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J Overgaard

Publications and source records attributed to J Overgaard.

At least 73 records · Page 4Linked to original sources
PubMed1998

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer.

The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median follow-up of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay. The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.

Adult↗
PubMed1998

Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting.

The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. Median length of follow-up was 15 years. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151) mm2. MVD was statistically significantly correlated with clinical stage (P < 0.0001) and histopathological grade (P < 0.0001). When dichotomized by the median counts, MVD was shown to be significantly associated (P = 0.0001) with disease-specific survival in the entire population as well as in the theoretically curable clinically localized subpopulation. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population (P = 0.0004), as well as in the clinically localized cancer population (P < 0.0001). These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.

Aged↗
PubMed1998

Characterization and radiosensitivity of fibroblasts derived from squamous cell carcinomas of the head and neck, and the surrounding oral mucosa.

Recently, extensive stromal fibroblast contamination has been reported in the modified Courtenay-Mills soft agar clonogenic assay for cellular in vitro radiosensitivity in tumour biopsies. The aim of the present study was to evaluate the hypothesis that an immunocytochemical analysis added to the modified Courtenay-Mills soft agar clonogenic assay provides a measure of both fibroblast and tumour cell radiosensitivity. Therefore, fibroblasts derived from squamous cell carcinomas of the head and neck, and from the surrounding oral mucosa were compared for immunocytochemistry, DNA ploidy, plating efficiency and surviving fraction of cells after a radiation dose of 2 Gy. The results of our study suggest that the stromal fibroblasts derived from tumour biopsies are representative of normal fibroblasts with respect to the characteristics examined using mucosal fibroblasts as normal controls.

Carcinoma, Squamous Cell↗
PubMed1998

The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma.

This study was designed to investigate the potential of shark cartilage extracts to inhibit the growth and metastatic spread of a murine solid tumour. The SCCVII carcinoma, implanted in the right rear foot of C3H mice, was used. Following tumour implantation, two different commercially available extracts of shark cartilage (Sharkilage and MIA Shark Powder) were dissolved in water and orally administered to the mice at doses that ranged from 5 to 100 mg per mouse. These injections were repeated on a daily basis for up to 25 days post-implantation of the primary tumour. Compared to non-drug-treated animals, daily administration of the shark cartilage extracts did not show any adverse toxicity (as measured by changes in body weight and lethality). More importantly, none of the shark cartilage doses tested had any retarding effect on the growth of the primary tumour, nor did they inhibit the development of metastases seen in the lungs of the tumour-bearing mice at autopsy. In conclusion, our results offer no support for the proposed use of shark cartilage extracts as an anti-cancer therapy.

Animals↗
PubMed1998

Radiosensitivity of normal fibroblasts from breast cancer patients assessed by the micronucleus and colony assays.

PURPOSE: To investigate whether radiation-induced micronucleus formation as expressed by the cytochalasin-blocked Mn-assay correlates with cellular radiosensitivity measured by a colony assay in primary fibroblast cultures from cancer patients. MATERIALS AND METHODS: Studies were made on skin fibroblasts from 36 breast cancer patients. The micronucleus assay was performed using treatment with cytochalasin-B to create binucleate cells. Response was scored in terms of the percentage of binucleate cells with micronuclei, also as the number of micronuclei per binucleate cell. The data were related to previously published results of cell survival measurements on these cell lines. RESULTS: Neither endpoint for micronucleus formation showed a correlation with radiosensitivity by the colony assay. The fraction of fibroblasts that reach mitosis without micronuclei also failed to correlate with cell survival. CONCLUSIONS: Among these primary fibroblast cell lines radiation-induced micronucleus formation was not associated with radiosensitivity as measured by a colony assay.

Adult↗
PubMed1998

Tumor cell proliferation and survival in patients with prostate cancer followed expectantly.

PURPOSE: Prostate cancers have different biological potentials, and aggressive tumors are difficult to identify when still localized. Tumor cell proliferation determined by MIB-1 expression has been suggested as an important predictor for outcome in several human cancers including the prostate. We test the possible prognostic value of tumor cellular proliferation in prostate cancer patients treated with no intent to cure. MATERIALS AND METHODS: Formalin fixed, paraffin embedded tumor tissue obtained at the time of diagnosis from 221 patients originating from a well known complete Danish prostate cancer population was immunohistochemically investigated. The tumor cell proliferation rate was determined using the MIB-1 antibody. Tumors were clinically localized in 57% of the patients. RESULTS: Tumor cell proliferation rate expressed by the MIB-1 score significantly correlated with tumor stage (p <0.001) and malignancy grade (p <0.001). The MIB-1 score, divided into low and high by the median value, showed significant association with disease specific survival in the entire study population (p <0.0001), as well as in the 125 patients suffering from clinically localized disease (p=0.018). Multivariate analyses showed that MIB-1 was a significant (p=0.0003) prognostic factor in the entire population, including advanced disease stages. However, in the theoretically curable clinically localized subpopulation MIB-1 was not significant (p=0.08) contrary to histopathological grade (p=0.02), erythrocyte sedimentation rate (p=0.02) and T classification (p=0.035). CONCLUSIONS: Prostate tumor cell proliferation, expressed by MIB-1 immunoreactivity, demonstrated significant association with disease specific survival. However, MIB-1 is a close alternative to histopathological grade in describing the natural history of clinically localized prostate cancer. The additional prognostic value and the practical consequence of tumor cell proliferation remain to be clarified.

Aged↗
PubMed1998

Molecular genetic analysis of easily accessible breast tumour DNA, purified from tissue left over from hormone receptor measurement.

In order to establish a large panel of normal and tumour DNA from primary breast cancer patients, we looked for a source of easily accessible, good quality breast tumour DNA. Following routine hormone receptor analysis at the hospital the leftover pellets contained the nuclei from the tumour tissue. We collected 670 pellets over a period of 2 1/4 years and isolated a large amount of DNA (on average 400 microg per pellet). To control the quality of this tumour DNA, we analysed 41 pellets and matching normal DNA for loss of heterozygosity (LOH), with 11 microsatellite markers along chromosome 17. This chromosome is well described for breast cancer. LOH is a sensitive method, requiring good quality and pure tumour DNA. Contamination with normal DNA will blur the results. We found a high rate of LOH, ranging from 33 to 74%, which is in agreement with other reports, and therefore recommend this rich source of breast tumour DNA for molecular biological analysis.

Breast Neoplasms↗
PubMed1998

Association between in vivo iododeoxyuridine labeling, MIB-1 expression, malignancy grade and clinical stage in human prostate cancer.

Large variability in the biological behavior of prostate cancer makes prognostic markers important. The extent of tumor cell proliferation has been suggested as an important predictor of clinical outcome. Fifty-five patients suspected of having or with previously diagnosed prostate cancer were labeled in vivo with IdUrd (a thymidine analogue incorporated into DNA in S-phase cells) by intravenous infusion before transurethral resection. IdUrd-labeled cells and MIB-1-positive cells were detected by immunohistochemistry. We found statistically significant associations between the tumor cell proliferation rates measured by in vivo IdUrd labeling and MIB-1 expression in formalin-fixed paraffin-embedded tumors. Good correlations were also found between S-phase fraction, MIB-1 expression, clinical stage and malignancy grade. These results make larger retrospective studies on archival tissue meaningful.

Aged↗
PubMed1998

Immunohistochemical determination of tumor angiogenesis measured by the maximal microvessel density in human prostate cancer.

Tumor growth beyond a certain size requires angiogenesis. Experimental evidence shows that once tumors leave the pre-angiogenic phenotype to become angiogenic, metastases often start to evolve. The aim of this study was to develop a reproducible immunohistochemical technique and method to characterize the neovascularization in archival prostate cancer tissue by quantifying the microvessel density (MVD). Archival tumor specimens from 64 consecutively diagnosed prostate cancer patients were immunostained for von Willebrand Factor (vWF), endothelial antigen and for CD31 combined with the use of different digestive enzymes (trypsin and pronase) and heating in a microwave oven. Both the mean and the maximal MVD, and the reproducibility of the method were estimated. Finally, the mean MVD, the maximal MVD, and clinical characteristics were correlated with the crude survival of the patient population. The immunohistochemical staining for vWF to measure the maximal MVD was found to be a reproducible method of characterizing the individual tumor. Both a univariate and a multivariate analysis demonstrated that the maximal MVD, in contrast to the mean MVD, was significantly associated with survival in prostate cancer patients. We conclude that evaluation of angiogenesis by immunostaining the endothelial cells for vWF measured by the MVD in the most vascularized areas of the tumor is a reproducible method of characterizing the individual prostate tumor. Maximal MVD proved to be an independent prognostic parameter useful in conjunction with other known prognostic markers in human prostate cancer.

Aged↗
PubMed1998

Techniques to assess the oxygenation of human tumors. State of the art.

There is now good evidence that the oxygenation status of certain types of human tumors plays an important role in determining the response of those tumors to therapy. More recent evidence suggests that oxygenation status can also influence local tumor aggressiveness and metastatic spread. As a consequence significant effort is being made to find relevant methods for assessing tumor oxygenation status and thereby allowing for the selection of patients that should be given additional/alternative therapies to improve response. In this paper we will review the importance of tumor oxygenation status and discuss the potential clinical methods for monitoring that are currently available.

Animals↗
PubMed1997

Steepness of the dose-response curve as a function of volume in an experimental tumor irradiated under ambient or hypoxic conditions.

PURPOSE: Radiation dose-response curves play a fundamental role in the attempts to optimize radiotherapy, and it is a major task in clinical and experimental radiation research to characterize and quantify the factors that determine the position and shape of dose-response curves. A convenient measure of the steepness of radiation dose-response curves is the normalized dose-response gradient, gamma, which represents the increase in response, in percentage points, for a 1% increase in dose. Theoretically, the normalized dose-response gradient should increase with increasing clonogenic cell number or, assuming a constant clonogen density, with increasing tumor volume. The aim of this study was to test this hypothesis over a range of tumor volumes and to study how this relationship is affected by heterogeneity in tumor oxygenation. METHODS AND MATERIALS: A C3H mouse mammary carcinoma implanted in the feet of female CDF1 mice was used. Groups of tumors with various volumes were irradiated with single graded radiation doses in air or after making them artificially hypoxic by clamping. The end point used was tumor control defined as complete absence of a macroscopic relapse within 90 days after irradiation. A Poisson dose-response model was assumed to describe tumor control probability in each volume group. The dose needed to control 37% of the tumors (D37) and the normalized dose-response gradient at this dose (gamma37) were estimated by the maximum likelihood method. In another group of animals with tumors in the same volume range, oxygenation status was assessed by a polarographic needle electrode. The percentage of pO2 values <3 mmHg was selected to represent the relative volume of the tumor with radiobiological hypoxia. RESULTS: The D37 values increased as a function of tumor volume under both clamped and ambient conditions. For tumors irradiated under clamped conditions, gamma37 increased with increasing tumor volume throughout the range of volumes studied. However, for tumors irradiated under ambient conditions, there was an initial increase in gamma37 with tumor volume up to 100 mm3 with no further increase beyond that volume. As the tumor volume increased, both the level of hypoxia and the tumor-to-tumor heterogeneity in that level increased. CONCLUSIONS: This study has confirmed the hypothesis that gamma37 increases with increasing tumor volume when tumors are irradiated under clamped condition. The increased heterogeneity of the hypoxic volume fraction with increasing tumor volume could explain why the steepness of the dose-response curve did not increase with increasing tumor volume when irradiation was done under ambient condition.

Animals↗
PubMed1997

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗
PubMed1997

The natural history of prostate carcinoma based on a Danish population treated with no intent to cure.

BACKGROUND: Prostate carcinoma is one of the most commonly diagnosed cancers among Western males. In Denmark, the traditional therapeutic approach to prostate carcinoma regardless of tumor stage has been limited to palliative procedures. This conservative approach combined with a complete cancer and personal registration in Denmark provides an opportunity to describe the still debatable natural history of prostate carcinoma. METHODS: The data, originating from hospital records and death certificates, included a complete prostate carcinoma population residing in Aarhus County diagnosed between January 1, 1979 and December 31, 1983. The patients were retrospectively followed from diagnosis until death (median length of follow-up, 15.0 years). RESULTS: The total number of 719 new cases of prostate cancer were diagnosed without any screening programs. Forty-five percent of patients were diagnosed incidentally, and 31% of all patients had organ-confined disease (T1a-T2, Nx, M0). The disease specific survival rates at 1, 5, and 10 years were 80%, 38%, and 17%, respectively, and 62% of the patients died primarily of prostate carcinoma. A multivariate analysis demonstrated a statistically significant relationship between disease specific death and T classification, tumor differentiation, and erythrocyte sedimentation rate at diagnosis. CONCLUSIONS: Prostate carcinoma patients have a poor survival and the majority of the patients diagnosed suffer and die from their disease rather than with it. Nevertheless, approximately one-third of patients neither suffer nor die from their disease. Therefore, the development of prognostic markers to improve the identification of patients who will benefit from early aggressive treatment is important. [See editorial on pages 827-33, this issue.]

Aged↗
PubMed1997

[Prostatic cancer: an expensive dilemma].

The aim of this retrospective study is to describe the increasing human suffering as well as the Health-Service costs in Denmark due to palliative treatment of prostate cancer, at a time characterized by a still more aggressive therapeutic approach to prostate cancer but without effective prognostic factors. All 719 prostate cancer patients with residence in Aarhus County diagnosed over a five year period (01.01.79-31.12.83) identified by the Danish Cancer Registry were registered. The data originates from hospital case records and Death Certificates. The national incidence of prostate cancer has increased dramatically even without screening programs. These patients have a considerable need for hospital care and palliative treatment of their cancer disease from the time of diagnosis until death. Based on these data the Danish hospital expenses in 1995 due to palliative treatment of prostate cancer were calculated to amount 0.72% of the total National Health Budget.

Aged↗
PubMed1997

[Centralized follow-up of patients treated for head and neck cancer].

In a prospective study, the value of the clinical follow-up after treatment for head and neck cancer has been assessed. A total of 407 visits in 377 patients were recorded during a three month period in 1993 at the two major radiotherapy departments in Denmark. The results showed that 61% of follow-up visits included one or more problems either related to treatment morbidity or tumour recurrence. About 50% of all visits included treatment related normal tissue problems, and 30% had problems that required intervention. Although the majority of problems occurred within a few years after treatment, 47% of patients at three to four years observation time still had one or more problems. A total of 34 new tumour recurrences were found in the period, and of these 11 (32%) were asymptomatic. It is concluded that head and neck cancer patients have both tumour and normal tissue problems several years after the end of treatment. Since effective salvage treatment improves local control significantly, early detection of possible recurrence is important. A follow-up period of four to five years is recommended-preferably by qualified experts in the management of both recurrent disease and treatment morbidity.

Centralized Hospital Services↗
PubMed1997

Nicotinamide as a radiosensitizer in tumours and normal tissues: the importance of drug dose and timing.

BACKGROUND AND PURPOSE: Nicotinamide is a radiation sensitizer currently undergoing clinical testing. This was an experimental study to determine the importance of drug dose and time interval between drug administration and irradiation for radiosensitization. MATERIALS AND METHODS: Nicotinamide (50-500 mg/kg) was injected intraperitoneally into CDFI or C3H mice and drug plasma pharmacokinetics were determined by HPLC. Radiosensitization was measured in tumours and normal tissues after local irradiation. The tumours were a C3H mammary carcinoma, the KHT sarcoma and the SCCVII carcinoma. Tumour response was assessed using either growth delay (C3H) or clonogenic survival (KHT/SCCVII). Normal tissue toxicities evaluated included early responding skin (development of moist desquamation of the foot) and late responding bladder (reservoir function estimated by cystometry) and lung (ventilation rate measured by plethysmography). RESULTS: All nicotinamide peak plasma concentrations were seen within 30 min after injection. Irradiating tumours at peak times resulted in enhancement ratios (ERs) of 1.27 (C3H), 1.75 (KHT) and 1.45 (SCCVII) with high nicotinamide doses and 1.27 (C3H), 1.28 (KHT) and 1.36 (SCCVII) after giving clinically relevant doses (100-200 mg/kg). Lower ERs were observed when the time interval between drug injection and irradiation was increased beyond the peak time. Irradiating normal tissues at peak times after injecting 100-200 mg/kg nicotinamide gave ERs of 1.20 (skin), 0.90 (bladder) and 1.02 (lung). CONCLUSIONS: Clinically achievable doses of nicotinamide will enhance tumour radiation damage while having minimal effects in normal tissues, but for the best tumour effect radiation should be given at the time of peak plasma drug concentrations.

Animals↗