bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Factors for Surgically Treated Lung Adenocarcinoma Patients, with Special Reference to Smoking Habit
Authors: Sobue Tomotaka , Suzuki Takaichiro , Fujimoto Isaburo , Doi Osamu , Tateishi Ryuhei , Sato Takeo
Published: August 2005

Prognostic factors for lung adenocarcinoma patients who had been treated surgically at the Center for Adult Diseases, Osaka, in 1978–87 (N = 267) were analyzed In terms of year of operation, sex, age at operation, postsurgical stage, grade of differentiation, and smoking habit. Survival was improved for later year of operation (1983–87), younger age at operation, stage I or II, well or moderately differentiated adenocarcinoma, and nonsmoking status in univariate analysis. A proportional hazards model including the above variables showed that stage III and stage IV patients had 4.06 and 8.81 times higher risk of death compared to stage I and II patients. Poorly differentiated adenocarcinoma showed 2.01 times higher risk of death than well or moderately differentiated adenocarcinoma. Earlier year of operation and female status showed 1.70 and 1.82 times higher risk of death, respectively, as compared to each reference group. All these hazard ratios showed statistical significance. Current smokers who smoked 1,000 or more on the cigarette index showed 2.38 times higher risk of death than nonsmokers with statistical significance. This indicates that smoking is another independent prognostic factor for patients who undergo operations for adenocarcinoma of the lung.
Two Types of DNA Ligase I Activity in Lymphoblastoid Cells from Patients with Bloom's Syndrome
Authors: Kurihara Takayuki , Teraoka Hirobumi , Inoue Masao , Takebe Hiraku , Kouichi Kouichi
Published: August 2005

DNA ligases I and II were separated by hydroxylapatite (HA) column chromatography in cell‐free extracts of lymphoblastoid cell lines (LCLs) derived from two unrelated patients with Bloom's syndrome (BS) and two healthy individuals. The specific activity of ligase I from the crude extract was consistently lower in GM3403, a BS LCL from an Ashkenazi Jewish patient, than in normal control LCLs. By contrast, the level of ligase I activity in BSL‐2KA, another BS LCL derived from a Japanese patient, was equivalent to those in normal LCLs, although GM3403 and BSL‐2KA shared the feature of exceedingly high frequency of spontaneous sister‐chromatid exchange. The levels of total ligase activity in crude extracts without the separation into the two forms, however, were approximately two‐fold higher for the two BS LCLs than for the normal LCLs. Partial purification by chromatography on a DEAE‐cellulose 23 column and a phosphocellulose column did not affect the superiority of the two BS LCLs over the normal LCLs in the specific activity of the total ligases. Nonetheless, subsequent application to an HA column again resulted in much less elevation of the specific activity of ligase I for GM3403 than for BSL‐2KA and control LCLs. The levels of ligase II activity, accounting for 4‐13% of total ligase activity, were similar among the LCLs examined. Irrespective of the extent of purification, essentially no difference in the heat lability of DNA ligase I was detected among the four LCLs. These findings suggest that there may exist among BS LCLs at least two types of subtle abnormality of DNA ligase I itself and/or a putative substance modulating the enzyme function.
c‐Ki‐rasPoint Mutations in Ductectatic‐type Mucinous Cystic Neoplasms of the Pancreas
Authors: Yanagisawa Akio , Kato Yo , Ohtake Keiko , Kitagawa Tomoyuki , Ohashi Kazuhiko , Hori Masaharu , Takagi Kunio , Haruo Haruo
Published: August 2005

Ductectatic‐type mutinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K‐ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT–GAT (Gly–Asp) with the remaining one, found in a cancer, being GGT–GTT (Gly–Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K‐ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma‐carcinoma sequence in the evolution of this type of neoplasm and we suggest that K‐ras activation may be an important event in the phase of adenoma development.
Quercetin Induces Recombinational Mutations in Cultured Cells as Detected by DNA Fingerprinting
Authors: Suzuki Satoshi , Takada Toshinori , Sugawara Yoshiko , Muto Terukazu , Ryo Ryo
Published: August 2005

Quercetin, a fiavonoid, is found in many fruits and vegetables. This drug was previously shown to affect the metastatic potential of mouse tumor cells. Mutagenicity of quercetin was examined by means of DNA fingerprint analysis using the Pc‐1 probe that efficiently detects mutations due to recombination. Treatment of BMT‐11 and FM3A tumor cells with 55 μM quercetin resulted in gain and loss of bands in the fingerprints in both cell lines. The frequencies of the clones having undergone mutation were 3/11 and 6/26, respectively. This suggests that quercetin is mutagenic and induces recombination. This result seems to provide a molecular basis for the phenotypic variations of BMT‐11 tumor cells induced by quercetin.
Sensitivity and Specificity of Lung Cancer Screening in Osaka, Japan
Authors: Sobue Tomotaka , Suzuki Takaichiro , Matsuda Minoru , Horai Takeshi , Kajita Akiyoshi , Kuriyama Keiko , Fukuoka Masahiro , Kusunoki Yoko , Kikui Masanori , Ryu Shin‐ei , Isaburo Isaburo
Published: August 2005

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981–1985. As a screening policy, all attendants were examined by miniature chest X‐ray, and the high‐risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3‐day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X‐ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test‐negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981‐1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.
Inhibitory Effect of Dietary Perilla Oil Rich in the n‐3 Polyunsaturated Fatty Acid α‐Linolenic Acid on Colon Carcinogenesis in Rats
Authors: Narisawa Tomio , Takahashi Masahiro , Kotanagi Hitoshi , Kusaka Hisashi , Yamazaki Yoshihiko , Koyama Hirofumi , Fukaura Yoko , Nishizawa Yukio , Kotsugai Mieko , Isoda Yoshihiro , Hirano Jiro , Noritoshi Noritoshi
Published: August 2005

The inhibitory effect of dietary perilla oil rich in the n‐3 polyunsaturated fatty acid α‐linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N‐methyl‐N‐nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n‐6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil‐fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid‐induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil‐fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti‐tumor‐promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.
Induction of Renal Cell Tumors in Rats and Mice, and Enhancement of Hepatocellular Tumor Development in Mice after Long‐term Hydroquinone Treatment
Authors: Shibata Masa‐Aki , Hirose Masao , Tanaka Hikaru , Asakawa Emiko , Shirai Tomoyuki , Ito Nobuyuki
Published: August 2005

Hydroquinone (HQ) was administered to F344 rats and B6C3F1 mice of both sexes at a level of 0.8% in the diet for two years. This treatment induced renal tubular hyperplasia as well as adenomas, predominantly in males of both species, and was associated with chronic nephropathy in rats. In addition, the occurrence of epithelial hyperplasia of the renal papilla was increased in male rats. Foci of cellular alteration of the liver were significantly reduced in number by HQ in rats, but in contrast, were increased in mice, where development of hepatocellular adenoma was also enhanced in males. The incidence of squamous cell hyperplasia of the forestomach epithelium was significantly higher in mice of both sexes given HQ than in the controls, but no corresponding increase in tumor development was observed. The present study strongly indicates potential renal carcinogenicity of HQ in male rats and hepatocarcinogenicity in male mice. Thus, it is possible that HQ, which is present in the human environment, may play a role in cancer development in man.
Inhibitory Effect of Sarcophytol A on Development of Spontaneous Hepatomas in Mice
Authors: Yamauchi Osamu , Omori Masahide , Ninomiya Mitsuo , Okuno Masataka , Moriwaki Hisataka , Suganuma Masami , Fujiki Hirota , Yasutoshi Yasutoshi
Published: August 2005

The inhibitory effect of sarcophytol A, a cembrane‐type diterpene isolated from a marine soft coral, Sarcophyton glaucum, on development of spontaneous hepatomas was investigated in C3H/HeNCrj mice. A total of 80 mice were divided equally into two groups. The experimental and control groups were given basal diets with and without 0.01% sarcophytol A, respectively. At week 65 of the experiment, mice were examined for hepatomas. The percentages of hepatoma‐bearing mice of the subgroup with three or more tumors and the tumor diameters of the group treated with sarcophytol A were smaller than those of the control group. Ridit analysis revealed that these differences were statistically significant. The body weight gain, and the food intake were not significantly different between these two groups. Analysis of blood serum revealed that feeding the diet containing 0.01% sarcophytol A for 65 weeks did not show any adverse effects. These results suggest that sarcophytol A inhibits the development of spontaneous hepatomas without toxicity, and should he considered as a possible cancer chemopreventive agent for hepatomas in humans.
Discrimination of Mitotic Cells Using Anti‐p105 Monoclonal Antibody to Analyze the Mode of Action of Etoposide and Podophyllotoxin in Human Gastric Cancer Cells
Authors: Ohyama Shigekazu , Yonemura Yutaka , Tsugawa Kouichirou , Miyazaki Itsuo , Tanaka Motohiro , Sasaki Takuma
Published: August 2005

Anti‐p105 monoclonal antibody was used to discriminate between M‐phase and G2‐phase of gastric cancer cells. P105 is a proliferation‐associated nuclear antigen and its expression increases with cell cycle progression, especially in the mitotic phase. As an example of cell cycle analysis, the modes of action of etoposide and podophyllotoxin were examined by multiparameter flow cytometry. We found that etoposide caused G2 block and retarded S phase transit and podophyllotoxin caused potential M phase block in gastric cancer cells. This cell cycle analysis by using anti‐p105 monoclonal antibody should be useful for analysis of the actions of anti‐tumor agents, especially for M phase analysis, because of its convenience and reliability.
A Possible Error in the Interpretation of Gastric Carcinoma
Authors: Rubio Carlos , Hirota Teruyuki , Itabashi Masayuki , Hirohashi Setsuo , Yo Yo
Published: August 2005

Isolated clusters of pyloric cells having homogeneous, eosinophilic (i.e., “glassy”) cytoplasm were present in 6 (18.2%) of 33 consecutive gastrectomy specimens. Clusters with “glassy” cells displayed either a glandular arrangement or appeared as cohesive clusters. Cohesive clusters could be misinterpreted as signet‐ring cell adenocarcinoma. However, remnants of the apical mucous secretion from the “ordinary” pyloric cells, the nuclei usually near the free border of the cells, as well as the negative reaction in the “glassy” cytoplasm for neutral and acid mucins, helped to differentiate them from signet‐ring adenocarcinoma cells.
Cancer Incidence in Hawaiian Japanese: Migrants from Okinawa Compared with Those from Other Prefectures
Authors: Stemmermann Grant N. , Nomura Abraham M. Y. , Chyou Po‐Huang , Kato Ikuko , Tetsuo Tetsuo
Published: August 2005

Japanese men in Hawaii whose ancestral roots were in Okinawa were compared to Japanese migrants from all other prefectures. The Okinawan migrants have acquired fewer cancers than men from other prefectures (P=0.12). No one primary site accounts for this difference. Stomach cancer rates showed the largest difference between the two migrant groups. This replicates the experience of Okinawans and non‐Oldnawans in Japan itself. Lymphosarcoma mortality rates are much higher in Okinawa than in all Japan, but this difference is not reproduced in Hawaiian migrants. This could be explained by a post migrational decrease in HTLV‐I‐related acute T‐cell lymphoma/leukemia. Cancer of the mouth, pharynx and esophagus has decreased in all Japanese migrants, but the decrease is much greater among Okinawan migrants, suggesting they have escaped exposure to risk factors peculiar to the Okinawan environment. Colon cancer is more common in migrant Japanese than in U.S. whites. The dramatic increase in the frequency of this tumor affects Okinawan and non‐Okinawan migrants to an equal degree.
Renal Pelvic Carcinoma which Shows Metastatic Potential to Distant Organs, Induced by N‐Butyl‐N‐(4‐hydroxybutyl)nitrosamine in NON/Shi Mice
Authors: Murai Takashi , Mori Satoru , Hosono Motoko , Takeuchi Yasuyoshi , Ohara Tadao , Makino Susumu , Takeda Reiji , Hayashi Yoshiyuki , Shoji Shoji
Published: August 2005

Renal pelvic carcinoma was induced in mice by giving N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN). Initially, differences in renal pelvic carcinogenesis by BBN were examined in three male mouse strains: NON/Shi, which demonstrate spontaneous hydronephrosis with incidences of 10‐30%, and DS/Shi and B6C3F1, which do not exhibit hydronephrosis. When mice of these strains were given 0.05% BBN in the drinking water for 12 weeks followed by water without BBN for 8 weeks, renal pelvic carcinoma morphologically similar to human carcinomas developed in 8 of 23 NON/Shi mice (35%). Metastasis to the lung was found in one of them (13%). B6C3F1 and DS/Shi mice had no pelvic tumors, but the response to urinary bladder carcinogenesis in NON/Shi mice was nearly equal to that in DS/Shi and B6C3F1 mice. These results suggest that renal pelvic carcinogenesis is related to the presence of stagnant urine containing carcinogen in the renal pelvis. In a second experiment, we examined renal pelvic carcinogenesis in NON/Shi mice given BBN for 4 weeks followed by water without BBN for 32 weeks. The incidence of renal pelvic carcinoma (28%) was similar to that in the first experiment, but the incidence of metastasis was markedly elevated to 60%. These results indicate that BBN treatment can induce renal pelvic carcinoma which often metastasizes to the lung in NON/Shi mice.
Possible Application to Medium–term Organ Bioassays for Renal Carcinogenesis Modifiers in Rats Treated with N–Ethyl–N–hydroxyethylnitrosamine and Unilateral Nephrectomy
Authors: Hiasa Yoshio , Konishi Noboru , Nakaoka Shingo , Nakamura Mitsutoshi , Nishii Seiji , Kitahori Yoshiteru , Masato Masato
Published: August 2005

The effects of the renal tumor promoters;β–cyclodextrin (β–C), DL–serine (DL–S), basic lead acetate (LA), trisodium nitrilotriacetate monohydrate (NTA) and potassium bromate (KB), and diethylene glycol (DEG) as a negative control, on early stage of renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N–ethyl–N–hydroxyethylnitrosamine (EHEN) administration. Wistar male rats were fed 1000 ppm EHEN diet for 2 weeks and the left kidney was removed at week 3, then the animals were divided into 7 groups of 15 rats each. These groups received the following treatments: 1000 ppm LA, 10000 ppm NTA or 500 ppm KB diet for I8 weeks from week 3; 45 mg/100 g body wt./day of β–C injected sc for 7 days; 100 mg/100 g body wt. of DL–S injected sc biweekly for 6 weeks; 5% DEG in drinking water as a negative control for two days. Five rats in each group were killed at weeks 8,12 and 20 and their kidneys were examined histologically. At week 20, the average numbers of adenomatons hyperplasias seen as preneoplastic lesions in the β–C, DL–S, LA, NTA or KB groups were significantly higher than those in the DEG or control groups. Thus within a relatively short period of 20 weeks, promoting effects of chemicals can be detected as a significant increase of adenomatous hyperplasias in this model.
Carcinogenesis Studies of Dichlorvos in Fischer Rats and B6C3F1 Mice
Authors: Chan Po C. , Huff James , Haseman Joseph K. , Alison Roger , Prejean J. D.
Published: August 2005

Dichlorvos (dichlorovinyl dimethyl phosphoric acid ester) is a cholinesterase inhibitor used widely as a contact and stomach insecticide for control of internal and external parasites. Carcinogenesis studies were conducted by administering dichlorvos in corn oil by gavage 5 times a week for 103 weeks to groups of 50 male and 50 female Fischer rats at 0, 4, or 8 mg/kg body weight, to groups of 50 male B6C3F1 mice at 0,10, or 20 mg/Ag, and to groups of 50 female B6C3F1 mice at 0, 20, or 40 mg/kg. During the course of the studies, body weights and survival rates of the male and female rats and mice were not different from those of their respective controls; females of both species appeared to gain more weight than controls. Neoplasms induced by dichlorvos included adenomas of the exocrine pancreas (male rats), mononuclear cell leukemia (male rats), and squamous cell papilloma of the forestomach (male and female mice; two other female mice had squamous cell carcinomas). Lesions observed in female rats that may have been due to dichlorvos administration included adenomas of the exocrine pancreas and fibroadenomas of the mammary gland. The results demonstrated that dichlorvos is carcinogenic for Fischer rats and B6C3F1 mice.
Relation of 8‐Hydroxydeoxyguanosine Formation in Rat Kidney to Lipid Peroxidation, Glutathione Level and Relative Organ Weight after a Single Administration of Potassium Bromate
Authors: Sai Kimie , Takagi Atsuya , Umemura Takashi , Hasegawa Ryuichi , Kurokawa Yuji
Published: August 2005

Changes in kidney levels of 8‐hydroxydeoxyguanosine (8‐OH‐dG), lipid peroxidation (LPO), glutathione (GSH) and relative organ weight were examined 6, 24, 48, 72 and 96 h after a single i.p. administration of potassium bromate (KBrO3) at a dose of 70 mg/kg to male F344 rats. The 8‐OH‐dG level was significantly increased 24 h after the treatment at this dose and thereafter gradually decreased. On the other hand, significant elevation in LPO level was observed from 6 h after the treatment with a continuous increase up to a plateau at 48 h and no subsequent drop. GSH level was significantly raised from 6 to 72 h, and relative kidney weight varied in almost the same manner as the 8‐OH‐dG level. Investigation of the dose‐response relation revealed the 8‐OH‐dG and LPO levels to be significantly increased from a dose of 40 mg/kg KBrO3 in a dose‐dependent manner. The results suggest that enhanced formation of 8‐OH‐dG in kidney DNA due to KBrO3 is closely related to the increase in LPO levels.
Induction of DNA Replication and Cell Growth in Rat Liver by Obstructive Jaundice
Authors: Terasaki Masaki , Kuriki Hiroshi , Nimura Yuji , Shionoya Shigehiko , Kojima Kiyohide , Yoshida Shonen
Published: August 2005

Obstructive jaundice, produced by ligating the common bile duct, induced a transient DNA replication followed by cell proliferation in rat liver. At 48 h after the operation, DNA polymerase α activity started to increase and reached its maximum level (more than twice the control) at day 4. At day 7, the enzyme level had decreased to the control level. Pulse‐labeling experiment using radioactive thymidine showed that the rate of DNA synthesis increased approximately 2.5‐fold in the same pattern as that of DNA polymerase α The mitotic index in hepatocytes also increased 10‐fold at day 4 and then decreased. The proliferation of liver cells induced by obstructive jaundice mimics the regeneration of partially hepatectomized liver, although the response was slightly delayed and the proliferation was transient.
Human Monoclonal Antibody Detects a Cell Surface Antigen Expressed on Hematopoietic Malignant Cells of Lymphoid Lineage
Authors: Iizasa Toshihiko , Yamaguchi Yutaka , Tagawa Masatoshi , Fujisawa Takehiko , Saito Hiroaki , Kondo Haruki , Matsuo Yoshinobu , Minowada Jun , Taniguchi Masaru
Published: August 2005

An antigen with a molecular weight of 150 kilodaltons expressed on certain leukemia and lymphoma cells was recognized by a human monoclonal antibody (3H12), which had been established by the fusion of lymphocytes from a small cell lung cancer patient with a mouse myeloma cell line (P3U1). Peripheral blood mononuclear cells from 3 out of 4 cases with lytnphoid crisis of chronic myelogenous leukemia (CML) were positively stained by 3H12, while cells from 5 cases with myeloid crisis of CML did not react to this antibody. The antibody did not show any reactivity to cells from the chronic phase of CML, other types of leukemias or normal hematopoietic cells. We further examined 29 cell lines of hematopoietic origin and found that 2 undifferentiated cells (BV‐173 and K‐562) reacted to the 3H12 antibody. In addition, we found that 3 out of 6 Burkitt lymphoma cells (DAUDI, RAJI and HR1K) reacted to 3H12. Taken together, these results suggest that the antigen recognized by 3H12 is a differentiation‐associated antigen expressed on immature lymphoid cells, and could potentially be a reliable cell lineage marker.
Enhancing Effect of a Choline–deficient Diet on Alterations of Hepatic Drug–metabolizing Enzymes in Hepatitis– and Hepatoma–predisposed Rats (LEC Rats)
Authors: Sugiyama Toshihiro , Matsunaga Mikako , Jain Suresh K. , Jain Sadhana , Ikeda Yoshitaka , Taniguchi Naoyuki
Published: August 2005

Marked alterations of hepatic drug–metabolizing enzymes were observed in hepatitis– and hepatoma–predisposed rats (LEC rats) fed a choline–deficient diet. The diet enhanced the development of hepatitis with severe jaundice. The levels of two major classes of cytochrome P–450, P–450PB and P–450MC, were markedly decreased. GST–Yp was dramatically increased, whereas GST–Ya, Ybl and Yb2 were decreased. LEA rats (the control rats to LEC) fed a choline–deficient diet mimicked LEC rats fed a normal diet in terms of the above enzyme alterations, indicating that hypomethylation is involved in the pathogenesis of hepatitis and hepatoma in LEC rats. Such hypomethylation may initiate the hepatocytes that spontaneously develop hepatitis and hepatoma.
Use of Universal and Type‐specific Primers in the Polymerase Chain Reaction for the Detection and Typing of Genital Human Papillomaviruses
Authors: Maid Hideo , Saito Shigeru , Ibaraki Tamotsu , Ichijo Motohiko , Yoshie Osanm
Published: August 2005

By using polymerase chain reaction (PCR), we have developed a system for type‐specific as well as universal detection of genital human papillomaviruses (HPVs). Primers and probes for specific detection of HPV‐16, ‐18 and ‐33 were synthesized from the E7 open reading frame (ORF). They were capable of detecting corresponding HPV types with high specificity and sensitivity. Primers for detection of a broad spectrum of HPV (universal primers) were synthesized from the LI ORF. The universal primers were shown to be capable of amplifying HPV‐6b, ‐11, ‐16, ‐18, ‐33, ‐52b and ‐58. The system was applied to various cervical tissue specimens from Japanese patients. They consisted of 26 normal specimens, 18 from cervical dysplasias and 29 from cervical carcinomas. HPV was detected in none of the normal specimens. On the other hand, many of the specimens from cervical dysplasias and carcinomas were found to be positive for HPV, especially HPV‐16. Except for one, all the specimens which were positive with the type‐specific PCRs were also positive with the universal PCR. Furthermore, substantial numbers of specimens were found to be positive only with the universal PCR. Cloning and sequencing of DNA segments amplified by the universal primers were undertaken to characterize some of the unknown HPVs. Our PCR system may thus be useful for the specific detection of the three major types of oncogenic HPVs and also for the detection of a broad spectrum of HPVs including possibly novel HPV types.
Changes in Hematologic Parameters during Treatment with Medroxyprogesterone Acetate for Breast Cancer
Authors: Yamamoto Hitoshi , Noguchi Shinzaburo , Miyauchi Keisuke , Inaji Hideo , Imaoka Shingi , Koyama Hiroki , Iwanaga Takeshi
Published: August 2005

To elucidate the etiology of the thrombogenic effects of high‐dose medroxyprogesterone acetate (MPA) in the treatment of breast cancer, hematologic parameters were sequentially assessed in 12 patients receiving MPA 800 mg p.o. daily for 6 months as adjuvant hormone therapy after mastectomy. The results were as follows. (1) Coagulation system: levels of factor VII and fibrinogen decreased significantly, whereas factors II and IX increased significantly, with a shortened activated partial thromboplastin time. (2) Fibrinolytic system: plasminogen and α2‐lasmin inhibitor‐plasmin complex increased, whereas fibrinogen degradation products remained low. (3) Anticoagulation system: antithrombin III increased significantly. (4) These changes were most marked after 2 or 4 weeks of MPA treatment, and returned to the pretreatment level one month after discontinuation of treatment. (5) No patients in this study developed thromboembolic disease during or after MPA administration. These results indicate that MPA may induce a hypercoagulable state, but this state does not directly lead to the development of thrombosis.
Four Forms of Cytochrome P‐450 in Human Fetal Liver: Purification and Their Capacity to Activate Promutagens
Authors: Kitada Mitsukazu , Taneda Masaki , Itahashi Koshiro , Kamataki Tetsuya
Published: August 2005

Four forms of cytochrome P‐450 were separated and purified to electrophoretic homogeneity from human fetal livers. These forms of cytochrome P‐450, termed P‐450HFLa, P‐450HFLb, P‐450HFLc and P‐450HFLd, were distinguishable from each other in their molecular weights, spectral properties, immunochemical properties and mutagen‐producing activities from promntagens. The molecular weights of P‐450HFLa, b, c and d were estimated to be 51,500, 49,000, 51,500 and 50,000, respectively. Antibodies to P‐450HFLa recognized P‐450HFLc but not P‐450HFLb or d, and antibodies to rat P‐448‐H (P‐450IA2) cross‐reacted with P‐450HFLb but not with other forms of cytochrome P‐450. The N‐terminal amino acid sequence of P‐450HFLc was highly homologous, but not identical, to that of P‐450HFLa. Each form of cytochrome P‐450 catalyzed mutagenic activation of aflatoxin Bl (AFB1), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) and 2‐amino‐6‐methyldipyrido‐[l,2‐a:3′,2′‐d]imidazole (Glu‐P‐1) at different rates. P‐450 HFLa showed activities to produce mutagen(s) from AFB1, IQ and to a lesser extent from Glu‐P‐1. P‐450 HFLb activated IQ at a faster rate than did the other forms. P‐450 HFLc produced a mutagen from AFB1 and Glu‐P‐1 but not from IQ. P‐450 HFLd did not activate these promutagens at significant rates.
Possible Underestimation of the Incidence Rate of Prostate Cancer in Japan
Authors: Shimizu Hiroyuki , Ross Ronald K. , Bernstein Leslie
Published: August 2005

We adjusted the prostate cancer incidence rate in Japan for differences between Japan and the US in the proportion of latent prostate carcinoma identified at autopsy and of localized tumors among all carcinomas of the prostate. The adjusted incidence rate of prostate cancer in Japanese in Japan by this method is estimated to be between 24.9 and 33.3 per 100,000 population, based on incidence rates from the population‐based cancer registries of Miyagi, Japan, and Los Angeles and Hawaii, USA. The rate estimated here is almost 3–4 times greater than the rate reported previously. The difference in the incidence rates of prostate cancer between Japanese in Japan and the US (32.2–49.8 per 100,000) may therefore be substantially smaller than previously thought.
Smoking Habits and Carcinoma of the Stomach: A Case‐Control Study
Authors: Saha Sisir K.
Published: August 2005

Over a period of 8 years, a case‐control study was carried out on smoking habits in 117 patients with carcinoma of the stomach and 234 controls, and a significant association of a particular method of smoking with the site of gastric carcinoma was found in the cancer patients. Furthermore, there was a highly significant difference in method of smoking between the cancer patients and the control group. The prevalence of smoking habit in the latter was 37%, of which 26% had swallowed the smoke regularly. In contrast, the incidence of smoking habit in the cancer patients was over 56%, of which 64% had swallowed the tobacco smoke. The difference is highly significant (P < 0.001). The study also suggests that the distal part, in particular, the antrum of the stomach was affected more frequently among the smokers of the cancer patients who had swallowed the smoke regularly but the cardiac end seemed to be involved more often in the other groups of the cancer patients. These included‘never‐smokers,’ex‐smokers and those smokers who did not swallow the smoke (P < 0.01). It is therefore concluded that the swallowing of tobacco smoke seems to influence the site of gastric carcinoma. The relative risk was six‐fold higher among the smokers who did swallow the smoke compared with the ‘never‐smokers’ of the control group.
Different Effects of Carbon Tetrachloride on Carcinogen–induced Hepatocellular Carcinoma and Normal Liver of the Rat: Lowered Lipid Feroxidation and Accelerated Necrosis in Cancer
Authors: Lertprasertsuke Nirush , Shinoda Masayuki , Takekoshi Susumu , Tsutsumi Yutaka , Yamamoto Yorihiro , Niki Etsuo , Watanabe Keiichi
Published: August 2005

To investigate molecular responses to lipid peroxidative stimuli in neoplastic cells, lipid peroxidation was induced in liver of rats bearing 3′‐methyl‐4‐dimethylaminoazobenzene‐induced hepatocellular carcinoma by injecting a high dose of carbon tetrachloride (CCL4), a strong lipoperoxidative reagent. Normal rat livers with or without CCl4 treatment served as controls. CCL4, administration markedly provoked fatty metamorphosis, visualized by oil red O staining, in normal livers while minimal fatty changes were seen in hepatocellular carcinomas, where necrosis was often observed instead. After CCl4 treatment, the thiobarbituric acid values (representing levels of lipid peroxides in the tissue) were increased two–fold in the untreated normal liver, but were unchanged in the cancer tissue. Levels of vitamin C, an acutely reactive antioxidant, measured by high‐performance liquid chromatography were not influenced by the CCL4 injection in the cancer tissue whereas a significant decrease was evident in normal livers. The total fatty acid content, measured by gas chromatography, was significantly lower in the cancer tissue than in the normal liver while the ratio of polyunsaturated fatty acids (PUFAs) in total fatty acids was little changed. Resistance of hepatocellular cancer cells to fatty metamorphosis and their susceptibility to necrosis induced by free radicals may be due to the paucity of the target PUFAs in their cell membrane fraction, resulting in low levels of lipid peroxides. Peroxidation of PUFAs might act as a “shock absorber” against free radical‐induced toxic cell death in normal cells.
Effects of Lactogenic Hormones on Morphological Development and Growth of Human Breast Epithelial Cells Cultivated in Collagen Gels
Authors: Takahashi Kazuhide , Suzuki Katsuo , Kawahara Satoru , Ono Tetsuo
Published: August 2005

We investigated the hormonal dependence of the growth and morphological development of human breast epithelial cells (HBEC) cultivated in collagen gels floating on serum–free medium. HBEC used had grown out from breast carcinoma tissue and from histologically non–malignant tissue fragments in the same mastectomy specimens. In the presence of ail three lactogenic hormones, hydrocortisone (HC), insulin (INS), and prolactin (PRL), both carcinoma–derived and histologically non–malignant tissue–derived HBEC grew and formed cell masses with protruding tubule–like extensions that consisted of a multilayer of cells. Deletion of any one of the hormones from the medium had no effect on cell growth of HBEC derived from either tissue type. However, morphological development, especially the morphology of the tubule–like extensions, was altered in the histologically non–malignant tissue–derived HBEC by deletion of HC or INS, and by deletion of HC, but not INS, in the carcinoma–derived HBEC. The present results suggest that the carcinomaderived HBEC have decreased responsiveness to INS as compared to that of HBEC derived from histologically non–malignant breast tissue.
In vitro Chemosensitivity Test of Human Gastric Carcinomas Using Collagen Gel Matrix
Authors: Ohyama Shigekazu , Tanaka Motohiro , Yonemura Yutaka , Kinoshita Kazuo , Miyazaki Itsuo , Sasaki Takuma
Published: August 2005

We retrospectively evaluated the usefulness of an in vitro human tumor culture system using a specialized collagen gel matrix derived from pig skin as a Chemosensitivity test for human gastric carcinomas, especially for scirrhous gastric carcinomas. Seven xenograft tumors derived from human gastric cancers were examined by using this system and the results were compared with the data obtained from a nude mouse assay. Xenograft tumors exhibited three‐dimensional growth on the collagen gel matrix like that in vivo. The drug sensitivity as measured by this assay at 10 times therapeutic peak plasma concentrations of the drugs corresponded with that measured by the nude mouse assay for all xenograft tumors. The correlation coefficients were 0.873 for cisplatin, 0.919 for etoposide, 0.880 for mitomycin C and 0.932 for adriamjcin. In the case of scirrhous gastric carcinoma, the drug sensitivity could be measured successfully in all 12 patients. This in vitro assay system has advantages as a Chemosensitivity test because of its convenience, rapidity, and in vivo‐like three‐dimensional tumor growth. This system should contribute to the development of chemotherapy for scirrhous gastric carcinomas.
Epigenetic Control of Tumor Cell Morphology
Authors: Horio Keizo , Yoshikura Hiroshi , Kawabata Masahiro , Odawara Takashi , Sudo Katsuko , Fujitani Yohei , Lee Ganghong , Iwamoto Aikichi
Published: August 2005

XC cell line derived from a single rat cell transformed by the Prague strain of Rons sarcoma virus produced morphologically different colonies. Among them, two distinct cell types consisting of thick, fusiform cells (L‐type), and of flat, polygonal cells (R‐type) were apparent. By repeated subclonings, pure cultures, L1 and R1, respectively, were obtained. These clones underwent morphological conversion during prolonged culture; L‐type colonies appeared in the R‐type clone and vice versa. The kinetic curve suggested that the conversion was multi‐stepped. When inoculated into nude mice, L‐type cells produced much larger tumors at a higher frequency than R‐type cells, and the tumors induced by these two clones were histologically different. The expression of v‐src gene was higher in L‐type than in R‐type cells at both mRNA and protein levels.
Methylation and Expression of Human Pepsinogen Genes in Normal Tissues and Their Alteration in Stomach Cancer
Authors: Ichinose Masao , Miki Kazumasa , Wong Ricky N. S. , Tatematsu Masae , Furihata Chie , Konishi Toshiro , Matsushima Masashi , Tanji Masao , Sano Junjiro , Kurokawa Kiyoshi , Takahashi Takayuki , Kageyama Takashi , Tang Jordan J. N. , Takahashi Kenji
Published: August 2005

In normal human tissues, pepsinogen A mRNA was expressed only in the fundic mucosa of the stomach, whereas pepsinogen C mRNA was expressed in all regions of the stomach mucosa and also in the proximal duodenal mucosa. The distributions of these mRNAs were consistent with those of pepsinogens A and C in the gastroduodenal mucosa. Methylation analysis of DNAs from normal tissues with methylation‐sensitive restriction enzymes, Hpa II and Hha I, revealed that pepsinogen A and C genes are hypomethylated in tissues producing pepsinogens A and C, suggesting a role of DNA methylation in the regulation of the differential expression of the genes for the two human pepsinogens during normal differentiation. In stomach cancer tissues and cancer cell lines, the expressions of the pepsinogen genes were decreased or lost, in good accordance with their pepsinogen productions. No gross structural changes of the pepsinogen genes were observed in these cancers, but the methylation patterns of the pepsinogen genes were found to be altered in different ways in different cancers. The functional significance of the altered methylation is unknown; however, these results suggest that considerable heterogeneity of the methylation patterns occurs in human stomach cancers.
Characterization of a 54 kDa, α1Antitrypsin‐like Protein Isolated from Ascitic Fluid of an Endometrial Cancer Patient
Authors: Tanaka Naotake , Sekiya Souei , Takamizawa Hiroyoshi , Kato Noriko , Moriyama Yoichi , Fujimura Shinji
Published: August 2005

A protein factor which stimulated [3H]thymidine uptake into free hepatocytes prepared from normal mouse liver was detected in the ascitic fluid of gynecological cancer patients. The factor was subsequently further purified from the ascitic fluid of an endometrial cancer patient by DEAE‐Sephacel, Sephadex G‐150 and Phenyl‐Sepharose CL‐4B column chromatographies, and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) showed a single protein band of 54,000 Da, designated tentatively as 54K ascitic protein (54K‐AP). 54K‐AP was similar to human Qt‐antitrypsin (α1‐AT) in terms of SDS‐PAGE and immunological behavior, but was slightly different in terms of amino acid sequence and isoelectric point. Although 54K‐AP inhibited the activities of bovine trypsin and a‐chymotrypsin as did human α1‐AT, 54K‐AP inhibited the plasminogen activator released from human endometrial cancer Ishikawa cells more efficiently than α1‐AT. Because, in contrast to normal serum, the serum from the endometrial cancer patients stimulated [3H]thymidine uptake into hepatocytes, the possibility arises that 54K‐AP could he produced hy the cancer host as a defence mechanism against the cancer.
Interleukin‐2‐inducible Killer Activity and Its Regulation by Blood Monocytes from Autologous Lymphocytes of Lung Cancer Patients
Authors: Sone Saburo , Kunishige Eiji , Fawzy Farid , Yanagawa Hiroaki , Nil Akihiko , Maeda Ken‐ichi , Atagi Shinji , Heike Yuji , Nishioka Yasuhiko , Mizuno Kazuhito , Ogura Takeshi
Published: August 2005

The ability of blood lymphocytes of newly diagnosed lung cancer patients to respond to interleukin 2 (IL‐2) to become IL‐2‐activated killer (LAK) cells and its regulation by autologous monocytes were examined. LAK activity was measured by 31Cr release assay. The abilities of lymphocytes among blood mononuclear cells (MNC) of subjects of different ages without malignancies to generate LAK activity against NK‐cell resistant Daudi cells and lung adenocarcinoma (PC‐9) cells were very similar. The LAK activity of blood MNC of lung cancer patients was also nearly the same as that of blood MNC of control subjects. There was no significant difference in IL‐2‐inducible LAK activity between MNC of patients with small cell lung cancer (SCLC) and those of patients with non‐SCLC. Monocytes and lymphocytes were separated from blood MNC on a one‐step Percoll gradient. Monocytes of lung cancer patients were found to augment in vitro induction of LAK activity by IL‐2 of autologous blood lymphocytes. In contrast, endotoxin‐stimulated monocytes suppressed LAK induction of autologous lymphocytes of cancer patients. These findings suggest that administration of IL‐2 and LAK cells induced in vitro may be of benefit in the treatment of lung cancer.
Reversal of Cisplatin Resistance with Amphotericin B in a Non‐small Cell Lung Cancer Cell Line
Authors: Morikage Toshihiko , Bungo Masami , Inomata Motoko , Yoshida Mitsuji , Ohmori Tohru , Fujiwara Yasuhiro , Nishio Kazuto , Saijo Nagahiro
Published: August 2005

The potentiation of anticancer agents by non‐anticancer drugs is one of the possible strategies for overcoming cellular resistance to chemotherapy. In order to overcome cis‐diamminedichloroplatinum‐(II) (CDDP) resistance, we evaluated the sensitizing effect on CDDP‐induced cytotoxicity of various non‐anticancer agents which might alter membrane transport, by means of a colorimetric [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyItetrazolium bromide] (MTT) assay. Drugs which have previously been demonstrated to modify multidrug resistance did not show a sensitizing effect to cisplatin. Only amphotericin B (AmB) selectively conquered CDDP resistance in the CDDP‐resistant cell line. A drug accumulation study done by the atomic absorption method demonstrated that the accumulation of CDDP in the resistant cell line recovered to the level of the parental cell line after treatment with AmB. Thus, AmB might overcome CDDP resistance by increasing the accumulation of CDDP.
Parathyroid Tumors in Atomic Bomb Survivors in Hiroshima: Epidemiological Study from Registered Cases at Hiroshima Prefecture Tumor Tissue Registry, 1974‐1987
Authors: Takeichi Nobuo , Dohi Kiyohiko , Yamamoto Hisashi , Ito Hisao , Mabuchi Kiyohiko , Yamamoto Tsutomu , Shimaoka Katsutaro , Yokoro Kenjiro
Published: August 2005

An examination of registered cases of parathyroid tumor in Hiroshima Prefecture between 1974 and 1987 revealed 23 cases. An epidemiological study showed that the incidence of parathyroid tumors in Hiroshima Prefecture was significantly higher in the total exposed, especially among the proximally exposed (within 2,000 m from the hypocenter), than in the control nonexposed group (P< 0.001). A similar trend was seen for parathyroid tumor associated with primary hyperparathyroidism.
Abnormal Expression of Blood Group–related Antigens in Uterine Endometrial Cancers
Authors: Tsukazaki Katsumi , Sakayori Motoko , Arai Hiroharu , Yamaoka Kanji , Kurihara Soju , Nozawa Shiro
Published: August 2005

The expression of A, B, and H group antigens, Lewis group antigens (Lewisa, Lewisb, Lewisx, and Lewisy), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometerial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewisb antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group–related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewisa, Lewisb, and Lc4 antigens, built on the type–1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewisx, Lewisy, and nLc4 antigens, built on the type–2 chain.
Ki‐ras Activation in Pancreatic Carcinomas of Syrian Hamsters Induced by N‐Nitrosobis(2‐hydroxypropyl)amine
Authors: Ushijima Toshikazu , Tsutsumi Masahiro , Sakai Ryuichi , Ishizaka Yukihito , Takaku Fumimaro , Konishi Yoichi , Takahashi Michihito , Sugimura Takashi , Nagao Minako
Published: August 2005

Five pancreatic carcinomas induced by N‐nitrosobis(2‐hydroxypropyl)amine in Syrian golden hamsters were analyzed for activation of Ki‐ras at codons 12 and 13, using the polymerase chain reaction and direct sequencing. The Ki‐ras gene was shown to be activated in four of the five carcinomas, and the results were further confirmed by subcloning and sequencing. All the mutations involved a G‐to‐A transition at the second position of codon 12, which resulted in a change at the amino acid level from glycine to aspartic acid. This mutation is identical with that reported for pancreatic tumors of Syrian hamsters induced by N‐nitrosobis(2‐oxopropyl)amine.
Local and Systemic Carcinogenic Effects of Alkylating Carcinogens in Rats Treated by Intravesicular Administration
Authors: Lijinsky William , Thomas Barbara J. , Kovatch Robert M.
Published: August 2005

Several nitrosamines and an azoxyalkane have been administered intravesically to groups of 12 female F344 rats, twice a week for 20 or 30 weeks. Many of the nitrosamines were as efficacious in giving rise to the same tumors of internal organs as when similar doses were administered orally, showing that absorption from the bladder was as rapid as from other sites. The tumors produced included lung and kidney tumors by nitrosodimethylamine, colon and Zymbal gland tumors by azoxymethane, liver tumors by methylnitrosoethylamine (but not by nitrosodimethylamine), liver and esophagus tumors by nitrosodiethylamine, liver and lung tumors by methylnitrosamino‐3‐pyridylbutanone, liver tumors by nitrosomorpholine, and tumors of the esophagus by methylnitroso‐n‐butylamine, 2,6‐dimethylnitrosomorpholine and methylnitrosamino‐N,N‐dimethylethylamine. Bladder tumors were induced by intravesicular administration of only low doses of nitrosobis‐(2‐oxopropyl)amine and to a lesser extent by methylnitroso‐n‐hexylamine and nitroso‐(2‐hydroxypropyl)(2‐oxopropyl)amine, which all induced tumors systemically in addition. The bladder mucosa seemed to lack enzymes necessary to activate most nitrosamines to locally acting proximate carcinogens, but was quite transparent to the passage of carcinogenic nitrosamines present in the urine into the body to induce tumors in distant organs.