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Cancer Therapy: Clinical

Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFNα2b

Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Stephanie R. Land, Soldano Ferrone and John M. Kirkwood
Wenjun Wang
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Howard D. Edington
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Uma N.M. Rao
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Drazen M. Jukic
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Stephanie R. Land
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Soldano Ferrone
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John M. Kirkwood
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DOI: 10.1158/1078-0432.CCR-06-1387 Published March 2007
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    Fig. 1.

    A, pSTAT3tyr705/STAT3 double immunostaining of melanoma cells in the lymph node metastases. Formaldehyde-fixed, paraffin-embedded tissues of nine cases with adequate biopsy samples pre-HDI and post-HDI therapy were available for evaluation of pSTAT3tyr705 and STAT3. Only seven cases had adequate biopsy samples available before and after HDI for analysis of tumor and eight cases for analysis of lymphocytes. Columns, mean; bars, SE. B, pSTAT3tyr705/STAT3 double immunostaining of lymphocytes in the lymph node metastases. Similar phenomena were observed among lymphocytes as in tumor cells. Columns, mean; bars, SE.

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    Fig. 2.

    A to C, pSTAT1tyr701 and pSTAT3tyr705 double immunostains of nodal melanoma cells. Snap-frozen tissues (total of 12 cases) pre-HDI and post-HDI therapy were stained for pSTAT1tyr701 or pSTAT3tyr705. Columns, mean; bars, SE. D to F, pSTAT1tyr701 and pSTAT3tyr705 double immunostains of nodal lymphocytes. Similar phenomena were observed among lymphocytes as in tumor cells. Points, mean; bars, SE.

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    Fig. 3.

    A, pSTAT1/pSTAT3 ratio in melanoma cells versus overall survival indicates that patients with higher pSTAT1/pSTAT3 ratios in pretreatment tumor samples have prolonged overall survival (P = 0.032). B, pSTAT1/pSTAT3 ratio in lymphocytes versus overall survival does not show significant correlation (P = 0.226). Low, patients whose pSTAT1/pSTAT3 ratio was at or below the median value; high, patients whose pSTAT1/pSTAT3 ratio was above the median value.

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    Fig. 4.

    High-dose IFNα2b up-regulates TAP2 in tumor cells and immune cells. Magnification, ×20. Red, TAP2; blue, counterstain. A1 to A5, pretreatment sections; B1 to B5, posttreatment sections; the red color (representing TAP2) is strongly increased in intensity and percentage of cells observed. Small yellowish brown particles, melanin. Black arrows, lymphoid cells.

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    Patient clinical information

    Patient no.Age (y)SexDisease statusDisease stage at original diagnosisHDI completedResponse
    Duration of disease-free interval (mo)Current status
    ClinicalPathologic
    80150MIT4aN2b(cl)1/3DRCRRMiD32Deceased
    80342MIT4bNxYesNRRMaD6Deceased
    80465FRT3aN0(s)YesNRRMaD1Deceased
    80541MRT1bN0(cl)YesPRRMiD49NED
    80656MRT3a(al)N0(cl)YesNRCR34MET
    80766FRT3bN0(s)YesNRRMaD32NED
    80956FIT4bN3(cl)YesNRRMaD6Deceased
    81060MIT4bN2b(cl)YesNRRMaD6Deceased
    81172FRT3aN0(cl)YesPRRMaD30NED
    81276MRTxN0(s)YesPRRMaD15MET
    81457FITxN3(cl)1/3DRPRRMaD4Deceased
    81762MIPTxN3(cl)1/3DRPRRMaD10NED
    • NOTE: Adapted from ref. 18.

      Abbreviations: M, male; F, female; I, initial presentation; R, regional lymph node recurrence; IP, isolated palpable nodal metastases arising from an unknown primary; cl, nodal staging based on clinical exam; s, nodal staging based on sentinel lymph node mapping and pathologic interpretation; DR, dose reduction; CR, complete response; PR, partial response; NR, no response; RMiD, residual microscopic disease; RMaD, residual macroscopic disease; NED, no evidence of disease; MET, metastatic disease.

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Clinical Cancer Research: 13 (5)
March 2007
Volume 13, Issue 5
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Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFNα2b
Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Stephanie R. Land, Soldano Ferrone and John M. Kirkwood
Clin Cancer Res March 1 2007 (13) (5) 1523-1531; DOI: 10.1158/1078-0432.CCR-06-1387

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Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFNα2b
Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Stephanie R. Land, Soldano Ferrone and John M. Kirkwood
Clin Cancer Res March 1 2007 (13) (5) 1523-1531; DOI: 10.1158/1078-0432.CCR-06-1387
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