Su-11248 SUGEN

Sakamoto KM.
Curr Opin Investig Drugs. 2004 Dec;5(12):1329-39.
PMID: 15648955
This is a paper about the chemistry involved with the drug Sugen or SU-11248, and its actions to inhibit receptor tyrosine kinases or RTKs (one of which is GIST's c-kit). Different trials against various types of cancer are described, including GIST. Here are a few quotes from the paper.
"SU-11248 has demonstrated activity against a variety of malignancies that are resistant to conventional chemotherapy, and is active in patients with GIST tumors that are resistant to imatinib.... In comparison with other RTK inhibitors, namely imatinib, SU-11248 clearly inhibits angiogenesis.....Early studies with SU-11248 suggest that it may cause more systemic toxicity than imatinib, due possibly to the wider spectrum of targets...including PDGF, Kit, FGC and VEGF receptors."
Entrez PubMed

Spontaneously ruptured gastrointestinal stromal tumor (GIST) of the jejunum mimicking acute appendicitis

Ajduk M, Mikulic D, Sebecic B, Gasparov S, Patrlj L, Erdelez L, Skopljanac
A, Staresinic M, Deskovic S, Sosa T, Sitic S.
Coll Antropol. 2004 Dec;28(2):937-41.
PMID: 15666631
This GIST was discovered when it ruptured, causing pain similar to appendicitis.
Entrez PubMed

Effect of imatinib (STI-571) on metastatic gastrointestinal stromal tumors: report of a case

Ando Y, Tsunoda T, Beck Y, Takayama T, Tahara H
Surgery Today 2005, 35(2):157-160
This case history describes shrinkage of liver and peritoneal metastases in a patient who was not given imatinib until 17 months after surgery.
Entrez PubMed

Update on the biology and therapy of gastrointestinal stromal tumors

D'Amato G, Steinert DM, McAuliffe JC, Trent JC.
Cancer Control. 2005 Jan-Feb;12(1):44-56.
PMID: 15668652
This is a review paper summarizing information about GIST.
free access via PubMed
Entrez PubMed

New Drugs in Cancer Therapy, National Tumor Institute, Naples, 17-18 June 2004

Caponigro F, Basile M, Rosa VD, Normanno N.
Anticancer Drugs. 2005 Feb;16(2):211-221.
PMID: 15655420
Entrez PubMed

The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1458 cases from 1992 to 2000

Tran T, Davila JA, El-Serag HB.
Am J Gastroenterol. 2005 Jan;100(1):162-8.
PMID: 15654796
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High Efficacy of Imatinib for Recurrent Gastrointestinal Stromal Tumor in the Jejunum: A Case Report

Kimiyoshi Yokoi, Noritake Tanaka, Shoji Kyouno, Noriyuki Ishikawa, Tomoko Seya, Takashi Shirakawa, Yoshiyuki Takahashi, Yoshiharu Ohaki, Kiyohiko Yamashita and Takashi Tajiri
Journal of Nippon Medical School 2004 71: 114-119.
PMID 15260086
free access via journal
J Nippon Med Sch

Cystic changes in intraabdominal extrahepatic metastases from gastrointestinal stromal tumors treated with imatinib

Kim HC, Lee JM, Choi SH, Han H, Kim SS, Lee SH, Han JK, Choi BI.
Korean J Radiol 2004, 5:157-163.
PMID 15467412
free access via PubMed link to Korean J Radiol
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Malignant gastrointestinal stromal tumor of the gallbladder

Park JK, Choi SH, Lee S, Min KO, Yun SS, Jeon HM.
J Korean Med Sci. 2004 Oct;19(5):763-7.
PMID: 15483360
Free access in PubMed or through jkms.kams.or.kr
Entrez PubMed

A treatment using STI571 for jejunal gastrointestinal stromal tumor (GIST) accompanied with liver metastasis and peritoneal dissemination

Okamoto K, Muguruma N, Aoki R, Sato Y, Nakamoto J, Imoto Y, Okamura S, Ito
S, Okitsu H, Sano T.
Intern Med. 2004 Dec;43(12):1151-6.
PMID: 15645649
Entrez PubMed

Loss of heterozygosity of chromosome 9p and loss of p16ink4A expression are associated with malignant gastrointestinal stromal tumors

Sabah M, Cummins R, Leader M, Kay E
Modern Pathology 2004, 17: 1364-1371.
This paper presents gene mutation differences between malignant GISTs and GISTs with low malignant potential.
Free access at journal site!
Modern Pathology

The era of molecular therapy in the treatment of gastrointestinal soft-tissue sarcoma: the GIST paradigm

This is a summary article based on a March 2004 sympoisium at the Society of Surgical Oncology meeting.
Society of Surgical Oncology

Management of gastrointestinal stromal tumours: from diagnosis to treatment

Bucher P, Villiger P, Egger J-F, Bubler LH, Morel,P.
Swiss Medical Weekly 2004, 134:145-153.
This is a good summary paper.
Free access from journal site!
Swiss Medical Weekly

Rediscovering GIST: differential diagnosis of GIST in the era of molecularly targeted therapy

This is a 16-page booklet made available by Novartis, manufacturer of Gleevec (spelled Glivec in this international edition published 8/2002).
You can print it out using Adobe Acrobat.
Novartis

Loss of chromosome 13q is a frequently acquired event in genetic progression of soft tissue sarcomas in the abdominal cavity

Weng WH, Lerner M, Grander D, Ahlen J, Villablanca A, Pang ST, Wejde J, Lui WO, Larsson C. Int J Oncol. 2005 Jan;26(1):5-16.
PMID: 15586219
These authors compared many types of sarcoma, including GIST, and found that loss of chromosome 13q was common.
Using the issue and page numbers above, you can get free access to the entire paper at International Journal of Oncology.
Int J Oncol
You can read the abstract at PubMed.
Entrez PubMed

Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the imatinib era

Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B,
Sablinska K, Kindblom LG
Cancer. 2005 Jan 12; [Epub ahead of print]
PMID: 15648083
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Pharmacokinetic Resistance to Imatinib Mesylate: Role of the ABC Drug Pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the Oral bioavailability of Imatinib

Burger H, Nooter K.
Cell Cycle. 2004 Dec 22;3(12) [Epub ahead of print]
PMID: 15611623
These authors discuss how a biological "drug pump" can reduce the effective concentration of Gleevec.
Entrez PubMed

Spindle cell sarcoma: a rare cause of a large abdominal mass

Bills V, Iqbal R, Haqqani M, Clague JE.
Age Ageing. 2005 Jan;34(1):88-9.
PMID: 15591490
This short case history of a kit-negative tumor illustrates the difficulty of differential diagnosis for rare tumors. It is possible that other physicians might have called this a kit-negative GIST.
Entrez PubMed

Indications for imatinib mesylate therapy and clinical management

Guilhot F.
Oncologist, 2004, 9:271-281.
This review discusses management of Gleevec side effects.
Free full-text access in PubMed.
Entrez PubMed

The development of imatinib as a therapeutic agent for chronic myeloid leukemia

Deininger M, Buchdunger E, Druker BJ.
Blood. 2004 Dec 23; [Epub ahead of print]
PMID: 15618470
Although this paper is not directly about GIST, it gives relevant information about Gleevec. A section called "late side effects" discusses Gleevec and reproduction. The authors report the outcomes of 18 pregnancies reported to Novartis in women whose partner was taking Gleevec, resulting in 4 normal infants, 2 by-choice abortions, 1 spontaneous abortion, 1 death in utero, and 10 with no outcome information yet. In women taking Gleevec themselves, 26 pregnancies are known to Novartis, resulting in 11 by-choice abortions, 5 miscarriages, 2 normal infants, 1 abnormal infant, and 7 pregnancies with no outcome information yet. The authors also allude to unpublished Novartis data about genitourinary tumors in rats treated for 24 months with Gleevec at 30-60 mg/kg body weight. (A kg is 2.2 pounds, so for a 150-pound person this would be 68 kg x 30-60 mg = 2045mg to 5090 mg). This is a high dose for sure, 2 to 6 times more than the highest dose ever prescribed for humans. At any rate, these rats showed "increased frequency of genitourinary tumors" -- how much is not specified. The authors go on to say that preliminary examinations of human data have not indicated increased incidence of bladder, kidney, or prostrate tumors, but monitoring is advised.
Entrez PubMed

Discovery of BMS-354825, a Dual Src/Abl Kinase Inhibitor with Potent Antitumor Activity in Preclinical Assays

Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, Castaneda S, Cornelius LA, Das J, Doweyko AM, Fairchild C, Hunt JT, Inigo I, Johnston K, Kamath A, Kan D, Klei H, Marathe P, Pang S, Peterson R, Pitt S, Schieven GL, Schmidt RJ, Tokarski J, Wen ML, Wityak J, Borzilleri RM.
J Med Chem. 2004 Dec 30;47(27):6658-61.
PMID: 15615512
This paper describes the drug BMS-354825, which is currently in Phase I trials in patients with solid tumors including GIST.
Entrez PubMed

Acid-base profiling of imatinib (Gleevec) and its fragments

Szakacs Z, Beni S, Varga Z, Orfi L, Keri G, Noszal B.
J Med Chem 2005 48:249-255.
PubMed ID 15634018
Entrez PubMed

Endosonographic diagnosis of recurrent gastrointestinal stromal tumors associated with Carney's syndrome

Lipcan MT, Loren DE, Palazzo JP, Bibbo M, Dimarino AJ, Cohen S.
Gastroenterology. 2005 Jan;128(1):169-74.
PMID: 15633134
Entrez PubMed

Giant malignant gastrointestinal stromal tumors: recurrence and effects of treatment with STI-571

Chen TW, Liu HD, Shyu RY, Yu JC, Shih ML, Chang TM, Hsieh CB.
World J Gastroenterol. 2005 Jan 14;11(2):260-3.
PMID: 15633227
Full text available free in PubMed.
Entrez PubMed

Novel kinase inhibitors for the treatment of imatinib-mesylate-resistant gastrointestinal stromal tumors

This brief article is free-access.
Author: Michael Heinrich, MD
Source: Physicians Educational Resource Letter
PERLP Publications

Gastrointestinal Stromal Tumors of the Stomach: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 1765 Cases With ... Followup

Miettinen M, Sobin LH, Lasota J.
Am J Surg Pathol. 2005 Jan;29(1):52-68.
PMID: 15613856
Entrez PubMed

Loss of heterozygosity on chromosome 22q in gastrointestinal stromal tumors (GISTs): a study on 50 cases

Lasota J, Wozniak A, Kopczynski J, Dansonka-Mieszkowska A, Wasag B,Mitsuhashi T, Sarlomo-Rikala M, Lee JR, Schneider-Stock R, Stachura J, Limon J,Miettinen M.
Lab Invest. 2004 Dec 06; [Epub ahead of print]
PMID: 15580284
Entrez PubMed

Adverse reactions during imatinib and lansoprazole treatment in gastrointestinal stromal tumors

Severino G, Chillotti C, De Lisa R, Del Zompo M, Ardau R.
Ann Pharmacother. 2005 Jan;39(1):162-4.
PMID: 15546944
Entrez PubMed

A recurrent duodenal gastrointestinal stromal tumor with a frameshift mutation resulting in a stop codon in KIT exon 13

Vu HA, Xinh PT, Kikushima M, Zhu Y, Tokuhara M, Tani M, Shimizu T, Saito K,Tokunaga K, Sato Y.
Genes Chromosomes Cancer. 2005 Feb;42(2):179-83.
PMID: 15543597
Entrez PubMed

Imatinib (Gleevec(R))-induced hepatotoxicity

Ayoub WS, Geller SA, Tran T, Martin P, Vierling JM, Poordad FF.
J Clin Gastroenterol. 2005 Jan;39(1):75-77.
PMID: 15599217
Entrez PubMed

Kit as a human oncogenic tyrrosine kinase

Kitamura Y, Hirotab S.
Cell Mol Life Sci. 2004 Dec;61(23):2924-31.
PMID: 15583854
Entrez PubMed

Gastrointestinal stromal tumor presenting as a recurrent vaginal mass

Ceballos KM, Francis JA, Mazurka JL.
Arch Pathol Lab Med. 2004 Dec;128(12):1442-4.
PMID: 15578893
Entrez PubMed

Differential protein expression profile in gastrointestinal stromal tumors

Landuyt B, Prenen H, Debiec-Rychter M, Sciot R, A de Bruijn E, van Oosterom AT.
Amino Acids. 2004 Dec;27(3-4):335-7.
PMID: 15549490
Entrez PubMed

Mesenteric gastrointestinal stromal tumor in a patient with neurofibromatosis

Sinha R, Verma R, Kong A.
AJR Am J Roentgenol. 2004 Dec;183(6):1844-6. No abstract available.
PMID: 15547245
Entrez PubMed

Gastrointestinal stromal tumors in patients with neurofibromatosis: imaging features with clinicopathologic correlation

Levy AD, Patel N, Abbott RM, Dow N, Miettinen M, Sobin LH.
AJR Am J Roentgenol. 2004 Dec;183(6):1629-36.
PMID: 15547202
Entrez PubMed

CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET

Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, JohnsonMM, Macapinlac HA, Podoloff DA.
AJR Am J Roentgenol. 2004 Dec;183(6):1619-28.
PMID: 15547201
Entrez PubMed