In liver metastases from small intestinal neuroendocrine tumors, SSTR2A expression is heterogeneous.

We examined somatostatin receptor type 2A (SSTR2A) expression in primary and metastatic small intestinal neuroendocrine tumors (SI-NETs). We retrieved 156 liver metastases from 26 patients (10 males, 16 females) who had two or more liver lesions resected. A representative formalin-fixed paraffin-embedded section of tumor tissue from each liver metastasis and from the primary tumor, when available, were immunohistochemically stained for SSTR2A.

Liver metastases of small intestine neuroendocrine tumors: Ki-67 heterogeneity and World Health Organization grade discordance with primary tumors.

Objectives: We examined Ki-67 heterogeneity within single and between synchronous liver metastases of small intestine neuroendocrine tumors.

Methods: There were 27 patients (10 men and 17 women) with two or more liver metastases. The Ki-67 index was used to classify the tumors into World Health Organization grade 1, 2, or 3.

Bone cancer.

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors.

Signal transduction pathway analysis in desmoid-type fibromatosis: transforming growth factor-β, COX2 and sex steroid receptors.

Despite reports of sex steroid receptor and COX2 expression in desmoid-type fibromatosis, responses to single agent therapy with anti-estrogens and non-steroidal anti-inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co-express these targets. Clearly, further understanding of the signaling pathways deregulated in desmoid tumors is essential for the development of targeted molecular therapy.

Nuclear p63 expression in osteoblastic tumors.

Expression of the p63 tumor suppressor protein has been reported in the mononuclear stromal cells of giant cell tumor of the bone, which may represent osteoblast-precursor cells. Only a limited number of osteoblastic tumors have been studied for p63 expression thus far. We therefore examined whether p63 may serve as a marker for osteoblastic differentiation in osteosarcomas or as a differential diagnostic marker to distinguish osteoblastoma from osteosarcoma.

Signal transduction pathway analysis in fibromatosis: receptor and nonreceptor tyrosine kinases.

Despite reports of receptor tyrosine kinase activation in desmoid-type fibromatosis, therapeutic benefits of kinase inhibitor therapy are unpredictable. Variability in signal transduction or cellular kinases heretofore unevaluated in desmoid tumors may be responsible for these inconsistent responses. In either case, a better understanding of growth regulatory signaling pathways is necessary to assess the theoretical potential of inhibitor therapy.

Morphologic and immunophenotypic analysis of desmoid-type fibromatosis after radiation therapy.

The morphologic changes seen in desmoid-type fibromatosis after radiotherapy have not been well studied, and the degree of cytologic atypia, cellularity, mitotic activity, and lesional necrosis found in desmoid-type fibromatosis treated with ionizing radiation has not been thoroughly assessed. Therefore, we evaluated a series of primary and locally recurrent desmoid-type fibromatoses resected at variable intervals after radiation therapy (XRT) and compared their histopathologic and immunophenotypic features with paired pathologic specimens that were obtained before radiotherapy. The morphologic characteristics of desmoid-type fibromatoses resected before and after radiotherapy were not significantly different in 7 of the 8 cases studied.

Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules.

Purpose: To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide.

Patients And Methods: Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.

Developing an in-training examination for fellows: the experience of the American Society of Clinical Oncology.

The American Society of Clinical Oncology (ASCO) developed its own test -- the Medical Oncology In-Training Examination (MedOnc ITE) -- as a tool to assess trainees' knowledge of the clinical oncology subspecialty, establish consistency in educational standards across training programs, identify areas of strength and weakness in individual programs, and stimulate intraprogrammatic reading and discussion. The Accreditation Council for Graduate Medical Education Outcome Project provided additional incentive for ASCO to develop an ITE. The examination was developed in 4 years.

The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study.

Purpose: Microtubules play a critical role in many cellular functions, including cell division and mitosis. ABT-751 is a novel sulfonamide antimitotic that binds to the colchicine site on beta-tubulin that leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 was investigated in this phase 1 trial designed to assess its maximum tolerated dose (MTD), dose-limiting toxicity (DLT), tolerability, and pharmacokinetics.

Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer.

Objectives: Determine the toxicity, tolerability, and pharmacokinetics of SU5416, a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, coadministered with bolus 5-fluorouracil (5-FU), leucovorin, and irinotecan (IFL) in untreated patients with metastatic colorectal cancer.

Methods: SU5416 (85 or 145 mg/m2) was administered twice weekly throughout a 6-week period along with standard IFL (4 weeks on/2 weeks off). Plasma samples were assayed for SU5416, irinotecan, and SN-38 by reverse-phase HPLC.

Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients.

Background: Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.

Phase I and pharmacokinetic study of prinomastat, a matrix metalloprotease inhibitor.

Purpose: Prinomastat is a matrix metalloprotease (MMP) inhibitor with selectivity for MMPs 2, 3, 9, 13, and 14. Inhibition of these MMPs has been postulated to block tumor invasion and metastasis. This Phase I, dose-escalation study was designed to evaluate the acute and chronic toxicities of various doses of prinomastat and to determine prinomastat pharmacokinetics.

A phase I dose-escalation and pharmacokinetic study of brostallicin (PNU-166196A), a novel DNA minor groove binder, in adult patients with advanced solid tumors.

Purpose: This study was performed to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetics of brostallicin, a nonalkylating DNA minor groove binder and a synthetic derivative of distamycin A, given as a weekly i.v. infusion.