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J Wennerberg

Publications and source records attributed to J Wennerberg.

At least 73 records · Page 4Linked to original sources
PubMed1990

Unrelated clonal chromosomal aberrations in carcinomas of the oral cavity.

Short-term cultures from 12 oral squamous cell carcinomas were cytogenetically investigated. A normal karyotype was found in 3 tumors, 2 of which had many nonclonal changes. Clonal chromosome abnormalities were detected in the remaining 9 cases, in 6 of them in the form of 2 or 3 abnormal clones. In 5 cases the different clones were cytogenetically unrelated, suggesting a multiclonal origin. Numerous additional nonclonal changes were present in 4 of the 9 tumors with clonal aberrations. None of the structural aberrations, clonal or nonclonal, were found in more than one case; nor did any of the rearrangements correspond to cancer-associated aberrations known from other tumors. The aberration breakpoints of the present series and of previously reported tongue cancer clustered to bands 1p32, 1p22, 1p11, 1q21, 1q23, 1q25, 1q32, 1q42, 1q44, 2q31, 3p11, 4q35, 7p22, 11p15, 11q13, 12q24, and 17q25.

Aged↗
PubMed1990

Frequent rearrangement of chromosomal bands 1p22 and 11q13 in squamous cell carcinomas of the head and neck.

We report the finding of clonal structural chromosome abnormalities in short-term cultures from 15 squamous cell carcinomas of the head and neck region. When the distribution of chromosomal breakpoints in these 15 tumors and in the 16 head and neck carcinomas previously described are assessed, a marked clustering is seen at bands 1p22 and 11q13, which are rearranged in eight and nine tumors, respectively. No other band was involved in aberrations in more than five tumors. Cytogenetic evidence of gene amplification was seen in four tumors, three times in the form of homogeneously staining regions (twice located in 11q13), and in one tumor as double minutes. Among the candidate genes for such amplification are BCLI, INT2, and HSTI, all of which map to 11q13, and NRAS, which maps to 1p22. All these oncogenes have previously been shown to be amplified in subsets of head and neck carcinomas. We conclude that bands 1p22 and 11q13 are nonrandomly involved in chromosomal rearrangements in head and neck carcinomas and suggest that activation of oncogenes located in these bands may proceed via cytogenetic mechanisms.

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PubMed1990

Multiple clonal chromosome aberrations in squamous cell carcinomas of the larynx.

Short-term cultures from five squamous cell carcinomas of the larynx were subjected to cytogenetic analysis. In the first three cases, two, three, and 10 chromosomally abnormal clones were detected. Single clonal abnormalities were found in cases 4 and 5. In addition to the clonal aberrations, a number of nonclonal changes were also present in all five tumors. None of the aberrations, clonal or nonclonal, was found in more than one tumor, nor did the rearrangements correspond to any of the consistently cancer-associated aberrations known from other tumors. The remarkably diverse karyotypic picture of the five squamous cell larynx carcinomas, in particular the finding of cytogenetically unrelated clones in three of them, suggests that some of these neoplasms are polyclonal rather than monoclonal.

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PubMed1990

Metoclopramide enhances the effect of ionizing radiation on xenografted squamous cell carcinoma of the head and neck.

The commonly used drug metoclopramide, a benzamide derivative, has been shown previously in our laboratory to enhance the effect of cisplatin on xenografted squamous cell carcinomas of the head and neck. In the present study, we show that metoclopramide also enhances the effect of ionizing radiation. Two human squamous cell carcinoma lines of the head and neck xenografted to nude mice have been used. Doses of radiation were chosen (5 and 8 Gy single doses) which caused only a slight retardation of tumor growth when administered alone. Tumor response to ionizing radiation was assessed with and without metoclopramide (2.0 mg kg-1), and administered at the time of radiation and 24 and 48 hr after treatment. The effects of these schedules on the tumors were compared using the reduction of the area under the growth curves and specific growth delay. The dose schedule with metoclopramide alone did not induce any significant reduction in the area under the growth curves. The addition of metoclopramide to the radiated groups caused a significant enhancement of the radiation-induced reduction of the area under the growth curves in both of the tumor lines studied.

Animals↗
PubMed1989

A relationship between retinol and cellular retinol-binding protein concentrations in human squamous cell carcinomas.

The retinol and retinyl ester concentrations in human xenografted squamous cell carcinomas, with various concentrations of cellular retinol-binding protein (CRBP), were studied, as well as the in vivo uptake and esterification in these tumours of labelled retinol, presented as a complex with plasma RBP. The mean retinol concentration in the different tumours was in the range 3.7-6.2 nmol/g protein, and the mean CRBP concentration was between 16 and 69 nmol/g protein. There was a statistically significant correlation between the retinol and the CRBP concentrations in the same tumour (P less than 0.001; r = 0.622). Calculation of the maximal extent of retinol-saturation of CRBP showed low values (range: 9-26%). Retinyl palmitate, the predominant retinyl ester, comprised approx. 70% of the retinyl esters in the tumours. There was no correlation between the concentration of CRBP and that of retinyl palmitate. The uptake of [3H]retinol from intravenously injected retinol-RBP complex was similar in the four human squamous cell carcinomas studied, and not related to their CRBP concentration. 20% of the radioactivity in tumour specimens was lipid soluble, as compared to 96% in liver specimens, showing that in the former a higher fraction metabolised to polar compounds. Taken together, our results suggest that in these squamous carcinoma cells, factors other than cellular CRBP content are the major determinants of net cellular uptake and esterification of retinol. The cellular retinol concentration, on the other hand, appears proportional to CRBP content.

Carcinoma, Squamous Cell↗
PubMed1989

Basosquamous papilloma. A benign epithelial skin tumor with multiple cytogenetic clones.

Cytogenetic analysis of short-term cultures from a basosquamous papilloma revealed the following mosaic karyotype: 46,XX,t(2;5)(q31;q31),t(8;15)(p21;q21)/46,XX,t(7;17)(p13;p13)/47,XX, t(3;20)(q12;p13),+7/46,XX,t(1:12)(p12;q13). The finding of four abnormal, cytogenetically unrelated clones suggests a multicellular origin of this benign skin tumor. None of the structural rearrangements encountered have previously been associated with neoplasia.

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PubMed1989

Clonal chromosome aberrations in a keratoacanthoma and a basal cell papilloma.

Clonal chromosome abnormalities were found in short-term cultures from two epithelial skin tumors, a basal cell papilloma and a keratoacanthoma. The three-way translocation t(2;6;11)(q21;q27;p13) was the sole clonal rearrangement in the basal cell papilloma. The karyotype of the keratoacanthoma was more complex: 46,XX,der(2)(2pter----2p13::2p11----cen----2q37: :5q33----5qter),der(2) (:2p13----cen----2q37::6q23----6qter),der(5)t(2; 7;5)(q37;q11;q33),der(6) (6pter----cen----6q23::2p13----2pter),der(7)t(2; 7;5)(q37;q11;q33), del(13)(q11q14). In addition, several nonclonal structural changes were seen in both tumors.

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PubMed1989

Diverse chromosome abnormalities in squamous cell carcinomas of the skin.

Short-term cultures from three invasive squamous cell carcinomas of the skin were cytogenetically analyzed. Clonal chromosome aberrations were found in all tumors. In the first case, two of three abnormal clones were related, and in the second case, two of five clones demonstrated cytogenetic similarities. Both clones detected in case 3 had a structural rearrangement in common. Several nonclonal changes were seen in all three cases in addition to the clonal aberrations. None of the rearrangements detected, clonal or nonclonal, corresponds to any of the consistently cancer-associated aberrations known from other neoplasms. The remarkably diverse karyotypic picture of the three squamous cell carcinomas, in particular the finding of unrelated clones in two of them, hints that these neoplasms may be poly-rather than monoclonal. The lack of a common cytogenetic denominator argues that if chromosomal changes are of pathogenetic importance in this tumor type, a wide variety of apparently dissimilar changes exist that are roughly equal in their capacity to malignantly transform skin epithelium.

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PubMed1989

Metoclopramide enhances the effect of cisplatin on xenografted squamous cell carcinoma of the head and neck.

The chromatin-bound enzyme adenosine diphosphate ribosyl transferase is activated by DNA-damaging agents. Substances that inhibit the enzyme, such as benzamide analogues, are known to increase the cytotoxicity of ionising radiation and cytotoxic drugs. The purpose of the present study was to investigate whether the anti-emetic drug metoclopramide, a benzamide derivative (4-amino-N-2-(diethylaminoethyl)-5-chloro-2-methoxybenzamide; MCA), potentiates the effect of cisplatin (cis-diammine-dichloroplatinum; CDDP) on squamous cell carcinoma (SCC). For that purpose human SCC of the head and neck (i.e. tumour line AB and EH) xenografted to nude mice were used. Two administration schedules were tested: (a) MCA (2.0 mg kg-1 i.p.) one hour before CDDP (7.5 mg kg-1 i.p.); and (b) MCA (3 x 2.0 mg kg-1) given concomitant to, 24 and 48 hours after CDDP (7.5 mg kg-1) administration. Treatment efficacies were compared using the area under the growth curves (AUC), tumour volumes and specific growth delay (SGD). There was no mortality and no weight loss of significance in any treatment group. MCA alone did not induce any significant reduction in AUC, tumour volume or SGD with either treatment schedule. CDDP alone gave a significant reduction of tumour growth in tumour line AB but not in tumour line EH. In schedule (a) the addition of MCA did not give any additive effect. However, in schedule (b), for both tumour lines, MCA enhanced the effect of CDDP by significantly reducing the AUC (AB: P less than 0.0001; EH: P less than 0.001) and increasing SGD (AB: P less than 0.012; EH: P less than 0.001) when compared to the tumours given CDDP alone. These effects were observed at a MCA dose currently being administered to humans.

Animals↗
PubMed1989

Growth potential of acoustic neuromas.

Tumor samples from 32 patients with acoustic neuroma operated with translabyrinthine approach were analyzed with flow cytometric technique with respect to ploidy and cell cycle phase distribution. In all cases the diagnosis of acoustic neuroma was verified histologically, two patients had Recklinghausen's disease. None of the tumors showed aneuploid cell lines. Median S-phase fraction was 6.8% (range 1.4 to 19.9%). The spread of S-phase values had a greater range for the smaller tumors (volume less than or equal to 2 cm3) of the material. There was no correlation neither between the fraction of cells in S-phase and age of the patient, nor between the fraction of cells in S-phase and tumor size. The present finding with a great variability in S-phase values does not support an expectant attitude regarding surgical intervention in patients with acoustic neuromas.

Age Factors↗
PubMed1988

The effect of cisplatin and fluorouracil on xenografted human squamous cell carcinoma of the head and neck.

In combined modality treatment, cisplatin and fluorouracil are considered to act synergistically. The assumption is based on results in murine leukemias and has not hitherto been tested on human squamous cell carcinoma. In the present study, cisplatin and fluorouracil, used singly and in combination, were tested on two human squamous cell carcinomas of the head and neck, xenografted to nude mice. Cisplatin (7.5 mg/kg) was given as a single-dose intraperitoneal injection and fluorouracil as repeated intraperitoneal injections every eight hours for four days to a total dose of 200 mg/kg. The toxicity of the cisplatin and fluorouracil combination was lower (27%) than that of fluorouracil alone (50%). Both drugs gave a dose-dependent inhibition of tumor volume growth. Using gained growth delay as endpoint, cisplatin and fluorouracil therapy exhibited a synergistic effect on both tumor lines.

Animals↗
PubMed1988

Changes in histology and cell kinetics during the growth course of xenografted squamous cell carcinoma.

Two xenografted tumor lines, established from squamous cell carcinomas of the head and neck, were studied with respect to the growth parameters of the Gompertz function and changes in growth rate, cell cycle phase distribution, and histologic pattern during the course of growth. The tumors were transplanted subcutaneously in the back. Both tumor lines exhibited growth curves compatible with Gompertzian growth. The parameters of the Gompertz function differed significantly between the tumor lines. Tumor volume doubling time also varied during the course of growth. Flow cytometric analysis of cell cycle phase distribution showed an initial decrease in the fraction of cells in S-phase, parallel with an increase in the fraction of cells in GO/1-phase. As much as 50% of the cells were mouse-derived in tumors less than 100 mm3 in volume, after which the proportion of mouse-derived cells decreased to below 10%. This variation correlated with changes in the histopathologic picture.

Animals↗
PubMed1988

Unique karyotypic abnormalities in a squamous cell carcinoma of the larynx.

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the larynx, a type of carcinoma in which chromosome aberrations have hitherto not been reported. The tumor karyotype was 46,XY,inv(2)(p22q24),t(9;13)(q34;q12),t(11;18)(q23;q21). None of these abnormalities have been described in carcinomas before.

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PubMed1988

Multiple unrelated clonal chromosome abnormalities in an in situ squamous cell carcinoma of the skin.

We have cytogenetically analyzed short-term cultures from an in situ squamous cell carcinoma of the skin (Bowen's disease). The following mosaic tumor karyotype was found: 46,XX, -1, +der(1)(pter----p22::q11----cen----p22:), -9, +der(9)t(1;9)(q11; p24)/46,XX,t(3;6) (q21;p21)/46,XX,t(5;14)(q13;q24),t(7;18)(q32;q11)/46,XX,t(8;11)(p22;q13) /46, XX,t(8;11) (p22;q13),t(15;17) (q13;q24)/46,XX,t(12;15)(q12;p11). None of the rearrangements correspond to previously known cancer-associated abnormalities. Two of the clones are obviously related, and it is reasonable to assume that the t(15;17) developed as an evolutionary change in a cell that already contained t(8;11)(p22;q13). Since five clones without cytogenetic similarities were found in this in situ skin carcinoma, we suggest that the tumor was of polyclonal origin. It is impossible to decide whether all, or indeed any, of the visible abnormalities constitute pathogenetically essential primary changes, or merely represent chromosomal markers of secondary importance in tumorigenesis.

Carcinoma in Situ↗