Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor
Heikki Joensuu, M.D., Peter J. Roberts, M.D., Maarit Sarlomo-Rikala, M.D., Leif C. Andersson, M.D., Pekka Tervahartiala, M.D., David Tuveson, M.D., Ph.D., Sandra L. Silberman, M.D., Ph.D., Renaud Capdeville, M.D., Sasa Dimitrijevic, Ph.D., Brian Druker, M.D., and George D. Demetri, M.D.
Gastrointestinal stromal tumors are a group of mesenchymal neoplasmsthat arise from precursors of the connective-tissue cells ofthe gastrointestinal tract.1 They occur predominantly in middle-agedand older persons, and approximately 70 percent of the tumorsare found in the stomach, 20 to 30 percent are found in thesmall intestine, and less than 10 percent are found elsewherein the gastrointestinal tract.1 Recent studies have shown thatcells in gastrointestinal stromal tumors express a growth factorreceptor with tyrosine kinase activity termed c-kit. This receptor,the product of the proto-oncogene c-kit, can be detected byimmunohistochemical staining for CD117, which appears to bethe most specific diagnostic criterion for the diagnosis ofgastrointestinal stromal tumors.2 The ligand for the c-kit receptoris stem-cell factor, also known as steel factor or c-kit ligand.3Mutations of c-kit that cause constitutive activation of thetyrosine kinase function of c-kit are detectable in most gastrointestinalstromal tumors and appear to play a central part in the pathogenesisof these tumors.4,5 These mutations result in ligand-independenttyrosine kinase activity, autophosphorylation of c-kit, uncontrolledcell proliferation, and stimulation of downstream signalingpathways, including those involving phosphatidylinositol 3-kinaseand mitogen-activated protein kinases. Gastrointestinal stromaltumors are notoriously unresponsive to cancer chemotherapy,and there is no effective therapy for advanced, metastatic disease.6
We used STI571 (Glivec, Novartis, Basel, Switzerland),7 an inhibitorof the tyrosine kinase activity of c-kit, in a patient witha gastrointestinal stromal tumor.
Case Report
In October 1996, a 50-year-old, previously healthy woman presentedwith mild abdominal discomfort and a large mass in the upperabdomen. Two tumors, 6.5 and 10 cm in diameter, were removedfrom the stomach by proximal gastric resection, and the greateromentum and mesocolic peritoneum were removed because of thepresence of multiple metastatic nodules 1 to 2 mm in diameter.Histologic examination of the specimens revealed more than 20cells undergoing mitosis per 10 high-power fields and identifiedthe masses as a gastrointestinal stromal tumor. The diagnosiswas confirmed by immunostaining for CD117, and a c-kit mutationconsisting of a deletion of 15 bp from exon 11 was detectedin tumor DNA amplified by the polymerase chain reaction.8
Recurrent tumors in the left upper abdomen, two liver metastases,and multiple small intra-abdominal metastases were excised inFebruary 1998, and in September 1998 six more liver metastasesand an ovarian metastasis were removed. Seven cycles of chemotherapywith mesna, doxorubicin, ifosfamide, and dacarbazine were givenfrom November 1998 to March 1999 for additional liver metastases,but there was no clinical response. In March 1999, progressionof the disease prompted removal of a metastasis that was obstructingthe large bowel and 45 smaller metastases by laparotomy. Thepatient was treated between April 1999 and February 2000 with400 mg of thalidomide once daily and 900,000 U of subcutaneousinterferon alfa three times a day, but by February 2000 theliver metastases were progressing in size and number, and severalnew intra-abdominal and mesenteric metastases were documentedby magnetic resonance imaging (MRI).
The patient then agreed to participate in this study of STI571.The institutional review board of Helsinki University CentralHospital approved the study, and the patient gave written informedconsent. Treatment with four 100-mg capsules of STI571 oncedaily was started in March 2000. This dose was based on evaluationsof the safety and tolerability of STI571 in patients with chronicmyeloid leukemia.9 Toxicity was assessed at follow-up visitsevery two to four weeks, and blood-cell counts and blood chemicalvalues were analyzed every one to two weeks. The response totreatment was assessed with dynamic MRI, positron-emission tomography(PET) with [18F]fluorodeoxyglucose as a tracer, and serial needlebiopsies of a liver metastasis.
Methods
Immunostaining for CD117 was performed with a polyclonal rabbitantibody (sc-168, Santa Cruz Biotechnology, Santa Cruz, Calif.)diluted 1:200 and for Ki-67 antigen, a marker of cell proliferation,with another polyclonal rabbit antibody (A0047, Dako, Glostrup,Denmark) diluted 1:150. Staining was analyzed with a detectionkit (ChemMate Peroxidase/DAB, Dako) designed to be used withan automated immunostaining system (TechMate 500 Medical Systems,Ventana, Tucson, Ariz.).
Results
Evaluation of the Response by MRI
When measured as the sum of the products of two perpendicularaxes of each of eight large liver metastases, the size of thetumor one day before the start of treatment with STI571 was112.5 cm2. On subsequent MRI scans, the size of the tumor wasas follows: 67 cm2 (after 2 weeks of treatment), 54 cm2 (at1 month), 42 cm2 (at 2 months), 36 cm2 (at 4 months), 33 cm2(at 5.5 months), and 28 cm2 (at 8 months). No new lesions appeared,and 6 of the 28 liver metastases disappeared. At the peripheralrim of the hepatic metastases, the considerable contrast enhancementthat had been seen on the dynamic MRI scans (a finding consistentwith the presence of viable tumor) before the beginning of STI571treatment was dramatically reduced; indeed, no enhancement wasseen on dynamic MRI scans obtained during treatment. In addition,many of the metastases became hypodense (Figure 1). As of February2001, the tumor at all sites continued to respond to treatment,and the patient remained clinically well.
Figure 1. Transaxial Gadolinium-Enhanced T1-Weighted MRI Studies of the Upper Abdomen.
Before STI571 therapy (Panel A), multiple metastatic lesions were present in the liver. Contrast enhancement of the metastases was highly heterogeneous, with strong enhancement at the periphery. Enhancement was less intense in the central parts of the metastases, suggesting necrosis. After four weeks of treatment with STI571 (Panel B), the metastases had a cyst-like appearance. After eight months of treatment (Panel C), the metastases were smaller, and some had disappeared.
Evaluation by PET Scanning with [18F]Fluorodeoxyglucose
Multiple liver metastases and increased accumulation of [18F]fluorodeoxyglucosein the right renal pelvis and ureter, a finding indicative ofhydronephrosis, were seen on a PET scan obtained four days beforetreatment with STI571 was started (Figure 2A). On a PET scanobtained one month after STI571 was started, no abnormal uptakeof [18F]fluorodeoxyglucose was seen in the liver or right kidney(Figure 2B). In a finding consistent with the changed, hypodenseappearance of metastases on MRI, "cold" areas, with less uptakeof [18F]fluorodeoxyglucose than in the surrounding liver parenchyma,were seen at the sites of liver metastases on a PET scan obtainedtwo months after STI571 was started.
Figure 2. PET Studies with [18F]Fluorodeoxyglucose as the Tracer.
Before STI571 therapy (Panel A), there were multiple metastases in the liver and upper abdomen. There was also marked retention of [18F]fluorodeoxyglucose in the right renal pelvis and ureter, a finding indicative of hydronephrosis. After four weeks of treatment (Panel B), there was no abnormal uptake of tracer in the liver or right kidney.
Histologic Findings
Serial needle-biopsy specimens of a ventrally located livermetastasis obtained one and two months after STI571 treatmentwas started showed a marked decrease in the density of the tumorcells, as well as myxoid degeneration and scarring, with nosigns of an inflammatory reaction or necrosis (Figure 3). Thefew remaining cells in the myxoid background were probably pyknotictumor cells and not mast cells, according to their immunohistochemicalcharacteristics (positive for CD117 and negative for CD45 andGiemsa stain). These cells did not stain for the cell-proliferationmarker Ki-67, suggesting that they were not actively dividing.Endothelial cells within the lesion were histologically normal,with no suggestion of cytotoxic effects.
Figure 3. Histologic Appearance of the Primary Gastrointestinal Stromal Tumor (Hematoxylin and Eosin [Panels A, B, and C] and Immunostaining for Ki-67 [Panels D and E] and CD117 [Panels F and G]).
In 1996, frequent mitotic figures were present (Panel A, x400). In 2000, a pretreatment biopsy specimen from a cellular liver metastasis (Panel B, x200) had a high frequency of Ki-67–positive nuclei (Panel D, x200) and staining for CD117 (Panel F, x200). After three weeks of STI571 treatment, histologic examination of the liver metastasis showed myxoid degeneration and a few pyknotic cells (Panel C; hematoxylin and eosin, x200), no staining for Ki-67 (Panel E, x200), and only a few, scattered CD117-positive cells (Panel G, x200).
Side Effects of STI571
STI571 was well tolerated, with only mild, transient nausearelated to the swallowing of the capsules; this minor symptomimproved when the drug was taken with food. No clinically significantchanges were noted in the peripheral blood-cell counts or bloodchemical values. No drug-related adverse effects on the liver,kidneys, or heart were observed. All of the main subjectiveadverse effects were mild (grade 1 according to version 2.0of the Common Toxicity Criteria of the National Cancer Institute10)and consisted of an increased frequency of bowel movements (twoto four a day), occasional muscle cramps in the legs, and slight,transient ankle edema. The World Health Organization performancestatus improved from 1 (indicating the presence of cancer-relatedsymptoms) to 0 (normal) during STI571 therapy.
Discussion
There is no effective therapy for unresectable or metastaticgastrointestinal stromal tumor, which is invariably fatal. STI571,a phenylaminopyrimidine derivative, is a small molecule thatselectively inhibits the enzymatic activity of several tyrosinekinases, including ABL and the BCR-ABL fusion protein of chronicmyeloid leukemia and Philadelphia chromosome–positiveacute lymphoblastic leukemia; platelet-derived growth factorreceptor; and the product of the c-kit gene. This selectiveactivity of STI571 suggests that it has a relatively narrowspectrum of anticancer activity. Our results indicate that inhibitionby STI571 of the constitutively active mutant c-kit tyrosinekinase of gastrointestinal stromal tumors is an effective therapyfor these tumors.
Our patient had a rapidly progressive metastatic gastrointestinalstromal tumor that was resistant to chemotherapy. She had acomplete metabolic response within one month after the startof STI571 treatment, as shown by negative findings on PET andthe 52 percent decrease in tumor volume on MRI. Many of theliver metastases became hypodense, and the tumor enhancementon dynamic MRI was markedly reduced, suggesting decreased viability.Histopathological evaluation of serial needle-biopsy specimensof a liver metastasis confirmed the anticancer activity of thistreatment. With treatment, extensive fibrosis, myxoid degeneration,and a few scattered, nonproliferating CD117-positive cells replacedthe abundant, frequently mitotic, Ki-67–positive gastrointestinalstromal-tumor cells. The absence of visible damage to the vascularendothelial cells in the biopsy specimens indicated the selectiveaction of STI571 in this patient. These responses have now continuedduring more than 11 months of treatment. In addition, the toxicityof STI571 therapy was minimal and consisted mainly of mild dyspepsiaand a slightly increased frequency of bowel movements.
In addition to its activity in BCR-ABL–positive leukemias,STI571 may be active in solid tumors that rely on the expressionof c-kit, ABL, or platelet-derived growth factor receptor. Amongthe solid tumors, gastrointestinal stromal tumors may be especiallyresponsive to STI571 because they uniformly express c-kit andbecause a tumor-specific c-kit mutation appears to be the chiefcause of this neoplasm. Our patient's favorable response toSTI571 supports the concept that specific inhibition of tyrosinekinase is a clinically useful therapeutic intervention for tumorsin which aberrant tyrosine kinase signaling is critical.
We are indebted to J. Lasota and M. Miettinen (Department ofSoft Tissue Pathology, Armed Forces Institute of Pathology,Washington, D.C.) for allowing us to refer to the results ofc-kit mutation analysis in this patient; to H. Minn (Turku PETCenter, University of Turku, Turku, Finland) for skillful analysesof PET images; to Christopher Fletcher, Jonathan Fletcher, andSamuel Singer (Departments of Pathology and Surgical Oncology,Dana–Farber Cancer Institute, Brigham and Women's Hospital,and Harvard Medical School, Boston); and to Charles D. Blankeand Michael C. Heinrich (Department of Medical Oncology, OregonHealth Sciences University, Portland) for helpful discussions.
Source Information
From the Departments of Oncology (H.J.) and Radiology (P.T.), Helsinki University Central Hospital, Helsinki, Finland; the Department of Surgery, Turku University Central Hospital, Turku, Finland (P.J.R.); the Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (M.S.-R., L.C.A.); the Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge (D.T.); the Center for Sarcoma and Bone Oncology, Department of Adult Oncology, Dana–Farber Cancer Institute and Harvard Medical School, Boston (D.T., G.D.D.); Novartis Oncology, East Hanover, N.J. (S.S.), and Basel, Switzerland (R.C., S.D.); and the Department of Medical Oncology, Oregon Health Sciences University, Portland (B.D.). Drs. Joensuu and Roberts contributed equally to the article.
Address reprint requests to Dr. Joensuu at the Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 180, FIN-00029, Helsinki, Finland.
References
Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 1999;30:1213-1220. [CrossRef][Web of Science][Medline]
Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998;11:728-734. [Web of Science][Medline]
Zsebo KM, Williams DA, Geissler EN, et al. Stem cell factor is encoded at the S1 locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990;63:213-224. [CrossRef][Web of Science][Medline]
Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-580. [Free Full Text]
Lux ML, Rubin BP, Biase TL, et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 2000;156:791-795. [Free Full Text]
Plaat BE, Hollema H, Molenaar WM, et al. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol 2000;18:3211-3220. [Free Full Text]
Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561-566. [CrossRef][Web of Science][Medline]
Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M. Mutations in exon 11 of c-kit occur preferentially in malignant versus benign gastrointestinal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999;154:53-60. [Free Full Text]
Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-1037. [Free Full Text]
Cancer Therapy Evaluation Program. Common toxicity criteria, version 2.0. Bethesda, Md.: National Cancer Institute, March 1998.
Demetri, G. D., Wang, Y., Wehrle, E., Racine, A., Nikolova, Z., Blanke, C. D., Joensuu, H., von Mehren, M.
(2009). Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors. JCO
27: 3141-3147
[Abstract][Full Text]
Renouf, D. J., Wilson, L., Blanke, C. D.
(2009). Successes and Challenges in Translational Research: The Development of Targeted Therapy for Gastrointestinal Stromal Tumours. Clin. Cancer Res.
15: 3908-3911
[Abstract][Full Text]
Contractor, K. B., Aboagye, E. O.
(2009). Monitoring Predominantly Cytostatic Treatment Response with 18F-FDG PET. JNM
50: 97S-105S
[Abstract][Full Text]
Sheu, J. J.-C., Hua, C.-H., Wan, L., Lin, Y.-J., Lai, M.-T., Tseng, H.-C., Jinawath, N., Tsai, M.-H., Chang, N.-W., Lin, C.-F., Lin, C.-C., Hsieh, L.-J., Wang, T.-L., Shih, I.-M., Tsai, F.-J.
(2009). Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma. Cancer Res.
69: 2568-2576
[Abstract][Full Text]
Huynh, H., Lee, J. W.J., Chow, P. K.H., Ngo, V. C., Lew, G. B., Lam, I. W.L., Ong, H. S., Chung, A., Soo, K. C.
(2009). Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor. Molecular Cancer Therapeutics
8: 152-159
[Abstract][Full Text]
Heinrich, M. C., Owzar, K., Corless, C. L., Hollis, D., Borden, E. C., Fletcher, C. D.M., Ryan, C. W., von Mehren, M., Blanke, C. D., Rankin, C., Benjamin, R. S., Bramwell, V. H., Demetri, G. D., Bertagnolli, M. M., Fletcher, J. A.
(2008). Correlation of Kinase Genotype and Clinical Outcome in the North American Intergroup Phase III Trial of Imatinib Mesylate for Treatment of Advanced Gastrointestinal Stromal Tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. JCO
26: 5360-5367
[Abstract][Full Text]
Yamaguchi, U., Nakayama, R., Honda, K., Ichikawa, H., Hasegawa, T., Shitashige, M., Ono, M., Shoji, A., Sakuma, T., Kuwabara, H., Shimada, Y., Sasako, M., Shimoda, T., Kawai, A., Hirohashi, S., Yamada, T.
(2008). Distinct Gene Expression-Defined Classes of Gastrointestinal Stromal Tumor. JCO
26: 4100-4108
[Abstract][Full Text]
Mabasa, V. H, Taylor, S. C., Chu, C. C., Moravan, V., Johnston, K., Peacock, S., Knowling, M.
(2008). Verification of imatinib cost-effectiveness in advanced gastrointestinal stromal tumor in British Columbia (VINCE-BC study). J Oncol Pharm Pract
14: 105-112
[Abstract]
Mussi, C., Schildhaus, H.-U., Gronchi, A., Wardelmann, E., Hohenberger, P.
(2008). Therapeutic Consequences from Molecular Biology for Gastrointestinal Stromal Tumor Patients Affected by Neurofibromatosis Type 1. Clin. Cancer Res.
14: 4550-4555
[Abstract][Full Text]
Montero, J. C., Lopez-Perez, R., San Miguel, J. F., Pandiella, A.
(2008). Expression of c-Kit isoforms in multiple myeloma: differences in signaling and drug sensitivity. haematol
93: 851-859
[Abstract][Full Text]
Gioni, V., Karampinas, T., Voutsinas, G., Roussidis, A. E., Papadopoulos, S., Karamanos, N. K., Kletsas, D.
(2008). Imatinib Mesylate Inhibits Proliferation and Exerts an Antifibrotic Effect in Human Breast Stroma Fibroblasts. Mol Cancer Res
6: 706-714
[Abstract][Full Text]
Tabone-Eglinger, S., Subra, F., El Sayadi, H., Alberti, L., Tabone, E., Michot, J.-P., Theou-Anton, N., Lemoine, A., Blay, J.-Y., Emile, J.-F.
(2008). KIT Mutations Induce Intracellular Retention and Activation of an Immature Form of the KIT Protein in Gastrointestinal Stromal Tumors. Clin. Cancer Res.
14: 2285-2294
[Abstract][Full Text]
Van den Abbeele, A. D.
(2008). The Lessons of GIST--PET and PET/CT: A New Paradigm for Imaging. The Oncologist
13: 8-13
[Abstract][Full Text]
Judson, I. R.
(2008). Imatinib for Patients With Liver or Kidney Dysfunction: No Need to Modify the Dose. JCO
26: 521-522
[Full Text]
Gibbons, J., Egorin, M. J., Ramanathan, R. K., Fu, P., Mulkerin, D. L., Shibata, S., Takimoto, C. H.M., Mani, S., LoRusso, P. A., Grem, J. L., Pavlick, A., Lenz, H.-J., Flick, S. M., Reynolds, S., Lagattuta, T. F., Parise, R. A., Wang, Y., Murgo, A. J., Ivy, S. P., Remick, S. C.
(2008). Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. JCO
26: 570-576
[Abstract][Full Text]
Blanke, C. D., Demetri, G. D., von Mehren, M., Heinrich, M. C., Eisenberg, B., Fletcher, J. A., Corless, C. L., Fletcher, C. D.M., Roberts, P. J., Heinz, D., Wehre, E., Nikolova, Z., Joensuu, H.
(2008). Long-Term Results From a Randomized Phase II Trial of Standard- Versus Higher-Dose Imatinib Mesylate for Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing KIT. JCO
26: 620-625
[Abstract][Full Text]
Blanke, C. D., Rankin, C., Demetri, G. D., Ryan, C. W., von Mehren, M., Benjamin, R. S., Raymond, A. K., Bramwell, V. H.C., Baker, L. H., Maki, R. G., Tanaka, M., Hecht, J. R., Heinrich, M. C., Fletcher, C. D.M., Crowley, J. J., Borden, E. C.
(2008). Phase III Randomized, Intergroup Trial Assessing Imatinib Mesylate At Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing the Kit Receptor Tyrosine Kinase: S0033. JCO
26: 626-632
[Abstract][Full Text]
Joensuu, H., De Braud, F., Coco, P., De Pas, T., Putzu, C., Spreafico, C., Bono, P., Bosselli, S., Jalava, T., Laurent, D., Casali, P. G.
(2008). Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate. Ann Oncol
19: 173-177
[Abstract][Full Text]
Boss, D. S., Olmos, R. V., Sinaasappel, M., Beijnen, J. H., Schellens, J. H. M.
(2008). Application of PET/CT in the Development of Novel Anticancer Drugs. The Oncologist
13: 25-38
[Abstract][Full Text]
Holdsworth, C. H., Badawi, R. D., Manola, J. B., Kijewski, M. F., Israel, D. A., Demetri, G. D., Van den Abbeele, A. D.
(2007). CT and PET: Early Prognostic Indicators of Response to Imatinib Mesylate in Patients with Gastrointestinal Stromal Tumor. Am. J. Roentgenol.
189: W324-W330
[Abstract][Full Text]
Jones, C., Rodriguez-Pinilla, M., Lambros, M., Bax, D., Messahel, B., Vujanic, G. M, Reis-Filho, J. S, Pritchard-Jones, K.
(2007). c-KIT overexpression, without gene amplification and mutation, in paediatric renal tumours. J. Clin. Pathol.
60: 1226-1231
[Abstract][Full Text]
Skubitz, K. M., D'Adamo, D. R.
(2007). Sarcoma. Mayo Clin Proc.
82: 1409-1432
[Abstract][Full Text]
Armbrust, T, Sobotta, M, Ramadori, G
(2007). Follow up of three cases after adjuvant treatment of high risk gastrointestinal stromal tumors with Imatinib. Ann Oncol
18: 1123-1125
[Full Text]
Sleijfer, S., Wiemer, E., Seynaeve, C., Verweij, J.
(2007). Improved Insight into Resistance Mechanisms to Imatinib in Gastrointestinal Stromal Tumors: A Basis for Novel Approaches and Individualization of Treatment. The Oncologist
12: 719-726
[Abstract][Full Text]
Choi, H., Charnsangavej, C., Faria, S. C., Macapinlac, H. A., Burgess, M. A., Patel, S. R., Chen, L. L., Podoloff, D. A., Benjamin, R. S.
(2007). Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria. JCO
25: 1753-1759
[Abstract][Full Text]
Pollack, I. F., Jakacki, R. I., Blaney, S. M., Hancock, M. L., Kieran, M. W., Phillips, P., Kun, L. E., Friedman, H., Packer, R., Banerjee, A., Geyer, J. R., Goldman, S., Poussaint, T. Y., Krasin, M. J., Wang, Y., Hayes, M., Murgo, A., Weiner, S., Boyett, J. M.
(2007). Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report. Neuro Oncol
9: 145-160
[Abstract][Full Text]
Jamali, F. R., Darwiche, S. S., El-Kinge, N., Tawil, A., Soweid, A. M.
(2007). Disease Progression Following Imatinib Failure in Gastrointestinal Stromal Tumors: Role of Surgical Therapy. The Oncologist
12: 438-442
[Abstract][Full Text]
Blay, J.-Y., Le Cesne, A., Ray-Coquard, I., Bui, B., Duffaud, F., Delbaldo, C., Adenis, A., Viens, P., Rios, M., Bompas, E., Cupissol, D., Guillemet, C., Kerbrat, P., Fayette, J., Chabaud, S., Berthaud, P., Perol, D.
(2007). Prospective Multicentric Randomized Phase III Study of Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors Comparing Interruption Versus Continuation of Treatment Beyond 1 Year: The French Sarcoma Group. JCO
25: 1107-1113
[Abstract][Full Text]
Yeh, C.-N., Chen, T.-W., Lee, H.-L., Liu, Y.-Y., Chao, T.-C., Hwang, T.-L., Jan, Y.-Y., Chen, M.-F.
(2007). Kinase Mutations and Imatinib Mesylate Response for 64 Taiwanese with Advanced GIST: Preliminary Experience from Chang Gung Memorial Hospital. Ann. Surg. Oncol.
14: 1123-1128
[Abstract][Full Text]
Bozulic, L., Morin, P. J., Hunter, T., Hemmings, B. A.
(2007). Meeting Report: Targeting the Kinome--20 Years of Tyrosine Kinase Inhibitor Research in Basel. Sci Signal
2007: pe8-pe8
[Abstract][Full Text]
Haller, F., Detken, S., Schulten, H.-J., Happel, N., Gunawan, B., Kuhlgatz, J., Fuzesi, L.
(2007). Surgical Management After Neoadjuvant Imatinib Therapy in Gastrointestinal Stromal Tumours (GISTs) with Respect to Imatinib Resistance Caused by Secondary KIT Mutations. Ann. Surg. Oncol.
14: 526-532
[Abstract][Full Text]
Wu, Y., Zhu, X., Ding, Y.
(2007). Diagnosis and Treatment of Gastrointestinal Stromal Tumors of the Stomach: Report of 28 Cases.. Annals of Clinical & Laboratory Science
37: 15-21
[Abstract][Full Text]
Gold, J. S., van der Zwan, S. M., Gonen, M., Maki, R. G., Singer, S., Brennan, M. F., Antonescu, C. R., De Matteo, R. P.
(2007). Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors. Ann. Surg. Oncol.
14: 134-142
[Abstract][Full Text]
Stewart, D. R, Corless, C. L, Rubin, B. P, Heinrich, M. C, Messiaen, L. M, Kessler, L. J, Zhang, P. J, Brooks, D. G
(2007). Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1. J. Med. Genet.
44: e61-e61
[Abstract][Full Text]
Kantarjian, H. M., Talpaz, M., Giles, F., O'Brien, S., Cortes, J.
(2006). New Insights into the Pathophysiology of Chronic Myeloid Leukemia and Imatinib Resistance. ANN INTERN MED
145: 913-923
[Abstract][Full Text]
Lassau, N., Lamuraglia, M., Chami, L., Leclere, J., Bonvalot, S., Terrier, P., Roche, A., Le Cesne, A.
(2006). Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography.. Am. J. Roentgenol.
187: 1267-1273
[Abstract][Full Text]
Delbaldo, C., Chatelut, E., Re, M., Deroussent, A., Seronie-Vivien, S., Jambu, A., Berthaud, P., Le Cesne, A., Blay, J.-Y., Vassal, G.
(2006). Pharmacokinetic-Pharmacodynamic Relationships of Imatinib and Its Main Metabolite in Patients with Advanced Gastrointestinal Stromal Tumors.. Clin. Cancer Res.
12: 6073-6078
[Abstract][Full Text]
(2006). Image of the month--answer.. Arch Surg
141: 1044-1044
[Full Text]
Meza-Zepeda, L. A., Kresse, S. H., Barragan-Polania, A. H., Bjerkehagen, B., Ohnstad, H. O., Namlos, H. M., Wang, J., Kristiansen, B. E., Myklebost, O.
(2006). Array Comparative Genomic Hybridization Reveals Distinct DNA Copy Number Differences between Gastrointestinal Stromal Tumors and Leiomyosarcomas.. Cancer Res.
66: 8984-8993
[Abstract][Full Text]
Matsukuma, S., Yoshihara, M., Kasai, F., Kato, A., Yoshida, A., Akaike, M., Kobayashi, O., Nakayama, H., Sakuma, Y., Yoshida, T., Kameda, Y., Tsuchiya, E., Miyagi, Y.
(2006). Rapid and Simple Detection of Hot Spot Point Mutations of Epidermal Growth Factor Receptor, BRAF, and NRAS in Cancers Using the Loop-Hybrid Mobility Shift Assay. J. Mol. Diagn.
8: 504-512
[Abstract][Full Text]
Linton, K M, Taylor, M B, Radford, J A
(2006). Response evaluation in gastrointestinal stromal tumours treated with imatinib: misdiagnosis of disease progression on CT due to cystic change in liver metastases. Br. J. Radiol.
79: e40-e44
[Abstract][Full Text]
Gabillot-Carre, M., Lepelletier, Y., Humbert, M., de Sepuvelda, P., Hamouda, N. B., Zappulla, J. P., Liblau, R., Ribadeau-Dumas, A., Machavoine, F., Letard, S., Baude, C., Hermant, A., Yang, Y., Vargaftig, J., Bodemer, C., Morelon, E., Lortholary, O., Recher, C., Laurent, G., Dy, M., Arock, M., Dubreuil, P., Hermine, O.
(2006). Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells. Blood
108: 1065-1072
[Abstract][Full Text]
Tornillo, L, Terracciano, L M
(2006). An update on molecular genetics of gastrointestinal stromal tumours.. J. Clin. Pathol.
59: 557-563
[Abstract][Full Text]
Kersting, C, Packeisen, J, Leidinger, B, Brandt, B, von Wasielewski, R, Winkelmann, W, van Diest, P J, Gosheger, G, Buerger, H
(2006). Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue sarcomas. J. Clin. Pathol.
59: 585-590
[Abstract][Full Text]
Tarn, C., Skorobogatko, Y. V., Taguchi, T., Eisenberg, B., von Mehren, M., Godwin, A. K.
(2006). Therapeutic Effect of Imatinib in Gastrointestinal Stromal Tumors: AKT Signaling Dependent and Independent Mechanisms.. Cancer Res.
66: 5477-5486
[Abstract][Full Text]
Hahn, S. M., Fraker, D. L., Mick, R., Metz, J., Busch, T. M., Smith, D., Zhu, T., Rodriguez, C., Dimofte, A., Spitz, F., Putt, M., Rubin, S. C., Menon, C., Wang, H.-W., Shin, D., Yodh, A., Glatstein, E.
(2006). A Phase II Trial of Intraperitoneal Photodynamic Therapy for Patients with Peritoneal Carcinomatosis and Sarcomatosis. Clin. Cancer Res.
12: 2517-2525
[Abstract][Full Text]
Thomson, J., Schofield, P., Mileshkin, L., Agalianos, E., Savulescu, J., Zalcberg, J., Jefford, M.
(2006). Do oncologists discuss expensive anti-cancer drugs with their patients?. Ann Oncol
17: 702-708
[Abstract][Full Text]
Hong, X., Choi, H., Loyer, E. M., Benjamin, R. S., Trent, J. C., Charnsangavej, C.
(2006). Gastrointestinal Stromal Tumor: Role of CT in Diagnosis and in Response Evaluation and Surveillance after Treatment with Imatinib.. RadioGraphics
26: 481-495
[Abstract][Full Text]
Warakaulle, D. R., Gleeson, F.
(2006). MDCT Appearance of Gastrointestinal Stromal Tumors After Therapy with Imatinib Mesylate. Am. J. Roentgenol.
186: 510-515
[Abstract][Full Text]
von Schulthess, G. K., Steinert, H. C., Hany, T. F.
(2006). Integrated PET/CT: Current Applications and Future Directions. Radiology
238: 405-422
[Abstract][Full Text]
Rao, A. S., Kremenevskaja, N., von Wasielewski, R., Jakubcakova, V., Kant, S., Resch, J., Brabant, G.
(2006). Wnt/{beta}-Catenin Signaling Mediates Antineoplastic Effects of Imatinib Mesylate (Gleevec) in Anaplastic Thyroid Cancer. J. Clin. Endocrinol. Metab.
91: 159-168
[Abstract][Full Text]
Kondo, S., Yamaguchi, U., Sakurai, S., Ikezawa, Y., Chuman, H., Tateishi, U., Furuta, K., Hasegawa, T.
(2005). Cytogenetic Confirmation of a Gastrointestinal Stromal Tumor and Ewing Sarcoma/Primitive Neuroectodermal Tumor in a Single Patient. Jpn J Clin Oncol
35: 753-756
[Abstract][Full Text]
McLean, S. R., Gana-Weisz, M., Hartzoulakis, B., Frow, R., Whelan, J., Selwood, D., Boshoff, C.
(2005). Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala. Molecular Cancer Therapeutics
4: 2008-2015
[Abstract][Full Text]
Scher, H. I., Sawyers, C. L.
(2005). Biology of Progressive, Castration-Resistant Prostate Cancer: Directed Therapies Targeting the Androgen-Receptor Signaling Axis. JCO
23: 8253-8261
[Abstract][Full Text]
Jefford, M., Savulescu, J., Thomson, J., Schofield, P., Mileshkin, L., Agalianos, E., Zalcberg, J.
(2005). Medical paternalism and expensive unsubsidised drugs. BMJ
331: 1075-1077
[Full Text]
Bell, D. W., Lynch, T. J., Haserlat, S. M., Harris, P. L., Okimoto, R. A., Brannigan, B. W., Sgroi, D. C., Muir, B., Riemenschneider, M. J., Iacona, R. B., Krebs, A. D., Johnson, D. H., Giaccone, G., Herbst, R. S., Manegold, C., Fukuoka, M., Kris, M. G., Baselga, J., Ochs, J. S., Haber, D. A.
(2005). Epidermal Growth Factor Receptor Mutations and Gene Amplification in Non-Small-Cell Lung Cancer: Molecular Analysis of the IDEAL/INTACT Gefitinib Trials. JCO
23: 8081-8092
[Abstract][Full Text]
Theou, N., Gil, S., Devocelle, A., Julie, C., Lavergne-Slove, A., Beauchet, A., Callard, P., Farinotti, R., Le Cesne, A., Lemoine, A., Faivre-Bonhomme, L., Emile, J.-F.
(2005). Multidrug Resistance Proteins in Gastrointestinal Stromal Tumors: Site-Dependent Expression and Initial Response to Imatinib. Clin. Cancer Res.
11: 7593-7598
[Abstract][Full Text]
Sleijfer, S., Seynaeve, C., Verweij, J.
(2005). Using Single-Agent Therapy in Adult Patients with Advanced Soft Tissue Sarcoma Can Still Be Considered Standard Care. The Oncologist
10: 833-841
[Abstract][Full Text]
Baird, K., Davis, S., Antonescu, C. R., Harper, U. L., Walker, R. L., Chen, Y., Glatfelter, A. A., Duray, P. H., Meltzer, P. S.
(2005). Gene Expression Profiling of Human Sarcomas: Insights into Sarcoma Biology. Cancer Res.
65: 9226-9235
[Abstract][Full Text]
Martin, J., Poveda, A., Llombart-Bosch, A., Ramos, R., Lopez-Guerrero, J. A., del Muro, J. G., Maurel, J., Calabuig, S., Gutierrez, A., de Sande, J. L. G., Martinez, J., De Juan, A., Lainez, N., Losa, F., Alija, V., Escudero, P., Casado, A., Garcia, P., Blanco, R., Buesa, J. M.
(2005). Deletions Affecting Codons 557-558 of the c-KIT Gene Indicate a Poor Prognosis in Patients With Completely Resected Gastrointestinal Stromal Tumors: A Study by the Spanish Group for Sarcoma Research (GEIS). JCO
23: 6190-6198
[Abstract][Full Text]
Rossi, G, Sartori, G, Valli, R, Bertolini, F, Bigiani, N, Schirosi, L, Cavazza, A, Luppi, G
(2005). The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour. J. Clin. Pathol.
58: 991-993
[Abstract][Full Text]
Carter, T. A., Wodicka, L. M., Shah, N. P., Velasco, A. M., Fabian, M. A., Treiber, D. K., Milanov, Z. V., Atteridge, C. E., Biggs, W. H. III, Edeen, P. T., Floyd, M., Ford, J. M., Grotzfeld, R. M., Herrgard, S., Insko, D. E., Mehta, S. A., Patel, H. K., Pao, W., Sawyers, C. L., Varmus, H., Zarrinkar, P. P., Lockhart, D. J.
(2005). Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc. Natl. Acad. Sci. USA
102: 11011-11016
[Abstract][Full Text]
Rubin, B. P., Antonescu, C. R., Scott-Browne, J. P., Comstock, M. L., Gu, Y., Tanas, M. R., Ware, C. B., Woodell, J.
(2005). A Knock-In Mouse Model of Gastrointestinal Stromal Tumor Harboring Kit K641E. Cancer Res.
65: 6631-6639
[Abstract][Full Text]
Petti, F., Thelemann, A., Kahler, J., McCormack, S., Castaldo, L., Hunt, T., Nuwaysir, L., Zeiske, L., Haack, H., Sullivan, L., Garton, A., Haley, J. D.
(2005). Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a novel thiophene kinase inhibitor OSI-930. Molecular Cancer Therapeutics
4: 1186-1197
[Abstract][Full Text]
Juurikivi, A, Sandler, C, Lindstedt, K A, Kovanen, P T, Juutilainen, T, Leskinen, M J, Maki, T, Eklund, K K
(2005). Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis. Ann Rheum Dis
64: 1126-1131
[Abstract][Full Text]
Korja, M, Finne, J, Salmi, T T, Haapasalo, H, Tanner, M, Isola, J
(2005). No GIST-type c-kit gain of function mutations in neuroblastic tumours. J. Clin. Pathol.
58: 762-765
[Abstract][Full Text]
Loughrey, M B, Mitchell, C, Mann, G B, Michael, M, Waring, P M
(2005). Gastrointestinal stromal tumour treated with neoadjuvant imatinib. J. Clin. Pathol.
58: 779-781
[Abstract][Full Text]
Nunobe, S., Sano, T., Shimada, K., Sakamoto, Y., Kosuge, T.
(2005). Surgery Including Liver Resection for Metastatic Gastrointestinal Stromal Tumors or Gastrointestinal Leiomyosarcomas. Jpn J Clin Oncol
35: 338-341
[Abstract][Full Text]
Antonescu, C. R., Besmer, P., Guo, T., Arkun, K., Hom, G., Koryotowski, B., Leversha, M. A., Jeffrey, P. D., Desantis, D., Singer, S., Brennan, M. F., Maki, R. G., DeMatteo, R. P.
(2005). Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation. Clin. Cancer Res.
11: 4182-4190
[Abstract][Full Text]
Yoshiji, H., Noguchi, R., Kuriyama, S., Ikenaka, Y., Yoshii, J., Yanase, K., Namisaki, T., Kitade, M., Masaki, T., Fukui, H.
(2005). Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats. Am. J. Physiol. Gastrointest. Liver Physiol.
288: G907-G913
[Abstract][Full Text]
Li, F. P., Fletcher, J. A., Heinrich, M. C., Garber, J. E., Sallan, S. E., Curiel-Lewandrowski, C., Duensing, A., van de Rijn, M., Schnipper, L. E., Demetri, G. D.
(2005). Familial Gastrointestinal Stromal Tumor Syndrome: Phenotypic and Molecular Features in a Kindred. JCO
23: 2735-2743
[Abstract][Full Text]
Kelloff, G. J., Hoffman, J. M., Johnson, B., Scher, H. I., Siegel, B. A., Cheng, E. Y., Cheson, B. D., O'Shaughnessy, J., Guyton, K. Z., Mankoff, D. A., Shankar, L., Larson, S. M., Sigman, C. C., Schilsky, R. L., Sullivan, D. C.
(2005). Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development. Clin. Cancer Res.
11: 2785-2808
[Abstract][Full Text]
Blay, J.-Y., Bonvalot, S., Casali, P., Choi, H., Debiec-Richter, M., Dei Tos, A. P., Emile, J.-F., Gronchi, A., Hogendoorn, P. C. W., Joensuu, H., Le Cesne, A., Mac Clure, J., Maurel, J., Nupponen, N., Ray-Coquard, I., Reichardt, P., Sciot, R., Stroobants, S., van Glabbeke, M., van Oosterom, A., Demetri, G. D., On behalf of the GIST consensus meeting panelists,
(2005). Consensus meeting for the management of gastrointestinal stromal tumors * Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol
16: 566-578
[Abstract][Full Text]
Tanaka, A., Konno, M., Muto, S., Kambe, N., Morii, E., Nakahata, T., Itai, A., Matsuda, H.
(2005). A novel NF-{kappa}B inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors. Blood
105: 2324-2331
[Abstract][Full Text]
De Giorgi, U., Verweij, J.
(2005). Imatinib and gastrointestinal stromal tumors: Where do we go from here?. Molecular Cancer Therapeutics
4: 495-501
[Abstract][Full Text]
Busalacchi, P. J. B. Sr., de la Calle, M. A. C., Torroba, A., del Rio, S. T.
(2005). Gastrointestinal Stromal Tumor with Metastases in an Adult Woman Treated with Imatinib Mesylate: MDCT Findings. Am. J. Roentgenol.
184: S58-S61
[Full Text]
Sihto, H., Sarlomo-Rikala, M., Tynninen, O., Tanner, M., Andersson, L. C., Franssila, K., Nupponen, N. N., Joensuu, H.
(2005). KIT and Platelet-Derived Growth Factor Receptor Alpha Tyrosine Kinase Gene Mutations and KIT Amplifications in Human Solid Tumors. JCO
23: 49-57
[Abstract][Full Text]
Lennartsson, J., Jelacic, T., Linnekin, D., Shivakrupa, R.
(2005). Normal and Oncogenic Forms of the Receptor Tyrosine Kinase Kit. Stem Cells
23: 16-43
[Abstract][Full Text]
Uccini, S., Mannarino, O., McDowell, H. P., Pauser, U., Vitali, R., Natali, P. G., Altavista, P., Andreano, T., Coco, S., Boldrini, R., Bosco, S., Clerico, A., Cozzi, D., Donfrancesco, A., Inserra, A., Kokai, G., Losty, P. D., Nicotra, M. R., Raschella, G., Tonini, G. P., Dominici, C.
(2005). Clinical and Molecular Evidence for c-kit Receptor as a Therapeutic Target in Neuroblastic Tumors. Clin. Cancer Res.
11: 380-389
[Abstract][Full Text]
Choi, H., Charnsangavej, C., Faria, S. d. C., Tamm, E. P., Benjamin, R. S., Johnson, M. M., Macapinlac, H. A., Podoloff, D. A.
(2004). CT Evaluation of the Response of Gastrointestinal Stromal Tumors After Imatinib Mesylate Treatment: A Quantitative Analysis Correlated with FDG PET Findings. Am. J. Roentgenol.
183: 1619-1628
[Abstract][Full Text]
Went, P. Th., Dirnhofer, S., Bundi, M., Mirlacher, M., Schraml, P., Mangialaio, S., Dimitrijevic, S., Kononen, J., Lugli, A., Simon, R., Sauter, G.
(2004). Prevalence of KIT Expression in Human Tumors. JCO
22: 4514-4522
[Abstract][Full Text]
Fagin, J A
(2004). How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol
183: 249-256
[Abstract][Full Text]
Demetri, G. D., Titton, R. L., Ryan, D. P., Fletcher, C. D.M.
(2004). Case 32-2004 - A 68-Year-Old Man with a Large Retroperitoneal Mass. NEJM
351: 1779-1787
[Full Text]
O'Hare, T., Pollock, R., Stoffregen, E. P., Keats, J. A., Abdullah, O. M., Moseson, E. M., Rivera, V. M., Tang, H., Metcalf, C. A. III, Bohacek, R. S., Wang, Y., Sundaramoorthi, R., Shakespeare, W. C., Dalgarno, D., Clackson, T., Sawyer, T. K., Deininger, M. W., Druker, B. J.
(2004). Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood
104: 2532-2539
[Abstract][Full Text]
Corless, C. L., Fletcher, J. A., Heinrich, M. C.
(2004). Biology of Gastrointestinal Stromal Tumors. JCO
22: 3813-3825
[Abstract][Full Text]
Heymach, J. V., Desai, J., Manola, J., Davis, D. W., McConkey, D. J., Harmon, D., Ryan, D. P., Goss, G., Quigley, T., Van den Abbeele, A. D., Silverman, S. G., Connors, S., Folkman, J., Fletcher, C. D. M., Demetri, G. D.
(2004). Phase II Study of the Antiangiogenic Agent SU5416 in Patients with Advanced Soft Tissue Sarcomas. Clin. Cancer Res.
10: 5732-5740
[Abstract][Full Text]
Dietz, A. B., Souan, L., Knutson, G. J., Bulur, P. A., Litzow, M. R., Vuk-Pavlovic, S.
(2004). Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood
104: 1094-1099
[Abstract][Full Text]
West, R. B., Corless, C. L., Chen, X., Rubin, B. P., Subramanian, S., Montgomery, K., Zhu, S., Ball, C. A., Nielsen, T. O., Patel, R., Goldblum, J. R., Brown, P. O., Heinrich, M. C., van de Rijn, M.
(2004). The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status. Am. J. Pathol.
165: 107-113
[Abstract][Full Text]
Tang, X, Boxer, M, Drummond, A, Ogston, P, Hodgins, M, Burden, A D
(2004). A germline mutation in KIT in familial diffuse cutaneous mastocytosis. J. Med. Genet.
41: e88-e88
[Full Text]
Ozvegy-Laczka, C., Heged""s, T., Varady, G., Ujhelly, O., Schuetz, J. D., Varadi, A., Keri, G., Orfi, L., Nemet, K., Sarkadi, B.
(2004). High-Affinity Interaction of Tyrosine Kinase Inhibitors with the ABCG2 Multidrug Transporter. Mol. Pharmacol.
65: 1485-1495
[Abstract][Full Text]
Raspollini, M. R., Amunni, G., Villanucci, A., Pinzani, P., Simi, L., Paglierani, M., Taddei, G. L.
(2004). c-Kit Expression in Patients with Uterine Leiomyosarcomas: A Potential Alternative Therapeutic Treatment. Clin. Cancer Res.
10: 3500-3503
[Abstract][Full Text]
Wolff, N. C., Randle, D. E., Egorin, M. J., Minna, J. D., Ilaria, R. L. Jr.
(2004). Imatinib Mesylate Efficiently Achieves Therapeutic Intratumor Concentrations in Vivo but Has Limited Activity in a Xenograft Model of Small Cell Lung Cancer. Clin. Cancer Res.
10: 3528-3534
[Abstract][Full Text]
Eisenberg, B. L., Judson, I.
(2004). Surgery and Imatinib in the Management of GIST: Emerging Approaches to Adjuvant and Neoadjuvant Therapy. Ann. Surg. Oncol.
11: 465-475
[Abstract][Full Text]
Dziba, J. M., Ain, K. B.
(2004). Imatinib Mesylate (Gleevec; STI571) Monotherapy Is Ineffective in Suppressing Human Anaplastic Thyroid Carcinoma Cell Growth in Vitro. J. Clin. Endocrinol. Metab.
89: 2127-2135
[Abstract][Full Text]
Bono, P., Krause, A., von Mehren, M., Heinrich, M. C., Blanke, C. D., Dimitrijevic, S., Demetri, G. D., Joensuu, H.
(2004). Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood
103: 2929-2935
[Abstract][Full Text]
Stefanou, D., Batistatou, A., Zioga, A., Arkoumani, E., Papachristou, D. J., Agnantis, N. J.
(2004). Immunohistochemical Expression of Vascular Endothelial Growth Factor (VEGF) and C-KIT in Cutaneous Melanocytic Lesions. INT J SURG PATHOL
12: 133-138
[Abstract]
Raspollini, M. R., Amunni, G., Villanucci, A., Baroni, G., Taddei, A., Taddei, G. L.
(2004). c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study. Ann Oncol
15: 594-597
[Abstract][Full Text]
Neville, K., Parise, R. A., Thompson, P., Aleksic, A., Egorin, M. J., Balis, F. M., McGuffey, L., McCully, C., Berg, S. L., Blaney, S. M.
(2004). Plasma and Cerebrospinal Fluid Pharmacokinetics of Imatinib after Administration to Nonhuman Primates. Clin. Cancer Res.
10: 2525-2529
[Abstract][Full Text]
Kaelin, W. G. Jr.
(2004). Gleevec: Prototype or Outlier?. Sci Signal
2004: pe12-pe12
[Abstract][Full Text]
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