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Biomedical subjects

C A Olsson

Publications and source records attributed to C A Olsson.

At least 145 records · Page 8Linked to original sources

The influence of cytoreductive surgery on the response to chemotherapy of a rat renal cancer.

The potential ability of cytoreductive surgery to increase the effectiveness of chemotherapy (vindesine) was tested utilizing male Wistar Lewis rats transplanted simultaneously with intraperitoneal and flank implants of a spontaneously arising renal adenocarcinoma. Cytoreduction was accomplished in some animals by removing the flank tumor 5-7 weeks following implantation; all animals received vindesine (IP injection of 0.5 mg/kg on two successive weeks). While vindesine reduced tumor growth, in no case did the addition of cytoreductive surgery enhance the effect of chemotherapy. The addition of cytoreductive surgery to marginally effective chemotherapy was found to be ineffective or even detrimental.

Animals↗

Primary transitional cell carcinoma of prostatic periurethral ducts.

Primary transitional cell carcinoma of the prostatic periurethral ducts is a distinct histologic variety of prostate carcinoma. Traditional methods of therapy for adenocarcinoma of the prostate are ineffective. A review of the literature suggests that appropriate radical surgical therapy should be considered for early control of this disease.

Adenocarcinoma↗

Surgical management of Stage B or C prostatic carcinoma: radical surgery vs radiotherapy.

Radical prostatectomy provides an excellent degree of disease control for the longest period of time in patients with localized prostatic cancer. Although advocates of radiation therapy point to nearly identical survival curves for patients treated with either interstitial or external techniques, an analysis of disease-free survival suggests that radical prostatectomy yields the best long-term "cure." Crude fifteen-year survival rates of 50 per cent may be achieved with radical prostatectomy, compared with 20 per cent to 25 per cent associated with radiation therapy. Additional experience with long-term survival data is necessary before a final conclusion can be drawn from comparison of the two treatment modalities.

Brachytherapy↗

Staging lymphadenectomy should be an antecedent to treatment in localized prostatic carcinoma.

Our own data, as well as those of many other workers, suggest that clinicians cannot depend on primary lesion Gleason scoring alone to predict the incidence of positive nodes in patients with prostatic cancer. We continue to find node involvement in 20 per cent or more of patients with Gleason 2 through 4 primary lesions. Furthermore, we continue to find that a large number (nearly 40%) of patients with Gleason 8 through 10 primary tumors do not have lymph node spread. Because of the significance of node status on patient prognosis and its potential impact on treatment decisions, we continue to advocate surgical lymph node staging in patients with localized prostate cancer.

Carcinoma↗

Misonidazole as a chemosensitizer in the treatment of the Dunning prostate cancer model.

Utilizing a Dunning prostate tumor model, we investigated the ability of misonidazole, a compound with known radiosensitizing properties, to act as a chemosensitizer when administered in combination with the alkylating agent cyclophosphamide. This combination caused a decrease in tumor growth rate when compared to the growth of the tumor in animals receiving cyclophosphamide alone. However, only at toxic levels was this decrease statistically significant (p less than 0.01).

Animals↗

Alterations of physical and biochemical parameters of the R3327-CP rat prostate adenocarcinoma following hormonal manipulation of the host.

Several physical and biochemical parameters of a rapidly growing, hormonally responsive, poorly differentiated strain of Dunning R3327 rat prostatic adenocarcinoma (the CP strain) were monitored for 1 month during growth in control and hormonally manipulated male Fischer X Copenhagen rats. The tumor was implanted into control rats and into rats 1 month following orchiectomy. Twenty-nine days following tumor implantation, 1 group of unoperated rats was orchiectomized while the rats implanted subsequent to orchiectomy were repleted with pharmacological doses of testosterone. At 2 and 4 weeks following treatment, half the original number of rats from each group were sacrificed and the growth rate (doubling time), per cent of aneuploid cells and androgen receptor levels (total, cytoplasmic and nuclear) were determined for each tumor. Orchiectomy increased tumor doubling time, while testosterone repletion decreased it, demonstrating the hormonal dependence of this tumor strain. Orchiectomy also decreased the levels of aneuploid cells in the tumor; however, repletion of testosterone to rats orchiectomized prior to implantation did not restore the aneuploid cell number to control levels. A sensitive indicator of the hormonal status of the tumor was the per cent of androgen receptors in the nucleus. Tumors grown in rats orchiectomized after implantation had the lowest percentage of androgen receptor in the nucleus while orchiectomized rats repleted with testosterone had the highest percentage. Comparison of the levels of androgen receptors in the tumors from the various groups (androgen receptor per gram of tissue) unexpectedly revealed that tumors grown in the orchiectomized rats had slightly higher total receptor levels than did control tumors, while the tumors of orchiectomized rats repleted with testosterone had lower amounts than did the control tumors. In contrast to these findings, the prostates of orchiectomized rats replenished with testosterone had higher levels of total androgen receptor than did the prostates of control rats.

Adenocarcinoma↗

Androgen receptor assays in advanced prostatic cancer.

Most technical obstacles in performing biochemical androgen receptor assays on malignant prostatic tissue have been surmounted. The available data, while suggesting that nuclear androgen receptor content in malignant tissues may be a useful criterion in this regard, remain meager and contradictory. The authors suggest that the clinical nature of prostatic cancer, including the tendency for metastases to occur in osseous and deep lymphatic regions and the heterogeneous intermingling of benign and malignant elements in the primary tumor, may preclude the success of biochemical assays for androgen receptors to predict hormonal dependency of prostatic tumors.

Binding Sites↗

Steroid receptor-nuclear matrix interactions. The role of DNA.

The interaction of sex steroid hormone receptors with the nuclear matrix (NM) of target and non-target tissue was investigated using a simple in vitro binding assay. Steroid receptors can recognize acceptor sites on the NM of target cells; androgen receptor binds with the highest apparent affinity to rat prostate NM; similarly estrogen receptor binds with the highest apparent affinity to uterine NM. Furthermore, the steroid receptor-NM interaction depends upon the hormonal status of the animal. The binding of androgen receptor to rat prostate NM was drastically reduced upon hormone withdrawal (castration) and fully recovered upon hormonal stimulation. When NM were prepared by an alternate method (DNase I digestion prior to high salt extraction) known to digest "active" chromatin, no preferential receptor binding to target tissue NM was observed. Although the NM fraction contains less than 1% of the total nuclear DNA, the matrix-associated DNA sequences seem to be, at least in part, responsible for specific receptor recognition. DNA extracted from the prostate NM was shown to be a potent competitor for androgen receptor binding as measured by DNA-cellulose competition experiments. Moreover, this DNA recognition also depends upon the hormonal status of the animal. These studies are consistent with the notion that hormonal manipulation induces changes in the NM-associated DNA sequences of steroid hormone target tissue.

Animals↗

Acid phosphatase localization in prostatic carcinoma. A comparison of monoclonal antibody to heteroantisera.

A series of 39 prostatic carcinomas was characterized in terms of grade, stage, histologic pattern, and serum acid phosphatase values. These cases were studied immunohistochemically with two different heteroantisera, a goat and rabbit antiserum, and with a monoclonal antibody to prostatic acid phosphatase (PAP). Eighty-three percent of carcinomas had some degree of PAP positivity when stained by the goat anti-PAP. Seventy percent were positive with the rabbit antiserum, and 59% showed positivity with the monoclonal antibody. Microacinar patterns were consistently the most positive for PAP, followed by cribriform patterns. The least positivity was observed in the undifferentiated, single-file and sheet-like patterns. Likewise, there was more PAP positivity in the lower Gleason and Mostofi grades. When the serum PAP positivity (done by counterimmunoelectrophoresis [CIEP]) was compared with tissue positivity (using the same goat antiserum), 37% were positive in both serum and tissue; 48% were negative in serum, but positive in tissue; and in only 9% the tissue sample was negative when the serum was positive. Based on these data, conclusions are drawn about the significance of the serum acid phosphatase elevations and the role of monoclonal antibodies and heteroantisera in clinical-diagnostic and research work.

Acid Phosphatase↗

Keyhole-limpet haemocyanin (KLH) immunotherapy of murine transitional cell carcinoma.

The antigenicity of transitional cell carcinoma of the bladder has stimulated the search for effective immunotherapeutic agents in the treatment of this disease. Non-specific immunotherapy with local (intravesical/intralesional) and systemic Keyhole Limpet Haemocyanin (KLH) in a FANFT induced murine bladder tumor model was studied. Results showed no difference between control or treated groups in either tumor growth or animal survival.

Animals↗

Adjuvant chemotherapy for stage D1 adenocarcinoma of prostate.

In a series of 112 patients undergoing pelvic lymphadenectomy for clinically localized prostate cancer, 37 were found to have pelvic lymph node metastases. After prostatic irradiation, these 37 patients were divided into groups receiving adjunctive chemotherapy versus no additional treatment. The patients were followed for a period ranging from twelve to sixty-five months for evidence of disease progression. Of the 12 patients administered chemotherapy, disease progression was documented in 4 (average time to progression was fifteen months). In contrast, of the 25 patients receiving no additional treatment, 12 exhibited evidence of gross metastatic disease within an average interval of 11.6 months. One death has been recorded in the chemotherapy group at twenty-nine months after diagnosis; 4 deaths have occurred in patients receiving no systemic therapy (average time to death was eighteen months).

Adenocarcinoma↗

Sensitivity of computed tomography in evaluation of pelvic lymph node metastases from carcinoma of bladder and prostate.

Pelvic lymph node evaluation by computed tomography was correlated with histologic diagnosis in patients with prostate and bladder carcinoma. Based on computed tomography alone, the stage of the carcinomas would have been underestimated in 38 per cent of cases and overestimated in 6 per cent. Over-all, the sensitivity of pelvic CT scanning in detecting lymph node involvement was only 14 per cent with specificity of 89 per cent. Although this series is relatively small and both second and fourth generation scanners were used, the limitations of computed tomography in recognizing minimal nodal disease or microscopic invasion of adjacent organs is reemphasized.

Evaluation Studies as Topic↗

Steroid effects on protein synthesis in cultured smooth muscle cells from rat aorta.

To examine the direct effects of steroids on vascular smooth muscle, we have incubated rat aortic vascular smooth muscle cells in culture either steroid-free, or with natural and synthetic corticosteroids (RU26988, dexamethasone, corticosterone, 9 alpha-fluorocortisol, aldosterone, deoxycorticosterone) or sex steroids (estradiol, 5 alpha-dihydrotestosterone). At the end of 24 h, cultures were pulsed with [35S]methionine for 2 h, the cells lysed, and patterns of incorporation of isotope into protein determined by two-dimensional gel electrophoresis and autoradiography. Neither estradiol nor 5 alpha-dihydrotestosterone altered protein synthetic profiles compared with control (steroid-free) incubations. In contrast, cultures exposed to the six corticosteroids at 10(-7) M showed an identical pattern of response (6 proteins increased, 6 proteins decreased). This response appears to be glucocorticoid specific, since the mineralocorticoids (9 alpha-fluorocortisol, aldosterone, and deoxycorticosterone) did not have any effects over and above those seen with the pure glucocorticoid RU26988. We interpret these data as evidence for a putative glucocorticoid domain of at least 12 proteins in rat vascular smooth muscle cells. In contrast, there appear to be no comparable estrogen-, androgen-, or mineralocorticoid-specific changes in these cells.

Animals↗

Limitations of DNA histogram analysis by flow cytometry as a method of predicting chemosensitivity in a rat renal cancer model.

Analysis of DNA histograms obtained from rat renal cancer cells stained with propidium iodide and submitted to flow cytometry revealed a tumor cell population with prominent 2C and 4C peaks and with usually less than 10% each of S-phase or hyper-4C cells. The presence of an increased proportion of 4C cells was found to depend on the age and size of the tumor nodule. Sampling replicate portions of the same tumor or different tumors of the same size and age frequently revealed highly variable 4C:2C ratios. Treatment of animals bearing this tumor with a single i.p. injection of cyclophosphamide (CY), under conditions known to reduce the tumor burden by 80% within 1 week, or with 5-fluorouracil (FUra), which is ineffective against this tumor, in many cases did not yield changes in DNA histograms that permitted one to distinguish the effective drug. Either no marked difference in histogram shape occurred after therapy, or FUra induced more striking differences in cell cycle position than did CY. In tumor generations with greater than 15% S-phase cells, treatment with CY resulted in multiple effects on DNA histograms. These included detecting increased numbers of moribund cells (hypo-2C), a decrease in 4C cells, and an increase in hyper-4C cells. These changes did not occur with the ineffective agent FUra. The tumors grown in vitro show no evidence of replication of 4C cells. The DNA histograms of late-log-phase cultures have a major 2C peak and a minor S plus G2 hump. Since neither the untreated tumor in vivo nor that grown in vitro has a major hyper-4C cell population, it is probable that the tumor stem cells are chiefly 2C (diploid-hyperdiploid). Treatment in vitro of late-log-phase cultures with CY or FUra produces DNA histograms which permit identification of the effective agent. After CY, a major part of the cell population was hypo-2C (moribund) cells.

Animals↗

Ileal ureter and renal autotransplantation.

In selected cases of recurrent renal calculi, surgery to facilitate the passage of stones from the kidney is required. Surgical techniques designed to fulfill these requirements have included the creation of substitute wide-bore ureter from bowel (ileal interposition) or from the urinary bladder (Boari-Ockerblad bladder flap), the latter usually requiring renal autotransplantation to the ipsilateral or contralateral pelvis. The clinical circumstances in which such surgical procedures are warranted are discussed, as are details of operative technique.

Drainage↗