical applications.

The invention discloses a pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer and application thereof, the pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer is one of the following chemical structural formulas: R1 and R2 are selected from one of hydrogen, methyl and methoxyl, and R3 is selected from one of hydrogen, methyl and methoxyl. The pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer provided by the invention has the following advantages: the phototoxicity to normal tissues and cells is low, and the photosensitizer has very excellent tumor cell targeting ability; the fluorescent probe gathers in a physiological environment, but does not have the problem of fluorescence quenching, and the active oxygen generation ability is enhanced; according to the present invention, with the application of the nano-material, the prepared nano-material has the deep tissue penetration ability under the excitation of near-infrared light, and has the good photo-thermal and photodynamic synergistic treatment effect on the human-derived tumor xenograft (PDX) model and the bacterial infection, such that the prepared nano-material has the good photo-thermal and photodynamic synergistic treatment effect on the human-derived tumor xenograft (PDX) model and the bacterial infection.