Latest ArticlesTo 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.
Control of cell cycle progression plays a significant role in tumor development. The cyclin-dependent kinase (CDK) family governs cell cycle progression, and the activations of CDK4 and CDK6 allow cells to transit from G1 phase to S phase to start mitosis. Overactivation of CDK4/6 is closely related to tumor progression, thus CDK4/6 can be used as a potential target of oncotherapy. CDK4/6 inhibitors can not only arrest the tumor cells at G1 phase to prevent tumor overgrowth, but also affect the tumor microenvironment and enhance immune activity. Trilaciclib is a small-molecule CDK4/6 inhibitor, which is highly efficient, selective and reversible. Trilaciclib administrated before chemotherapy can temporarily block the hematopoietic stem cells and progenitor cells in bone marrow at G1 phase to reduce the cytotoxic damage caused by chemotherapy, thus protecting bone marrow and the immune system. Trilaciclib was first approved by FDA in the United States in February 2021 for extensive stage small cell lung cancer (ES-SCLC) before platinum/etoposide or topotecan chemotherapy to reduce the incidences of myelosuppression in adult patients. In July 2022, National Medical Products Administration (NMPA) also approved the administration of trilaciclib in patients with ES-SCLC who had not previously received systemic chemotherapy. In addition, the positive effects of trilaciclib on overall survival (OS) were observed in patients with triple-negative breast cancer (TNBC) treated with chemotherapy. Other clinical studies related to trilaciclib were still ongoing. This review summarizes the anti-tumor mechanisms of trilaciclib and the relative preclinical and clinical studies, aiming to provide further reference for clinical application and future research.
Lung cancer is one of the most common cancers worldwide. As reported in 2020, there were approximately 2.2 million new cases of lung cancer worldwide, accounting for 11.4% of newly diagnosed malignant tumors. Additionally, there were 1.8 million deaths resulting from lung cancer in 2020, representing about 18% of all cancer-related deaths globally. Lung cancer remains the leading cause of cancer-associated morbidity and mortality in China. Despite the increasing popularity of immunotherapy and targeted therapy, chemotherapy remains one of the most dominant treatment modalities for lung cancer (particularly for small-cell lung cancer). However, chemotherapeutic drugs in clinical practice lack specificity and kill normal cells while killing tumor cells, especially cells that are relatively active in proliferation or metabolism. Chemotherapy-induced myelosuppression (CIM) is the most common dose-limiting and potentially fatal complication in cancer therapy and a key factor affecting the course and dose of chemotherapy, and nearly 90% of chemotherapeutic drugs may be associated with myelosuppression. Myelosuppression is the biggest obstacle to cancer chemotherapy. Myelosuppression seriously affects the life quality of cancer patients, reduces patient compliance, delays treatment, and even threatens the lives of patients, which we should pay attention to in clinical practice. At present, the main treatment regimens for bone marrow suppression are those follows, such as drugs promoting neutrophils, red blood cells, thrombopoietic drugs and blood transfusion. As the world's first approved CDK4/6 inhibitor with full myeloprotection, the use of trilaciclib before chemotherapy is effective in reducing the incidences of CIM. This review aims to summarize the relevant research progress in recent years from the mechanism of bone marrow suppression, related treatment measures of bone marrow suppression after chemotherapy for lung cancer, and provides further ideas and clinical basis for clinical application, monitoring and management of CIM.
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.
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 excavate and analyze signals of immune checkpoint inhibitors (ICIS) related adverse events of acute kidney injury through data mining methods based on the big data of FAERS, and to provide a reference for the safe clinical use of ICIS drugs.
Case reports were collected from April 2011 to March 2021 with immune checkpoint inhibitors (ICIS) as the first suspected drug and acute kidney injury (AKI) as the preferred term. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) were used to study the relationship between ICIS and acute kidney injury. The incidence time, mortality and hospitalization rate of acute kidney injury were further studied.
1 528 cases of acute kidney injury were included. The proportion of people aged over 65 was the highest, reaching 65.38%. Males were about twice as large as females (64.66% vs 31.87%). Patients with chest cancer reported the most acute kidney injury (32.98%), followed by skin cancer (26.11%) and urogenital cancer (18.72%). Acute kidney injury was most reported in nivolumab monotherapy (54.78%). Cimepritimab had the strongest signal in immune checkpoint inhibitor monotherapy, which may be related to the patient population. The median onset time of acute kidney injury was 49 days in immune checkpoint inhibitor monotherapy regimens (interquartile range [IQR] 1~1 720).
The mechanism of action of immune checkpoint inhibitors differs from traditional cytotoxic and targeted drugs. The proper balance between activation and inhibition of immune molecule function is the key to a strong immune response, and sufficient attention should be given to its efficacy and safety.
Chemotherapy still plays pivotal roles in the comprehensive treatment of tumors. Chemotherapy-induced myelosuppression (CIM) is the most common adverse event of chemotherapy, which has posed serious impacts on the anti-tumor efficacy of chemotherapy and the quality of patients' lives, and also resulted in increased treatment burden of patients and more medical resources at the same time. Trilaciclib is a highly potent, selective, reversible cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Clinical data showed that trilaciclib could temporarily arrest bone marrow cells in G1 phase to reduce the incidences of CIM and the proportion of chemotherapy dose adjustment and delay, increasing the tolerance of chemotherapy and reducing the economic burden. This article systematically elaborates on the CIM-caused hazards, clinical prevention, and current status of treatment of CIM, as well as the roles of trilaciclib in the prevention of CIM and its economic value, aiming to provide scientific reference for patients to select reasonable prevention and therapeutic treatment regimens of CIM.
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.
Chemotherapy-induced myelosupression (CIM) is the most common toxicity of chemotherapy drugs. Usually, more than 80% of chemotherapy drugs lead to myelosuppression, and CIM is usually characterized by neutropenia, thrombocytopenia and erythrocytopenia. Dose reduction and delayed administration of chemotherapy drugs by CIM seriously reduce the life quality of patients and the overall anti-tumor effect of chemotherapy. As the first drug approved for bone marrow protection, trilaciclib is a highly effective, selective and reversible cyclin-dependent kinase (CDK) 4/6 inhibitor, which can temporarily block cell cycle of hematopoietic stem/progenitor cells and immune cells in G1 phase, so as to reduce the damage caused by chemotherapy and protect bone marrow protection. In April 2021, trilaciclib was approved by FDA as a myelo preservation in the United States. In July 2022, trilaciclib was approved by the National Medical Products Administration for marketing in China, and the first indication of trilaciclib in China was for patients with extensive stage small-cell lung cancer. In this review, the mechanisms of action, pharmacokinetics, drug interaction mechanism, clinical evaluation, safety and other related research progress of trilaciclib are systematically reviewed, aiming to provide further reference and basis for clinical practice.
Lupus nephritis (LN) is a common and serious organ damage of systemic lupus erythematosus (SLE), and is one of the main causes of death in SLE patients. Conventional medication has limited efficacy and many adverse reactions. With the continuous deepening of research on the molecular mechanism of LN, therapeutic drugs and methods targeting specific pathogenic targets are constantly emerging, attracting great attention from clinical doctors and immunologists. Based on the pathogenesis of LN, this article reviews the clinical application and progress in related clinical research of targeted therapy drugs for LN, in order to provide a basis for clinicians to more accurately diagnose and treat SLE and LN, reduce LN kidney damage, and maintain long-term remission of the disease.
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