title: Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer.
abstract: BACKGROUND
  Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed.
  
  
  METHODS
  To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size.
  
  
  RESULTS
  In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent.
  
  
  CONCLUSIONS
  We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.
authors: Department of Thoracic and Head and Neck Medical Oncology, Sheba Medical Center, Sheba, Israel.
authors: Takeshi
authors: T
authors: Isobe
authors: Amir
authors: A
authors: Onn
authors: Daniel
authors: D
authors: Morgensztern
authors: Jörg J
authors: JJ
authors: Jacoby
authors: Wenjuan
authors: W
authors: Wu
authors: Tomoaki
authors: T
authors: Shintani
authors: Satoshi
authors: S
authors: Itasaka
authors: Keiko
authors: K
authors: Shibuya
authors: Peter J
authors: PJ
authors: Koo
authors: Michael S
authors: MS
authors: O'Reilly
authors: Roy S
authors: RS
authors: Herbst
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D017239:Paclitaxel / Q000494:pharmacology*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin