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Biomedical subjects

D E Kenady

Publications and source records attributed to D E Kenady.

At least 19 recordsLinked to original sources
PubMed1992

Resistance to tamoxifen with persisting sensitivity to estrogen: possible mediation by excessive antiestrogen binding site activity.

The growth of a large proportion of estrogen receptor-positive breast tumors is stimulated by estrogen and can often be controlled through antiestrogen therapy. Resistance to antiestrogen (AE) therapy can occur while tumors retain the expression of estrogen receptors (ERc) and remain functionally responsive to estrogens. The ability of specific antiestrogen binding sites (AEBS) to prevent AE from interacting with ERc has been examined as a possible mechanism through which this appropriation of AE could interfere with antiestrogen action. Comparisons were performed between uterine preparations where ERc activity exceeded AEBS binding and liver preparations where AEBS binding predominated. Identical estimates of ERc activity were obtained in uterine preparations using either [3H]estradiol or [3H]-4OH-tamoxifen and radioinert diethylstilbestrol (alpha,alpha'-diethyl-4,4'-stilbenediol) to estimate nonspecific binding. AEBS binding was observed only when [3H]-4OH-tamoxifen was used, while binding to Type II sites was resolved only with [3H]estradiol. When excess AEBS activity predominated, analyses with radiolabeled estrogen and antiestrogen present simultaneously showed that virtually all of the antagonist was bound to AEBS with little of the antagonist available to associate with ERc. In an effort to relate these observations to AE resistance per se, ERc and AEBS were measured in MCF-7 human breast cancer cells (ERc-positive, responsive to estrogens and antiestrogens) and in variant AE-insensitive LY-2 human breast cancer cells (ERc-positive, responsive only to estrogens). In AE-resistant LY-2 cells, the ratio of AEBS:ERc was approximately three times greater than in MCF-7 cells. Examination of 128 human breast carcinomas revealed that AEBS activity was present and could exceed ERc activity. Importantly, the partition of significant AE away from ERc was observed in human specimens. These observations identify a biochemical mechanism for antiestrogen resistance through which AE access to ERc can be totally incapacitated while sensitivity to estrogens continues. These observations indicate that AEBS activity, in addition to ERc activity, may provide helpful information for predicting the response of certain cancers to hormonal therapy.

Animals↗
PubMed1992

Management of local recurrence in well-differentiated thyroid carcinoma.

Local recurrence of well-differentiated thyroid carcinoma has a reported mortality approaching 50%. The University of Kentucky experience was reviewed to determine whether aggressive surveillance and treatment with reoperation and/or I-131 ablation increased survival following recurrence. Records of 66 consecutive patients with well-differentiated thyroid carcinoma treated at the University of Kentucky Medical Center (1980-1989) were reviewed. Forty-nine cases of papillary carcinoma and 17 cases of follicular carcinoma were studied; median follow-up was 68 months. At presentation, patients with follicular carcinoma were older (48 versus 35 years; P less than 0.05) and more frequently had metastatic disease (17% versus 2%, P less than 0.05). Fifty-eight (88%) patients were alive and disease-free at last follow-up. Fifteen patients (24%) had developed recurrent disease; median time to recurrence was 24 months. Multivariate regression examined the variables of age, sex, histology, tumor size, cervical adenopathy, capsular and vascular invasion, multicentricity, and surgical procedure. While distant metastases affected actuarial survival, no factor independently predicted local recurrence. In six patients with local recurrence, nonpalpable disease was detected by I-131 scan. All were treated with ablation and remain disease-free (mean follow-up 42 months). Eight patients with local recurrence presented with palpable lesions; seven underwent surgery. While two patients developed repeated local recurrences, the other five remain disease-free (mean follow-up 52 months). Early detection and aggressive treatment of local recurrence improve survival in patients with well-differentiated thyroid carcinoma. To facilitate use of I-131, we advise total thyroidectomy for patients with well-differentiated thyroid carcinoma.

Adenocarcinoma↗
PubMed1992

Optimizing primary treatment for advanced laryngeal and pyriform sinus carcinoma.

Advocates of chemotherapy plus radiation as the definitive treatment for patients with advanced laryngeal cancer often cite older studies that attribute cure rates of less than 50% to laryngectomy plus radiation. The outcomes of patients with stage III and IV laryngeal and pyriform sinus carcinoma from 1980 to 1989 (96 patients) were compared with those of patients treated from 1962 to 1977 (84 patients). Demographics, the extent of disease, and nodal involvement were similar between the groups. There were more operative complications (45% versus 22%; p < 0.01) and deaths (10% versus 2%; p < 0.01) in the patients who underwent irradiation preoperatively. Overall survival was improved in the recent group compared with the early group (73% versus 54% at 5 years; p < 0.03), as was disease-free survival (64% versus 38% at 5 years; p < 0.02). Results of treatment for advanced laryngeal and pyriform sinus carcinoma have improved significantly. These modern results should be used to evaluate newer treatment modalities.

Combined Modality Therapy↗
PubMed1992

Diagnosis and treatment of thyroid, adrenal, and thymic tumors.

The authors review 41 recent articles concerning the diagnosis and treatment of thyroid, adrenal, and thymic tumors. Diagnostic and evaluative techniques for thyroid nodules are inexact; fine-needle aspiration cytology offers the best results. Most authors favor total thyroidectomy and postoperative 131I ablation. The issue of elective versus therapeutic cervical lymphoidectomy remains controversial. Chemotherapy is of very little use in treating differentiated thyroid carcinoma. The most useful follow-up technique is whole-body scanning in conjunction with thyroglobulin determination. Persistent hypercalcitoninemia after surgery for medullary thyroid carcinoma is not uncommon and does not necessarily indicate demonstrably recurrent disease. In imaging adrenal tumors, magnetic resonance imaging appears to have some advantages over computed tomography. Pheochromocytomas may not always present classically; a clear understanding of the biochemical diagnosis is essential. Patients with thymomas have a good prognosis. Surgical treatment of encapsulated thymomas is appropriate, although more extensive thymomas are best treated multimodally.

Adrenal Gland Neoplasms↗
PubMed1992

A randomized comparison of patient-controlled versus standard analgesic requirements in patients undergoing cholecystectomy.

In the current study, 55 patients undergoing elective cholecystectomy were randomly allocated to receive postoperative analgesia (morphine sulfate) administered through either patient-controlled intravenous (PCA) or standard intramuscular (IM) routes. There were no significant differences in length of hospitalization or required dose of morphine sulfate. Patients randomized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days. In addition, they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine. Theoretically, PCA regimens can deliver narcotic analgesia at a higher and more varied rate (with fewer side effects) compared with standard IM narcotic delivery, which is more limited by considerations of clinical doses. In PCA dosing, patients should experience less time in pain and sedation. The results of the current study support this premise.

Adult↗
PubMed1991

Intraoral sebaceous carcinoma.

An instance of sebaceous carcinoma that presented as a mass in the left buccal mucosa is described. This is the first known report in the English-language literature of a sebaceous carcinoma presenting as an intraoral tumor. The light and electron microscopic findings are described. The histologic differential diagnosis, clinical behavior, and appropriate therapy are discussed. Previously reported intraoral sebaceous neoplasms and sebaceous carcinomas of the parotid are reviewed.

Adenocarcinoma↗
PubMed1991

Diagnosis and treatment of primary adrenal tumors.

The authors review 21 articles concerning primary adrenal tumors published in 1989. Specifically, the articles deal with the radiologic evaluation of the adrenal mass, functional evaluation of adrenal tumors, technical and perioperative considerations of adrenalectomy, and adrenocortical carcinoma. Several conclusions can be drawn from these recent articles. First, diagnostic accuracy should improve with advances in magnetic resonance imaging and improvements in fine needle aspiration technology. Second, the size of an asymptomatic nonfunctional adrenal mass requiring removal still remains to be definitively determined. Third, adrenocortical carcinomas are generally curable only if small and localized. Finally, adjuvant treatment regimens for more advanced adrenocortical carcinomas using mitotane, suramin, and conventional multiagent chemotherapy need to be evaluated in randomized trials.

Adenoma↗
PubMed1991

Treatment of thyroid malignancies.

Clinically significant thyroid malignancies are relatively uncommon, although their prevalence in autopsy series ranges up to 11%. New data confirm an increased incidence of carcinoma in solitary thyroid nodules in younger patients and a greater likelihood for younger patients to present with metastatic disease. Treatment of differentiated thyroid carcinoma is controversial, although many series indicate excellent results with total thyroidectomy. Although iodine-131 ablation has been standard in most centers after total thyroidectomy when residual thyroid tissues are present, new data indicate that selective use of this therapy may be appropriate. Prophylactic neck dissection does not improve survival or lessen recurrence in differentiated thyroid cancers and may increase morbidity. It should, therefore, be reserved for the patient with clinically enlarged cervical nodes.

Adenocarcinoma↗
PubMed1991

Primary solid neoplasms of the greater omentum.

Primary solid tumors of the greater omentum are rare, with only 42 reported cases. Malignant hemangiopericytomas constitute only three of these cases. The 40-year-old patient described in this report had abdominal pain, a palpable abdominal mass, early satiety, and weight loss. At laparotomy a large omental hemangiopericytoma was excised, and no other evidence of disease was grossly evident. Eighteen months after initial laparotomy, the patient had widespread progression of the tumor and, despite chemotherapy, died 2 months later. A review of reported cases shows that abdominal discomfort (56%) and mass (35%) are the most common clinical characteristics of a primary omental tumor. Weight loss, ascites, and peritoneal implants usually indicate malignancy. Rare long-term follow-up prevents definitive conclusions regarding therapy and prognosis. At present, surgical excision alone appears to be the treatment of choice, with no demonstrable benefit from either chemotherapy or radiation.

Adult↗
PubMed1990

Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors.

16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers.

Animals↗
PubMed1990

Primary biliary and pancreatic carcinoma after renal transplantation.

Renal transplant recipients have an increased risk of malignancies. We have described a 41-year-old man in whom adenocarcinoma of the gallbladder developed during the first year after renal transplantation. He also had a nonfunctioning pancreatic islet cell tumor during the fifth year after transplantation. He was the first known renal transplant recipient to be a long-term survivor of adenocarcinoma of the gallbladder.

Adenocarcinoma↗
PubMed1989

Intermolecular engagement of estrogen receptors indicated by the formation of a high molecular weight complex during activation.

After exposure to ligand at 0-4 degrees C, estrogen receptors from mouse uteri characteristically eluted between thyroglobulin (Mr 669,000) and ferritin (Mr 443,000) during size-exclusion HPLC. However, when preparations were warmed with ligand under mild activating conditions, most or all of the receptor was observed as a much larger complex, which eluted between dextran blue 2000 and thyroglobulin. Formation of the large complex required ligand, was inhibited by molybdate, and occurred even in 0.4 M KCl. Slower ligand dissociation characterized the large complex, indicating that activated receptors were included preferentially. This large complex did not form when charged cytosols were aged, concentrated, or precipitated, indicating that formation was not the result of random aggregation. After exposure to conditions commonly used for activation (25 degrees C, 60 min), most receptor existed as a very large, monodisperse complex of finite size, predicting an ordered structure for these large complexes that should be useful for defining the types of proteins which can interact with estrogen receptors. Formation of the large complex was not impeded or disrupted by EDTA, RNase, DNase I, thiourea, or mercaptoethanol; however, the capacity to form this large complex was not demonstrated by preparations that had been exposed to trypsin or by the small receptor forms obtained after salt extraction. Proteolytic sensitivity and lack of sensitivity to RNase or DNase indicate that interactions between receptors and other proteins are involved in peak A formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Medullary thyroid cancer and Graves' disease.

A focus of medullary thyroid cancer was found at frozen section analysis of tissue from a patient with Graves' disease undergoing thyroid lobectomy. An increased incidence of papillary-follicular thyroid cancer has been noted in Graves' disease. This report describes the unique association of medullary thyroid cancer and Graves' disease.

Adenocarcinoma↗
PubMed1986

Antagonism to estradiol in the mouse: reduced entry of receptors complexed with 4-hydroxytamoxifen into a Mg2+-soluble chromatin fraction.

Antagonism to estradiol has been examined in murine uteri. When tamoxifen was administered simultaneously with estradiol (0.05 microgram/mouse), it was able to act as an antagonist over the dosage range 0.05-50 micrograms/mouse. The metabolite 4-hydroxytamoxifen (4OH-tamoxifen) had high affinity for estrogen receptors and was a slightly better antagonist over the dosage range 0.005-1 microgram/mouse. After uteri were exposed to either [3H] estradiol or [3H]4OH-tamoxifen, receptors complexed with [3H] estradiol penetrated a chromatin region, which was released as the Mg2+-soluble chromatin fraction after DNAase I treatment more readily than receptors complexed with [3H]4OH-tamoxifen. [3H]4OH-tamoxifen-receptor complexes could not be driven into the Mg2+-soluble chromatin fraction by increasing the ligand concentration during translocation. Relative to [3H]estradiol, significantly more [3H]4OH-tamoxifen was observed to associate with uterine cells and to penetrate the nucleus so that neither restricted entry nor extranuclear partitioning could explain the failure of [3H]4OH-tamoxifen-receptor complexes to enter the Mg2+-soluble chromatin. Bleomycin, an agent that interrupts DNA continuity, did not interfere with the appearance of estrogen receptor activity in the Mg2+-soluble chromatin fraction. Preincubation of intact uteri in the presence of molybdate (20 mM) did inhibit the appearance of receptor activity in this chromatin fraction; however, this effect did not occur through inhibition of receptor activation, but, rather, through the lowering of receptor activity in all chromatin fractions. In the studies reported here, the chromatin positioning of estrogen receptors complexed with estradiol appeared to be distinct from the positioning of receptors complexed with 4OH-tamoxifen. These observations suggest an additional basis from which the mechanisms separating the actions of estrogen agonists and antagonists can be approached.

Animals↗
PubMed1979

Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Antineoplastic Agents↗