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266 A submicroscopic homozygous deletion at the D3S3 locus in a cell line isolated from a small cell lung carcinoma Rabbius P, Bergh J, Douglas I, Collins F, Waters J. MRC Clinical Oncology and Radiotherapeutics. MRC Centre. Hills Road, Cambridge CB2 2QH. Genes Chromosomes Cancer 1990;2:231-8. We have used I4 DNA probes, which detect I9 differenl restriction enzyme length polymorphisms, to search for heterozygosityon chro- mosome 3 in five cell lines isolated from patients with small cell lung carcinoma. The cell lines on karyotype analysis did not show the deletion in chromosome3 characteristic of this disease.Our objective was to determine if allelic loss had occurred by some chromosomal mechanism other thandeletion. Two of the cell linesare consistent with allelic loss having occured by whole chromosomeloss and reduplica- tion. The third may have lost only the shortarm due to i(3q) formation. The fourth cell line has an i(3q) chromosome,together with a translo- cation product involving the distal portion of the shortarm of chromo- some 3. Lack of evidence of heterozygosityfor this distal portion of 3p suggeststhatacopyolthe3phomologueis involvedintbetranslocalion and therefore does not explain allelic lossof the other homologue.The fifth, while also likely to have lost one chromosomehomologue,has a submicroscopicdeletion on all chromosome 3s. only detectable by RFLP analysis. Such homozygous deletions have recently proved useful in the isolationof tumour suppressor genes. Modulation of ~53 gene expression and cytokeratin 18 in retinoid- mediated invasion suppressed lung carcinoma eells Ledinko N, Costamino RL. Helene W. Toolan institute for Medical Research, 100 Hospital Drive, VTO5201. Anticancer Res 1990;10:1335- 40. The effect of retinoid-inducedsuppression of in vitro invasiveability of A549 human lung carcinoma ce.lIs on p53 gene expression and cytokeratin (CK) I8 level was investigated. Inductionof suppression of cell invasion wasaccompanied by an increasein amounts ofp53 mRNA and protein and a decrease in CK18. Moreover, the ~53 mRNA and protein levels increased coordinately with time in relationship to the degreeof invasion-suppression. The resultsindicatethatp53 expression is involved in alteration of the lung cell metastaticphenotype.and that p53 is an important marker for this process. In vitro natural kilter and Iymphokine-activated killer activity in patients with bronchogenic carcinoma Dunlap NE, Lane VG, Cloud GA, Tilden AB. Department ofMedicine. Division of Pulmonary and Critical Care Medicine, Cancer Center. University of Alabama Medical Center and Veterans Administration Hospital, Birmingham, AL 35294. Cancer 1990;66:1499-1504. The authors examined peripheral blood mononuclearcells from 45 patientswith bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/ or interleukin-2 (IL-2, 100 U/ml). Our results show that lymphocytes from patientswith bmnchogeniccarcinoma can acquire LAK activity. but the level ofactivity acquired was significantly lower comparedwith lymphocytes fmm 25 control subjects when IL-2 cultures were supple- mented with 10% autologous human serum (AHS) (15.6% f 2.1% specific release versus 26.0% f 2.9% specific release, P = 0.004). The LAK activity,definedascytotoxicityofan NK-resistant cell line.of the patients’lymphocytes was augmented when cells were cullured with both IL-2 and IFN comparedwith IL-2 alone (P= 0.0001. paired l-lest). Conml subjects were unchanged(P = 0.09). There was no significanl difference between groupsof patientswith different histologictypes of tumor or different stages of disease.The NK activity, defined as killing of NK-sensitive K-562targetcells. of the patients’ lymphocytes wasnot signiticantly different from that of the controls’ lymphocytes (42.8% f 3.0% specific release versus49.3% f 3.3% specific release. P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogeniccarcinoma. l%trogen and progesterone receptors in bronchogenic carcinoma Cagle PT. Mcdy DR. Schwartz MR. Baylor College of Medicine, Department of Pathology, One Baylor Plaza. Houston. TX 77030. Cancer Rcs 1990;50:6632-5. Although the lung is not usually considereda major targel organ of sex hormones, epidemiological observations, studies of pulmonary neoplasms in laboratory animals, and investigations of carcinomas derived from other ‘nontarget’ organs suggestthat sex hormonesmay have a role in the pathogenesis of bronchogenic carcinoma. TO contirm that esuogen (ER) and progesterone receptors are present in humanlung cancers, 19 resected lung cancers were examined for receptors usinga prelabeled sucrosegradient method. Three squamous cell carcinomas were positive for ER (%.9 fmol/mg cytosol protein). Three squamous cell carcinomas, two adenocarcinomas, and one small cell carcinoma were positive for progesteronereceptors (z-6.9 fmol/mg cytosol pro- tein). One tumor, a squamous cell carcinoma arising in a woman who smoked, had an ER level of 301 fmol/mg, a highly positive level even for breastcancers.These observations may provide a basisfor adjuvant hormonal therapy in selected lung cancer patients. Recurrent chromosome aberrations in human lung squamous cell carcinomas Viegas-Pequignot E. Flury-Herard A, De Cremoux H, Chlecq C, Bignon I, Dutrillaux 9. (IRA 620 C.N.R.S., lnstitut Curie. Section de Biologic. Structure et Mutagenese Chromosomiques. 26 rue d’ lllm, 75231 Paris Cedex 05. Cancer Genet Cytogenet 1990;49:3749. Cytogenetic study of seven cases of previously untreated lung squamous cell carcinomas (SQC) is reported. Chromosome numbers vary fmm 38 to 538, with a majority of hypotriploid karyotypes with complex rearrangements.The numbers of recorrent imbalances were evaluated in considering the average number of chromosomes or chromosome segments in each analyzed metaphase and for each case. Indecreasingorderof frequency,deRcienciesfor3p.5q,8p.Y,5p, IOp, 13, and, to a lesser degree, for 8q. 9. IOq, 11 pter. 14, 15, and 21 were observed; the excesses principally involve lg. 3q, and 74. In three tumors, homogeneously staining regions were observed at various chromosome sites. Most chromosome rearrangementsoccurred after breakage in constitutive hetercchromatin, and no recurrentbreakpoints were found in euchmmatin except lIpl5. The major consequences of these anomalies may be chmmosomal imbalances.leading lo hemizy- gosity and perhapsrelated to gene dosage, rather than to alterationsof genes. CCK-antagonists interact with CCK-B receptors on human small cell lung cancer cells Staley J, Jensen RT, Moody TW. Department of Biochemistry and Health Sciences, George Washington University School of Medicine and Molecular Biology, 2300 Eye Street NW, Washington, DC 20037. Peptides 1990;11:1033-6. The ability of cholecystokinin (CCK) receptorantagonists to interact withCCKreceptorsinsmall lungcancer(SCLC)cellswasinvestigated. L-365.260, CCK-8, L-364.718. CBZ-CCK(27-32)-NH, and proglu- mide anajogue 10 inhibited specific %CCK-8 binding to SCLC cells with IC, values of 0.2,2,500, lOO,CkX and 500,000 nM, respectively. Gastrin-I and CCK-8 elevated thecytosolic Ca” when SCLC cells were loadedwithFura2-AM. L-365,260inhibitedthecytosolicCa”increase causedby 10 nM CCK-8 in a dose-dependcnl manner.The effects of 10 nM L-365.260 were reversed by high concentrations of CCK-8. These data indicatethat L-365,260 functions as a reversibleCCK-8 antagonist using SCLC cells. Pathology Primary peduncutated leiomyosarcoma of the lung Pate1SR, Jindrak KF, Anandarao N. Division of Pulmonary Disease. MethodistHospital.506SixthS1, Brooklyn, NY 11215. NY State J Med 1991;91:30-1. Primary mesenchymaltumors account for a small percentageof all pulmonary neoplasms.Primary leiomyosarcoma of the lung is a very rare tumor. Since me fust reportedcaseby Davidsonin 1907. fewer than IOOcaseshavebeenreported inureEnglish literature.Wepresentacasc of primary pedunculated leiomyosarcoma of the lung, which to OUT knowledge represents the second such reported case.

Estrogen and progesterone receptors in bronchogenic carcinoma

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266

A submicroscopic homozygous deletion at the D3S3 locus in a cell line isolated from a small cell lung carcinoma Rabbius P, Bergh J, Douglas I, Collins F, Waters J. MRC Clinical

Oncology and Radiotherapeutics. MRC Centre. Hills Road, Cambridge

CB2 2QH. Genes Chromosomes Cancer 1990;2:231-8. We have used I4 DNA probes, which detect I9 differenl restriction

enzyme length polymorphisms, to search for heterozygosity on chro- mosome 3 in five cell lines isolated from patients with small cell lung carcinoma. The cell lines on karyotype analysis did not show the deletion in chromosome 3 characteristic of this disease. Our objective was to determine if allelic loss had occurred by some chromosomal mechanism other than deletion. Two of the cell lines are consistent with allelic loss having occured by whole chromosome loss and reduplica- tion. The third may have lost only the short arm due to i(3q) formation. The fourth cell line has an i(3q) chromosome, together with a translo- cation product involving the distal portion of the short arm of chromo- some 3. Lack of evidence of heterozygosity for this distal portion of 3p suggeststhatacopyolthe3phomologueis involvedintbetranslocalion and therefore does not explain allelic loss of the other homologue. The fifth, while also likely to have lost one chromosome homologue, has a submicroscopic deletion on all chromosome 3s. only detectable by RFLP analysis. Such homozygous deletions have recently proved useful in the isolation of tumour suppressor genes.

Modulation of ~53 gene expression and cytokeratin 18 in retinoid- mediated invasion suppressed lung carcinoma eells Ledinko N, Costamino RL. Helene W. Toolan institute for Medical

Research, 100 Hospital Drive, VTO5201. Anticancer Res 1990;10:1335- 40.

The effect of retinoid-induced suppression of in vitro invasive ability of A549 human lung carcinoma ce.lIs on p53 gene expression and cytokeratin (CK) I8 level was investigated. Induction of suppression of cell invasion wasaccompanied by an increase in amounts ofp53 mRNA and protein and a decrease in CK18. Moreover, the ~53 mRNA and protein levels increased coordinately with time in relationship to the degree of invasion-suppression. The results indicate thatp53 expression is involved in alteration of the lung cell metastatic phenotype. and that p53 is an important marker for this process.

In vitro natural kilter and Iymphokine-activated killer activity in patients with bronchogenic carcinoma Dunlap NE, Lane VG, Cloud GA, Tilden AB. Department ofMedicine.

Division of Pulmonary and Critical Care Medicine, Cancer Center.

University of Alabama Medical Center and Veterans Administration

Hospital, Birmingham, AL 35294. Cancer 1990;66:1499-1504. The authors examined peripheral blood mononuclear cells from 45

patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/ or interleukin-2 (IL-2, 100 U/ml). Our results show that lymphocytes from patients with bmnchogenic carcinoma can acquire LAK activity. but the level ofactivity acquired was significantly lower compared with lymphocytes fmm 25 control subjects when IL-2 cultures were supple- mented with 10% autologous human serum (AHS) (15.6% f 2.1% specific release versus 26.0% f 2.9% specific release, P = 0.004). The LAK activity,definedascytotoxicityofan NK-resistant cell line.of the patients’ lymphocytes was augmented when cells were cullured with both IL-2 and IFN compared with IL-2 alone (P= 0.0001. paired l-lest). Conml subjects were unchanged (P = 0.09). There was no significanl difference between groups of patients with different histologic types of tumor or different stages of disease. The NK activity, defined as killing of NK-sensitive K-562targetcells. of the patients’ lymphocytes wasnot signiticantly different from that of the controls’ lymphocytes (42.8% f 3.0% specific release versus 49.3% f 3.3% specific release. P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma.

l%trogen and progesterone receptors in bronchogenic carcinoma Cagle PT. Mcdy DR. Schwartz MR. Baylor College of Medicine,

Department of Pathology, One Baylor Plaza. Houston. TX 77030. Cancer Rcs 1990;50:6632-5.

Although the lung is not usually considered a major targel organ of sex hormones, epidemiological observations, studies of pulmonary neoplasms in laboratory animals, and investigations of carcinomas derived from other ‘nontarget’ organs suggest that sex hormones may have a role in the pathogenesis of bronchogenic carcinoma. TO contirm that esuogen (ER) and progesterone receptors are present in human lung cancers, 19 resected lung cancers were examined for receptors using a prelabeled sucrose gradient method. Three squamous cell carcinomas were positive for ER (%.9 fmol/mg cytosol protein). Three squamous cell carcinomas, two adenocarcinomas, and one small cell carcinoma were positive for progesterone receptors (z-6.9 fmol/mg cytosol pro- tein). One tumor, a squamous cell carcinoma arising in a woman who smoked, had an ER level of 301 fmol/mg, a highly positive level even for breast cancers. These observations may provide a basis for adjuvant hormonal therapy in selected lung cancer patients.

Recurrent chromosome aberrations in human lung squamous cell carcinomas Viegas-Pequignot E. Flury-Herard A, De Cremoux H, Chlecq C, Bignon I, Dutrillaux 9. (IRA 620 C.N.R.S., lnstitut Curie. Section de Biologic. Structure et Mutagenese Chromosomiques. 26 rue d’lllm,

75231 Paris Cedex 05. Cancer Genet Cytogenet 1990;49:3749. Cytogenetic study of seven cases of previously untreated lung

squamous cell carcinomas (SQC) is reported. Chromosome numbers vary fmm 38 to 538, with a majority of hypotriploid karyotypes with complex rearrangements. The numbers of recorrent imbalances were evaluated in considering the average number of chromosomes or chromosome segments in each analyzed metaphase and for each case. Indecreasingorderof frequency,deRcienciesfor3p.5q,8p.Y,5p, IOp, 13, and, to a lesser degree, for 8q. 9. IOq, 11 pter. 14, 15, and 21 were observed; the excesses principally involve lg. 3q, and 74. In three tumors, homogeneously staining regions were observed at various chromosome sites. Most chromosome rearrangements occurred after breakage in constitutive hetercchromatin, and no recurrent breakpoints were found in euchmmatin except lIpl5. The major consequences of these anomalies may be chmmosomal imbalances. leading lo hemizy- gosity and perhaps related to gene dosage, rather than to alterations of genes.

CCK-antagonists interact with CCK-B receptors on human small cell lung cancer cells Staley J, Jensen RT, Moody TW. Department of Biochemistry and

Health Sciences, George Washington University School of Medicine

and Molecular Biology, 2300 Eye Street NW, Washington, DC 20037.

Peptides 1990;11:1033-6. The ability of cholecystokinin (CCK) receptor antagonists to interact

withCCKreceptorsinsmall lungcancer(SCLC)cellswasinvestigated. L-365.260, CCK-8, L-364.718. CBZ-CCK(27-32)-NH, and proglu- mide anajogue 10 inhibited specific %CCK-8 binding to SCLC cells with IC, values of 0.2,2,500, lOO,CkX and 500,000 nM, respectively. Gastrin-I and CCK-8 elevated thecytosolic Ca” when SCLC cells were loaded withFura2-AM. L-365,260inhibitedthecytosolicCa”increase caused by 10 nM CCK-8 in a dose-dependcnl manner. The effects of 10 nM L-365.260 were reversed by high concentrations of CCK-8. These data indicate that L-365,260 functions as a reversible CCK-8 antagonist using SCLC cells.

Pathology

Primary peduncutated leiomyosarcoma of the lung Pate1 SR, Jindrak KF, Anandarao N. Division of Pulmonary Disease.

MethodistHospital.506SixthS1, Brooklyn, NY 11215. NY State J Med 1991;91:30-1.

Primary mesenchymal tumors account for a small percentage of all pulmonary neoplasms. Primary leiomyosarcoma of the lung is a very rare tumor. Since me fust reported case by Davidson in 1907. fewer than IOOcaseshavebeenreported inureEnglish literature. Wepresentacasc of primary pedunculated leiomyosarcoma of the lung, which to OUT knowledge represents the second such reported case.