Faculty Bibliography

BACKGROUND: We analyzed morbidity and mortality, sites of recurrence, and possible prognostic factors in 95 (78 male, 17 female) patients with MPM on phase I-III trials since 1990. A debulking resection to a requisite, residual tumor thickness of < or = 5 mm was required for inclusion. METHODS: Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms. Pleurectomy (n = 39) or extrapleural pneumonectomy (EPP; n = 39) was performed. Seventeen patients could not be debulked. Preoperative EPP platelet counts (404,000) and mean tumor volume (491 cm3) were greater than that seen for pleurectomy (344,000, 114 cm3). RESULTS: Median survival for all patients was 11.2 months, with that for pleurectomy 14.5 months, that for EPP 9.4 months, and that for unresectable patients 5.0 months. Arrhythmia (n = 14; 15%) was the most common complication, and there were two deaths related to surgery (2.0%). Tumor volume of > 100 ml, biphasic histology, male sex, and elevated platelet count were associated with decreased survival (p < 0.05). Both EPP and pleurectomy had equivalent recurrence rates (27 of 39 [69%] and 31 of 39 [79%], respectively); however, 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional (p2 = 0.013). CONCLUSIONS: Debulking resections for MPM can be performed with low operative mortality. Size and platelet count are important preoperative prognostic parameters for MPM. Patients with poor prognostic indicators should probably enter nonsurgical, innovative trials where toxicity or response to therapy can be evaluated

PURPOSE: To describe localization studies in nine patients with ectopic parathyroid adenomas in the aortopulmonary window. MATERIALS AND METHODS: Nine patients with ectopic parathyroid tissue (eight adenomas, one hyperplastic gland) in the aortopulmonary window were examined with ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, and scintigraphy. Diagnostic arteriography (n = 4) and venous sampling (n = 3) were performed in the first four patients; arteriography for the purpose of staining was attempted in the last five patients. RESULTS: The results of CT and MR imaging studies were positive in eight of nine patients (89%) and five of eight patients (63%), respectively. The results of thallium/technetium scintigraphy were negative in three patients scanned (0%), but the results of a repeat study in one patient were positive (33%). Sestamibi scans were positive in six of six patients (100%). Single photon emission CT was performed in all six patients and enabled distinction between adenomas in the aortopulmonary window and those in the thymus. CONCLUSION: Ectopic parathyroid glands in the aortopulmonary window are usually detected at sestamibi scintigraphy, and SPECT is helpful in distinguishing these adenomas from more common adenomas in the anterior mediastinum. CT and MR imaging studies can also enable this distinction, but imaging must extend below the aortic arch

Octreotide scanning is increasingly being used to detect tumours with somatostatin receptors. Moreover, there is growing interest in the use of somatostatin analogues for the treatment of tumours with somatostatin receptors. This review documents the use at our institution of the octreotide scan in three patients with intrathoracic pathology, and comments on overall experience in the literature with this technology

We investigated the structure and the expression of various oncogenes in three of the most common human bone tumors-osteosarcoma (36 samples from 34 patients), giant cell tumor (10 patients), and chondrosarcoma (18 patients)-in an attempt to identify the genetic alterations associated with these malignancies. Alterations of RB and p53 were detected only in osteosarcomas. Alterations of c-myc, N-myc, and c-fos were detected in osteosarcomas and giant cell tumors. Ras alterations (H-ras, Ki-ras, N-ras) were rare. Chondrosarcomas did not contain any detectable genetic alterations. Our results suggest that alterations of c-myc, N-myc, and c-fos oncogenes occur in osteosarcomas, in addition to those previously described for the tumor suppressor genes RB and p53. Moreover, statistical analyses indicate that c-fos alterations occur more frequently in osteosarcoma patients with recurrent or metastatic disease

Uterine leiomyoma is an estrogen-responsive tumor, and the present studies examine the ability of the antiestrogen tamoxifen to modulate leiomyoma cell growth. Tamoxifen is an effective form of hormonal therapy for breast cancer, although the mechanism by which tamoxifen inhibits tumor growth is not well understood and may involve mechanisms other than the action of tamoxifen as an estrogen antagonist. Tamoxifen was found to inhibit the proliferation of three of five leiomyoma-derived cell lines (ELT cell lines) in vitro, including an estrogen receptor-negative cell line. The ability of tamoxifen to decrease leiomyoma growth was found to correlate with expression of insulin-like growth factor I (IGF-I) by the tumor cells, suggesting that the inhibitory effects of tamoxifen were associated with expression of this growth factor. The existence of an IGF-I autocrine loop in the cells was investigated, because transcripts for both IGF-I and its cognate receptor were expressed in the tamoxifen-responsive cell lines. An IGF-I RIA demonstrated secreted IGF-I protein in serum-free medium conditioned by the IGF-I-expressing cell line ELT 3, and this same medium supported the growth of IGF-requiring MCF-10A cells, indicating the presence of biologically active IGF-I in the conditioned medium. Exogenous IGF-I stimulated ELT 3 cell proliferation, confirming that this growth factor is mitogenic for leiomyoma cells. IGF-I neutralizing antibody inhibited ELT 3 growth, indicating that the levels of IGF-I produced by the leiomyoma cells were physiologically significant. These data demonstrate the existence of an IGF-I autocrine loop in tamoxifen-sensitive leiomyoma cells, supporting the hypothesis that the presence of an IGF-I autocrine loop predicts uterine fibroid responsiveness to tamoxifen

We evaluated the effect of antisense insulin-like growth factor (IGF) receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1R) genes was identified from H9A RNA using reverse transcription-PCR and Northern analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promoter HSP70) containing a cDNA fragment corresponding to base pairs 1-309 of IGF-1R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. The expression vector in genomic DNA was detected with PCR analysis as a 173-bp fragment on ethidium bromide gels. The effects of the expression vectors were then evaluated in vitro under active (at 39 degrees C) or inactive (at 34 degrees C) conditions. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (P2 < 0.02). At 34 degrees C, cell growth of A3 sense- and B9 antisense-transfected cells was not significantly different. In vivo tumorigenicity was evaluated in hamsters inoculated with 10(5) A3 sense- or B9 antisense-transfected cells. The A3 sense clones resulted in greater numbers of tumors in vivo compared to the B9 antisense clone (P2 = 0.0001). When genomic DNA from tumors that developed in A3 sense and B9 antisense animals was analyzed for the expression vectors, a 173-bp fragment amplified from the expression vector was identified in the sense tumors but not in antisense B9 or wild-type H9A tumors, indicating a loss of the vector from the antisense clones that proliferated in vivo. The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma

Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by polymerase chain reaction (PCR) with primers that amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Southern blot hybridization, and sequence analysis revealed that these samples also contained sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein. These results indicate that SV40-like sequences are present in human bone tumors