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Biomedical subjects

F J Volenec

Publications and source records attributed to F J Volenec.

At least 19 recordsLinked to original sources

Adjuvant immunotherapy for melanoma.

Adjuvant immunotherapy was administered to 84 lymph-node-negative and 25 lymph-node-positive melanoma patients. This active specific homologous cell protein preparation was given after aggressive surgery and given over 2 years. Projected and observed survival rates are presented as well as other clinical and pathologic characteristics such as female-to-male ratio, site of primary, level and depth of invasion. The projected 5-year survival rates are 90% for all stage I with 89% for females and 94% for males. Lower extremity stage I projected 5-year survival rate was 88% for all, 87% for females, and 100% for males. The projected 5-year survival rate for stage II was 68% overall and 100% for lower extremity. Only two of five patients with an unknown primary have expired. All of these results are improved over expected survival. Hopefully a randomized prospective study will be stimulated to ascertain the basis for this improvement.

Aged↗

Treatment of primary breast cancer with immunotherapy. Comparison with adjuvant chemotherapy and radiation therapy.

For the first time, data on 78 breast cancer patients treated by modified radical mastectomy and adjuvant immunotherapy have been reported. Thirty-nine lymph node negative patients with uninvolved lymph nodes had a projected 5 year survival rate of 94 percent and 39 patients with involved nodes had a projected 5 year survival rate of 77 percent and a disease-free survival rate of 70 percent. Results have been presented according to UICC staging. The 100 percent survival rate of stage I patients has been compared with rates obtained by treatment of breast cancer with radiation therapy as the principal modality. The preliminary data are promising enough to warrant randomized, prospective trials with the other adjuvant modalities.

Antineoplastic Agents↗

The role of the regional lymph node in breast cancer: a comparison between nodal and systemic reactivity.

Confusion remains concerning the role of the regional lymph node in the containment of cancer. Numerous investigators using a variety of assays have reported often conflicting results concerning the immunocompetency of lymphocytes residing in regional nodes. Forty-two axillary lymph nodes from ten stage I and stage II breast cancer patients were studied in lymphocyte blast assays using mitogens and breast cancer antigen (BCA). Three general response patterns to BCA were identified which were related primarily to tumor size. In the patients with the smallest primary tumor (0.5 cm), lymphocytes in the nodes reacted to a much greater extent than peripheral blood lymphocytes (PBL). In two of three patients with intermediate-size tumor (1.0 to 1.5 cm), a mixed pattern of responses was seen with both stimulation suppression occurring within the nodes of the same patient. In the four patients with the largest tumors (2.0 to 3.0 cm), 15 of 19 nodes had a lower stimulation index (SI) than the corresponding PBL. From the results of this study it appears that regional lymph nodes are dynamic immunologic structures which regress in responsiveness as tumor burden increases.

Antigens, Neoplasm↗

Immunologic responsiveness of patients with cancer: relationship to tumor type, stage and prognosis.

Data on cellular immunity of 39 patients with breast cancer and 29 patients with malignant melanoma, is presented. T/B lymphocyte ratios, lymphocyte blastogenesis (LB) with PHA and with cancer antigen preparations were carried out from two to four weeks after cancer surgery, and immediately after eight weeks of immunostimulation with a tumor-specific vaccine. Distinct differences were observed. Small breast cancers do not seem to evoke a host immune response, while small melanomas are associated with a state of immune stimulation. After immunotherapy LB in these breast cancer patients shows significant stimulation while LB in the melanoma patients changed from stimulation to normal response. Quite different results were obtained in patients with Stage II cancers; breast cancer patients showed immune stimulation which did not change after immunotherapy. The melanoma patients showed low normal immune response, which changed to high normal after immunotherapy. Patients with Stage III breast cancer and melanoma were similar in their poor immune responsiveness. Possible mechanisms are offered for these differences.

Antigens, Neoplasm↗

Immunologic responsiveness of the breast cancer patient.

Lymphocytic infiltration of the primary breast cancer and sinus histiocytosis of the axillary lymph nodes are indications of a favorable prognosis. Similarly, skin test responsiveness such as with DNCB or with tumor extracts correlates in general with stage of disease. This presentation will bring forth preliminary data on cellular immunity of breast cancer patients. Circulating lymphocytes (PBL) were stimulated with mitogens and a breast cancer antigen. PBL from patients with a primary tumor less than 2.4 cm in size reacted as though no immune stimulus existed. PBL from patients with a lump from 2.5 to 5.0 cm in size showed evidence of immune stimulation. An increase in size of the primary tumor over 5 cm and an increase in the number of axillary lymph nodes with metastasis were associaed with a diminution in cellular immunity. However, data from an adjuvant immunotherapy program show that cellular immunity can be improved in certain patients by immunization. Such patients continued to remain disease free, while patients whose cellular immunity was poor or not improved by adjuvant immunotherapy tended to develop recurrent disease.

Antigens, Neoplasm↗

Mouse colostomy model for studies on large bowel cancer.

The development of appropriate animal model systems has been proposed as a means of facilitating the study of human colorectal cancer. This report describes the development and use of a blind-colorectal pouch in a carcinoma mouse model. The blind-pouch was prepared in C57BL/6J mice by surgically exteriorizing the descending colon and producing two stomata in the abdominal wall. The proximal stoma served as an end colostomy and the distal stoma created as a mucous fistula. Surgical closure of the anus thus provided a colorectal pouch. In pilot studies it was found that N-methyl-N-nitrosourea (MNU) and radiation together but neither separately produced tumors in the pouch of surviving mice. Further, inoculation of C38 syngeneic tumor cell suspension into the pouch and immediate closure resulted in tumor takes within three to four weeks. The use of this model in carcinogenesis and the immunology of colon cancer simulate the human colorectal cancer problem more closely than previous animal models.

Animals↗

Autoantigens in breast cancer tissue.

Two antigens in specimens of human breast cancer have been identified as autoantigens. One antigen appears to be an IgG Fc fragment; the other, an IgG Fab fragment. Antibodies in sera of cancer patients directed against these antigens have also been identified. These autoantibodies occur in patients with breast cancer as well as other cancers, and rarely in patients with non-cancerous disease or in people screened in a detection center for breast diseases. The breast cancer patient found to have antibody directed against the IgG Fab antigen falls into a group that has improved two-year survival statistics over groups of patients who lack this antibody.

Antibodies, Neoplasm↗

Burn wound biopsy bacterial quantitation: a statistical analysis.

Sequential paired punch biopsy samples were taken from three separate locations on each of four burn patients and were quantitated for the number of viable bacteria per gram of tissue. The range (log10 0.02 to log10 1.51) and the standard deviation (log10 0.67) were determined for each pair. The 95 per cent confidence interval based on any single observation, x, was determined to be x +/- 1.31. It is concluded that the burn wound biopsy is a reliable procedure for quantitating organisms in a burn wound and that changes in sequential samples give an indication of the dynamics of infection in the burn patients.

Bacteria↗

Metabolic profiles of thermal trauma.

The study was designed to establish where significant correlations exist in a variety of metabolic substrates and hormone mediators in patients sustaining thermal injury. The factors studied were insulin, human growth hormone, cortisol, glucagon, free fatty acid, triglyceride and glucose. Incorporated into this design was an evaluation of the impact of quantitated severity of injury upon these correlations. In patients sustaining a low severity of injury (Probability of death (p = 2.2 to 33.9) there appeared a loss of glucose regulation in conjunction with insulin resistance without significant interplay of other factors studied. In contrast, patients sustaining high severity injury (p = 46.9 to 100) evidenced correlations between glucagon and glucose (negative), cortisol and free fatty acid indicating a significant role of hyperglucagonemia in these patients. A discriminant function analysis was employed to incorporate all significant variables into a probability model. Only insulin, glucose and glucagon appeared in the optimal classification equation.

Adolescent↗

Mononuclear cell analysis of peripheral blood from burn patients.

Mononuclear and polymorphonuclear cells isolated by Ficoll-hypaque density-gradient sedimentation from peripheral blood of 25 burn patients at 3-to 4-day intervals during hospitalization were subjected to morphologic analysis. The aim was to identify all cells isolated and to examine the cell population characterized as B-lymphocytes. Patterns of response comprised of lymphocytes, monocytes, neutrophils, and precursor cells in varying stages of maturity were delineated. Shortly after thermal trauma, isolated cell pools from all patients contained high proportions of immature cells. In surviving patients during convalescence, the cell pools had increasing proportions of mature cells and corresponding declines in immature cell types. Patients who died did not produce large populations of mature cells at any time during their hospitalization. Cells identified morphologically as lymphocytes were accounted for by E-rosette assay (T-lymphocytes). Cells previously identified as B-lymphocytes appeared morphologically to be monocytes, were positive for Fc and complement receptor activity, and were phagocytically active.

B-Lymphocytes↗

Quantification of serum IgE in patients with burns.

IgE levels in the serum of individuals with burns were sequentially measured and compared to IgE levels in normal control blood donors. Following a burn, the levels of IgE protein showed a significant, although modest, increase, usually evident of IgE protein showed a significant, although modest, increase, usually evident between days 14 and 22. In an occasional patient, the IgE levels rose by as much as five times in value during this period. Because of the complexity of the clinical situation associated with the burn patients, we cannot ascribe these elevations of IgE to the burn per se, but must consider the possibility of other factors, especially those involved in the treatment of the burn as well as the infection. The magnitude of the elevation of IgE in the burn patients (geometric mean=272 ng/ml) was considerably lower than the magnitude of the elevations seen in atopic dermatitis and generalized neurodermatitis (geometric means=2265 and 2071 ng/ml, respectively). Thus simple trauma to the skin is not a sufficient explanation for the elevated serum IgE levels in atopic dermatitis and generalized neurodermatitis.

Adult↗

Autoantibodies to an altered IgG in human breast cancer.

Recent studies have shown that antibody in the serum of patients with carcinoma of the breast reacts with two distinct antigens obtained from breast cancer tissue. Hence, there are two antibodies. The first antibody reacts against the Fc fragment of immunoglobulin and is also found in the sera of patients with benign breast disease and certain inflammatory lesions and, therefore, does not seem to have any significant meaning for the patient with carcinoma of the breast. The second antibody is directed against the Fab fragment of human immunoglobulin that is found in breast cancer tissue. Recent experiments have shown that in immunodiffusion tests, this autoantibody reacts not with normal IgG(Fab), but rather with heat-aggregated Ig(Fab). It is thought that tumor-associated antibodies react with antigens on the tumor cell surface. Intracellular enzymes then proceed to fragment the attached antibody, leaving the Fab fragments attached on the cell surface. With intact immunosurveillance, the host appreciates this altered immunoglobulin (Fab). It is suggested that the autoantibody then formed against this fragment reacts with the fragment attached to the tumor cell, thereby allowing the tumor cell to be destroyed. Clinical data supporting this hypothesis are derived from the fact that 9 patients having this autoantibody to the Fab fragment are alive at 1 year after their carcinoma of the breast.

Adenofibroma↗

Role of tumor immunity in ovarian cancer.

Antigens associated with ovarian cancer tissue have been identified by the use of heteroantisera. It has also been reported that lymphocytes from patients with ovarian cancer responded to phytohemagglutinin (PHA) and keyhole-limpet hemocyanin (KLH) but had failed to respond to autologous tumor extracts. In our series, pretreatment sera from 37 patients with stage III and IV ovarian cancer failed to react with ovarian cancer antigen preparations. After therapy, serum from only three patients was reactive: all three patients were treated by chemoimmunotherapy. Preliminary data from this clinical trial for treating stage III and IV ovarian cancer with chemotherapy, immunotherapy, or combined chemoimmunotherapy show that survival of patients treated by chemotherapy or immunotherapy corresponded to that of nonresponders to L-PAM therapy as described in another study. Interestingly, combined chemoimmunotherapy produced a survival curve depicting significant improvement, similar to that for the responders to L-PAM therapy reported in that study.

Antibodies, Neoplasm↗

Interferon in nasal secretions and sera of calves after intranasal administration of avirulent infectious bovine rhinotracheitis virus: association of interferon in nasal secretions with early resistance to challenge with virulent virus.

Calves which had received avirulent infectious bovine rhinotracheitis virus (AV-IBR) by intranasal (IN) administration developed detectable levels of interferon (IF) in nasal secretions as early as 40 hr later. Peak titers (1:640) of IF appeared in secretions 72 to 96 hr after administration of virus, and titers of 1:80 to 1:320 were maintained through the 8th day. Lower titers (1:5 to 1:10) of IF were detected in sera obtained on the 4th to 8th days after administration of virus. Peak titers of IF in respiratory tract secretions were accompanied by a 100- to > 1,000-fold reduction in the levels of AV-IBR present in the secretions. Serum antibody was not detected prior to the 8th day after administration of AV-IBR. Calves which received AV-IBR by the IN route 72 or 96 hr earlier were refractory to challenge with virulent infectious bovine rhinotracheitis virus (IBR), whereas calves receiving AV-IBR 18 or 40 hr earlier became clinically ill following challenge. The temporal association between appearance of IF in respiratory tract secretions and onset of protection against challenge suggests a cause and effect relationship. No IF was detected in either nasal secretions or sera of calves receiving modified IBR virus by intramuscular injection. Following subsequent IN challenge of these calves, IF was detected in nasal secretions as early as 24 hr postchallenge and was maintained at titers of 1:40 to 1:80 for approximately 4 days, even in the absence of virus recovery. Greater ease of local IF induction with IBR virus in calves previously sensitized with that virus is suggested.

Administration, Intranasal↗