Search PubMed⌕ Search

Biomedical subjects

J Tennvall

Publications and source records attributed to J Tennvall.

At least 37 records · Page 2Linked to original sources
PubMed1996

Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method.

This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.

Adenocarcinoma↗
PubMed1995

Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats.

The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m. (IM tumor), were divided into four study groups: controls, ECIA, preload, and combined preload+ECIA. The preload+ECIA procedure reduced the whole-body and plasma activity by 48 and 89%, respectively. After such combined procedure, the uptake of 125I-labeled L6-biotin in SR tumors was unchanged, while the uptake in normal tissues was considerably reduced. Tumor (T):bone marrow ratio was then increased by 17.5 times (after ECIA) and by 4.5 times (24 h after ECIA). Similar enhancements were achieved for T:liver and T:kidney ratios. For the IM tumors, the ratios were not as high as for SR tumors. The effects on T:normal ratios of preload+ECIA in combination were synergistic. The combined procedure resulted both in an increased uptake and prolonged persistence of 125I-labeled L6-biotin in the SR tumors and also in a reduction of corresponding uptake values in organs critical for radiation.

Animals↗
PubMed1995

A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung.

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous-infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.

Aged↗
PubMed1995

Determination of nonendemic nasopharyngeal carcinoma by in situ hybridization for Epstein-Barr virus EBER1 RNA: sensitivity and specificity in cervical node metastases.

After time-consuming and costly investigations, patients with neck metastases from an occult primary often receive unnecessarily large radiation volumes to treat a possible origin in the nasopharynx. In this study a colorimetric antisense Epstein-Barr early ribonucleoprotein 1 (EBER1) oligonucleotide probe specific for Epstein-Barr virus RNA was hybridized in situ to metastatic tissue obtained from 18 nasopharyngeal, 54 oral and pharyngeal, and 12 occult carcinomas derived from an unselected population. All 16 nonkeratinizing nasopharyngeal carcinomas (NPCs) were positive for EBER1. Both cases of keratinizing NPC and all 54 other metastases were negative. A single positive case of occult carcinoma indicated its origin from NPC. In retrospect, 7 patients with occult carcinoma had received unnecessary treatment with irradiation to the nasopharynx. Nasopharyngeal carcinoma appears to be a less common origin of occult carcinoma than previously considered. In the proper clinicopathologic context EBER1 in situ hybridization (EBER1-ISH) allows exclusion of NPC with a high degree of accuracy. Thus unnecessarily large radiation volumes and their adverse sequelae may be reduced in the treatment of occult carcinoma. Conversely, a positive result of ISH allows exclusion of further extensive diagnostic procedures.

Adolescent↗
PubMed1994

Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group.

BACKGROUND: Anaplastic carcinoma of the thyroid (ACT) rarely can be cured, but every effort should be made to improve prognosis and, above all, prevent death due to suffocation or large local tumor ulceration. METHODS: From 1984 to 1992, 33 consecutive patients with ACT were treated prospectively according to a combined treatment program consisting of hyperfractionated radiotherapy, doxorubicin, and debulking surgery. Preoperative radiotherapy was administered to a target dose of 30 Gy and postoperatively to a total dose of 46 Gy. Radiotherapy was performed 5 days a week. The daily fraction was 1.0 Gy x 2 until 1988, after which it was 1.3 Gy x 2. Otherwise, the therapy remained unchanged. Twenty milligrams of doxorubicin were administered intravenously per week. Debulking surgery was possible in 23 patients (70%). RESULTS: No patient failed to complete the protocol because of toxicity. There were no signs of local recurrence in 16 patients (48%). In only eight patients (24%) was death attributed to local failure. In four patients, survival with no evidence of disease exceeded 2 years. Improvement in local tumor control was marginally significant (P = 0.08) in the 17 patients treated in the latter part of the study, with no sign of local disease in 11 patients and deaths due to local failure in only 2 patients. The improved local control could not be attributed to any differences between the two series. CONCLUSION: Combination modality treatment of ACT is feasible and effective despite the patients' advanced age and locally advanced disease. There was a tendency for local control to be improved after accelerated radiotherapy.

Aged↗
PubMed1994

A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio.

The idea of applying extracorporeal immunoadsorption (ECIA) in radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The authors here report on the development of new concept using a general method for ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats heterotransplanted with either human melanomas or human lung carcinoma were injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At 24 or 48 hours after the injection, ECIA was performed by pumping blood through a hollow-fiber plasma filter. The separated plasma then was passed through an absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours. By this ECIA method, the tumor-to-normal tissue ratios were increased in various tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.

Animals↗
PubMed1994

Radio-immunotherapy dosimetry with special emphasis on SPECT quantification and extracorporeal immuno-adsorption.

Results from therapeutic trials with radiolabelled monoclonal antibodies are difficult to compare, because of lack of accurate macroscopic and microscopic dosimetry for both tumours and normal tissues. Requirements for such a dosimetry are covered in the paper. Accurate in vivo dosimetric measurement techniques for verification of calculated absorbed doses are also needed to verify treatment planning. In the review, important topics related to dosimetry in therapeutic trials in RIT are covered, such as, absorbed-dose calculations and activity-quantification techniques for planar imaging and SPECT. The latter is particularly discussed, including a summary of different correction techniques. Absorbed-dose calculations and treatment-planning techniques are also discussed. Possible ways of enhancing the therapeutic ratio are reviewed, especially the novel technique with extracorporeal immuno-adsorption. The review could form the basis of the development of future treatment-planning protocols and for dosimetry calculations in radio-immunotherapy, considering some of the most important parameters for approaching an accurate in vivo dosimetry.

Antibodies, Monoclonal↗
PubMed1994

Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats.

In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.

Animals↗
PubMed1993

DNA analysis as a predictor of the outcome of induction chemotherapy in advanced head and neck carcinomas.

We investigated whether flow cytometric DNA index and/or ploidy status are predictors of response to chemotherapy and survival. Fifty consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck received induction chemotherapy consisting of three courses of cisplatin (100 mg/m2) and a subsequent 120-hour infusion of fluorouracil (1000 mg/m2 per 24 hours) repeated every 3 weeks. Chemotherapy was followed by radiotherapy to a median target dose of 65 Gy and subsequent surgery for residual tumor. The median observation time was 27 months (range, 24 to 57 months). Flow cytometric DNA analysis was based on formalin-fixed and paraffin-embedded tissue from pretreatment tumor biopsy specimens. Complete response after induction chemotherapy was achieved in only 12% (2/17) of patients with diploid tumors compared with 39% (13/33) of those with nondiploid tumors. Among patients with nondiploid tumors, DNA index was higher for those responding to chemotherapy compared with the nonresponders. Complete response to chemotherapy was apparently a prerequisite for survival in the nondiploid group. Of the patients not responding to chemotherapy but responding to subsequent radiotherapy, survival was better among those with diploid tumors than among those with nondiploid tumors.

Adult↗
PubMed1993

T3N0 glottic carcinoma: DNA S-phase as a predictor of the outcome after radiotherapy.

In consecutive series of 326 laryngeal cancer patients, of 29 (9%) with stage T3N0 glottic carcinomas, 23 achieved complete local remission after curative radiotherapy and form the basis of the present investigation. Flow cytometry determinations of DNA-ploidy status and the S-phase fraction, and a "histopathological malignancy grading system" were evaluated as possible patient- and/or tumor-related predictors of local recurrence. Twelve patients (52%) were continuously disease-free after radiotherapy, whereas 10 (43%) manifested local recurrence, and one distant metastasis. The radiotherapy delivered to patients who later suffered from a local recurrence did not differ from those being continuously disease-free. The frequency of local recurrence was significantly correlated to patients whose primary tumours manifested a low S-phase fraction (p < 0.05). A low S-phase fraction may indicate slowly proliferating tumour-cells, which become more radioresistant on exposure to a series of fractionated doses, as their reassortment into sensitive phases will be proportionately slower.

Adult↗
PubMed1993

Radioimmunotherapy dosimetry--a review.

Results from therapeutic trials in systemic radiation therapy with radiolabelled monoclonal antibodies are difficult to compare, because of lack of accurate dosimetry. This applies macroscopically as well as microscopically for both tumours and normal tissues. For treatment planning in radioimmunotherapy both the macroscopic and the microscopic absorbed dose distribution must be known. The former is based on a proper knowledge of parameters, such as activity quantitation techniques in both planar and SPECT imaging, different correction techniques, and high activity measurements. Absorbed dose calculations and treatment planning techniques are based on analytical or Monte Carlo calculations. The PET technique with higher resolution is also suggested for radioimmunotherapy planning. Accurate in vivo absorbed dose measurement techniques to verify the calculated absorbed doses are needed in treatment planning. Monitoring the absorbed rate is desirable to assess radiobiological effect. Several ways of enhancing the therapeutic ratio are suggested, especially novel technique with extracorporeal immunoadsorption. An important topic is small scale dosimetry, which is based on techniques for detailed imaging of activity distributions to calculate the absorbed dose distribution.

Adsorption↗
PubMed1993

Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA).

Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.

Adenocarcinoma↗
PubMed1992

Leukaemia incidence after iodine-131 exposure.

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

Adolescent↗
PubMed1992

Cancer mortality after iodine-131 therapy for hyperthyroidism.

Cancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131I between 1950 and 1975. The patients were matched with the Swedish Cause-of-Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.

Age Factors↗
PubMed1992

Malignant melanoma of the nasal cavity and nasopharynx treated with cisplatin and accelerated hyperfractionated radiation.

Primary malignant melanoma of the nasal cavity and paranasal sinuses is an uncommon disease, accounting for only 0.5-2% of all malignant melanomas. The primary treatment has been surgery. The frequency of local recurrence is high and recurrence is also the major determinant of treatment failure. Here we report on six patients with locally advanced disease, four of whom were too advanced for surgery, who were treated with accelerated hyperfractionated radiation in combination with cis-platinum. Three of four patients treated for local recurrent disease achieved a local cure and died of disseminated disease after 9-21 months. One patient given preoperative cisplatin and radiation is still alive with no evidence of disease 34 months after the completion of treatment. The present protocol may be a useful approach to obtain local control with the possibility of long-term cure.

Aged↗
PubMed1992

Radiotherapy for unresectable endocrine pancreatic carcinomas.

Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or alpha-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas.

Adenoma, Islet Cell↗