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Biomedical subjects

H Strander

Publications and source records attributed to H Strander.

At least 37 records · Page 2Linked to original sources

Long-term adjuvant interferon treatment of human osteosarcoma. A pilot study.

During the period from 1971 to 1990 all osteosarcoma patients referred to the Karolinska Hospital without signs of metastases received human leukocyte interferon (IFN) as adjuvant treatment. Patients referred between 1985 and 1990 were given more intensive human leukocyte IFN treatment, i.e. a standard dose of 3 MU s.c. daily for 3-5 years. These 19 patients, all followed for 5 years, were included in a pilot study which entailed patients with central localization where radical surgery was not feasible. Metastases developed in 9 patients, of whom 3 had local recurrences. Sixty-three percent are free of disease at 5 years. Side-effects were negligible and long-term toxicity practically non-existent. It is suggested that a randomized multicenter IFN trial should be instituted on patients with poor prognosis receiving chemotherapy and/or that IFN treatment should be combined with other therapeutic modalities--irradiation, chemotherapy or anti-angiogenic substances--in osteosarcoma.

Bone Neoplasms↗

Adjuvant interferon treatment in human osteosarcoma.

An update of the adjuvant trial on osteosarcoma in Sweden comparing patients receiving natural interferon (IFN) alpha with a high-dose chemotherapy group and a nonadjuvant group is presented. The overall survival for the IFN group is 49%, for the chemotherapy group 54%, and for the nonadjuvant group 35%. Trial evaluation was complicated by group differences with respect to various clinicopathologic features of prognostic significance. The role of IFN in the treatment of osteosarcoma can still not be established.

Bone Neoplasms↗

Interferon treatment of human malignancies--a short review.

Interferon (IFN) therapy can induce remissions in human malignancies and has been established as a treatment of choice in several diseases. The clinical effects of IFNs are especially obvious in the treatment of hematological malignancies and virus-associated tumor diseases. Most other types of malignant solid tumors are less likely to respond to IFN as monotherapy and optimal therapeutic schedules are yet to be developed. It is of special interest that combinations of IFNs with other treatment modalities have yielded an increased response rate in several diseases. Several studies on the use of IFN as adjuvant therapy are under way. It is possible, if not likely, that the antitumor effects of IFNs are mediated by different cellular effects in cooperation. These may differ between different malignancies. Mainly based on studies comparing in vitro sensitivity of malignant cells to clinical effects on the same tumor, we suggest that the direct effects of IFNs on the malignant cell are of major importance for the antitumor action of IFN. A deepened insight into the cellular aspects of the antitumor action of these cytokines is a prerequisite for the optimal use of IFNs in the treatment of tumors in man.

Humans↗

Treatment of advanced condylomata acuminata with semi-purified and purified human leukocyte interferon.

Twelve patients with advanced condylomata acuminata were treated by systemic human leukocyte interferon (IFN) therapy. Semi-purified and purified preparations were both able to affect condylomatous growth. Treatment of the patients at various periods of their disease resulted in one complete remission, 6 partial remissions, 4 minimal responses while one case showed progressive disease. Side-effects were unexpectedly common in these advanced patients and 4 of them had to stop IFN treatment.

Adult↗

Dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A phase I-II trial.

Dacarbazine-vindesine-cisplatin treatment was evaluated in a phase II study of patients with disseminated malignant melanoma after the dose of cisplatin had been determined in a phase I study. Dose of dacarbazine was 250 mg/m2 X V every 4 weeks, vindesine 3 mg/m2 once every week, and cisplatin 100 mg/m2 every 4 weeks. Forty patients with advanced disseminated malignant melanoma are available for response. Complete remissions were obtained in three patients (8%) and partial remissions in 12 patients (30%). The total response rate was 38%. Median response duration was 4 months. Toxicity was unacceptable in five cases (nephrotoxicity, one patient; ototoxicity, two patients; hypotonia, one patient; gastrointestinal toxicity, one patient). The conclusion is that the combination dacarbazine-vindesine-cisplatin gives rise to a high response rate in patients with advanced disseminated malignant melanoma. Despite its considerable toxicity, the regimen should be tested on patients with a limited tumor burden.

Antineoplastic Combined Chemotherapy Protocols↗

Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial.

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.

Adult↗

Dacarbazine versus dacarbazine-vindesine in disseminated malignant melanoma: a randomized phase II study.

In a phase II study 119 patients with disseminated malignant melanoma were randomized to receive treatment with dacarbazine alone or in combination with vindesine. The study was designed to reveal an additive response rate when the drugs were combined. Dacarbazine was given i.v. at 250 mg m-2 per day X V every 4 weeks. In the combination regimen vindesine given at 3 mg m-2 per week was included. One hundred and ten patients were available for evaluation of response. With dacarbazine 4/51 patients obtained a complete remission (8%) and 5/51 patients a partial remission (10%). Overall response rate was 18%. With dacarbazine-vindesine 8/59 patients obtained a complete remission (13%) and 7/59 patients a partial remission (12%). Overall response rate was 25%. The difference in response rates observed between the treatment arms is not statistically significant. Median response duration was 123 days for dacarbazine patients and 171 days for patients receiving dacarbazine-vindesine (difference not statistically significant).

Adult↗

Clinical evaluation of treatment with interferon.

Interferons (IFNs) are biological response modifiers with antiviral and antitumoral efficacy. They are produced by almost all cells and the IFN system as a whole is an integrated part of body regulation and defence. Exogenous IFN therapy has been used since 1970 and some viral and tumor diseases respond to such therapy. Doses and schedules giving optimal effects are being worked out. IFNs are probably most valuable for the treatment of some chronic viral diseases and their effects on some benign and malignant tumors hold considerable promise for future improved applications.

Humans↗

The action of interferons on virus-associated human neoplasms.

Interferons (IFNs) exert antitumour effects on a number of virus-associated human neoplasms. Encouraging results have been obtained especially for papillomavirus and HIV-associated tumours. The exact mechanisms that cause IFN to exert antitumour effects are as yet unknown. IFN therapy is attended by dose-dependent side effects. IFN schedules should be improved and combination schemes formulated for optimal effect. The role of IFNs in tumour cells and normal cells should be elucidated to pinpoint the part played by the IFN system during the development of tumour diseases in humans.

Humans↗

A phase II study on escalating interferon doses in advanced ovarian carcinoma.

Twenty-four patients with advanced and therapy-resistant ovarian carcinoma were treated with escalating daily doses of human leukocyte interferon (IFN). Doses ranged from 3 X 10(6) to 27 X 10(6) IU/day. Fatigue, fever, thrombocytopenia, and leukopenia were the limiting factors in the escalation of doses. Of nine patients treated for at least 2 months, there were two patients with partial remissions and six with stable disease. Ascites production present in four patients became reduced in three. The level of 2',5'-oligoadenylate synthetase in peripheral blood lymphocytes increased following initiation of IFN therapy. We conclude that IFN-alpha can exert an antitumor effect in some patients with ovarian carcinoma that have previously failed on other therapy regimens.

2',5'-Oligoadenylate Synthetase↗

Characterization of EBV-carrying B-cell populations in healthy seropositive individuals with regard to density, release of transforming virus and spontaneous outgrowth.

Peripheral or tonsil lymphocyte populations of EBV-seropositive donors give rise to EBV-carrying LCLs upon in vitro explantation. Such lines can arise either by a 2-step mechanism, namely release of virus from some of the explanted cells followed by infection of previously uninfected B cells, or by direct outgrowth of virus-harboring B cells (Rickinson et al., 1974; Dalens et al., 1975; Hinuma and Katsuki 1978; Katsuki et al., 1979). We observed that cells responsible for both the 2-step mechanism and for direct outgrowth are found in the purified B-cell compartment. Virus release was more frequent than direct outgrowth. The majority of virus-releasing cells were found in the low-density fraction that contains large, activated B blasts. Cells that were capable of spontaneous outgrowth in the presence of the viral inhibitor PFA and of virus-neutralizing antibody gave rise to cell lines that carried the sex chromosome marker of the original donor, rather than that of admixed cord blood lymphocyte of the opposite sex. Such cells were found in both the low- and the high-density fractions. The majority of the EBV-carrying B cells in vivo are thus low-density blasts. Rare small B cells of high density harboring EBV were capable of spontaneous outgrowth. This may be indicative of a host control mechanism that is removed upon cultivation in vitro.

B-Lymphocytes↗

Influence of alpha-interferon therapy on blood lymphoid cells. Studies on antibody production, mixed lymphocyte culture response, mitogen responsiveness and 2'-5'oligoadenylate synthetase activity.

The influence of natural alpha-interferon (alpha-IFN) therapy (3 X 10(6) units i.m. daily) on blood lymphoid cells was studied in 20 patients with gynecological neoplasias (7 patients with condylomata accuminata and 13 patients with ovarian carcinoma). There was a statistically significant increase in the intracellular levels of 2'-5'oligoadenylate synthetase 1 day after the first injection of IFN and with few exceptions this activity remained increased during 3 months of treatment. In most of the patients, the capacity of blood lymphoid cells to produce IgA, IgG, and IgM following stimulation with pokeweed mitogen was decreased 1 day after the first injection of IFN and with few exceptions it remained low during 6 months of IFN therapy. In most patients there was a decrease in the capacity of lymphoid cells to act as stimulator or responder cells in a mixed lymphocyte culture during IFN therapy. The alpha-IFN therapy had no major influence on the response of lymphoid cells to mitogens. We conclude, that neither this nor our previous studies on the influence of IFN therapy on immunological functions have given support to the hypothesis that the antitumor action of IFN is mediated by the immune system.

2',5'-Oligoadenylate Synthetase↗

Influence of interferon on the growth of primary ovarian carcinoma cells in a semi-solid agar system: comparison with clinical effects of interferon therapy.

The sensitivity of primary human ovarian cancer cells to interferon (IFN) was studied in vitro by the use of a tumor cloning system in semi-solid agar. Tumor colonies were found in 37% (34/93) of the experiments with tumor cells from ascites and in 35% (6/17) of the experiments with solid tumors. The relative colony-forming ability could not be correlated to prior treatment. In 15 out of 18 patients the ascitic tumor cells were sensitive to IFN-alpha. Sensitivity was found in one test out of three with solid tumors. The sensitivity was dependent on the dose of IFN but could vary for the natural IFNs alpha and gamma. In seven patients the relation between in vitro and in vivo sensitivity of the tumor cells to IFN could be studied. Any correlation between in vitro and in vivo sensitivity could not be revealed in this small group of patients.

Adult↗

Comparison of growth inhibiting effect of natural and recombinant interferon-alpha on human osteosarcomas in nude mice.

Of five tested human osteosarcoma xenografts growing in nude mice, two could be growth-arrested by both natural interferon-alpha (nIFN-alpha) and recombinant IFN-alpha 2c (rIFN-alpha 2c). The other three less sensitive xenografts could only be partly growth-inhibited by the nIFN-alpha while no effect was seen with rIFN-alpha 2c. The leukocyte-derived IFN, thus, appeared to have higher antitumor activity per antiviral unit than the recombinant-produced IFN. It is questionable whether this observed difference is of practical relevance for clinical trials employing different IFN-alpha preparations.

Animals↗

Does successful interferon treatment of tumor patients require life-long treatment?

Case histories of 5 tumor patients treated with natural leukocyte interferon-alpha (IFN-alpha) are presented. One patient with juvenile laryngeal papillomatosis responded well to interferon treatment, but the disease recurred when therapy was withdrawn. Upon reinstitution of treatment, the patient once again responded well. Another patient with myelomatosis also responded well to interferon therapy and in this case, too, the tumor recurred when interferon treatment was withdrawn. Reinstitution of interferon therapy was, however, unsuccessful. One patient with generalized giant cell tumor of bone responded with regression after more than 5 years of interferon treatment. Another patient with pulmonary osteosarcoma metastases, having received irradiation and interferon combination therapy followed by sole interferon treatment, responded well with a lasting stationary radiogram after 6 years of interferon treatment. One patient with malignant glioma, showing signs of tumor growth during the first few months of interferon therapy, eventually responded, and became disease-free after 6 years. The latter 3 patients are continuously receiving interferon therapy although more than 5 years have elapsed since their interferon therapy was initiated. It is suggested that interferon therapy for malignant tumors be given for life (or to progression of disease) in responding patients. Such a concept entails biological implications for interferon therapy in general and for antitumor action of interferons in particular. Other possible clinical schedules should only be constructed within the framework of controlled clinical trials.

Adult↗

The capacity of blood lymphoid cells to produce alpha- and gamma-interferon is decreased during alpha-interferon therapy.

The influence of alpha-interferon (alpha-IFN) therapy on the capacity of blood lymphoid cells to produce alpha- and gamma-interferon (IFN) was studied in 21 patients with gynecological tumors, i.e., ovarian carcinoma (14 patients) or condylomata accuminata (7 patients). The mean capacity of the lymphoid cells to produce alpha-IFN in response to Sendai virus was increased, although not statistically significant, as compared to an age- and sex-matched control group, whereas the mean capacity of the patients' blood lymphoid cells to produce gamma-IFN in response to PHA or PWM was slightly decreased as compared to the control group. One day after the first injection of alpha-IFN there was a statistically significant decrease in the capacity of blood lymphoid cells to produce alpha-IFN and this decrease remained after 3 months of IFN therapy in most patients investigated. One week after initiation of alpha-IFN therapy there was a statistically significant decrease in the capacity of the cells to produce gamma-IFN in response to PHA or PWM and in most patients studied this decrease remained after 3 months of treatment. We conclude that the capacity of blood lymphoid cells to produce IFN is suppressed during exogenous alpha-IFN therapy.

Adult↗