No abstract

Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.

The epothilones are a novel class of non-taxane microtubule-stabilizing agents obtained from the fermentation of the cellulose degrading myxobacteria, Sorangium cellulosum. Preclinical studies have shown that the epothilones are more potent than the taxanes and active in some taxane-resistant models. Similar to paclitaxel and other taxanes, the epothilones block cells in mitosis, resulting in cell death. The chief components of the fermentation process are epothilones A and B, with epothilones C and D found in smaller amounts. Trace amounts of other epothilones have also been detected. Pre-clinical studies have shown that epothilone B is the most active form, exhibiting significantly higher antitumor activity than paclitaxel and docetaxel. Several phase I and phase II clinical trials are ongoing with epothilone B and BMS 247550, an epothilone B analog. Preliminary reports indicate these agents are active against human cancers in heavily pre-treated patients. The epothilones appear to be well tolerated, with a side effect profile that is similar to that reported with the taxanes. This article will review some basic aspects of epothilone chemistry and biology, and pre-clinical and preliminary clinical experience with epothilone B and its analog, BMS 247550.

P reliminary data have indicated that overexpression of HER-2/neu is correlated with more aggressive disease, an increased metastatic potential, and a poorer prognosis in patients with breast carcinoma. 1-3 Trastuzumab, a humanized anti-HER-2 antibody, reportedly is unable to penetrate the blood-brain-barrier and to our knowledge its efficacy in patients with brain metastases remains unclear. 4 -6 We conducted a retrospective study to evaluate whether patients with HER-2/neu-positive breast carcinoma have an increased risk of developing brain metastases.After approval from the institutional review board of West Virginia University, the pathology reports of 703 breast carcinoma patients who were diagnosed between April 1998 and January 2003 were reviewed. Based on immunohistochemistry or fluorescence in situ hybridization positivity, all patients who were positive for HER-2/neu were identified and their medical charts reviewed with regard to their course of disease and sites of metastases.Of the 703 patients studied, 164 (23%) were found to be positive for HER-2/neu; a sufficient oncologic history was available for 102 patients. Thirty-one patients (30%) developed distant metastases (95% confidence interval [95% CI], 0.223-0.399) during follow-up lasting a median of 57 months. Brain metastases were reported to have developed in 15 of these 31 patients (48%)(95% CI, 0.320 -0.652). A proportional hazards model was fit to the data to explore the association between patient age and time to the development of metastases. A significantly positive association (P ϭ 0.01) was found to exist between the two variables. Other models for censored data (Weibul, log-normal, and exponential models) were fitted and were found to produce nearly identical P values (Fig. 1).The results of this small retrospective study demonstrate that younger women with HER-2/neu-positive breast carcinoma may have a higher risk of developing brain metastases than previously reported for the general metastatic breast carcinoma patient population. This 442

No abstract

Erlotinib or other novel protein kinase pathway inhibitors should be evaluated further in patients with aggressive thyroid cancer variants, who may exhibit these and perhaps other tyrosine kinase mutations.

We report a case of occult breast cancer presenting as paraneoplastic sensory and motor neuropathy. The paraneoplastic antibody panel was negative and no other unknown identifiable antibody could be detected in the serum. Systemic treatment with four cycles of Adriamycin and cyclophosphamide was given with no significant improvement in the neurologic condition. We reviewed the literature of the last 10 years and identified 31 reported cases of paraneoplastic neurologic syndrome due to breast cancer. Paraneoplastic antibodies could be found in only 36% of patients, no identifiable antibodies in 32% of patients, and unknown antibodies in 16% of patients. The status of the paraneoplastic antibodies was not reported in 16% of patients. Only 29% of patients responded to chemotherapy with improvement in neurologic deficits. The role of systemic treatment in the progression of neurologic impairment is unclear.

In addition to tumor grade and stage, both a high MIB-1 index and a noneuploid or aneuploid DNA histogram of a given RCC have the potential to identify tumor patients with an impaired prognosis.