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  • American Association for Cancer Research (AACR)  (3)
  • Naito, Yoshiki  (3)
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  • American Association for Cancer Research (AACR)  (3)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1393-1393
    Abstract: Background: CSCs are defined as minor cell population which have higher tumor-initiating ability, self-renewal ability and multilineage potential. Although CSCs in oral squamous cell carcinoma (OSCC) were identified by several surface antigen (e.g., CD44, CD133) or ALDEFLOUR assay, it is still elusive which are universal markers for CSC in OSCC. The aim of this study is to clarify potential CSC markers for a OSCC cell line using a combination of cell surface markers, CD44v3 and CD24. Materials and Methods: A OSCC cell line, SAS, was used in the experiment. CD44v3+/CD24− cell fraction was sorted from SAS cells with a FACSAria II and compared with the other three fractions (CD44v3+/CD24+, CD44v3− /CD24−, CD44v3−/CD24+ cell fraction) in cell proliferation, drug resistance and sphere forming ability. mRNA expression levels of various genes, such as stemness genes, anti-apoptosis genes and hypoxia-related genes, were compared among the fractions using quantitative real-time reverse transcriptase-polymerase chain reaction. Results: The proportion of CD44v3+/CD24−, CD44v3+/CD24+, CD44v3−/CD24−, CD44v3−/CD24+ cells was 34.9%, 39.8%, 14.2% and 11.0%, respectively. CD44v3+/CD24− cells showed a higher sphere forming ability, and drug resistance for CDDP, 5-FU and Cetuximab and expressed higher mRNA levels of CSC property-related genes (ABCG2, Oct-4, Nanog) and a hypoxia-related gene (HIF-1α) than the other cell fractions. There were no significant differences in cell proliferation among the fractions. Conclusion: The results suggest that CD44v3+/CD24− cell fractions in SAS possess CSC-like properties. The investigation of tumorigenic capacity in NOD/SCID mice is now under way. Citation Format: Keita Todoroki, Sachiko Ogasawara, Jun Akiba, Masamichi Nakayama, Yoshiki Naito, Jingo Kusukawa, Hirohisa Yano. CD44v3-positive (CD44v3+) and CD24-negative (CD24−) cells possess cancer stem cell (CSC)-like properties in a human oral squamous cell carcinoma cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1393. doi:10.1158/1538-7445.AM2015-1393
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4762-4762
    Abstract: BACKGROUND: The resection rate and survival period of resectable pancreatic ductal adenocarcinoma (PDAC) have increased gradually. Unfortunately, only 15-20% of patients have resectable disease at diagnosis, with the remainder presenting with distant metastatic or locally advanced tumors. Borderline resectable PDAC (BR-PDAC) is defined as a tumor that involves the portal vein (PV) and/or superior mesenteric vein (SMV), and has low resectability. However, there are many practical advantages to neoadjuvant chemoradiotherapy (NAC-RT) for BR-PDAC. Although the clinical effects of NAC-RT in BR-PDAC have been discussed, only a few studies have reported pathological features. We herein studied the effect of NAC-RT on the histological features of BR-PDAC. MATERIALS AND METHODS: Tissue samples of 14 patients with BR-PDAC undergoing NAC-RT (NAC-RT group; male: 7 patients, female: 7 patients; average age:64.8+8.1 years) and 78 patients with conventional PDAC (control group), resected at the Kurume University Hospital were obtained. The BR-PDACs had PV and/or SMV invasion at initial clinical diagnosis. All patients with BR-PDAC underwent NAC-CRT, comprising chemotherapy and external beam irradiation (50.4 Gy). The microvessel invasion (MVI), lymphovascular invasion (LVI), neural invasion (NI), portal vein invasion (PVI), extrapancreatic plexus invasion (PLI), and TNM classification in the surgical specimens were examined. All statistical analyses were performed using StatMate IV (ATMS, Tokyo, Japan). All statistical tests were two-tailed, and P & lt; 0.05 was considered statistically significant. RESULTS: The distribution of stages in the NAC-RT group was as follows: stage IA (n = 5, 36%), IIA (n = 6, 43%), IIB (n = 3, 21%). The pathological grade was determined to be G1 in 9 cases (64%), G2 in 4 cases (28%) and G3 in 1 case (8%). The difference in average tumor size between the NAC-RT and control groups was significant (P & gt; 0.001). Lymph node metastases were significantly infrequently observed in the NAC-RT group compared with the control (P=0.009). The NAC-RT group had a significant lower MVI (29%, 4/14) and LVI (57%, 8/14) than the control group (MVI: P & lt;0.001, LVI: P=0.011). However, there was no significant difference in NI (P=0.129). Ten patients without PVI and /or PLI in the NAC-RT group (71%) had significantly better prognosis than those in the control group (P=0.029), although there was no significant difference in overall survival rates between both groups (P=0.100). CONCLUSIONS: NAC-RT might be more advantageous by inhibiting local invasion, hematogenous and lymphatic metastasis, and could contribute to a better prognosis in patients with BR-PDAC, partly due to the prevention of PVI and/or PLI in pancreatic cancer. Citation Format: Yoshiki Naito, Masamichi Nakayama, Hiroto Ishikawa, Kenjiro Takahashi, Toru Hisaka, Koji Okuda, Masaru Fukahori, Yusuke Ishida, Yoshinobu Okabe, Yutaro Mihara, Masahiko Tanigawa, Jun Akiba, Takuji Torimura, Hirohisa Yano. Clinicopathologic findings of borderline resectable pancreatic cancer after neoadjuvant chemoradiotherapy [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 4762.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 514-514
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers and is associated with an extremely poor prognosis, since it is difficult to diagnose pancreatic cancer at an early stage despite its remarkably aggressive features. However, the molecular mechanism underlying the development of aggressive PDAC remains elusive. Rho guanine nucleotide exchange factors (ARHGEFs) are known to activate the RhoA signaling pathway in several types of tumor, although its association with the outcome of PDAC has not been reported. Here, we report that a higher expression of ARHGEF15 is significantly associated with a poor prognosis among PDAC patients, and an increase in ARHGEF15 expression plays pivotal roles in the enhancement of cellular motility and the proliferation of PDAC cells. Firstly, we found that a higher level of ARHGEF15 was significantly correlated with a poor prognosis among 39 Japanese patients with PDAC using global gene expression profiling with an Affymetrix microarray. We then showed that RNA interference-mediated gene silencing of ARHGEF15 inactivated the RhoA signaling pathway when examined using a RhoA pull-down assay. Next, the assessment of cellular migration using both a transwell chamber assay and a wound healing assay showed that ARHGEF15 silencing down-regulated cellular migration and invasive ability in pancreatic cancer cell lines with high levels of endogenous ARHGEF15 expression. Since the RhoA signaling pathway is involved in cell proliferation, we also examined the effect of ARHGEF15-silencing on cell viability and observed that ARHGEF15-knockdown markedly retarded cellular growth in the pancreatic cell lines. In parallel with the gene-silencing studies, the effect of ARHGEF15-overexpression was also investigated in pancreatic cell lines with low levels of endogenous ARHGEF15 expression. We observed opposite phenotypes to those observed in the gene-silencing studies: increased cellular motility and viability, compared with the controls, was observed as a result of overexpression. This is the first study to suggest that a higher expression of ARHGEF15 was correlated with a poor prognosis among patients with pancreatic cancer. In addition, these data suggested that the overexpression of ARHGEF15 contributed to a poor prognosis among PDAC patients by enhancing tumor motility and proliferation, suggesting that ARHGEF15 could be a prognostic biomarker as well as a novel therapeutic target for PDAC. Citation Format: Hiroto Fukushima, Makiko Yasumoto, Sachiko Ogasawara, Jun Akiba, Yuhei Kitasato, Yoshiki Naito, Masamichi Nakayama, Yoshinobu Okabe, Masafumi Yasunaga, Hiroyuki Horiuchi, Etsuko Sakamoto, Hiraku Itadani, Shinji Mizuarai, Shinji Oie, Hirohisa Yano. ARHGEF15 is associated with a poor prognosis in patients with pancreatic ductal adenocarcinoma through a mechanism involving the enhancement of cellular motility and proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 514. doi:10.1158/1538-7445.AM2015-514
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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