KOBV Portal

1

Online Resource

Elimination of donor-specific alloreactivity prevents cytomegalovirus-accelerated chronic rejection in rat small bowel and heart transplants1

Orloff, Susan L. ; Streblow, Daniel N. ; Soderberg-Naucler, Cecilia ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2002

In: Transplantation Vol. 73, No. 5 ( 2002-03), p. 679-688

add to watchlist on the watchlist

Details

In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 73, No. 5 ( 2002-03), p. 679-688

Type of Medium: Online Resource

ISSN: 0041-1337

URL: Article

DOI: 10.1097/00007890-200203150-00005

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2002

detail.hit.zdb_id: 2035395-9

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

2

Online Resource

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

Heinrich, Michael C. ; Owzar, Kouros ; Corless, Christopher L. ; [et al.]

American Society of Clinical Oncology (ASCO) ; 2008

In: Journal of Clinical Oncology Vol. 26, No. 33 ( 2008-11-20), p. 5360-5367

add to watchlist on the watchlist

Details

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 33 ( 2008-11-20), p. 5360-5367

Abstract: Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all patients benefit equally. In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing. Patients and Methods We examined the relationship between kinase genotype and treatment outcome for 428 patients enrolled on the North American phase III study SWOG S0033/CALGB 150105 and treated with either 400 mg or 800 mg daily doses of imatinib. Results The presence of KIT exon 11–mutant genotype (n = 283) correlated with improved treatment outcome when compared with KIT exon 9–mutant (n = 32) and wild-type (WT; n = 67) genotypes for objective response (complete response [CR]/partial response [PR] , 71.7% v 44.4% [P = .007]; and 44.6% [P = .0002] , respectively); time to tumor progression (TTP; median 24.7 months v 16.7 and 12.8 months, respectively); and overall survival (OS; median 60.0 months v 38.4 and 49.0 months, respectively). The survival outcomes for patients with exon 9–mutant, exon 11–mutant or WT GIST were not affected by imatinib dose. However, there was evidence of improved response rates for patients with exon 9–mutant tumors treated with imatinib 800 mg versus 400 mg (CR/PR, 67% v 17%; P = .02). Patients who had CD117-negative GIST had similar TTP but inferior OS compared with patients who had CD117-positive disease, which suggests that patients who have CD117-negative GIST may benefit from imatinib treatment. In addition, we identified novel but rare mutations of the KIT extracellular domain (exons 8 and 9). Conclusion We confirmed the favorable impact of KIT exon 11 genotype when compared with KIT exon 9 and wild-type genotype for patients with advanced GIST who are treated with imatinib.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2008.17.4284

RVK:

XA 52760

RVK:

XA 10000

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2008

detail.hit.zdb_id: 2005181-5

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

3

Online Resource

Molecular Target Modulation, Imaging, and Clinical Evaluation of Gastrointestinal Stromal Tumor Patients Treated with Sunitinib Malate after Imatinib Failure

Demetri, George D. ; Heinrich, Michael C. ; Fletcher, Jonathan A. ; [et al.]

American Association for Cancer Research (AACR) ; 2009

In: Clinical Cancer Research Vol. 15, No. 18 ( 2009-09-15), p. 5902-5909

add to watchlist on the watchlist

Details

In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 18 ( 2009-09-15), p. 5902-5909

Abstract: Purpose: To evaluate sunitinib activity and potential cellular and molecular correlates in gastrointestinal stromal tumor (GIST) patients after imatinib failure, in addition to assessing the safety and pharmacokinetics (PK) of different dose schedules. Experimental Design: In this open-label, dose-ranging, phase I/II study, 97 patients with metastatic imatinib-resistant/intolerant GIST received sunitinib at doses of 25, 50, or 75 mg/d on one of three schedules. Serial tumor imaging was done using computed tomography and [18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning. PK and cell proliferation and KIT phosphorylation status in tumor biopsies were also analyzed. Results: Clinical benefit was observed in 52 patients (54%: 7 objective partial responses, 45 stable disease ≥6 months). Decreased tumor glycolytic activity was shown in most patients within 7 days of starting sunitinib using [18F]fluoro-2-deoxy-d-glucose positron emission tomography. Sunitinib treatment was associated with reduced tumor cell proliferation by & gt;25% in 52% of cases analyzed and reduced levels of phospho-KIT in tumor biopsies (indicating target modulation). The recommended dose schedule was 50 mg/d for 4 weeks followed by 2 weeks off treatment. On the 50-mg dose across all schedules, 79% of PK-evaluable patients achieved total drug trough concentrations above the target concentration (50 ng/mL) within 14 days of dosing. In addition, adverse events were generally mild to moderate in severity. Conclusion: Cellular and molecular analyses showed that sunitinib clinical activity is associated with inhibition of KIT in GIST following imatinib failure, illustrating the rational approach used to develop a therapy aimed at the underlying oncogenic signaling pathway aberrancy. (Clin Cancer Res 2009;15(18):5902–9)

Type of Medium: Online Resource

ISSN: 1078-0432 , 1557-3265

URL: Article

DOI: 10.1158/1078-0432.CCR-09-0482

RVK:

XA 36791

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2009

detail.hit.zdb_id: 1225457-5

detail.hit.zdb_id: 2036787-9

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

4

Online Resource

Protein Kinase C θ (PKCθ) Expression and Constitutive Activation in Gastrointestinal Stromal Tumors (GISTs)

Duensing, Anette ; Joseph, Nora E. ; Medeiros, Fabiola ; [et al.]

American Association for Cancer Research (AACR) ; 2004

In: Cancer Research Vol. 64, No. 15 ( 2004-08-01), p. 5127-5131

add to watchlist on the watchlist

Details

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 64, No. 15 ( 2004-08-01), p. 5127-5131

Abstract: KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C θ (PKCθ) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCθ is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/0008-5472.CAN-04-0559

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2004

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

5

Online Resource

A RAT SMALL BOWEL TRANSPLANT MODEL OF CHRONIC REJECTION: HISTOPATHOLOGIC CHARACTERISTICS1

Orloff, Susan L. ; Yin, Qiang ; Corless, Christopher L. ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 1999

In: Transplantation Vol. 68, No. 6 ( 1999-09), p. 766-779

add to watchlist on the watchlist

Details

In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. 6 ( 1999-09), p. 766-779

Type of Medium: Online Resource

ISSN: 0041-1337

URL: Article

DOI: 10.1097/00007890-199909270-00008

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 1999

detail.hit.zdb_id: 2035395-9

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

6

Online Resource

KIT-Negative Gastrointestinal Stromal Tumors : Proof of Concept and Therapeutic Implications

Medeiros, Fabiola ; Corless, Christopher L ; Duensing, Anette ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2004

In: The American Journal of Surgical Pathology Vol. 28, No. 7 ( 2004-07), p. 889-894

add to watchlist on the watchlist

Details

In: The American Journal of Surgical Pathology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 7 ( 2004-07), p. 889-894

Type of Medium: Online Resource

ISSN: 0147-5185

URL: Article

DOI: 10.1097/00000478-200407000-00007

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2004

detail.hit.zdb_id: 2029143-7

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

7

Online Resource

Rhabdomyosarcomatous Differentiation in Gastrointestinal Stromal Tumors After Tyrosine Kinase Inhibitor Therapy : A Novel Form of Tumor Progression

Liegl, Bernadette ; Hornick, Jason L. ; Antonescu, Cristina R. ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2009

In: American Journal of Surgical Pathology Vol. 33, No. 2 ( 2009-02), p. 218-226

add to watchlist on the watchlist

Details

In: American Journal of Surgical Pathology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 2 ( 2009-02), p. 218-226

Type of Medium: Online Resource

ISSN: 0147-5185

URL: Article

DOI: 10.1097/PAS.0b013e31817ec2e6

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2009

detail.hit.zdb_id: 2029143-7

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

8

Online Resource

Monoclonal Antibody DOG1.1 Shows Higher Sensitivity Than KIT in the Diagnosis of Gastrointestinal Stromal Tumors, Including Unusual Subtypes

Liegl, Bernadette ; Hornick, Jason L. ; Corless, Christopher L. ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2009

In: American Journal of Surgical Pathology Vol. 33, No. 3 ( 2009-03), p. 437-446

add to watchlist on the watchlist

Details

In: American Journal of Surgical Pathology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 3 ( 2009-03), p. 437-446

Type of Medium: Online Resource

ISSN: 0147-5185

URL: Article

DOI: 10.1097/PAS.0b013e318186b158

RVK:

XA 10000

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2009

detail.hit.zdb_id: 2029143-7

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

9

Online Resource

Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors

Heinrich, Michael C. ; Corless, Christopher L. ; Blanke, Charles D. ; [et al.]

American Society of Clinical Oncology (ASCO) ; 2006

In: Journal of Clinical Oncology Vol. 24, No. 29 ( 2006-10-10), p. 4764-4774

add to watchlist on the watchlist

Details

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 29 ( 2006-10-10), p. 4764-4774

Abstract: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem. Patients and Methods One hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity. Results Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways. Conclusion Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2006.06.2265

RVK:

XA 52760

RVK:

XA 10000

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2006

detail.hit.zdb_id: 2005181-5

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

10

Online Resource

Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor

Heinrich, Michael C. ; Corless, Christopher L. ; Demetri, George D. ; [et al.]

American Society of Clinical Oncology (ASCO) ; 2003

In: Journal of Clinical Oncology Vol. 21, No. 23 ( 2003-12-01), p. 4342-4349

add to watchlist on the watchlist

Details

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 21, No. 23 ( 2003-12-01), p. 4342-4349

Abstract: Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. Patients and Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. Results: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P 〈 .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. Conclusion: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2003.04.190

RVK:

XA 52760

RVK:

XA 10000

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2003

detail.hit.zdb_id: 2005181-5

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Kooperativer Bibliotheksverbund

Berlin Brandenburg