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Biomedical subjects

J Wennerberg

Publications and source records attributed to J Wennerberg.

At least 91 records · Page 5Linked to original sources
PubMed1988

Multiple apparently unrelated clonal chromosome abnormalities in a squamous cell carcinoma of the tongue.

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the tongue, a tumor type in which chromosome aberrations hitherto have not been reported. No less than 12 pseudodiploid clones were detected, giving the tumor karyotype 46,X,der(X)t(X;1)(q26;p32),der(1)(Xqter----Xq26::1p32 ----cen----1q42:), del(13)(q11q21),t(15;?) (q26;?)/46,XX,t(1;?)(p34;?),inv(2)(p21q11)/46,XX,t(1;10)(p32;q24)/ 46,XX, + der(1)(12pter----12p11::1p11----cen----1q32:: 11q13----11q22::1q32----1q42:), del(11)(q13q22), -12, der(17)t(1;17) (q42;p13)/46,XX,inv(1)(p22q44)/47,XX,del(1)(q32),der(17)t(1; 17)(p22;q25), der(1)inv(1) (q25q44)t(1;17)(p22;q25),ins(14;7)(q11;q22q36), + 14/46,XX,t(1;4)(q23;q35)/46, XX,t(1;21) (q25;q22),t(2;10)(q31;q26),t(22;?)(q12;?)/46,XX,del(1)(q32)/46,XX, t(1;8)(q44;q21)/46,XX, t(2;21)(q11;p11)/46,XX,t(9;11)(q34;q13). The large number of apparently unrelated abnormalities leads us to suggest that the carcinoma may have been of multiclonal origin.

Aged↗
PubMed1986

Studies of cellular retinol-binding protein (CRBP) in squamous-cell carcinomas of the head and neck region.

Cellular retinol-binding protein (CRBP) concentration was determined by radioimmunoassay in biopsies from normal mucosa and squamous-cell cancers of the head and neck region in 26 patients. The plasma concentrations of retinol, retinol-binding protein (RBP), prealbumin, albumin, orosomucoid and alfa1-antitrypsin were also determined. In all patients the tumours contained significantly higher concentrations of CRBP (median = 185 micrograms/g tissue protein; range: 27-1,017 micrograms/g) than normal mucosa (median = 14 micrograms/g tissue protein; range 6-97 micrograms/g). CRBP could not be detected in patient plasma. The tumor/normal mucosa CRBP concentration ratio showed a significant inverse correlation to a histopathological malignancy grade score evaluating the tumour-host relationship, suggesting that tumours with high CRBP relative to normal mucosa are biologically less aggressive. Tumour CRBP showed no correlation either to CRBP concentration in normal mucosa, or to plasma retinol or plasma retinol-binding protein concentration. CRBP concentration in normal mucosa, however, showed a significant correlation to plasma retinol-binding protein concentration. Most of the patients had low levels of plasma retinol and retinol-binding protein compared to matched controls. Whether this has any relationship to the development of the tumour, or whether the active inflammation induced by the cancer leads to a low plasma retinol concentration, is unknown.

Adult↗
PubMed1984

Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck after mitomycin C and cisplatin treatment.

Cell kinetic studies are of interest for clarifying the concepts of chemotherapeutic strategy in the multimodality therapy of advanced squamous-cell carcinoma of the head and neck. A poorly-differentiated squamous-cell carcinoma of the head and neck heterotransplanted to nude mice was used for analyses of chemotherapeutically induced cell cycle perturbations. The heterotransplanted tumour, in its 15th or later passages in nude mice, was treated with either Mitomycin C or cisplatin. After determination of dose-response relationships and toxicity, treated tumours were biopsied at different times and cell cycle distribution pattern, 3HTdR incorporation into DNA, histology and tumour volume were recorded. Mitomycin C and cisplatin gave the same pattern of cell cycle perturbations, although the changes induced by cisplatin were more profound. There was an initial increase of the fraction of cells in the S phase, concomitant with a reduction of the fraction of cells in G0 + G1 phase. When these perturbations were normalized a transient increase of the fraction of cells in G2 + M phase was observed. However, while cisplatin caused an initial transient depression of DNA synthesis, the Mitomycin-C-treated tumours exhibited a short-lasting increase of DNA-synthesis. The maxima of the induced changes in cell cycle phase distribution and DNA-synthesis lasted for only 24-48 h, which may be of importance for scheduling combinations of drugs. Though both drugs induced profound changes in tumour volume growth and cell kinetics, there was no change in the histopathological picture of the treated tumours. Routine histopathological examination is thus not likely to be of value evaluating the effect of chemotherapy.

Animals↗
PubMed1984

Changes in growth pattern of human squamous-cell carcinomas of the head and neck during serial passages in nude mice.

Six human squamous-cell carcinomas of the head and neck heterotransplanted to nude mice were studied with respect to changes in tumour volume doubling time (DT), cell cycle phase distribution and clonal composition during serial passages. The tumours exhibited a statistically significant decrease in DT between the first and third or fourth passages towards a constant value. The changes in DT are likely to depend on a reduction of cell loss factor. Five of the original tumours and serially passed heterotransplants were analyzed with flow cytometry. Two tumours were diploid and remained so after heterotransplantation. Three tumours had one diploid and one aneuploid cell population. At heterotransplantation there was a selection of clones and only the aneuploid cell populations could be recovered from the heterotransplants in the first as well as in later passages.

Animals↗
PubMed1982

Histologic pattern and growth in two human testis cancers before and after transplantation to nude mice.

A yolk sac tumor of the testis and a testicular germ cell tumor with a mixed pattern were serially transplanted to athymic mice. The morphologic pattern in light microscope of each of the transplanted tumours were similar to that of the donor tumor, and both the donor and the transplanted tumors revealed alphafetoprotein reactivity by immunohistochemical staining. The observed growth of the mixed tumor in the donor and in the transplants fitted well with an estimation by the Gompertz equation. The ultrastructure of the transplanted tumors were similar to those previously described for testicular tumors with similar histologic patterns.

Adult↗
PubMed1982

Lactate dehydrogenase isoenzyme 1 (LDH-1) in athymic mice with xenografts of a human testicular germ cell tumor.

Lactate dehydrogenase (LDH) and LDH isoenzyme activities were determined in tumor tissue, tumor cystic fluid, and serum from athymic mice with transplants of a human testicular germ cell tumor. High activity of LDH-1 was found in tumor tissue and tumor cystic fluid. By histochemical staining LDH was found in all tumor cells. Most tumor cells had a faint staining reaction while some cells dispersed throughout the tumor had a strong staining reaction. The serum LDH-1 in athymic mice with tumor transplants correlated markedly with the tumor volume. The results indicate that serum LDH-1 was derived from the testicular germ cell tumor transplants.

Animals↗
PubMed1982

Heterotransplantation of two human tumours in athymic mice and asplenic-athymic mice.

The growth in athymic mice (Balb/c nu/nu mice) and athymic-asplenic mice (BALB/c nu/nu Dh/ + "lasat" mice) of two human tumour lines (one nasopharyngeal carcinoma and one testicular germ cell tumour), established in athymic mice, were compared. No significant difference in take rate was observed: 13 of 16 inocula grew in athymic mice and 11 of 12 inocula in lasat mice. Estimated by the square root of the relative tumour size related to time, the tumour growth was slightly, but insignificantly, less in lasat mice than in athymic mice. When the transplants removed from either athymic or lasat were compared by light microscopical examination, each of the two tumours demonstrated a similar appearance. The atypic mice prospered, while the lasat mice failed to thrive in similar laboratory surroundings. Thus this study does not confirm that heterotransplantation of human solid tumours on lasat mice is preferable to transplantation in athymic mice.

Animals↗
PubMed1982

Metastasis of a cultured human bladder carcinoma cell line transplanted into nude athymic mice.

Earlier reports concerning metastasis from human tumors transplanted to nude mice indicate that the metastatic potential is correlated with invasive subcutaneous growth. It also seems that cultured cell lines are more prone to metastasis than heterotransplanted solid tumors. A malignant human uroepithelial tumor, grown in culture since 1970, was injected subcutaneously to six nude mice. All animals developed locally invasive tumor nodules. Postmortem examination revealed metastatic growth in the pancreas, in the mesenteric fat tissue, in the stomach wall and intestines and in the lymphatic vessels of mesentery. The findings are well in accordance with earlier reports.

Animals↗
PubMed1981

Human malignant melanoma heterotransplanted to nude mice.

Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

Animals↗
PubMedDate not supplied

Prognostic factors in head and neck cancer: histologic grading, DNA ploidy, and nodal status.

Histopathologic malignancy score and DNA ploidy were investigated as prognostic factors for 72 cases of squamous cell carcinoma of the head and neck (HNSCC). The malignancy grading was based upon four different morphologic characteristics for the tumor cell population and four characteristics for the tumor-host relationship. DNA ploidy was determined through flow cytometry on fresh-frozen tumor samples. The median malignancy score was 20, with 71% of the tumors scoring less than 20 being diploid and 68% of the tumors scoring greater than or equal to 20 being nondiploid (p = 0.003). Univariate analysis revealed that tumors scoring less than 20 and diploid tumors had a significantly higher proportion of complete response and better survival as compared to tumors scoring greater than or equal to 20 and nondiploid tumors, respectively. There was a tendency toward better survival among patients without regional metastasis (N0) as compared with patients with regional spread (N+), whereas the other single factors, patient age, clinical stage, histologic grade, and tumor size did not correlate with prognosis. In N+ patients both malignancy score and DNA ploidy were predictive for survival, whereas in N0 patients only malignancy score was related to prognosis. A multivariate analysis showed that the combination of malignancy score and nodal status were the strongest predictors for survival. DNA ploidy did not contribute further information in this test, due to its close relation with the histopathologic malignancy score.

Adult↗
PubMedDate not supplied

Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck.

BACKGROUND: The progression of tumor growth requires the recruitment of new blood vessels. It has been suggested that the degree of neovascularization would correlate with clinical prognosis. The purpose of the present study was to ascertain whether tumor vascularization correlated with clinical outcome in cases of primary squamous cell carcinoma of the head and neck (SCCHN). METHODS: In tumor biopsies from 48 patients, microvessel density was determined by immunohistochemistry based on polyclonal antibodies against factor VIII related endothelial antigen. Computerized image analysis was used to evaluate the staining intensity per histologic area. The degree of staining was quantitated and expressed as microvessel density, low and high microvessel density subgroups being compared with regard to survival. RESULTS: Median survival was 10 months in the subgroup with very low microvessel density scores, as contrasted to 69 months in the remainder with high scores (p = 0.08). Neither the patient's age, TNM status, clinical stage, nor histologic grade was related to microvessel density. Among the patients who eventually died of SCCHN (n = 23), there was a subgroup of patients with complete response to radiotherapy. This subgroup had significantly higher microvessel density and longer survival than did the patients who responded poorly or not at all to radiotherapy. CONCLUSION: The findings suggest that in SCCHN the degree of vascularization might be used as a predictor of response to radiotherapy.

Adult↗
PubMedDate not supplied

Distribution of non-diploid flow-cytometric DNA indices and their relation to the nodal metastasis in squamous cell carcinomas of the head and neck.

Squamous cell carcinomas of the head and neck (HNSCC) evolve from diploid epithelial cells of the mucosa. At the time of diagnosis about two thirds of clinically diagnosed HNSCC are non-diploid according to flow-cytometric (FCM) analysis, indicating that during tumour progression there must be an acquisition and accumulation of chromosomal aberrations. At diagnosis one third to one half of HNSCC have clinically positive neck nodes. The objective of the present study was to see whether the progression to a metastatic phenotype is reflected in the distribution of FCM DNA ploidy in node-negative and node-positive HNSCC. The series comprised 200 patients with HNSCC. Tumour samples were obtained from diagnostic biopsies or primary surgery. A multistep preparation method and propidium iodide staining of nuclear DNA content was used for FCM. One hundred and forty one (71%) of the tumours were non-diploid. Only two tumours were hypodiploid (DNA index 0.73 and 0.93, respectively). Ten of the tumours exhibited two non-diploid stem cell lines. The frequency of non-diploidy in node-negative tumours was 65% and in node-positive ones about 80%. The frequency distribution of non-diploid DNA indices clustered in the hypotetraploid region (with a modal value of 1.71-1.74) and did not differ between node-negative and node-positive tumours. The hypothesis that the disposition to metastasis is reflected in the frequency distribution of non-diploid DNA indices could thus not be verified.

Adult↗
PubMedDate not supplied

Heterotransplantation of human head and neck tumours into nude mice.

Multimodality therapy of advanced malignant tumours of the head and neck includes surgery, radiotherapy and chemotherapy. However, the cure rate for these tumours is low and guidelines for the selection and timing of therapy are needed. For such guidelines, tumour cell kinetic parameter studies, e.g. cell proliferation, may be a suitable approach. In the present study an in vivo system for tumour cell kinetic studies, the nude mice system, has been evaluated for malignant human head and neck tumours. The overall 'take' rate for heterotransplanted human tumour grafts was 35%. The take rate was not influenced by the sterility state of the specimen. An advanced tumour stage showed a tendency to a higher take rate than less advanced tumour stages. In the tumour cell kinetic study the rate of DNA synthesis, measured by incorporation of radioactively labelled thymidine ( [3H]TdR) into DNA, was analysed in human malignant head and neck tumours and in serially heterotransplanted tumours. The rate of DNA synthesis was found to increase during the first serial passages though the histopathological picture remained unchanged. The increased rate of DNA synthesis may be explained by the recruitment of Go cells or by stem cell selection. These findings are discussed and may provide a basis for therapeutic guidelines.

Animals↗
PubMedDate not supplied

Beta 2-microglobulin in squamous cell carcinomas of the head and neck and in tumours heterotransplanted into nude athymic mice.

Beta 2-microglobulin (beta 2m) is a small polypeptide, related to the immunoglobulins and present on nucleated cells as part of the strong transplantation antigens. Elevated plasma levels have been recorded in patients with various malignant diseases. Human beta 2m has also been detected immunohistochemically in carcinomas transplanted into nude mice, and in the plasma of tumour-bearing mice. In the present study the occurrence of human beta 2m was studied in the plasma of 26 patients with squamous cell carcinoma (SCC) of the head and neck and in six heterotransplanted carcinoma lines. Extractable beta 2m was measured in seven SCC of the head and neck and in the six heterotransplanted tumour lines. Immunohistochemically detectable beta 2m was studied in 20 SCC and in six heterotransplanted tumour lines. Only 3 of 26 patients (12%) had elevated p-beta 2m levels. Stage IV tumours seemed to have more p-beta 2m (though within the normal range) than did less advanced tumours. There was no correlation between the total amount of extractable beta 2m in the patients' tumours and p-beta 2m. However, there was an association between the concentration of beta 2m in the tumours and p-beta 2m. Human beta 2m could be detected in the plasma of mice with tumours from all tumour lines, and there was a tendency toward an association between tumour size and p-beta 2m. The ratio of p-beta 2m/tumour volume differed between the tumour lines. Tumour volume doubling time (DT) was determined for the various tumour lines, and there was a correlation between DT and beta 2m concentration of the tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Cellular retinol-binding protein in mucosa, in benign and malignant non-squamous cell tumours of the head and neck.

The measurement and localisation of cellular retinol-binding protein (CRBP), in samples of normal oral mucosa, larynx papilloma and malignant lymphoma of the oropharynx, was performed with a radioimmunoassay and immunolocalisation techniques. As compared with CRBP concentration in normal mucosa, those in laryngeal papilloma were significantly higher, but those of malignant lymphoma were similar. CRBP concentrations were highest in maturing keratinocytes within the prickle cell layers of normal mucosa and in laryngeal papillomas, as estimated on the basis of immunoreactivity to CRBP. The retinyl palmitate concentrations in extracts of oral mucosa correlated to the retinol concentrations, both in plasma and mucosal extracts, but not to the CRBP content in mucosal extracts. The immunolocalisation of a cellular retinoic acid-binding protein (CRABP) like antigen in normal oral mucosa showed much the same picture with strongest staining of the maturing keratinocytes of the prickle cell layers.

Adult↗
PubMedDate not supplied

Cell cycle time, growth fraction and cell loss in xenografted head and neck cancer.

In a previous cell kinetic study with DNA flow cytometry (FCM) on xenografted human squamous cell carcinoma of the head and neck (HNSCC), there were significant variations in cell cycle phase distribution during early growth of the transplanted tumors. The object of the present study was to investigate further the cell kinetic mechanisms associated with variation in the growth rate of HNSCC. Xenografts from the same tumor line were examined on three different occasions: 12, 25 and 36 days following transplantation into nude mice. Cell cycle time "Tc", tumor growth fraction (GF) and cell loss factor were determined by computerized curve-fit analysis from percentage labelled mitoses curves. The mean growth curve of the tumors was logistic, with tumor doubling time (Td) ranging from 7.39 days to 8.86 days, and increasing as tumor volume increased. Although growth rate was higher in younger tumors, the cell cycle was longer with a median "Tc" of 69 hours on day 12 versus 34 hours on day 36. There were only minor variations in cell cycle phase distribution as measured by FCM. The growth fraction decreased slightly from 80% to 69% between day 12 and day 36, whereas cell loss factor increased markedly from 49% on day 12 to 78% on day 36. The results of the study emphasize the fact that cell loss is one of the most important cell kinetic determinants of tumor growth rate. This should be borne in mind when calculating proliferative cell kinetics in HNSCC.

Animals↗
PubMedDate not supplied

Increased response to cisplatin after long-term serial passage of a squamous cell carcinoma xenograft.

We have retrospectively investigated the response to cisplatin of a squamous cell carcinoma of the head and neck xenografted to nude mice during nine years of serial transplantation. Tumour growth rate decreased gradually. After nine years and over 100 passages, there was a sudden increase in cisplatin sensitivity. Histopathological examination showed that, of two histopathologically different subpopulations present in earlier passages, the predominant one was no longer detectable. The DNA-index did not change.

Animals↗