Gastric Myeloid Sarcoma Mimicking a Scirrhous Gastric Cancer

14070 Background: Scirrhous gastric carcinoma, a diffusely infiltrating also known as linitis plastica-type carcinoma, carries the highest mortality of all gastric cancers. Scirrhous carcinoma cells with amplification of the activated K-samII gene, which encodes fibroblast growth factor receptor type 2 (FGF-R2), have a growth advantage during tumor progression The poor prognosis carried by scirrhous gastric cancer is closely associated with amplification of the K-samII/FGF-R2, a tyrosine kinase growth factor receptor. Ki23057, a newly developed small molecule acting K-samII/FGF-R2 inhibitor, is a kinase inhibitor that competes with ATP for the binding site in the kinase, thus strongly blocking phosphorylation of FGF-R2. The aim of the current study is to clarify the possibility of molecular target therapy with Ki23057 for treating scirrhous gastric cancer. Methods: Five human gastric cancer cell lines were used. OCUM-2MD3 and OCUM-8 were derived from scirrhous carcinomas. MKN-7, MKN-45 and MKN-74 cells were derived from non-scirrhous carcinomas. In vitro effects of Ki23057 on cell growth were determined by calculating the number of cancer cells. The influences of Ki23057 on the MAP kinase and PI3 kinase signaling pathways and the apoptosis pathway in the gastric cancer cells were also examined. For in vivo experiments, the Ki23057 was administered orally to mouse models of peritoneal dissemination. Results: K-samII amplification was found in OCUM-2MD3 and OCUM-8 cells, but not in MKN-7, MKN-45, or MKN-74 cells. Ki23057 significantly inhibited the proliferation of scirrhous cancer cells, but not non- scirrhous gastric carcinoma cells. Ki23057 decreased phosphorylation of K-samII/FGF-R2, ERK and Akt, and increased apoptosis in scirrhous cancer lines. The oral Ki23057 administration significantly (p<0.001) prolonged survival of mice with peritoneal dissemination following injection of OCUM-2MD3 scirrhous cancer cells. Conclusions: A novel K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, appears therapeutically promising in scirrhous gastric carcinoma with K-samII amplification. No significant financial relationships to disclose.

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Impact of S-1 plus cisplatin neoadjuvant chemotherapy in scirrhous gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.198 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 198-198

Author(s):

Chikara Kunisaki ◽

Hirochika Makino ◽

Jun Kimura ◽

Ryo Takagawa ◽

Amane Kanazawa ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Lymph Node ◽

Prognostic Factor ◽

Neoadjuvant Chemotherapy ◽

Pathological Response ◽

Curative Gastrectomy ◽

Scirrhous Gastric Cancer ◽

Lavage Cytology ◽

Gastric Cancer Patients

198 Background: This study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3 week regime of the fluoropyrimidine, S-1 (40 mg/m2, orally, twice daily), with cisplatin (60 mg/m2, intravenously, day 8) were administered to patients, separated by a 2 week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n=27). We compared overall survival and prognostic factors in these patients with a non-neoadjuvant group (n=19). Results: For all patients, univariate analysis identified non-curative gastrectomy and positive lavage cytology as adverse prognostic factors; extended lymph node dissection was a positive prognostic factor. Multivariate analysis showed that non-curative resections independently influenced prognosis (hazard ratio=2.902, p=0.011). In the SP group, positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after SP chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusions: After SP neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.

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