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Nulear magnetic resonance relaxation times for human lung cancer and lung tissues
Abstracts/Lung
Cancer
127 food items. All cohort members were followed for cancer incidence through the state wide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cawer risk. Intake in the upper three quartiles of plant derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, compared with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6,95 percent confidence interval = 0.4-0.9). This prospective cohort study suggests that high intake of fat of plant origin may lx associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women.
Lung caocer in Estonia in 1968-87: implieations Aarcleid
T. Leinsalu
Bios~o~ist~s. Institute Tallinn. Eur J Cancer
M, Rahu
Time trends and public health
M, Baburin
of Experimental,
Clinical
A. Dept. Medicine.
o/Epidemiology/ Hiiu 42, EEOO16
Pros 1994;3:419-25. Changes in lung cancer incidence and mortality in Estonia were studied for 20 years (I 968-87). A steady upward trend was observed for me” and women. The 1983-8711968-72 age-standardized incidence rate ratio was I .22 (95% confidence mtcrvsl (CI) 1.15-1.29) in men and 1.34 (95% CI 1.16-1.54) in women. The corresponding mortality rate ratio was I .26 (95% CI I. 18-l .34) in men and 1.35 (95% CI 1.16-1.57) in women. The age-specific incidence and mortality rates increased clearly towards the younger birth cohorts. For men and women, the increase was most evident for the age group 45-64 years. In women there was a more rapid increw in incidence and mortality than in men. It may be a result of a substantial increase of tobacco smoking, particularly among women, after the World War II. The high and still rising occurrence of lung cancer is closely related to the high prevalence of smoking; in addition, high tar yields in domestic cigarettes could have been responsible for an elevated lung cancer risk during the past decades. There is no tobacco control programme in Estonia, and existing legislation and regulations do not defend the nonsmoking population.
Basic biology Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues Matsuura Y, Shioya S, Kurita D, Ohta T, Suds S, Haida M, Fukwaki M, Ohta Y Deparbnmt of Internal Medicine. Tokai Univ. School Kanagawa 259-11. Jpn J Thorac Dis 1994;32:1159-63.
of Medicine.
Isehara,
We investigated the nuclear magnetic resonance (NMR) relaxation times, T, and T,, for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinoma, five necrotic squamous cell carcinoma, 15 adcncarcinoma, hvo benign mesothclioma, and I3 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were comlatcd with histological changes. The values of T, and T, for squamous cell carcinoma and mesothclioms were significantly longer than those of adcnocarcinoma and fibrotic lung tissue. There were no significant differences in values of T, and T, bchvcen adenocarcinoma and lung tissue. The values of T, and T, for benign mesothclioma were similar to those of squamous cell carcinoma, which suggested that increases in T, and T, are not specific to malignant tissues.
Lung tumor induction in A/J mice and clastogenie effects in CD-l mice of the .quence4ective DNA alkylating agents (+)-CC-1065 and (-)cc-1065 DA, Branstetter LXJ, Yu RL, Aaron CS. Upjohn Laborafories, 317. Kalamazoo, MI 49001. Nat Toxins 1995;3:3240. The in viva genotoxic effects of the antitumor antibiotic, (+)&Z-1065, and its unnatural cnantiomer. (-)-CC-1065, were investigated in two mouse models. These hvo compounds alkylate AT-rich regions of double stranded DNA with distinct sequence selectivitics. (+)-CC-l065 dose-dependently increased the
12 (1995)
265-329
chromosomal aberration frequency in bone marrow cells of CD-I mice from I .2 f 0.8% in vehicle control animals to 5.0 f I .2%, I I .4 f 3.9%, and 20.6 l 2.3% 24 hours following single intravenous doses of 2. 4, and 8 i&g, respectively. (-h CC-1065 was significantly less potent with a maximal response at 8 ig/kg approximately one-third of that observed for(+)-CC-1065. (+)-CC-1065 induced a significant (P % O.OS), three-fold increase in the number of lung tumors/ mouse in strain A/J mice from 0.27 f 0.15 for vehicle control animals to 0.83 f 0.15 24 weeks following a single intravenous dose of 8 igikg. This cffcct was paralleled by corresponding threefold increases in the percentage of mice with hlmors and the percentage of mica with multiple tumors, compared to vehicle controls. (-)-CC-l065 at 8 igikg induced 0.67 -t 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)-CC-1065. The above results demonstrate that single intravenous doses of (+)-CC-1065 and (-)-CC-1065 Munich cause chmmosomal damage in CD-1 mice also induce an increased incidence of lung tumors in A/J mice. (+p CC-1065 may have a slightly greater gcnotoxic potential in viva than its unnatural emmtiomer. This may be attributable to differences in the DNA binding sequence selectivities of the two compounds, Furthermore, when compared on a imolcslkg basis, (+)-CC-1065 is > 7,000 x more potent than N-cthyl-Nnitmsourea at inducing a similar tumorigenic response in the A/J mouse lung hlmor bioassay.
Tiirclated carcinomas
cffccta ufenzymatic
dii
tion on model human lung
Howard RB, Shroyer KR, Marcell T, Swanson LE. Pagura ME, Mulvin DW et al. Lab 9888. Lunotfeld Research Institite, Mt. Sinai Hospital, 600 Universiry Avenue, Toronto, Ont. MSG 1X5. Cytometry 1995;19:146-53. Enzyme cocktails used to prepare tumor cell suspensions may influence yield, viability, and cytology, thus time-related cocktail effects on model human lung carcinomas were examined. AS49, NCI-H125, and NCI-H460 carcinomas were completely disaggrcgated et 25°C over 2 h with either (mg/ml) collagena& DNAse (C/D, l/0.1), collagenase~yaluronidssc/DNAse (C/H/D, I/0.1/0. I), or polymyxa protease/DNAsc VP/D, 3/0.1). Trypan blue viabilitics, total yields, viable yields, end flow cytometric percent tumor cells (TC) were measured every 20-30 min (n = 4-7 per tumor type). The final percentages of TC, mononuclear cells (MN), polymorphonuclenr cells @‘MN), lymphocytes, and necrotic cells were determined by cytology (n = 4-S per tumor type). The timedependent measurements showed that I) disaggregation was progressive and complete with all cocktails; 2) viability was stable or increasing with all cocktails; 3) percent TC was stable for all cocktails, but lower for PP D than C/D in final suspensions, and 4) PP/D gave lowr final total yields, higher final viabilities, but the same final viable yields as the C cocktails, suggesting selective elimination of dead cells by PP/D. Final cytology measurements showed that PP/D gave a lower percent MN and a higher percent PMN than C cocktails. Cocktail effects may importantly influence cell suspension properties.
Bumaa papillomavirus type 18 DNA and E&E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung Kinoshita
I, Osaka-Akita
H, Shindoh
M, Fujino M, Akic K, Kata M et al. First
Deparbmm~ o/Medicine, Hokkaido University School 7, Kita-ku, Sapporo 060. Br J Cancer 1995;71:344-9.
Medicine,
North
IS. Wesr
To provide an accurate evaluation of the association of human papillomsvirus QIPV) with lung cancer, 36 cases of lung cancer were analysed for HPV DNAs by polymerax chain reaction @‘CR) with dot-blot and Southern blot analyses, and for the transcripts from the E6-E7 transforming region by in situ hybridisation (LSH). HPV-I8 DNA was detected in three (8%) of 36 specimens, histologically, in one(lO%)of IO squamous mllcarcinomasand hw (9%)of22 adenocarcinomas. Neither HPV-I6 nor -33 DNA was detected in any cases examined. Expression of E6-E7 mRNA was confimwd in the cases which contained HPV-18 DNA. HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.
Linscman
Luborafmy
Detectioa nfc-myc
and c-sk mRNA in human non-small cell lungcaocer
Kawamata 0. First Deparbnent of Surgeq Okayama Vniversi~ Sch. ofMedicine. O&ama. Lung Cancer (Japan) 1994;34:1003-1010 c-myc and c-sis mRNA were detected in surgical specimens of non-small cell
Cancer
127 food items. All cohort members were followed for cancer incidence through the state wide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cawer risk. Intake in the upper three quartiles of plant derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, compared with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6,95 percent confidence interval = 0.4-0.9). This prospective cohort study suggests that high intake of fat of plant origin may lx associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women.
Lung caocer in Estonia in 1968-87: implieations Aarcleid
T. Leinsalu
Bios~o~ist~s. Institute Tallinn. Eur J Cancer
M, Rahu
Time trends and public health
M, Baburin
of Experimental,
Clinical
A. Dept. Medicine.
o/Epidemiology/ Hiiu 42, EEOO16
Pros 1994;3:419-25. Changes in lung cancer incidence and mortality in Estonia were studied for 20 years (I 968-87). A steady upward trend was observed for me” and women. The 1983-8711968-72 age-standardized incidence rate ratio was I .22 (95% confidence mtcrvsl (CI) 1.15-1.29) in men and 1.34 (95% CI 1.16-1.54) in women. The corresponding mortality rate ratio was I .26 (95% CI I. 18-l .34) in men and 1.35 (95% CI 1.16-1.57) in women. The age-specific incidence and mortality rates increased clearly towards the younger birth cohorts. For men and women, the increase was most evident for the age group 45-64 years. In women there was a more rapid increw in incidence and mortality than in men. It may be a result of a substantial increase of tobacco smoking, particularly among women, after the World War II. The high and still rising occurrence of lung cancer is closely related to the high prevalence of smoking; in addition, high tar yields in domestic cigarettes could have been responsible for an elevated lung cancer risk during the past decades. There is no tobacco control programme in Estonia, and existing legislation and regulations do not defend the nonsmoking population.
Basic biology Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues Matsuura Y, Shioya S, Kurita D, Ohta T, Suds S, Haida M, Fukwaki M, Ohta Y Deparbnmt of Internal Medicine. Tokai Univ. School Kanagawa 259-11. Jpn J Thorac Dis 1994;32:1159-63.
of Medicine.
Isehara,
We investigated the nuclear magnetic resonance (NMR) relaxation times, T, and T,, for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinoma, five necrotic squamous cell carcinoma, 15 adcncarcinoma, hvo benign mesothclioma, and I3 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were comlatcd with histological changes. The values of T, and T, for squamous cell carcinoma and mesothclioms were significantly longer than those of adcnocarcinoma and fibrotic lung tissue. There were no significant differences in values of T, and T, bchvcen adenocarcinoma and lung tissue. The values of T, and T, for benign mesothclioma were similar to those of squamous cell carcinoma, which suggested that increases in T, and T, are not specific to malignant tissues.
Lung tumor induction in A/J mice and clastogenie effects in CD-l mice of the .quence4ective DNA alkylating agents (+)-CC-1065 and (-)cc-1065 DA, Branstetter LXJ, Yu RL, Aaron CS. Upjohn Laborafories, 317. Kalamazoo, MI 49001. Nat Toxins 1995;3:3240. The in viva genotoxic effects of the antitumor antibiotic, (+)&Z-1065, and its unnatural cnantiomer. (-)-CC-1065, were investigated in two mouse models. These hvo compounds alkylate AT-rich regions of double stranded DNA with distinct sequence selectivitics. (+)-CC-l065 dose-dependently increased the
12 (1995)
265-329
chromosomal aberration frequency in bone marrow cells of CD-I mice from I .2 f 0.8% in vehicle control animals to 5.0 f I .2%, I I .4 f 3.9%, and 20.6 l 2.3% 24 hours following single intravenous doses of 2. 4, and 8 i&g, respectively. (-h CC-1065 was significantly less potent with a maximal response at 8 ig/kg approximately one-third of that observed for(+)-CC-1065. (+)-CC-1065 induced a significant (P % O.OS), three-fold increase in the number of lung tumors/ mouse in strain A/J mice from 0.27 f 0.15 for vehicle control animals to 0.83 f 0.15 24 weeks following a single intravenous dose of 8 igikg. This cffcct was paralleled by corresponding threefold increases in the percentage of mice with hlmors and the percentage of mica with multiple tumors, compared to vehicle controls. (-)-CC-l065 at 8 igikg induced 0.67 -t 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)-CC-1065. The above results demonstrate that single intravenous doses of (+)-CC-1065 and (-)-CC-1065 Munich cause chmmosomal damage in CD-1 mice also induce an increased incidence of lung tumors in A/J mice. (+p CC-1065 may have a slightly greater gcnotoxic potential in viva than its unnatural emmtiomer. This may be attributable to differences in the DNA binding sequence selectivities of the two compounds, Furthermore, when compared on a imolcslkg basis, (+)-CC-1065 is > 7,000 x more potent than N-cthyl-Nnitmsourea at inducing a similar tumorigenic response in the A/J mouse lung hlmor bioassay.
Tiirclated carcinomas
cffccta ufenzymatic
dii
tion on model human lung
Howard RB, Shroyer KR, Marcell T, Swanson LE. Pagura ME, Mulvin DW et al. Lab 9888. Lunotfeld Research Institite, Mt. Sinai Hospital, 600 Universiry Avenue, Toronto, Ont. MSG 1X5. Cytometry 1995;19:146-53. Enzyme cocktails used to prepare tumor cell suspensions may influence yield, viability, and cytology, thus time-related cocktail effects on model human lung carcinomas were examined. AS49, NCI-H125, and NCI-H460 carcinomas were completely disaggrcgated et 25°C over 2 h with either (mg/ml) collagena& DNAse (C/D, l/0.1), collagenase~yaluronidssc/DNAse (C/H/D, I/0.1/0. I), or polymyxa protease/DNAsc VP/D, 3/0.1). Trypan blue viabilitics, total yields, viable yields, end flow cytometric percent tumor cells (TC) were measured every 20-30 min (n = 4-7 per tumor type). The final percentages of TC, mononuclear cells (MN), polymorphonuclenr cells @‘MN), lymphocytes, and necrotic cells were determined by cytology (n = 4-S per tumor type). The timedependent measurements showed that I) disaggregation was progressive and complete with all cocktails; 2) viability was stable or increasing with all cocktails; 3) percent TC was stable for all cocktails, but lower for PP D than C/D in final suspensions, and 4) PP/D gave lowr final total yields, higher final viabilities, but the same final viable yields as the C cocktails, suggesting selective elimination of dead cells by PP/D. Final cytology measurements showed that PP/D gave a lower percent MN and a higher percent PMN than C cocktails. Cocktail effects may importantly influence cell suspension properties.
Bumaa papillomavirus type 18 DNA and E&E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung Kinoshita
I, Osaka-Akita
H, Shindoh
M, Fujino M, Akic K, Kata M et al. First
Deparbmm~ o/Medicine, Hokkaido University School 7, Kita-ku, Sapporo 060. Br J Cancer 1995;71:344-9.
Medicine,
North
IS. Wesr
To provide an accurate evaluation of the association of human papillomsvirus QIPV) with lung cancer, 36 cases of lung cancer were analysed for HPV DNAs by polymerax chain reaction @‘CR) with dot-blot and Southern blot analyses, and for the transcripts from the E6-E7 transforming region by in situ hybridisation (LSH). HPV-I8 DNA was detected in three (8%) of 36 specimens, histologically, in one(lO%)of IO squamous mllcarcinomasand hw (9%)of22 adenocarcinomas. Neither HPV-I6 nor -33 DNA was detected in any cases examined. Expression of E6-E7 mRNA was confimwd in the cases which contained HPV-18 DNA. HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.
Linscman
Luborafmy
Detectioa nfc-myc
and c-sk mRNA in human non-small cell lungcaocer
Kawamata 0. First Deparbnent of Surgeq Okayama Vniversi~ Sch. ofMedicine. O&ama. Lung Cancer (Japan) 1994;34:1003-1010 c-myc and c-sis mRNA were detected in surgical specimens of non-small cell