Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposi's sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.
The complete nucleotide sequence of the transforming gene of a mouse sarcoma virus has been determined. It codes for a protein of 374 amino acids. The nucleotide sequence of the junctions between a murine leukaemia virus and cellular sequences leading to the formation of the viral transforming gene have also been elucidated. The viral transforming sequence and its cellular homologue share an uninterrupted stretch of 1,159 nucleotides, with few base substitutions. The predicted amino acid sequence of the mouse sarcoma virus transforming gene was found to share considerable homology with the proposed amino acid sequence of the avian sarcoma virus oncogene (src) product.
Introduction Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor–positive breast cancer. Patients and Methods Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy. Results Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks (P < .0036). Conclusion Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.
The purpose of this technical report is to determine the reproducibility of flow cytometry data for ploidy and cell cycle kinetics using paraffin-embedded blocks of breast cancer tissue. One block from each of 39 tumors was studied in this report with each block having multiple sections analyzed independently. All of these sections gave ploidy analyses, while only 34 gave cell kinetic values. The standard deviation for the DNA index value in the multiple analysis study was less than 0.1 in all but three cases. The cell kinetic values gave larger variability, and the actual values were dependent on the method of analysis. Comparison of the variability for each method of analysis could not predict which procedure was superior. These results would indicate that ploidy is a reproducible value, while cell kinetic parameters should only be used as an indicator of proliferative activity that has been normalized to the mean or median of a large set of observations processed and analyzed by the same procedure.Key terms: Breast cancer, cell kinetics, ploidy analysis, variability of analysis A review was performed on 65 articles published between 1983 and 1986 that had cited Hedley's procedure (6) on the use of paraffin-embedded (PE) sections for DNA analysis. These reports cited at least 26 different tissues, with colon, breast, and lymphoma being the most frequently analyzed types. There were seven general reviews, 43 with ploidy analysis, 14 with ploidy and cell kinetic analyses, and one with cell kinetic analysis only. This would indicate that cell kinetics is used in only 26% (15/58) of these studies. Because of the interest in this procedure, the following study was performed in order to establish objective criteria to evaluate the flow cytometry data obtained from PE blocks. This report provides information obtained from a reproducibility study of paraffin-embedded breast cancer tissues but could be applied to other tissues. MATERIALS AND METHODSThirty-nine PE tumor samples from primary biopsies were selected from a larger study of 650 node-positive breast cancer patients. Three to four 50-pm consecutive sections were sliced from each PE block, processed, stained, and analyzed independently by Hedley's procedure (6) except for the use of Fisher's Hemo-DE instead of xylene to dissolve the paraffin. Following hydration, pepsination, and centrifugation, the single-cell pellet was stained with a nuclear isolation media (10) containing propidium iodide (PI), and 37 pg/ml of RNAase (75k unitdmg). This solution was made fresh daily in order to prevent loss of RNAase activity. The stained nuclei were analyzed on a fluorescence-activated cell sorter (FACS) 440 flow cytometer with a n argon ion laser as the excitation source (i.e., 448 nmj, and the parameters for the emitted light were analyzed for forward and 90" light scatter, pulse width (to discriminate doublets), and red fluorescence (630 nMj of PI to determine DNA content per nucleus. In most cases 40,000 events were measured per analysis. The resulting data were acquir...
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