Latest ArticlesImmunotherapy 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.
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.
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 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.
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.
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.
Small 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.
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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