Search PubMed⌕ Search

Biomedical subjects

M Flentje

Publications and source records attributed to M Flentje.

At least 109 records · Page 6Linked to original sources
PubMed1994

Evaluation of AgNOR and Ki-67 antigen as cell kinetic parameters in oral dysplasias and carcinomas.

The mean numbers of argyrophil nucleolar organizer regions (AgNORs) and the Ki-67 antigen expression as proposed cell kinetic parameters were evaluated in 80 biopsies of suspected oral dysplasias and 40 probes of oral squamous cell carcinomas. No statistical relationship was found between the mean numbers of AgNORs and nucleoli per cell. However, the mean numbers of AgNORs per nucleus and the percentages of cells in S-phase as determined by flow cytometry show a correlation. Related to the histological degree of dysplasia, both AgNOR counts and percentages of cells in S-phase reveal a similar pattern of distribution. With values widely spread, the percentages of Ki-67 positive cells increase according to the histopathological degree of malignancy. Also, a correlation between the percentages of Ki-67 positive cells and cells in S-phase was evident. Therefore, both the AgNOR counts and the Ki-67 antigen are considered to be valuable tools for cell kinetic reference and can be considered supplementary methods to flow cytometry in diagnosis and therapy of oral cancer.

Carcinoma, Squamous Cell↗
PubMed1994

[Effect of a cisplatin-5-fluorouracil combination chemotherapy on malignant transformation of the epithelium of mouth mucosa].

In a prospective study we examined the effect of preoperative chemotherapy with cisplatinum and 5-fluorouracil (5-FU) in 40 patients with advanced carcinoma of the oral cavity. Histopathologic grading, cell kinetics and immunohistochemical parameters of the mucosa were determined at two different locations. Prior to therapy, histologic dysplasias in the mucosa "close" to the tumor were observed in 75 percent of the patients. Dysplastic changes of the mucosa "far" from tumor were also found in more than one-third of the patients. Our results show that more advanced dysplasias improve only temporarily under the influence of preoperative systemic chemotherapy. Moreover, new dysplasias appearing during chemotherapy and persisting after its termination are probably induced. The results point to a possible carcinogenic potential of the combined chemotherapy schema used.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Results of radiotherapy and combined modality treatment in early stage high grade non-Hodgkin's lymphoma.

PURPOSE: In combined modality treatment of early stage, high grade non-Hodgkin's lymphoma disease status after initial chemotherapy was analyzed to evaluate the impact of remission status on survival. Analysis of relapse patterns was performed to assess efficacy of radiation doses and volume. PATIENTS AND METHODS: Fifty-four patients with early stage high grade non-Hodgkin's lymphoma were treated with radiotherapy alone or with initial chemotherapy followed by involved field irradiation. Overall survival, relapse-free survival and relapse patterns were analyzed. RESULTS: In patients treated with radiotherapy alone (stage I n = 15, stage II n = 8) overall survival rate was 69%, relapse-free survival was 35% at 3 years. Patients achieving combined modality treatment (stage I n = 5, stage II n = 26) showed an actuarial 3 year overall survival of 78%, relapse-free survival was 62%. Complete remission status after chemotherapy was an important factor for durable disease control. Those patients, who achieved complete remission after chemotherapy showed an actuarial relapse-free survival of 75% at 3 years. Patients with partial remission or progressive disease after chemotherapy had a poor outcome (relapse-free survival 35%). Analysis of the first manifestation of lymphoma progression after radiotherapy in relation to the treatment portals demonstrated radiotherapy to be highly effective in achieving local control. Only 8% of recurrences occurred within the irradiated volume. 56% of failures were found in non-contiguous sites to the former radiation portals. CONCLUSION: This analysis suggests that effective chemotherapy in combination with involved field radiotherapy in CS I (with risk factors) and especially in CS II patients is necessary to control extension of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1994

Tangential breast irradiation: comparison of patient positioning and beam parameters after planning investigation at a CT scanner and a simulator with CT option.

PURPOSE: A prerequisite for the exact planning of a radiotherapy is the precise accordance of the patient positioning during the planning CT and the therapy simulation. How far possible differences between patient set-up during the planning CT at a therapy simulator with CT option or a conventional CT influence the planned dose distribution is investigated by the example of the tangential breast irradiation. PATIENTS AND METHODS: In 18 patients transverse sections for treatment planning of tangential breast irradiation were made both using a diagnostic CT scanner and a therapy simulator with CT option. For patient positioning the patient outlines were compared. Furthermore, the treatment plans which were based independently on both transverse sections were compared. RESULTS: In the mean deviations of 1 resp. 0 mm (SD = 7 resp. 8 mm) between the ventral and lateral outlines of the breast were found. The mean breast diameter between the Z-points was 5 mm wider in the simulator CT based plans (SD = 14 mm). The field width was 6 mm wider (SD = 8 mm), the beam angle 1 degree steeper (SD = 4 degrees). The calculated monitor units differed 1% (SD = 6%). None of the differences between measured parameters reached statistical significance. A significant correlation was only seen for the interrelated contours (anteroposterior and lateral diameters). CONCLUSION: The results of this investigation show no difference between treatment set-up and treatment planning using information of a CT scanner or a simulator with CT option for tangential breast irradiation.

Breast Neoplasms↗
PubMed1994

Flow cytometric measurement of proliferating cell nuclear antigen (PCNA) in solid tumors.

PURPOSE: The importance of cell kinetic parameters for prognosis and therapeutic strategy is widely accepted in oncology. Repopulation is a major problem in radiotherapy of head and neck tumors. Various assays exist for measuring the proliferation characteristics of individual tumors. However, the existing methods have several drawbacks. MATERIALS AND METHODS: PCNA (proliferating cell nuclear antigen) is expressed in a cell cycle dependent manner. There is a DNA-bound, S-phase specific fraction and a nucleoplasmatic, extractable fraction, which is detectable in all phases except G0. We describe a method for simultaneous measurement of PCNA and DNA in solid tumors using flow cytometry. The assay was applied to three different sublines (AT1, HI, H) of the Dunning rat prostate tumor R3327 and biopsies of twelve human head and neck squamous cell carcinomas. The PCNA-assay was compared to the standard BrdUrd-assay (bromodeoxyuridine) by simultaneous measurement of PCNA and BrdUrd in the animal tumors. RESULTS: Percentages of PCNA-positive cells of 29 +/- 4% (AT1), 25 +/- 7% (HI) and 3 +/- 1% (H) were calculated for the animal tumors with good rank correlation with the BrdUrd-LI. The PCNA-indices for human tumors ranged from 5 +/- 1% up to 70 +/- 9%. CONCLUSION: The flow cytometric PCNA-assay can be applied to standard biopsy material and yields reproducible results with an intratumor variation of about 5% which is small compared to the wide range of PCNA-indices in our series. The method may enhance the pretherapeutic assessment of tumor proliferation kinetics.

Animals↗
PubMed1993

Renal tolerance to nonhomogenous irradiation: comparison of observed effects to predictions of normal tissue complication probability from different biophysical models.

PURPOSE: A patient series was analyzed retrospectively as an example of whole organ kidney irradiation with an inhomogenous dose distribution to test the validity of biophysical models predicting normal tissue tolerance to radiotherapy. METHODS AND MATERIAL: From 1969 to 1984, 142 patients with seminoma were irradiated to the paraaortic region using predominantly rotational techniques which led to variable but partly substantial exposure of the kidneys. Median follow up was 8.2 (2.1-21) years and actuarial 10-year survival (Kaplan-Meier estimate) 82.8%. For all patients 3-dimensional dose distributions were reconstructed and normal tissue complication probabilities for the kidneys were generated from the individual dose volume histograms. To this respect different published biophysical algorithms had been introduced in a 3-dimensional-treatment planning system. RESULTS: In seven patients clinical manifest renal impairment was observed (interval 10-84 months). An excellent agreement between predicted and observed effects was seen for two volume-oriented models, whereas complications were overestimated by an algorithm based on critical element assumptions. CONCLUSIONS: Should these observations be confirmed and extended to different types of organs corresponding algorithms could easily be integrated into 3-dimensional-treatment planning programs and be used for comparing and judging different plans on a more biologically oriented basis.

Adult↗
PubMed1993

Increased dose-rate effect in V79-multicellular aggregates (spheroids). Relation to initial DNA lesions and repair.

Survival of exponentially growing V79 monolayer cells was measured after irradiation at low dose-rate (up to 1.1 Gy/h) and at high dose-rate (2.5 Gy/min) and compared to corresponding survival data of V79 spheroid cells. The so-called contact effect, the increased radioresistance of cells irradiated in spheroids, was expressed to a greater extent with low dose-rate exposure. Lesion fixation by hypertonic treatment was more pronounced in spheroid versus monolayer cells and abolished the contact effect. The reduced radiosensitivity of V79 spheroid cells could not be related to a reduced number of initial DNA lesions or a higher capacity to rejoin DNA breaks (measured by neutral elution). These findings suggest that the ratio of lesion repair to fixation/misrepair may differ between cells from spheroids and monolayer culture thus influencing the response of cells to dose-rate changes differentially.

Animals↗
PubMed1993

Lethality of heavy ion-induced DNA double-strand breaks in mammalian cells.

Cell killing and the production of DNA double-strand breaks (dsbs) were measured in parallel for V79 cells and a human tumour cell line (Caski) following exposure to radiations of differing linear energy transfer (LET) including accelerated heavy ions. Dsb induction was assessed by neutral filter elution (pH 7.4) and elution from agarose plugs in pulsed-field electrophoresis. The elution data were consistent with linear lesion induction and allowed to derive dsb yields or production cross-sections (sigma dsb), respectively. Both cell lines as well as the two elution approaches gave comparable results. sigma dsb was found to rise up to the heaviest ions used (LET = 11,500 keV/microns) but relative biological effectiveness was always smaller than unity. Slopes of the exponential survival curves (final slope with 60Co-radiation) were normalized to the respective dsb yields and allowed to calculate the relative lethality per induced dsb. This parameter increased with LET up to about 300 keV/microns followed by a steep decline for the very heavy ions. The extent of dsb rejoining was concomitantly reduced with ionization density.

Cell Death↗
PubMed1993

Sensitivity of neutral filter elution but not PFGE can be modified by non-dsb chromatin damage.

Hamster V79 fibroblast cells and human squamous carcinoma cells (Caski) were exposed to 60Co radiation and DNA double-strand break (dsb) induction was analysed by DNA elution at neutral pH from polycarbonate filter or out of an agarose matrix in pulsed-field electrophoresis (PFGE). While dsb yields were equal for the two cell lines (using 125-iodine calibration) a reduced responsiveness of filter elution was found for V79 versus Caski cells. This difference could be abolished when additional single-strand breaks (ssb) were introduced by an incubation at 10(-4) M H2O2 for up to 40 min that itself did not give a response in neutral elution. No such lack of specificity for the detection of dsb was seen in electrophoretic elution where also the influence of peroxide incubation was absent. The presumed potential of ssb to modify dsb detection was paralleled by the kinetics of dsb rejoining: a pronounced transient increase of DNA elution from filters was observed for V79 cells (less prominent with Caski cells) at 15-40 which is thought to reflect the occurrence of secondary ssb from incisions during base damage repair. Rejoining measured by PFGE did not show this behaviour. The results suggest that ssb may aid decondensation of the chromatin during lysis of cells required for an efficient release of dsb fragments when supported on filters, but which depends on cell type and is less critical in electrophoretic elution out of an agarose matrix. This involvement of ssb in the neutral filter elution assay appears to be contrary to published data obtained with different experimental systems. The finding of an increase of DNA elution from filters due to hyperthermia at 45 degrees C is also taken to indicate an involvement of non-dsb chromatin damage in the response of filter elution at neutral pH with V79 but not with Caski cells.

Animals↗
PubMed1993

Measurement of the proliferative activity of three different sublines of the Dunning rat prostate tumor R3327.

The development of the BrdUrd assay has greatly facilitated the measurement of proliferation in both human and experimental tumors. The potential doubling time (Tpot) was reported to be the most promising parameter to serve as a predictive assay to select patients for new treatment modalities such as accelerated fractionation and fast neutrons. We compared flow cytometry and immunochemistry applied to three sublines of the Dunning rat prostate tumor with differing differentiation. The anaplastic R3327-AT subline has a labeling index (LI) of 7 +/- 0.5% and 8.8 +/- 3.7 measured with flow cytometry and histology respectively, S-phase duration (Ts) of 8 h, a Tpot of 4.7 days and a cell loss factors (phi) of 15%. Proliferating cells are homogeneously distributed. The moderately well differentiated R3327-HI subline shows a LI of 5% (flow cytometry 5 +/- 0.5%, immunohistochemistry 5 +/- 2%), Ts of 10.7 h, Tpot of 8.9 days and phi of 10%. The well differentiated subline R3327-H has two cell populations (DNA-index 1.6) and a labeling index of 3.7 +/- 0.5% measured with flow cytometry and 2.2 +/- 0.4% with immunochemistry.

Animals↗
PubMed1993

Integration of coronal magnetic resonance imaging (MRI) into radiation treatment planning of mediastinal tumors.

Influence of MR-imaging on definition of treatment volume was studied prospectively in 43 patients undergoing radiotherapy for mediastinal malignancy (twelve Morbus Hodgkin, four non-Hodgkin-lymphoma, 26 lung cancer, one nephroblastoma). Conventional treatment planning using a simulator and all available information from axial CT-scanning and posterior-anterior and lateral radiographs was compared to a MRI-assisted procedure. Contours from coronary MR-sections acquired in treatment position were superposed onto the simulator radiograph using a subtrascope (MRI-simulation). MR-imaging using T1-weighted sequences resulted in excellent delineation of tumor masses from mediastinal fat, airways and vascular structures. The high soft tissue contrast allowed an exact and reproducible transfer of tumor contours onto the simulator radiograph. This led to changes in field configuration in 11/43 patients concerning mainly tumor extension infracarinally and in the caudal parts of the lung hili. Superiority of MRI-assisted simulation was noted as usefulness of axial CT-scanning to delineate margins was compromised in these areas by partial volume effects of tangentially represented structures and suboptimal contrasted vascular spaces.

Carcinoma, Bronchogenic↗
PubMed1992

Additive effects of cisplatin and radiation in human tumor cells under oxic conditions.

The interaction of cisplatin and irradiation was studied in vitro in four human cell lines. Additive effects were observed for the combination given either simultaneously or sequentially. No influence on recovery was seen in split-dose experiments. It is concluded that radiosensitization cannot be presumed in every clinical setting of combined treatment with radiation and cisplatin.

Cell Survival↗
PubMed1992

Adeno-associated virus sensitizes HeLa cell tumors to gamma rays.

Infection with the helper virus-dependent human parvovirus adeno-associated virus (AAV) is known to interfere with cellular transformation in vitro and oncogenesis in vivo. Here we report on sensitization to gamma irradiation by AAV infection of cells in culture and of tumors established from HeLa cells grafted into immunodeficient (nude) mice: infection of HeLa cells with AAV type 2 enhanced cell killing and reduced plating efficiency after irradiation compared with uninfected cells. Similarly, HeLa cell tumors in nude mice displayed a reduced growth rate and were more sensitive to gamma irradiation when the animals were infected with AAV type 2 prior to or after tumor cell inoculation. Since no pathogenicity is known for AAV, the ability of this virus to render radiotherapy of human tumor cells more efficient may up open novel approaches in cancer treatment.

Animals↗
PubMed1991

[Effects of lonidamine alone or in combination with radiotherapy on survival and metabolism in human and rodent cell lines].

In vitro investigations on the combined effect of radiation and Lonidamine in one human (LXI) and two rodent cell lines (3T3, V79) showed not a clear radiosensitizing effect. Especially no inhibiting influence on the repair of potentially lethal damage of V79 cells was found. Incubation at lower pH values (6.7 to 6.9) caused no increasing effects. Lonidamine induced damage on the mitochondrial dehydrogenase-system was quantitatively measured with a modified MTT-assay.

Adenocarcinoma↗
PubMed1991

[Radiotherapy of laryngeal cancer].

The specific anatomical and biological situation of larynx cancer gives radiotherapy an important part in primary management of this tumour. In early stages (T1, T2) surgery and radiotherapy achieve equivalent survival, but with the latter, normal speech can be maintained in most cases. Treatment techniques for supraglottic and glottic cancers differ due to their different risk of lymphatic spread. Local relapse is between 10 and 30% depending on extent and localisation of the tumour, but 3/4 of these patients can be salvaged by surgery. In advanced laryngeal cancer a combination of surgery and irradiation is the mainstay of treatment. New radiation options, especially hyperfractionated irradiation, seem to achieve local control even in advanced disease. The good results of local treatment expose the considerable risk of second malignancies (particularly all lung cancer) in this group of patients.

Glottis↗
PubMed1991

[Additive effects of carboplatin (CBDCA) and Co-60 gamma rays in human tumor cells in vitro].

In vitro investigations on the combination effect of radiation and carboplatin (CBDCA) in three human cell lines (HeLa, MRI-186 Caski) show purely additive effects. Study of the molecular lesions gave considerable differences in the time course of repair of radiation induced DNA-double strand-breaks and of formation of DNA-crosslinks by carboplatin. However, sequential treatment with intervals of up to +/- 24 hours resulted also in an additive effect. In the experimental systems studied, a true radiosensitization was not demonstrated.

Adenocarcinoma↗
PubMed1990

Evaluation of recurrent bronchogenic carcinoma by computed tomography.

Thirty-five patients with strongly suspected recurrent tumor of the lung and definitely positive computed tomography (CT) scan were reviewed. The patients had undergone surgery (group A, n = 17) or radiation therapy (group B, n = 18). TNM-staging of lung cancer in both groups revealed similar results. Small cell carcinoma (P less than 0.05), central tumors (P less than 0.003), and elderly patients (P less than 0.05) were more often found in group B. Disease-free interval was longer in patients with tumor resection (45.5 v 11.7 months, P less than 0.007) and depended on T-stage in irradiated cases (P less than 0.05). Local recurrence with or without mediastinal lymph node involvement occurred in all irradiated patients; 3 of 16 surgical patients showed isolated mediastinal lymph node enlargement without tumor relapse (not seen by plain chest roentgenographs). Plain films failed to detect nearly 20% of the space-occupying lesions, which could easily be identified by CT. In one patient the suspected tumor recurrence turned out to be a tuberculous infiltration. A second lung cancer (no tumor recurrence) was pathohistologically assumed in three of the resected cases with an interval from 10-181 mo after surgery. On the basis of these findings, CT-monitoring can be recommended when the patient is resected for cure. Some patients will benefit by an early diagnosis of a local-regional tumor recurrence when the time until the necessary secondary treatment may be shortened. Long-term survival may be achieved in a small group of these patients.

Carcinoma, Bronchogenic↗