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Functional studies on the anti-pathoangiogenic properties of CM101 (1998)

Yan, He-Ping ; Carter, Clint E. ; Wang, En-ze ; [et al.]

Springer

Angiogenesis 2 (1998), S. 219-233

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ISSN: 1573-7209

Keywords: Anti-tumor action ; complement ; cytokines ; endothelial cells ; immunohistochemistry ; polysaccharide ; RT-PCR

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101) which has been previously described as GBS toxin. CM101 infused i.v. into tumor-bearing mice causes rapid tumor neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth and tumor apoptosis. CM101 has successfully completed phase I studies in refractory cancer patients with very encouraging results. We have now demonstrated a mechanism of action for CM101. Using a normal mouse tumor model, we have examined tumor and normal tissues which were harvested at 0, 5, 15, 30 and 60 min post-infusion of either CM101 or dextran. We present evidence that CM101 is rapidly (within the first 5 min) bound to the tumor neovasculature. Complement is activated by the alternative pathway (C3) and leukocytes start to infiltrate the tumor within the first 5 min. Through RT-PCR and immunohistochemical techniques, we demonstrate that proinflammatory cytokines, interleukin-6 and tumor necrosis factor (TNF)-α, are up-regulated in infiltrating leukocytes and TNF receptor 2 is up-regulated in the targeted tumor neovasculature. Combined, these events constitute possible explanations for the observed pathophysiology of tumor ablation.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1009258801899

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Diagnostic criteria and cancer risk of proliferative breast lesions (1993)

Jensen, Roy A. ; Dupont, William D. ; Page, David L.

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 53 (1993), S. 59-64

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ISSN: 0730-2312

Keywords: Atypical hyperplasia ; breast cancer ; cancer risk ; hyperplasia ; family history ; premalignancy ; proliferative disease ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Breast cancer risk assessment in women following a benign breast biopsy is a promising area with regard to intermediate endpoint determination, and has been particularly fostered by the consensus agreement concerning the risk attributed to specific diagnoses [1]. Several recent studies have largely verified this approach [2-4], and a recent report demonstrates general agreement among most expert pathologists regarding diagnostic criteria for these lesions [5]. However, in a limited number of cases, determining exact levels of risk for individual patients has been problematic as a result of a failure by pathologists to achieve consensus on diagnostic criteria for these same lesions. This situation has arisen primarily because it is much more tenable to disagree over subjective diagnostic criteria, than it is to argue with robustly supported epidemiological data. Without agreement on reproducible diagnostic criteria, widely promulgated consensus risk estimates for these specific histologic entities are no longer applicable. In addition, those individuals who choose different diagnostic criteria for proliferative breast lesions fail to realize that the terminology, epidemiological risk estimates, and diagnostic criteria used by Dupont and Page are inexorably linked. Since the publication of the consensus statement [1], those using the terms “atypical ductal hyperplasia” and “atypical lobular hyperplasia” have by default accepted the diagnostic criteria of Dupont and Page. Therefore, surgical pathologists who desire to make use of the consensus risk estimates must familiarize themselves with diagnostic criteria for the various histologic entities that comprise proliferative disease of the breast as defined by Dupont and Page [6]. This presentation will concentrate on the importance of a combined histologic and cytologic approach to diagnose proliferative breast lesions, and will specifically focus on usual hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia, and both ductal and lobular carcinoma in situ.

Additional Material: 4 Ill.