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Biomedical subjects

K M Tveit

Publications and source records attributed to K M Tveit.

At least 55 records · Page 3Linked to original sources

[Endocavitary radiotherapy of rectal cancer].

Most patients with rectal carcinomas undergo surgery, either a resection with anastomosis or Miles' operation with permanent colostomy. Endocavitary radiotherapy is an alternative to surgery in patients with small carcinomas (Dukes' A) or adenovillous adenomas. The treatment is cheap, simple, gives good local tumour control, has low morbidity and does not require hospitalization. The Norwegian Radium Hospital has recently started to use this method in selected cases of rectal carcinomas.

Adenoma↗

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.

Adult↗

Carcinoembryonic antigen in anal carcinoma.

Patients with squamous cell carcinoma of the anal canal occasionally present with an elevated level of carcinoembryonic antigen (CEA) in serum. The present study was performed to evaluate the clinical importance of this observation. Serum CEA was measured in 106 patients prior to chemo- and radiotherapy and during follow-up. Twenty patients had elevated serum CEA level before treatment. In 6 of 12 cases, serum CEA did not normalize after successful treatment and in 4 of 7 cases it rose no further despite progressive disease. CEA-positive tumours were more often poorly differentiated than CEA-negative tumours. There was no significant correlation between serum CEA, tumour CEA and prognosis. We conclude that measurement of serum CEA and staining of tumour CEA lack clinical importance.

Adult↗

[Anus cancer].

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Anus Neoplasms↗

Amplification and protein over-expression of the neu/HER-2/c-erbB-2 protooncogene in human breast carcinomas: relationship to loss of gene sequences on chromosome 17, family history and prognosis.

c-erbB-2 gene amplification and protein over-expression were investigated in 89 primary tumours and 24 metastases from Norwegian breast cancer patients. Amplification occurred in 22.5% of the primary tumours and 50% of the metastases. The amplification was negatively correlated to the oestrogen receptor (ER) content in both the primary tumours and the metastases. No significant differences between amplified and non-amplified tumours were observed with regard to node status, clinical stage, tumour size or menopausal status, although correlations of borderline significance were found between node status, clinical stage and high degree of gene amplification. All the amplified tumours were of the invasive ductal type. Follow-up data of patients observed for more than 1 year showed a significantly higher recurrence rate in the c-erbB-2 amplified group. Allele loss of chromosome 17p and of 7q was seen in 55% and 48% of the tumours respectively. No significant correlation was found between these losses and clinico-histological parameters. More than 50% of the tumours with a loss of 17q sequences had an amplification of c-erbB-2 which is located on 17q12-21, indicating that only one of the chromosomes may be involved in the amplification of the c-erbB-2. A trend towards a correlation between loss of 17q and high degree of amplification were found. No correlation was found between positive family history of breast cancer and c-erbB-2 gene amplification, nor loss of 17p or 17q sequences. Our data support the hypothesis that amplification correlates with aggressive tumour behaviour, and thus may be used as a prognostic factor in breast carcinomas. The allele losses on 17p and 17q points to tumour suppressor gene or genes on this chromosome, although not as predisposing genes in families.

Breast Neoplasms↗

Drug sensitivity testing of human breast cancer.

A survey of drug sensitivity testing of human breast cancer is given. The purpose of sensitivity testing, the tumour material studied, and the various in vivo and in vitro assays that are being used are discussed. Moreover, examples of results obtained are presented.

Animals↗

Computed tomography of the urinary bladder shortly after radiation therapy for rectal carcinoma.

Eighteen patients with rectal carcinoma were examined with computed tomography (CT), before and shortly after preoperative irradiation. Changes in the bladder that could be mistaken for tumor growth did not occur at CT. However, considerable individual variations were seen. Radiation therapy did not result in increased contrast enhancement of the bladder wall after irradiation. The bladder wall thickness increased somewhat during and after treatment and the bladder volume was reduced. Localized thickening with little contrast enhancement was seen in the anterior bladder wall in 3 patients. One case of irradiation cystitis was noted. Edema was seen in the perivesical fat, but could in no case be mistaken for tumor growth.

Aged↗

Benzylidene-glucose: no effect after all?

Several promising reports on the treatment of human cancer with various benzaldehyde derivatives have been published during the last decade. The present phase II study was performed to investigate whether the rather sensational results of one such derivative, benzylidene-D-glucose (BG), could be confirmed. The study included 14 patients with metastases from adenocarcinomas of the colon and rectum. The patients were treated with BG according to the recommended regimen for 8 weeks, after which tumor response was evaluated. Neither clinical tumor regression nor side effects were observed. The present study does not confirm the extremely good results previously reported by others. We conclude that BG is not an active agent in colorectal cancer.

Adenocarcinoma↗

Colony forming ability of human breast carcinomas: lack of prognostic significance.

To study whether colony growth in vitro reflects the prognosis of breast cancer patients, specimens from a total number of 138 patients with primary breast carcinomas were cultivated in the Courtenay-Mills soft agar method. The plating efficiency (PE) values were related to various clinical and histopathological parameters. No significant correlation was found between colony forming ability and menopausal status, histopathology, TNM-status or steroid hormone receptor status. The crude survival of the patients was not significantly correlated to the in vitro growth of the tumours; neither was there any difference in relapse-free survival between patients whose tumours failed to grow in vitro and those having growing tumours (PE greater than 0). A multivariate survival analysis of 115 patients with primary tumours without distant metastases revealed that the PE was not a significant independent prognostic indicator, as it gave no additional prognostic information above that of node and ER status. It is concluded that routine measurement of colony formation in vitro is not warranted in the management of breast cancer.

Adult↗

Primary treatment of carcinoma of the anus by combined radiotherapy and chemotherapy.

Twenty-four patients with carcinoma of the anus were treated with a combined regimen of external irradiation (50 Gy) and mitomycin C and 5-fluorouracil. A relatively large number of patients with locally advanced disease were included. A local complete response rate of 87.5% was obtained. The major acute toxicity was dermatitis/mucositis, necessitating a split course in 14 cases. After treatment four patients had persistent anal incontinence. After an observation period of 40-70 months 14 of the patients were alive without disease. We conclude that the conservative combined radiotherapy/chemotherapy regimen is an effective treatment also of advanced anal carcinoma, with tolerable toxicity and with promising survival results.

Adult↗

Cultivation of human breast carcinoma in soft agar. Experience with 237 fresh tumour specimens.

A total of 237 breast carcinomas have been studied with the Courtenay-Mills (C-M) soft agar method. Cell yields and plating efficiencies (PE) were recorded after various enzyme treatments. The highest cell yields and PEs were obtained with the combination of collagenase 0.5%, hyaluronidase 1000 IE ml-1 and DNase 0.1% and an incubation time of 2 h. Eighty percent of the specimens gave greater than 10 colonies, and 60% formed greater than 30 colonies permitting chemosensitivity studies. The C-M method gave significantly higher PEs than the Hamburger-Salmon (H-S) method. Hormone supplements (insulin, oestradiol, progesterone, hydrocortisone) and also reduced agar concentrations (less than 0.3%) gave marginal stimulation of colony formation. In chemosensitivity studies involving doxorubicin, vincristine and 4-OOH-cyclophosphamide, the C-M method gave dose-response relationships without plateaus.

Breast Neoplasms↗

Predictive chemosensitivity testing in malignant melanoma: reliable methodology--ineffective drugs.

A retrospective and a prospective trial were carried out in patients with malignant melanomas to investigate the predictive value of an in vitro chemosensitivity assay based on the Courtenay and Mills soft agar cultivation method. Evaluable in vitro chemosensitivity data for the three agents DTIC, CCNU, and vinblastine were obtained in 153 cases. In the retrospective study in which the patients received chemotherapy without prior knowledge of the test results, 50 in vitro/in vivo correlations (40 patients) were made, and in the prospective study, where patients received the single agent most active in vitro, 55 correlations (45 patients) were performed. In both studies the sensitivity of the test (the ability to identify patients who will respond to chemotherapy) was approximately 100% and the specificity (the ability to identify patients who will not respond) was 87-98%. Depending on whether 'no change' and 'mixed response' were classified as sensitivity or resistance, the predictive value of a negative test was approximately 100% and that of a positive test 37.5-87.5%. The response rate was low in both series, and although it was somewhat higher in the prospective than in the retrospective trial, the difference was not significant. The median survival time was not significantly different in the two treatment series. We conclude that the chemosensitivity assay here used is reliable and has predictive value, but that the chemotherapeutic agents currently available for treatment of melanoma are too ineffective to warrant routine use of the assay in this disease.

Dacarbazine↗

An immunocytochemical method for assaying oestrogen receptors in breast cancers. A comparison with the steroid binding assay.

The presence of oestrogen receptors was studied in 105 human breast carcinomas using monoclonal antibodies (Abbott ER-ICA kit). The oestrogen receptors of neoplastic cells were semiquantitatively measured and correlations were made to receptor values determined by a dextran-coated charcoal (DCC) steroid binding assay and to histological grade. Immunoreactive cells were found in about 2/3 of the tumours. Usually only a fraction of the cells within each tumour were immunoreactive, and the staining intensity varied among different cells. In general, well differentiated tumours had a greater proportion of immunoreactive cells than poorly differentiated ones. In most cases (65/98) a good agreement was found between the ER-ICA method and the DCC assay. However, in 33 cases discrepancies were demonstrated.

Breast Neoplasms↗

Sequential 5-fluorouracil and methotrexate. Negative experience in metastatic colorectal cancer.

Forty-two patients with measurable advanced colorectal cancer were treated with sequential methotrexate (MTX) and 5-fluorouracil (5-FU), followed by folinic acid rescue. Twenty-one patients had received prior chemotherapy, mainly 5-FU (group 1) and remaining 21 patients had not been previously treated by cytotoxic agents (group 2). Two different treatment schedules were used. Regimen I (27 patients): MTX 250 mg/m2 was infused over 1 hour. Two hours from start 5-FU 600 mg/m2 was given as intravenous bolus. Folinic acid rescue started 24 hours after MTX infusion. Regimen II (15 patients): MTX 250 mg/m2 was given as 1-hour infusion. Three hours after the start of MTX a 46-hour 5-FU infusion (2000 mg/m2) was started. Folinic acid rescue as in regimen I. The chemotherapy courses were repeated every second week. After 3 cycles only one patient had partial response, 33 had no change and 8 progressive disease. The median time until progression was 2 1/2 months in group 1 and 4 months in group 2. The median survival was 7 months in group 1 and 10 1/2 months in group 2. Almost identical results were obtained by the two treatment schedules. The toxicity of both regimens was low.

Antineoplastic Combined Chemotherapy Protocols↗

Survival curves after X-ray and heat treatments for melanoma cells derived directly from surgical specimens of tumours in man.

X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters.

Adult↗

Chemosensitivity measurements of human tumour cells by soft agar assays are influenced by the culture conditions.

To investigate the influence of culture conditions on the in vitro responses of tumour cells to anticancer drugs, the sensitivities observed with the soft agar methods of Hamburger & Salmon (1977) (H-S) and of Courtenay & Mills (1978) (C-M) were compared. In all cases the ID50 values were determined from dose-response curves. Six human tumour cell lines exposed to 10 different agents, and 9 patients' melanomas exposed to 5 different agents, were examined. In the studies of cell lines the H-S method gave higher sensitivity values than the C-M method in 38 out of 52 cases, whereas in 14 cases the results were the same. In the patients' tumours the H-S method gave higher sensitivity in 21 of 35 cases, equal sensitivity in 11, and lower sensitivity in 3 cases. In many instances the ID50 values obtained with the two test systems differed by factors of 10 or more, both in the case of cell lines and tumour specimens. Systematic alterations in the culture conditions indicated that the presence or absence of rat erythrocytes is the most important factor responsible for the differences observed. Also, other factors, such as supplements (in the H-S method) and the use of different serum types, appeared to influence both colony growth and chemosensitivity.

Agar↗

Selection of tumour cell subpopulations occurs during cultivation of human tumours in soft agar. A DNA flow cytometric study.

To examine whether selection of tumour cell subpopulations occurs during cultivation in soft agar, we compared in 23 human tumours of different histological types the DNA content of cells from colonies formed in soft agar (method of Courtenay and Mills, 1978) with that of the original tumour cells. The ploidy as well as the fraction of cells in S phase were determined from DNA histograms after staining of the nuclei with a propidium-iodide procedure and flow cytometric recordings. In 8 of 17 aneuploid tumours analysed, specific aneuploid subpopulations disappeared during cultivation or new aneuploid populations, not demonstrable in the original cell suspensions, appeared in the colonies. In 9 cases identical aneuploid populations were found in the colonies and the tumours. In one of 6 diploid tumours examined, aneuploid cell populations not revealed in the original cell suspension, were found in addition to diploid cells, whereas 5 tumours gave rise to colonies containing a purely diploid population. The results show that in a variety of human malignant tumours cultivation in soft agar may select specific aneuploid tumour cell populations.

Agar↗