HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To establish a mouse model of lung adenocarcinoma brain metastasis with human luc+-PC?9 cells stably expressing luciferase and to compare the evaluation values of bioluminescence imaging and18 F?FDG ( 18 F?flu?orodeoxyglucose) SPECT/CT in these models. Methods Suspension of luc+?PC?9 cells was injected into the left ventri?cle of BALB/c nude mice to establish a mouse model of brain metastasis from lung cancer. Bioluminescence imaging and18 F?FDG SPECT/CT were used to evaluate the metastasis of tumors as compared with HE?staining pathology as a golden standard. Results The success rate of brain metastases was 85% through injecting luc+?PC?9 cells into the left ventricle. The number of tumor cells was positively related to the intensity of light, with a linear correlation (R2 =0. 96). Fluores?cence was observed in the brain, spine and femur by bioluminescence imaging, and the metastases were confirmed by H&E pathological examination. 18 F?FDG SPECT/CT observed abnormal density collective foci in the spine or femur but not in the brain. Conclusions Injection of tumor cell suspension into the mouse left ventricle is a good method to establish a brain metastasis of lung cancer. Bioluminescence has a higher sensitivity and specificity in detecting brain metastasis and bone metastasis, with advantages of real?time, dynamical and non?invasive detection of tumor metastasis growth. 18 F?FDG SPECT/CT does not have superiority in detection of brain metastases but is suitable for detecting bone metastasis.