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Biomedical subjects

D N Carney

Publications and source records attributed to D N Carney.

At least 73 records · Page 4Linked to original sources
PubMed1990

Thromboembolism. A complication of weekly chemotherapy in the treatment of non-Hodgkin's lymphoma.

In a retrospective survey of 85 patients who received chemotherapy as treatment for non-Hodgkin's lymphomas, the authors found that clinically apparent thromboembolic disorders occurred in four of 11 patients receiving weekly chemotherapy, and in none of 74 patients who were treated on less intensive schedules, suggesting that intensive weekly chemotherapy is thrombogenic. The possible mechanisms of this effect are discussed.

Adolescent↗
PubMed1990

Non-M CK--a practical measure of creatine kinase isoenzymes in cancer patients.

The individual creatinine kinase (CK) isoenzymes CK-BB and CK-Macro II have previously been investigated as potential tumour markers. We believe there is a need for a system to measure those CK forms not usually present in serum. We have studied a CK-MB immunoinhibition kit which measures all residual CK activity following inactivation of M-subunit activity. In 162 patients with cancer we found no difference in grading (+ or -) between detailed isoenzyme studies and the simple non-M assay. In 33 samples with elevated non-M CK, detailed analysis showed BB alone (45%), Macro II alone (9%), or both (36%). Raised activities were mainly found in patients with small cell lung cancer (SCLC) (17/40; 43%) and GI Tumours (6/11; 55%). In patients with SCLC, elevated activities were associated with disseminated disease. Preliminary evidence indicates that Non-M CK may also be a simple means of monitoring initial treatment response.

Biomarkers, Tumor↗
PubMed1990

c-erbB-2 oncoprotein expression in primary human tumors.

Using a specific antiserum (21N) to the c-erbB-2 oncoprotein, a total of 405 primary malignant human tumors arising in the breast (n = 191), lung (n = 110), colon/rectum (n = 23), bladder (n = 48), prostate (n = 23), and skin (n = 10) were stained immunohistochemically to detect those tumors that over-expressed this putative transmembrane receptor. Malignant cells showed intense positivity for this oncoprotein in 17% of the breast carcinomas, 4% of the colorectal tumors, 2% of the bladder tumors, and 1% of the nonsmall cell lung carcinomas. No positive staining was evident in the prostate, skin, or small cell lung carcinomas. This study shows that over-expression of the c-erbB-2 oncoprotein is common in breast cancer but relatively rare in the other malignancies studied. In addition, this oncoprotein can be identified readily in routine paraffin-embedded tissue.

Breast Neoplasms↗
PubMed1990

Intratubular germ cell neoplasia of the testis: identification by placental alkaline phosphatase immunostaining and argyrophilic nucleolar organizer region quantification.

We assessed the value of placental alkaline phosphatase (PLAP) immunostaining and argyrophilic nucleolar organizer region (AgNOR) quantification as techniques for the identification of intratubular germ cell neoplasia (ITGCN), and compared them with hematoxylin-eosin and periodic acid-Schiff staining. We examined 46 malignant testicular germ cell tumors for the presence of ITGCN; 43 had sufficient tubules available for assessment. We also examined 16 cryptorchid testes, 16 testicular biopsies from 10 subfertile men, and 12 normal adult intrascrotal testes. In tubules adjacent to invasive tumors, hematoxylin-eosin staining identified 30 cases (70%) of ITGCN, while PLAP and AgNOR staining identified 36 cases (84%). All the seminomas (18) and 22 of 28 nonseminomatous germ cell tumors were PLAP-positive and had high AgNOR counts. Intratubular germ cell neoplasia was not identified in the other groups examined; germ cells in these groups were PLAP-negative and had low AgNOR counts. Cells of ITGCN showed cytoplasmic block positivity with periodic acid-Schiff staining but this was not a consistent finding. We conclude that ITGCN is present adjacent to most invasive germ cell tumors, and is reliably identified by hematoxylin-eosin staining when fully developed. Periodic acid-Schiff staining was not helpful as normal spermatogonia were also positive. Staining with PLAP and AgNOR were useful diagnostic adjuncts, but results with PLAP were easier to interpret.

Alkaline Phosphatase↗
PubMed1990

Single-agent oral etoposide for elderly small cell lung cancer patients.

Among new patients with small cell lung cancer (SCLC), 20% to 25% are over 70 years of age and account for 8,000 cases annually in the United States. For such patients, intensive, aggressive, cytotoxic, combination chemotherapy is not often used because of its association with unacceptable morbidity and mortality rates. However, treatment of these patients is often indicated, if not demanded. Etoposide is among the most active agents for the treatment of SCLC; both oral (PO) and intravenous preparations are available. The bioavailability of etoposide PO ranges from 15% to 75%. We carried out a phase II trial of etoposide PO in elderly patients (greater than or equal to 70 years of age) with a confirmed histologic diagnosis of SCLC. Patients were treated with etoposide capsules 800 mg/m2, with the total dose divided over 5 consecutive days. Cycles were repeated every 3 to 4 weeks for a total of six cycles. All treatment was administered on an outpatient basis. Staging procedures were confined to physical examination, chest x-ray, and laboratory investigations. Further staging procedures were carried out only if clinically indicated. In September 1985, 53 patients (35 male, 18 female) with a median age of 73 years (range, 70 to 95) were treated. After staging, 24 patients (45%) had limited disease (LD); the remaining 29 patients had extensive disease (ED). Overall response was 79% (complete response [CR], 17%; partial response, 62%). CRs were seen in 8 of 24 patients (33%) with LD and in 1 of 29 patients (3%) with ED. Median survival of all patients was 9.5 months (range, 1 to 22+) with 20 patients still alive; the toxicity rate was acceptable. Total alopecia developed in all patients, whereas significant neutropenia (8%) and thrombocytopenia (6%) were rare. There were no treatment-related deaths or hospital admissions. In this study, we showed activity of etoposide PO in patients with SCLC; these results were comparable with those reported for more intensive combination regimens. For elderly patients, etoposide PO provides excellent palliative treatment, with a high response rate and significant prolongation of survival. In addition, therapy is associated with minimal toxicity and can be administered entirely on an outpatient basis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1990

Phase II study of carboplatin and cyclophosphamide combination chemotherapy for the treatment of advanced ovarian cancer.

The efficacy and toxicity of intravenous carboplatin (300 mg/m2) and cycloprosphamide (600 mgs/m2) was evaluated in 44 newly diagnosed patients with advanced stage epithelial ovarian cancer. Cycles were administered at four weekly intervals for a total of 6 cycles, and therapy was provided on an out-patient basis without prehydration or forced diuresis. During treatment patients were assessed by physical, gynaecological and radiological examinations. Forty-four patients with a median age of 54 years (range 28-76) were entered into the study. The majority of patients had serous cystadenocarcinoma, 82% had stage III or IV disease and 87% had grade II or III histologic subtype. Optimal debulking surgery was carried out in only 46% of patients. The overall response rate to carboplatin/cyclophosphamide was 73%, with 55% achieving a clinical complete response. The median survival for all patients was 18+ months (range 2-41+). For those patients who received optimum surgery, median survival was 26+ months, compared with 11+ months for those whose lesion could not be completely resected. Treatment was well tolerated by most patients, with significant nausea and vomiting (WHO grade III-IV) observed in only 11% of 226 cycles of therapy. Myelosuppression was acceptale, with a mean nadir white cell count 4.3 x 10(9)/L (range 1.4-9.0) and a mean nadir platelet count of 273 X 10(9)/L (range 39-536) observed on day 21. There were no therapy-related infective episodes. Significant alopecia developed in 4 patients, but significant nephrotoxicity, ototoxicity or neurotoxicity has not been observed in any patients. This study demonstrates that combination carboplatin/cyclophosphamide is well tolerated in women with advanced stage epithelial ovarian cancer and produces overall response rates and median survival similar to those obtained with cisplatin-containing chemotherapy.

Adult↗
PubMed1989

Neuron-specific enolase can be used as the sole guide to treat small-cell lung cancer patients in common clinical practice.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuron-specific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR + PR), SD or PD was 98%. Importantly no false-positive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.

Biomarkers, Tumor↗
PubMed1989

The prognostic value of post chemotherapy serum CA 125 in epithelial ovarian cancer.

In a study of 33 newly diagnosed patients with ovarian cancer, we have correlated serum levels of the tumour marker CA 125 with disease stage, response to cytotoxic therapy and survival. Elevated levels were found in 22/28 patients (79%) with Stage III/IV disease, compared with 0/5 patients with Stage I disease and 7/38 patients (19%) with non-ovarian malignancies. Of 15 patients with measurable disease, serum CA 125 levels correlated with clinical response to treatment in 11; the remaining 4 patients had persistently elevated CA 125 levels in spite of clinical response and subsequently developed early relapse. Among the 13 patients with no measurable disease, 11 remained in clinical and radiological remission with treatment, with a fall to normal CA 125 levels; 2 patients who had persistently elevated CA 125 levels developed disease recurrence after completion of chemotherapy. Sequential measurements of CA 125 for up to 2 years in 8 patients showed that rising CA 125 levels preceded clinical relapse by a median of 3 months. The most important prognostic value of CA 125 was the level following 3 cycles of chemotherapy, independent of clinical status--median survival for 15 patients with normal CA 125 at 3 months was 15+ months compared with a median survival of 6 months in 13 patients who had elevated CA 125 at 3 months. These data confirm that 1) serum CA 125 levels are more sensitive than clinical or radiological assessment in monitoring response/relapse in ovarian cancer and 2) the CA 125 level after 3 cycles of chemotherapy is of major prognostic value in predicting survival.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

c-erB-2 oncoprotein expression in malignant and nonmalignant breast tissue.

Using a specific polyclonal antibody (21N) to the c-erbB-2 oncoprotein, a total of 200 primary breast carcinomas of various histological types and 46 benign breast lesions, were immunohistochemically stained, to identify those tissues over-expressing this putative transmembrane receptor. Positivity for this oncoprotein was evident as an intense brown granular staining predominantly located at the cell membrane and was present in 17% (n = 34) of the primary breast carcinomas investigated. With the exception of one case of apocrine metaplasia, none of the remaining benign breast samples (n = 45) were positive for this oncoprotein. This study shows that overexpression of the c-erb B-2 oncoprotein is easily identifiable and can be detected on paraffin embedded sections using an immunohistochemical technique. The results obtained correlate well with other c-erbB2 detection systems and in addition, positivity for this oncoprotein is mostly confined to the malignant phenotype.

Breast Neoplasms↗
PubMed1989

Resolution of small cell lung cancer intracranial metastases with standard dose chemotherapy.

Brain metastases are a well recognized problem in patients with small cell lung cancer (SCLC). Most patients are treated with whole brain cranial irradiation therapy which frequently improves symptoms. In this report we present data on two patients who achieved radiologically confirmed complete resolution of brain metastases treated with standard dose chemotherapy for SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa.

The monoclonal antibody Ki-67 identifies a nuclear antigen that is expressed in proliferating cells in G1, G2, S, and M phases of the cell cycle. An immunoperoxidase method and this antibody were used to identify proliferating cells in sections of colorectal tissues--normal colon (n = 10), colorectal polyps (n = 20), and adenocarcinoma (n = 28). Colorectal adenomas showed a uniform distribution of positive nuclear staining throughout the sections, including the cells of the adenoma surface, while staining in the normal mucosa was confined to the middle third and lower third of the crypts. Areas of polyps with numerous Ki-67-positive epithelial cells invariably showed immature or dysplastic histology and, conversely, glands that lacked such histologic features had low Ki-67 staining frequency or were negative. In adenomas, nuclei located toward the luminal surface of glands were more likely to be Ki-67-positive than those located basally in the cells. The mean Ki-67 score (a measure of positive staining nuclei) for adenomas was 45.5 compared to a mean score of 66.3 for adenocarcinomas in the carcinomas studied (P less than .001). Ki-67 score did not correlate with histologic grade or Duke's stage. Ki-67 staining can be used to characterize the proliferative characteristics of normal colonic mucosa, adenomas, and carcinomas.

Adenocarcinoma↗
PubMed1989

Immunohistology of lung cancer.

Over the past decade the use of monoclonal antibodies has greatly advanced our knowledge of the biological properties and heterogeneity that exist within human tumours, and in particular in lung cancer. Early studies suggested that both the lack of specificity of individual antibodies and heterogeneity in antigenic expression would limit their widespread application in clinical practice. However, improvements in antibody selection techniques and a greater understanding of the epitopes detected with these antibodies have slowly led to the development of antibodies with improved specificity. While preliminary studies of the immunohistology of lung cancer suggest that these antibodies may be of value in histologic typing, predicting chemosensitivity and detecting bone marrow metastases, larger clinical trials are required before immunohistology becomes standard clinical practice in lung cancer studies. With such studies it is likely that the role of lung cancer immunohistology will become better defined. It is also certain through our greater understanding of lung cancer biology and heterogeneity that monoclonal antibodies will in the future play a major role in imaging diagnostic techniques, and in specific targeted therapies where antibodies directed against autocrine growth factors or their receptors, oncogene protein products, or conjugated with pharmacologic agents may replace the highly toxic, non-specific chemotherapeutic approaches of today.

Antibodies, Monoclonal↗
PubMed1989

Breast carcinoma kinetics. Argyrophilic nucleolar organizer region counts correlate with Ki67 scores.

This study assessed the value of argyrophilic nucleolar organizer region (AgNOR) staining as a potential technique for the estimation of cell kinetics in conventional histology sections, in benign and malignant breast lesions. Using a silver staining technique and immunohistochemistry, the authors correlated the numbers of argyrophilic nucleolar organizer regions (AgNORs) and Ki67 scores in 70 breast carcinomas and 27 benign breast lesions. Epithelial cells in fibrocystic disease and fibroadenomas contained a mean of 2.65-6.8 small uniform AgNORs per cell, whereas malignant cells contained 4.6-26.9 frequently highly irregular AgNORs. In benign tissue, Ki67 scores ranged from 0 to 4%; in malignant tumors, Ki67 scores ranged from 3.0 to 98%. The correlation between AgNOR counts and Ki67 scores was highly significant (P less than 0.001). The authors concluded that AgNOR counts performed on routine formalin-fixed paraffin sections furnish significant kinetic information. Furthermore, the difference in AgNOR counts between benign and malignant tumors is such that they may be of diagnostic value.

Adenofibroma↗
PubMed1989

A phase II study of oral etoposide in elderly patients with small cell lung cancer.

Thirty five previously untreated patients with small cell lung cancer older than 70 years were treated with oral etoposide (800 mg/m2 over five consecutive days) every four weeks. Twenty two patients had extensive disease and 13 limited disease. The overall response rate was 71%. The median survival for patients with limited diseases was 16 (range 6-32) months and for patients with extensive disease nine (range 4-17) months. There was mild haematological toxicity and alopecia but no major toxicity. It is concluded that etoposide in this dose regimen is an effective and well tolerated treatment for elderly patients with small cell lung cancer.

Administration, Oral↗
PubMed1989

Osteosarcoma: use of MR imaging and MR spectroscopy in clinical decision making.

Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased.

Adolescent↗