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Metabolic targeting with recombinant methioninase combined with palbociclib regresses a doxorubicin-resistant dedifferentiated liposarcoma.
Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Kentaro; Miyaki, Masuyo; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Higuchi, Takashi; Singh, Arun S; Chmielowski, Bartosz; Nelson, Scott D; Russell, Tara A; Eckardt, Mark A; Dry, Sarah M; Li, Yunfeng; Singh, Shree Ram; Chawla, Sant P; Eilber, Fritz C; Tsuchiya, Hiroyuki; Hoffman, Robert M.
Affiliation
  • Igarashi K; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Kawaguchi K; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
  • Kiyuna T; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
  • Miyake K; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
  • Miyaki M; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
  • Yamamoto N; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Hayashi K; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Kimura H; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Miwa S; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Higuchi T; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan.
  • Singh AS; Division of Hematology-Oncology, University of California, Los Angeles, CA, USA.
  • Chmielowski B; Division of Hematology-Oncology, University of California, Los Angeles, CA, USA.
  • Nelson SD; Department of Pathology, University of California, Los Angeles, CA, USA.
  • Russell TA; Division of Surgical Oncology, University of California, Los Angeles, CA, USA.
  • Eckardt MA; Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
  • Dry SM; Department of Pathology, University of California, Los Angeles, CA, USA.
  • Li Y; Department of Pathology, University of California, Los Angeles, CA, USA.
  • Singh SR; Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov.
  • Chawla SP; Sarcoma Oncology Center, 2811 Wilshire Blvd, Suite 414, Santa Monica, CA, 90403, USA. Electronic address: santchawla@gmail.com.
  • Eilber FC; Division of Surgical Oncology, University of California, Los Angeles, CA, USA. Electronic address: fceilber@mednet.ucla.edu.
  • Tsuchiya H; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan. Electronic address: tsuchi@med.kanazawa-u.ac.jp.
  • Hoffman RM; AntiCancer, Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.
Biochem Biophys Res Commun ; 506(4): 912-917, 2018 12 02.
Article in En | MEDLINE | ID: mdl-30392912
Liposarcoma is the most common type of soft tissue sarcoma. Among the subtypes of liposarcoma, dedifferentiated liposarcoma (DDLPS) is recalcitrant and has the lowest survival rate. The aim of the present study is to determine the efficacy of metabolic targeting with recombinant methioninase (rMETase) combined with palbociclib (PAL) against a doxorubicin (DOX)-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) model. A resected tumor from a patient with recurrent high-grade DDLPS in the right retroperitoneum was grown orthotopically in the right retroperitoneum of nude mice to establish a PDOX model. The PDOX models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, DOX; G3, PAL; G4, recombinant methioninase (rMETase); G5, PAL combined with rMETase. Tumor length and width were measured both pre- and post-treatment. On day 14 after initiation, all treatments significantly inhibited tumor growth compared to the untreated control except DOX. PAL combined with rMETase was significantly more effective than both DOX, rMETase alone, and PAL alone. Combining PAL and rMETase significantly regressed tumor volume on day 14 after initiation of treatment and was the only treatment to do so. The relative body weight on day 14 compared with day 0 did not significantly differ between each treatment group. The results of the present study indicate the powerful combination of rMETase and PAL should be tested clinically against DDLPS in the near future.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Pyridines / Carbon-Sulfur Lyases / Recombinant Proteins / Doxorubicin / Drug Resistance, Neoplasm / Liposarcoma Type of study: Clinical_trials Limits: Aged / Animals / Humans / Male Language: En Journal: Biochem Biophys Res Commun Year: 2018 Type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Pyridines / Carbon-Sulfur Lyases / Recombinant Proteins / Doxorubicin / Drug Resistance, Neoplasm / Liposarcoma Type of study: Clinical_trials Limits: Aged / Animals / Humans / Male Language: En Journal: Biochem Biophys Res Commun Year: 2018 Type: Article Affiliation country: Japan