PubMed Health⌕ Search

Biomedical subjects

N Wilking

Publications and source records attributed to N Wilking.

At least 37 records · Page 2Linked to original sources
PubMed1997

Gastrointestinal Tract Cancer Liaison Office: an attempt to organise clinical research in Europe.

The Gastrointestinal Tract Cancer Liaison Office (GITCLO) was developed in an attempt to organise the increasing body of clinical research in gastrointestinal tumours in Europe. This paper represents an analysis, by tumour localisation, of the trials collected for the second edition of the GITCLO booklet. The list of cooperative groups, chairmen and study coordinators is given with their respective telephone and telefax numbers. A total of 84 trials were collected, conducted by 46 co-operative groups in 14 countries. For each organ and stage of disease, a summary of concepts investigated is given with the references of the study co-ordinator. Obviously, too many questions are raised at the same time. In colorectal cancer, for example, a total of 41 trials exploring 22 concepts are currently open for patients' registration. We hope that the present attempt to clarify the situation of clinical research in the field of gastrointestinal cancers in Europe will speed up therapeutic progress in the best interest of the patients.

Colorectal Neoplasms↗
PubMed1997

Tamoxifen and secondary tumours. An update.

The nonsteroidal antiestrogen tamoxifen is the most widely used anticancer drug. In women with breast cancer, adjuvant therapy with tamoxifen reduces relapse and improves overall survival. In advanced breast cancer, the response rate is more than 50% in hormonal dependent disease. In women treated with adjuvant tamoxifen the incidence of new primary breast cancers is decreased. This latter observation has led to the initiation of prevention trials. In 1989 the first report from a large prospective randomised trial showed a significant increase of endometrial carcinoma among women treated with adjuvant tamoxifen. This effect may be linked to the somewhat paradoxical estrogenic properties of tamoxifen. The endometrial effects should be considered in the long term use of tamoxifen, and should also be taken into account in the evaluation of the prevention trials. Animal data indicate that tamoxifen can induce tumours in other organ systems, for example the liver, but no increase in primary liver cancer has been reported from the randomised trials. In some of these trials an increase in other gastrointestinal cancers (e.g. colon and gastric carcinoma) has been observed. The mechanism behind this may be different from that of the endometrium. In animal systems, tamoxifen has shown to induce DNA damage, with formation of DNA adducts. The risk of secondary gastrointestinal cancer needs to be further evaluated. The adverse effects of tamoxifen have led to the development of new anti-estrogenic drugs and other estrogen reducing agents (e.g. aromatase inhibitors).

Animals↗
PubMed1996

Subcutaneous metastasis from an ovarian carcinoma disappeared following tamoxifen therapy.

In a 78-year-old woman who had been treated for a breast cancer, a subcutaneous metastasis was diagnosed. This metastasis disappeared following a 3-months' treatment with tamoxifen. Only then was the primary tumour found to be ovarian carcinoma rather than a mammary one. This and other reports indicate that hormonal agents may also be considered as a third line of treatment in ovarian carcinoma.

Aged↗
PubMed1996

A phase II study in advanced breast cancer: ZD1694 ('Tomudex') a novel direct and specific thymidylate synthase inhibitor.

ZD1694 ('Tomudex'), a novel, direct and specific thymidylate synthase (TS) inhibitor, was developed in a collaborative research programme between Zeneca Pharmaceuticals and the Institute of Cancer Research (UK) and entered clinical trials in 1991; phase II studies began in 1992, using 3.0 mg m-2 every 3 weeks as a short 15 min infusion. Forty-six patients entered a phase II study of ZD1694 in advanced breast cancer. A total of 74% of patients had received prior systemic therapy (either as adjuvant cytotoxic or hormonal therapy or hormone therapy for advanced disease); 39% had received prior adjuvant cytotoxic chemotherapy. All patients had measurable disease and 50% had liver metastases. In all 43 patients were evaluable for response. Of these patients 26% achieved complete (CR) or partial response (PR) (95% Cl 14-42%). A response rate of 44% was seen in liver metastases. Two patients achieved CR of 265 and 301 days' duration respectively, one in locoregional disease, and one in liver metastases. The most common grade 3/4 adverse events were nausea and vomiting (11%), diarrhoea (11%) and leucopenia (20%). Grade 3/4, self-limited and reversible increases in transaminases were seen in 22% of patients. ZD1694 has useful single agent activity in patients with hormone-refractory advanced breast cancer, comparable with that reported for other anti-metabolites, with acceptable tolerability.

Adult↗
PubMed1996

Inhibition of tumor cell growth by monoterpenes in vitro: evidence of a Ras-independent mechanism of action.

(+)-Limonene (d-limonene) and related monoterpenes show chemopreventive activity against rodent mammary carcinoma and inhibit the growth of cancer cells in vitro. One suggested mechanism for the anti-tumorigenic effect of (+)-limonene is inhibition of the post-translational isoprenylation of growth controlling Ras oncoproteins. We have here examined the growth inhibitory effect of (+)-limonene and other related monoterpenes on PANC-1 pancreas carcinoma cells (carrying a K-ras mutation) and on 12V-H-ras-transformed rat fibroblasts. (+)- and (-)-perillyl alcohol, 7-methyl-perillyl alcohol, (+)-limonene oxide and (+)-perillic acid methyl ester were all found to efficiently inhibit cell growth at 1 mM, whereas (+)-limonene caused an approximately 50% growth reduction at 5 mM. Whereas BZA-5B, an inhibitor of Ras farnesyl transferase, was found to induce morphological reversion of 12V-H-ras-transformed cells, (+)-perillyl alcohol and (+)-limonene did not induce reversion. Furthermore, monoterpenes did not decrease MAP kinase enzyme activity or collagenase promoter activity in PANC-1 cells, two functions known to be down-stream from Ras. We conclude that although effective in inhibiting the growth of tumor cells harboring activated ras oncogenes, limonene and (+)-perillyl alcohol are unlikely to act by inhibiting Ras function.

Alkyl and Aryl Transferases↗
PubMed1995

Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen is being increasingly used for the treatment of breast cancer and is undergoing study for the primary prevention of breast cancer. However, concerns have been raised that the drug may increase the incidence of new primary malignancies, such as endometrial, liver, and colorectal cancers. PURPOSE: Our goal was to assess the carcinogenic risks associated with long-term use of tamoxifen in women with early stage breast cancer. METHODS: The incidence of new primary cancers among 2729 women participants of the Stockholm Trial was determined at a median follow-up of 9 years. In this trial, after primary surgery, postmenopausal patients aged less than 71 years with unilateral invasive breast cancer were randomly allocated to receive either 2 years of adjuvant tamoxifen (40 mg daily) or no adjuvant endocrine therapy. Information on second cancers was obtained by retrospective linkage to the Swedish Cancer Registry. To increase statistical power, a joint analysis of the incidence of endometrial and gastrointestinal cancers was performed in the following three major studies in Scandinavia evaluating adjuvant tamoxifen therapy: the Stockholm Trial, the Danish Breast Cancer Group Trial, and the South-Swedish Trial. These studies included a total of 4914 patients with a median follow-up of 8-9 years. All P values were calculated from two-tailed tests of statistical significance. RESULTS: In the Stockholm Trial, there was a statistically significant (P = .008) reduction in the incidence of second primary cancers in the contralateral breast among the tamoxifen-treated patients. However, there was a nearly sixfold increase in endometrial cancers (P < .001) and a threefold increase in gastrointestinal cancers in the tamoxifen-treated patients. The results of the joint studies showed a statistically significant increase in endometrial cancers among the tamoxifen-treated patients (relative risk [RR] = 4.1; 95% confidence interval [CI] = 1.9-8.9). There was also an excess of gastrointestinal cancers associated with tamoxifen. Most of this excess involved colorectal cancers (RR = 1.9; 95% CI = 1.1-3.3) and stomach cancer (RR = 3.2; 95% CI = 0.9-11.7). There was no substantial increase in any other type of gastrointestinal cancer (e.g., liver cancer) among the tamoxifen-treated patients. CONCLUSION: The endometrium and gastrointestinal organs may be target sites for tamoxifen-induced carcinogenesis in humans. IMPLICATIONS: The increased incidence of colorectal and stomach cancers reported here should be regarded as tentative until supported by long-term data from a larger number of tamoxifen trials. Also, appropriate surveillance of cancer incidence is warranted for the protection of participants enrolled in current tamoxifen chemoprevention trials.

Aged↗
PubMed1995

The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group.

BACKGROUND: From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. METHODS: Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. RESULTS: At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 "curatively" operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). CONCLUSIONS: Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group.

Adult↗
PubMed1995

[High-dose chemotherapy in breast cancer. Promising results in combination with stem cell support].

Thirty-three women with breast cancer have undergone high dose chemotherapy with autologous stem cell support at Huddinge Hospital. Twenty-eight patients had stage IV disease while five patients had disease stage II or III with involvement of > 10 axillary lymph nodes. Patients who received peripheral stem cells had a shorter duration of neutropenia than patients who received autologous bone marrow (p < 0.001). The transplant related mortality was 3 per cent. The calculated progression free survival was 39 per cent at 24 months after high dose therapy in women with stage IV chemosensitive breast cancer. Patients who got a complete remission after standard dose chemotherapy had a better survival rate than patients who got a partial remission. All women with refractory disease progressed within five months from therapy. Four out of five patients with disease stage II or III are progression free with the longest follow-up time of 46 months. High dose chemotherapy with stem cell support can be given with acceptable toxicity. The follow-up time is short but the results are promising, in particular for women who obtain a complete remission before the high dose therapy starts.

Adult↗
PubMed1995

Influence of prior and subsequent pregnancy on breast cancer prognosis.

PURPOSE AND METHODS: The prognostic influence of pregnancies 5 years before (n = 173) and after (n = 50) breast cancer diagnosis was investigated in 2,119 women less than 50 years of age with a primary operable breast cancer. The main end point was distant metastasis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In the analyses of the effect of pregnancy after diagnosis of breast cancer, a Cox model with a time-dependent covariate was applied. RESULTS: Women with a pregnancy before diagnosis had slightly larger tumors than the control group. However, they did not differ with respect to nodal status and estrogen receptor (ER) status. There was no evidence that women with a pregnancy during the 5-year period preceding breast cancer diagnosis had a worse prognosis compared with women without pregnancy during the same period. Similarly, there was no evidence that women with a pregnancy after breast cancer diagnosis had a worse prognosis. CONCLUSION: The hormonal changes associated with pregnancy thus seem to have little, if any, influence on the prognosis of breast cancer. In the present study, at least, there was no indication of a worse prognosis. In fact, the relative hazard for women who became pregnant after diagnosis of breast cancer in comparison with women without a subsequent pregnancy was 0.48 (P = .14), which suggested a possible decreased risk of distant dissemination.

Adult↗
PubMed1994

Metabolism of estrone sulfate by normal breast tissue: influence of menopausal status and oral contraceptives.

The metabolism of [3H]estrone sulfate ([3H]E1S) was studied in normal breast tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC users and in 9 untreated postmenopausal women. [3H]E1S was converted into estrone ([3H]E1) and estradiol-17 beta ([3H]E2) by tissue samples from all three groups of women, with only minor formation of other unconjugated compounds. The rate of [3H]E2 formation was significantly higher in premenopausal women without OC than in postmenopausal women. Among premenopausal women, OC users had a significantly lower rate of total hydrolysis and of [3H]E1 formation than non-users. The rate of total hydrolysis of [3H]E1S in normal breast tissue from all three groups of women was similar to that in muscle, but the rate of [3H]E2 formation was ten times higher. Both total hydrolysis rate and rate of [3H]E2 formation were significantly lower in normal breast tissue than in breast carcinoma and in normal and neoplastic endometrium. The specific ability of normal breast tissue to convert E1S into the terminal biologically active estrogen E2 may be important for estrogenic stimulation of the breast in subjects with low circulating E2 levels. The lower rate of E1 formation in OC users may reflect an inhibitory effect of the progestagen compound in such preparations.

Adolescent↗
PubMed1994

Standardized precision radiotherapy in choroidal metastases.

Metastases in the choroid of the eye are frequent in patients with disseminated malignancy. We here report the results using the precision radiotherapy technique described by Schipper et al. to treat 14 of 17 consecutive patients (21 eyes) with symptoms from such metastases. A beam defining collimator was used and a lateral field was given with the treated eye individually fixed. Varying fractionations and doses were used. The biologically effective dose for early effects (BED3) was 47 to 90 Gy and for late effects (BED10) 28 to 59 Gy. In 14 eyes (82%) the metastases regressed completely. The visual acuity was stabilized or improved in all patients and none needed local surgery. Three patients developed signs of radiation retinopathy, but only in one case the visual function was compromised. With this standardized technique no individualized dose planning was needed, the risk of radiation cataract was minimized and a dry eye avoided.

Adolescent↗
PubMed1993

Radiation-induced breast cancer: long-term follow-up of radiation therapy for benign breast disease.

BACKGROUND: From the 1920s through the 1950s, radiation therapy was used in Sweden as a treatment for benign breast diseases. It is now known that exposure of the breast to ionizing radiation increases the relative risk of subsequent breast cancer, especially for younger women. However, the degree to which the patient's age contributes to the elevation of risk for subsequent development of breast cancer is not yet completely understood. PURPOSE: The purpose was to study the risk of breast cancer after irradiation of the female breast and, in particular, to analyze the duration of the effect and the risk for women older than 40 years at first exposure. METHODS: In this cohort study, data were obtained through population-based registers. The exposed group consisted of 1216 women (median age, 40 years) who, during the period spanning 1925 through 1954, received radiation therapy for benign breast disease. The reference group consisted of 1874 women (median age, 36 years) who had the same diagnosis during that time period but did not receive radiation therapy. The radiation doses were determined from the original medical records (mean dose, 5.8 Gy; range, 0.003-50.1 Gy). The follow-up lasted up to 60 years after first exposure. The incidence rate ratio was analyzed with Poisson regression models. RESULTS: The total number of breast cancers in the exposed cohort was 198 versus 101 in the unexposed cohort. Overall, the radiation-associated incidence rate ratio was 3.58 (95% confidence interval = 2.77-4.63). The dose-response gradient was statistically significant (P < .001) but leveled off at higher doses. The incidence rate ratios decreased starting about 25 years after first exposure but were at increased levels throughout the entire follow-up period. The incidence rate ratio decreased with age at first exposure but was significantly increased (P < .001) even when the age at time of first exposure was greater than 40 years. CONCLUSIONS: Total dose, age at first exposure, and time since first exposure were all determinants of the incidence rate ratio of breast cancer after exposure of the breast to ionizing radiation. A statistically significant increase in the incidence of breast cancer following radiation treatment of various benign breast diseases was observed even among women older than 40 years at the time of first treatment. IMPLICATIONS: These findings need to be considered when weighing the relative benefits versus risks of generalized screening of younger women for breast cancer by mammography.

Adult↗
PubMed1993

Lack of correlation between anxiety parameters and oestrogen receptor status in early breast cancer.

Correlation between anxiety parameters and oestrogen receptor levels (ER) were investigated in 89 patients with primary breast cancer. Patients were divided into two groups, ER poor (< 0.05 fmol/microgram DNA) and ER rich (> 0.05 fmol/microgram DNA). No differences were found between anxiety levels, determined by a modified Hospital Anxiety and Depression (HAD) scale, in the two groups. This report does not support the findings from other studies, claiming an association between psychological parameters and oestrogen receptor status, which is believed to be a prognostic predictor.

Adult↗
PubMed1993

Oestrogenic effects of adjuvant tamoxifen in postmenopausal breast cancer.

Oestrogenic influence of the non-steroidal anti-oestrogen tamoxifen may have consequences for the morbidity pattern among women on long-term adjuvant treatment. Subclinical oestrogenic effects of adjuvant tamoxifen on the tissue level was studied among 16 postmenopausal women in three different organ systems: the pituitary, the liver and bone. After 3 months of adjuvant tamoxifen prolactin levels decreased 66% (P < 0.001) in comparison with pretreatment levels. There was an 80% increase in basal growth hormone after 3 months of treatment in comparison with pretreatment levels, which did not reach statistical significance (P = 0.07). Sex hormone binding globulin levels increased 39% (P < 0.01) and IGF-1 (somatomedin C) levels decreased 20% (P < 0.05). The levels of bone GLA protein (BGP; osteocalcin), a marker of bone osteoblastic activity, decreased 28% (P < 0.01). In 13 of the patients bone mineral density (BMD) was measured before treatment and after 1 year. No significant change in BMD was observed. The results thus suggest a clear oestrogenic effect of tamoxifen on the pituitary, liver and bone in postmenopausal women.

Aged↗
PubMed1993

Effects of early discharge from hospital after surgery for primary breast cancer.

OBJECTIVE: To evaluate the effects of early discharge from hospital on women being operated on for primary breast cancer. DESIGN: Open study in self-selected patients. SETTING: Karolinska and Sabbatsberg Hospitals, Stockholm. SUBJECTS: 169 consecutive patients operated on for primary breast cancer. MAIN OUTCOME MEASURES: All patients were asked to fill in a questionnaire about their perception of their disease and factors associated with the operation. RESULTS: 118/169 patients participated, and of these 28 (24%) chose early discharge with the drain still in place. They were compared with the 90 patients (76%) who were discharged without a drain. The median stay in hospital for those who chose early discharge was 2 days, and for those who remained in hospital until the drain was removed, 6 days. There were no differences between the groups in type or incidence of complications, and the groups were equally satisfied with their length of hospital stay and their treatment in hospital. Those who opted for early discharge were significantly younger than those who did not (mean SD) 52 (14) compared with 62 (13) years, p = 0.001). CONCLUSION: Early discharge from hospital with the drain still in place after operation for primary breast cancer was not found to be associated with any untoward events.

Age Factors↗