In vitro chemoresistance testing in well-differentiated carcinoid tumors

John M. Lyons, Jeffrey Abergel, Jessica L. Thomson, Cathy T. Anthony, Yi Zarn Wang, Lowell B. Anthony, J. Philip Boudreaux, James Strauchen, Muhammad Idrees, Richard R P Warner, Eugene A. Woltering

Research output: Contribution to journalArticle

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Abstract

Background: Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. Methods: Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. 3H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. Results: Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent. Conclusions: This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalAnnals of Surgical Oncology
Volume16
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

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Carcinoid Tumor
Drug Resistance
Drug Therapy
Pharmaceutical Preparations
Antineoplastic Agents
In Vitro Techniques
Growth
Fluorouracil
Doxorubicin
Thymidine
Clinical Trials

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Lyons, J. M., Abergel, J., Thomson, J. L., Anthony, C. T., Wang, Y. Z., Anthony, L. B., ... Woltering, E. A. (2009). In vitro chemoresistance testing in well-differentiated carcinoid tumors. Annals of Surgical Oncology, 16(3), 649-655. https://doi.org/10.1245/s10434-008-0261-z

In vitro chemoresistance testing in well-differentiated carcinoid tumors. / Lyons, John M.; Abergel, Jeffrey; Thomson, Jessica L.; Anthony, Cathy T.; Wang, Yi Zarn; Anthony, Lowell B.; Boudreaux, J. Philip; Strauchen, James; Idrees, Muhammad; Warner, Richard R P; Woltering, Eugene A.

In: Annals of Surgical Oncology, Vol. 16, No. 3, 03.2009, p. 649-655.

Research output: Contribution to journalArticle

Lyons, JM, Abergel, J, Thomson, JL, Anthony, CT, Wang, YZ, Anthony, LB, Boudreaux, JP, Strauchen, J, Idrees, M, Warner, RRP & Woltering, EA 2009, 'In vitro chemoresistance testing in well-differentiated carcinoid tumors', Annals of Surgical Oncology, vol. 16, no. 3, pp. 649-655. https://doi.org/10.1245/s10434-008-0261-z
Lyons JM, Abergel J, Thomson JL, Anthony CT, Wang YZ, Anthony LB et al. In vitro chemoresistance testing in well-differentiated carcinoid tumors. Annals of Surgical Oncology. 2009 Mar;16(3):649-655. https://doi.org/10.1245/s10434-008-0261-z
Lyons, John M. ; Abergel, Jeffrey ; Thomson, Jessica L. ; Anthony, Cathy T. ; Wang, Yi Zarn ; Anthony, Lowell B. ; Boudreaux, J. Philip ; Strauchen, James ; Idrees, Muhammad ; Warner, Richard R P ; Woltering, Eugene A. / In vitro chemoresistance testing in well-differentiated carcinoid tumors. In: Annals of Surgical Oncology. 2009 ; Vol. 16, No. 3. pp. 649-655.
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abstract = "Background: Well-differentiated, {"}typical{"} carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. Methods: Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. 3H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. Results: Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81{\%}) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69{\%}, followed by doxorubicin at 67{\%}. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent. Conclusions: This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.",
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AU - Lyons, John M.

AU - Abergel, Jeffrey

AU - Thomson, Jessica L.

AU - Anthony, Cathy T.

AU - Wang, Yi Zarn

AU - Anthony, Lowell B.

AU - Boudreaux, J. Philip

AU - Strauchen, James

AU - Idrees, Muhammad

AU - Warner, Richard R P

AU - Woltering, Eugene A.

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N2 - Background: Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. Methods: Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. 3H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. Results: Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent. Conclusions: This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.

AB - Background: Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. Methods: Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. 3H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. Results: Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent. Conclusions: This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.

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