ABSTRACT
OBJECTIVE@#To investigate the relationship between CT features of metastatic calcification and the response to chemotherapy in colorectal cancer metastases.@*METHODS@#A total of 27 patients with 30 sites of calcified metastases who underwent chemotherapy combined with targeted therapy (cetuximab) between January 2011 and December 2016 comprised this retrospective study population. Two radiologists independently evaluated the occurrence of tumor calcification before and after treatment, and evaluated the tumor response after therapy. According to the response evaluation criteria in solid tumors (version 1.1), the best curative effect evaluation of the patients was recorded. The patients were divided into groups as below: (1) Patients who showed complete response (CR) and partial response (PR) were assigned to the response group, and the stable disease (SD) and progressive disease (PD) were assigned to the non-response group. (2) Patients showed CR or PR, or patients showed SD with longer progress free survival (PFS) were assigned to the benefit group, and the remaining patients were assigned to the no benefit group. The difference of different imaging calcification features (morphology, maximum density, and density-time slope) were analyzed.@*RESULTS@#The most common site of metastases calcification was liver (63.3%), followed by lymph nodes (26.7%). There were 12 cases in the response group, 15 cases in the non-response group; and 13 cases in the benefit group, 14 cases in the no benefit group. The density time growth slope was higher in the response group when compared with the non-response group (P=0.025). The proportion of thhe patients with increased number of calcified foci in the benefit group (61.5%) was higher than that in the no benefit group (14.3%), P=0.018. There was no significant difference in the maximum density between the groups. The calcification of liver metastases were all amorphous calcification, with central calcification (36.8%), eccentric calcification (36.8%), garland calcification (15.8%) and diffuse calcification (10.6%). The lymph node metastases could be diffuse (75.0%), and curve or eggshell calcification (25.0%). There was no statistical difference between the groups.@*CONCLUSION@#In patients with advanced colorectal cancer metastases treated with cetuximab combined chemotherapy, rapid growth of calcification density and increased calcification number may be valuable imaging features of therapeutic efficacy. The maximal calcification density and morphology of calcification are not related to the therapeutic efficacy.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Calcinosis , Colorectal Neoplasms , Liver Neoplasms , Retrospective Studies , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
ABSTRACT
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.