Latest ArticlesSmall cell lung cancer (SCLC) is characterized by a high degree of malignancy, with poor prognosis and high-growth fraction. About two-thirds of patients have developed distant metastasis at the time of diagnosis with rapid disease progression and high recurrence rates. Currently, topotecan-based chemotherapy remains the standard second-line treatment of SCLC with unfavorable disease remission, and less than one-fourth of patients have benefited from its efficacy. Chemotherapy-induced myelosuppression (CIM) is the most common toxicity in cancer chemotherapy, and severe CIM will reduce the dose intensity and anti-tumor efficacy of chemotherapy. Trilaciclib is a short-acting intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor administered prior to chemotherapy to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy, which has been approved by NMPA for prevention of CIM in SCLC in July 2022. Previous results showed that trilaciclib yielded favorable bone marrow protection during chemotherapy, but its anti-tumor effects in second-line treatment of SCLC have not been determined. This paper reports a case of a patient with advanced small-cell lung cancer with multiple metastases who obtained progression-free survival time of more than 1 year using trilaciclib combined with topotecan as second-line treatment.
Small-cell lung cancer (SCLC) is one of the most malignant subtypes of lung cancer with rapid tumor progression and a poor prognosis, and also one of the malignancies most difficult to cure in clinical practice. Currently, platinum-based chemotherapy remains the first-line standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Full-dose chemotherapy is warranted for the best efficacy, and the effective rate of first-line treatment is 60%~80% (full-dose), while chemotherapy-induced myelosuppression (CIM) is the main reason hindering adequate chemotherapy. Granulocyte colony-stimulating factor (G-CSF) is commonly used to deal with neutropenia in clinical practice, while this traditional treatment may even cause the depletion of bone marrow hematopoietic reserve function and damage to the normal bone marrow hematopoietic function of patients. Currently, trilaciclib has been approved for the prevention of myelosuppression in ES-SCLC, which can protect hematopoietic stem cells/progenitor cells (HSPCs) fundamentally. In this paper, we report a case of a patient with ES-SCLC treated in our department receiving bone marrow protection with trilaciclib combined with chemotherapy, aiming to provide reference and basis for further research.
Immunotherapy combined with chemotherapy has been established as the standard first-line treatment in advanced esophageal cancer (EC). Myelosuppression is the most common side effects of chemotherapy, and severe myelosuppression often leads to prolonged cycles of chemotherapy and reduced doses of chemotherapy, thereby reducing the intensity and potential anti-tumor efficacy of chemotherapy. At present, granulocyte-stimulating factor (G-CSF) is widely used to stimulate the differentiation of bone marrow hematopoietic progenitor cells to treat chemotherapy-induced myelosuppression (CIM). Trilaciclib is a short-acting and reversible CDK4/6 inhibitor, which can provide systemic protection of bone marrow hematopoiesis, and was approved by NMPA in July 2022 for the prophylactic treatment of myelosuppression in extensive-stage small cell lung cancer (ES-SCLC). However, trilaciclib has not been widely used in clinical practice. Therefore, this paper reports a case of one patient with advanced EC who was treated by trilaciclib to prevent CIM in our department, aiming to provide further reference and basis for further investigation.
The investigation shows that malignant tumor is one of the major diseases threatening human health and life safety. In recent years, the cancer prevalence and mortality rate remain high, making anti-tumor drug research a hot field of drug research and development. For a better understanding of the industry development situation and to grasp the latest development of antitumor drug patent applications, Derwent Innovations Index was used for mining and analysis on the patent document against cancer drugs. At the same time, we complemented public patent data in recent years, as well as the overall intelligence information updates, statistics, analysis, and visualization, in order to provide information reference and decision support for the research and development of anti-tumor drugs and medicine.
Molecular targeted therapy has become a research hotspot in the field of cancer therapy in recent years. Regorafenib belongs to the multi-target tyrosine kinase inhibitor class of antitumor drug developed by Bayer company, which was approved by NMPA in March 2017. This article introduces the status of regorafenib-related Chinese patent applications and focuses on combing and analyzing the development context of patent technology, in order to provide reference for the drug R&D and patent portfolio for relevant domestic pharmaceutical companies.
Non-alcoholic fatty liver disease (NAFLD) is a common chronic metabolic disease characterized by the accumulation of fat in the liver. The onset and progression of NAFLD are associated with a variety of metabolic abnormalities, including obesity, diabetes mellitus, and hyperlipidemia. Due to its high prevalence and risk worldwide, NAFLD has become an important issue in public health. However, to date, treatments for NAFLD are very limited, with no relevant drugs approved for marketing in Europe, America, or China and clinical trials of new drugs have gained no progress in recent years. This paper reviews the therapeutic targets, clinical research progress of new drugs, and new treatment strategies for NAFLD, in addition to summarizing the reasons for the high failure rate of NASH clinical trials and proposing corresponding solutions, aiming at providing ideas and reference for new drug development.
Tumor therapy has always been the focus of study. Due to the variability of tumor cells, the complexity of the tumor microenvironment and other factors, the problems such as multidrug resistance of tumors, reduced drug delivery efficiency are obtained. In recent years, increasing attention has been paid to biomimetic vectors, in which cancer cell membrane (CCM) is a new type of nano-carrier with the characteristics of homologous targeting, immune escape and penetrating biological barrier. Using CCM as a bionic carrier to coat different types of nanoparticles (NPs) can achieve effective tumor targeting and advantages in tumor therapy. This review introduces the biomimetic vector of CCM, briefly describes the preparation process of NPs coated with CCM, summarizes the research of CCM in tumor drug delivery and tumor vaccine, and discusses the future development prospects of CCM.
To analyze the pattern, characteristics and causes of protocol violation in anti-tumor drug clinical trials from the perspective of ethical review. The number and categories of violation projects were retrospectively analyzed and compared in different departments and the area of clinical trials (domestic or international). The impact of protocol violation on clinical trials carried out in our hospital from 2018 to 2021 was also analyzed. From 2018 to 2021, 1256 protocol violation cases occurred in clinical trials of anti-tumor drugs carried out in our hospital. The number of continuous protocol violations (318, 25.32%) was the largest, and the number of researchers' failure to cooperate with supervision/audit (6, 0.50%) was the fewest. The difference in the number of protocol violation between internal and surgical, domestic and global clinical trials were both statistically significant (P<0.01). The proportion of protocol violations affecting the safety, rights of subjects and trials results were 5.81%, 4.78% and 5.41%, respectively. Various protocol violations may occur during clinical trials of anti-tumor drugs. In order to improve the quality of clinical trials, it can be effectively avoided by strengthening quality control and conducting targeted training for the research team and subjects.
To study the cytotoxicity effect of NK cells on breast cancer cells in vitro, and the cytotoxicity and possible mechanism of NK cells combined with low concentration lapatinib on breast cancer cells.
CCK-8 method was used to detect the effect of different concentrations of lapatinib on the proliferation of breast cancer cells for 24 h, 48 h and 72 h. LDH Assay Kit was applied to detect cytotoxicity of NK cells and NK cells combined with lapatinib on tumor cells. Changes of HER-2 expression on the surface of MDA-MB-231 and BT549 breast cancer cells before and after treatment with lapatinib and the ligand expression of NK cell activated and inhibitory receptors on breast cancer cell surface were both evaluated by flow cytometry.
The inhibitory effect of lapatinib on the proliferative activity of breast cancer cells was proportional to the time and concentration of action. The inhibitory rate on the proliferation of HER-2 high-expression breast cancer cells was greater than that of HER-2 low-expression breast cancer cells. NK cells had certain cytotoxicity against breast cancer cells, and lapatinib (The final concentration of lapatinib was 0.1 μmol·L-1 in HER-2 high-expression breast cancer cells MDA-MB-453 and BT474 and 3.125 μmol·L-1 in HER-2 low-expression breast cancer cells MDA-MB-231 and BT549) combined with NK cells could significantly improve the killing efficiency of NK cells against breast cancer cells. Lapatinib (3.125 μmol·L-1) could increase the expression level of HER-2 on the surface of HER-2 low-expression breast cancer cells after interacting with HER-2 low-expression breast cancer cells.
Lapatinib improves the killing activity of NK cells against breast cancer cells in vitro, and its synergistic mechanism may be related to the increased expression of HER-2 on the surface of breast cancer cells by lapatinib.
To investigate the in vivo and in vitro antibacterial activity of doxycycline combined with levofloxacin on carbapenem-resistant Klebsiella pneumoniae (CRKP).
Eight clinically isolated CRKP strains were collected in Yichun People's Hospital, and the minimum inhibitory concentration (MIC) of 8 CRKPs was determined using microbroth dilution method in vitro. The antibacterial effect of the two drugs was judged by checkerboard dilution method. The time-sterilization curve was further applied to evaluate the combined bactericidal effect of the two drugs. Crystal violet staining semi-quantitative biofilm method was used to determine the inhibitory effect and elimination effect of the combination of two drugs on biofilm formation. In vivo, a model of acute lung infection of mice was established by nasal instillation of CRKP bacteria, and the mental state of mice was recorded. The bacterial load of lung tissues, the levels of serum inflammatory factor C-reactive protein (CRP), IL-6 and pathological morphological changes were evaluated and analyzed.
The MIC of doxycycline to 8 CRKP strains was 4~256 ug·mL-1, levofloxacin to 8 strains of CRKP MIC of 16~256 ug·mL-1. The checkerboard method showed that doxycycline combined with levofloxacin had an 80% synergistic or additive effect on 8 CRKP strains. The time-sterilization curve showed that after the treatment of doxycycline combined with levofloxacin on CRKP2 and CRKP7 for 24 hours, the number of bacteria decreased by ≥2 lg CFU·mL-1 compared with the initial bacterial number, showing bacteriostatic or bactericidal effects. The results of crystal violet staining showed that the combination of doxycycline and levofloxacin had inhibitory and destructive effects on CRKP biofilms. Animal experiments showed that compared with the model group, the combined group mice had a good mental state, and the loading levels of lung tissue, C-reactive protein (CRP) and IL-6 significantly reduced (P<0.001). The results of HE staining showed that the alveolar structure was clear, the inflammatory cells reduced, and the hyperemia area reduced in the drug administration group compared with the model group, and the differences were statistically significant (P<0.001).
In vitro experiments show that doxycycline combined with levofloxacin has a synergistic antibacterial or bactericidal effect on CRKP, and in vivo experiments show that doxycycline combined with levofloxacin can reduce inflammatory indexes, effectively treat bacterial infections in lung tissue, exerting good antibacterial effect in vivo.
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