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Correspondence re: K. Neben et al., High Plasma Basic Fibroblast Growth Factor Concentration Is Associated with Response to Thalidomide in Progressive Multiple Myeloma. Clin. Cancer Res., 7: 2675–2681, 2001.

Gundersen Lutheran Cancer Care, 1836 South Avenue, Founders Building, La Crosse, Wisconsin 54601

In the study by K. Neben and colleagues (1) , it is notable that the median plasma level of b-FGF¹ in the control group (42.9 pg/ml) is unusually high. In our review of the literature (unpublished), the mean or median plasma or serum b-FGF in healthy controls is usually less than 7.5 pg/ml (range, 2.2–11.8 pg/ml; Refs. 3, 4, 5, 6, 7 ). Unlike vascular endothelial growth factor, b-FGF levels in the plasma and serum are similar. Besides technical reasons, a number of factors, including sex, age, phase of menstrual cycle, and circadian variations, may potentially affect angiogenic factor levels in healthy people (7 , 8) . It would be helpful to know whether any of these factors are identifiable in their control group.

FOOTNOTES

¹ The abbreviation used is: b-FGF, basic fibroblast growth factor.

Received 2/25/02; accepted 5/ 8/02.

REFERENCES

1. Neben K., Moehler T., Egerer G., Kremer A., Hillengass J., Benner A., Ho A. D., Goldschmidt H. High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Clin. Cancer Res., 7: 2675-2681, 2001.[Abstract/Free Full Text]
2. Go R. S., Horstman A. H. Circulating basic fibroblast growth factor (B-FGF) and vascular endothelial growth factor (VEGF) levels in cancer patients: Implications for anti-angiogenic therapy. Proc. Am. Soc. Clin. Oncol., 22(Suppl. 2): 3031 2002.
3. Duensing S., Atzpodien J. Increased intracellular and plasma levels of basic fibroblast growth factor in B-cell chronic lymphocytic leukemia. Blood, 85: 1978-1980, 1995.[Free Full Text]
4. Aguayo A., Kantarjian H., Manshouri T., Gidel C., Estey E., Thomas D., Koller C., Estrov Z., O’Brien S., Keating M., Freireich E., Albitar M. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood, 96: 2240-2245, 2000.[Abstract/Free Full Text]
5. Fuhrmann-Benzakein E., Ma M. N., Rubbia-Brandt L., Mentha G., Ruefenacht D., Sappino A. P., Pepper M. S. Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int. J. Cancer, 85: 40-45, 2000.[CrossRef][Medline]
6. Sezer O., Jakob C., Eucker J., Niemoller K., Gatz F., Wernecke K., Possinger K. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma. Eur. J. Haematol, 66: 83-88, 2001.[CrossRef][Medline]
7. Pichon M. F., Moulin G., Pallud C., Pecking A., Floiras J. L. Serum bFGF (basic fibroblast growth factor) and CA 15.3 in the monitoring of breast cancer patients. Anticancer Res., 20: 1189-1194, 2000.[Medline]
8. Malamitsi-Puchner A., Tziotis J., Tsonou A., Protonotariou E., Sarandakou A., Creatsas G. Changes in serum levels of vascular endothelial growth factor in males and females throughout life. J. Soc. Gynecol. Investig., 7: 309-312, 2000.[Medline]
9. Haus E., Dumitriu L., Nicolau G. Y., Bologa S., Sackett-Lundeen L. Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer. Chronobiol. Int., 18: 709-727, 2001.[Medline]

Reply

Department of Internal Medicine V, University of Heidelberg, 69115 Heidelberg, Germany

We agree with Ronald Go and Andrew Horstman that the median bFGF¹ level (42.9 pg/ml) of our control group (n = 22) is higher as compared with that in the studies mentioned. Because biological factors like age gender phase of menstral cycle circadian rhythms are known to influence the secretion of angiogenic cytokines (1 , 2) , we tried to define a representative control group for our multiple myeloma patients. The median age (56 years) of our group containing 13 males 9 females (median bFGF levels 45.5 40.4 pg/ml respectively) might be higher than in previous studies (3 , 4) . For some practical reasons most of our samples were obtained in the morning between 10 a.m. 12 noon. All of the plasma samples of our control group the multiple myeloma patients were stored at -80°C analyzed together. We are not able to give any information about the menstrual cycle phase of the women.

For bFGF measurement, we used the conventional (Quantikine) as well as the high sensitive (Quantikine HS) bFGF quantitative sandwich enzyme immunoassays provided by R&D Systems (Minneapolis, MN). In contrast to the comment of Go and Horstman, bFGF levels tend to be 4–5 times higher in EDTA plasma compared with serum samples, according to the manufacturer’s instructions. Because peripheral blood platelets contain bFGF (5) and a high thrombocyte count was reported to be strongly associated with high serum levels of bFGF (6) , caution is warranted to allow for an exact measurement of bFGF levels. Although we found no statistically significant correlation between the platelet count and the corresponding bFGF levels, an effect of the anticoagulant (EDTA) used in our series on the stability of thrombocytes cannot be totally ruled out.

FOOTNOTES

The abbreviation used is: bFGF, basic fibroblast growth factor.

To whom requests for reprints should be addressed, at Department of Internal Medicine V, University of Heidelberg, Hospitalstr. 3, 69115 Heidelberg, Germany. Phone: 49-6221-56-8008; Fax: 49-6221-56-5813; E-mail: k.neben{at}dkfz.de

Received 4/18/02; accepted 5/ 8/02.

REFERENCES

1. Malamitsi-Puchner A., Tziotis J., Tsonou A., Protonotariou E., Sarandakou A., Creatsas G. Changes in serum levels of vascular endothelial growth factor in males and females throughout life. J. Soc. Gynecol. Investig., 7: 309-312, 2000.
2. Haus E., Dumitriu L., Nicolau G. Y., Bologa S., Sackett-Lundeen L. Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer. Chronobiol. Int., 18: 709-727, 2001.
3. Fuhrmann-Benzakein E., Ma M. N., Rubbia-Brandt L., Mentha G., Ruefenacht D., Sappino A. P., Pepper M. S. Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int. J. Cancer, 85: 40-45, 2000.
4. Sezer O., Jakob C., Eucker J., Niemoller K., Gatz F., Wernecke K., Possinger K. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma. Eur. J. Haematol., 66: 83-88, 2001.
5. Brunner G., Nguyen H., Gabrilove J., Rikin D. B., Wilson E. L. Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells. Blood, 81: 631-638, 1993.[Abstract/Free Full Text]
6. Salven P., Orpana A., Teerenhovi L., Joensuu H. Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin’s lymphoma: a single-institution study of 200 patients. Blood, 96: 3712-3718, 2000.[Abstract/Free Full Text]

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