Recent patents on anti-cancer drug discovery最新文献

Introduction: Maintenance therapy aimed to strengthen the first-line chemotherapy and improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created patented prescriptions "Fuzheng jiedu Quyu Method" recipe (FJQR), which was considered as an adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a maintenance treatment in HER-2 negative GC patients.

Methods: We performed the analysis of 129 patients with HER-2 negative GC who entered the maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December 2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they received fluoropyrimidine alone. Capecitabine was orally 1000mg/m², Qd, half an hour after meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR), quality of Life (QOL), TCM syndrome and safety.

Results: The mPFS in the treatment group was significantly prolonged compared with the control group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5 months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively lighter, and the incidence of grade III-IV AEs could be significantly reduced.

Conclusion: FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in HER-2 negative GC, with good efficacy and safety.

Background: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated.

Objective: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells.

Methods: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3β/β-catenin signaling pathway was detected by Western Blot.

Results: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3β(Ser9), β-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells.

Conclusion: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3β/β-catenin signaling pathway.

Background: Terminalia chebula (T. chebula) comprising chebulinic acid as its principle active constituent is used to cure various diseases. T. chebula and chebulinic acid are used as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, antimutagenic, radioprotective, cardioprotective, antiproliferative, antiarthritic, anticaries, and so on.

Objective: The objective of this current study is to give an overview of the recent literature and patents of T. chebula and chebulinic acid including methods of its isolation/extraction and their application in the prevention of various cancers and other diseases.

Methods: Present research and patents highlighting the anti-cancer potential of T. chebula and chebulinic acid have been studied and discussed keeping in view the scientific novelty and impact.

Results: Both T. chebula and chebulinic acid are currently being explored for their anticancer potential in vitro and in vivo. They are either incorporated alone or in combination with other plants or drugs to show their activity and many clinical trials are also going on various potentials of the plant and chebulinic acid. Novel extraction techniques are also explored and patented. Efforts are being made to improve the bioavailability by developing Novel herbal drug delivery systems of the plant extract or chebulinic acid itself.

Conclusion: Anti-cancer potential of T. chebula and chebulinic acid may be well established by promising clinical trials and may open new interventions in various tumors. Clinical trials in conjunction with standard therapies are required to explore and validate the actual potential of T. chebula and chebulinic acid respectively.

Background: Multidrug resistance (MDR) of cancer cells is a major obstacle to efficient cancer chemotherapy. Combination therapy is expected to enhance the anticancer effect and reverse MDR. Numerous patents involve different kinds of nanoparticles for the co-delivery of multiple chemotherapeutics, but the FDA has approved none.

Objective: In this study, oxymatrine (OMT) and glycyrrhizin (GL) were co-loaded into phytosomes as the core of nanocarriers, and the shell was cross-linked with chitosan (CS) and hyaluronic acid (HA) with the capability for the controlled, sequential release and the targeted drug uptake.

Methods: Phospholipid complexes of OMT and GL (OGPs) were prepared by a solvent evaporation technique and could self-assemble in an aqueous solution to form phytosomes. CS and HA were sequentially coated on the surface of OGPs via electrostatic interactions to obtain CS coated OGPs (CS-OGPs) and HA modified CS-OGPs (HA-CS-OGPs), respectively. The particle size and zeta potential were measured to optimize the formulations. In vitro cytotoxicity and cellular uptake experiments on HepG2 cells were performed to evaluate the anticancer activity.

Results: OGPs were obtained with nano-size around 100 nm, and CS and HA coating on phytosomes could change the particle size and surface potential. The drug loading of OMT and GL showed that the nanocarriers could maintain a fixed ratio of 1:1. The in vitro release experiments indicated the release of OMT and GL was pH-dependent and sequential: the release of OMT from CS-OGPs and HA-CS-OGPs was significantly increased at pH 5.0 compared to the release at pH 7.4, while GL exhibited sustained released from CS-OGPs and HA-CS-OGPs at pH 5.0. Furthermore, in vitro cytotoxicity and cellular uptake experiments on HepG2 cells demonstrated that the co-delivery system based on phytosomes had significant synergistic anti-tumor activities, and the effects were enhanced by CS and HA modification.

Conclusion: The delivery of OMT and GL via HA-CS-OGPs might be a promising treatment to reverse MDR in cancer therapy.

Background: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid.

Objective: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using Cannabis to treat cancer.

Methods: The research was carried out in the free and online database Espacenet, using the descriptors "cancer" and "Cannabis or cannabidiol" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study.

Results: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry.

Conclusion: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.

Background: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis.

Objective: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion.

Methods: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting.

Results: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-β II receptor to ligand Activin A.

Conclusion: HCG restrained the Smad signaling pathway by antagonizing TGF-β signaling in GCTB. HCG may serve as a useful patent to treat GCTB.

Background: The aim of two-sample Mendelian randomization (MR) with a large sample size was to explore the causal cholelithiasis impact on acute pancreatitis and pancreatic cancer.

Methods: We performed the two-sample MR analysis with two models. Publicly available summary- level information for cholelithiasis was acquired from the Genome-Wide Summary Association Studies (GWAS) of FinnGen Biobank. The inverse variance weighted (IVW) method was the main method to obtain the MR estimates. Other methods were also used as supplementary methods, including MR-Egger, maximum likelihood, MR-Robust Adjusted Profile Score (MR-RAPS), weighted median, penalised weighted median method, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method.

Results: After the selection of genetic instrumental variables (IVs), 11 single nucleotide polymorphisms (SNPs) (Model 1) and 22 SNPs (Model 2) were used to explore the effect of cholelithiasis on acute pancreatitis, and 10 SNPs (Model 1) and 24 SNPs (Model 2) on pancreatic cancer. The findings obtained by the fixed-effect IVW method with both Model 1 and Model 2 showed that genetically predicted cholelithiasis was significantly related to the elevated acute pancreatitis risk (Model 1: OR: 1.001, 95% CI: 1.000-1.002, p <0.001; Model 2: OR: 1.001, 95% CI: 1.000-1.002, p <0.001). Moreover, cholelithiasis would also raise the pancreatic cancer risk (Model 1: OR: 1.676, 95% CI: 1.228-2.288, p = 0.001; Model 2: OR: 1.432, 95% CI: 1.116-1.839, p = 0.005).

Conclusion: Genetically predicted cholelithiasis was significantly related to the elevated risk of acute pancreatitis and pancreatic cancer. More attention should be paid to patients with cholelithiasis for the primary prevention of pancreatic-related diseases.