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期刊论文 7

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复发性头颈部肿瘤 1

恶性黑色素瘤 1

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转移性肝癌 1

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Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uvealmelanoma

《医学前沿（英文）》 2022年 第16卷 第5期   页码 784-798 doi: 10.1007/s11684-021-0911-0

摘要： More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gαq/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gαq/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gαq/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.

关键词： uveal melanoma     mutant GNAQ/11     palmitoylation     BCL2     combination target therapy    

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associated with improved survival and increased response to immune checkpoint blockade in metastatic uvealmelanoma: results from a retrospective multicenter trial

《医学前沿（英文）》   页码 878-888 doi: 10.1007/s11684-023-0993-y

摘要： Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma     liver-directed therapy     immune checkpoint blockade     SIRT     anti-PD-1     anti-CTLA-4    

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NETO2 promotes melanoma progression via activation of the Ca/CaMKII signaling pathway

《医学前沿（英文）》 2023年 第17卷 第2期   页码 263-274 doi: 10.1007/s11684-022-0935-0

摘要： Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

关键词： melanoma     neuropilin and tolloid-like 2     Ca2+/CaMKII signaling pathway    

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Celecoxib in combination with retinoid CD437 inhibits melanoma A375 cell

Jianwen REN, Zhenhui PENG, Birong GUO, Min PAN

《医学前沿（英文）》 2009年 第3卷 第1期   页码 108-112 doi: 10.1007/s11684-009-0015-8

摘要： This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437) and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant melanoma A375 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G /M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2±2.51)%, apoptosis rate: (35.91±1.80)%]. CD437 at 10 μmol/L inhibited proliferation, induced apoptosis and G /G cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6±2.38)%, apoptosis rate: (28.03±0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drug alone [proliferation inhibiting rate: (68.92±1.72)%, apoptosis rate: (42.09±1.05)%, both <0.05] and could decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G /M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G /G cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of human melanoma.

关键词： celecoxib     CD437     melanoma A375 cell     apoptosis     cycle arrest    

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Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its

HUANG Hongying, LIU Guangchao, QI Yijun, DU Yaowu, CHEN Jugao, MA Yuanfang

《医学前沿（英文）》 2008年 第2卷 第2期   页码 186-190 doi: 10.1007/s11684-008-0035-9

摘要： The aim of this study is to explore inhibitory activity of Bifidobacterium adolescent combined with cisplatin on the growth of melanoma (B16) in mice and the underlying mechanism. C57 mice were inoculated with B16 cancer cells to construct mouse model of melanoma and treated with bifidobacterium adolescent combined with cisplatin. Ratios of inhibitory activity on the growth of melanoma (B16) were calculated. Pathology changes of the tumor were observed by HE staining. B16 cell cycles were examined on a flow cytometer. Lymphocyte proliferation was measured with MTT assay and the T-cell subset was measured by double marked fluorescence. When bifidobacterium of 10 cfu/L was injected, the ratio of inhibitory activity on the growth of melanoma (B16) reached 54%, which was similar to that of cisplatin group. The ratio of inhibitory activity reached 74.45% when the mice were treated by bifidobacterium combined with cisplatin. HE staining shows that bifidobacterium inhibited B16 cell proliferation and enhanced the cisplatins killing activity on B16 cells. The results of flow cytometry demonstrated that B16 cell proliferation was arrested at G stage after treatment with bifidobacterium. The B16 cell proliferation was arrested at S stage after treatment with cisplatin. The CD4+ percentage increased and the difference was significant compared with the normal group after treatment with bifidobacterium, indicating that T-cell immune activity was enhanced. Treatment with bifidobacterium combined with cisplatin can enhance the inhibitory activity on the growth of melanoma (B16) of cisplatin. The mechanism of the inhibitory activity on B16 cell proliferation is correlated with the enhanced immune activity in mice.
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Bacteria-mediated tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis and promoting apoptosis

《医学前沿（英文）》 2022年 第16卷 第6期   页码 873-882 doi: 10.1007/s11684-022-0925-2

摘要： Tumor growth is an angiogenesis-dependent process and accompanied by the formation of hypoxic areas. Tumstatin is a tumor-specific angiogenesis inhibitor that suppresses the proliferation and induces the apoptosis of tumorous vascular endothelial cells. VNP20009, an attenuated Salmonella typhimurium strain, preferentially accumulates in the hypoxic areas of solid tumors. In this study, a novel Salmonella-mediated targeted expression system of tumstatin (VNP-Tum5) was developed under the control of the hypoxia-induced J23100 promoter to obtain anti-tumor efficacy in mice. Treatment with VNP-Tum5 effectively suppressed tumor growth and prolonged survival in the mouse model of B16F10 melanoma. VNP-Tum5 exhibited a higher efficacy in inhibiting the proliferation and inducing the necrosis and apoptosis of B16F10 cells in vitro and in vivo compared with VNP (control). VNP-Tum5 significantly inhibited the proliferation and migration of mouse umbilical vascular endothelial cells to impede angiogenesis. VNP-Tum5 downregulated the expression of anti-vascular endothelial growth factor A, platelet endothelial cell adhesion molecule-1, phosphorylated phosphoinositide 3 kinase, and phosphorylated protein kinase B and upregulated the expression of cleaved-caspase 3 in tumor tissues. This study is the first to use tumstatin-transformed VNP20009 as a tumor-targeted system for treatment of melanoma by combining anti-tumor and anti-angiogenic effects.

关键词： Salmonella VNP20009     tumstatin     B16F10     melanoma     apoptosis     angiogenesis    

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中子俘获疗法临床应用国际进展

张紫竹,金从军,刘凯,张国珍,杨立军

《中国工程科学》 2012年 第14卷 第8期   页码 100-105

摘要：

硼中子俘获疗法（BNCT）目前在国际上已经临床应用于千余例患者,并取得了较好的治疗效果。主要对BNCT的原理、发展历史及国际BNCT临床进展情况作了主要介绍。对脑胶质瘤、恶性黑色素瘤、复发性头颈部肿瘤及转移性肝癌BNCT临床治疗情况及治疗效果作了较详细的讨论。

关键词： BNCT     脑胶质瘤     恶性黑色素瘤     复发性头颈部肿瘤     转移性肝癌    

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标题 作者 时间 类型 操作

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uvealmelanoma

期刊论文

associated with improved survival and increased response to immune checkpoint blockade in metastatic uvealmelanoma: results from a retrospective multicenter trial

期刊论文

NETO2 promotes melanoma progression via activation of the Ca/CaMKII signaling pathway

期刊论文

Celecoxib in combination with retinoid CD437 inhibits melanoma A375 cell

Jianwen REN, Zhenhui PENG, Birong GUO, Min PAN

期刊论文

Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its

HUANG Hongying, LIU Guangchao, QI Yijun, DU Yaowu, CHEN Jugao, MA Yuanfang

期刊论文

Bacteria-mediated tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis and promoting apoptosis

期刊论文

中子俘获疗法临床应用国际进展

张紫竹,金从军,刘凯,张国珍,杨立军

期刊论文