title: Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts.
abstract: OBJECTIVE
  Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia.
  
  
  METHODS
  We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities.
  
  
  RESULTS
  Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment.
  
  
  CONCLUSIONS
  In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong. nikkilee@hku.hk.
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Kin Tak
authors.initials: KT
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Mei Yuk
authors.initials: MY
authors.lastname: Choi
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Ho Yu
authors.initials: HY
authors.lastname: Lam
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Lai Nar
authors.initials: LN
authors.lastname: Tung
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Fei Chuen
authors.initials: FC
authors.lastname: Tzang
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Heron
authors.initials: H
authors.lastname: Han
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Ian P Y
authors.initials: IP
authors.lastname: Lam
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Sui Yi
authors.initials: SY
authors.lastname: Kwok
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Sze Hang
authors.initials: SH
authors.lastname: Lau
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Man
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.|Queen Mary Hospital, Pokfulam, Hong Kong.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Tong
authors.affiliation: New B Innovation Limited, Kowloon, Hong Kong.
authors.forename: Bing L
authors.initials: BL
authors.lastname: Wong
authors.affiliation: Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong. slaw@hku.hk.|Queen Mary Hospital, Pokfulam, Hong Kong. slaw@hku.hk.
authors.forename: Simon
authors.initials: S
authors.lastname: Law
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008819:Mice, Nude; D010100:Oxygen / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; C000595252:YQ23 compound; D002945:Cisplatin; D010100:Oxygen; D005472:Fluorouracil
keywords: Chemotherapeutic drug responses; Esophageal squamous cell carcinoma; Oxygen carrier; YQ23