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Biomedical subjects

O H Pearson

Publications and source records attributed to O H Pearson.

At least 55 records · Page 3Linked to original sources
PubMed1980

Effect of ovariectomy on hormone receptors and growth of N-nitrosomethylurea-induced mammary tumors in the rat.

Estrogen receptor(s) (ER), progesterone receptor(s) (PGR), androgen receptor(s) (ANR), and prolactin receptor(s) (PRLR) were measured in N-nitrosomethylurea-induced mammary tumors in intact female Sprague-Dawley rats and in rats 9 days after ovariectomy. Following ovariectomy, 12 of 15 tumors regressed to 47.7 +/- 5.5% of the original size (hormone-dependent tumors), while the remaining three had arrest of growth reaching 88.8 +/- 7.3% of their original sizes. Cytosol ER level was 50.3 +/- 6.6 fmol/mg protein in tumors of intact rats and was significantly lower (25.6 +/- 8.3 fmol/mg, p < 0.025) in the ovariectomized group. PGR was abundantly present in ten of 13 tumors of intact rats (mean, 144.5 +/- 46.8) but was undetectable in five of six hormone-dependent tumors after ovariectomy (p < 0.01). ANR ws detectable at low levels in only four of 13 tumors of intact rats but in none of six hormone-dependent tumors after ovariectomy. PRLR was not significantly different in tumors of intact and ovariectomized rats (20.6 +/- 2.4 and 15.6 +/- 1.8 fmol/mg, respectively). In three tumors that had arrest of growth after ovariectomy, the levels of ER, PGR, ANR, and PRLR were not significantly different from those of the hormone-dependent tumors. We conclude that the majority of N-nitrosomethylurea-induced rat mammary tumors are hormone dependent. ER, PGR, and PRLR were abundantly present in the majority of these tumors, while ANR was present in only four of 13 tumors. The levels of ER and PGR were significantly lower following ovariectomy, while PRLR was not significantly changed.

Animals↗
PubMed1980

Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

Actuarial Analysis↗
PubMed1979

Antihormone treatment of stage IV breast cancer.

The antiestrogen Tamoxifen (T), given orally to 113 patients with stage IV breast cancer, induced objective remission in 50%. Duration of remission in the first 39 patients, with minimum 27 months follow up, is 18 + months; these results are equal to those of surgical hypophysectomy. T prolonged survival in responders. Older age, previous response to endocrine therapy and positive estrogen receptors predicted response to T. T was effective in hypophysectomized patients in whom serum growth hormone and prolactin were undetectable, but serum ostrogens were present in low amount, suggesting a direct stimulatory effect of estrogens at the tumor level. Hypophysectomy induced further palliation after treatment with T, indicating that pituitary hormones may also play a role in the growth of some human breast cancers. Side effects from T were minimal. T is the initial treatment of choice for postmenopausal women with hormone responsive stage IV breast cancer.

Breast Neoplasms↗
PubMed1979

Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth.

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.

Adult↗
PubMed1978

Hypophysectomy for stage IV breast cancer.

Transnasal, transsphenoidal microsurgical hypophysectomy is a useful therapeutic procedure for patients with Stage IV breast cancer which can be peformed in selected patients with minimal morbidity and mortality. Functionally complete hypophysectomy can be accomplished with regularity, and anything less than this is considered to be a technical failure despite the fact that remissions may occur after incomplete hypophysectomy. In view of the recent outstanding results with antiestrogen therapy in patients with breast cancer, we recommend this as the initial treatment in those patients who are good candidates for endocrine therapy. Hypophysectomy has been shown to induce improvement after antiestrogen treatment, particularly in those patients who have had an initial response to antiestrogens as well as in a few patients who failed to benefit. Estrogen receptor measurements in the tumor tissue have been shown to be useful in selecting patients for hypophysectomy as well as for antiestrogen therapy. Prolactin receptors have been found in about 50 per cent of human breast cancers, and their potential usefulness in selecting patients for hypophysectomy is being explored. Hypophysectomy is a definitive therapeutic procedure that should not be used as a last resort in the terminally ill patient.

Adrenalectomy↗
PubMed1978

Prolactin induces its own receptors in rat liver.

Attempts to restore PRL receptors (PRL-R) in liver membranes of hypophysectomized rats with injections of PRL have so far been only partly successful. In the present study, bovine PRL (bPRL) was mixed with polyvinylpyrrolidone (PVP) in order to sustain PRL blood levels with a single injection a day. PRL-R were measured by displacement of the binding of [125I]ovine PRL (lactoperoxidase oxidation) to a 5000 x g particulate fraction of liver by unlabeled ovine PRL. The number of binding sites was calculated by Scatchard analysis and expressed as femtomoles per mg protein. PRL-R were 85 +/- 12 fmol/mg in normal intact female rats. Seven days posthypophysectomy, PRL-R were undetectable. Daily injections of bPRL with PVP for 10 days fully restored PRL-R (117 +/- 32 fmol/mg). No significant change in PRL-R was noted when bPRL was injected with bovine GH (bGH; 120 +/- 23 fmol/mg), bovine LH (bLH; 84 +/- 14 fmol/mg), bGH plus bLH (90 +/- 12 fmol/mg), or estrogens (79 +/- 12 fmol/mg). Daily injections of bGH or bLH, alone or in combination, or estrogens with PVP failed to restore PRL-R. These results demonstrate a direct role of PRL in stimulating the production of its own receptors when a sustained blood level of the hormone is achieved.

Animals↗
PubMed1978

Pituitary function after removal of pituitary microadenomas in Cushing's disease.

Pituitary function has been studied sequentially after transsphenoidal removal of pituitary microadenomas in two men with Cushing's disease. Patient 1 gradually regained normal glucocorticoid levels with normal diurnal variation, metyrapone responsiveness, and low dose dexamethasone suppressibility (17-hydroxycorticosteroid, 6.5-0.9 mg/24 h). GH levels rose from 1 to 35 ng/ml during insulin hypoglycemia and from 2.3 to 27 ng/ml during arginine infusion. PRL secretion rose normally in response to thorazine, and gonadotropin and TSH levels remained normal. Patient 2 regained significant metyrapone responsiveness by 9 months postoperatively (11-deoxycortisol rose to 11.7 micrograms/dl), had a normal spontaneous nocturnal rise in PRL secretion, and normal levels of testosterone and thyroid hormones. The return to normal of cortisol-ACTH dynamics and GH responsiveness in Patient 1 and the normal nocturnal surge in PRL secretion in Patient 2 imply that in these patients the etiology of Cushing's disease was not related to hypothalamic dysfunction.

17-Ketosteroids↗
PubMed1978

Role of pituitary hormones in the growth of human breast cancer.

Hypophysectomy was performed in 28 women with Stage IV breast cancer who were treated initially with antiestrogens. Six of 13 patients who responded to tamoxifen and 2 of 12 who failed to benefit from tamoxifen obtained remissions from hypophysectomy. The remissions average 11+ months. Three of 8 patients treated initially with antiestrogens have responded to androgen therapy. The results suggest that hormones other than estrogen, which appears to play a major role, may be involved in stimulating the growth of some human breast cancers. Prolactin receptors were detectable in 51% of human breast cancers and were detected in both estrogen receptor-positive and -negative tumors. Preliminary clinical correlations suggest that prolactin receptors will not be useful in predicting response to antiestrogen therapy.

Breast Neoplasms↗
PubMed1978

Recent advances in diagnosis and management of galactorrhea.

Using prolactin suppression (L-dopa) and provocative (thorazine) tests along with the clomid test the intactness of hypothalamico-pituitary axis was assessed in a group of eight patients with galactorrhea syndrome. Pituitary neoplasm was suspected in three cases on the basis of elevated plasma prolactin and its abnormal response to L-dopa, thorazine, and clomid tests. Trans-sphenoidal exploration of the pituitary gland in these three cases confirmed the diagnosis. In these cases, however, the commonly used parameters for evaluation of the pituitary gland (skull X ray, visual field measurement, echoencephalogram, etc.) failed to reveal the presence of the pituitary lesions. In two of the three cases, normal menses recurred following extirpation of the tumors and conception was achieved successfully. In the remaining patient the operation failed to remove the entire pituitary lesion and it was necessary to irradiate the pituitary gland as the patient continued to have persistent galactorrhea and hyperprolactinemia. The importance of the prolactin assay, and its response to stimulation and suppression tests for proper evaluation of galactorrhea was fully discussed.

Adult↗
PubMed1977

Current status of estrogen and progesterone receptors in breast cancer.

Breast cancer is often hormone responsive, since growth or regression of tumors can often be modulated by appropriate endocrine manipulations. Estrogen and progesterone appear to be major hormones involved in regulation of breast tumor growth. It has been recently argued that a more accurate marker of hormonal responsiveness might result if an end product of an intact estrogen response system were measured instead of the initial hormone binding step. Progesterone receptor (PgR) has been investigated in this regard since it can be readily measured in human breast tumors and there is clear evidence in experimental breast tumor model systems that PgR is under acute estrogen control. PgR is rarely found in ER- metastatic breast tumors but is present in approximately 59% of ER+ metastatic tumors, especially in those tumors with high levels of ER. Preliminary clinical correlation of ER, PgR and response to endocrine therapy is encouraging. The response rate is significantly higher if the tumor contains both ER and PgR than if the tumor contains ER alone.

Adrenalectomy↗
PubMed1977

Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor.

The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Treatment of breast cancer with antiestrogen: approach to medical hypophysectomy?

Tamoxifen (ICI 46474), an antiestrogen, was given to 89 selected patients with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Forty-seven percent of the patients had objective tumor regression averaging 11+ months with 25 of 42 women still in remission. In the first 39 patients where the minimum follow-up period is 16 months the average duration of remission is more than 15 months with 8 of 19 patients still in remission. These results are approaching those of surgical hypophysectomy, where, in our experience the average remission lasts about 18 months. Thus, Tamoxifen is a highly effective antitumor agent and is probably the initial treatment of choice for women with hormone responsive breast cancer. Antiestrogen induced objective remissions in 5 of 19 patients who had previously responded to surgical hypophysectomy, and 5 additional patients showed no progression of disease lasting 15+ months. Estradiol and estrone were detectable in the serum of these patients whereas, prolactin and growth hormone were not detectable. Thus, antiestrogen can induce remissions in some patients in the absence of the pituitary gland, and this constitutes additional palliation and provides evidence that estrogens can directly stimulate tumor growth. Four of 7 patients who obtained remissions from Tamoxifen obtained further improvement from hypophysectomy, and 1 of 8 patients who failed to benefit from antiestrogen improved after hypophysectomy. These results suggest that prolactin and growth hormone may also play a role in stimulating tumor growth in some patients.

Animals↗
PubMed1976

Antiestrogen-induced remissions in stage IV breast cancer.

Tamoxifen (NSC-180973, ICI-46474), an antiestrogen, was administered to 39 women with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Patients were selected as eligible for endocrine ablative treatment and with disease not so aggressive as to jeopardize further treatment in case the experimental drug failed. Objective remission was obtained in 19 patients (49%) with a mean duration of 11+ months and ten patients are still in remission. No progression was seen in seven patients (18%) lasting 13+ months with only one patient in relapse. Thirteen patients (33%) have failed. Objective remission was obtained in two premenopausal women even though menstrual cycles were not suppressed; bilateral oophorectomy in one of these patients induced a second remission after relapse from tamoxifen. Objective remissions were obtained in two women with proven complete hypophysectomy a direct action of antiestrogens at the tumor level. Positive estrogen receptors were suggestive of being a good predictor of response. Menopausal status and dominant site of metastasis did not affect the response to tamoxifen in this small series. Tamoxifen did not alter prolactin secretion, and side effects from the drug were usually mild and transient in nature. We conclude that tamoxifen is an effective antitumor agent in patients with stage IV breast cancer; further studies are necessary to determine whether it will equal the therapeutic effect of oophorectomy, adrenalectomy, and hypophysectomy.

Adrenalectomy↗