Arthur Vogel

The platelet-derived growth factor

Platelet-derived growth factor (PDGF) is a basic (pI congruent to 10) 30 000 molecular weight protein circulating in normal blood sequestered within the platelet alpha-granules. It binds with high affinity (Kd = 10(-11) M) to a specific cell-surface receptor found on many connective tissue cell types in culture. It is active in stimulating the metabolism and multiplication of connective tissue cells at very low concentrations (ED50 = 10(-11) M). It is likely that PDGF is released from platelets at sites of vascular damage and that it contributes toward the cell proliferation and connective tissue formation seen in healing wounds and in arteriosclerotic lesions. PDGF which does not bind to responsive cells at the wound site is largely inactivated by a plasma binding protein and is rapidly cleared from the circulation.

Trisomy 8 in primary esthesioneuroblastoma

Esthesioneuroblastoma is a rare malignancy believed to be derived from neuroectodermal stem cells within the olfactory epithelium. We have obtained the karyotype of a primary esthesioneuroblastoma following brief (7-day) in vitro culture, and have determined that the only observable cytogenetic anomaly is the presence of an additional chromosome 8. Previously, the karyotypes of two cell lines established from metastatic esthesioneuroblastomas have been reported to contain the equivalent of three copies of chromosome 8, in addition to other chromosomal aberrations, including the reciprocal translocation, t(11;22)(q24;q12). Examination of the cytogenetic literature suggests that an extra copy of chromosome 8 is a common occurrence in undifferentiated small round cell tumors frequently observed to carry the t(11;22), including esthesioneuroblastoma, Ewings sarcoma, peripheral neuroepithelioma, Askins tumor, and rhabdomyosarcoma. These data, combined with our report of a small round cell tumor with the karyotype 47,XY, +8, indicate that trisomy 8 may be a common phenomenon in these tumors, and may also provide some sort of selective advantage to these tumor types.

Monoclonal Antibodies to Intermediate Filament Proteins

Surgical pathologists base diagnoses upon characteristic features of neoplasms such as gland formation, papillary structures, and the spindle shape of tumor cells. Tumors without obvious differentiated features pose diagnostic problems because they lack the features that allow an accurate identification of tumor type. In such situations, one depends upon ultrastructural analysis by electron microscopy or relatively nonspecific histochemical stains to gain a clue as to the identity of the neoplasm. Clearly, what has been lacking in diagnostic pathology is a set of well-characterized tissue-specific reagents capable of distinguishing among different cells. Recently, anti-intermediate filament protein antibodies have been employed to distinguish cell type in poorly differentiated neoplasms.

Differential diagnosis of genitourinary tumors using monoclonal antibodies to intermediate filament proteins

Definitive diagnosis of poorly differentiated and metastatic neoplasms may be impossible using conventional histologic criteria. Recent developments in cell biology and immunology now enable us to answer such difficult diagnostic problems. Several varieties of structural proteins can be identified in malignant cells using monoclonal antibodies. The composition of these proteins can yield information regarding the origin of a neoplasm. Intermediate filaments are one such family of structural proteins. By characterization of these proteins, using a panel of monoclonal antibodies, poorly differentiated tumors may be definitively classified as carcinomas, sarcomas, lymphomas, or neural tumors. This approach to tumor diagnosis is now applicable to difficult problems in clinical urology.