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MYC family DNA amplification in 126 tumor cell lines from patients with small cell lung cancer
Abstracts MYC family DNA amplification in 126 tumor cell with small cell lung cancer Johnson BE. Russell E, Simmom ,\M et al. Nuq Brunch,
J Cell
National
Biochem
Nuwl
Mrdicul
1996;62
Suppl.
c‘; !zter NCI.
Bethesda.
lines
from
Mrdiccrl MD
patients
Oncolog?, 30889-510.
24.210-7.
We identified 126 tumor cell iines established from patients with small cell cancer at the NCI-Navy hiedical Oncology Branch from 1977 through 1993. Extensive clinical il~!brmation was available on 96 patients from whom these cell lmes were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the I6 years of the study (P = 0.0081. MYC family DNA amplification was present in I6 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (I 1%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P=O.OOl). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.0001 and 0.05, respectively). Frequent involvement of chromosome 3p alterations in lung carcinogenesis: Allelotypes of 215 established cell lines at six chromosome 3p loci Buchhagen DL. Depurtment of Mm/~?rtr. Nutionul Nurul Medical Cmrrr, Uniformed Se-r Unir. of Heulth .Qi., Bethesda MD 208/4. J Cell Biochem 199662 Suppl. 24:198-2OY. We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3~): D353 (3plZZpl3), D3530 (3p13), D352 (3pl4mp21.1), D3S32 (3~21). D3F1552 (3~21). and THRB (3~24). Eighty-seven small cell lung cancer (SCLC). 93 non-small cell lung cancer (14SCLC). 6 extrapulmonary SCLC, 6 mesothelioma. and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D353 (3%), D352 (3%). D3Fl552 (lo’%)), and THRB (6%) when compared with frequencies of 8, 42. 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D353 (5%). DFl552 (17%), and THRB (15%). Adenocarcinema (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D353. In addition to D353, the lowest frequencies of heterozygoslty were been ,tt D3Fl552 for Ad (9%), D352 for large cell carcinomas (8%), and THRB for adenosquamous (0%). bronchioloalveolar (0%). and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D353 locus (3pl2-~13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D352 (3p14-pZl.l), D3F1552 (3~21). and THRB (3P24) IOCI. Effect of swami” on squamous differentiation and apoptosis in three human non-small cell lung cancer cell lines Lokshin A. Levitt ML. Allegheny Grnerul Hospital. Pittsburgh. PA /5-7/Z. J Cell Biochem 1996:62 Suppl. 24:186-97. Non-small cell lung cancer (NSCLC) is fatal m approximately 90% of all cases due to the failure of systemic therapy. secondary to resistance to chemotherapy. In such malignancies new therapeutic paradigms are needed. One such approach takes advantage of normal physiologic
growth regulatory mechanisms, such as terminal cellular differentiation or apoptosis. Suramin. as an antineoplastic drug, has shown efficacy in the treatment of prostate cancer and is capable of promoting differentiating in several human cancer cell lines. Little is known about the differentiating effects of suramin in lung cancer. In the present investigation we evaluated the ability of suramin to induce cross-linked envelope (CLE) formation, as a common marker for squamous differentiation and apoptosis, in three representative human non-small cell lung cancer lines: NCI-H226 (squamous). NCI-H358 (Bronchoalveolar (adenocarcinoma)). and NCI-R596 (adenosquamous). Among agents that we have tested. suramin demonstrated the unique ability to induce spontaneous CLE formation in the two cell lines with squamous features, NCI-H226 and NCI-H596. Suramin induced CLE formation was accompanied by DNA fragmentation, a marker for apoptosis, in NCI-H596 and NCI-H358. but not in NCI-H226. Stimulation of CLE formation by suramin correlated with the rapid induction of both type II transglutaminase (TG) activity and involucrin expression. These parameters were protein synthesis independent, suggesting post-translational mechanisms of suramin activity. Induction of differentiation] apoptosis markers by suramin did not correlate with its effect on growth. Modulation of signal transduction is a likely candidate mechanisms for suramin activity in lung cancer. The relationship between growth, squamous differentiation. and apoptosis is considered. Steroid-hormone receptors in cell lines and tomor cancer Kaiser U, Hofmann J, Schilli M et al. Division ogl’,
Department
Buldingrr
of Internal
Strusse,
3.5033
Medicine,
Murburg.
Philipps
Int J Cancer
biopsies
of human
lung
of Hematolog,v/OitcolUnioersitut Marburg.
1996;67:357-64.
Female gender is a significant independent favorable prognostic factor in lung cancer To study the possible role of sex hormones in lung cancer. the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry. &and-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation. NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in I3 and androgen receptor in 12 out of 17 cases examined: sex-steroid-receptor expression was virtually absent in SCLC cell line>. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sexsteroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of I6 cases. vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer. Pattern Seregni
of mocin gene expression in normal and neoplastic lung tissues E, Botti C, Lombardo C et al. DiGone di Medicina Nucleare.
I.st. Nuzionale
Anticancer
Studio
Cura
Res 1996; I6:2209-
Tumori.
cia
G Venetian
I, 20133
Miluno.
13.
This work evaluates the expression in lung cancer of the most well characterized mu& genes (MUCI. MUCZ, MUC3) and of the recently described MUC4 in lung tissues. to check a correlation between the expression of any particular gene and this tumor. Hybridization with synthetic oligonucleotides obtained from a part of the sequences of MUCI, MUC?, MUC3 and MUC4, was performed on blotted RNA from 18 lung cancer tissue specimens and from IO normal tissues samples taken, when possible. from the normal lung counterpart. By means of Northern blot analysis MUCI revealed to be the most
J Cell
National
Biochem
Nuwl
Mrdicul
1996;62
Suppl.
c‘; !zter NCI.
Bethesda.
lines
from
Mrdiccrl MD
patients
Oncolog?, 30889-510.
24.210-7.
We identified 126 tumor cell iines established from patients with small cell cancer at the NCI-Navy hiedical Oncology Branch from 1977 through 1993. Extensive clinical il~!brmation was available on 96 patients from whom these cell lmes were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the I6 years of the study (P = 0.0081. MYC family DNA amplification was present in I6 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (I 1%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P=O.OOl). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.0001 and 0.05, respectively). Frequent involvement of chromosome 3p alterations in lung carcinogenesis: Allelotypes of 215 established cell lines at six chromosome 3p loci Buchhagen DL. Depurtment of Mm/~?rtr. Nutionul Nurul Medical Cmrrr, Uniformed Se-r Unir. of Heulth .Qi., Bethesda MD 208/4. J Cell Biochem 199662 Suppl. 24:198-2OY. We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3~): D353 (3plZZpl3), D3530 (3p13), D352 (3pl4mp21.1), D3S32 (3~21). D3F1552 (3~21). and THRB (3~24). Eighty-seven small cell lung cancer (SCLC). 93 non-small cell lung cancer (14SCLC). 6 extrapulmonary SCLC, 6 mesothelioma. and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D353 (3%), D352 (3%). D3Fl552 (lo’%)), and THRB (6%) when compared with frequencies of 8, 42. 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D353 (5%). DFl552 (17%), and THRB (15%). Adenocarcinema (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D353. In addition to D353, the lowest frequencies of heterozygoslty were been ,tt D3Fl552 for Ad (9%), D352 for large cell carcinomas (8%), and THRB for adenosquamous (0%). bronchioloalveolar (0%). and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D353 locus (3pl2-~13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D352 (3p14-pZl.l), D3F1552 (3~21). and THRB (3P24) IOCI. Effect of swami” on squamous differentiation and apoptosis in three human non-small cell lung cancer cell lines Lokshin A. Levitt ML. Allegheny Grnerul Hospital. Pittsburgh. PA /5-7/Z. J Cell Biochem 1996:62 Suppl. 24:186-97. Non-small cell lung cancer (NSCLC) is fatal m approximately 90% of all cases due to the failure of systemic therapy. secondary to resistance to chemotherapy. In such malignancies new therapeutic paradigms are needed. One such approach takes advantage of normal physiologic
growth regulatory mechanisms, such as terminal cellular differentiation or apoptosis. Suramin. as an antineoplastic drug, has shown efficacy in the treatment of prostate cancer and is capable of promoting differentiating in several human cancer cell lines. Little is known about the differentiating effects of suramin in lung cancer. In the present investigation we evaluated the ability of suramin to induce cross-linked envelope (CLE) formation, as a common marker for squamous differentiation and apoptosis, in three representative human non-small cell lung cancer lines: NCI-H226 (squamous). NCI-H358 (Bronchoalveolar (adenocarcinoma)). and NCI-R596 (adenosquamous). Among agents that we have tested. suramin demonstrated the unique ability to induce spontaneous CLE formation in the two cell lines with squamous features, NCI-H226 and NCI-H596. Suramin induced CLE formation was accompanied by DNA fragmentation, a marker for apoptosis, in NCI-H596 and NCI-H358. but not in NCI-H226. Stimulation of CLE formation by suramin correlated with the rapid induction of both type II transglutaminase (TG) activity and involucrin expression. These parameters were protein synthesis independent, suggesting post-translational mechanisms of suramin activity. Induction of differentiation] apoptosis markers by suramin did not correlate with its effect on growth. Modulation of signal transduction is a likely candidate mechanisms for suramin activity in lung cancer. The relationship between growth, squamous differentiation. and apoptosis is considered. Steroid-hormone receptors in cell lines and tomor cancer Kaiser U, Hofmann J, Schilli M et al. Division ogl’,
Department
Buldingrr
of Internal
Strusse,
3.5033
Medicine,
Murburg.
Philipps
Int J Cancer
biopsies
of human
lung
of Hematolog,v/OitcolUnioersitut Marburg.
1996;67:357-64.
Female gender is a significant independent favorable prognostic factor in lung cancer To study the possible role of sex hormones in lung cancer. the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry. &and-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation. NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in I3 and androgen receptor in 12 out of 17 cases examined: sex-steroid-receptor expression was virtually absent in SCLC cell line>. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sexsteroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of I6 cases. vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer. Pattern Seregni
of mocin gene expression in normal and neoplastic lung tissues E, Botti C, Lombardo C et al. DiGone di Medicina Nucleare.
I.st. Nuzionale
Anticancer
Studio
Cura
Res 1996; I6:2209-
Tumori.
cia
G Venetian
I, 20133
Miluno.
13.
This work evaluates the expression in lung cancer of the most well characterized mu& genes (MUCI. MUCZ, MUC3) and of the recently described MUC4 in lung tissues. to check a correlation between the expression of any particular gene and this tumor. Hybridization with synthetic oligonucleotides obtained from a part of the sequences of MUCI, MUC?, MUC3 and MUC4, was performed on blotted RNA from 18 lung cancer tissue specimens and from IO normal tissues samples taken, when possible. from the normal lung counterpart. By means of Northern blot analysis MUCI revealed to be the most