1.A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression.
Cheng WANG ; Minghao ZHANG ; Shunyao LI ; Miaomiao GONG ; Ming-Yu LUO ; Mo-Cong ZHANG ; Jing-Hua ZOU ; Ningxiang SHEN ; Lu XU ; Hui-Min LEI ; Ling BI ; Liang ZHU ; Zhengting WANG ; Hong-Zhuan CHEN ; Lu ZHOU ; Ying SHEN
Acta Pharmaceutica Sinica B 2024;14(11):4819-4831
Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8+ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.
2.Investigation on clinical features and prognostic factors in patients with localized primary small bowel stromal tumors
Rong FAN ; Jie ZHONG ; Zhengting WANG ; Lifen YU ; Yu WANG ; Yonghua TANG ; Yanbo ZHU ; Weiguo HU
Chinese Journal of Digestion 2010;30(5):289-292
Objective To retrospectively investigate the clinical features of localized primary small bowel stromal tumors (SBSTs) and the impacting factors for prognosis.Methods The clinical and pathological data of 89 consecutive SBSTs patients,with pathologically confirmed,who underwent complete resection in Ruijin hospital between January 2003 and September 2007 were collected and analyzed.All patients were followed up for assessment of tumor recurrence and metastasis.The impacts of clinical and pathologic factors on rate of disease free survival (DFS) of the patients was evaluated.Results In total of 89 follow-up patients,15 patients were diagnosed with tumor recurrence and 9 of them died.The tumor size,mitotic index and pathological risk stratification were statistically related with DFS (P=0.000,P=0.006,P=0.000,respectively) by using Kaplan-Meier univaritate analysis.Tumor size and mitotic index were proved to be independent prognostic factors for tumor recurrence by multivariate analysis COX regression model.Conclusions Tumor size and mitotic index are related with tumor recurrence,and can be regarded as independent predictive factors of tumor recurrence.
3.Radiologicai appearances of mediastinal ganglioneuromas
Qingling HUANG ; Guangming LU ; Longjiang ZHANG ; Zhongqiu WANG ; Xueman JI ; Zhengting ZHU ; Caiyun YUAN
Chinese Journal of Radiology 2008;42(8):858-861
Objective To analyze the radiolngical findings of mediastinal ganglioneuroma and to improve its diagnostic accuracy. Methods Imaging data of 8 cases of pathologically proven mediastinal ganglioueuroma were restrospectively analyzed. Results These tumors could occur in the anterior mediastinum, middle mediastinum or posterior mediastinum, with a preference for the posterior mediastinum (6/8). No specific clinical symptoms and signs were observed. Well-defined enlargrment of mediastinum with homogeneous density was shown on plain X-Ray. CT scanning was performed in 7 cases, including non-contrast scan alone (n = 3 ), both non-coutrast and contrast-enhanced scans ( n = 4). Round or oval shaped, well circumscribed, homogeneous or slightly heterogeneous, hypadense masses were demonstrated on non-contrast scan. Spotty calification could be found in a few cases. Homogeneous or slightly heterogeneous enhancement was seen following the intravenous injection of contrast material. Large tumors showed a tendency of wedging into the space between adjacent organs and structures, and encasing the nearby large vessels. MR without contrast was performed in 1 case. T1 WI showed isointensity to adjacent muscle, T2WI showed homogeneous hyperintensity. Multi-planar reconstruction provided more information concerning the relationship of the mass lesions with neighboring structures. Conclusion Mediastinal ganglioneuromas have some specific characterstics on imaging studies, which could assist in pre-operative diagnosis and surgical planning.

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