Regional hyperthermia combined with high energy shock wave treatment on Dunning prostate tumors

Male Copenhagen rats implanted with Dunning R3327 prostate carcinoma were treated with regional hyperthermia and high energy shock waves (HESW). Twenty-four rats were divided into four equal groups. All rats in one group were matched with the corresponding rats in the other three groups according to tumor size. Hyperthermia was created by the resistive heating of a 22-gauge 1.5-cm needle; HESW were generated by the Dornier XL-1 experimental lithotripter. In two hyperthermia treatments administered 48 hours apart, the tumor was heated to 46.5 degrees C for 2 hours; HESW treatment involved 1,600 shocks at 18 kV. Twenty-nine days after initiation of this study, animals were sacrificed and tumor growth calculated. Tumor growth in group 1 (combined hyperthermia and HESW) was significantly delayed between the 7th and 29th day (p = 0.05). In group 2 (HESW alone), tumor growth was significantly delayed between the 7th and 22nd day (p = 0.01), while tumor growth in group 3 (hyperthermia alone) was delayed between the 3rd and 22nd day (p = 0.02). On day 22, mean percent change in tumor growth in the control group exceeded that of group 1 by 449% (p = 0.015) as well as that of groups 2 and 3, by 350% (p = 0.034) and by 268% (p = 0.049), respectively. As previous reports demonstrate the efficacy of hyperthermia in combination with irradiation or chemotherapy for the treatment of prostate carcinoma, our results indicate hyperthermia in combination with HESW may also be a useful treatment modality.     

Prostate cancer vaccines in combination with additional treatment modalities

Immunologic Research - Immunotherapy has been investigated in both preclinical studies and clinical trials as a new therapy for prostate cancer. Vaccines, including those that utilize dendritic...     

Vaccine immunotherapy for prostate cancer: from mice to men

Immunologic Research - Preclinical studies demonstrated the ability of an adenovirus/PSA (Ad/PSA) vaccine to induce strong anti-PSA immune responses, and these responses were capable of destroying...     

Effects of relaxation and stress on the capsaicin-induced local inflammatory response

OBJECTIVE: Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. METHODS: Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. RESULTS: The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. CONCLUSIONS: These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.     

CELLULAR REQUIREMENTS FOR THE REJECTION OF SKIN ALLOGRAFTS IN RATS

The role of bone marrow-derived cells in the rejection of skin allografts in rats was investigated. Lewis rats, rendered tolerant of BN antigens and bearing healthy grafts, were thymectomized, irradiated with 900 rad, and injected with varying doses of either normal isologous bone marrow, normal lymph node cells, and/or lymph node cells presensitized to BN antigens. In some experiments rats were also adoptively sensitized to tuberculin. Results showed that, although necessary for the elicitation of tuberculin skin reactions, bone marrow cells are not needed for the rejection of previously tolerated skin allografts. Rats receiving lymph node cells alone rejected their grafts in about 6–7 days. In addition, rats injected with bone marrow alone also rejected their grafts, although significantly later than did lymph node cell recipients, indicating that rat marrow contains a population of cells capable of reacting to transplantation antigens. These cells were found capable of reacting to major transplantation antigens but not minor as they were ineffective in causing the rejection of Ag-B compatible Fischer skin grafts. From experiments utilizing bone marrow from neonatally thymectomized donors and cells treated with an antiserum to rat T cells, these competent cells in the marrow were shown to be thymus derived.     

Development of an epithelial tissue culture line from human prostatic adenocarcinoma.

The development of a tissue culture line of human prostatic adenocarcinoma is described. The culture (HPC-36), derived from tumor tissue explants, is a pure epithelial culture with characteristics of neoplastic cells, including a large nuclear size relative to the amount of cytoplasm, multiple nucleoli within the nucleus, many mitotic figures, the formation of multinucleated giant cells and the loss of contact inhibition. The cells also stained positively for acid phosphatase and have been grown in monolayer and suspension cultures. The HPC-36 cells presently are being studied to determine whether they are true descendants of the cancer cells.     

Effects of acute stress, relaxation, and a neurogenic inflammatory stimulus on interleukin-6 in humans

Effects of three experimental manipulations: mental stress, relaxation, and a nociceptive inflammatory stimulus, capsaicin, on levels of interleukin-6 (IL-6) were examined. Fifty subjects were pre-trained in relaxation and then randomized to a stress (Stroop test), relaxation (tape), or control (video) manipulation. Subjects participated in an evening reactivity session including 20 min of stress, relaxation, or control followed by a capsaicin injection in the forearm. Cardiovascular variables and levels of IL-6 were measured before and after the manipulation, and at regular intervals up to 60 min post-capsaicin. Group assignment did not differentially affect change in IL-6 over time, either before or after capsaicin. Small but significant increases in IL-6 were seen at 60 min post-capsaicin. These findings suggest that an acute stress manipulation does not modulate IL-6 within this time frame. Although IL-6 did increase following a neurogenic inflammatory stimulus, it did so subsequent to the maximum flare, suggesting that flare mechanisms are independent of IL-6.     

A novel immunological model for the study of prostate cancer.

The Dunning R-3327 rat prostatic adenocarcinoma is a widely accepted model for in vivo experimental studies of prostate cancer. We have previously derived phenotypically distinct cell lines from a s.c. tumor resulting from the inoculation of the R-3327-5 subclone into Copenhagen rats. In this study, we report studies using a gelatin sponge model for the delivery of tumor cells and the retrieval of tumor-specific leukocytes responsive to different prostatic cell lines. S.c. preimplanted sponges were inoculated with tumor cells previously selected for differential properties of tumor formation and metastasis and examined for leukocyte content at time points of 1, 3, and 5 weeks after tumor cell inoculation. Cytospin and flow cytometric analyses revealed fewer tumor-associated leukocytes present in sponges inoculated with tumorigenic R-3327-5' and R-3327-5'B lines, with lesser sponge degradation, than in experiments with the nontumorigenic R-3327-5'A line, suggestive of a tumor cell-induced immunomodulatory mechanism. Morphological studies indicate an intermittent tumor growth pattern that gradually disappears in sponges inoculated with the nontumorigenic R-3327-5'A cells but a robust growth pattern in sponges inoculated with the tumorigenic cell lines. Cytokine analyses show the secretion of higher levels of active transforming growth factor-beta by the more invasive and metastatic lines. Total transforming growth factor-beta levels are higher in the epithelial, tumorigenic R-3327-5'B line. Additionally, the more tumorigenic lines secrete interleukin 10, a potent immunosuppressive molecule. In this report, we demonstrate the ability to retrieve viable leukocyte populations from a prostate tumor line bearing sponges, which offers an important model for further in vitro and in vivo manipulations and holds promise for testing adoptive immunotherapeutic strategies.     

Experimental hypersensitivity pneumonitis in the rat: histopathology and T-cell subset compartmentalization

The pathogenesis of hypersensitivity pneumonitis (HP) appears to depend largely on T-cell specificity and interactions with monocytes/macrophages. We studied T-cell subset populations, defined by surface membrane markers with putative functional correlates, present in lung parenchyma and bronchoalveolar spaces of sensitized LEW rats following acute and chronic inhalational challenges with antigen. Our initial hypothesis was that the CD4+ RT6- (TDH) subset, the effector cell of delayed hypersensitivity, would dominate in HP lesions and that CD8+ RT6+ (TS) or CD8+ CD45R+ (TS) subsets, constituting putative suppressor T-cell populations, would dominate in lungs of animals with resolving lesions. We found, however, a heterogeneous population involving all eight of the T-cell subsets that were evaluated. Percentages of the RT6+ phenotype diminished as T cells moved from peripheral blood to lung. Dominant numbers of T cells in acute HP included CD8+ RT6- (TCYT) and CD8+ CD45R- (TCYT) subsets, with putative cytotoxic T-cell activity, in addition to CD4+ RT6- (TDH) cells. We did not demonstrate increases in T suppressor cells as the disease waned.