1.A Novel Germline Mutation in BRCA1 Causes Exon 20 Skipping in a Korean Family with a History of Breast Cancer.
Kyong Ah YOON ; Sun Young KONG ; Eun Ji LEE ; Jeong Nam CHO ; Suhwan CHANG ; Eun Sook LEE
Journal of Breast Cancer 2017;20(3):310-313
Germline mutations in the BRCA1 and BRCA2 genes are strong genetic factors for predispositions to breast, ovarian, and other related cancers. This report describes a family with a history of breast and ovarian cancers that harbored a novel BRCA1 germline mutation. A single nucleotide deletion in intron 20, namely c.5332+4delA, was detected in a 43-year-old patient with breast cancer. This mutation led to the skipping of exon 20, which in turn resulted in the production of a truncated BRCA1 protein that was 1773 amino acids in length. The mother of the proband had died due to ovarian cancer and had harbored the same germline mutation. Ectopically expressed mutant BRCA1 protein interacted with the BARD1 protein, but showed a reduced transcriptional function, as demonstrated by the expression of cyclin B1. This novel germline mutation in the BRCA1 gene caused familial breast and ovarian cancers.
Adult
;
Amino Acids
;
BRCA1 Protein
;
Breast Neoplasms*
;
Breast*
;
Cyclin B1
;
Exons*
;
Genes, BRCA1
;
Genes, BRCA2
;
Germ-Line Mutation*
;
Humans
;
Introns
;
Mothers
;
Ovarian Neoplasms
2.CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors.
Jaemin LEE ; Jinhoi SONG ; Eun Soo KWON ; Seongyea JO ; Min Kyung KANG ; Yeon Jeong KIM ; Yeonsil HWANG ; Hosung BAE ; Tae Heung KANG ; Suhwan CHANG ; Hee Jun CHO ; Song Cheol KIM ; Seokho KIM ; Sang Seok KOH
Experimental & Molecular Medicine 2016;48(9):e261-
CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.
Angiopoietin-2
;
Animals
;
Carcinogenesis
;
Endothelial Cells
;
Heterografts
;
In Vitro Techniques
;
Mice
;
Monocytes*
;
Neoplasm Metastasis
;
Pancreatic Neoplasms
;
Receptor, TIE-2
;
Transcription Factor AP-1
;
Tumor Burden
;
Tumor Microenvironment
3.The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique
Hong-Tao HU ; Zhe WANG ; Myung Ji KIM ; Lu-Shang JIANG ; Shi-Jun XU ; Jaeyun JUNG ; Eunji LEE ; Jung-Hoon PARK ; Nader BAKHEET ; Sung Hwan YOON ; Kun Yung KIM ; Ho-Young SONG ; Suhwan CHANG
Cancer Research and Treatment 2021;53(3):733-743
Purpose:
We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.
Materials and Methods:
RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.
Results:
We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.
Conclusion
We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
4.The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique
Hong-Tao HU ; Zhe WANG ; Myung Ji KIM ; Lu-Shang JIANG ; Shi-Jun XU ; Jaeyun JUNG ; Eunji LEE ; Jung-Hoon PARK ; Nader BAKHEET ; Sung Hwan YOON ; Kun Yung KIM ; Ho-Young SONG ; Suhwan CHANG
Cancer Research and Treatment 2021;53(3):733-743
Purpose:
We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.
Materials and Methods:
RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.
Results:
We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.
Conclusion
We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.