Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient derived orthotopic xenograft nude-mouse models

被引：34

作者：

Igarashi, Kentaro ^{[1
,2
,3
]}

Kawaguchi, Kei ^{[1
,2
]}

Kiyuna, Tasuku ^{[1
,2
]}

Miyake, Kentaro ^{[1
,2
]}

Miyake, Masuyo ^{[1
,2
]}

Singh, Arun S. ^{[4
]}

Eckardt, Mark A. ^{[5
]}

Nelson, Scott D. ^{[6
]}

Russell, Tara A. ^{[7
]}

Dry, Sarah M. ^{[6
]}

Li, Yunfeng ^{[6
]}

Yamamoto, Norio ^{[3
]}

Hayashi, Katsuhiro ^{[3
]}

Kimura, Hiroaki ^{[3
]}

Miwa, Shinji ^{[3
]}

Tsuchiya, Hiroyuki ^{[3
]}

Singh, Shree Ram ^{[8
]}

Eilber, Fritz C. ^{[7
]}

Hoffman, Robert M. ^{[1
,2
]}

机构：

[1] AntiCancer Inc, San Diego, CA 92111 USA

[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA

[3] Kanazawa Univ, Dept Orthopaed Surg, Kanazawa, Ishikawa, Japan

[4] Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA USA

[5] Yale Sch Med, Dept Surg, New Haven, CT USA

[6] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA

[7] Univ Calif Los Angeles, Div Surg Oncol, Los Angeles, CA USA

[8] NCI, Basic Res Lab, Frederick, MD 21701 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 497卷 / 04期

关键词：

Soft-tissue sarcoma; Drug resistant; PDOX; Salmonella typhimurium A1-R; Tumor-targeting; Efficacy; RED FLUORESCENT PROTEIN; HUMAN COLON-CANCER; ANTI-CEA ANTIBODY; EWINGS-SARCOMA; PDOX MODEL; CHEMOTHERAPY; RESISTANT; EFFICACY; COMBINATION; MICE;

D O I：

10.1016/j.bbrc.2018.02.174

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium Al-R (S. typhimurium Al-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium Al-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. Published by Elsevier Inc.

引用

页码：1055 / 1061

页数：7

共 45 条

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