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E V Sugarbaker

Publications and source records attributed to E V Sugarbaker.

15 recordsLinked to original sources
PubMed1991

Intercellular transfer of drug resistance.

The effect of L-phenylalanine mustard (L-PAM) on heterogeneous cell populations containing sensitive and resistant cells was evaluated by flow cytometric analysis of DNA damage. Cell cultures were treated with L-PAM for 1 h, fixed, and stained with anti-DNA monoclonal antibody which detects DNA damage induced by alkylating agents. DNA damage was significantly lower in sensitive A2780 cells cocultured with resistant A549 or A2780/PAM cells than in A2780 cells grown separately. Decrease of DNA damage in sensitive cells did not occur when sensitive and resistant cells were grown in common medium without direct contact. Transfer of drug resistance in cocultures was prevented by phorbol ester which is known to inhibit metabolic cooperation via cell junctions. Treatment of cocultures with buthionine sulfoximine increased DNA damage in resistant cells and prevented decrease of DNA damage in sensitive cells. Glutathione (GSH) content in A2780 cells cocultured with A549 cells was significantly higher than GSH content in A2780 cells grown separately. We conclude that decreased response of sensitive cells in cocultures was induced by contact transfer of GSH from GSH-rich resistant cells to sensitive cells. Intercellular transfer of drug resistance demonstrated by analysis of DNA damage was confirmed by colony formation assay. Treatment with L-PAM and Adriamycin killed all cells in A2780/MDR and A549 cultures. Coculture of these lines survived combination treatment because transfer of GSH to multidrug-resistant cells from GSH-rich A549 cells induced resistance to L-PAM and Adriamycin in a single cell. The presence of 2% A549 cells increased resistance of A2780/MDR cells to L-PAM. Phorbol ester eliminated resistance of coculture to combination treatment. Metabolic cooperation between cell subsets with different mechanisms of drug resistance induced resistance to treatment with drugs of different classes (multiclass drug resistance). Inhibition of cell cooperation may improve the response of tumors to combination chemotherapy.

Antimetabolites↗
PubMed1979

Cancer metastasis: a product of tumor-host interactions.

Metastasis continues to be the most devastating event for the patient with an established primary cancer. The most significant therapeutic problems are: (1) treatment of patients with established macrometastases, (2) identification of patients who have micrometastases and (3) the development of adequate adjunctive therapies for micrometastases. It is hoped that our evolving understanding of the biology of experimental metastasis and the high level of premium quality laboratory research ongoing in this area will result in further resolution of this clinical problem or, at least, a better understanding of this most extreme expression of the malignant phenotype.

Animals↗
PubMed1979

Some characteristics of metastasis in man.

The studies of experimental cancer metastasis are only truly meaningful to the degree that knowledge applicable to the therapeutic problem of cancer metastasis in man ensues from them. The salient features of cancer metastasis in man, therefore, are important to the laboratory researcher, for they provide a framework for which the relevance of an experimental model system must be judged. This brief discussion of some of the clinical characteristics of metastasis in man demonstrates the wide spectrum of biologic behavior and the complex multifaceted nature of this problem. It must be concluded that a complex interaction between tumor cells and host mechanisms eventually governs whether or not metastasis occurs in man.

Carcinoma, Squamous Cell↗
PubMed1979

Flow cytometry: general principles and applications to selected studies in tumor biology.

The cell populations derived from normal tissues and solid tumors comprised many different cell types. Within each cell type there is a distribution of cells in different phases of the cell cycle and/or metabolic states (ie, differing rates of protein, RNA, and other macromolecular syntheses). Flow cytometry and companion instrumentation now promise to aid in rapid quantitative analyses of heterogeneous cell populations, thus finding broad applicability in many areas of cancer research and treatment. Since it is projected that this analytical technique will greatly expend our knowledge in tumor biology, it seems appropriate to review the basis principles of the methodology and to demonstrate recent applications in several areas of current research. After reviewing basis principles, a detailed description of one specific flow cytometer, the PHYWE-ICP-22, with its computer interface as developed in this laboratory is described. Subsequently, applications of this methodology to analyses of tumor cell kinetics, assays of blastogenesis, and studies of human colon cancer are presented as specific, current applications of flow cytometry. It is anticipated that this overview of flow cytometry along with some current applications will provide a background understanding for the inevitable rapid future developments in this area of research.

Animals↗
PubMed1978

Inflammatory oncotaxis.

Tumor recurrence after a prolonged disease-free interval suggests that neoplastic cells may remain dormant within the host. Activation and growth of these metastatic focuses may occur secondary to inflammation at sites distant from the primary tumor. The concept of inflammatory oncotaxis is presented as a mechanism of cancer cell attraction and facilitation of transcapillary migration into tissue spaces. Physicians should focus astutely on internal and external sites of inflammation as possible focuses for tumor recurrence in the follow-up of the cancer patient.

Aged↗
PubMed1977

Mechanisms and prevention of cancer dissemination: an overview.

Synthesizing data from many experimental and clinical courses, a current working model for tumor dissemination has been constructed. Several aspects of this model are being exploited to therapeutic advantage for the patient with cancer. Surgeons should continue to exercise the principles of en bloc tumor resection and employ maneuvers to minimize iatrogenic tumor dissemination .

Animals↗
PubMed1976

Survival and regional disease control after isolation-perfusion for invasive stage I melanoma of the extremities.

Excision of the primary and isolation-perfusion with 1-phenylalanine mustard was the treatment in 199 patients with invasive Stage I melanoma of the extremities with the goal of improving regional disease control and long-term survival. The determinant survival in patients followed 5-15 years was 83%; Berkson-Gage survivals were 98% at 2 years, 88% at 5 years, and 84% at 10 years. The site of first recurrence was determined in all 49 (25%) patients who failed treatment: three (2%) developed local recurrence, six (3%) developed intransit recurrence, 24 (13%) developed positive regional lymph nodes, 15 (8%) developed systemic metastases, and one developed local recurrence plus positive regional nodes. Of these 49 patients failing treatment, 15 (31%) are currently surviving with no evidence of disease after retreatment of the recurrence. These data are compared to historical controls in the literature. It is concluded that regional control rates are improved by perfusion and that survival has probably been improved. In 14 patients treated by perfusion without local excision, regional control and survival was poor. Single drug (L-PAM) perfusion with the techniques employed is effective in controlling regional subclinical disease, but the primary should be widely excised.

Adolescent↗
PubMed1976

Squamous cell carcinoma of the oropharynx: why we fail.

The squamous cancers of the oropharynx in 384 patients were staged according to a T and N system. Three hundred seventy-one of them were treated for cure at a time when modern surgical and radiotherapeutic technics were available. The patient records were analyzed in regard to five year survival, factors influencing treatment failure, and the effect of new primary cancers. Failure to eradicate the cancer at the primary site remains the largest reason for the patients' demise, but as aggressive local and regional treatment becomes more successful, greater numbers of patients survive only to become victims of distant metastases and second primary cancers.

Carcinoma, Squamous Cell↗
PubMed1976

Analysis of survival and disease control in stage I melanoma of the head and neck.

From 1958 through 1969, 357 patients were treated for melanoma of the head and neck. Of these, 166 had invasive, clinical stage I disease. All patients had wide local excision of the primary. Elective regional node dissection was performed in sixty-nine patients and in the remaining ninety-seven observation only was elected. Retrospective analysis of these 166 patients considered (1) survival and disease control, (2) sites and timing of failures, and (3) the effect of sex, site, type of biopsy, skin grafting, and regional node dissection on disease control and survival. More than 80 per cent of the local recurrences developed within the first twenty-four months. Similarly, in the patients not undergoing initial neck dissection, 80 per cent of those who subsequently had clinically positive regional nodes did so within twenty-four months. In the sixty-nine patients undergoing elective regional node dissection, the survival rate was 33.5 per cent at five and ten years in those with histologically positive nodes. Those patients with elective neck dissections having histologically negative nodes had a survival rate of 75.8 and 67.1 per cent at five and ten years, respectively.

Adolescent↗
PubMed1976

Melanoma of the trunk: the results of surgical excision and anatomic guidelines for predicting nodal metastasis.

From 1958 through 1969, inclusive, 418 patients with melanoma of the trunk were treated at the M. D. Anderson Hospital and Tumor Institute. Of these, 128 patients (31%) had Stage I disease and were treated by excision with observation of regional nodes in all except five patients. Retrospectively these Stage I patients were analyzed regarding (1) survival, (2) sites and timing of treatment failures, (3) the relation of the primary site to eventual nodal metastasis, and (4) the variables of sex, size, and location on the trunk, which also were correlated with disease control. The results show: (1) actuarial survival rate of 65.7% and 55.7% at 5 and 10 years, respectively; (2) positive regional lymph nodes (RLN) evolved in 34 patients (28%), systemic metastases in 18 patients (15%), local recurrence (LR) in four patients, LR plus RLN in one patient, and intransit metastases in three patients as the first evidence of failure. Over 90% of LR and positive RLN developed within 24 months. Many intransit recurrences and systemic metastases occurred later and account for much of the biologic variability attributed to melanomas: (3) the anatomy of the lymphatics of the trunk as described by Sappey is an excellent guide to the site of first nodal metastasis, (4) a midline or near-midline primary site correlated with regional failure (p less than 0.05). More men failed regionally than did women (p less than 0.05). In retrospective calculation, 184 regional node dissections would have been required for probable salvage of 13 patients (10%) if surgical treatment for subclinical disease had been used routinely.

Female↗
PubMed1975

Prophylactic isolation-perfusion as the primary therapy for invasive malignant melanoma of the limbs.

The most common causes of treatment failure in patients with malignant melanoma treated by surgical therapy alone are local or regional recurrences. These are presumed to be due to occult metastasis present at the time of the initial treatment. In an effort to control this occult regional disease, 202 patients with Stage I malignant melanoma underwent isolation-perfusion with 1-phenylalanine mustard between the years 1960 and 1970. The 2-5 and 10-year determinate survival rates were 98%, 86% and 83%, respectively. In these patients, 2% developed local recurrences, 3% developed intransit metastasis, 18% developed positive regional lymph nodes and 6% developed disseminated disease, as their first evidence of recurrence. Over 40% of these patients were benefitted by further therapy. When regional perfusion is used, the question of prophylactic lymph node dissection need not arise. There was one surgical death in this series and only a few patients had symptomatology referable to their limbs beyond 3 months.

Adolescent↗