bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charcoal cigarette filters and lung cancer risk in Aichi Prefecture, Japan
Authors: Muscat Joshua E. , Takezaki Toshiro , Tajima Kazuo , Stellman Steven D. 
Published: May 2005

The lung cancer mortality rate has been lower in Japan than in the United States for several decades. We hypothesized that this difference is due to the Japanese preference for cigarettes with charcoal‐containing filters, which efficiently absorb selected gas phase components of mainstream smoke including the carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone. We analyzed a subset of smokers (396 cases and 545 controls) from a case‐control study of lung cancer conducted in Aichi Prefecture, Japan. The risk associated with charcoal filters (73% of all subjects) was evaluated after adjusting for age, sex, education and smoking dose. The odds ratio (OR) associated with charcoal compared with ‘plain’ cigarette filters was 1.2 (95% confidence intervals [CI] 0.9, 1.6). The histologic‐specific risks were similar (e.g. OR = 1.3, 95% CI 0.9, 2.1 for adenocarcinoma). The OR was 1.7 (95% CI 1.1, 2.9) in smokers who switched from ‘plain’ to charcoal brands. The mean daily number of cigarettes smoked in subjects who switched from ‘plain’ to charcoal brands was 22.5 and 23.0, respectively. The findings from this study did not indicate that charcoal filters were associated with an attenuated risk of lung cancer. As the detection of a modest benefit or risk (e.g. 10–20%) that can have significant public health impact requires large samples, the findings should be confirmed or refuted in larger studies. (Cancer Sci2005; 96: 283 –287)
Possible antitumor activity of 1‐(3‐C‐ethynyl‐β‐d‐ribo‐pentofuranosyl)cytosine (ECyd, TAS‐106) against an established gemcitabine (dFdCyd)‐resistant human pancreatic cancer cell line
Authors: Kazuno Hiromi , Sakamoto Kazuki , Fujioka Akio , Fukushima Masakazu , Matsuda Akira , Sasaki Takuma 
Published: May 2005

We established a variant of MIAPaCa‐2 human pancreatic cancer cells that is resistant to 2′,2′‐difluorodeoxycytidine (gemcitabine, dFdCyd), MIAPaCa‐2/dFdCyd, and elucidated the biochemical characteristics and mechanism of dFdCyd‐resistance in these cells. We also evaluated 1‐(3‐C‐ethynyl‐β‐d‐ribo‐pentofuranosyl)cytosine (ECyd, TAS‐106, RNA polymerase inhibitor), a new anticancer ribonucleoside, for antitumor activity against the resistant cells in vitro and in vivo. MIAPaCa‐2/dFdCyd cells were 2541‐fold more resistant to dFdCyd than parental MIAPaCa‐2 cells, and the major mechanism of the dFdCyd‐resistance was found to be a decrease in the intracellular pool of dFdCyd and its active metabolites, which would result in a decrease in incorporation of dFdCyd triphosphate into DNA. This finding was confirmed by the discovery of decreased deoxycytidine kinase activity, increased cytidine deaminase and ribonucleotide reductase activity, and increased 5′‐nucleotidase mRNA expression in the MIAPaCa‐2/dFdCyd cells. The cytotoxicity of TAS‐106 as an antitumor nucleoside analog was similar in both parental and dFdCyd‐resistant cells, with IC50 values of 6.25 and 6.27 nM, respectively, and this finding was supported by similar intracellular uptake and metabolism of TAS‐106 in both cell lines. We also evaluated the in vivo antitumor activity of TAS‐106 against MIAPaCa‐2 and dFdCyd‐resistant MIAPaCa‐2/dFdCyd tumors implanted into nude mice. The tumor growth inhibition rate of weekly additions of TAS‐106 (7 mg/kg, iv) against parental and dFdCyd‐resistant tumors was 73% and 76%, respectively, while that of dFdCyd administered twice a week (240 mg/kg, iv) was 84% and 34%, respectively. These results suggest that TAS‐106 would contribute to the treatment of patients with advanced pancreatic carcinomas in whom dFdCyd‐based chemotherapy has failed. (Cancer Sci 2005; 96: 295 –302)
Suppression of azoxymethane‐induced colon cancer development in rats by a prostaglandin E receptor EP1‐selective antagonist
Authors: Niho Naoko , Mutoh Michihiro , Kitamura Tomohiro , Takahashi Mami , Sato Hidetaka , Yamamoto Hiroshi , Maruyama Takayuki , Ohuchida Shuichi , Sugimura Takashi , Wakabayashi Keiji 
Published: May 2005

Prostaglandin E2 is involved in colon carcinogenesis through its binding to the PGE2 receptor subtypes EP1, EP2, EP3 and EP4. We have demonstrated that administration of ONO‐8711, an EP1‐selective antagonist, suppresses development of AOM‐induced ACF in C57BL/6 mice and F344 rats. ONO‐8711 also reduced the numbers of intestinal polyps in Min mice. In the present study, we investigated the long‐term effects of ONO‐8711 on colon cancer development in rats treated with AOM. Male F344 rats were injected subcutaneously with AOM (15 mg/kg body weight) once a week for the first 2 weeks to develop colon cancer. Administration of 400 or 800 p.p.m. ONO‐8711 in their diets for 32 weeks reduced the incidence, multiplicity and volume of colon carcinomas. The incidence of colon adenocarcinomas in AOM‐treated rats was 97, 83 and 76% (P < 0.05) in the 0, 400 and 800 p.p.m. of ONO‐8711 groups, respectively. The multiplicity of adenocarcinomas was also decreased significantly, being 3.31 ± 0.33, 2.34 ± 0.27 (P < 0.05) and 2.06 ± 0.34 (P < 0.01) with 0, 400 and 800 p.p.m. of ONO‐8711, respectively. Moreover, treatment with 800 p.p.m. ONO‐8711 reduced the mean volume of adenocarcinomas to 49% (P < 0.05) of the value for the AOM treatment alone. Furthermore, the BrdU labeling index was decreased significantly in colon cancer cells by 800 p.p.m. ONO‐8711. These results confirm that EP1 is involved in colon carcinogenesis and that EP1‐selective antagonists might be promising candidates for colon cancer chemopreventive agents. (Cancer Sci 2005; 96: 260 –264)
Dendritic cell immunotherapy with poly(d,l‐2,4‐diaminobutyric acid)‐mediated intratumoral delivery of the interleukin‐12 gene suppresses tumor growth significantly
Authors: Iwashita Yukio , Goto Shigeru , Tominaga Masayuki , Sasaki Atsushi , Ohmori Naoya , Goto Takeshi , Sato Syuji , Ohta Masayuki , Kitano Seigo 
Published: May 2005

A conventional DC‐based immunotherapy has been tested clinically for treatment of patients with advanced cancer but requires modification to further improve the clinical results. In this study, we evaluated the in vivo antitumor effects of DC therapy, non‐viral‐mediated IL‐12 gene therapy, and a combination of the two in a murine bilateral subcutaneous tumor model. DC therapy alone and IL‐12 gene therapy alone suppressed tumor growth at the injected sites. However, the antitumor effect on the distant contralateral tumor was insufficient. When DC therapy and IL‐12 gene therapy were carried out simultaneously, tumor growth was significantly suppressed bilaterally (P < 0.001). Cytolytic activity was augmented significantly in mice given the combination treatment compared to in mice treated with either DC or IL‐12 gene therapy alone (P < 0.05). Microvessel density of both tumors was significantly lower in mice subjected to the combination therapy than in mice treated otherwise (P < 0.05). Furthermore, no side‐effects were observed in the treated mice. DC therapy combined with non‐viral‐mediated intratumoral IL‐12 gene delivery has a synergistic antitumor effect not only on targeted tumors but also on contralateral distant tumors and may be of great potential as a therapeutic treatment for patients with advanced cancer. (Cancer Sci 2005; 96: 303 –308)
Tumor immunity against adult T‐cell leukemia
Authors: Kannagi Mari , Harashima Nanae , Kurihara Kiyoshi , Ohashi Takashi , Utsunomiya Atae , Tanosaki Ryuji , Masuda Masato , Tomonaga Masao , Okamura Jun 
Published: May 2005

Human T‐cell leukemia virus type‐I (HTLV‐I) causes adult T‐cell leukemia (ATL) in a small population of infected individuals after a long incubation period. Although the process of clonal evolution of ATL cells may involve multiple steps, ATL cells from half of the ATL cases still retain the ability to express HTLV‐I Tax, a key molecule of HTLV‐I leukemogenesis. A recent finding of reactivation of Tax‐specific cytotoxic T lymphocytes (CTL) in ATL patients after hematopoietic stem cell transplantation suggests the presence of Tax expression in vivo and potential contribution of the CTL to antitumor immunity. This is consistent with the results of a series of animal experiments indicating that Tax‐specific CTL limit the growth of HTLV‐I‐infected cells in vivo, although the animal model mimics only an early phase of HTLV‐I infection and leukemogenesis. Establishment of an insufficient HTLV‐I‐specific T‐cell response and an increased viral load in orally HTLV‐I‐infected rats suggests that host HTLV‐I‐specific T‐cell response at a primary HTLV‐I infection can be a critical determinant of persistent HTLV‐I levels thereafter. These findings indicate that Tax‐targeted vaccines may be effective for prophylaxis of ATL in a high‐risk group, and also for therapy of ATL in at least half the cases. (Cancer Sci 2005; 96: 249 –255)
Effect of proapoptosis protein on hepatocarcinogenesis
Authors: LI Bai , CAO Chuan‐Ping , MAO Gao‐Ping 
Published: May 2005

OBJECTIVE:  The goal of the present study was to determine how proapoptosis proteins regulate the progression of liver proliferative foci and tumorigenesis initiated by a chemical carcinogen, diethylnitrosamine (DEN).METHODS:  Bid‐deficient mice (15‐day‐old) were injected with 15 µg/g of DEN, then killed at 3 and 10 days, and 4 and 8 months after injection for analysis of hepatocellular proliferation, apoptosis and tumorigenesis.RESULT:  The rate of apoptosis in the hepatocytes of the wild‐type mice was significantly higher than in the Bid‐deficient mice at 10 days after DEN exposure (P < 0.0001); the results of BrdU labeling agreed with the measurement of apoptosis in these animals, showing an obvious increase in the wild‐type mice compared with the Bid‐deficient mice (P < 0.0001). Four months after DEN exposure, the number and size of lesion foci or nodules in the wild‐type mice were both greater than in the Bid‐deficient mice (P < 0.05 and P < 0.001, respectively), but there was no significant difference between the two groups of mice at 8 months.CONCLUSION:  These results suggest that a lack of apoptosis in liver tissue in the early stage after DEN exposure decreased some of the tumorigenesis potential of DEN.
Progress in inflammatory bowel disease
Authors: SINGLETON John W 
Published: May 2005

During the past 20 years, advances have been made in Crohn's disease and chronic ulcerative colitis. Despite impressive progress, it is still necessary to call these diseases ‘idiopathic’, as the details of their etiology remain obscure. Four areas will be reviewed in this article: genetics; intestinal inflammation; the relationship between the gut flora and the mucosa; and medical therapy.
Changes in gene expression profiles induced by parvovirus H‐1 in human gastric cancer cells
Authors: LIU Jiong , RAN Zhi Hua , XIAO Shu Dong , ROMMELAERE Jean 
Published: May 2005

OBJECTIVE  The autonomous parvovirus H‐1 exhibits preferential toxicity for transformed or tumor cells. The precise molecular mechanism of H‐1 virus‐associated cytotoxicity is not fully understood. The present study aimed at gaining more information about parvovirus‐induced cellular disturbances.METHODS  The H‐1 virus‐sensitive human gastric cancer cell line HGC27 was analyzed in the present study. cDNA microarrays were used to determine the global cellular gene expression changes which occur during the process of H‐1 virus‐induced death of HGC27 cells. A subset of differential expressed genes was further tested by RT‐PCR and Northern blot analyzes.RESULTS  A total of 920 genes belonging to various functional groups were found to be differentially expressed in H‐1 virus‐ versus mock‐infected cells in cDNA microarrays. Among them, 363 genes were upregulated, whilst 557 genes were downregulated. The differential expressions of some of these genes were further confirmed by RT‐PCR and Northern blot analysis.CONCLUSION  Some of genes known to be involved in cell signal transduction, apoptosis, DNA replication, DNA repair, DNA binding and transcription were differentially expressed after parvovirus H‐1 infection, they might play a role in H‐1 virus‐induced gastric cancer cell death. These genes represent interesting candidates to be tested at the functional level for their contribution to the disturbances triggered by H‐1 virus in tumor cells.
Modulation of multidrug resistance by andrographolid in a HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line
Authors: HAN Ying , BU Li Min , JI Xin , LIU Chun Yan , WANG Zhi Hong 
Published: May 2005

OBJECTIVE  To develop an HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line and to elucidate the effect of Andrographolid (AG), an extract from Andrographis paniculate, a medicinal herb on the HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line.METHODS  An HCT‐8 colorectal cancer cell line was used and a high concentration of 5‐Fluorouracid (5‐FU) was introduced at the beginning to induce drug resistance, then the concentration of 5‐FU was increased in gradients. Approximately 7 months later, the cells grew stably in 2.0 µg/mL of 5‐FU, and the cell line was named HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line. The resistant index of HCT‐8/5‐FU cells to 5‐FU, adriamycin (ADM), cisplatin (DDP) was checked by MTT test, and a growth curve was drawn. The morphological changes were observed by both light and electron microscope. The function of P‐170 was detected by rhodamine staining. After the application of AG and co‐administration of 5‐FU, ADM and DDP, the growth curves and inhibition rate as well as apoptosis rate of HCT‐8/5‐FU at different concentrations of AG were evaluated by MTT and flow cytometry. Rhodamine staining was used to investigate the possible mechanism involved by AG.RESULTS  The resistance index of HCT‐8/5‐FU to 5‐FU was 16.6, and a cross‐resistance to ADM and DDP was noticed. Compared with parental cells, HCT‐8/5‐FU cell's growth rate did not change significantly but the cell's morphology was remarkably changed as compared with parental cells. Overexpression of P‐170 by HCT‐8/5‐FU cell was indicated through rhodamine staining. AG at a low concentration showed weak inhibitory effect on HCT‐8/5‐FU. However, a remarkable inhibitory and apoptosis rate was shown when AG was co‐administered with 5‐FU, ADM and DDP, respectively. Interestingly AG alone could not induce apoptosis and change the cell cycles. AG might affect the expression of P‐170, which was indicated by rhodamine staining.CONCLUSIONS  The HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line has been successfully developed and because it has cross‐resistance to 5‐FU, ADM and DDP, it might serve as an ideal multidrug resistance (MDR) model for colorectal cancer research. The mechanism of HCT‐8/5‐FU resistance to chemotherapeutic agents might be related to the overexpression of P‐170. Low concentrations of AG alone have no significant inhibition on HCT‐8/5‐FU and fail to induce apoptosis and to change cell cycles. AG might act as a chemosensitizer when co‐administered with 5‐FU, ADM and DDP, and the mechanism of reversal modulation of multidrug resistance by AG in the HCT‐8/5‐FU resistant cell line might be related to its downregulation of overexpression of P‐170.
Diagnosis and management of regional portal hypertension
Authors: LIU Quan Da , ZHOU Ning Xin , ZHANG Wen Zhi , WANG Mao Qiang 
Published: May 2005

OBJECTIVE:  Regional portal hypertension (RPH) results from splenic vein thrombosis/occlusion, with emergence of gastric varices and severe upper gastrointestinal bleeding. Its diagnosis and management are summarized below.METHODS:  We reviewed our experience in 16 consecutive patients with RPH at Chinese PLA General Hospital between 2001 and 2004. The clinical manifestations, diagnostic methods and therapeutic modalities were analyzed retrospectively.RESULTS:  Among the 16 patients with RPH, 12 had co‐existing pancreatic diseases and 4 were of obscure origin. The main clinical findings were splenomegaly in 16 (100%), epigastric pain (mainly left upper abdomen) in 10 (63%), gastrointestinal bleeding in 7 (44%) and abdominal mass in 3 (19%). All had normal liver function tests. The main diagnostic methods used were ultrasound (US), computerized tomography (CT) and endoscopy. Splenic vein thrombosis could be identified by color Doppler ultrasound (7/7), enhanced CT could show its enlarged and tortuous short gastric vein, gastroepiploic vein, and collateral vessels around the splenic hilum (16/16). Isolated gastric varices (4/5) were mainly shown by esophagogastroscopy. Splenectomy was effective in controlling the variceal bleeding, but portal vein thrombosis occurred in 1 case. Endoscopic sclerotherapy had been carried out repeatedly in 2 cases, but was less effective (1/2, 50%).CONCLUSIONS:  Precise diagnosis of RPH can be achieved by clinical manifestations, US and CT. Therapeutic options should be individualized basing on the underlying diseases, however, splenectomy is more preferable for patients with bleeding varices, and endoscopic sclerotherapy can be tried.
In view of an optimal gut antifungal therapeutic strategy: an in vitro susceptibility and toxicity study testing a novel phyto‐compound
Authors: METUGRIACHUK Yussef , KUROI Olivia , PAVASUTHIPAISIT Kanok , TSUCHIYA Junji , MINELLI Emilio , OKURA Ruichi , FESCE Edoardo , MAROTTA F 
Published: May 2005

OBJECTIVE:  In view of the raising concern for gut fungal infection, the aim of the present research was to carry out a systematic in vitro study testing the antifungal activity and possible toxicity of a polygodial‐anethole compound (Kolorex) in several strains of Candida albicans and in other fungal pathogens.METHODS:  The in vitro susceptibility tests were carried out on 4 strains of C. albicans (C. krusei, C. lipolytica, C. tropicalis, C. utilis), Aspergillus flavus and A. fumigatus. Cultures were also analyzed by varying medium, pH and inoculum size, and a time‐course killing test was carried out.RESULTS:  In the present study the polygodyal–anethole compound showed remarkable in vitro activity against the most common fungi, which was significantly better than polygodyal alone. Moreover, such mixture compound was shown to exert its activity against a wide spectrum of fungi, including C. lipolytica and C. tropicalis, which required significantly higher MIC of polygodyal to be unfeasible in clinical application. The activity of the polygodyal–anethole compound was significantly better than polygodyal alone with high inoculum size and low pH. Moreover, it proved to exert a significantly faster biological activity against low inoculum.CONCLUSIONS:  This study suggests that the mixture compound Kolorex has a very good profile of antifungal activity in terms of effectiveness and spectrum of action while being devoid of any significant toxicity.
Analysis of clinical characteristics of dyspeptic symptoms in Shanghai patients
Authors: LI Xiao Bo , LIU Wen Zhong , GE Zhi Zheng , ZHANG Da Rong , ZHAO Yun Jia , DAI Jun , XUE Han Bin , XIAO Shu Dong 
Published: May 2005

OBJECTIVE:  To improve the management of dyspepsia by analyzing the clinical characteristics of dyspeptic symptoms in patients from Shanghai.METHODS:  782 patients with functional dyspepsia (FD) or organic dyspepsia (OD) completed a questionnaire about dyspepsia. The questionnaire asked participants to score 12 previously validated common upper abdominal symptoms. The clinical characteristics of dyspepsia including severe symptoms; and the relationship between symptoms and meals were then analyzed.RESULTS:  Among the 782 dyspeptic patients, 543 cases (69.4%) were classed as FD and 239 (30.6%) OD. The proportion of males was significantly higher in the OD group. There was no difference in average dyspepsia scores between the 2 dyspeptic groups (21.5 vs 20.4, P > 0.05), but the scores of ‘stomach’ pain and ‘stomach’ pain before meals were higher in OD patients than in FD patients (2.65 ± 1.11 vs 2.16 ± 0.92, 2.26 ± 1.26 vs 1.79 ± 0.92, P < 0.05). In 45.2% of the OD patients and 47.7% of the FD patients, respectively, the severity of symptoms was not related to meals. In subgroups of ulcer‐like, dysmotility‐like and unspecified dyspepsia, the proportion of patients with symptoms not related to meals was 59.6%, 50.9% and 35.2%, respectively. 2.5% (6/239) of OD patients presented with progressive dysphagia, compared with 2.8% (15/543) of FD patients who presented with intermittent dysphagia. Approximately 8.8% (21/239) of OD patients reported dramatic weight loss accompanied with other severe symptoms, compared with 5.9% (32/543) of FD patients who had no other severe symptoms. A shift in symptom subtypes during the follow‐up period was found in 13.8% of FD patients. The infection rate of Helicobacter pylori was higher in the OD group than in the FD group (53.1%vs 42.2%, P < 0.01), but no difference was found among the three subgroups of FD patients (P > 0.05). Halitosis was more often found in dyspeptic patients with H. pylori infection (44.9%vs 17.0% in OD, 47.3%vs 25.4% in FD, P < 0.01).CONCLUSIONS:  When dyspepsia patients present with ‘stomach’ pain or ‘stomach’ pain before meals, a diagnosis of OD should be considered. Intermittent dysphagia, weight loss not accompanied with other severe symptoms, and halitosis (more often seen in patients with H. pylori infection) might be regarded as the relatively unique symptoms of dyspepsia in some FD patients. In FD, we found that the severity of dyspepsia symptoms was not related to meals in half of the patients, and symptom subtypes might shift over time, this adds difficulty to the management of FD.
Synergistic effects of matrine and 5‐fluorouracil on tumor growth of the implanted gastric cancer in nude mice
Authors: HU Mei Jie , ZENG Hui , WU Yun Lin , ZHANG Yong Ping , ZHANG Shu , QIAO Min Min , FU Hua 
Published: May 2005

OBJECTIVE:  To investigate the inhibitive effects of matrine and 5‐fluorouracil (5‐FU) on the growth of human gastric adenocarcinoma cell line SGC‐7901 when transplanted into nude mice and to investigate the bone marrow toxicity of these compounds.METHODS:  50 mg/kg and 100 mg/kg matrine with 50 mg/kg 5‐FU, and 50 mg/kg matrine only, 50 mg/kg 5‐FU only were intraperitoneally injected to observe their inhibitive effects by calculating the relative tumor volume (RTV) and tumor inhibition rates (IR%) as shown by the number of nucleated cells and bone marrow cell colony culture.RESULTS:  The tumor inhibitive effect of the combined 100 mg/kg matrine and 50 mg/kg 5‐FU group was stronger than that of the combined 50 mg/kg matrine and 50 mg/kg 5‐FU groups (P < 0.05), and were also much stronger than that of the control group (50 mg/kg matrine only, 50 mg/kg 5‐FU only, P < 0.01). As for the bone marrow inhibition effect, there was no significant statistical difference between the combination group and 5‐FU alone group. In the cultured bone marrow cell colony, exuberant growth was seen in the combination group, but not in the control group.CONCLUSIONS:  The inhibitive effect of combined matrine and 5‐FU on the growth of transplanted human gastric cancer in nude mice is superior to that of matrine or 5‐FU alone. Combined matrine and 5‐FU can increase the inhibitive effect on proliferative hemopoietic bone marrow cells in nude mice and does not affect the resting bone marrow stem cells.
Comparison of deterministic and stochastic approaches to global optimization
Authors: Liberti Leo , Kucherenko Sergei 
Published: May 2005

AbstractIn this paper, we compare two different approaches to nonconvex global optimization. The first one is a deterministic spatial Branch‐and‐Bound algorithm, whereas the second approach is a Quasi Monte Carlo (QMC) variant of a stochastic multi level single linkage (MLSL) algorithm. Both algorithms apply to problems in a very general form and are not dependent on problem structure. The test suite we chose is fairly extensive in scope, in that it includes constrained and unconstrained problems, continuous and mixed‐integer problems. The conclusion of the tests is that in general the QMC variant of the MLSL algorithm is generally faster, although in some instances the Branch‐and‐Bound algorithm outperforms it.