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Biomedical subjects

J Kulmala

Publications and source records attributed to J Kulmala.

At least 19 recordsLinked to original sources
PubMed2002

Osteodistraction of a previously irradiated mandible with or without adjunctive hyperbaric oxygenation: an experimental study in rabbits.

The purpose of this study was to analyse the effects of irradiation and hyperbaric oxygenation (HBO) on mandibular osteodistraction (OD). Eighteen rabbits were divided into three groups: 1. Irradiation (R), 2. Irradiation+HBO (R-HO), and 3. Control group (C). Animals of groups R and R-HO received in the mandible irradiation 22.4 Gy in four 5.6 Gy fractions (equivalent to 50 Gy/25 fractions). In addition, group R-HO was given HBO at 2.5 ATA for 90 min per day 18 times preoperatively. Unilateral osteotomy was made 1 month after completion of radiotherapy. After a 1 week latency period bone distraction was started at rate of 1 mm per day, continued for 2 weeks, and left to consolidate for 4 weeks. Amount of new bone was measured histomorphometrically from midsagittal sections. Area of new bone was equal in all groups. Bone was more mature and bone spicules better organized in group C than in groups R and R-HO. Cartilaginous cells were found in distracted bone in all groups but larger chondroid islands were evident only in group R. It seems that despite delayed bone formation, OD can be performed after radiotherapy. HBO had a beneficial effect on bone quality of a previously irradiated mandible.

Animals↗
PubMed2001

Disturbances in craniofacial morphology in children treated for solid tumors.

Because of increased survival rates in childhood cancer, special interest has been focused on the side-effects of the therapy and the quality of life in long-term survivors. Our aim was to investigate craniofacial growth in children who had received different kinds of antineoplastic therapies for solid tumors. A total of 40 children treated in the Turku University Central Hospital were examined and divided into three different groups. Group 1 comprised 18 children treated for intracranial tumors with cranial irradiation (CRI) and chemotherapy (CT) including alkylating agents. Seven children out of 18 in this group received growth hormone (GH) therapy. In Group 2, 11 children with extracranial solid tumors also received multiagent CT including alkylating agents, but no CRI. Group 3 consisted of 11 children treated for Wilm's tumor with CT, which did not include alkylating agents or CRI. A total of 19 linear and four angular variables from the lateral cephalograms of the subjects were measured. Most deviations in craniofacial structures were found in children treated with combined CRI and multiagent CT. All disturbances were seen in the vertical measurements which were reduced when compared to the matched controls. It seems reasonable to assume that impaired growth following combined radio- and chemotherapy, as well as GH treatment, particularly affects cartilage-mediated growth. However, the deviations seen in the present study were fairly minor and did not usually require clinical consideration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma.

PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign.

Adult↗
PubMed2000

Adhesion of inactivated probiotic strains to intestinal mucus.

It has been suggested that probiotics should be viable in order to elicit beneficial health effects. Inactivation of probiotics has been suggested to interfere with the binding to the mucosa and thereby with the immune modulating activity of probiotics. The effect of different inactivation methods on the mucus adhesion of nine probiotic strains was studied. Inactivation by heat or gamma-irradiation generally decreased the adhesive abilities. However, heat treatment increased the adhesion of Propionibacterium freudenreichii and gamma-irradiation enhanced the adhesion of Lactobacillus casei Shirota. Inactivation by u.v. was not observed to modulate the adhesion of the tested strains and it was concluded to be the most appropriate method for studying non-viable probiotics and preparing control products.

Bacterial Adhesion↗
PubMed1999

Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro.

BACKGROUND: The combination of paclitaxel and cisplatin is standard for patients with newly diagnosed epithelial ovarian carcinoma. The role of another taxane, docetaxel, currently is being studied. Due to its milder nonhematologic toxicity carboplatin increasingly is being substituted for cisplatin in taxane-based combinations. The purpose of this study was to compare the combination of carboplatin-paclitaxel with carboplatin-docetaxel in ovarian carcinoma in vitro, and to assess the type of interaction, if any. METHODS: Sensitivity to carboplatin and the concomitant use of a taxane and carboplatin was studied in 4 ovarian carcinoma cell lines using the 96-well plate clonogenic assay. Chemosensitivity was expressed as the IC50 value (i.e., the drug concentration causing 50% inhibition of clonogenic survival). IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. Synergism was studied by the area under the survival curve ratios (AUC ratios), obtained by numeric integration. The AUC ratio and the surviving fraction (SF) value after the administration of taxane alone were compared using the Student t test for paired data. RESULTS: The IC50 values for carboplatin were between 0.5-1.6 microgram/mL; there was only a 3.2-fold difference between individual cell lines. Carboplatin administered concomitantly with a taxane had either an additive or supra-additive growth inhibitory effect on all four ovarian carcinoma cell lines. A supra-additive effect occurred after simultaneous exposure of the cells to carboplatin at all tested paclitaxel concentrations in three of four cell lines (UT-OC-3, UT-OC-5, and SK-OV-3). The carboplatin-docetaxel combination had a supra-additive effect at the two highest docetaxel concentrations in two cell lines (UT-OC-4 and UT-OC-5) and at the highest docetaxel concentration in the other two cell lines (UT-OC-3 and SK-OV-3). CONCLUSIONS: Carboplatin has a synergistic effect when used with paclitaxel or docetaxel. A supra-additive effect is achieved with a wider range of paclitaxel concentrations than docetaxel concentrations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Effects of paclitaxel with or without cremophor EL on cellular clonogenic survival and apoptosis.

Paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant cremophor EL. Cremophor EL has been reported to reverse P-glycoprotein-mediated multidrug resistance (MDR) at doses which are clinically achievable. It has also been reported to have a cytotoxic effect per se. In this study we used two different methods to evaluate the survival of cells exposed to paclitaxel with or without cremophor EL and the vehicle alone. Two laryngeal SCC cell lines (UT-SCC-19A and UT-SCC-29) and two ovarian adenocarcinoma cell lines (UT-OC-3 and UT-OC-5) established in our laboratory were investigated. Northern hybridisation was used to study the mdr-1 mRNA expression of the cell lines. With sensitive Northern analyses, these four lines yielded mdr-1 mRNA signals of the expected 4.5 kb size and of variable intensity, generally at higher levels than those in the positive control cell line KB. The 96-well plate clonogenic assay was used to obtain the fraction survival data and apoptosis was recorded by time-lapse video microscopy. Both methods indicate that cremophor EL alone has no effect on cellular survival. Consequently, paclitaxel without cremophor EL is as active as paclitaxel with cremophor EL in vitro.

Adenocarcinoma↗
PubMed1999

Additive and supra-additive cytotoxicity of cisplatin-taxane combinations in ovarian carcinoma cell lines.

The purpose of this study was to compare the growth-inhibitory effect of cisplatin-paclitaxel with that obtained with a cisplatin-docetaxel combination and to assess the type of interaction. Concomitant use of taxanes and cisplatin was studied in seven human ovarian carcinoma cell lines, using the 96-well plate clonogenic assay. Chemosensitivity was expressed in terms of IC50 values, the drug concentration causing 50% inhibition of clonogenic survival. The type of interaction was studied using the area under the survival curve ratios (AUC ratios) obtained by numerical integration. Comparison of the AUC ratio and the surviving fraction (SF) value after taxane alone was made using Student's t-test. The influence of the drug concentration was tested by one-way analysis of variance (Anova). A supra-additive or additive effect was seen when seven ovarian carcinoma cell lines were exposed to paclitaxel or docetaxel concomitantly with cisplatin. A supra-additive effect was found in four cell lines (UT-OC-3, UT-OC-4, UT-OC-5 and SK-OV-3) after simultaneous use of cisplatin with all docetaxel concentrations tested, and in two cell lines (UT-OC-4 and SK-OV-3) when cisplatin was used concomitantly with paclitaxel. A more pronounced supra-additive effect was seen with the combination of cisplatin and docetaxel. The degree of supra-additivity was dose dependent, with increasing synergy after a higher taxane dose. The data obtained in this study suggest that a supra-additive or additive effect can be achieved in ovarian carcinoma with the concomitant use of cisplatin and a taxane.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Characterization of prethymic progenitors within the chicken embryo.

The thymic primordium in both birds and mammals is first colonized by cells emerging from the intra-embryonic mesenchyme but the nature of these precursors is poorly understood. We demonstrate here an early embryonic day 7 prethymic population with T lymphoid potential. Our work is a phenotypic analysis of, to date, the earliest embryonic prethymic progenitors arising in the avian para-aortic area during ontogeny. The phenotype of these cells, expressing the cell surface molecules alpha2beta1 integrin, c-kit, thrombomucin/MEP21, HEMCAM and chL12, reflects functional properties required for cell adhesion, migration and growth factor responsiveness. Importantly, the presence of these antigens was found to correlate with the recolonization of the recipient thymus following intrathymic cell transfers. These intra-embryonic cells were also found to express the Ikaros transcription factor, the molecular function of which is considered to be prerequisite for embryonic lymphoid development.

Animals↗
PubMed1999

Genome size variation in Hordeum spontaneum populations

Populations of wild barley, Hordeum spontaneum (C. Koch), originating from 10 ecologically and geographically different sites in Israel, were assessed for genome size. Measurements were obtained by flow cytometry using propidium iodide staining. Genome sizes ranged from 9.35 to 9.81 pg. Variance analysis indicated a significant difference between populations. Genome sizes were positively correlated with mean January temperature. Our results corroborate previous findings of intraspecific variation in genome size from different plant species. The positive correlations between climate and genome size suggest that the latter is adaptive and determined by natural selection.

Journal Article↗
PubMed1998

Radiosensitivity of dermal and tumor fibroblasts derived from the same patient.

The in vitro radiosensitivity of dermal fibroblasts has been found to vary between individuals, and a number of studies have also shown that this parameter correlates with radiation-induced late injuries in clinical radiotherapy. In addition, certain genetic disorders are known to effect radiosensitivity, e.g. normal tissues of patients homozygous or heterozygous for the ataxia teleangiectasia gene show unusual sensitivity to radiation both in vivo and in vitro. Thus, it has been assumed that there is a genetically determined component resulting in a certain intrinsic cellular radiation response in an individual. To study this possible relationship between different cells of a specific patient, we established eight pairs of dermal and tumor fibroblast cultures. The donor patients had either adenocarcinoma of the uterus or squamous cell carcinoma (SCC) of the head and neck. The radiosensitivity of these strains was determined by a 96-well plate clonogenic assay, previously used by us for radiosensitivity testing of cancer cells. From a paired comparison, the values for the cell fraction surviving 2.0 Gy (SF2), of both fibroblast strains, were found to be on the same level in five out of eight cases. In patient 6, the SF2 of tumor fibroblasts was significantly higher than that of dermal fibroblasts (P=0.0014). In two additional cases the tendency was the same, but not statistically significant. As groups, the two types of fibroblasts did not differ from each other, mean SF2 values of 0.24+/-0.07 and 0.21+/-0.05, respectively. The SF2 of tumor fibroblasts from SCC patients proved to be significantly higher than that of the adenocarcinoma patients (P=0.030). These preliminary results indicate that the in vitro radiosensitivity of tumor fibroblasts correlates with normal cell sensitivity in many cases, but not in all. The radiosensitivity of tumor fibroblasts also seems to follow the level of in vitro radiosensitivity determined for the corresponding histological type of tumor cells. Further studies are needed to determine more closely the relationship between the radiosensitivities of tumor cells and tumor fibroblasts, thus evaluating the possibility of testing radiosensitivity from tumor fibroblasts in order to estimate tumor response.

Adenocarcinoma↗
PubMed1996

In vitro concurrent paclitaxel and radiation of four vulvar squamous cell carcinoma cell lines.

BACKGROUND: The antitubule agent paclitaxel causes a cell cycle blockage in the most radiosensitive part of the cell cycle, the G2/M phase. The possible radiosensitizing effect of paclitaxel was tested in four vulvar (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and UM-SCV-4) squamous cell carcinoma (SCC) cell lines. METHODS: A 96-well plate clonogenic assay was performed with paclitaxel and radiation, both separately and concomitantly. Survival data were fitted to the linear quadratic model. The area under the curve, equivalent to the mean inactivation dose (D), was obtained by numerical integration. The effect of paclitaxel on radiosensitivity was measured as the AUC ratio (paclitaxel plus radiation: radiation alone). This ratio was compared with the surviving fraction (SFP) after paclitaxel alone. RESULTS: Paclitaxel concentrations of 0.4 to 2.0 nanomolar (nM) caused 1 to 70% inhibition of clonogenic survival. The AUC values of the cell lines were 1.9 to 2.9 gray. A full additive effect was observed when paclitaxel and radiation were administered concurrently; however, a supra-additive effect never occurred. The type of paclitaxel radiation interaction was not affected by the concentration of the drug nor did the type of interaction vary between cell lines studied. CONCLUSIONS: Paclitaxel and radiation used concomitantly produced a clear additive effect at all concentrations and in all vulvar carcinoma cell lines tested. Although no supra-additive effect was observed, the additive effect already in nM concentrations could be beneficial in clinical use and, therefore, requires further investigation.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Cytotoxicity of bleomycin and external radiation in squamous cell cancer cell lines of head and neck.

Bleomycin, a natural antibiotic toxic to dividing cells, has been successfully used in combinations for treatment of recurrent head and neck cancer. In this study, we investigated five recently established head and neck squamous cell cancer lines (UT-SCC-2, UT-SCC-8, UT-SCC-9, UT-SCC-12A, UT-SCC-19A) in terms of response to bleomycin and radiation treatment. Experiments were carried out using the 96-well plate clonogenic assay for concentration determinations causing 20% (IC20), 50% (IC50), and 90% (IC90) inhibition of clonogenic survival and dose-response calculations for bleomycin. Survival fraction after a radiation dose of 2 Gy (SF2) was used as a measure for radiation sensitivity. The sensitivity for bleomycin was in good accordance with radiation sensitivity except for cell line UT-SCC-9. This was the cell line most sensitive to radiation (SF2 = 0.25 +/- 0.03) but was fairly resistant to chemotherapy (IC50 = 11.5M). Sensitivity patterns may suggest partly different mechanisms of action.

Antibiotics, Antineoplastic↗
PubMed1995

Characterization and radiosensitivity of UT-EC-2A and UT-EC-2B, two new highly radiosensitive endometrial cancer cell lines derived from a primary and metastatic tumor of the same patient.

UT-EC-2A was established from a patient with moderately differentiated Stage III endometrial adenocarcinoma with squamous metaplasia. UT-EC-2B was established from the same patient 17 months later from a metastasis in the left supraclavicular fossa. The origin of these cell lines was confirmed by DNA identity testing. Nude mice tumors produced by UT-EC-2A and UT-EC-2B cells recapitulated the histology of the original human tumors. Flow cytometric DNA contents of both primary and metastatic human tumors as well as corresponding nude mice tumors were diploid. The S-phase fractions of both cell lines were > or = 30%. The UT-EC-2A cell line was cytogenetically normal. The UT-EC-2B cell line had quite simple karyotype at low passage with an extra i(18p) and a deletion 21q, but at higher passages an additional three-way translocation 5;14;19 was observed. Radiosensitivity of the cell lines was tested with the 96-well plate clonogenic assay. The areas under the survival curves corresponding to the mean inactivation doses of UT-EC-2A and UT-EC-2B were 0.65 +/- 0.10 and 0.60 +/- 0.06 Gy, respectively. Measured survival at 2.0 Gy (SF2) was 0.042 for UT-EC-2A, 0.044 for UT-EC-2B, and 0.2 for skin fibroblasts. These cell lines are among the most radiosensitive human cancer cell lines described in the literature. Studying the characteristics of primary and metastatic cells derived from the same patient provides an opportunity to evaluate tumor progression.

Adenocarcinoma↗
PubMed1995

Comparison of cellular radiosensitivity between different localizations of head and neck squamous-cell carcinoma.

The prognosis of carcinomas arising from various sites in the head and neck varies even when the stage of the disease is taken into consideration, e.g. laryngeal carcinoma has a more favourable prognosis compared to oral-cavity malignancies. The purpose of this study was to evaluate intrinsic cellular radiosensitivity as one possible explanation for the observed differences in the survival rates of different anatomical groups. The radiation survival curves were determined for well characterized cell lines derived from laryngeal carcinoma (n = 14), pharyngeal carcinoma (n = 6), carcinoma of the oral cavity (n = 14) and the skin of the face (n = 3). The intrinsic radiosensitivity was expressed as area under the survival curve (AUC) values, and this cellular parameter was compared with clinical data and survival of the patients. The intrinsic radiosensitivity in the whole group varied between 1.0 Gy and 2.8 Gy with an average of 1.9 Gy. The mean AUC values for the laryngeal cell lines were 2.0 Gy +/- 0.2, for the oral cavity 1.8 +/- 0.3 Gy, for the pharynx 1.8 +/- 0.2 Gy and for cutaneous carcinoma 2.1 +/- 0.1 Gy. There was a slight difference between the groups of glottic and supraglottic cell lines (mean 1.8 +/- 0.2 Gy and 2.1 +/- 0.3 Gy, respectively), which is consistent with the differences in clinical curability of these cancers. Otherwise, the differences in cellular radiosensitivity of the carcinoma groups studied did not reach statistical significance. These results indicate that the intrinsic radiosensitivity of squamous-cell carcinoma (SCC) of the larynx does not significantly differ from that of SCC of other sites of the head and neck. Variations in the intrinsic radiosensitivity do not as such seem to explain the observed differences in radiocurability of SCC variously localized in the head and neck.

Carcinoma, Squamous Cell↗
PubMed1995

The intrinsic radiosensitivity and sublethal damage repair capacity of five cervical carcinoma cell lines tested with the 96-well-plate assay.

We have tested the intrinsic radiosensitivity and capacity for sublethal damage repair (SLDR) in split-dose experiments with the 96-well plate clonogenic assay. Four out of five cell lines were squamous-cell carcinoma (SCC) lines (CaSki, ME-180, HX151c, HX156c) and one cell line was established from glassy-cell carcinoma (UM-GCC-1). Comparison of radiosensitivities was by with D value, the mean inactivation dose. D for these cell lines varied from 1.7 Gy to 2.5 Gy. As a group, cervical carcinoma cell lines were more radioresistant than endometrial adenocarcinoma cell lines tested with the same assay, but more radiosensitive than vulvar SCC lines. Three cell lines showed clear SLDR, but two cell lines were unable to carry out this function. Furthermore, cell lines capable of SLDR also showed significant increase in survival when D values were compared after the radiation dose was split into three instead of two fractions. These results indicate the importance of adding another radiobiological parameter to the intrinsic radiosensitivity when predictive tests are planned.

Carcinoma↗
PubMed1995

Low-dose and conventional-dose high resolution CT of pulmonary changes in breast cancer patients treated by tangential field radiotherapy.

Twenty-seven consecutive breast cancer patients receiving tangential field radiation therapy were followed by high resolution CT (HRCT) in order to compare the accuracy of reduced-dose HRCT and conventional-dose HRCT in the evaluation of subtle pulmonary changes. Thin section 1-mm HRCT images were obtained at identical levels at 120 kVp, with 320 mAs, 200 mAs, 160 mAs, 120 mAs and 60 mAs settings. HRCT was performed during the planning of radiotherapy and 4, 8 and 24 weeks after the completion of radiotherapy. Radiation was administered according to an individual CT-based plan by tangential fields with 4 or 6 MV photons to the whole breast given with 5 fractions of 1.9 Gy weekly to a total dose of 50 Gy. The tumor bed was boosted by electrons to 60 Gy. Pathological changes were detected in 21 examinations of 10 patients: 9 patients out of 27 (33%) showed radiation induced changes; 1 patient developed metastases within the irradiated volume. Septal thickening appeared in 5 patients at 4 weeks and in another 5 patients at 8 weeks. Parenchymal consolidation was detected in 1 patient at 4 weeks and in 5 patients at 8 weeks. HRCT using 160 mAs yield good quality images of subtle radiation induced injuries. The diagnostic validity of HRCT using lower than 160 mAs depends on the detail analyzed.

Adult↗
PubMed1995

Squamous cell carcinoma is highly sensitive to taxol, a possible new radiation sensitizer.

We studied the sensitivity of seven cell lines established from laryngeal carcinoma to the cytotoxic drug paclitaxel (Taxol) in vitro. In all four cell lines tested for growth inhibition, paclitaxel reduced growth at low concentrations, and in two cell lines growth was completely inhibited at a paclitaxel concentration of only 1 x 10(-8) M. Flow cytometric data showed a G2/M block in all seven cell lines after exposure to paclitaxel for 24 h at a concentration of 1 x 10(-8) M. This concentration is about one-one hundredth fold smaller than those measured in serum after a single intravenous dose of about 200 mg/m2. The high in vitro sensitivity of laryngeal cancer cell lines to paclitaxel,and the G2/M block suggest that the drug may potentially be used in conjunction with radiotherapy.

Carcinoma, Squamous Cell↗