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Biomedical subjects

K Mattson

Publications and source records attributed to K Mattson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Comparison of DNA and karyotype ploidy in malignant mesothelioma.

The correlation between flow cytometric analysis and classical karyotyping was examined in malignant mesothelioma. Flow cytometry was used to determine the DNA ploidy mainly from paraffin blocks of 31 mesotheliomas, of which the S-phase fraction (SPF) could be defined in 17 tumors. Chromosomal results were available from 27 of these tumors. For the comparisons, both the modal (the most common) and the mean (the average) chromosome numbers were determined. A significant correlation was observed between ploidy pattern, i.e., DNA indexes and modal as well as mean chromosome numbers (p = 0.004 and p = 0.006, respectively). Otherwise the comparison between the mean chromosome numbers and DNA index proved more relevant. Although the majority of the tumors (16 of 27) had a normal modal chromosome number of 46, only 5 tumors had a normal mean chromosome number, and the remaining 22 had an abnormal number, reflecting the divergent chromosomal abnormalities. Furthermore, comparison of SPF with mean chromosome numbers disclosed a parabolic relationship; i.e., when mean chromosome number corresponded to diploid, near-diploid, or near-tetraploid cell, SPF was low, but SPF was at the maximum when mean chromosome number ranged between 60 and 63. Because SPF is an indicator of cell proliferation, this might suggest that the number of chromosomes as such also corresponds with the growth characteristics of malignant mesothelioma.

Adult↗
PubMed1992

Interphase cytogenetics on paraffin sections of malignant pleural mesothelioma. A comparison to conventional karyotyping and flow cytometric studies.

We performed in situ hybridization (ISH) studies of malignant pleural mesotheliomas to detect numerical aberrations of chromosomes 1 and 7 in interphase nuclei of paraffin sections of 13 cases that had been analyzed previously by conventional karyotyping and flow cytometry. The hybridizations were performed with the biotin-labeled probes recognizing repetitive DNA sequences in the (peri)centromeric regions of chromosomes 1 (1q12) and 7(7cen). Application of histologic sections allowed us to analyze the tumor cells only. Comparison of the karyotype and ISH studies showed that the same chromosome copy numbers were detectable by both methods in 13 (chromosome 1) and in 12 (chromosome 7) cases evaluable by ISH. DNA indexes determined in the paraffin-embedded tumor material corresponded with the ISH findings. As compared with karyotype analysis, ISH showed a larger heterogeneity in chromosome copy numbers. The results can be divided into three groups: 1) Monosomy or disomy of chromosomes 1 and 7 was detected by both methods in two cases; 2) in four cases, disomy of both chromosome 1 and 7 was observed in most of the cells by ISH analysis, and karyotype analysis had shown clear polyploidization in three of these cases; 3) in seven cases, supernumerary copies of chromosomes 1 and/or 7 were present in an evident fraction (27-80%) of the cells analyzed by ISH, and karyotype analysis confirmed the aberrant copy numbers in five of these cases. On the other hand, ISH showed copy numbers not detected by karyotype analysis in six of the seven cases. Thus, by combining karyotype and interphase cytogenetic studies, complementary information about chromosomal aberrations in mesothelioma is obtained.

Chromosome Aberrations↗
PubMed1992

N-acetylcysteine in combination with radiotherapy in the treatment of non-small cell lung cancer: a feasibility study.

N-Acetylcysteine (NAC) is a free radical scavenger and could therefore act as a radioprotector. To test the feasibility of administering NAC in combination with radiotherapy, we studied 10 patients with inoperable non-small cell lung cancer who were receiving hyperfractionated radiotherapy (RT) of 1.25 Gy B.I.D. (6-h interval) up to a total dose of 60 Gy/48 fractions/32 days. They were given NAC concomitantly with RT: 100 mg/kg i.v. 30 min before the first RT session followed by 30 mg/kg as an i.v. infusion over 7 h; and 600 mg inhaled 30 min before and after each RT session. The patients were assessed by serial CT scans and lung function studies during a 1-year follow-up period. The treatment regime was feasible, but expensive in time and resources. Normal tissue reactions and tumour responses were similar to those in a control group.

Acetylcysteine↗
PubMed1992

Natural alpha-interferon in combination with hyperfractionated radiotherapy in the treatment of non-small cell lung cancer.

Our previous study in patients with small-cell lung cancer indicated that natural alpha interferon might be a radiosensitiser. In this study we considered 20 patients with inoperable non-small cell lung cancer, who were randomly assigned to receive either hyperfractionation radiotherapy alone, 1.25 Gy twice a day (6 hr interval), 60 Gy/48F/32d; or the same radiotherapy concurrently with alpha interferon. Patients in the radiotherapy+alpha interferon arm received 3 x 10(6) IU natural alpha interferon intramuscularly and 1.5 x 10(6) IU inhaled via a dosimeter-equipped jet nebulizer 30 min before each radiotherapy session. Tumor response and radiation-induced lung injury were assessed by serial chest radiographs, computerized tomography scans and lung function studies, during a 1 year follow-up period. No patient in either arm achieved complete response. On the other hand, five patients in the radiotherapy arm and six in the radiotherapy+interferon arm experienced partial response, and the corresponding figures for stable disease were three and one. Combined treatment with radiotherapy and inhaled and intramuscular interferon proved feasible but laborious, for both patients and staff. Pneumonitis and/or oesophagitis in the radiotherapy+interferon arm were moderate to severe, and only two patients tolerated the treatment without any modifications. No treatment modifications were necessary in the radiotherapy arm. The early deaths in the radiotherapy+interferon arm may have been treatment-related. The optimal way to combine interferon and radiotherapy to further evaluate its role as a radiosensitiser needs further studies in larger series.

Adenocarcinoma↗
PubMed1992

Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation.

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.

Adult↗
PubMed1992

Malignant mesothelioma: clinical characteristics, asbestos mineralogy and chromosomal abnormalities of 41 patients.

The clinical characteristics and the results of mineral fibre and cytogenetic analyses were coordinated prospectively for 41 patients with confirmed malignant pleural mesothelioma. A correlation was found between high total fibre concentration, and partial or total loss of chromosomes 1, 4 and 9 and chromosomal rearrangements involving a breakpoint at 1p11-p22. There was also a correlation between crocidolite/amosite as the main fibre type and partial or total loss of chromosomes 1, 3 and 4 and chromosomal rearrangements involving del (3p). Positive prognostic factors were female gender, low total fibre concentration (less than 10(6) fibres per g dried lung tissue), anthophyllite as the main fibre type and normal chromosome 7. In addition, we found 4 patients with malignant mesothelioma who had been exposed mainly to anthophyllite fibres (total lung fibre concentrations of 1.2, 0.4, 0.2 and 0.1 x 10(6) fibres per g dried lung tissue). This would seem to indicate that there may be a carcinogenic role for anthophyllite.

Adult↗
PubMed1992

Natural interferon alfa as maintenance therapy for small cell lung cancer.

We performed a 3-armed phase III study between 1982 and 1990 to evaluate low dose natural interferon alfa (nIFN-alpha) as a maintenance therapy in small cell lung cancer (SCLC) following induction chemotherapy (CT) and consolidation radiotherapy (RT). All patients received four cycles of CT (cyclophosphamide, vincristine, etoposide), followed by split-course RT (55 Gy in 20 fractions over 7 weeks). 410 patients entered the study. 237 patients who completed induction CT + RT and were classified as responders (complete response + partial response) were randomly assigned to arm 1: low dose nIFN-alpha (91 patients); arm 2: maintenance CT, six cycles of CAP (cyclophosphamide, doxorubicin, cisplatin) (59 patients); or arm 3: control arm (no maintenance treatment) (87 patients). Halfway through the study the CAP arm was discontinued. There was no difference in median survival between the groups (IFN: 11 months, CAP: 11 months, control: 10 months), but a clear difference in long-term survival and in survival in the limited disease group, favouring nIFN-alpha maintenance therapy. Proportional hazards regression analysis also showed a significant effect of IFN treatment on survival. Our results suggest a role for nIFN-alpha in maintaining a clinically disease-free status achieved with other treatment modalities.

Aged↗
PubMed1992

Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines.

Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno-chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4-epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1992

Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients.

This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma.

Adult↗
PubMed1992

Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study.

PURPOSE: The aims of this study were to assess the effect of adjuvant chemotherapy on overall survival, disease-free survival, and relapse pattern, as well as its toxicity in patients who underwent radical surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred ten patients with T1-3N0 (World Health Organization [WHO] 1981) NSCLC underwent radical surgery during the period of 1982 through 1987. After surgery, the patients were randomized to receive adjuvant chemotherapy (n = 54) (cyclophosphamide 400 mg/m2, doxorubicin 40 mg/m2, and cisplatin 40 mg/m2 [CAP] for six cycles) or no active treatment (n = 56). RESULTS: After 10 years from the start of the study, 61% of patients were alive in the chemotherapy group and 48% were alive in the control group (P = .050). Seventeen patients (31%) in the CAP group and 27 patients (48%) in the control group had a recurrence during the follow-up period (P = .01). The 5-year survival rate was 67% in the chemotherapy group and was 56% in the control group (P = .050). The patients in the chemotherapy group who completed the planned treatment had a slightly better 5-year survival than those whose chemotherapy was discontinued (72.5% v 50.3%; P = .15). Chemotherapy-related gastrointestinal toxicity grade 3 to 4 (WHO) occurred in 63% and was the main reason why patients refused further planned therapy. CONCLUSION: Our results suggest that patients with NSCLC at pathologic stage I who have undergone radical surgery benefit from adjuvant chemotherapy.

Adult↗
PubMed1992

Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.

Adult↗
PubMed1992

[Interferon treatment in small-cell lung cancer].

The article consists of an account of Finnish experience in the clinical use of natural, and to a lesser extent, recombinant alpha-interferon in the treatment of lung cancer, including the results of research into interferon treatment of small cell lung cancer carried out by the Lung Cancer Group at University Hospital, Helsinki.

Carcinoma, Small Cell↗
PubMed1991

Malignant mesothelioma: the antiproliferative effect of cytokine combinations on three human mesothelioma cell lines.

Tumour necrosis factor (TNF) combined with gamma-interferon (IFN gamma) is known to have antiproliferative effects on many tumour cells, both in vitro and in vivo. We investigated whether human mesothelioma cells would respond in a similar way. Mesothelioma cell lines established from primary tumours did not respond significantly in vitro to either TNF or IFN gamma alone but were inhibited by combinations of TNF and IFN gamma at concentrations as low as 5 ng/ml. In contrast, a mesothelioma cell line established from a metastatic tumour was sensitive to IFN gamma both alone and in combination with TNF but not to TNF alone. We also looked at the responses of one primary tumour cell line and the metastatic tumour cell line to alpha-interferon (IFN alpha) both alone and in combination with TNF. Both cell lines were sensitive to IFN alpha but were more sensitive to the THF/IFN alpha combination. We conclude that these low dose combinations of cytokines are worth further investigation in the development of mesothelioma therapy.

Cell Line↗
PubMed1991

Mitoxantrone in malignant pleural mesothelioma: a study by the EORTC Lung Cancer Cooperative Group.

46 patients with malignant pleural mesothelioma were entered in a phase II study of mitoxantrone 14 mg/m2 every 3 weeks. Histology was confirmed by a pathology panel. None of the patients had received previous chemotherapy. Toxicity was mainly mild gastrointestinal and haematological side-effects. Out of 34 patients evaluated for response, only 1 partial response was recorded. Mitoxantrone at this dose and schedule has marginal activity in malignant mesothelioma.

Adult↗
PubMed1991

Diploid predominance and prognostic significance of S-phase cells in malignant mesothelioma.

70 histologically verified, malignant mesotheliomas were analysed by flow cytometry for DNA content and S-phase fraction (SPF) of tumour cells. 60% (42/70) were DNA diploid. 18 of the 28 aneuploid tumours were near-diploid with DNA indices of 1.3 or less. SPF could be calculated in 51 cases. SPF was significantly higher in aneuploid (median 16.0%) than in diploid tumours (median 5.6%). DNA ploidy was not a prognostic determinant; survival was the same for both aneuploid and diploid tumours. SPF, however, was significantly correlated (P = 0.039) with prognosis. Patients who had tumours with a low SPF survived almost twice as long as those with a high SPF. Thus malignant mesothelioma has a peculiar DNA ploidy pattern compared with many other solid tumours, with a predominance of diploid or near-diploid type cells. As in many other tumours, SPF may be used as a clinically relevant prognostic indicator.

Adult↗
PubMed1991

Procollagen-III in serum, plasminogen activation and fibronectin in bronchoalveolar lavage fluid during and following irradiation of human lung.

In the search for predictors of late radiation-induced lung injury we studied procollagen type III peptide concentration (P-III-P) in serum as well as fibronectin and plasminogen activation in bronchoalveolar lavage (BAL) fluid during and following irradiation of human lung. The patients received either high-dose hemithorax irradiation for pleural mesothelioma (11 patients) or high-dose irradiation with individually shaped fields for non-small cell lung cancer (12 patients). The severity of radiation fibrosis was assessed clinically from CT scans 6 months and 12 months after treatment. Four scores were used: severe, moderate, mild, or normal. Radiological lung injury varied from "severe" (9 patients) to near absence of injury-"normal" (6 patients). Serum levels of P-III-P, when measured weekly during the 5-week period of radiotherapy or at several time-points after treatment, did not show consistent changes, nor did the levels correlate with the score for radiation fibrosis as assessed by CT scanning. Changes in fibronectin levels or in markers of plasminogen activation in BAL fluid did not correlate with the development of late lung injury. The levels of BAL fluid plasmin and plasminogen activator as assessed zymographically, but not the free net enzyme values, showed a tendency to be elevated in patients with severe radiation-induced lung injury, suggesting a possible role for inhibitors of the plasminogen activation cascade in the process of radiation-induced lung injury.

Adult↗