Approximately 80% of all malignant brain tumors are gliomas, which are primary brain tumors. The most prevalent subtype of glioma, glioblastoma multiforme (GBM), is also the most deadly. Chemotherapy, immunotherapy, surgery, and conventional pharmacotherapy are currently available therapeutic options for GBM; unfortunately, these approaches only prolong the patient’s life by 5 years at most. Despite numerous intensive therapeutic options, GBM is considered incurable. Accumulating preclinical data indicate that overt antitumoral effects can be induced by pharmacologically activating endocannabinoid receptors on glioma cells by modifying important intracellular signaling cascades. The complex mechanism underlying the endocannabinoid receptor-evoked antitumoral activity in experimental models of glioma may inhibit the ability of cancer cells to invade, proliferate, and exhibit stem cell-like characteristics, along with altering other aspects of the complex tumor microenvironment. The exact biological function of the endocannabinoid system in the development and spread of gliomas, however, is remains unclear and appears to rely heavily on context. Previous studies have revealed that endocannabinoid receptors are present in the tumor microenvironment, suggesting that these receptors could be novel targets for the treatment of GBM. Additionally, endocannabinoids have demonstrated anticancer effects through signaling pathways linked to the classic features of cancer. Thus, the pharmacology of endocannabinoids in the glioblastoma microenvironment is the main topic of this review, which may promote the development of future GBM therapies.

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO-positive acute myeloid cell transplantation.Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO-positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022.Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3-12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II-IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III-IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2-3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8(+) T lymphocyte count increased gradually, while the CD4(+) T lymphocyte count did not change significantly.Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO-positive post-transplant relapse, and most patients can achieve long-term survival with this regimen.

Objectives: To explore the efficacy and safety of high-dose cytarabine combined with PD-1 inhibitors and demethylation drugs in relapsed and refractory acute myeloid leukemia (R/R-AML) in Chinaand to investigatethe dynamic changes of Treg cells, CD4+ T cells, CD8+ T cells, TNF-α, INF-γ, and IL-6 in the prognosis of the disease. Methods:A total of three patients with R/R-AML treated in our department were included in the study. None of the three patients had received at least two courses of standard chemotherapy before and did not obtain remission.The cellular immunity and cytokines were evaluated on the 1st, 8th, 15th, and 22nd day of the treatment.In the study,eligible R/ R-AML patients (n=3) were treated with azacytidine 75mg/m2 d1-d7, cytarabine 2g/m2 d1-d5, PD-1 inhibitor 200mg d1、d14.The efficacy were evaluated by CR, PR, ORR, PFS, OS, and ED. The safety were evaluated by hematological and non-hematological toxicity. Results: Among the three patients, one patient achieved CR, and one patient achieved PR. The patient who achieved CR successfully underwent allo-HSCT. One patient did not achieve remission and died of disease progression. Three patients were well tolerated to chemotherapy, and non-hematological toxicity was mainly respiratory tract infection, gastrointestinal reaction, and liver function damage.At present, no immune-related tissue injury was observed. Grade III-IV hematologic toxicity was the major adverse reaction, and the longest duration of agranulocytosis was 22 days.The proportion of Treg cells decreased, and the proportion of CD4+ T cells and CD8+ T lymphocytes increased in 2 patients after treatment. One patient received CR and underwent allo-HSCT. One patient showed an increase in the proportion of Treg cells, but there was no significant dynamic change in CD4+ T lymphocytes and CD8+ T lymphocytes. INF-γ increased in 1 patient. Dynamic changes in IL-10, IL-6, and TNF-α were not observed. Conclusions: PD-1 inhibitor combined with high dose cytarabine based chemotherapy may be a salvage treatment for R/R-AML. The dynamic changes of CD4+ T lymphocyte, CD8+ T lymphocyte, Treg cell, and INF-α may reflect the therapeutic effect in advance. Disclosures No relevant conflicts of interest to declare.

The aim of this study was to analyze the error variation in the applicator placement during the first and second radiotherapy session for cervical cancer. We recruited 22 patients with cervical cancer treated with radiotherapy. According to the image output in the first and second CT-Sim inspection, we conducted comparative analysis of image fusion to accurately measure the errors in applicator position in the horizontal (X-), longitudinal (Y-) and vertical (Z)-axes. The calibration processing was implemented in accordance with the data error measured and the location parameters, such as the angle and depth of the applicator. Electronic portal imaging technology (EPID) was used to calibrate posture change amplitude for the extracorporeal irradiation of patients, and dynamic measurement with applicator position was used to describe the error of the parameters. Finally, the data from two measurements in CT-Sim, digital reconstruction radiography (DRR) and EPID were compared. After calibration, the mean value of error of the applicator were significantly smaller. Image registration planning for error parameter calibration of applicator position can effectively reduce the applied horizontal spatial position error in radiotherapy treatment, and improve the accuracy and effectiveness during treatment.