bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 mutation pattern of esophageal squamous cell carcinomas in a high risk area (Southern Brazil): Role of life style factors
Authors: Pütz Arno , Hartmann Antonio A. , Fontes Paulo R.O. , Alexandre Claudio O.P. , Silveira Daniela A. , Klug Stefanie J. , Rabes Hartmut M. 
Published: August 2002

AbstractIn an attempt to correlate the TP53 mutation pattern of squamous cell carcinomas of the esophagus (ESCC) and life style factors of patients from the high risk area Rio Grande do Sul, Brazil, 135 ESCC were analyzed, after prescreening by p53 immunohistochemistry, by SSCP and DNA sequencing of TP53, exon 5–9. Forty‐nine somatic TP53 mutations (and 1 case with p53 polymorphism) were identified as missense (n = 39), frameshift (n = 6), silent (n = 1), amber (n = 1) or intron border mutations (n = 2) that cause splicing aberrations. They were preferentially found in exon 5 (36.7%) and exon 8 (32.7%). Several mutations were located in the mutation hot spot codons 248, 273 and 282, mainly at CpG sites. Transition mutations were observed in 53.1% (among them 50% G > A), transversion mutations in 34.7% (among them 47.1% G > T) and frameshifts in 12.2%, the latter 2 mainly in smokers and alcohol drinkers. Transitions were more prevalent in females than in males (p < 0.05). TP53 mutations, mainly transversions, were more frequently found in heavy smokers (p = 0.03), with the same tendency after chronic alcohol consumption. Comparison with the worldwide IARC database disclosed differences in the TP53 mutation pattern of the Brazilian tumors, with a higher accumulation of TP53 mutations in exon 8 and a higher prevalence of transition mutations. Mutations at the reported hot spot codon 176 were missing. Although difficult because of the documented coexposure to various life style risk factors in most patients of this series, the hypothesis is proposed that besides smoking and alcohol drinking the commonly consumed hot mate tea in this high risk area for ESCC is responsible for this different pattern of TP53 mutations because of chronic hyperthermic irritation and inflammation in the esophagus with an endogenous formation of radicals or carcinogenic factors that lead to a higher prevalence of transition mutations. © 2001 Wiley‐Liss, Inc.
Intratumoral immunotoxin treatment of human malignant brain tumors in immunodeficient animals
Authors: Engebraaten Olav , Hjortland Geir Olav , Juell Siri , Hirschberg Henry , Fodstad Øystein 
Published: August 2002

AbstractTreatment of malignant brain tumors remains a clinical challenge. New treatment modalities are under investigation and among these are intratumoral infusion of immunotoxins that bind to specific cell surface molecules on the malignant cells. We have compared the efficacy of the 425.3‐PE immunotoxin (which targets the epidermal growth factor [EGF] receptor) with the well‐known immunotoxin Tfn‐CRM107 (which targets the transferrin receptor), for the treatment of subcutaneous and intracranial human gliomas in nude animals. Bolus intratumoral administration of 1 μg Tfn‐CRM107 or 425.3‐PE into sc U87Mg tumors in nude mice reduced the tumor volume to 29 and 79%, respectively, of that in the control group 18 days after start of treatment. Higher doses of Tfn‐CRM107 were toxic to the animals, whereas 425.3‐PE was tolerated, with a dose‐response relationship of up to 8 μg, a dose that reduced the tumor volume to 2% of control. In nude rats, treatment of intracerebral U87Mg tumors with Tfn‐CRM107 proved ineffective and doses above 10 ng/animal were toxic to tumor‐bearing rats. In contrast, intratumoral administration of 4 μg 425.3‐PE increased symptom‐free survival from 23 days to 40 days, with 2/9 surviving more than 90 days. We have recently shown that immunodeficient rats inoculated intracerebrally with precultured glioblastoma biopsy specimens develop highly infiltrative brain tumors. Direct interstitial infusion of immunotoxins into such tumors reduced the number of animals with detectable tumors at autopsy after 3 months, from 8/9 in the control animals to 4/6 and 2/6 in animals treated with Tfn‐CRM107 and 425.3‐PE, respectively. In conclusion, the anti‐EGF receptor immunotoxin 425.3‐PE exhibited promising efficacy, comparable to or better than that of Tfn‐CRM107, an immunotoxin that in early clinical trials has been found to give responses in patients with brain tumors. © 2001 Wiley‐Liss, Inc.
Tumor‐specific CD8+ T lymphocytes derived from the peripheral blood of prostate cancer patients by in vitro stimulation with autologous tumor cell lines
Authors: Housseau Franck , Langer Daniel A. , Oberholtzer Samuel D. , Moorthy Anitha , Levitsky Hyam I. , Pardoll Drew M. , Topalian Suzanne L. 
Published: August 2002

AbstractTo identify tumor‐associated antigens as putative targets for developing immunotherapies against prostate cancer, we investigated the ability of T cells derived from the peripheral blood lymphocytes of prostate cancer patients to recognize autologous tumor cells. The technical challenge of growing in vitro carcinoma cell lines from small prostate cancer samples was previously addressed by immortalization of early epithelial cell cultures with the HPV16 transforming proteins E6 and E7 and by genetic characterization of the carcinoma and normal prostate cell lines. In our study, peripheral blood lymphocytes were stimulated in vitro using autologous IFNγ‐treated prostate carcinoma cells transduced with the B7.1 molecule as a source of T‐cell costimulation. Tumor‐specific CD8+ T lymphocytes were obtained from 3 of 6 prostate cancer patients tested and included T cells restricted by classical and nonclassical HLA molecules. In 1 case, we demonstrated that the prostate cancer‐reactive T cells were TCRα/β+ and recognized autologous tumor cells but not autologous normal cells in the context of HLA‐B or ‐C molecules. These results validate the approach of in vitro stimulation of peripheral blood lymphocytes from prostate cancer patients with autologous tumor cell lines to isolate prostate cancer‐specific T cells and demonstrate the existence of a functionally diverse immune response against prostate cancer. Published 2001 Wiley‐Liss, Inc.
A phase I‐II study of docetaxel‐ifosfamide‐cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer
Authors: Kosmas Christos , Tsavaris Nicolas B. , Makatsoris Thomas , Onyenadum Adimchi , Vadiaka Maria , Stavroyianni Niki , Sepsas Evangelos , Dimitropoulos Dimitris , Rokana Sofia , Kalofonos Haralambos P. 
Published: August 2002

AbstractIn an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel‐ifosfamide‐cisplatin (DIP) based on our previous experience with paclitaxel‐ifosfamide‐cisplatin. Patients with advanced NSCLC (stages III‐IV), WHO‐PS≤2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80–100 mg/m2 day 1), ifosfamide (4–5 g/m2) and cisplatin (80–100 mg/m2), both divided over days 1 and 2 every 21 days. G‐CSF (lenograstin) was administered from days 4–13. Fifty‐five patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40–72); PS = 1 (0–2); gender = 48 males, 7 females; stages IIIA = 8, IIIB = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6), brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose‐limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m2‐Ifosfamide: 5 g/m2‐Cisplatin: 100 mg/m2) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m2‐Ifosfamide: 5 g/m2‐Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase II testing. Among evaluable patients in phase II, 31/46 (67%; CI = 54–81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2–21+), median time to progression (TTP) 8 months (1–23+) and median overall survival (OS) 13 months (2–23+). The 1‐year survival was 57%. Grade (Gr) 3/4 toxicities included neutropenia 39/46 with 27 developing Gr4 (≤7 days) and 20% FN managed successfully with broad‐spectrum antibiotics, thrombocytopenia Gr3 3/46‐Gr4 1/46, no Gr3 neuropathy, Gr1‐2 CNS toxicity in 12, no renal toxicity, 15 Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I‐II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2‐drug regimens will be warranted. © 2001 Wiley‐Liss, Inc.
Inhibition of metalloproteinases enhances the internalization of anti‐CD30 antibody Ki‐3 and the cytotoxic activity of Ki‐3 immunotoxin
Authors: Hansen Hinrich P. , Matthey Bärbel , Barth Stefan , Kisseleva Tatiana , Mokros Thilo , Davies Stephen J. , Beckett R. Paul , Foelster‐Holst Regina , Lange Hans H. , Engert Andreas , Lemke Hilmar 
Published: August 2002

AbstractCD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti‐CD30 antibody‐based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor‐α converting enzyme (TACE). This metalloproteinase releases the soluble ectodomain of CD30 (sCD30), which is able to neutralize immunotherapeutic agents before these reach their target cells. Such constitutive CD30 cleavage is enhanced after binding of most anti‐CD30 antibodies, leading to a downregulation of CD30 and an increase of sCD30 in the cell environment. Here, we demonstrate that CD30 shedding from the cell line Karpas 299 could effectively be blocked by the hydroxamic acid‐based metalloproteinase inhibitors BB‐3644 (IC50 = 180 nM), BB‐2116 (IC50 = 230 nM), BB‐94 (batimastat, IC50 = 230 nM) and BB‐2516 (marimastat, IC50 = 1 μM). This inhibition reduced the concentration of sCD30 in the cell environment to the background level, prolonged the persistence of the anti‐CD30 antibody Ki‐3 on Karpas 299 cells and favored its internalization. Moreover, a nontoxic concentration of the inhibitor BB‐3644 significantly increased the cytotoxic activity of the anti‐CD30 ricin A‐chain immunotoxin Ki‐3.dgA towards the CD30+ Hodgkin‐derived cell line L540. Hence, the metalloproteinase inhibitor BB‐3644 may be a promising compound to improve the immunotherapy of CD30+ malignancies. © 2001 Wiley‐Liss, Inc.
Human papillomavirus 16 load in normal and abnormal cervical scrapes: An indicator of CIN II/III and viral clearance
Authors: van Duin Mark , Snijders Peter J.F. , Schrijnemakers Henri F.J. , Voorhorst Feja J. , Rozendaal Lawrence , Nobbenhuis Marielle A.E. , van den Brule Adriaan J.C. , Verheijen René H.M. , Helmerhorst Theo J. , Meijer Chris J.L.M. 
Published: August 2002

AbstractThe relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high‐grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case‐control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real‐time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN ≤ I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6–33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN ≤ I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1–9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high‐grade CIN lesion. © 2002 Wiley‐Liss, Inc.
Invasive bladder carcinoma: A pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin
Authors: Zouhair Abderrahim , Ozsahin Mahmut , Schneider Dominique , Bauer Jean , Jichlinski Patrice , Roth Arnaud , Douglas Pelham , Miralbell Raymond 
Published: August 2002

AbstractFrom November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49–86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m2) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was sucessfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four‐year overall and disease‐specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4‐year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low‐stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population. © 2001 Wiley‐Liss, Inc.
Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma
Authors: Fawole Adeshina S. , Simpson David J. , Rajagopal Ramesh , Elder Jackie , Holland Tracey A. , Fryer Anthony , Deakin Mark , Elder James B. , Farrell William E. 
Published: August 2002

AbstractRecent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple‐steps responsible for initiation and progression. © 2002 Wiley‐Liss, Inc.
Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine
Authors: Salaspuro Ville , Hietala Jaana , Kaihovaara Pertti , Pihlajarinne Liisa , Marvola Martti , Salaspuro Mikko 
Published: August 2002

AbstractHigh alcohol intake is an independent risk factor for upper gastrointestinal (GI)‐tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol‐associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2‐deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L‐cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L‐cysteine‐containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L‐cysteine tablet compared to placebo was 59% (CL95% 43%, 76%). Area under the curve (AUC0–320min) with the L‐cysteine and placebo tablet were 54.3 ± 11 μM × hr and 162 ± 34.2 μM × hr (mean ± SEM), respectively (p = 0.003). After alcohol intake, up to two‐thirds of carcinogenic acetaldehyde can be removed from saliva with a slow‐releasing buccal L‐cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI‐tract cancers, especially among high‐risk individuals. © 2001 Wiley‐Liss, Inc.
Channelling and filtering migration: Hungary's bilateral labour migration agreements
Authors: Hárs Ágnes 
Published: August 2002

AbstractNew forms of mobility are being shaped in Europe which both challenge traditional explanations of mobility and contribute to popular fears of mobility. But what makes people move, and which economic indicators effectively explain migration? Does the projected migration pressure from Central/Eastern Europe actually exist? The answer to this question is often posed in terms of mainstream economic arguments concerning wage/income differences, but this offers only a partial explanation of migration. This paper considers attempts to control migration, channelling foreign labour from the countries of Central and Eastern Europe through different bilateral agreements, under different conditions, to European Union countries, as a way of admitting selected types of labour while excluding others. Surprisingly little is known about such programmes, and the paper considers who is attracted to these programmes, and the nature of the engine of this channelled labour migration? A statistical, socio‐demographic, labour‐market analysis of participants in these schemes, with special emphasis on the Hungarian case, is presented. The question is posed as to whether such bilateral agreements offer a means to control the expected European migration ‘shock’, and concludes that this is not the aim of these schemes. Copyright © 2002 John Wiley & Sons, Ltd.
Lessons learned from study of the developmental impact of parental alcohol use
Authors: Carmichael Olson Heather , O'Connor Mary J. , Fitzgerald Hiram E. 
Published: August 2002

AbstractThis overview outlines the magnitude of the impact of parental substance abuse on children's development. The aim of this special issue is described: to encourage research productivity by promoting integration between two traditionally separate literatures with quite different theoretical perspectives: (1) the effects of prenatal substance exposure; and (2) the impact on children of postnatal rearing by parents addicted to substances. Because study of the developmental impact of parental alcohol use has a long research tradition, lessons learned can guide the field. Thus, this overview focuses on the role of maternal drinking in the emergence of childhood psychopathology, a topic of interest to infant mental health. As an example, this article features multiple findings from O'Connor's programmatic research, which is built upon current models of development and integrated theoretical perspectives, and includes both lower and higher risk samples. These data show that women in a middle‐class sample who drank more heavily during pregnancy had infants with higher levels of negative affect and insecure attachments. At ages 5–6, a greater percentage of these alcohol‐exposed children showed significant levels of depression than expected for their age. Prenatal alcohol exposure and maternal depression both contributed significantly to prediction of preschoolers' depression, and findings could not be explained by mother's current drinking. Congruent results from a higher risk sample show how cumulative risk can exacerbate problems, and extend earlier data by documenting the mother–child interplay that can maintain or reduce the deleterious effects of prenatal alcohol exposure over time. Results are discussed in light of current theory about the early emergence of internalizing disorders, with implications for research and intervention. This overview ends by introducing the articles in this special issue, and how each contributes to advancing its aim. ©2001 Michigan Association for Infant Mental Health.
The current state of paddy agriculture in Japan1
Authors: Sato Hitoshi 
Published: August 2002

AbstractThis document is a published version of the keynote speech made at the Asian Regional Workshop on Sustainable Development of Irrigation and Drainage for Rice Paddy Fields held in Tokyo in July 2000, hosted by the Japanese National Committee of the ICID.This report outlines the current state of paddy agriculture in Japan, focusing on the history of paddy field development, current status of paddy field improvements, the formation of rules on water use, and the roles of land improvement districts, which form the basis of managing agricultural water in Japan. It also highlights the present situation of agriculture in Japan, directions of relevant efforts and initiatives, and the importance of enhancing multiple functions of paddy agriculture for the national livelihood as well as securing a stable food supply.Paddy agriculture is an effective way of achieving both agricultural production and environment conservation functions in the Asian monsoon region. However, in the face of limited land and water resources as well as rapidly increasing population, a stable food supply will be difficult to attain in the future without the development and the establishment of irrigation and drainage technologies for paddy fields, and the dissemination and sharing of these technologies. Copyright © 2001 John Wiley & Sons, Ltd.