Induction of the estrogen-regulated "24K" protein by heat shock.

We have previously demonstrated an estrogen-regulated protein, termed 24K, in human breast cancer cell lines and human tumor biopsies. The presence of the protein correlates well with the presence of steroid hormone receptors. We have cloned a partial complementary DNA to 24K and show that the nucleotide and deduced amino acid sequence contains a striking homology to the low molecular weight heat shock proteins of Drosophila and the mammalian alpha-crystallins.

Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification.

Multiple drug resistance (MDR), consisting of acquired cross resistance to anthracyclines, vinca alkyloids, and other antineoplastic antibiotics, has been described in a variety of cell lines. This MDR phenotype is associated with overexpression and sometimes amplification of a gene coding for a 170 kDa glycoprotein, termed P-glycoprotein. To understand the role of this mechanism in clinical breast cancer, 248 breast cancer specimens representing both untreated primary and refractory relapsing disease were probed for evidence of P-glycoprotein gene amplification or overexpression using Southern, Northern, or Western blot techniques.

HER-2/neu oncogene protein and prognosis in breast cancer.

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens.

Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter.

Phase II study of esorubicin (4'-deoxydoxorubicin) in advanced or metastatic squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

Twenty-eight patients with advanced, measurable squamous carcinoma of the uterine cervix were treated with 62 courses of esorubicin at doses ranging from 20-35 mg/m2 every three weeks. All patients were evaluable for response and toxicity. All patients had received prior therapy including radiation therapy in 28, chemotherapy in 23, and surgery in 11.

Treatment of stage III breast cancer. A panel discussion.

A major question in oncology today concerns the most appropriate therapy for locally advanced breast cancer. Realistic goals include effective local treatment and a prolonged disease-free interval for these patients, most of whom have incurable disease. Here, our panel discusses the roles of surgery, radiation therapy, chemotherapy, and hormonal therapy, and the proper sequencing of these modalities.

New biologic prognostic factors in breast cancer.

Long-accepted prognostic factors for breast cancer patients include the number of axillary lymph nodes positive for cancer; size of the primary; histopathologic features such as nuclear grade, histologic grade, and mitotic index; and the estrogen and progesterone receptor status. Unfortunately, these factors are relatively insensitive in predicting which women are particularly at risk of relapse. Newer discoveries which are or may be better prognosticators of a breast cancer patient's future course include growth factors, oncogenes, thymidine labeling index, and measurement of DNA ploidy status by flow cytometry.

Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.

More accurate prediction of the prognosis in women with node-negative breast cancer may improve physicians' ability to identify the patients most likely to benefit from systematic adjuvant therapy. With this in mind, we performed DNA flow-cytometric measurements of ploidy and the fraction of cells in the synthesis phase of the cell cycle (S-phase fraction) on 395 specimens of node-negative breast cancer from our bank of frozen tumors, using the aliquots of pulverized frozen tissue from steroid-receptor assays. The median duration of follow-up in patients still alive at the time of analysis was 59 months.

Chromosomal assignments of human 27-kDa heat shock protein gene family.

The 27-kDa human heat shock protein (hsp27) is dually regulated by both estrogen and heat shock treatment. Its function is obscure, but the high degree of homology to the lens alpha-crystallins and to the small heat shock proteins of Drosophila suggests that it may serve a structural function. There are at least three related human hsp27 sequences.

Phase I trial of trimetrexate glucuronate on a five-day bolus schedule: clinical pharmacology and pharmacodynamics.

Trimetrexate glucuronate (TMTX), a nonclassical folate antagonist, has been evaluated clinically on several schedules. We have studied TMTX administered as an iv bolus for 5 consecutive days every 3 weeks in 35 patients with advanced solid tumors. Drug was given at doses ranging from 7.

Prognostic factors for recurrence and survival in axillary node-negative breast cancer.

The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx.

Prognostic factors in breast cancer.

There are several independent but interrelated prognostic factors predictive of recurrence and survival in breast cancer. These include axillary nodal status, histopathology, steroid receptors, proliferative rate, ploidy, and oncogene amplification. Axillary nodal status has been the traditional mainstay predictor for recurrence and survival in primary breast cancer.

Pain control in breast cancer. A panel discussion.

Pain can be a prominent finding in breast cancer patients. It may occur in the setting of the postmastectomy period, related to the disruption of normal neural pathways or the development of lymphedema. In advanced disease, the management of pain from nerve compression or bone metastases requires special approaches.

Estrogen receptor expression in human breast cancer associated with an estrogen receptor gene restriction fragment length polymorphism.

Estrogen receptor (ER) content is a well-known predictor of clinical outcome in human breast cancer. The recent cloning of a human ER complementary DNA has made possible the characterization of the ER gene on a molecular level. We have examined in human breast cancers a single, two-allele restriction fragment length polymorphism using the restriction enzyme PvuII.

Clinical and pharmacologic reappraisal of dichloromethotrexate.

Dichloromethotrexate (DCMTX) has been the subject of sporadic clinical development for the last 30 years. Although DCMTX was developed in hopes of discovering a more potent antifolate, the potential pharmacologic and toxicologic advantages of the analog have become of greater interest. This phase I and pharmacokinetic trial of DCMTX given on days 1, 8, and 15 every 28 days was undertaken to test these potential advantages.

Development of polyclonal and monoclonal antibodies to iodinated contrast media.

Two independent systems were developed to produce antibodies to diatrizoate. In the rabbit model polyclonal antibodies were produced that showed cross-reactivity to certain other contrast agents, analogues and serum proteins. In the mouse model monoclonal antibodies were produced that reacted only with diatrizoate, metrizamide, and ovalbumin.