The effects of dimethyl sulphoxide (DMSO) are in some respects similar to those of retinoids. DMSO has the ability to penetrate cellular membranes and to enhance the penetration of other molecules. It may be reasonable to assume that DMSO treatment results in differentiation of cells, possibly through membrane-mediated events. This may be of importance for the study of the carcinogenic process. The release of a certain amount of lysosomal enzymes to the extracellular space is a normal function of the cell (Hickman & Neufeld, 1972), and a certain release of the cytoplasmic and lysosomal enzymes to the extracellular space is not necessarily deleterious for the cells (Volden, Haugen & Skrede, 1980). The purpose of the present investigation was to study the possible effects of DMSO on methylcholanthrene-induced skin carcinogenesis. Since the uptake of lysosomal enzymes by cultured cells appears to involve a membrane receptor process, the effects of the carcinogen and the solvents on the rate of secretion of lysosomal enzymes and lactate dehydrogenase from HeLa cells were investigated.

In a randomized clinical trial, 87 patients with inoperable, extensive non-small cell lung cancer (NSCLC) were randomized to receive either combination chemotherapy (cisplatin at 70 mg/m2 intravenously [i.v.] on day 1 and etoposide at 100 mg/m2 i.v. on day 1 and 200 mg/m2 orally on days 2 and 3) or symptomatic treatment. No statistically significant differences in survival time were found between the two treatment techniques. A major problem in the interpretation of the results was the use of semicurative radiation therapy (3000 to 4200 cGy) to the primary tumor and mediastinum, which was given with symptomatic intent. Three long-term survivors were seen in the latter group.

59 patients with histological verified squamous cell carcinoma of the head and neck, 39 with primary disease and 20 with relapse were given carboplatin and 5-fluorouracil (5-FU) in escalated carboplatin doses. The starting dose with carboplatin was 200 mg/m2 and the dose was escalated to 300 mg/m2, 350 mg/m2, 400 mg/m2 and thereafter by 20 mg/m2 per step. All patients received a dose of 1000 mg/m2 5-FU as a continuous infusion for 5 days. The myelotoxicity was moderate. No patients had grade 4 haemoglobin toxicity, while 7 patients had grade 3 toxicity. 2 patients had grade 4 leucocyte toxicity and 1 patient had grade 3. 4 patients were observed with a grade 4 platelet toxicity. 2 early deaths occurred at a dose level of 420 mg/m2. 18 out of 39 patients in primary treatment responded while 2 out of 20 patients treated for relapse responded. On the basis of the present study the maximum tolerable dose for carboplatin in combination with 5-FU 1000 mg/m2 is between 350 and 400 mg/m2.

We compared two groups of patients with squamous cell carcinoma of the larynx. Group 1 consisted of 483 patients treated from 1958 through 1978. Primary surgery was selected in 41% pre- or postoperative radiation therapy in 16% and primary radiation therapy in 43%. Group 2 consisted of 247 patients treated from 1978 through 1983. Primary surgery was selected in only 1.6%, pre- or postoperative radiation therapy in 23%, and primary radiation therapy, with surgery in reserve for residual or recurrent carcinoma, in 76%. Although the results were comparable for patients with early stage tumors in the two groups, significantly higher local-regional tumor control rates and corrected survival rates were recorded for patients with advanced tumors in group 2. More patients survived with a cancer-free functional larynx, the surgical salvage rates were higher, the complication rates and the death rates lower in group 2 compared to group 1.

Abstract. Hairless mice were continuously labelled with 10μCi of tritiated thymidine ([3H]TdR) every 4 h for 8 d, and the proportions of labelled basal and differentiating cells were recorded separately. the mitotic rate was measured by the stathmokinetic method and the cell cycle distributions were measured by flow cytometry of isolated basal cells at intervals during the labelling period. the mitotic rate of the [3H]TdR‐injected animals did not deviate from control values during the first 5 d. Computer simulations of the data based on various mathematical models were made, and three main conclusions were obtained: (1) a large spread in transit times through the G1 phase was found, together with a very narrow distribution in maturation time of differentiating cells; (2) about 20% of the differentiating cells were estimated to leave the basal cell layer directly after mitosis. This is consistent with results obtained from different sets of data; and (3) during continuous labelling more than 90% of the cells are labelled during each passage through the S phase.

A combination of cisplatin (70 mg/m2 i.v. day one) and etoposide (100 mg/m2 i.v. day one, 200 mg/m2 orally days 2 and 3) repeated every third week to a maximum of 4 cycles were compared with high voltage radiotherapy, 42 Gy given in 15 fractions over a 3-week period to patients with inoperable non-small cell lung cancer (a shield was used in the posterior field to reduce the total spinal dose < 40 Gy). One hundred and eighteen patients received radiotherapy; the median survival was 10.6 months compared to 10.5 months for the 116 chemotherapy patients (p = 0.81). The objective response rate (CR + PR) was 42% for the radiotherapy and 21% for the chemotherapy group (p = 0.009). At progression it was optional to cross over to the other treatment modality or to receive phase II chemotherapy. Thirty patients primarily treated with radiotherapy and 54 allocated to chemotherapy received second line antineoplastic treatment.

In a randomized trial, patients with inoperable non-small cell lung cancer with limited disease were randomly given either radiotherapy (42 Gy) or combination chemotherapy with cisplatin, 70 mg/m2, and etoposide, 100 mg/m2, given every third week with a maximum of 4 cycles. The patients were asked to fill in a questionnaire concerning psychosocial well-being, medical and treatment related symptoms, physical function and everyday activity. Of the chemotherapy patients 61% reported nausea 5 weeks after their last chemotherapy session and 44% had spells of vomiting. Only 14% of the radiotherapy patients had nausea and 5% vomited 14 weeks after start of treatment. Of the radiotherapy patients 64% experienced dysphagia compared to 8% of the chemotherapy patients 6 weeks after the start of treatment.

DNA-histograms were obtained by flow cytometry (FCM) of nuclei prepared from fresh bladder carcinoma biopsies and from 100 micron sections of paraffin-embedded material from the same biopsies. Linear regression analysis of ploidy values from fresh material versus those from paraffin blocks showed excellent correlation (R2 = 0.957). Owing to the high background, the paraffin-embedded material was less suited for analysis of S-phase fraction. It is concluded that DNA FCM of nuclei obtained from paraffin-embedded bladder carcinoma biopsies yields reliable results concerning ploidy, but does not permit evaluation of the S-phase fraction.

The serum concentrations of IgAp and IgMr associated secretory component (SIgA and SIgM) of 98 patients with neoplasms of the breast were measured. Of the 56 patients with carcinomas, 11 had increased concentrations of circulating SIgM, which was almost twice as sensitive as SIgA as a marker for carcinoma. Concentrations of circulating SIgA and SIgM were independent of expression of secretory component, IgA, and carcinoembryonic antigen (CEA); histological tumour grade; and tumour cell DNA ploidy, whereas a weak correlation between SIgA and SIgM and circulating CEA was seen. The three patients who had liver metastases indicated had particularly high concentrations of circulating SIgA and SIgM, whereas no difference was generally seen between patients with malignancy and those with benign tumours.

One hundred patients operated for large bowel carcinoma were divided into a distinct aneuploid group of 63, and a near diploid one of 37. Flow cytometry was used for determination of the DNA ploidy pattern. All tumours in the aneuploid group contained one or more aneuploid cell populations. All patients were followed clinically from 3.5 to 7.8 years. The corrected 5 year survival was 64% and 49% for patients with near diploid and aneuploid tumours, respectively (not significant). Significant differences in corrected survival time were not observed for Dukes' stages A, B, and C patients pooled, nor for Dukes' stage D patients. However, for Dukes' stage C patients alone, there was a tendency (P = 0.10) for patients with near diploid tumours to show a better survival. A highly significant predominance of aneuploid tumours was seen in males, in contrast to an equal distribution of aneuploid and near diploid tumours in females. A slight predominance of aneuploid tumours in the left colon and rectum was seen. Both these findings indicate the influence of environmental factors (hormonal, anatomical, phenotypical) on the development of tumours with a particular DNA ploidy pattern.

Two groups of patients were compared. In group 1, consisting of 304 patients treated from 1958 to 1972 (minimum observation time of 5 years), the local and regional control rate was 35 per cent. In group 2, consisting of 126 patients treated 1978 to 1983 (median observation time of 58 months), the local and regional control rate was 60 per cent (p less than 0.0001). The local and regional control rates were improved for all stages, but the differences were significant only for stages T1N0, T2N0, T3N0 and TXN2,3. The actuarial survival rates also showed improvement in group 2 patients. The incidence of treatment failure, with regard to the neck alone or tongue and neck combined, decreased from 51 per cent to 27 per cent with the newer techniques. The greatest improvement was observed in patients with T1N0 and T2N0 tumors. There was also a decrease in the failure rates in patients with the more advanced tumors.

In 100 patients with large bowel carcinomas, the tumors were divided into a distinctly aneuploid (AN) group (63) and a near diploid (ND) group (37) by flow cytometric (FCM) DNA quantitation of cell suspensions. Preoperative plasma CEA levels were determined in all patients. Thirty-eight patients with AN and 28 patients with ND tumors were operated on for cure and had normal plasma CEA levels postoperatively. These two groups had regular CEA plasma measurements as part of the clinical follow-up. In the AN group, 12 of 15 patients have had recurrence preceded by CEA elevation. In the ND group, however, only one of eight recurrences was preceded by a rise in CEA level; the one with elevation also had increased plasma CEA prior to operation. It thus seems that a low CEA output of ND tumors explains many of the "false-negative" CEA measurements in disseminated cases. It is concluded that, in addition to patients with an elevated preoperative plasma CEA level, all patients with aneuploid tumors should be subjected to repeated plasma CEA measurements as part of the follow-up program.

Single cell suspensions from 16 biopsies from 15 patients with metastatic or recurrent malignant melanoma were prepared according to the method described by Vindeløv (1977) and the nuclear DNA content was measured by a laboratory-built flow cytometer. The DNA histograms thus obtained were compared with those obtained from suspensions of single nuclei from the same biopsies after formalin fixation and paraffin embedding, according to the method of Hedley et al. (1983). Linear regression analysis of ploidy values from fresh material compared with those from paraffin blocks showed a strong correlation (R2 = 0.85), while that of the S-phase fraction was somewhat weaker (R 2 = 0.66). It is concluded that archival wax preparations of malignant melanoma cell populations are suitable for FCM analysis of ploidy, and to a lesser extent for analysis of fraction of cells in various cell cycle phases.

Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with different DNA ploidy pattern and serial post-operative determinants performed in the 64 who had been operated for cure. The follow-up period was 312–8 yr. All CEA measurements were performed consecutively with a RIA (Roche), and subsequently repeated in one batch with on EIA (Roche) based on a monoclonal antibody. Both assays showed a similar number of ‘false-negative’ CEA levels pre-operatively—varying from 69% in aneuploid (AN) Dukes' A to 8% in AN Dukes' D tumours, and from 75% in near diploid (ND) Dukes' A to 40% in ND Dukes' D tumours. The sensitivity for detecting recurrence in patients with tumours of either ploidy pattern was slightly better with EIA than with RIA. A difference between the AN and ND group was shown somewhat better wit RIA, the sensitivity in the AN group being 79% and the median lead time 7 months compared to 13% and 2 months in the ND group. The corresponding figures with EIA were 71% and 7 months for the AN group and 63% and 112months for the ND group. However, all but one of the patients with ND DNA pattern who showd recurrence-associated CEA elevation with EIA also had an elevated level pre-operatively. We conclude that all patients operated for cure should be followed by regular CEA measurements post-operatively if they had an elevated CEA level prior to operation. In addition, patients with AN tumour should be followed with serial CEA measurements even in the absence of pre-operative elevation. The two assays should probably be considered fairly equal from a clinical point of view.

Cell suspensions of 59 primary operable mammary carcinomas in women were subjected to flow cytometric DNA analyses. The results were correlated to histopathological grading, clinical staging, menopausal status and estrogen receptor status. Thirty-two tumors showed a DNA peak above +25% of murine lymphocyte level and were named distinct aneuploid (AN). Twenty-seven tumors did not show such a peak and were named near diploid (ND). Low histopathological malignancy grade was associated with a high frequency of ND tumors (P less than 0.05). Small tumors (T1) were predominantly ND (14/19), while larger tumors (T2-3) showed a high frequency of AN tumors (27/40) (P less than 0.01). Tumors occurring in post-menopausal women were often AN, while those arising in premenopausal women were frequently ND (P less than 0.06). No clear correlation was found between the DNA ploidy pattern and estrogen receptor status. There was a tendency that patients with AN tumors had a higher frequency of relapses during the first 4-5 years of follow-up than those with ND breast carcinomas.

Suspensions of single cell nuclei were obtained from 31 different samples of 7-9 years old paraffin-embedded bladder cancer biopsies. The DNA content of the ethidium-bromide-stained nuclei was analyzed by flow cytometry (FCM). The tumour stemline ploidy, as determined by FCM, was compared with that obtained by Feulgen scanning absorption cytometry (SACM) in imprints obtained from the same biopsy before it was fixed. Fifteen tumours that were diploid by FCM were also diploid by SACM. All of the 16 tumours with non-diploid DNA-stemlines by FCM were non-diploid by SACM, though minor differences between the ploidy values were occasionally seen when the results of the two methods were compared. The background activity due to cell debris was considerable and resulted in a mean variation coefficient (CV) of 5.1% for human spleen cells fixed and embedded before preparation for FCM in the same way as the tumour samples. In the tumour samples there was a large and unpredictable variation of the ratio between the DNA values of chicken erythrocytes (internal standard) and diploid cells. In some specimens this ratio would have resulted in incorrect evaluation of the FCM DNA histogram. The following method for evaluation of FCM histograms is therefore proposed: Single peak histograms obtained from paraffin embedded tissue should always be interpreted as representative for a diploid cell population. In FCM histograms from paraffin-embedded tissue with more than one peak, the first peak should be considered as representing diploid cells.