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C Ingvar

Publications and source records attributed to C Ingvar.

At least 19 recordsLinked to original sources
PubMed1999

Different patterns of chromosomal imbalances in metastasising and non-metastasising primary breast carcinomas.

In an attempt to identify chromosomal abnormalities that may be associated with a metastatic phenotype, we investigated the pattern of chromosomal gains and losses in 66 node-positive and 63 node-negative primary breast carcinomas. For both subgroups of tumours, losses were more common than gains and the losses were most often the result of structural aberrations. The exceptions were the long arm of chromosome 1, and chromosomes 7, 8, 12, 18 and 20, which were more often gained than lost. Node-negative tumours were preferentially characterised by loss of 6q10-21 and loss of 16q, whereas loss of chromosome 18 was significant for node-positive tumours. Other aberrations that tended to be associated with one of the phenotypes, though not statistically significant, were gain of chromosome 18 and loss of chromosome 10 in node-negative tumours, and gain of chromosome 14 and loss of 12p in node-positive tumours. Our data show that there are differences among the genetic lesions present in node-negative and node-positive breast tumours. Int. J. Cancer (Pred. Oncol.) 84:370-375, 1999.

Breast Neoplasms↗
PubMed1999

Clinical and histopathological characteristics in relation to aetiological risk factors in cutaneous melanoma: a population-based study.

In this population-based, case-control study from Sweden using data collected from 1988 to 1990, an increased risk of melanoma was associated with the number of sunburns, propensity to freckle, the number of raised naevi and a family history of melanoma. Furthermore, a decreased risk was associated with occupational sun exposure. The purpose of this study was to investigate whether different histopathological features of the melanoma and clinical factors were related to the different aetiological risk factor patterns. All the confirmed primary cutaneous melanomas (n = 366) were included in the study. Both univariate analyses with tests for interaction and multivariate analyses were performed. Patients with melanoma on the trunk and patients with thin melanomas had an excess of close relatives with a history of melanoma (odds ratios [ORs] = 2.7 and 2.3, respectively). A relationship was also seen between melanomas in younger persons and a family history of melanoma (OR = 2.6). The presence of raised naevi on the arm had a tendency to be closer related to melanoma of the nodular type (OR = 4.3) than melanoma of the superficial spreading type (OR = 1.6). Patients with outdoor occupations during summer had a decreased risk of developing melanoma on the extremities. Melanoma diagnosed in patients born before 1939 had an association with sunburns (OR = 1.9) and freckling (OR = 2.0), while melanomas in patients born in 1939 or later were related to a family history of melanoma (OR = 2.2). These results suggest that different histopathological and clinical features of melanoma are associated with different risk factor patterns, which may imply diverging tumour genesis.

Adolescent↗
PubMed1999

Effects of compression bandaging with or without manual lymph drainage treatment in patients with postoperative arm lymphedema.

We examined the effects of low stretch compression bandaging (CB) alone or in combination with manual lymph drainage (MLD) in 38 female patients with arm lymphedema after treatment for breast cancer. After CB therapy for 2 weeks (Part I), the patients were allocated to either CB or CB + MLD for 1 week (Part II). Arm volume and subjective assessments of pain, heaviness and tension were measured. The mean lymphedema volume reduction for the total group during Part I was 188 ml (p < 0.001), a mean reduction of 26% (p < 0.001). During Part II the volume reduction in the CB + MLD group was 47 ml (p < 0.001) and in CB group 20 ml. These differences were not significant (p = 0.07). A percentage reduction of 11% (p < 0.001) in the CB + MLD group and 4% in the CB group was significantly different (p = 0.04). In both the CB and the CB + MLD group, a decrease of feeling of heaviness (p < 0.006 and p < 0.001, respectively) and tension (p < 0.001 for both) in the arm was found, but only the CB + MLD group showed decreased pain (p < 0.03). Low stretch compression bandaging is an effective treatment giving volume reduction of slight or moderate arm lymphedema in women treated for breast cancer. Manual lymph drainage adds a positive effect.

Adult↗
PubMed1998

Cytogenetic findings in invasive breast carcinomas with prognostically favourable histology: a less complex karyotypic pattern?

Seventeen invasive primary breast carcinomas of histological types usually considered to be prognostically favourable (2 medullary, 3 papillary, 3 tubular, and 9 mucinous carcinomas) were analysed as part of an ongoing study of the cytogenetics of breast cancer. Thirteen of the tumours (7 mucinous, 2 medullary, 2 papillary, and 2 tubular carcinomas) showed clonal chromosome aberrations. Trisomy 7 and i(1q) were present as sole and recurrent aberrations in the mucinous tumours. The 2 tubular carcinomas and I papillary carcinoma had simple numerical changes only, whereas the second papillary tumour had a balanced translocation as the sole anomaly. Both medullary carcinomas had chromosome numbers in the triploid range, with clones displaying structural and numerical changes. Our data, especially when collated with information on previously published cases of mucinous, papillary, tubular, and medullary breast carcinomas, show that the former 3 histological types, in keeping with their recognised prognostic advantage, appear to exhibit relatively simple karyotypic changes, i.e., numerical aberrations, balanced translocations, and near-diploid chromosome numbers. Medullary carcinomas on the other hand, appear to have more complex karyotypes, similar to those described for the more common ductal and lobular subtypes of breast carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

Cytogenetic changes in benign proliferative and nonproliferative lesions of the breast.

Cytogenetic analysis of short-term cultures from 69 cases of fibrocystic breast changes and 10 samples of normal mammary tissue revealed clonal chromosome aberrations in six fibrocystic lesions. All the histologically normal tissue samples had a normal karyotype. The frequency of cytogenetically abnormal cases seems to correlate with the degree of histopathologic changes of the tissue; nonproliferative lesions may have clonal chromosome alterations, but at a low frequency. Whether women with karyotypically altered fibrocystic "disease" have a higher risk of developing invasive breast cancer, compared with women without microscopically visible genetic anomalies in fibrocystic lesions, remains unknown.

Adult↗
PubMed1998

Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A randomised phase III trial.

In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P was given i.v. at a dose of 100 mg/m2 day 1 every 4 weeks. There was no statistically significant difference in overall survival between the treatment arms (P = 0.22). Increased toxicity was observed in the treatment arm containing P of which leucopenia, alopecia and nausea/vomiting were the most pronounced. The median time to progression was significantly longer in patients treated with DVP (4.2 versus 2.2 months, P = 0.007). In conclusion, adding P to DV did not change overall survival but did significantly increase toxicity.

Adolescent↗
PubMed1998

Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.

PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.

Adult↗
PubMed1998

Zilascorb(2H), a low-toxicity protein synthesis inhibitor that exhibits signs of anticancer activity in malignant melanoma.

Zilascorb(2H) is a benzaldehyde derivative giving rise to strong protein synthesis inhibition. It has shown antitumor activity against human malignant melanoma grown as xenografts in nude mice. The effect was manifest only after prolonged daily treatment and was quickly reversible when treatment was stopped. Drug-induced fever was the dose-limiting toxicity observed during clinical phase I studies of zilascorb(2H). The object of the present study was to assess antitumor activity, safety and tolerability of the drug in melanoma patients. Sixteen patients with disseminated malignant melanoma were included, all presenting with WHO performance status 0-2 and adequate organ functions. Previous chemo- or radiotherapy was accepted, while patients with known CNS metastases were excluded. Due to its low solubility and quickly reversible activity, zilascorb(2H) 1400 mg was infused by the patients twice daily through a venous access port for up to 12 weeks. Induction of tumor regression was demonstrated in one patient, who was, however, withdrawn from treatment after 2 weeks because of recurrent fever and fatigue. All the 12 patients evaluable for antitumor activity had progressive disease. Zilascorb(2H) was well tolerated, except for fever reactions and reversible liver toxicity. Most patients learned quickly how to handle a venous access port, but daily self-administration of i.v. infusions became too cumbersome to justify further patient inclusion despite the tumor regression observed. We conclude that zilascorb(2H) seems to have the potential for antitumor activity in metastatic malignant melanoma and is well tolerated. Daily self-administration of drug infusions is not desirable for long periods and zilascorb(2H) tablets have been developed. Because of its favorable toxicity profile, especially compared to other protein synthesis inhibitors, zilascorb(2H) may be particularly interesting for combinations with other anticancer drugs.

Adult↗
PubMed1997

Efficient selection of scFv antibody phage by adsorption to in situ expressed antigens in tissue sections.

The present report describes the development and application of an efficient method for the direct adsorption/selection of antibody phage using antigens expressed in situ in cryostat tissue sections. In a model system, scFv phage directed towards an epitope on the GA733-2 epithelial glycoprotein expressed in colorectal carcinoma tissue could be specifically enriched up to 1500 fold in single-pass experiments and a million fold after three rounds of selection. Enrichment efficacy was directly proportional to the fraction of antigen positive area over the total area. Sufficient enrichment was achieved at an area fraction of less than four percent, thereby permitting the selection of antibodies to sub-populations of cells or to tissue sub-structures. The general usefulness of the method was demonstrated when a combinatorial scFv antibody phage library derived from melanoma immunized non-human primates was selected in tissue sections of metastatic melanoma. Individual scFv antibodies from enriched phage populations demonstrated different binding specificities, reflected in extracellular and cellular tissue staining patterns which included tumor cell surface reactivity. This method should be particularly useful for the identification of antigens which are only expressed during specific in vivo conditions, and overcomes a major limitation of currently used selection protocols.

Adsorption↗
PubMed1997

Karyotypic abnormalities in fibroadenomas of the breast.

Short-term cultures of 50 fibroadenomas of the breast were cytogenetically analyzed. Nine tumors were found to display clonal chromosome aberrations. One had multiple, cytogenetically unrelated clones, whereas the others had a single abnormal clone each. Four cases had one balanced translocation as the sole anomaly, and one had a complex intrachromosomal rearrangement of chromosome 3, leading to loss of 3p material. One fibroadenoma had a single numerical aberration, and one had supernumerary ring chromosomes. The remaining 2 cases had both numerical and structural aberrations. The only recurrent alterations were trisomy 20 and rearrangement of chromosome arm 1p. The finding of similar chromosomal aberrations in fibroadenomas and carcinomas suggests that women with karyotypically abnormal fibroadenomas may have an increased risk of developing subsequent breast cancer. If so, different chromosome anomalies might have different pathogenetic and/or prognostic significance.

Adolescent↗
PubMed1997

Cutaneous malignant melanoma in southern Sweden 1965, 1975, and 1985. Prognostic factors and histologic correlations.

BACKGROUND: There is a worldwide increase in the incidence of cutaneous malignant melanoma (CMM) among whites. In Sweden, a five-fold increase has been recorded since 1960, although the increase in mortality rate is substantially lower. Tumor thickness is recognized as the most important histologic prognostic factor for primary melanoma. In a previous study, the authors did not find any significant decrease in mean tumor thickness over the period 1965-1985 in their region. In the current study, prognostic factors for melanoma were evaluated for this time period. METHODS: In a population-based study, 468 cases of invasive melanoma, diagnosed in the years 1965, 1975, and 1985, were histopathologically reexamined. The level of invasion, tumor thickness, regressive reaction, ulceration, presence of inflammatory cells, presence of benign nevus cells, and site of presentation were studied. In 461 of these 468 patients, it was possible to correlate the histopathologic factors with survival. RESULTS: In univariate analyses, the parameters of presence of ulceration, increasing tumor thickness, male gender, nodular type of melanoma, and older age at diagnosis were significantly related to a shortened overall survival. In various multivariate models with adjustment for age and the factors studied simultaneously, ulceration, increasing tumor thickness, and male gender were significantly associated with a poor prognosis. Correlations between the factors studied were noted. It was observed that older patients tended to have thicker tumors. Thick melanomas correlated to a deeper level of invasion (Clark's), nodular growth pattern, ulceration, less inflammation, and less regression compared with thin, less invasive melanomas. Women had significantly fewer inflammatory cells and fewer signs of regression in their tumors compared with men. CONCLUSIONS: In multivariate analyses adjusted for age, increasing tumor thickness, older age, ulceration, and male gender were significantly associated with a poor prognosis among patients with invasive CMM. None of these factors showed a significant change for the years 1965, 1975, and 1985. Thus, a change in the prognostic factors studied does not explain the increased survival of melanoma patients for this time period.

Adult↗
PubMed1996

Novel germline p16 mutation in familial malignant melanoma in southern Sweden.

The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.

Carrier Proteins↗
PubMed1996

Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases.

A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grade and mitotic activity of the tumor. Whereas all lobular carcinomas were karyotypically normal or near-diploid, more than 3 aberrations and sometimes near-triploid or near-tetraploid karyotypes were common findings in ductal carcinomas, especially in grade-III tumors and in tumors showing high mitotic activity in vivo. Karyotypes with cytogenetically unregulated clones and unbalanced structural chromosomal rearrangements were more frequent in infiltrating than in in situ carcinomas but, at least as far as the second of these 2 characteristics is concerned, especially in infiltrating carcinomas that also had an in situ component. The presence of cytogenetic polyclonality correlated with tumor grade. Although recurrent chromosome aberrations were significantly more common in ductal than in lobular carcinomas, none of these breast cancer-associated anomalies seemed to be specific for any particular clinicopathologic parameter. The associations between modal chromosome number and mitotic activity and between cytogenetic polyclonality and tumor grade were found to be statistically significant in multivariate models. No correlations was seen between the karyotypic findings and tumor size or the presence of axillary-lymph-node metastases.

Adult↗
PubMed1996

Chromosome aberrations in prophylactic mastectomies from women belonging to breast cancer families.

Short-term cultures of samples from eight prophylactic mastectomies from five unrelated women who were genetically predisposed to breast cancer were analyzed cytogenetically. Clonal chromosome abnormalities were detected in five breasts. Three samples from two women had aberrations involving the short arm of chromosome 3, with a breakpoint in 3p14 in common. Three samples from three women had rearrangements of 1q. Two of them, one of which also displayed a 3p14 rearrangement, shared a breakpoint in 1q41. Both 1q41 and, in particular, 3p14 have been reported to be rearranged frequently in malignant breast proliferations. Whether alterations of genes in these bands are essential in mammary tumorigenesis and, if so, whether they are equally important in sporadic and in hereditary cases remains to be explored.

Adult↗
PubMed1996

Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors.

The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.

Adolescent↗
PubMed1996

Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors.

In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was found that certain specific types of prescribed drugs, i.e. beta-blockers, hydralazines and benzodiazepines, may increase the risk of melanoma development. However, these associations were diminished, at least for benzodiazepines, after controlling for host factors. As these findings are unconfirmed, and may be due to chance or confounding, further studies are warranted. The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits. Our results do not suggest an association between oral contraceptives and melanoma. Furthermore, reproductive factors were not independent risk factors for melanoma. However, increasing number of live births seemed to be protective (P for trend = 0.01). There is a need for further research to be able to draw firm conclusions on the relation between number of live births and melanoma. The results based on histopathological re-examinations and those based on tumour registry data were essentially the same.

Adolescent↗
PubMed1996

Reproducibility of a self-administered questionnaire for assessment of melanoma risk.

BACKGROUND: The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region. METHODS: Repeat questionnaires were completed on two occasions, 1-3 years apart, by 670 randomly selected subjects. In addition, exposure data from a case-control study were used to estimate the effect of misclassification. RESULTS: Overall, there was a fair to good consistency between the answers on the two occasions for the various epidemiological variables. Exposure variables identified as risk factors for melanoma development were reasonably reproducible. The estimated proportion of agreement, A, ranged from 0.74 to 0.92, the average correct classification rate (assuming common sensitivity and specificity), pi, was > or = 0.85 and the kappa coefficient, kappa, ranged between 0.52 and 0.83. However, the question on number of raised naevi on the arm was an exception since it had a lower test-retest reliability (A = 0.62, pi = 0.77, kappa = 0.40). When using data from the case-control study, the effect of the estimated random misclassification was found to only slightly bias odds ratios toward one. CONCLUSION: Our questionnaire, used for assessment for melanoma risk, provided information with fair to good test-retest reliability, and corrected odds ratios were found to be only slightly higher than observed odds ratios.

Adolescent↗