F M Sirotnak

Summary

Affiliation: Memorial Sloan-Kettering Cancer Center
Country: USA

Publications

  1. ncbi request reprint Co-administration of probenecid, an inhibitor of a cMOAT/MRP-like plasma membrane ATPase, greatly enhanced the efficacy of a new 10-deazaaminopterin against human solid tumors in vivo
    F M Sirotnak
    Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 6:3705-12. 2000
  2. ncbi request reprint Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase
    F M Sirotnak
    Department of Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 6:4885-92. 2000
  3. ncbi request reprint A peptidomimetic inhibitor of ras functionality markedly suppresses growth of human prostate tumor xenografts in mice. Prospects for long-term clinical utility
    F M Sirotnak
    Laboratory for Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cancer Chemother Pharmacol 46:79-83. 2000
  4. ncbi request reprint Studies with CWR22 xenografts in nude mice suggest that ZD1839 may have a role in the treatment of both androgen-dependent and androgen-independent human prostate cancer
    Francis M Sirotnak
    Program in Molecular Pharmacology and Therapeutics and Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 8:3870-6. 2002
  5. ncbi request reprint Markedly decreased binding of vincristine to tubulin in vinca alkaloid-resistant Chinese hamster cells is associated with selective overexpression of alpha and beta tubulin isoforms
    F M Sirotnak
    Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Biochem Biophys Res Commun 269:21-4. 2000
  6. ncbi request reprint Carrier-mediated membrane transport of folates in mammalian cells
    F M Sirotnak
    Program in Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Annu Rev Nutr 19:91-122. 1999
  7. ncbi request reprint Experimental therapeutics with a new 10-deazaaminopterin in human mesothelioma: further improving efficacy through structural design, pharmacologic modulation at the level of MRP ATPases, and combined therapy with platinums
    N Z Khokhar
    Program in Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 7:3199-205. 2001
  8. ncbi request reprint Chromosomal localization of the murine RFC-1 gene encoding a folate transporter and its amplification in an antifolate resistant variant overproducing the transporter
    K Roy
    Program in Cell Biology and Genetics, Graduate School of Medical Sciences, Cornell University, New York, New York, USA
    Cancer Genet Cytogenet 105:29-38. 1998
  9. doi request reprint Pralatrexate with vitamin supplementation in patients with previously treated, advanced non-small cell lung cancer: safety and efficacy in a phase 1 trial
    Christopher G Azzoli
    Memorial Sloan Kettering Cancer Center, New York City, New York, USA
    J Thorac Oncol 6:1915-22. 2011
  10. ncbi request reprint Organization, structure and alternate splicing of the murine RFC-1 gene encoding a folate transporter
    B Tolner
    Laboratory for Molecular Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Gene 189:1-7. 1997

Collaborators

Detail Information

Publications35

  1. ncbi request reprint Co-administration of probenecid, an inhibitor of a cMOAT/MRP-like plasma membrane ATPase, greatly enhanced the efficacy of a new 10-deazaaminopterin against human solid tumors in vivo
    F M Sirotnak
    Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 6:3705-12. 2000
    ....
  2. ncbi request reprint Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase
    F M Sirotnak
    Department of Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 6:4885-92. 2000
    ..They also suggest significant clinical benefit from ZD1839 in combination with a variety of widely used cytotoxic agents...
  3. ncbi request reprint A peptidomimetic inhibitor of ras functionality markedly suppresses growth of human prostate tumor xenografts in mice. Prospects for long-term clinical utility
    F M Sirotnak
    Laboratory for Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cancer Chemother Pharmacol 46:79-83. 2000
    ..These studies sought to evaluate the antitumor properties of an inhibitor of ras functionality, L-744,832, which acts at the level of its associated protein farnesyltransferase...
  4. ncbi request reprint Studies with CWR22 xenografts in nude mice suggest that ZD1839 may have a role in the treatment of both androgen-dependent and androgen-independent human prostate cancer
    Francis M Sirotnak
    Program in Molecular Pharmacology and Therapeutics and Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 8:3870-6. 2002
    ..The effect of ZD1839 was also examined in combination with either bicalutamide ("Casodex") or cytotoxic agents against a hormone-dependent or -independent variant of CWR22, respectively...
  5. ncbi request reprint Markedly decreased binding of vincristine to tubulin in vinca alkaloid-resistant Chinese hamster cells is associated with selective overexpression of alpha and beta tubulin isoforms
    F M Sirotnak
    Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Biochem Biophys Res Commun 269:21-4. 2000
    ..These results would appear to provide an underlying basis for the large decrease in [(3)H]VCR binding by tubulin in these variant Chinese hamster cells and a major component of their acquired resistance to this vinca alkaloid...
  6. ncbi request reprint Carrier-mediated membrane transport of folates in mammalian cells
    F M Sirotnak
    Program in Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Annu Rev Nutr 19:91-122. 1999
    ..Detailed mechanisms as to the regulation of RFC-1 transcription are now emerging along with other information on structure and function of the transporter and its alteration following mutation...
  7. ncbi request reprint Experimental therapeutics with a new 10-deazaaminopterin in human mesothelioma: further improving efficacy through structural design, pharmacologic modulation at the level of MRP ATPases, and combined therapy with platinums
    N Z Khokhar
    Program in Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 7:3199-205. 2001
    ..These results strongly suggest that PDX has significant potential in the treatment of human pleural mesothelioma, particularly when coadministered with probenecid or combined with platinum compounds...
  8. ncbi request reprint Chromosomal localization of the murine RFC-1 gene encoding a folate transporter and its amplification in an antifolate resistant variant overproducing the transporter
    K Roy
    Program in Cell Biology and Genetics, Graduate School of Medical Sciences, Cornell University, New York, New York, USA
    Cancer Genet Cytogenet 105:29-38. 1998
    ..These results document the amplification at the site of a putative HSR in an L1210 cell variant of the RFC-1 gene regulating expression of the one-carbon, reduced folate transporter...
  9. doi request reprint Pralatrexate with vitamin supplementation in patients with previously treated, advanced non-small cell lung cancer: safety and efficacy in a phase 1 trial
    Christopher G Azzoli
    Memorial Sloan Kettering Cancer Center, New York City, New York, USA
    J Thorac Oncol 6:1915-22. 2011
    ..This phase 1 study evaluated the safety of higher pralatrexate doses with vitamin supplementation to minimize toxicities...
  10. ncbi request reprint Organization, structure and alternate splicing of the murine RFC-1 gene encoding a folate transporter
    B Tolner
    Laboratory for Molecular Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Gene 189:1-7. 1997
    ..The findings pertaining to alternates of exon 1 suggest that the transcription of RFC-1 variants results from two different promoters...
  11. ncbi request reprint A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors
    Christopher G Azzoli
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 13:2692-8. 2007
    ..This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer...
  12. ncbi request reprint Regulation of transcription of the murine gamma-glutamyl hydrolase gene. Delineation of core promoter A and the role of LYF-1, E2F and ETS-1 in determining tumor-specific expression
    Naoko Masumoto
    Program in Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Gene 291:169-76. 2002
    ..This is an interesting finding in light of our earlier results which located promoter B and two associated alternates of exon 1 of this gene on chromosome 17...
  13. ncbi request reprint Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promoters and alternatively spliced transcripts with 5' end heterogeneity
    B Tolner
    Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Gene 211:331-41. 1998
    ....
  14. ncbi request reprint The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index
    Yuhong She
    Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 9:3773-8. 2003
    ..We subsequently investigated the extent to which ZD1839 might improve radiation therapy (RT) in similar animal models of human cancer within the limits of tolerance at a relevant organ site...
  15. ncbi request reprint Phase I and pharmacological study of two schedules of the antifolate edatrexate in combination with cisplatin
    S A Laurie
    Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA
    Clin Cancer Res 7:501-9. 2001
    ..Responses were seen in both head and neck and non-small cell lung cancer patients. For Phase II studies, use of cisplatin 60 mg/m2 and edatrexate 80 mg/m2, both given biweekly, is recommended...
  16. ncbi request reprint Molecular cloning of the murine cMOAT ATPase
    F Fritz
    Laboratory for Molecular Therapeutics, Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Biochim Biophys Acta 1492:531-6. 2000
    ..cMOAT mRNA was also detected in mouse kidney at a low level but was not detected in other mouse organs or tumors except the Hep 1-6 murine hepatoma where expression was also in the form of the same two mRNA variants...
  17. ncbi request reprint RFC-1 gene expression regulates folate absorption in mouse small intestine
    J H Chiao
    Molecular Pharmacology and Therapeutics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 272:11165-70. 1997
    ..These results strongly suggest that pH-dependent folate absorption in this tissue is regulated by RFC-1 gene expression...
  18. ncbi request reprint Transcription of the mouse RFC-1 gene encoding a folate transporter. Multiplicity and properties of promoters with minimum requirements for their basal activity
    B Tolner
    Program of Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Gene 231:163-72. 1999
    ..These data show that both promoters regulating expression of the RFC-1 gene utilize closely spaced Sp1 sites in tandem to sustain basal transcription, at least in NIH3T3 cells, in a manner characteristic of TATA-less promoters...
  19. ncbi request reprint Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate
    L M Krug
    Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA
    Clin Cancer Res 6:3493-8. 2000
    ..These studies will also quantitate the expression of genes controlling internalization (RFC-1) and polyglutamylation of PDX in tumor cells as correlates of response...
  20. ncbi request reprint Additional organizational features of the murine folylpolyglutamate synthetase gene. Two remotely situated exons encoding an alternate 5' end and proximal open reading frame under the control of a second promoter
    K Roy
    Program of Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 272:5587-93. 1997
    ..An unusual splice variant identified infrequently in a mouse liver cDNA library was 2.67 kilobases in size and incorporated exons A1a and A1b and a segment of the downstream promoter region along with exons B1c and B1b and exons 2-15...
  21. ncbi request reprint Microarray analysis of prostate cancer progression to reduced androgen dependence: studies in unique models contrasts early and late molecular events
    F M Sirotnak
    Department of Medicine, Program of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Mol Carcinog 41:150-63. 2004
    ....
  22. ncbi request reprint Organization and structure of the mouse gamma-glutamyl hydrolase gene and the functional identification of its promoter
    T Esaki
    Program in Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Gene 234:93-100. 1999
    ..The transcription of the luciferase gene that resulted in these cells established the identity of this region as an active promoter for the mouse GH gene...
  23. ncbi request reprint Additional organizational features of the murine gamma-glutamyl hydrolase gene. Two remotely situated exons within the complement C3 gene locus encode an alternate 5' end and proximal ORF under the control of a bidirectional promoter
    N Masumoto
    Program of Molecular Pharmacology and Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, 10021, New York, NY, USA
    Gene 268:183-94. 2001
    ..Deletion of specific regions of sequence within this promoter have different effects depending upon the orientation (forward or reverse) within the reporter gene construct...
  24. ncbi request reprint A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in patients with advanced solid tumors
    Matthew G Fury
    Division of Solid Tumor Oncology, Head and Neck Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY 10021, USA
    Cancer Chemother Pharmacol 59:467-75. 2007
    ....
  25. ncbi request reprint Despite some expression of folate receptor alpha in human mesothelioma cells, internalization of methotrexate is predominantly carrier mediated
    Nushmia Z Khokhar
    Program of Molecular Pharmacology and Experimental Therapeutics and Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Thorac Cardiovasc Surg 123:862-8. 2002
    ....
  26. ncbi request reprint 10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer
    Lee M Krug
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University New York, New York 10021, USA
    Clin Cancer Res 9:2072-8. 2003
    ..The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial...
  27. ncbi request reprint Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma
    Lee M Krug
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Thorac Oncol 2:317-20. 2007
    ..In mesothelioma cell lines and xenografts, pralatrexate demonstrated significant antitumor activity...
  28. ncbi request reprint Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts
    M Motwani
    Gastrointestinal Oncology Research Laboratory, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Clin Cancer Res 7:4209-19. 2001
    ..Thus, flavopiridol combined with CPT-11 may provide a completely new therapeutic approach in the treatment of colon cancer...
  29. ncbi request reprint Cloning of mouse gamma-glutamyl hydrolase in the form of two cDNA variants with different 5' ends and encoding alternate leader peptide sequences
    T Esaki
    Program in Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Gene 219:37-44. 1998
    ..Abundance of GH mRNA among tumors varied from low to high, with no discernible correlation with their tissue of origin...
  30. ncbi request reprint Activity of a novel anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against human lymphoma is superior to methotrexate and correlates with tumor RFC-1 gene expression
    Eunice S Wang
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 6306, USA
    Leuk Lymphoma 44:1027-35. 2003
    ..These results demonstrate that the PDX has markedly greater potential activity against human NHL than MTX and warrants further preclinical and clinical evaluation...
  31. ncbi request reprint Organization and alternate splicing of the murine folylpolyglutamate synthetase gene. Different splice variants in L1210 cells encode mitochondrial or cytosolic forms of the enzyme
    K Roy
    Program in Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, Cornell University, New York, New York 10021, USA
    J Biol Chem 271:23820-7. 1996
    ....
  32. ncbi request reprint Different antifolate-resistant L1210 cell variants with either increased or decreased folylpolyglutamate synthetase gene expression at the level of mRNA transcription
    K Roy
    Program in Molecular Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 270:26918-22. 1995
    ..These results provide the first examples of constitutively altered transcriptional regulation of FPGS activity associated with acquired resistance to antifolates...
  33. ncbi request reprint Drg1, a novel target for modulating sensitivity to CPT-11 in colon cancer cells
    Monica Motwani
    Gastrointestinal Oncology Research Laboratory, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 62:3950-5. 2002
    ..Taken together, our data suggest that Drg1 is a novel gene that plays a direct role in resistance to CPT-11. Inhibition of Drg1 may provide a new means to increase the sensitivity of colon cancer cells to CPT-11...
  34. ncbi request reprint Studies with ZD1839 in preclinical models
    Francis M Sirotnak
    Laboratory for Molecular Therapeutics, Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Semin Oncol 30:12-20. 2003
    ..Ongoing preclinical studies continue to support the importance of EGFR-TK activity in the biology of solid tumors...
  35. ncbi request reprint The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation-induced apoptosis in colon and gastric cancer cells
    Christoph Jung
    Gastrointestinal Oncology Research Laboratory, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 9:6052-61. 2003
    ..In view of this, we elected to evaluate the effect of flavopiridol on potentiating RT-induced apoptosis in the human colon cancer cell line HCT-116 and the gastric cancer cell line MKN-74...