bluuebunny/crossref_metadata_2025 huggingface dataset:
New Open‐Chain and Cyclic Tetrapeptides, Consisting of α‐, β2‐, and β3‐Amino‐Acid Residues, as Somatostatin Mimics – A Survey
Authors: Seebach Dieter , Dubost Estelle , Mathad Raveendra I. , Jaun Bernhard , Limbach Michael , Löweneck Markus , Flögel Oliver , Gardiner James , Capone Stefania , Beck Albert K. , Widmer Hans , Langenegger Daniel , Monna Dominique , Hoyer Daniel
Published: September 2008

Cyclo‐β‐tetrapeptides are known to adopt a conformation with an intramolecular transannular hydrogen bond in solution. Analysis of this structure reveals that incorporation of a β2‐amino‐acid residue should lead to mimics of ‘α‐peptidic β‐turns’ (cf. A, B, C). It is also known that short‐chain mixed β/α‐peptides with appropriate side chains can be used to mimic interactions between α‐peptidic hairpin turns and G protein‐coupled receptors. Based on these facts, we have now prepared a number of cyclic and open‐chain tetrapeptides, 7–20, consisting of α‐, β2‐, and β3‐amino‐acid residues, which bear the side chains of Trp and Lys, and possess backbone configurations such that they should be capable of mimicking somatostatin in its affinity for the human SRIF receptors (hsst1–5). All peptides were prepared by solid‐phase coupling by the Fmoc strategy. For the cyclic peptides, the three‐dimensional orthogonal methodology (Scheme 3) was employed with best success. The new compounds were characterized by high‐resolution mass spectrometry, NMR and CD spectroscopy, and, in five cases, by a full NMR‐solution‐structure determination (in MeOH or H2O; Fig. 4). The affinities of the new compounds for the receptors hsst1–5 were determined by competition with [125I]LTT‐SRIF28 or [125I] [Tyr10]‐CST14. In Table 1, the data are listed, together with corresponding values of all β‐ and γ‐peptidic somatostatin/Sandostatin® mimics measured previously by our groups. Submicromolar affinities have been achieved for most of the human SRIF receptors hsst1–5. Especially high, specific binding affinities for receptor hsst4 (which is highly expressed in lung and brain tissue, although still of unknown function!) was observed with some of the β‐peptidic mimics. In view of the fact that numerous peptide‐activated G protein‐coupled receptors (GPCRs) recognize ligands with turn structure (Table 2), the results reported herein are relevant far beyond the realm of somatostatin: many other peptide GPCRs should be ‘reached’ with β‐ and γ‐peptidic mimics as well, and these compounds are proteolytically and metabolically stable, and do not need to be cell‐penetrating for this purpose (Fig. 5).
Five New Pregnane Glycosides from the Root Barks of Periploca sepium
Authors: Feng Jia‐Quan , Zhao Wei‐Min
Published: September 2008

Five new pregnane glycosides, perisepiumosides A–E (1–5, resp.), along with the seven known constituents 6–12, were isolated from the root barks of Periploca sepium Bge. (Asclepiadaceae), a traditional Chinese medicine used for the treatment of rheumatoid arthritis and wounds. Their structures were characterized on the basis of spectroscopic analyses.
Children with endemic Burkitt lymphoma are deficient in EBNA1‐specific IFN‐γ T cell responses
Authors: Moormann Ann M. , Heller Kevin N. , Chelimo Kiprotich , Embury Paula , Ploutz‐Snyder Robert , Otieno Juliana A. , Oduor Margaret , Münz Christian , Rochford Rosemary
Published: September 2008

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and is linked to Epstein–Barr virus (EBV) and Plasmodium falciparum coinfections early in life. Epstein–Barr nuclear antigen 1 (EBNA1) is the sole viral latent antigen expressed in BL tumors. Loss of EBNA1‐specific immune surveillance could allow eBL emergence. Therefore, EBNA1‐specific T cell responses were analyzed by IFN‐γ ELISPOT in Kenyan children with eBL and compared to healthy children with divergent malaria exposure. Significantly fewer children with eBL, 16% (7/44) had EBNA1‐specific IFN‐γ responses in contrast to healthy children living in a malaria holoendemic area or in an area with sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders, respectively (p < 0.003). Children with eBL maintained IgG1 dominated antibody responses to EBNA1 similar to healthy children suggesting a selective loss of IFN‐γ secreting EBNA1‐specific T cells in the presence of intact humoral immunity. CD8+ T cell responses to EBV lytic and latent antigens not expressed in the tumors were similarly robust in eBL patients compared to healthy children. In addition, CD4+ T cell responses to a malaria protein, merozoite surface protein 1, were present in lymphoma patients. This study demonstrates a selective loss of EBNA1‐specific T cell responses in children with eBL and suggests a potential immunotherapeutic target for this EBV‐associated lymphoma. © 2008 Wiley‐Liss, Inc.
The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae
Authors: Nakajima Takeshi , Yamashita Satoshi , Maekita Takao , Niwa Tohru , Nakazawa Kazuyuki , Ushijima Toshikazu
Published: September 2008

Aberrant DNA methylation is deeply involved in human cancers, but its inducers and targets are still mostly unclear. Helicobacter pylori infection was recently shown to induce aberrant methylation in gastric mucosae, and produce a predisposed field for cancerization. Here, we analyzed the presence of target genes in methylation induction by H. pylori and the mechanism for the gene specificity. Noncancerous gastric mucosae were collected from 4 groups of individuals (with and without a gastric cancer, and with and without current H. pylori infection; N = 11 for each group), and methylation of promoter CpG islands of 48 genes that can be methylated in gastric cancer cell lines was analyzed by methylation‐specific PCR. In total, 26 genes were consistently methylated in individuals with current or past infection by H. pylori, whereas 7 genes were not methylated at all. In addition, 14 genes were randomly or intermediately methylated in individuals with gastric cancers and the remaining 1 gene was methylated in all the cases. The methylation‐susceptible genes had significantly lower mRNA expression levels than the methylation‐resistant genes. H. pylori infection did not induce mRNA and protein expression of DNA methyltransferases; DNMT1, DNMT3A or DNMT3B. Gene specificity was present in the induction of aberrant DNA methylation by H. pylori infection, and low mRNA expression, which could precede methylation, was one of the mechanisms for the gene specificity. These findings open up the possibility that a methylation fingerprint can be used as a novel marker for past exposure to a specific carcinogenic factor. © 2008 Wiley‐Liss, Inc.
Effects of sunitinib on tumor hemodynamics and delivery of chemotherapy
Authors: Czabanka Marcus , Vinci Mara , Heppner Frank , Ullrich Axel , Vajkoczy Peter
Published: September 2008

Current clinical protocols favor a combination of antiangiogenic/antivascular compounds with classical chemotherapy. However, it remains unclear to what extent an antiangiogenic/antivascular therapy influences the delivery of chemotherapy. Therefore, the aim of the present study was to characterize the effects of the antiangiogenic tyrosine kinase inhibitor sunitinib on tumor microhemodynamics and delivery of chemotherapy. SF126 tumor cells were implanted subcutaneously into nude mice and were analyzed repeatedly by intravital microscopy. Treatment with sunitinib was initiated 7 days after implantation. To assess the effects of sunitinib on tumor vasculature and hemodynamics, we analyzed total and functional vessel densities, microvascular diameter, and microvascular blood flow rate. To study the delivery of chemotherapy, autofluorescent doxorubicin was systemically administered and its vascular delivery to the tumor tissue was quantified. Histological analysis included endothelial cell proliferation, pericyte coverage of tumor vessels, and tumor cell proliferation. Sunitinib significantly suppressed tumor growth by both antivascular and antiangiogenic effects. However, a number of tumor vessels escaped antiangiogenic therapy. Interestingly, in these surviving blood vessels sunitinib treatment resulted in an increased microvascular blood flow rate resulting in an improved delivery of chemotherapy via these blood vessels. Besides its potent antiangiogenic and antivascular efficacy, sunitinib treatment results in improved microhemodynamics and blood flow in tumor blood vessels that escape therapy leading to an improved vascular delivery of chemotherapy. These results provide the basis for a potential chemosensitizing effect of sunitinib. © 2008 Wiley‐Liss, Inc.
Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the U.S. Agricultural Health Study
Authors: Koutros Stella , Lynch Charles F. , Ma Xiaomei , Lee Won Jin , Hoppin Jane A. , Christensen Carol H. , Andreotti Gabriella , Freeman Laura Beane , Rusiecki Jennifer A. , Hou Lifang , Sandler Dale P. , Alavanja Michael C.R.
Published: September 2008

Imazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr‐exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993–1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity‐weighted lifetime exposure days calculated as [years of use × days per year × intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer (p for trend 0.01) and colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans. Published 2008 Wiley‐Liss, Inc.
Up‐to‐date cancer survival: Period analysis and beyond
Authors: Brenner Hermann , Hakulinen Timo
Published: September 2008

Since its introduction in 1996, period analysis has been shown to be useful for deriving more up‐to‐date cancer survival estimates, and the method is now increasingly used for that purpose in national and international cancer survival studies. However, period analysis, like other commonly employed methods, is just a special case from a broad class of design options in the analysis of cancer survival data. Here, we explore a broader range of design options, including 2 model‐based approaches, for deriving up‐to‐date estimates of 5‐ and 10‐year relative survival for patients diagnosed in the most recent 5‐year interval for which data are available. The performance of the various designs is evaluated empirically for 20 common forms of cancer using more than 50‐year long time series of data from the Finnish Cancer Registry. Period analysis as well as the 2 model‐based approaches, one using a “cohort‐type model” and another using a “period‐type model”, all performed better than traditional cohort or complete analysis. Compared with “standard period analysis”, the cohort‐type model further increased up‐to‐dateness of survival estimates, whereas the period‐type model increased their precision. While our analysis confirms advantages of period analysis over traditional methods in terms of up‐to‐dateness of cancer survival data, further improvements are possible by flexible use of model‐based approaches. © 2008 Wiley‐Liss, Inc.
Oviduct‐specific glycoprotein is a molecular marker for invasion in endometrial tumorigenesis identified using a relevant mouse model
Authors: Wang Hong , Joshi Ayesha , Iaconis Lori , Solomon Garron J. , Xiang Zhaoying , Verhage Harold G. , Douglas Wayne , Ronnett Brigitte M. , Ellenson Lora Hedrick
Published: September 2008

The light microscopic distinction between complex atypical hyperplasia (CAH) and invasive endometrioid carcinoma (UEC) on endometrial sampling is problematic and often has significant clinical implications. Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. We used the previously described Pten+/−; Mlh1−/− mouse model. DNA was isolated from microdissected lesions (CAH and carcinoma) and analyzed for LOH and mutations of Pten and additional candidate genes. To identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. The majority of CAHs and carcinomas, arising in this model showed biallelic inactivation of Pten mediated through LOH or intragenic mutation of the wild‐type allele suggesting that complete loss of Pten is insufficient for the development of carcinoma. The global gene expression studies detected increased expression of oviduct‐specific glycoprotein (OGP) in carcinoma as compared with CAHs. This finding was validated using immunohistochemical staining in a collection of primary human UECs and CAHs. Our studies identify a molecular marker for invasive endometrial cancer that may have clinical significance, and highlight the usefulness of this mouse model in not only understanding the genetic underpinnings of endometrial carcinoma, but as a tool to develop clinically relevant biomarkers. © 2008 Wiley‐Liss, Inc.
Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and cancer tissues
Authors: Choi Jin‐Sung , Kim Kyung‐Hee , Jeon You‐Kyung , Kim Sung‐Hee , Jang Sang‐Geun , Ku Ja‐Lok , Park Jae‐Gahb
Published: September 2008

Promoter hypermethylation of the ADAM23 gene, which is normally involved in cell‐to‐cell and cell‐to matrix adhesion, has been reported in pancreatic, breast and brain cancer, and recently the role of this gene was examined in gastric cancer. In this study, we analyzed ADAM23 expression in colorectal cancer cell lines and examined its methylation by methylation‐specific PCR (MSP) and bisulfate‐modified DNA sequencing analysis. Methylated cells were treated with 5‐aza‐2′‐deoxycytidine to restore the ADAM23 expression. We then examined ADAM23 methylation status in colorectal cancer tissues and their corresponding normal tissues. We found that ADAM23 was aberrantly silenced or expressed at very low levels in 28 of the 32 (88%) colorectal cancer cell lines. MSP analysis showed that ADAM23 was methylated in 29 of 32 (91%) colorectal cancer cell lines and attenuated expression of ADAM23 was found to be related to hypermethylation in its promoter region. Moreover, the CpG dinucleotide methylation threshold of 70–90% was found to be required for complete silencing. In addition, when some cell lines without ADAM23 expression were treated with 5‐aza‐2′‐deoxycytidine, ADAM23 was reexpressed. In colorectal cancer tissues, the promoter region of ADAM23 was hypermethylated in 36 of 76 (47%). These results demonstrated that ADAM23 may be down‐regulated by aberrant promoter hypermethylation during the progression of colorectal cancer. © 2008 Wiley‐Liss, Inc.
At what costs will screening with CT colonography be competitive? A cost‐effectiveness approach
Authors: Lansdorp‐Vogelaar Iris , van Ballegooijen Marjolein , Zauber Ann G. , Boer Rob , Wilschut Janneke , Habbema J. Dik F.
Published: September 2008

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost‐effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN‐colon microsimulation model to estimate the costs and life‐years gained of screening persons aged 50–80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life‐years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost‐effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39–47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10‐yearly colonoscopy, where we compared to different intervals of colonoscopy screening. © 2008 Wiley‐Liss, Inc.
Increased frequency of hematopoietic malignancies in relatives of patients with lymphoid neoplasms: A French case–control study
Authors: Villeneuve Sara , Orsi Laurent , Monnereau Alain , Berthou Christian , Fenaux Pierre , Marit Gerald , Soubeyran Pierre , Huguet Françoise , Milpied Noël , Leporrier Michel , Hemon Denis , Troussard Xavier , Clavel Jacqueline
Published: September 2008

Lymphoid neoplasms (LNs), including non‐Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), lymphoproliferative syndrome (LPS) and multiple myeloma (MM), are among the most frequent cancers (∼17,000 new cases per year in France), after those related to smoking. LNs were investigated using the data from the ENGELA study. ENGELA is a multicenter hospital‐based case–control study that was carried out in France over the period September 2000–December 2004. In all, 822 cases (397 NHL, 149 LH, 168 SLP and 108 MM) and 752 controls were included and described 5,481 and 5,188 first‐degree relatives, respectively. A positive association with a familial history of hematopoietic cancer was observed for LN (OR = 1.7 [1.0–2.8]) overall and for LPS (OR = 3.2 [1.4–6.8]). The associations with HL (OR = 10.4 [2.0–53.8]) and NHL (OR = 2.4 [1.0–5.9]) were stronger for men. The associations were also stronger when the disease had been diagnosed before the relatives were aged 45 years. The results mainly support the involvement of genetic factors and suggest that at least some of those factors may be sex‐linked. However, the slight overrepresentation of affected spouses among the cases might also support the responsibility of environmental factors. © 2008 Wiley‐Liss, Inc.
A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c‐Src phosphorylation in VEGF‐induced human umbilical endothelial cells
Authors: Yi Zheng‐Fang , Cho Sung‐Gook , Zhao Hui , Wu Yuan‐yuan , Luo Jian , Li Dali , Yi Tingfang , Xu Xun , Wu Zirong , Liu Mingyao
Published: September 2008

Many angiogenesis inhibitors are derived from large plasma proteins. Previous studies showed that the Kringle5‐like domain (termed KV) in human apolipoprotein (a) is a potential antiangiogenic factor. However, its active region and the underling molecular mechanism remain elusive. Here, we identified an 11‐amino acid peptide (named KV11) as the key region for the antiangiogenic function of the KV domain of apolipoprotein (a). We demonstrate that KV11 inhibits angiogenesis in vitro by suppressing human umbilical vein endothelial cell migration and microtubule formation. KV11 inhibits angiogenesis in chicken chorioallantoic membrane assays and mouse corneal micropocket angiogenesis assays in vivo. KV11 peptide shows no effect on tumor cell growth or proliferation, but significantly inhibits tumor growth in SCID mouse xenograft tumor model (p < 0.01) by preventing tumor angiogenesis. We elucidate that KV11 peptide suppresses angiogenesis and tumor progression by targeting the c‐Src/ERK signaling pathways. Together, these studies provide the first evidence that KV11 from apolipoprotein KV domain has anti‐angiogenesis functions and may be an anti‐tumor drug candidate. © 2008 Wiley‐Liss, Inc.
Hydrazine, methylhydrazine and methylhydrazine sulfate carcinogenesis in swiss mice. failure of ammonium hydroxide to interfere in the development of tumors
Authors: Toth Bela
Published: September 2008

Solutions of hydrazine as 0.001%, methylhydrazine as 0.01%, methylhydrazine sulfate as 0.001%, and ammonium hydroxide as 0.3, 0.2 and 0.1% were administered continuously in the drinking water of 5‐ and 6‐week‐old randomly bred Swiss mice for their entire lifetime. Similarly ammonium hydroxide as a 0.1% solution was given to 7‐week‐old inbred C3H mice. Hydrazine and methylhydrazine sulfate significantly increased the incidence of lung tumors in Swiss mice, while methylhydrazine enhanced the development of this neoplasm by shortening its latent period. The ammonium hydroxide treatments in Swiss and C3H mice were, however, without carcinogenic effect, and did not inhibit the development of breast adenocarcinomas in C3H females, which are characteristic of these animals.

The present study thus proves for the first time the carcinogenicity of methylhydrazine, provides further evidence of the tumor‐inducing capability of hydrazine by itself and negates the possibility that the metabolite of hydrazine, ammonium hydroxide, could interfere in the development ofneoplasia.
Evidence for a clonal origin of head and neck tumors
Authors: Fialkow Philip J. , Martin George M. , Klein George , Clifford Peter , Singh Surjit
Published: September 2008

According to the inactive‐X hypothesis only one of the two genes at X‐linked loci is active in somatic cells of females. Thus, in women heterozygous for the A and B genes at the X‐linked glucose‐6‐phosphate dehydrogenase (G‐6‐PD) locus, single cells or clones of cells show either type A or type B enzyme. Similarly, pure tumors with a clonal origin arising in G‐6‐PD heterozygotes exhibit only type A or B enzyme, while those with multiple cell origin may show both A and B enzymes. The G‐6‐PD types of normal and neoplastic tissue were determined in 28 patients with tumors of the head and neck who were heterozygous at the G‐6‐PD locus. Normal tissues contained two enzyme types. Only one tumor from the 11 patients with anaplastic carcinoma of the nasopharynx was pure enough (i. e., with a relatively small number of non‐tumor cells) to allow firm conclusions. This tumor had a single enzyme phenotype and this is compatible with a clonal origin. Single enzyme phenotypes were also found in the two benign tumors and in single cases of plasmacytoma, melanoma, neuroblastoma and reticulum‐cell sarcoma. The data from three cases of carcinoma of the palate and from single cases of carcinoma of an ectopic salivary gland and the thyroid gland respectively are also compatible with a clonal origin. Only one relatively pure tumor had a double enzyme phenotype, but even in this case, the evidence for a multiple cell origin is not convincing. Thus, the data in this and other studies suggest that at least one step in the development of most human neoplasms occurs in a single cell, i. e., the mature tumors have a clonal origin.
Effect of local radiotherapy on the antibody levels against ebv‐induced early and capsid antigens (ea and vca) in patients with certain malignant tumours
Authors: Einhorn N. , Henle G. , Henle W. , Klein G. , Clifford P.
Published: September 2008

Antibodies to tumour‐related and EBV‐associated intracellular antigens were studied in 14 cases of Burkitt's lymphoma, 50 of nasopharyngeal carcinoma, 10 of maxillary carcinoma and 95 cases of other tumours, all of whom received radiotherapy in Nairobi. For up to 1 month after radiotherapy the cases of Burkitt's lymphoma recorded an increase in antibodies to early antigens (EA) amounting to, on average, about one titre step (p<0.001). During the same interval there was a small but significant increase in antibodies to viral capsid antigen (VCA) (mean 0.6 titre step; p<0.001). The patients with nasopharyngeal and maxillary carcinoma, too, showed a small but statistically significant increase in antibodies to VCA 2‐6 months after radiotherapy (p<0.01 and 0.001, respectively), but no increase in antibodies to EA. On the contrary, in nasopharyngeal carcinoma patients there was a significant decrease in antibodies to EA 2‐3 months after radiotherapy. In the group of other tumours there was no evidence of a change in antibodies to the intracellular antigens studied during any of the relevant intervals.
Properties of a murine sarcoma virus isolated from a tumor arising in an nzw/nzb f1 hybrid mouse. II. physical and biological characteristics
Authors: Gazdar Adi F. , Sarma Padman S. , Bassin Robert H.
Published: September 2008

The properties of a potent murine sarcoma virus (MSV), which was isolated after in vivo passage of a spontaneous tumor arising in an NZW/NZB F1 hybrid mouse, are described. The agent had the morphological and growth characteristics of a type C virus, and contained the group‐specific (gs) antigen of the murine leukemia‐sarcoma viruses. The virus induced discrete, focal lesions of transformed cells in mouse tissue‐culture cells. Focus formation usually followed a “two‐hit” titration pattern, and sarcoma virus preparations contained a large excess of an accompanying non‐transforming type C virus. The MSV was stable when stored at — 70° C; it was ether‐sensitive and had a buoyant density of 1.16g/cm3 when centrifuged in sucrose density gradients. These properties are similar to those of the Moloney (M‐MSV), Harvey (H‐MSV), and Kirsten (Ki‐MSV) isolates of MSV. When inoculated into hamsters, the new strain of MSV rapidly induced sarcomas. While the viruses produced by hamster and mouse tumors both contained the murine gs antigen, the host range of the MSV was altered by hamster passage. It failed to induce focal lesions in mouse and hamster cells, and did not induce sarcomas or leukemias when injected into newborn mice and hamsters. The antigenic properties and infectivity of the virus produced by hamster tumor cells were significantly different from the properties of the hamster leukemia pseudotype viruses obtained from hamster tumors induced by the other strains of MSV.
A prospective study of esophageal cytological atypia in linxian county
Authors: Lu Jian‐Bang , Yang Wen‐Xian , Dong Wen‐Zhou , Sang Jiu‐Yuan
Published: September 2008

Between I9TS and 1975, in Linxian county (LX), a prospective study of esophageal cytologrcal hyperplasia and atypia was conducted on 3 groups of subjects: 294 with marked atypia, 328 with mild hyperplasia and 336 normal controls; all were diagnosed by cytology. Results showed that no significant difference in incidence of esophageal cancer (EC) appeared between subjects with mild hyperplasia and controls, while the incidence of EC in subjects with marked atypia was 1,178.92/100,000 which was 2.39 (after age‐adjustment 2.90) times higher than that found in the control group and was of statistical significance (x2 = 8.92, p < 0.01). In all groups, the relatively high risk of contracting EC was closely associated with drinking ground water, smoking and a low standard of living. These results suggest that early treatment should be given to subjects with marked atypia, accompanied by preventive measures against carcinoma of the esophagus, such as hygienic drinking water, abstention from smoking and better living conditions.
Spatial relationship of chromosomes 9 and 22 at metaphase in patients with chronic myelogenous leukemia (CML)
Authors: Verma Ram S. , Thomas Samuel , Coleman Morton , Silver Richard T.
Published: September 2008

One hundred patients with Ph1‐chromosome‐positive chronic myelogenous leukemia (CML) with t(9;22) are included in the present investigation. The position of the Ph1 chromosome in relation to the normal as well as the abnormal chromosomes 9 was localized at metaphase in 1,000 bonemarrow cells. Our study suggests that the rearranged chromosomes, i.e., Ph1 and t(9;22), are closer together than their normal homologues. This impression is based on extensive statistical analysis. The intimate relationship may be due to the fact that they carry reciprocal genetic material responsible for a power of attraction between them. Alternatively, it is tempting to hypothesize that there may be a DNA sequence homology in the bands of chromosomes 9q and 22q involved in the reciprocal translocation perpetuating this relationship in subsequently generating cells during mitotic cell divisions. Furthermore, c‐abl and bcr genes might play some role in maintaining the spatial relationship.
Hormonal changes following tumor transplantation: Factors increasing corticosterone and the relationship of corticosterone to tumor‐induced anti‐inflammation
Authors: Normann S. , Besedovsky H. , Schardt M. , Del Rey A.
Published: September 2008

EL‐4 lymphoma cells transplanted to syngeneic C57BL/6J mice induced a biphasic decrease in inflammation and a biphasic increase in serum levels of corticosterone. In addition, this tumor altered serum levels of 3 other hormones, resulting in a biphasic decrease in insulin, an early decrease in protactin, and a terminal severe deficiency in thyroxine. Early changes occurred 16 to 48 hr after tumor transplantation and were of variable duration, while late‐phase defects developed during the last few days of life. Soluble factors associated with tumor growth may mediate certain hormonal changes since serum levels of corticosterone increased and insulin decreased following injection of tumorous ascites into normal mice. Further, injection of cell‐free tumor culture supernatants increased corticosterone levels. Hormonal changes following injection of soluble factors occurred after a delay of 16 hr indicating that the factors acted indirectly. Surgical adrenalectomy blocked the corticosterone increase induced by tumor transplantation or ascites injection and eliminated the anti‐inflammatory effect of tumor transplantation while significantly decreasing the effect associated with injection of tumorous ascites. Thus, the physiologically induced increase in serum levels of corticosterone reached anti‐inflammatory levels. Further, elevated levels of corticosterone are a major contributing factor to anti‐inflammation induced by tumorous ascites injection and constitute the principal mechanism of anti‐inflammation following tumor transplantation.
Differential effects on expression of IL‐2 receptors (p55 and p70) by the HTLV‐I pX DNA
Authors: Sabe Hisataka , Tanaka Atsushi , Siomi Haruhiko , Koyasu Shigeo , Yonehara Shin , Yahara Ichiro , Tagaya Yutaka , Sugie Katsuji , Teshigawara Keisuke , Yodoi Junji , Hatanaka Masakazu
Published: September 2008

Abnormal expression of the low‐affinity receptor for inter‐leukin‐2 (IL‐2R) is a characteristic of the HTLV‐I (+) leukemic T cells in adult T‐cell leukemia (ATL). Despite the expression of IL‐2R bearing Tac antigen (IL‐2R/pSS), leukemic cells of the majority of ATL patients do not proliferate in response to IL‐2. In the human NK cell line, YT, as well as in ATL‐derived T cells, the co‐expression of IL‐2R/p55 and the second IL‐2R without the Tac epitope (IL‐2R/p70) is required to produce high‐affinity IL‐2R. To study the effect of HTLV‐I on both of the IL‐2Rs, we transferred a fragment of HTLV‐I containing the p40X gene into YT cells. One of the 2 transfected YT clones (YT/pX‐5.1) had an increased level of expression of IL‐2R/p55. In contrast, expression of (L‐2R/p70 was unaffected, as determined by Scatchard analysis and the cross‐linking study using 125‐IL‐2. Our results show that the T‐cell phenotype is not required for induction of IL‐2R/p55 by p40X. We suggest that HTLV‐I infection induces a disproportionate induction of IL‐2R/pSS without significant enhancement of IL‐2R/p70 expression, resulting in the predominant expression of low‐affintty IL‐2R in ATL. IL‐2R/p70 may be a critical parameter determining the IL‐2 reactivity of HTLV‐I‐infected T cells as well as of normal lymphocytes.
Direct outgrowth of in vivo epstein‐barr virus (EBV)‐infected chronic lymphocytic leukemia (CLL) cells into permanent lines
Authors: Lewin Nongnit , Åman Pierre , Mellstedi Håkan , Zech Lore , Klein George
Published: September 2008

In the course of our efforts to characterize the EBV‐carrying cells that are responsible for direct growth or the 2‐step mechanism, based on virus release from the explanted cells and subsequent transformation of previously uninfected cells, we have encountered an unusual CLL patient who carried a small subpopulation of in vivo EBV‐infected leukemia cells. These were predominantly present in the low‐density fraction and grew into EBV‐carrying lines upon explantation after a relatively short latency period, 3‐4 weeks. Cytogenetic examination conclusively proved the leukemic origin of the established CLL lines. They carry a ring chromosome 15 and are trisomic for chromosome 12. The same changes are also found in the majority of the peripheral blood lymphocyte population. Taken together, our results suggest that the EBV‐genome and the cytogenetic changes may have contributed to the immortalization of the CLL cells in a complementary or synergistic fashion.
Frequent loss of heterozygosity at telomeric loci on 22q in sporadic colorectal cancers
Authors: Yana Ikuo , Kurahashi Hiroki , Nakamori Shoji , Kameyama Masao , Nakamura Tsutomu , Takami Motohisa , Mori Takesada , Takai Shinichiro , Nishisho Isamu
Published: September 2008

To date, several tumor‐suppressor genes responsible for the tumorigenesis of colorectal cancer have been identified. However, studies of loss of heterozygosity (LOH) have suggested several chromosomal regions which may contain additional tumor‐suppressor genes for colorectal cancer. To determine the extent and variation of allelic loss on 22q, on which LOH has been frequently observed, a total of 68 sporadic colorectal cancers was examined for LOH on the chromosome arm by means of 16 polymorphic DNA markers. LOH was observed in 28 tumors (41 %), of which 9 showed LOH at all informative loci. The remaining 19 tumors showed variable patterns of partial loss on 22q, delimiting the smallest region of overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated with a progression in terms of Dukes' stages. These results suggest that an additional tumor‐suppressor gene for colorectal cancer may exist on 22q distally to the NF2 locus and that inactivation of the gene may possibly play a role in the progression or metastasis of colorectal cancers. © 1995 Wiley‐Liss, Inc.
Deletion mapping of the long arm of chromosome 22 in human meningiomas
Authors: Akagi Kenzo , Kurahashi Hiroki , Arita Norio , Hayakawa Toru , Monden Morito , Mori Takesada , Takai Shinichiro , Nishisho Isamu
Published: September 2008

Cytogenetic and molecular genetic analyses have shown that a tumor‐suppressor gene for human meningioma is located on the long arm of chromosome 22. Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas. However, tumorigenesis of certain cases of meningioma cannot be fully explained by inactivation of the NF2 gene alone. Thus, to obtain some indication as to the existence of another tumorsuppressor gene, it seemed important to re‐examine the loss of heterozygosity (LOH) on 22q in sporadic meningioma. A total of 46 sporadic meningiomas was examined for LOH at 20 loci on 22q. LOH was observed in 29 tumors (63%), of which 13 (28%) showed different patterns of a partial loss of 22q. However, the NF2 locus was retained in one tumor that lost a more distal part of 22q. Moreover, 27 of the 28 tumors which showed LOH at the NF2 locus also lost alleles at more telomeric loci. These results raise the possibility that another tumor‐suppressor gene for meningioma may exist on 22q and that its localization may be distal to the D22S102 locus. © 1995 Wiley‐Liss, Inc.
Cancer risk after renal transplantation in the nordic countries, 1964–1986
Authors: Birkeland Sven A. , Storm Hans H. , Lamm Lars U. , Barlow Lotti , Blohmé Ingemar , Forsberg Bjorn , Eklund Bjorn , Fjeldborg Ole , Friedberg Michael , Frödin Lars , Glattre Eystein , Halvorsen Stein , Holm Niels V. , Jakobsen Amt , Jorgensen Hans E. , Ladefoged Jorgen , Lindholm Tore , Lundgren Goran , Pukkala Eero
Published: September 2008

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow‐up. Information on 5,692 Nordic recipients of renal transplants in 1964–1982 was linked with the national cancer registries (1964‐1986) and population registries. Person‐years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age‐ and calender‐specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person‐years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2‐ to 5‐fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10‐fold to 30‐fold above expectation, were associated with cancers of the lip, skin (non‐melanoma), kidney and endocrine glands, also with non‐Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva‐vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer. © 1995 Wiley‐Liss. Inc.
Mitoxantrone treatment of murine myeloid leukaemia sublines
Authors: Abubakar Aminu A. , Riches Andrew C.
Published: September 2008

The low‐cell‐dose (LD) and the high‐cell‐dose (HD) transplant variants of the SA7 murine myeloid leukaemia cell line have different growth characteristics and clinical presentations. In addition, the low‐cell‐dose transplant subline (SA7LD) was more responsive than the high‐cell‐dose variant (SA7HD) to mitoxantrone treatment in vivo. Bone‐marrow cells of mice cured of SA7LD leukaemia, as well as bone‐marrow cells of normal mice treated with priming doses of mitoxantrone in vivo became significantly (p = 0.012) less sensitive to subsequent treatment with mitoxantrone in vitro. This effect was detected by both the colony assay and the tritiated thymidine uptake assay. There appears to be a correlation between the ability of normal bone‐marrow cells present in leukaemic mice to develop this protective effect and their ability to survive chemotherapy with mitoxantrone. The protective effect was “lost” by bone‐marrow cells of mice dying while in remission. Doses of mitoxantrone that resulted in the loss of protective effect by bone‐marrow cells of normal mice were found to be fatal to SA7HD leukaemia‐bearing mice. However, these doses were not toxic to normal mice. © 1995 Wiley‐Liss, Inc.
Relationship between stages of mammary development and sensitivity to gamma‐ray irradiation in mammary tumorigenesis in rats
Authors: Yamanouchi Hiroshi , Ishii‐Ohba Hiroko , Suzuki Keiko , Onoda Makoto , Wakabayashi Katsumi , Inano Hiroshi
Published: September 2008

Mature Wistar‐MS rats were ovariectomized and treated with estradiol benzoate and/or progesterone. Control animals were treated with olive oil. The rats were then exposed to γ‐rays and implanted with a pellet of diethylstilbestrol. The incidence of mammary tumors in rats treated with estradiol benzoate or with progesterone was significantly higher than in rats in the non‐treated control group, whereas, in rats treated with both estradiol benzoate and progesterone, the incidence was not significantly different from that in the controls. Histological examination of the mammary tumors showed 2 types of neoplasm: adenocarcinoma and fibroadenoma. Interestingly, over half of all the tumors in the rats treated with estradiol benzoate were adenocarcinomas, while fibroadenomas were mainly induced in the rats treated with progesterone or with both estradiol benzoate and progesterone. The expression of estrogen and progesterone receptors in the tumor tissues showed some differences according to whether the groups were treated with estradiol benzoate or with progesterone. Morphologically, mammary glands at irradiation showed well‐developed lobuloalveoli in both the estradiol‐benzoate‐treated rats and in those rats treated with both estradiol benzoate and progesterone. This was consistent with the higher incorporation of [3H]thymidine into the DNA in the mammary glands of rats in both of these groups. Our findings suggest that a more advanced developmental stage of the mammary glands, dependent upon ovarian hormones, is related to a higher incidence of mammary tumors induced by irradiation. © 1995 Wiley‐Liss, Inc.
Reduction of tumour intracellular pH and enhancement of melphalan cytotoxicity by the ionophore nigericin
Authors: Wood P. J. , Sansom J. M. , Nhweli K. , Tannock F. F. , Stratford I. J.
Published: September 2008

Nigericin is an ionophore which permits the influx of H+ ions into cells down a concentration gradient, thus reducing intracellular pH (pHi) when extracellular pH is low. The effects of nigericin on the pHi of solid murine tumours in vivo were examined using31P magnetic resonance spectroscopy. Nigericin at 2.5 mg/kg i.p. reduced pHi by 0.2–0.3 pH unit in the KHT and RIF‐1 tumours but had no effect on pHi in the SCCVII/Ha tumour. In vitro studies have shown that reduced pH can increase the toxicity of melphalan. Therefore, the anti‐tumour effect of combining nigericin with melphalan was also examined. Nigericin at 2.5 mg/kg i.p. given before various doses of melphalan resulted in substantial delay in growth of the RIF‐1 tumour over that induced by melphalan alone. This observation was confirmed by an in vivo/in vitro excision assay, where nigericin given before melphalan produced a 30‐fold increase in cell killing. By contrast, no enhancement of melphalan‐induced cell killing by nigericin was observed in the KHT and SCCVII/Ha tumours, using growth delay and in vivo/in vitro excision assays, respectively. © 1995 Wiley‐Liss, Inc.
Down‐regulation of collagen XII in transformed mesenchymal cells
Authors: Kopp Martin U. , Croci Luigi P. , Trueb Beat
Published: September 2008

Collagen XII is a complex multidomain protein associated with the surface of interstitial collagen fibrils. This protein is produced in large amounts by fibroblasts cultivated in vitro. However, it is completely absent from cells transformed by the oncogene v‐myc or v‐src and from cells derived from a methyl‐cholanthrene‐induced fibrosarcoma. Since all these cells lack any mRNA for collagen XII, it seems likely that the synthesis is blocked at the transcriptional level. Experiments with a temperature‐sensitive mutant of Rous sarcoma virus demonstrated that a single oncogene product is sufficient to inhibit the synthesis. A reduction in the expression of collagen XII might have profound effects on the stability of the extracellular matrix of transformed cells. © 1995 Wiley‐Liss, Inc.
Experimental local therapy of human melanoma with lytic magainin peptides
Authors: Sloballe Peter W. , Lee Maloy W. , Myrga Michelle L. , Jacob Leonard S. , Herlyn Meenhard
Published: September 2008

Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI‐511 (an all‐D amino‐acid model magainin peptide) and MSI‐130 (a magainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI‐511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI‐511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long‐term damage to normal tissues. © 1995 Wiley‐Liss, Inc.
Epstein‐barr virus is localized in the tumour cells of nasal lymphomas of NK, T or B cell type
Authors: Tao Qian , Ho Faith C. S. , Loke Shee Loong , Srivastava Gopesh
Published: September 2008

Seven cases of nasal lymphoma were studied to identify the lineage of Epstein‐Barr virus (EBV)+ cells using dual‐labelling methods. Five cases were phenotypically and genotypically of natural killer cell (NK) type with germ‐line configuration of T‐cell receptor (TcR) β‐chain gene and immunoglobulin heavy‐chain joining region (lg/H) gene, with one case each of T‐ and B‐cell type showing rearranged TcRβ or lg/H and Λ‐light chain genes respectively. EBV genome was clonal in all these cases except in the B‐cell case where its clonality was undeterminable. Using in situ hybridization (ISH) for EBV‐encoded small nuclear RNA 1 and 2 (EBER), signal was detected in 45% to 88% of nucleated cells in the tumours. Immunostaining for EBV latent membrane protein‐1 (LMP) also revealed numerous LMP+ cells in 3/5 NK‐type cases and the T‐ and B‐cell cases. Using ISH for EBER combined with immunostaining for CD markers and double immunohistochemistry for LMP and CD markers, the predominant lineage of the EBV+ cells was identified as: CD2+CD3−CD19−CD20‐ CD45R0+CD56+CD68‐ in the NK‐type cases, CD2+CD3+CD19−CD20− CD45R0+CD56−CD68− in the T‐cell case and CD20+CD45R0−CD68‐ in the B‐cell case, in agreement with the genotype and phenotype of each tumour. These results show that, in EBV+ nasal lymphomas of NK, T‐ or B‐cell lineage, EBV was consistently associated with the tumour‐cell population and support the view that EBV serves a promoting role in the pathogenesis of different types of EBV+ nasal lymphoma. © 1995 Wiley‐Liss, Inc.