Spindle-type Cells Research Articles

Abstract 1069: Cxcl12 is involved in liver metastasis of intrahepatic cholangiocarcinoma

Abstract Background: Recurrences often happen in patients with intrahepatic cholangiocarcinoma (ICC) after radical hepatectomies. In addition, ICC has a poor sensitivity for chemotherapy. Most of the recurrence in ICC is liver metastasis, and how to control liver metastasis should be important to improve patients' prognosis. Purpose and Methods: Samples of ICC (primary and metastatic lesions) were collected as a multicenter study of the Kyushu Liver Surgery Study Group. cDNA microarray was performed using five frozen samples of ICC primary and metastatic sites; primary A - liver metastasis A1, re-liver metastasis A2, and primary B - liver metastasis B. Protein expression of the five high or low expression genes was evaluated by immunohistochemical staining using 25 primary ICC and 33 metastatic lesions; 22 cases of liver, 7 cases of lymph node, 2 cases of lung, 1 case of bone, and 1 case of adrenal gland. In in vitro experiments, ICC cell lines of the epithelial type (HuCCT-1, RBE) and the spindle type (SSP-25, HuH-28) were used. Results: Using cDNA microarray, genes of high expression (KRT83, CXCL12) and low expression (REG3G, OLFM4) were extracted in the metastatic site as compared with the primary tumor, evaluated by the sum of three pairs: primary A - liver metastasis A1, primary A - liver metastasis A2, and primary B - liver metastasis B. In addition, as a result of analyzing the results of the cDNA microarray with gene set enrichment analysis (GSEA), it was associated with a gene group related to the cell cycle, and CD168 was identified to be strongly correlated among them. In immunohistochemical staining, CXCL12 was significantly increased in liver metastasis compared to primary tumor (p = 0.0329), but there was no significant difference in the other 4 genes. Furthermore, in immunohistochemical staining, CXCR7, a receptor for CXCL12, was significantly increased in liver metastatic sites (p=0.0011). Next, in vitro experiments showed that gene expression of CXCL12 -CXCR4/CXCR7 differed depending on morphology: high in the spindle type cells (SSP25, HuH28) and low in the epithelial type cells (HuCCT-1, RBE). There was no significant difference in proliferative capacity between the two types of morphology, but the invasive ability was significantly higher in the spindle-shaped cell lines (p <0.05). By suppressing CXCL12, invasive ability was suppressed in both SSP-25 and HuH28 cells. Conclusions: CXCL12 may be involved in hepatic metastasis of ICC with organ specificity. Currently, the possibility of therapeutic application against CXCL12 in vivo is under consideration. Citation Format: Tatsunori Miyata, Yo-ichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ota, Susumu Eguchi, Shinichi Aishima, Hideo Baba, Hikaru Fujioka. Cxcl12 is involved in liver metastasis of intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1069.

Nodular fasciitis: a case series

Given its rarity, varied histological presentation and often pseudosarcomatous appearance, nodular fasciitis is frequently misdiagnosed on pre-operative, intra-operative and final analyses. Four cases of nodular fasciitis are reviewed. Physical and radiological findings were consistent with a parapharyngeal tumour, probably neurogenic, a level four neck mass suspicious for lymphoma; a sternoclavicular mass in a patient with a history of breast cancer suspicious for metastasis; and a cheek mass consistent with an accessory parotid tumour. Fine needle aspiration results were consistent with a neurogenic tumour in two patients and an undifferentiated malignancy in two patients. Frozen section examination most commonly included masses with spindle-type cells. The final diagnosis of nodular fasciitis was made only after permanent section and immunohistological analysis. In a patient with nonspecific results following investigation of a head or neck mass, nodular fasciitis should be considered. Use of appropriate immunohistochemical markers will aid in the final diagnosis.

Separation of carp ( Cyprinus carpio L.) thrombocytes by using a monoclonal antibody, and their aggregation by collagen

A monoclonal antibody against carp peripheral blood leucocytes was produced, and its reactivity analysed by flow cytometry and electron microscopy. The antibody reacted positively with 10–35% of the cells in a fraction of lymphocytes and thrombocytes that was separated by flow cytometry. Electron microscopy using immunogold labelling showed that this antibody reacted strongly with thrombocytes, but not with other leucocytes. By using a magnetic separator, leucocytes that were positive and negative for this antibody were separated. The positive cells were uniform, spindle-type cells that aggregated in the presence of collagen, while the negative cells did not aggregate. Light and electron microscopy showed that many positive cells changed to a spherical form after the addition of collagen and then 40–60% of these cells aggregated.

A Randomized Study of Methanol-Extraction Residue of Bacille Calmette-Guerin as Postsurgical Adjuvant Therapy of Uveal Melanoma

A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study.

Studies of mammary carcinoma metastasis in a mouse model system. I: Derivation and characterization of cells with different metastatic properties during tumour progression in vivo.

The biological and metastatic properties of cells from a murine mammary adenocarcinoma, MT1, were studied during serial transplantation in syngeneic hosts. Over 35 generations the tumour progressed from a well-differentiated, poorly metastatic neoplasm to an anaplastic highly metastatic state. At early passages the tumour yielded uniform cultures of cuboidal epithelial cells, at passage 17 both epitheloid and spindle type cells were present, and by passage 30 only spindle type cells were obtained. Epithelioid cell lines and clones when injected intravenously into syngeneic hosts produced lung colonies only, whereas spindle cell lines were capable of extensive extrapulmonary colonisation. Similar patterns of dissemination and growth were seen in spontaneous metastasis assays. In spite of the marked phenotypic differences in these 'subpopulations', their comparable ultrastructural features, oestrogen receptor levels, expression of MMTV antigens, DNA content and lectin binding profiles suggested a common cell lineage. It is proposed that these cell lines will be of use in the determination of tumour and host factors influencing tumour progression and the evolution of metastatic potential.