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Cited by 84Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerLung Cancer Treatments and Mutations

Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice

Open access
Jacoby, Jörg J., Erez, Baruch, Korshunova, Maria V., Williams, Ryan R., Furutani, Kazuhisa, Takahashi, Osamu, Kirkpatrick, Lynn, Lippman, Scott M. +3 more·2010·Journal of Thoracic Oncology
DOI 10.1097/jto.0b013e3181dc211fPMC PMC3782111
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Abstract

Introduction PX-478 is a potent small-molecule inhibitor of hypoxia-inducible factor 1alpha (HIF-1alpha). In prior preclinical studies, it had antitumor activity against various solid tumors in subcutaneous xenografts but had no measurable activity against a non-small cell lung cancer (NSCLC) xenograft. To determine the effectiveness of PX-478 against lung tumors, we investigated HIF-1alpha expression in several lung cancer cell lines, both in vitro and in vivo, and treated orthotopic mouse models of human lung cancer with PX-478. Methods Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice and were randomized 16 to 18 days after injection with daily oral treatment with PX-478 or vehicle for 5 days. Results In the PC14-PE6 NSCLC model, treatment with 20 mg/kg PX-478 significantly reduced the median primary lung tumor volume by 87% (p = 0.005) compared with the vehicle-treated group. PX-478 treatment also markedly reduced mediastinal metastasis and prolonged survival. Similar results were obtained in a second NSCLC model. In SCLC models, PX-478 was even more effective. In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001). The median survival duration was increased by 132%. In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008). Conclusions We demonstrated that the PX-478, HIF-1alpha inhibitor, had significant antitumor activity against two orthotopic models of lung adenocarcinomas and two models of SCLC. These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478.

Integrity signals

Registry

Crossref · 10.1097/jto.0b013e3181dc211f

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 21 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    Off-target effects may have contributed to tumor inhibition in the orthotopic models.

    “In summary, off-target effects, which has also been described recently22 for this drug, may have contributed to tumor inhibition in our model.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Palayoor, 2008, PX-478, an inhibitor of hypoxia-inducible factor-1alpha, enhances radiosensitivity of prostate carcinoma cells, Int J Cancer source
  • Findingown data

    In the NCI-H187 model, most mice have to be killed because of primary lung tumor burden, possibly before visible metastases develop.

    “but most mice have to be killed because of primary lung tumor burden, possibly before they develop visible metastases.”
    Quote in the paperSubstantial claim
  • Findingown data

    HIF-1α expression was seen in orthotopic tumor tissue from NCI-H187, NCI-N417, PC14PE6, and NCI-H441 cells in nude mice.

    “We observed HIF-1α expression in the tumor tissue of two SCLC cell lines, NCI-H187, and NCI-N417, and in tissue of the adenocarcinoma cell lines PC14PE6 and NCI-H441 (Figure 1C).”
    Quote in the paperSubstantial claim
  • Findingown data

    In vitro, PX-478 lowered HIF-1α protein expression in PC14PE6 cells by more than half.

    “and reduced HIF-1α protein expression in PC14PE6 cells by more than 50%.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    In the NCI-H187 model, combination therapy with paclitaxel did not further improve outcome.

    “Combination therapy with paclitaxel did not further improve the outcome, probably because of the high response rate obtained with PX-478 alone.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Premisecitation

    HIF-1 is overexpressed in 30-62% of NSCLC and 43-46% of SCLC cases, and this overexpression has been linked to worse overall survival.

    “HIF-1 is overexpressed in 30 to 62% of NSCLC and 43 to 46% of SCLC cases, and its overexpression has been associated with poorer overall survival.10 –15”
    Quote in the paperSubstantial claim3 of 6 sources checked
    • cites [10] Giatromanolaki, 2001, Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival, Br J Cancer source

      The paper reports HIF-1 expression in 68 of 108 operable NSCLC cases (62%; p. 881), supporting the upper end of the NSCLC range, but it does not establish the 30% lower end or report the claimed SCLC percentages. Its survival analysis found only a marginal association between HIF-1 expression and poorer prognosis (P = 0.08; p. 886); the stronger association with poor survival was for HIF-2. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [11] Giatromanolaki, 2003, DEC1 (STRA13) protein expression relates to hypoxia- inducible factor 1-alpha and carbonic anhydrase-9 overexpression in non-small cell lung cancer, J Pathol source
    • cites [12] Enatsu, 2006, Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung, Eur J Cardiothorac Surg source

      The Results report that strong HIF-1α expression was associated with reduced overall survival in patients with small-sized lung adenocarcinomas. The Discussion reports strong expression in 23 of 78 cases (29%), but the paper does not establish the claimed 30–62% range for NSCLC or 43–46% range for SCLC. Page numbers are unavailable in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [13] Hung, 2009, Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer, Thorax source

      The resectable-NSCLC results report HIF-1α overexpression in 32.2% of 87 tumours, within the claimed NSCLC range, and associate it with shorter overall survival (p = 0.005). The paper does not establish the full 30–62% NSCLC range or address the claimed 43–46% prevalence in SCLC. Page numbers were not provided for these passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [14] Ioannou, 2009, Hypoxia inducible factor-1 alpha and vascular endothelial growth factor in biopsies of small cell lung carcinoma, Lung source
    • cites [15] Karetsi E, Kerenidi T, Ioannou M, et al. Clinical significance of hypoxia inducible factor-1 alpha and VEGF expression in lung cancer. European Respiratory Society (ERS) Annual Meeting, Vienna, 2009; Abstract 283.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    NCI-H441 tumors were too small after 5 days of treatment to allow objective evaluation of apoptosis, microvessel density, or HIF-1α expression.

    “Tumors from the slow-growing NCI-H441 cell line were too small after 5 days of treatment (day 20 after tumor implantation) to allow an objective evaluation of apoptosis, microvessel density, or HIF-1α expression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H187 orthotopic SCLC model, 20 mg/kg PX-478 led to near complete tumor growth suppression, with median tumor volume reduced by 99% (p = 0.0001) and median left lung weight reduced by 91% (p = 0.0003) versus vehicle.

    “The high dose of PX-478 (20 mg/kg) led to near complete suppression of tumor growth, with a median tumor volume reduction of 99% (p = 0.0001) and a median left lung weight reduction of 91% (p = 0.0003, Table 2 and Figure 2D) compared with the vehicle control group.”
    • Also stated in: § Results · plain
      “In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H441 orthotopic adenocarcinoma model, 20 mg/kg PX-478 for 5 days decreased tumor volume by 90% (p = 0.0001) and left lung weight by 79% (p = 0.0004).

    “treatment with 20 mg/kg PX-478 for 5 days decreased tumor volume by 90% (p = 0.0001) and left lung weight by 79% (p = 0.0004) in this tumor model.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PX-478 was highly effective in the NCI-N417 SCLC model, although curative effects were not observed.

    “PX-478 was highly effective in the other SCLC model (NCI-N417), although curative effects were not observed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NCI-N417 orthotopic SCLC model, 20 mg/kg PX-478 daily for 5 days decreased median tumor volume by 97% (p = 0.008) and left lung weight by 87% (p = 0.002).

    “Treatment with the higher dose of PX-478 (20 mg/kg) daily for 5 days decreased the median tumor volume by 97% (p = 0.008) and left lung weight by 87% (p = 0.002)”
    • Also stated in: § Results · plain
      “In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vitro, HIF-1α expression differed among lung cancer cell lines and did not track with histologic type.

    “HIF-1α expression levels varied between cell lines and were independent of cell histologic type”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    NCI-N417 and NCI-H187 tumors had extended areas of necrosis and hypoxia, whereas PC14PE6 tumors had only small necrotic and hypoxic areas.

    “We killed several mice before the start of treatment and 5 days later and found extended areas of necrosis and hypoxia in NCI-N417 and NCI-H187 tumors, whereas PC14PE6 tumors had only small necrotic and hypoxic areas (as measured by pimonidazole binding, data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H187 survival experiment, all seven PX-478-treated mice killed before the end of the experiment had metastatic disease, some in multiple organs including lymph nodes, bone, brain, and liver.

    “All seven mice that were killed before the end of the experiment had metastatic disease, some in multiple organs, including the lymph nodes (four mice), bone (3), brain (2), and liver (1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H187 model, a 5-day course of PX-478 was curative in some mice and caused dramatic tumor regression in others.

    “In the model using NCI-H187 cells, a 5-day course of PX-478 was curative in some mice, and in other mice, it led to dramatic tumor regression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    In PC14-PE6 tumors, HIF-1α levels were higher and randomly distributed, and the tumors were not necrotic and less hypoxic.

    “In PC14-PE6 tumors, HIF-1α levels were higher and random, and the tumors were not necrotic and less hypoxic.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In NCI-H187 tumors, vehicle-treated cells had a high background of apoptotic cells, accompanied by necrotic areas.

    “In NCI-H187 tumors, a high background of apoptotic cells was visible in vehicle-treated cells; this was accompanied by necrotic areas.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H187 survival experiment, two of 10 PX-478-treated mice were healthy at day 140, and three others had no primary lung tumors when killed.

    “two of 10 mice in the PX-478-treated group were healthy at the end of the experiment (day 140 after injection); three others had no primary lung tumors on the day they were killed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Five days of PX-478 treatment induced profound apoptosis in tumor cells, statistically significant in PC14PE6 and NCI-N417 tumors.

    “treatment with PX-478 for 5 days induced profound apoptosis in tumor cells, as determined by cleaved caspase-3 staining and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (data not shown); this was statistically significant in PC14PE6 and NCI-N417 tumors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NCI-N417 SCLC model, PX-478 produced a marked reduction in tumor growth but no curative effects.

    “In the second SCLC model, based on NCI-N417 cells, we again observed a marked reduction in tumor growth; however, we observed no curative effects in the mice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NCI-H187 model, PX-478 had a curative effect in some mice and radically inhibited tumor growth in others.

    “In the NCI-H187 model, it had a curative effect in some mice and radically inhibited tumor growth in others.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the PX-478-treated group, primary tumor growth was controlled, and the mice developed metastases later.

    “However, in the PX-478-treated group, primary tumor growth was controlled, and the mice developed metastases later.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the PC14PE6 model, PX-478 treatment reduced mediastinal lymph node metastasis and pleural effusion.

    “Treatment with PX-478 also markedly reduced the occurrence of mediastinal lymph node metastasis and the production of pleural effusion.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PX-478 decreased tumor growth in a dose-dependent manner in the lung adenocarcinoma model and slightly but significantly improved survival when given as monotherapy for 5 days.

    “PX-478 treatment decreased tumor growth in a dose-dependent manner in the lung adenocarcinoma model and slightly but significantly improved survival when given as monotherapy for just 5 days.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The nonresponsiveness of A-549 tumors to PX-478 may be due to yet unknown genetic alterations in this cell line.

    “and may be due to yet unknown genetic alterations in this cell line.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Mice were randomized before treatment in the orthotopic lung tumor experiments.

    “mice (7–13 per group) were randomized and treated with 10 or 20 mg/kg oral PX-478 daily for 5 days”
    • Also stated in: § Orthotopic Lung Tumor Model · plain
      “mice were randomly treated with 20 mg/kg oral PX-478 daily for 5 days or vehicle.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    PX-478 was ineffective against A549 lung adenocarcinoma xenografts, which had only low HIF-1α expression in vitro and in vivo.

    “however, it was ineffective against A549 lung adenocarcinoma xenografts that showed only low expression of HIF-1α in vitro and in vivo.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Welsh, 2004, Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha, Mol Cancer Ther source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All experiments met current regulations and standards of the USDA, HHS, NIH, and MD Anderson Cancer Center.

    “All experiments met the current regulations and standards of the U.S. Department of Agriculture, the U.S. Department of Health and Human Services, the National Institutes of Health, and The University of Texas MD Anderson Cancer Center.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HIF-1 consists of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit.

    “which is composed of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit.6”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Semenza, 2007, Evaluation of HIF-1 inhibitors as anticancer agents, Drug Discov Today source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The NCI-H187, NCI-N417, and NCI-H441 cell lines were molecularly characterized.

    “NCI-H187, NCI-N417, and NCI-H441 cells were purchased from American Type Culture Collection (Manassas, VA) and molecularly characterized by the University of Texas MD Anderson Cancer Center Cell Line Characterization Shared Resource.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The effectiveness of PX-478 is positively correlated with HIF-1α expression in tumors.

    “Welsh et al.17 suggested that the effectiveness of PX-478 is positively correlated with HIF-1α expression in tumors.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Welsh, 2004, Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha, Mol Cancer Ther source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In addition to hypoxia, cytokines, growth factors, oncogenes, and mutations can raise HIF-1α expression and stability, mainly via PI3K/Akt, Ras/Raf/MAPK, and Smad signaling.

    “Besides hypoxia, several cytokines, growth factors, oncogenes, and gene mutations can increase the expression and stability of HIF-1α, mostly through activation of the phosphoinositide 3-kinase/Akt, Ras/Raf/mitogen-activated protein kinase, and Smad pathways.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Chan, 2007, HIF gene expression in cancer therapy, Methods Enzymol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Oral PX-478 might be converted in the GI tract into metabolites with cytotoxic or off-target effects.

    “It is possible that oral administration of PX-478 might lead to conversion of the drug into metabolites in the GI tract, which have cytotoxic effects or off-target effects”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    HIF-1α is expressed at varying levels in lung cancer cells in vitro under hypoxic conditions and in SCLC and NSCLC xenograft tumor tissue in vivo.

    “Together, these data demonstrate that HIF-1α is expressed at various levels in lung cancer cells in vitro under hypoxic conditions and in vivo in tumor tissues obtained from SCLC and NSCLC xenografts.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hypoxia is common in solid tumors, and how cells adapt to low oxygen is important for tumor progression and survival.

    “Hypoxia is a common feature in solid tumors, and cellular adaptation to hypoxia is critical to tumor progression and survival.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Semenza, 2007, Evaluation of HIF-1 inhibitors as anticancer agents, Drug Discov Today source

  • May combine two claims.

    Premisecitation

    Under hypoxia, oxygen-dependent hydroxylases are inhibited, HIF-1α is stabilized, and it partners with HIF-1β and other cofactors to induce genes for metabolic adaptation, apoptosis resistance, angiogenesis, and tumor invasion and metastasis.

    “However, Under hypoxic conditions, oxygen-dependent hydroxylases are inhibited and the HIF-1α subunit is stabilized and then it interacts with the HIF-1β subunit and other cofactors and induces the transcription of many genes involved in metabolic adaptation, apoptosis resistance, angiogenesis, and tumor invasion and metastasis.8”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Semenza, 2003, Targeting HIF-1 for cancer therapy, Nat Rev Cancer source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Under normal oxygen, HIF-1α is hydroxylated at two proline residues and then ubiquitinated by von Hippel-Lindau factor for proteosomal degradation.

    “Under normoxic conditions, the α subunit is rapidly hydroxylated at two proline residues and targeted for proteosomal degradation after ubiquitination by the von Hippel-Lindau factor.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6] Semenza, 2007, Evaluation of HIF-1 inhibitors as anticancer agents, Drug Discov Today source
    • cites [7] Yee Koh, 2008, HIF-1 regulation: not so easy come, easy go, Trends Biochem Sci source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HIF-1α mRNA expression was identified as one of three prognostic factors for overall survival in early-stage NSCLC.

    “HIF-1α mRNA expression was identified as one of three prognostic factors for overall survival in early-stage NSCLC.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Lau, 2007, Three-gene prognostic classifier for early-stage non small-cell lung cancer, J Clin Oncol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The lung microenvironment or different pharmacokinetics may influence how effectively PX-478 inhibits HIF-1α.

    “It is also likely that the microenvironment of the lung or different pharmacokinetics influences the effectiveness of PX-478 on HIF-1α inhibition”
    Quote in the paperNot a substantial claim
34 of 34

  • The paper relies on this without support.

    The best ways to treat lung cancer and the biological basis of resistance to radiation and chemotherapy are not known.

    “the optimal treatment modalities in lung cancer and the biologic mechanism of resistance to radiation therapy and chemotherapy are not understood.”

  • The paper relies on this without support.

    No prior scientific study has shown that PX-478 is active when tumors are grown in an orthotopic tissue environment.

    “However, no scientific studies have demonstrated the activity of the compound in an orthotopic tissue environment.”

  • The paper relies on this without support.

    Orthotopic mouse models of human lung cancer predict how human lung cancer patients will respond to PX-478.

    “These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478.”

  • The paper relies on this without support.

    The human lung cancer cell lines used in this study represent the biology of human NSCLC and SCLC.

    “Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice”

  • The paper relies on this without support.

    SCLC commonly spreads to distant organs early in the disease course.

    “SCLC is known for spreading early to distant organs”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Treatment schedules are described as lasting both one week and until study end

    Major

    The methods say the three-days-per-week and every-third-day PX-478 schedules continued until the end of the experiment. The results instead describe both schedules as lasting one week.

1 of 1

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Authors
Jacoby, J. J., Erez, B., Korshunova, M. V., Williams, R. R., Furutani, K., Takahashi, O., Kirkpatrick, L., Lippman, S. M., Powis, G., O'Reilly, M. S., & Herbst, R. S.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Herbst, Roy S.
ORCID
Venue
Journal of Thoracic Oncology
Publisher
Elsevier BV
Published
2010-07
Volume
5
Issue
7
Pages
940-949
ISSN
1556-0864 (ISSN-L)
DOI
10.1097/jto.0b013e3181dc211f
PMC
PMC3782111
OpenAlex
W2028916882
Cited by
84
References
24
Citations by year
2026: 5 · 2025: 7 · 2024: 10 · 2023: 3 · 2022: 11 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 8 · 2012: 7
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thoracic Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Foundation for the National Institutes of Health
  • Lung Cancer Research Foundation
  • National Cancer Research Institute
  • National Research Foundation
  • National Institutes of Health
  • National Cancer Institute (P01CA017094, R01CA098920)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
PX-478, HIF-1α inhibitors, hypoxia-inducible factor-1α, small cell lung cancer, lung adenocarcinoma, orthotopic mouse model, anticancer activity, mediastinal metastasis, tumor progression, survival
MeSH terms
Adenocarcinoma, Animals, Carcinoma, Non-Small-Cell Lung, Humans, Immunoenzyme Techniques, Lung Neoplasms, Lymphatic Metastasis, Male, Mice, Nude, Mustard Compounds, Phenylpropionates, Tumor Cells, Cultured, Blotting, Western, Survival Rate, Treatment Outcome, Apoptosis, Disease Progression, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Small Cell Lung Carcinoma

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