bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive aspergillosis in a patient with aplastic anemia receiving amphotericin B
Authors: Antoine Grogory A. , Gates Robert H. , Park Alfred O.
Published: February 2007

Invasive mycotic infections are becoming more commonplace in immune‐compromised hosts. Aspergillus species is the most commonly encountered fungal genus in our environment causing paranasal sinus fungal infection. Aspergillus paranasal sinus infections in the healthy host are readily treated and controlled. In the immune‐compromised host this common organism can rapidly become fatal even if recognized and treated appropriately. We present a case history of a patient who died from her disease despite radical surgery and antifungicidal therapy. Recent methods for early diagnosis will be reviewed. Only one other case has been reported in the literature of a patient developing fulminant aspergillosis sinusitis while receiving amphotericin B.
Intramuscular hemangioma of the head and neck: Report of a case involving the prevertebral muscles
Authors: Beecham James E. , Behrens Hans W.
Published: February 2007

Intramuscular hemangioma, a distinctive type of hemangioma occurring within skeletal muscle, accounts for approximately 1% of all hemangiomas. Most occur in the trunk and extremities, perhaps due to the relatively larger muscle mass in those areas. This report describes the first case of an intramuscular hemangioma of the prevertebral muscles. Intramuscular hemangioma is seldom diagnosed preoperatively, perhaps due to unfamiliarity with this uncommon lesion. Preoperative diagnosis is important, however, to properly evaluate feeding arterial blood supply and prevent potential operative morbidity. Surgical excision represents the treatment of choice. Intramuscular hemangioma should be considered in the differential diagnosis of deep head and neck masses.
Malignant oncocytoma of the maxillary sinus— An ultrastructural study
Authors: Mikhail Raouf A. , Reed Donald N. , Bybee David B. , Okoye Matthias I. , Dodds Max E.
Published: February 2007

A unique case of a malignant oncocytoma of the maxillary sinus is reviewed in detail. The ultrastructural findings are presented. The histologic and ultrastructural criteria that characterize onco‐cytes and the clinicopathologic features of benign and malignant oncocytomas are discussed. This case represents the eleventh reported case that would truly qualify as a malignant oncocytoma of the paranasal sinuses.
A Novel Synthesis of Highly Substituted Perhydropyrrolizines, Perhydroindolizines, and Pyrrolidines: Inhibition of the Peptidyl‐Prolyl cis/trans Isomerase (PPIase) Pin1
Authors: Siegrist Romain , Zürcher Martina , Baumgartner Corinne , Seiler Paul , Diederich François , Daum Sebastian , Fischer Gunter , Klein Christian , Dangl Markus , Schwaiger Manfred
Published: February 2007

In this paper, we describe the synthesis and biological evaluation of highly substituted perhydropyrrolizines that inhibit the peptidyl‐prolyl cis/trans isomerase (PPIase) Pin1, an oncogenic target. The enzyme selectively catalyzes the cis/trans isomerization of peptide bonds between a phosphorylated serine or threonine, and proline, thereby inducing a conformational change. Such structural modifications play an important role in many cellular events, such as cell‐cycle progression, transcriptional regulation, RNA processing, as well as cell proliferation and differentiation. Based on computer modeling (Fig. 2), the new perhydropyrrolizinone derivatives (−)‐1a,b, decorated with two substituents, were selected and synthesized (Schemes 1–3). While enzymatic assays showed no biological activity, 15N,1H‐HSQC‐NMR spectroscopy revealed that (−)‐1a,b bind to the WW recognition domain of Pin1, apparently in a mode that does not inhibit PPIase activity. To enforce complexation into the larger active site rather than into the tighter WW domain of Pin1 and to enhance the overall binding affinity, we designed a perhydropyrrolizine scaffold substituted with additional aromatic residues (Fig. 5). A novel, straightforward synthesis towards this class of compounds was developed (Schemes 4 and 5), and the racemic compounds (±)‐22a–22d were found to inhibit Pin1 with Ki values (Ki = inhibition constant) in the micromolar range (Table 2). To further enhance the potency of these inhibitors, the optically pure ligands (+)‐22a and (+)‐33b,c were prepared (Schemes 6 and 7) and shown to inhibit Pin1 with Ki values down to the single‐digit micromolar range. According to 15N,1H‐HSQC‐NMR spectroscopy and enzymatic activity assays, binding occurs at both the WW domain and the active site of Pin1. Furthermore, the new synthetic protocol towards perhydropyrrolizines was extended to the preparation of highly substituted perhydroindolizine ((±)‐43; Scheme 8) and pyrrolidine ((±)‐48a,b; Scheme 9) derivatives, illustrating a new, potentially general access to these highly substituted heterocycles.
New Triterpenoidal Saponins from Gypsophila repens
Authors: Elbandy Mohamed , Miyamoto Tomofumi , Lacaille‐Dubois Marie‐Aleth
Published: February 2007

Six new triterpene glycosides, repensosides A–F (1–6, resp.), were isolated from the roots of Gypsophila repens L. Their structures, established by extensive 1D‐ and 2D‐NMR spectroscopic experiments as well as MS analyses, were found to be based on gypsogenic acid (or gypsogenin) as aglycone, with three to nine branched or unbranched sugar moieties.
Semisynthesis of 3′(2′)‐O‐(Aminoacyl)‐tRNA Derivatives as Ribosomal Substrate
Authors: Cui Zhiyong , Zhang Biliang
Published: February 2007

An efficient synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated pCpA derivatives is described, which could lead to the production of (aminoacyl)‐tRNAs following T4 RNA ligase mediated ligation. The tetrahydrofuranyl (thf) group was used as a permanent protective group for the 2′‐OH of the cytidine moiety which can be removed during the purification of the 3′(2′)‐O‐aminoacylated‐pCpA. This approach allowed for a general synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated oligonucleotides. The fully protected pCpA 14 was synthesized by phosphoramidite chemistry and treated with NH3 solution to remove the 2‐cyanoethyl and benzoyl groups (→ 15; Schemes 1 and 2). The 2′‐O‐thf‐protected‐pCpA 15 was coupled with α‐amino acid cyanomethyl esters, and the products 20a–c were deprotected and purified with AcOH buffer to afford 3′(2′)‐O‐aminoacylated pCpA 21a–c in high yields. The 3′(2′)‐O‐aminoacylated pCpA were efficiently ligated with tRNA(− CA) to yield (aminoacyl)‐tRNA which was an active substrate for the ribosome.
Asymmetric Catalytic Hydroamination of Activated Olefins in Ionic Liquids
Authors: Fadini Luca , Togni Antonio
Published: February 2007

The addition of a series of both aliphatic and aromatic amines to electron‐poor olefins was investigated using [Ni(Pigiphos)(THF)]2+ as catalyst (with different counterions) in various ionic liquids based on imidazolium‐ and picolinium‐salt derivatives. The catalysts gave rise to selectivities comparable to those obtained when the reaction was conducted in neat organic solvents (ee up to 66%), but significant higher activities, with a total turnover number (TON) of up to 300.
Bubble behavior during boiling of subcooled binary mixtures on very thin wires
Authors: Wang Zhen , Peng Xiao‐Feng , Wang Xiao‐Dong
Published: February 2007

Experimental investigations were conducted to explore the characteristics of subcooled nucleate boiling of binary mixtures composed of water and ethanol on very thin wires, and an emphasis was addressed to observe bubble movement and bubble jet flow. The experiments exhibited many different bubble jet flows, such as continuous, discontinuous, diverged, bifurcate jet flows, and small bubble spraying, corresponding to different vapor bubble sizes and bubble‐moving modes such as bubble initial momentum and bubble‐generating frequency. The bubble movement within the jet flow also was analyzed. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(2): 105–111, 2007; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/htj.20142
Lattice Boltzmann simulation on flow fields connected with multiple side‐channels
Authors: Tsushima Shohji , Moriyama Koji , Hirai Shuichiro
Published: February 2007

For this study, using the lattice Boltzmann method (LBM), we conducted flow‐field analyses in which two straight channels were mutually connected with multiple side‐channels. Results showed that calculated flow fields can be categorized into three types of flow pattern depending on flow field geometry and flow conditions. The following typical flow patterns were identified: case 1, the incoming flow passes uniformly through the side channels; case 2, the flow passes preferentially through the side channel in the inlet and the outlet; and case 3, the flow passes mainly through the side channel of the outlet side. Results also indicate that these flow patterns depend on two dimensionless parameters: the ratio of permeability of the side channels to the channel width, and the Reynolds number. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(2): 96–104, 2007; Published online in Wiley InterScience (www. interscience.wiley.com). DOI 10.1002/htj.20143
Experimental research of boiling heat transfer of smooth and screwed tube
Authors: Li Maode , Chen Huier , Xiong Lihong , Lu Xihong
Published: February 2007

In this paper, based on the analog theory of heat transfer research, we performed an analog experiment on boiling heat transfer in smooth tube and screwed tubes. These are widely used in the high pressure generator of lithium bromide absorption refrigeration. From the experimental research, we obtained a series of results on the boiling heat transfer of a single smooth tube and three screwed tubes. The working condition is near the zone of bubble boiling and the overheat wall temperature ranges from 2–7 °C, with a fluid medium of pure water and salt water solution. These results agreed well with the known results, and are significant for the practical design and application of a high pressure generator of lithium bromide absorption for refrigeration. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(2): 74–84, 2007; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/htj.20145
Exergy transfer analysis of convection heat transfer
Authors: Li Maode , Chen Huier
Published: February 2007

In this paper, based on the fundamentals of thermodynamics and heat transfer, an analysis is made of the exergy transfer of convection heat transfer. Some exergy transfer differential equations are derived under constant thermophysical property and uncompressible laminar flow in the convection heat transfer process. Taking one‐ and two‐dimensional convection heat transfer as examples, respectively, the exergy functions are solved and calculated. Their results agree well with those results from thermodynamic analysis. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(2): 66–73, 2007; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/htj.20146
Three‐dimensional hydrodynamic and salinity transport modelling of Danshuei River estuarine system and adjacent coastal sea, Taiwan
Authors: Liu Wen‐Cheng , Hsu Ming‐Hsi , Kuo Albert Y.
Published: February 2007

A three‐dimensional, time‐dependent hydrodynamic and salinity model was applied to the Danshuei River estuarine system and adjacent coastal sea in Taiwan. The model forcing functions consist of tidal elevations along the open boundary and freshwater flows from the main stem and tributaries in the Danshuei River system. The bottom roughness height was calibrated and verified with model simulation of barotropic flow, and the turbulent diffusivities were calibrated through comparison of time‐series of salinity distributions. The overall model verification was achieved with comparisons of residual current and salinity distribution. The model simulation results are in qualitative agreement with the available field data.

The model was then used to investigate the tidal current, residual current, and salinity patterns under the low freshwater flow condition in the modelling domain. The results reveal that the extensive intrusion of saline water imposes a significant baroclinic forcing and induces a strong residual circulation in the estuary. The downriver net velocity in the upper layer increases seaward despite the enlargement of the river cross‐section in that direction. Strong residual circulation can be found near the Kuan‐Du station. This may be the result of the deep bathymetric features there. Copyright © 2007 John Wiley & Sons, Ltd.
Estimates of spatial variation in evaporation using satellite‐derived surface temperature and a water balance model
Authors: Bouwer Laurens M. , Biggs Trent W. , Aerts Jeroen C. J. H.
Published: February 2007

Evaporation dominates the water balance in arid and semi‐arid areas. The estimation of evaporation by land‐cover type is important for proper management of scarce water resources. Here, we present a method to assess spatial and temporal patterns of actual evaporation by relating water balance evaporation estimates to satellite‐derived radiometric surface temperature. The method is applied to a heterogeneous landscape in the Krishna River basin in south India using 10‐day composites of NOAA advanced very high‐resolution radiometer satellite imagery. The surface temperature predicts the difference between reference evaporation and modelled actual evaporation well in the four catchments (r2 = 0·85 to r2 = 0·88). Spatial and temporal variations in evaporation are linked to vegetation type and irrigation. During the monsoon season (June–September), evaporation occurs quite uniformly over the case‐study area (1·7–2·1 mm day−1), since precipitation is in excess of soil moisture holding capacity, but it is higher in irrigated areas (2·2–2·7 mm day−1). In the post‐monsoon season (December–March) evaporation is highest in irrigated areas (2·4 mm day−1). A seemingly reasonable estimate of temporal and spatial patterns of evaporation can be made without the use of more complex and data‐intensive methods; the method also constrains satellite estimates of evaporation by the annual water balance, thereby assuring accuracy at the seasonal and annual time‐scales. Copyright © 2007 John Wiley & Sons, Ltd.
Telomerase expression in lung preneoplasia and neoplasia
Authors: Lantuéjoul Sylvie , Salon Caroline , Soria Jean‐Charles , Brambilla Elisabeth
Published: February 2007

Telomeres are specialized structures at eukaryotic chromosomes ends, which role is to prevent them from degradation, end to‐end fusion and rearrangement. However, they shorten after each cellular division because of an incomplete DNA replication, acting in normal somatic cells as a mitotic clock for permanent proliferation arrest or senescence entry. Short telomeres are perceived as damaged DNA leading to p53/ATM pathway activation. In tumoral cells, a ribonucleoprotein complex termed telomerase enables telomere elongation. This complex, composed of 2 main components, the telomerase RNA component or hTR, the RNA template for telomere synthesis, and telomerase reverse transcriptase, the catalytic subunit, is reactivated in the majority of cancers, including those of the lung. In this review, we briefly present the main results on telomerase expression in various histological types of lung carcinoma and in bronchial carcinogenesis along with telomere attrition. Inhibition of one of the main components of the enzyme or limitation of telomere access by telomerase represent novel targets for cancer therapies and chemoprevention in high risk patients of lung cancer. © 2007 Wiley‐Liss, Inc.
6‐(1‐Oxobutyl)‐5,8‐dimethoxy‐1,4‐naphthoquinone inhibits lewis lung cancer by antiangiogenesis and apoptosis
Authors: Lee Hyo Jeong , Lee Hyo‐Jung , Song Gyu‐Yong , Li Guangxun , Lee Jae‐Ho , Lü Junxuan , Kim Sung‐Hoon
Published: February 2007

Lung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6‐(1‐oxobutyl)‐5,8‐dimethoxy‐1,4‐naphthoquinone (OXO) exhibits anti‐tumor activity against S‐180 sarcoma in vitro and in vivo. Here we studied the anti‐angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF‐stimulated than basic bFGF‐stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S‐phase arrest and mitochondria/caspase‐9 pathway mediated apoptosis, but also effectively down‐regulated the hypoxia‐induced expression of HIF‐1α and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti‐cancer effect was associated with decreased HIF‐1α and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti‐cancer activity through anti‐angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer. © 2007 Wiley‐Liss, Inc.
Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy
Authors: Lopes Rita Bayer , Gangeswaran Rathi , McNeish Iain A. , Wang Yaohe , Lemoine Nick R.
Published: February 2007

Pancreatic cancer is one of the most aggressive human tumors with a 5‐year survival rate of only 3% and a striking resistance to chemotherapy and radiotherapy. The search for new therapeutic approaches includes strategies exploiting the deregulation of apoptotic pathways commonly found in cancer cells. The IAP proteins are inhibitors of apoptosis that have altered activity in numerous cancer types and are implicated in resistance to chemotherapy, and therefore are potentially interesting as therapeutic targets. We investigated alterations in the expression of IAPs and their inhibitors in pancreatic adenocarcinoma by using real‐time PCR, in situ hybridization and immunohistochemistry. We found differential expression of various IAPs in this malignancy, and particularly we observed overexpression of cIAP‐2, survivin, livin and XIAP. We also looked for correlations between the expression of IAPs and resistance to paclitaxel, doxorubicin, CDDP and 5‐fluorouracil, and found that resistance to these drugs correlates most significantly with expression of cIAP‐2. Using RNAi to downregulate these proteins we further confirmed that the levels of cIAP‐2 and XIAP influence the response to the anti‐cancer drugs, although only marginally for 5‐FU. We conclude that anti‐tumor strategies based on the inhibition of particular IAPs can be useful in targeting pancreatic adenocarcinoma. © 2007 Wiley‐Liss, Inc.
Genetic polymorphisms in the one‐carbon metabolism pathway and breast cancer risk: A population‐based case–control study and meta‐analyses
Authors: Lissowska Jolanta , Gaudet Mia M. , Brinton Louise A. , Chanock Stephen J. , Peplonska Beata , Welch Robert , Zatonski Witold , Szeszenia‐Dabrowska Neonila , Park Sue , Sherman Mark , Garcia‐Closas Montserrat
Published: February 2007

Epidemiological evidence suggests that intake of folate and other B‐vitamins and genetic variants in the one‐carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population‐based case–control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one‐carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73–0.96) and 0.85 (0.62–1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p‐trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta‐analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one‐carbon metabolism pathway and breast cancer risk. © 2007 Wiley‐Liss, Inc.
Immunohistochemical localization of matrix metallloproteinase 2 and its specific inhibitor timp‐2 in neoplastic tissues with monclonal antibodies
Authors: Höyhtyã Matti , Fripman Rafiae L , Komarek Daniel , Porter‐Jordan Kathleen , Stetler‐Stevenson William G. , Liotta Lance A. , Liang Chi‐Minjg
Published: February 2007

Matrix metall oproteinase‐2 (MMP‐2), synthesized as a 631 amino‐acid proenzyme, is activated by cleavage of the first 80 amino acids and naturally inhibited by tissue inhibitor of metalloproteinase‐2 (TIMP‐2). We report here the production of MAbs against MMP‐2 and TIMP‐2 and their use in localizing the respective antigens on tumor tissues. The anti‐MMP‐2 MAb recognized the latent and activated MMP‐2 mutant protein (mutein) with C‐terminal deletion at amino acid 425, indicating that both N‐and C‐terminal amino acids of MMP‐2 are not important for its binding. The binding study of anti‐TIMP‐2 MAb, using several C‐terminally truncated TIMP‐2 muteins, showed that the amino acids 111–126 of TIMP‐2 are essential for the binding of this antibody. Besides their respective antigens, both MAbs also recognized the MMP‐2/TIMP‐2 complex. On frozen sections of breast tumor, anti‐MMP‐2 MAb stained mainly tumor‐cell cytoplasm with varying intensity, while anti‐TIMP‐2 MAb gave a stromal staining of varying intensity and a weak or absent staining of tumor‐cell cytoplasm, suggesting different localization of the proteins in these tumors. In addition, in 1/3 of the breast cases both antibodies also localized on tumor‐cell membranes. Similar cytoplasmic and stromal but not membrane staining patterns were observed in colon, gastric, endometrial, squamous‐cell, prostatic and ovarian carcinoma as well. Since MMP‐2 degrades type‐IV collagen, the major component of basement membranes, the differences between MMP‐2 and TIMP‐2 levels and localization in individual tumors may relate to the invasiveness of the tumor and thus provide predictive information. However, this aspect could not be discussed in this study because no biological and clinical parameters such as lymph‐node involvement or Dukes' stage of the tumors were available.
Increased tumorigenicity of human keratinocytes harboring human papillomavirus type 16 is associated with resistance to endogenous tumor necrosis factor‐α‐mediated growth limitation
Authors: Malejczyk Jacek , Malejczyk Magdalena , Majewski Slawomir , Breitburd Françoise , Luger Thomas A. , Jablonska Stefania , Orth Gerard
Published: February 2007

The aim of this study was to evaluate the relationship between tumorigenicity of cell sublines derived from weakly tumorigenic SKv‐e and SKv‐I keratinocytes harboring human papillomavirus type 16 (HPV 16) and their susceptibility to autocrine growth limitation mediated by tumor necrosis factor‐α (TNF‐α). These sublines displayed different in vitro proliferative potential which correlated with tumorigenicity in nu/nu mice. Recombinant TNF‐α inhibited in vitro growth of weakly tumorigenic parental SKv cell lines while it did not affect proliferation of their respective highly tumorigenic sublines. Resistance to TNF‐α correlated with both increased in vitro proliferation and tumorigenicity. Anti‐TNF‐α antibodies (Ab) significantly increased in vitro proliferation of weakly tumorigenic parental SKv cells up to the levels of their highly tumorigenic sublines. Growth of highly tumorigenic SKv cells was not affected. On the other hand, proliferation of SKv cells was affected neither by transforming growth factor‐β (TGF‐β) nor by anti‐TGF‐β Ab. All SKv cell sublines tested spontaneously released TNF‐α, as evaluated by a specific radioimmunoassay; however, the levels of the endogenous cytokine were not related to their proliferative potential and tumorigenicity. An increased resistance to the anti‐proliferative effect of TNF‐α may be associated with decreased expression of TNF‐α receptors (TNF‐αR) inasmuch as evaluation of 125 I‐TNF‐α binding and Northern‐blot analysis of TNF‐αR‐specific mRNA showed that highly tumorigenic SKv cell sublines expressed significantly lower numbers of TNF‐αR than their respective parental cells. These results show that an increased tumorigenicity of HPV 16‐harboring SKv keratinocytes may be, at least partially, due to escape from autocrine TNF‐α‐mediated growth limitation.
Aberrant crypt foci and colon tumors in F344 rats have similar increases in proliferative activity
Authors: Pretlow Theresa P. , Cheyer Christopher , Ann O'Riordan Mary
Published: February 2007

Increased proliferative activity has been described frequently in the colons of animals treated with colon carcinogens and of patients at increased risk of colon cancer; it has been proposed as an intermediate biomarker of colon cancer. Aberrant crypt foci, microscopic lesions identified in whole‐mount preparations of colons, are thought to be putative pre‐neoplastic lesions. The present studies were carried out to evaluate the proliferative activity of aberrant crypt foci at several different time periods, and of tumors after a single dose of azoxymethane (AOM) in F344 rats. Rats were injected with 5‐bromo‐2′‐deoxyuridine (BUdR) 1 hr before killing. Aberrant crypt foci and tumors were identified and marked in the whole‐mount specimens, embedded in glycol methacrylate, and evaluated for histochemically demonstrable hexosaminidase activity. Hexosaminidase is known to be altered in over 95% of aberrant crypt foci. Serial sections were evaluated for BUdR incorporation immunohistochemically with a monoclonal antibody. The mean proliferative activity of aberrant crypt foci in the distal colons was found to be 'increased 3‐to 4‐fold over that of the adjacent normal crypts at every time period analyzed (4 to 36 weeks) and was comparable to that seen in benign and malignant colon tumors in the same animals. The observed increase in proliferative activity further supports the hypothesis that aberrant crypt foci are putative pre‐neoplastic lesions. Similar aberrant crypt foci, identified in human colons at increased risk of colon cancer, may provide important biomarkers for this common human cancer.
Hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Chinese: A case‐control study
Authors: Tsai Jung‐Fa , Jeng Jen‐Eing , Ho Mei‐Shang , Chang Wen‐Yu , Lin Zu‐Yau , Tsai Juei‐Hsiung
Published: February 2007

To assess whether hepatitis B and C virus infection were risk factors for hepatocellular carcinoma (HCC), antibody to hepatitis C virus (anti‐HCV), hepatitis B surface antigen and e antigen (HBsAg and HBeAg) were tested in 150 HCC patients. Another 150 case‐control pairs matched individually by sex and age were also enrolled. Univariate analysis demonstrated that both the anti‐HCV and the carrier status of HBsAg and HBeAg were significantly associated with HCC. Multi‐variate analysis revealed that both anti‐HCV and HBsAg were risk factors for HCC. The population‐attributable risk was estimated as 14.2% for anti‐HCV alone, 59.4% for HBsAg alone and 8.0% for both anti‐HCV and HBsAg in Taiwan. In conclusion, both hepatitis B and C virus infection are independent risk factors for HCC in Chinese in southern Taiwan.
Expression of glucose transporters in head‐and‐neck tumors
Authors: Mellanen P. , Minn H. , Grénman R. , Härkönen P.
Published: February 2007

The expression of glucose transporter genes (GLUTI‐4) was studied in 20 head‐and‐neck tumors of 18 patients. All tumors—16 of which were squamous‐cell carcinomas (SCC)—expressed GLUTI and/or GLUT3 mRNA, while detectable levels of GLUT2 or GLUT4 mRNA were not observed. The signals for GLUTI and GLUT3 mRNAs varied markedly throughout the SCC tumor population but no clear relationship with the grade of differentiation was found. The high GLUT expression observed in some tumors was, not associated with amplification or rearrangement of the corresponding genes. Immunohistochemistry of 5 SCCs showed that GLUTI protein was located in tumor‐cell membranes in relation to the level of mRNA expression. We conclude that both GLUTI and GLUT3 are involved in basal glucose uptake of extracranial head‐and‐neck tumors. The increased expression of these high‐affinity GLUT isoforms may be related to the growth maintenance of cancer tissue in cases of limited supply of substrate e.g., in poorly vascularized tumor areas.
Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer
Authors: Dinjens Winand N. M. , Van Der Weiden Marcel M. , Schroeder Fritz H. , Bosman Fred T. , Trapman Jan
Published: February 2007

We have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary‐tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph‐node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single‐strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCRSSCP analysis, wereidentified by direct sequencing of the PCR product. Immunohistochemical and PCR‐SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph‐node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph‐node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.
A repertoire of monoclonal antibodies reveals extensive epitope heterogeneity in CEA purified from neoplasms originating from different organs
Authors: Hernando Juan José , Von Kleist Sabine , Grunert Fritz
Published: February 2007

The heterogeneity of carcinoembryonic antigen (CEA) from 5 individual hepatic metastases of tumours originating in different organs (I colon, I stomach and 3 breast adenocarcinomas) was analyzed with a repertoire of 56 αCEA murine MAbs. In each tumour preparation, the MAbs disclosed 2 distinct molecular species displaying remarkable variability in their apparent molecular weights (e.g. 130–170 kDa for the fast‐migrating CEA variant and 180–260 kDa for the slowly‐migrating one). After chemical deglycosylation this heterogeneity was abolished and 2 main proteins of 84 and 64 kDa were generated; the difference in their molecular weights could not be accounted for by differential glycosylation. Although 3 of the analyzed preparations were derived from individual adenocarcinomas of the breast, the glycosylated molecules differed considerably from one another, in their relative molecular mass. The MAbs used showed essentially 3 different recognition patterns according to their reactivity either with both CEA molecular weight variants, or just with the higher or the lower one. In a quantitative comparison of the immunoprecipitation yields of the MAbs with CEA, considerable immunological variability (ranging up to 26‐fold), as well as preferential expression of CEA epitopes, could be demonstrated among the 5 different preparations. Here again no uniform epitope presentation could be observed among the 3 breast tumours thus far tested. Comparison of the precipitation yields with the glycosylated and deglycosylated CEA species revealed that, whereas the CEA antigenic heterogeneity remained in some cases unchanged, most of the MAbs exhibited, in carbohydrate‐free CEA, the appearance of a new heterogeneity.
The influence of local tissue environment on epithelial basement membrane continuity in colorectal carcinomas
Authors: Hewitt Robert E. , Keeble William , Powe Desmond G. , Williamson Richard J. , Turner David R.
Published: February 2007

For colorectal carcinomas, there is evidence that marked discontinuity of the epithelial basement membrane (EBM) is associated with higher malignant potential. Since the meta‐static process appears to be selective, more discontinuous EBMs might be expected in secondary rather than in primary tumours. To test this prediction, we examined a series of 60 cases of colorectal carcinoma for which samples of lymph‐node or liver metastases were available. Sections were immunocyto‐chemically stained for laminin, and the continuity of tumour EBM was then assessed by observational rating as well as by detailed morphometric analysis for a sample of cases. Contrary to the above prediction, we find that EBMs tend to be more continuous in secondary tumours than in corresponding primary tumours. These results could be explained by the possibility that local tissue environmental factors have a major influence on EBM continuity. Supporting evidence comes from our previous observation that EBM is very discontinuous at the advancing edge of primary colorectal carcinomas, where the tumour is adjacent to collagen‐I‐deficient stroma. Further evidence from the present study is that the EBM is extremely discontinuous at the interface between metastases and specialised parenchymal tissue, but more continuous at the interface between metastases and stromal connective tissue. Since basement membranes affect the differentiation and behaviour of adjacent cells, these findings suggest that host tissues may influence invasive activity through their effects on EBM continuity.
TNF accelerates the S‐phase of the cell cycle in tumor cells
Authors: Volland Sabine , Amtmann Eberhard , Sauer Gerhard
Published: February 2007

The reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose. Therefore, the killing mechanism of TNF under conditions of reduced glucose supply was investigated. Flow cytometry experiments and studies of kinetics revealed that the S‐phase of the cell cycle was prolonged in the absence of glucose. After TNF treatment, the S‐phase was found to be shortened and the rate of H‐thymidine incorporation into DNA was increased, whereas EGF failed to exert such an effect. DNA synthesis and entry into mitosis are known to be regulated by cyclin A. In serum‐starved tumor cells (HeLa) we have observed increased cyclin A synthesis within 10 hr, in parallel with enhancement of DNA synthesis and shortening of the S‐phase after TNF treatment. We conclude that, under conditions of low glucose supply, TNF can assume the role of a growth factor in transformed cells.
Incidence of female breast cancer in relation to prevalence of risk factors in Denmark
Authors: Ewertz Marianne , Duffy Stephen W.
Published: February 2007

The extent to which changes in prevalence of risk determinants for female breast cancer could explain the temporal variation in incidence was examined using incidence figures from Denmark for the years 1943–1989. Significant increases in incidence were observed for more recent time periods and birth cohorts. Using deviance statistics from Poisson regression measures of variability explained, only a small proportion of the increase in incidence could be accounted for by fertility rates, average age at menarche and exposure to exogenous hormones. Dietary factors, on the other hand, accounted for the greater proportion of the variation observed by time period or birth cohort. In particular, there was a strong positive association of incidence with alcohol consumption and a negative association with carbohydrate intake.
Risk of genital human papillomavirus infection in women with human immunodeficiency virus‐induced immunosuppression
Authors: Ho Gloria Y. F. , Burk Robert D. , Fleming Irene , Klein Robert S.
Published: February 2007

This study examined the risk factors for genital human papillomavirus (HPV) infection, including HIV‐related immunosuppression as well as demographic and behavioral factors. Subjects were 207 women with known HIV serologic status, the majority of whom were intravenous drug users recruited from a methadone treatment program in the Bronx, New York. A structured questionnaire interview, cervico‐vaginal lavage, and CD4 cell measurements we're obtained. HPV genomes in the cervico‐vaginal cells were detected by Southern‐blot hybridization. HPV prevalence was 23% among HIV seronegatives, 45% among HIV seropositives with CD4 percent >20 and 61% among HIV seropositives with CD4 percent ≤20. Multivariate analysis identified the following independent risk factors that were significantly associated with HPV positivity: HIV‐related immunosuppression, <35 years of age, and never used oral contraceptive pills. HIV‐related immunosuppression was also associated with a stronger Southern‐blot signal strength. HIV infection, however, did not increase the susceptibility to HPV infection with the oncogenic types (16, 18, 31, 33 and 35). Women with HIV infection or immunosuppression had a higher prevalence of HPV infection with the oncogenic types, but they also had an increased prevalence of infection with other HPV types as compared to the HIV‐seronegative women. The results suggest that HIV‐related immunosuppression increases the risk of genital HPV infection and has an effect on HPV replication.
Mortality in a cohort of women given X‐ray therapy for metropathia haemorrhagica
Authors: Darby S. C. , Reeves G. , Key T. , Doll R. , Stovall M.
Published: February 2007

Mortality to January 1, 1991, has been studied in 2,067 women in Scotland given X‐ray therapy for metropathia haemorrhagica during the period 1940–1960. Average follow‐up was 28 years. Overall, 1,313 deaths were observed compared with 1,297.01 expected from Scottish rates [standardized mortality ratio (SMR): 1.01]. Mortality was increased for cancers of heavily irradiated pelvic sites (SMR 5+ years after irradiation: 1.46) following mean doses to organs in the vicinity of the pelvis in the range 2.6–5.3 Gy. For these cancers the SMR was higher 30+ years after irradiation than at 5–29 years, indicating that the effects of exposure last for over 30 years, and in this period bladder cancer mortality was exceptionally high (SMR = 4.91). Mortality was also raised for leukaemia (SMR 2+ years after irradiation: 2.05), following a mean bone‐marrow dose of 1.3 Gy, and for multiple myeloma (SMR 5+ years after irradiation: 2.59). For leukaemia the SMR was lower 30+ years after irradiation than at earlier periods, but remained greater than unity. For other cancers mortality was similar to Scottish rates, except for breast cancer for which mortality was low (SMR 5+ years after irradiation: 0.53), even in women aged over 50 at irradiation (SMR 5+ years after irradiation: 0.14). The deficit was principally due to a large deficit of breast cancer in women with ovarian doses of at least 5 Gy.
p53 gene mutations in oropharyngeal carcinomas: A comparison of solitary and multiple primary tumours and lymph‐node metastases
Authors: Zariwala Maimoona , Schmid Stephan , Pfaltz Madeleine , Ohgaki Hiroko , Kleihues Paul , Schäfer Reinhold
Published: February 2007

Despite the steadily increasing number of patients suffering from squamous‐cell carcinomas of the oropharyngeal region, little is known about the molecular steps involved in the induction of these neoplasms. We investigated oropharyngeal cancers from 38 patients for mutations in the p53 tumour‐suppressor gene. The majority of patients (74%) had a history of tobacco and alcohol abuse. Five had lymph‐node metastases, 3 had multiple primary carcinomas and 2 presented with multiple primary tumours and lymph‐node metastases. Exons 5 through 8 of the p53 gene were screened by single‐strand conformation polymorphism analysis followed by direct DNA sequencing. A total of 16 tumours (42%) contained point mutations which were scattered throughout exons 5 to 8. Most mutations (56%) were transitions, predominantly G→A. Among the transversions, G→T mutations prevailed; these have also been found in smoking‐related lung cancer. One carcinoma of the soft palate showed a mutation which was retained in a lymph‐node metastasis. In another patient, 2 primary carcinomas had different mutations, indicating that they had developed independently. Similar results were obtained in a case with a p53 mutation in the third of 3 primary tongue carcinomas which developed over a period of 23 years. One lymph‐node metastasis had a 12‐bp deletion which was not detected in any of the primary malignancies. The frequent occurrence of p53 mutations in oropharyngeal carcinomas supports the view that they play a role in the initiation or progression of the malignant phenotype.
Risk factors for oesophageal cancer in northeast China
Authors: Hu Jinfu , Nyrén Olof , Wolk Alicja , Bergström Reinhold , Yuen Jonathan , Adami Hans‐Olov , Guo Lihong , Li Hui , Huang Guirong , Xu Xinmin , Zhao Fengquin , Chen Yilang , Wang Chaoxu , Qin Huisheng , Hu Cunlin , Li Youngtang
Published: February 2007

A hospital‐based case‐control study of oesophageal cancer was carried out in the Heilongjiang Province, a low‐risk area for oesophageal cancer in China. From May 1985 to May 1989, 196 histologically confirmed cases and 392 controls with other (non‐neoplastic) diseases were personally interviewed in the wards of 5 major hospitals. Information was obtained about usual consumption in the early 1980s of 32 major contributors to the diet in the province, socio‐demographic status, smoking and alcohol consumption. Odds ratios (OR) were obtained from logistic regression models, and confounding was controlled by means of multivariate models. Smoking and alcohol consumption were major risk factors for oesophageal cancer in this population. Smokers of handmade cigarettes exhibited a particularly high risk. A near multiplicative synergism was found between smoking and alcohol consumption. There was a significant inverse dose‐risk trend for combined consumption of vegetables and fruits; a 300‐g increase per day lowered risk by 35%. Vitamin C intake was negatively associated with risk; a 100‐mg increase per day lowered risk by 39%. Our data suggest a modifying effect of vitamin C and β‐carotene on risk associated with smoking, but the power of analyses was low. Salt, salt‐preserved foods and pickled vegetables were not associated with increased risk. High temperature of meals and drinks was a strong risk indicator in this population. The strength of tea and overall tea consumption were independent determinants of the risk. © Wiley‐Liss, Inc.
Association of IgA‐anti‐Fab autoantibodies with disease stage in head‐and‐neck cancer
Authors: Süsal C. , Maier H. , Lorenz K. , Opelz G.
Published: February 2007

Patients with head‐and‐neck cancer commonly have immune defects. It was reported that these patients have raised serum IgA levels. We investigated whether IgA‐anti‐Fab autoantibodies, which occur in association with immune dysfunction, are present in patients with head‐and‐neck cancer. Sera of 101 patients with squamous‐cell carcinoma (SCCHN) and 8 patients with adenoid cystic carcinoma (ACCHN) of the head and neck were tested in ELISA for IgA‐anti‐Fab autoantibody activity. IgA‐anti‐Fab serum activity was significantly higher in both SCCHN and ACCHN patients than in healthy controls. In patients with SCCHN, an association between disease stage and IgA‐anti‐Fab activity was established. Stage‐IV patients had significantly higher IgA‐anti‐Fab than stage‐I patients or healthy controls. Stage‐II and stage‐III patients had intermediate levels. Extremely high IgA‐anti‐Fab activity was observed in 7 patients who died within 6 months following testing, suggesting a relationship of autoimmunity with terminal disintegration of physiological body functions. IgA‐anti‐Fab autoantibodies may explain the occurrence of immune defects in patients with head‐and‐neck cancer. © Wiley‐Liss, Inc.
Relationship between loss of estrogen and progesterone receptor expression and of 6q and 11q chromosome arms in breast cancer
Authors: Magdelenat H. , Gerrault‐Seureau M. , Dutrillaux B.
Published: February 2007

The expression of estrogen (ER) and progesterone (PR) receptors was quantified in a series of 95 cytogenetieally characterized breast cancers. The relationship between deficiencies of 6q and Mq arms (where genes for ER and PR are mapped, respectively) and ER and PR expression was analyzed. The range of variations in expression was very large by comparison to that of the number of chromosome arms. Furthermore, low expression without chromosome loss and high expression with chromosome loss were occasionally observed. Thus, major variations in ER and PR expression were independent of the number of copies of the corresponding gene. However, both the decrease in ER expression and 6q arm losses were correlated with cytogenetic evolution of the tumors, this correlation being less significant for PR and the 11 q arm. In addition, 6q‐ but not 11q‐ tumors have, on the average, a low ER/PR ratio, whereas 11q‐ but not 6q‐ tumors have a low PR/ER ratio. When all 6q‐ or 11q‐ tumors were compared to those with no 6q or 11q losses, the average ER or PR value of the former was about half of the later. These data suggest that, in addition to a regulatory change of non‐genetic origin, gene dosage effect plays a secondary, but significant, additional role. © Wiley‐Liss, Inc.
Production and tumour‐binding characterization of a chimeric anti‐CEA Fab expressed in Eschericwa coli
Authors: Chester Kerry A. , Robson Lynda , Keep Patricia A. , Pedlly R. Barbara , Boden Joan A. , Boxer Geoffrey M. , Hawkins Robert E. , Begent Richard H. J.
Published: February 2007

A recombinant chimeric Fab (rcFab), with Fv derived from the monoclonal A5B7 antibody to carcinoembryonic antigen (CEA), and with human CHI and Ck was cloned into pUC 19 and expressed in Escherichia coli. rcFab (10 to 12 mg per litre) was produced in bacterial culture fluid, and functional purified rcFab was isolated by affinity chromatography (using antibody to human Ck) and size‐exclusion gel filtration. The re Fab did not show reduced affinity for CEA, and reacted with human colorec‐tal tumours showing a typical anti‐CEA pattern by immunocyto‐chemistry; it was also stable after iodination. Biodistribution studies in nude mice bearing human tumour xenografts showed no toxicity and good turnout‐ localization. Therapeutic ratios at early time points were better than those obtained with whole murine antibody. The results demonstrate that bacterial I y produced anti‐CEA Fab is of use for tumour targeting. © Wiley‐Liss, Inc.