Biomedical subjects

E Munck-Wikland

Publications and source records attributed to E Munck-Wikland.

At least 37 records · Page 2Linked to original sources

PubMed1990

Control cells for image cytometric DNA analysis of esophageal tissue and the influence of preoperative treatment.

The nuclear DNA content of 4,960 normal cells in 30 esophagectomy specimens was assessed by image cytometry. In relation to intermediate squamous epithelial cells, the mean transmission values were 25.6% higher for basal squamous epithelial cells, 10.1% higher for fibroblasts and 16.2% lower for lymphocytes. The interslide coefficient of variation (CV) was similar for intermediate and basal squamous epithelial cells, 20.2% and 18.9%, respectively, while fibroblasts and lymphocytes displayed lower interslide CVs, 10.5% and 8.8%, respectively. In spite of their high interslide CVs, the mean DNA values of intermediate and basal squamous epithelial cells had the highest intraslide correlation. This correlation indicates that the preparative and analytical differences between slides that result in alterations in mean DNA values affect squamous epithelial cells of similar origin, size and shape in an analogous manner. Basal squamous epithelial cells replicate their DNA and contain more than the diploid amount; therefore, normal intermediate squamous epithelial cells are suggested as control cells to define the 2c reference value for further DNA studies on squamous epithelial lesions of the esophagus. Preoperative irradiation, with or without chemotherapy, did not alter the DNA values of the investigated control cells.

Adenocarcinoma↗

PubMed1988

Tumor markers carcinoembryonic antigen, CA 50, and CA 19-9 and squamous cell carcinoma of the esophagus. Pretreatment screening.

Pretreatment serum levels of the tumor markers carcinoembryonic antigen (CEA), CA 50, and CA 19-9 in 95 patients with squamous cell carcinoma of the esophagus and 32 age-matched controls were compared. Thirty-nine percent of the cancer patients showed elevated (greater than or equal to 5 micrograms/l) serum CEA levels, 41% had elevated (greater than or equal to 17 U/ml) CA 50 levels, and 13% showed elevated (greater than or equal to 37 U/ml) CA 19-9 levels. The tumor markers showed a considerable degree of complementarity, and combined tumor marker analysis increased the sensitivity to 59%. Raised CEA levels were found significantly more frequently in intrathoracically localized tumors than in cervical cancers. Patients surviving less than 6 months showed a higher rate of elevated CEA assays than those who survived 6 to 18 months. No certain correlation was established between tumor marker elevation and tumor stage or tumor differentiation.

Antigens, Neoplasm↗

PubMed1985

Esophagitis and cancer of the esophagus.

Early diagnosis is an important factor in the effort to increase the healing rates of esophageal cancer; another consideration is the establishment of a reliable method of identifying risk groups. Alcohol abuse is known to be associated with a higher risk of esophageal cancer. The current investigation, based on a retrospective study of the records of patients with esophageal cancer, reveals a strong connection between cancer development and chronic esophagitis due mainly to reflux in about 10% of the patients. In the literature this connection has been suspected but never so clearly shown. The clinical implication may be a more rigorous approach to long-standing esophagitis in elderly patients.

Aged↗

PubMedDate not supplied

Nuclear DNA content and p53 immunostaining in metachronous preneoplastic lesions and subsequent carcinomas of the oral cavity.

BACKGROUND: Clinical evaluation of preneoplastic lesions of the oral cavity is difficult. Histopathologic grading of dysplasias shows large variability and does not give reliable information concerning the risk for progression to cancer. METHODS: DNA image cytometry and p53 immunostaining were performed to describe the pattern of DNA aberration and p53 overexpression in confined preneoplastic lesions and in the subsequent carcinomas developing at the same site in 20 patients. RESULTS: Hyperplastic and/or inflammatory lesions showed a diploid DNA pattern in 81% of the cases and 23% were p53-positive. Dysplastic preneoplastic lesions showed a nondiploid/ aneuploid DNA pattern in 73% and 64% were p53-positive. The subsequent invasive carcinomas were nondiploid/aneuploid in 86% and p53-positive in 69% of cases. CONCLUSIONS: Analysis of nuclear DNA content and p53 immunostaining appears to be useful as an adjunct to histopathology in the evaluation of true precancerous lesions.

Adult↗

PubMedDate not supplied

Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.

In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.

Adult↗

PubMedDate not supplied

Low levels of endostatin in the urine from patients with malignant disease.

Endostatin, a C-terminal subfragment of collagen XVIII, and angiostatin, a family of fragments originating from the NH(2)-terminal portion of plasminogen, have been described as potent inhibitors of angiogenesis and malignant growth. We have earlier reported the presence of angiostatin fragments in urine from cancer patients. In this study, we investigated the occurrence of endostatin and the correlation between the amounts of endostatin and angiostatin in urine collected from 104 patients with different types of malignancies and in 16 controls. The amounts of endostatin were measured with a commercial immunoassay. Angiostatin fragments were quantitated by Western blot analysis. Only small amounts of endostatin were observed, both in patients and controls, and there was no significant difference in the amount of endostatin between the patients and the controls. Both endostatin and angiostatin concentrations in the urine showed a strong dependence on impaired kidney function, especially tubulus function, measured as the amount of urine alpha(1)-microglobulin. Interestingly, there was no significant correlation between endostatin and angiostatin concentrations in the patients with impaired kidney function (elevated urine albumin or urine alpha(1)-microglobulin), suggesting a possible difference in circulating concentrations of these inhibitors.

Adult↗

PubMedDate not supplied

Image cytometry DNA analysis of diethylnitrosamine-induced dysplasias and invasive squamous cell carcinomas of the esophagus in mice.

The nuclear DNA content was assessed by image cytometry in squamous epithelial dysplasias and invasive squamous cell carcinomas of the esophagus induced by diethylnitrosamine (DEN) in mice. The study comprises 48 lesions: 27 lesions with low grade (i.e. slight and moderate) dysplasia, 18 with high grade dysplasia (i.e. severe dysplasia and CIS), and 3 with invasive squamous cell carcinoma. In addition, 5 parallel run control specimens were also investigated. The results demonstrated that only 3.7% (or 1/27) low grade dysplasias but as much as 72.2% (or 13/18) high grade dysplasias, and all three invasive squamous cell carcinomas displayed non-diploid DNA values. Three of 18 high grade dysplasias and all three invasive squamous cell carcinomas demonstrated aneuploid cell nuclei. The results of the present work indicate that the esophageal mucosa of the mouse permit investigation--under controlled conditions--of the nuclear DNA alterations occurring during carcinogenesis in this organ. The results presented herein thus substantiate the theory of increasing DNA aberrations occurring during carcinogenesis in the human esophagus.

Animals↗

PubMedDate not supplied

Angiostatin fragments in urine from patients with malignant disease.

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.

Albuminuria↗

PubMedDate not supplied

TP53 mutations do not correlate with locoregional recurrence in stage I tongue carcinomas.

BACKGROUND: The abrogation of the TP53 gene is considered to play a central role in the development of human cancers. Exons 5-8 harbor mutations most frequently, mainly of the missense type, resulting in accumulation of the p53 protein. The importance of these alterations as prognostic factors, are issues of controversy. MATERIAL AND METHODS: Thirty-four patients suffering from stage I tongue carcinoma had been treated with a local surgical excision of the tumor. Seventeen patients had developed a local recurrence in the tongue or cervical (regional) metastases while 17 patients, matched for age and gender to the former group, had no recurring disease within follow-up. Protein p53 was detected through immunohistochemical (IHC) analysis using antibody CM1. Exons 5-8 of the TP53 gene were amplified through the Polymerase Chain Reaction (PCR). The presence of mutations analyzed by CDGE (Constant Denaturant Gel Electrophoresis) and detected mutations were subjected to sequencing. RESULTS: 20 out of 34 tumors (59%) showed mutated TP53, 18 tumors were IHC p53 positive, but the correlation between CDGE and IHC was only 56%. Sequencing of the gene was possible in 8 cases. CONCLUSIONS: Neither the presence of mutations nor immunostaining had any impact on the risk of recurrence expressed as life-table analysis of time to recurrence.

Adult↗

PubMedDate not supplied

Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx.

Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a histopathologically well-defined condition. There is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed immunohistochemical staining with a polyclonal antibody against recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS lesions which progressed to invasive cancer, within a follow-up time of 5 years, were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not progress were positive (37%) (p < 0.01). Our data showed that a positive laminin-5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.

Adult↗

PubMedDate not supplied

Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival.

BACKGROUND: Human papilloma virus (HPV), which is frequently present in tonsillar carcinoma seems to be a prognostically favourable factor for patient survival and also for low risk of relapse. Since HPV may abrogate the function of wild type p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53 status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and patient survival. MATERIALS AND METHODS: Pre-treatment primary tonsillar carcinoma specimens were obtained retrospectively from 40 patients, 21 complete responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage III and IV tumours. The paraffin-embedded biopsies were analysed for presence of HPV DNA, by general and type specific PCR, and for p53 overexpression by immunohistochemical staining with the murine Mab DO-1. RESULTS: It was possible to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53 immunostaining (p53+) were not correlated with response to RT, since 8/18 CR patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR patients were p53+. A tendency towards a survival benefit in patients with HPV+ tumours was observed and this tendency was significant for patients with stage IV HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A difference in survival between patients with p53+ cancer as compared to patients with p53- lesions was not demonstrated. In conclusion, although presence of HPV and p53 immunoreactivity in tonsillar carcinoma could not be related to RT response, determination of HPV and p53 status may still prove useful as predictive/prognostic markers.

Biomarkers, Tumor↗

PubMedDate not supplied

Image cytometry DNA analysis of dysplastic squamous epithelial lesions in the larynx.

The Feulgen-DNA content of cell nuclei from the human larynx was assessed in 62 lesions from 14 patients with dysplastic and cancerous lesions and in 14 control patients with non-neoplastic chronic laryngitis. All the carcinomas displayed aneuploid cell nuclei, and the cellular DNA content was substantially altered in dysplasias which later progressed to cancer in situ or invasive cancer. Thus the process of laryngeal carcinogenesis can be monitored not only by histological changes, but also by cellular DNA aberrations. Quantitative DNA analysis appears to be a complement to the histopathological evaluation of laryngeal lesions in the search for neoplasia.

Biopsy↗

PubMedDate not supplied

Carcinoembryonic antigen, CA 19-9 and CA 50 in monitoring human squamous cell carcinoma of the esophagus.

The serum levels of Carcinoembryonic antigen, CA 19-9 and CA 50 were assessed in 60 patients with squamous cell carcinoma of the esophagus during the course of the disease. In 53 patients, the effect of preoperative or final treatment on tumor marker levels could be analysed, and the change in tumor marker levels discriminated significantly the patients who showed tumor mass/symptom regress from the patients who displayed progress or undecided change. Progress later in the course of the disease was reflected by a statistically significant increase in all three tumor marker assays, and in 8/18 (44%) patients the tumor marker increase was seen prior to other signs of tumor progression. The appearance of distant metastases was associated (11/12) with increase in CEA levels.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

Toluidine staining of diethylnitrosamine-induced esophageal dysplasias in mice.

The dismal healing rate of esophageal cancer can be improved through identification of risk groups and deployment of methods to effect early diagnosis. Vital staining of epithelial surfaces is a method clinically used to detect carcinoma and dysplasia. Several reports have been published supporting the value of this technique in detecting tumours of different organs. Because of the large surface area of the esophageal mucosa, vital staining can offer a valuable tool for obtaining biopsies, with a high degree of accuracy. In the present investigation, experimentally induced esophageal tumours in mice with various degrees of dysplasia have been stained with toluidine blue. The colour uptake was correlated to the degree of dysplasia observed, as well as to epithelial damage. Toluidine blue uptake correlated significantly to both dysplasia and epithelial damage. The exact way in which toluidine blue is incorporated in the tissue is still not known and needs further investigation.

Animals↗

PubMedDate not supplied

Image cytometry DNA analysis of invasive squamous cell carcinoma of the esophagus.

The Feulgen-DNA content of squamous carcinoma cell nuclei from the human esophagus was assessed in punch biopsies from 47 untreated patients. Forty-four of the 47 biopsies (93.6%) demonstrated aneuploid cell populations, and the remaining 3 (6.4%) were non-diploid. Previous studies have demonstrated that in esophageal dysplasias adjacent to invasive squamous cell carcinoma, DNA in single cells is substantially altered. Thus the process of esophageal carcinogenesis can be monitored not only by histological changes, but also by DNA aberrations in single cells. Quantitative DNA measurement appears, therefore, to be a complement to the histological evaluation of esophageal lesions with suspected, but not unequivocal, evidence of neoplastic growth.

Adult↗

PubMedDate not supplied

Overexpression of p53 protein is common in premalignant head and neck lesions.

In order to determine whether or not the p53 gene is involved in the malignant transformation of the head and neck carcinoma HNSCC, we have analyzed archival specimens from 527 primary head and neck lesions and 27 corresponding lymph node metastases. Nuclear p53 protein was present in 107 of 190 (56%) dysplasias, 61 of 102 (60%) carcinoma in situ (CIS), and 262 of 493 (53%) carcinomas. The p53 score did not increase significantly with progression of these lesions from dysplasia to CIS and to carcinoma. All 357 normal samples of head and neck tissues were negative. The majority of the 172 sets of premalignant and malignant lesions displayed concordant p53 staining patterns. The staining was incongruous in only six cases. The p53 staining results were congruent in all 27 pairs of primary and metastatic (lymph nodes) tumors. These data strongly suggest that p53 protein could be altered in a very early phase of the head and neck tumorigenesis and is maintained during tumor progression and metastatic spread. Mutations in p53 were examined in 11 cases that exhibited high levels of p53 protein as detected by immunohistochemistry using PAb 1801 MAb. Mutation analysis was performed by direct sequencing of the PCR amplification products of exons 5 through 8, which contain greater than 90% of p53 mutations found in tumors. Three of 11 HNSCC had mutations at codon 130 (C to A), 193 (A to T), 283 (G to C), respectively. No mutations were found in the other 8 samples within the regions examined. However, they may have mutations in unsequenced regions of p53 or may have wild type protein that accumulates for other reasons.

Adult↗

PubMedDate not supplied

Involvement of aberrant p53 expression and human papillomavirus in carcinoma of the head, neck and esophagus.

Biopsies from 34 patients with cancer of the head, neck or esophagus, 2 laryngeal papillomas, and 2 normal tonsils were analysed for human papillomavirus (HPV), Epstein Barr virus (EBV) genomes and mutated or elevated levels of p53. In 4 biopsies p53 was also analysed by DNA sequencing. HPV type 31 was found in one laryngeal cancer with normal p53 and HPV type 16 in two tonsil cancers with aberrant p53 expression. EBV was detected by PCR in 11 biopsies, but in situ hybridisation and immunohistochemistry, did not confirm this finding. Aberrant p53 expression was observed in approximately half of the tumours. These results support the involvement of both aberrant p53 expression and HPV in the aetiology of squamous cell carcinoma of the head and neck.

Base Sequence↗

PubMedDate not supplied

Further studies on the carcinogenic-free interval following exposure in experimental esophageal tumorigenesis.

247 C57B1 male mice were killed after Diethylnitrosamine (DEN) treatment at various time intervals ranging from one day to nine months. The number of esophageal tumors was divided by the length of the resected esophagus (i.e. Tumor Index = TI). Animals treated for up to 2 months had a TI of 0.1. Since the histological examination of the esophagi in those animals revealed only normal histology, the conclusion drawn was that the TI of 0.1 was a methodological error in assessing esophageal tumors by transillumination. Three months' treatment with DEN resulted in a 9-fold increased TI and 6 months' treatment in a 69-fold increased TI. Other groups of animals treated with DEN for the same period of time were allowed to survive 7, 9 or 12 months without further treatment. Animals treated with DEN for 1 day but followed without further treatment for 7 months demonstrated a 3.5-fold increased TI. For animals treated with DEN for only 14 days, (TI 0.1) and followed for 7 months with a carcinogenic-free diet, a 7-fold TI was observed. For the group of animals treated for 3 months (TI 0.9) but allowed to survive to complete 7 months on a carcinogen-free diet, a 5-fold higher TI was recorded. DEN animals treated for 6 months (TI 6.9) but allowed to survive 3 additional months had a TI of 9.6. A similar TI, namely 9.7, was found when the carcinogen-free interval was prolonged for 6 more months. These results suggest that clones of esophageal cells are "programmed" for tumor growth at an early stage of DEN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗