bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of genetic background on tumorigenesis in p53‐deficient mice
Authors: Donehower Lawrence A. , Harvey Michele , Vogel Hannes , McArthur Mark J. , Montgomery Charles A. , Park Sang H. , Thompson Timothy , Ford Richard J. , Bradley Allan
Published: February 2007

Mice with disrupted germline p53 alleles have been engineered by us and others and have been shown to have enhanced susceptibility to spontaneous tumors of various types. We monitored a large number of p53‐deficient mice(p53+/− and p53−/−) and their wild‐type littermates(p53+/+) of two different genetic backgrounds(129/5v and mixed C57BL/6 × 129/5v) up to 2 yr of age.p53+/− and p53−/− 129/Sv mice show accelerated tumorigenesis rates compared with their p53‐deficient counterparts of mixed C57BL/6 × 129/Sv genetic background. The tumor spectra of the two strains of mice are similar except that almost half of 129/Sv p53−/− males develop malignant teratomas, whereas these tumors are rarely observed in C57BL/6 × 129/Sv mice and never in 129/Sv p53+/− males. In the study reported here, we further characterized the lymphomas that arose in the p53‐nullizygous mice and found that over three‐quarters of the lymphomas were of thymic origin and contained primarily immature(CD4+/CD8+) T‐cells, whereas the remainder originated in the spleen and peripheral lymph nodes and were of B‐cell type. The high incidence of early‐onset lymphomas in the nullizygous mice makes these animals a good lymphoma model, whereas the heterozygous mice may be a useful model for Li‐Fraumeni syndrome, a human inherited cancer predisposition.© 1995 Wiley‐Liss, Inc
Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis(Tsc2)
Authors: Hino Okio , Kobayashi Etsuko , Hirayama Youko , Kobayashi Toshiyuki , Kubo Yoshiaki , Tsuchiya Haruo , Kikuchi Yasushi , Mitani Hiroaki
Published: February 2007

We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene(Tsc2), the gene predisposing to renal carcinoma(a) in the Eker rat. The homozygous mutant condition is lethal at around the 13th day of fetal life. In heterozygotes, RCs invariably develop in the first year of life. Histologically, RCs develop through multiple stages from early preneoplastic lesions(i.e., phenotypically altered tubules) to adenomas. The wild‐type allele mutation has been found even in the earliest preneoplastic lesions, fitting Knudson's two‐hit hypothesis and supporting the hypothesis that Tsc2 is a tumor suppressor gene. In this study, homozygous deletion of the Ink4 homologue on rat chromosome 5q was observed in 14 of 24(58%) RC‐derived cell lines. This may represent involvement of a second tumor suppressor gene, contributing to tumor progression. Considering previous results of studies of homozygous deletion of the ifnα gene in five of 24 cases(21%) and the Ifnβ gene in one of 24 cases(4%), the order of the genes may be Ink4–Ifna— Ifnβ Microsatellite instability was not observed in 26 Eker rat tumors.© 1995 Wiley‐Liss, Inc
Predictions of rodent carcinogenicity testing results: Interpretation in light of the lave‐omenn value‐of‐information model
Authors: Omenn Gilbert S. , Stuebbe Seth , Lave Lester B.
Published: February 2007

The recent National Institute of Environmental Health Sciences/National Toxicology Program Carcinogen Prediction Challenge elicited a valuable array of predictions of the carcinogenicity of chemicals tested in the lifetime rodent bioassay. The data warrant additional analyses of the similarities and differences of the predictive methods. We provide here analyses of the sensitivity, specificity, and false‐positive/false‐negative tendencies of the different sets of predictions. Our value‐of‐information model provides guidance to testing agencies and regulatory agencies in determining the social value of additional information and setting up the framework for assessing the social consequences of different test strategies and nontest predictive methods. These considerations deserve attention in the second round of the Carcinogen Prediction Challenge.© 1995 Wiley‐Liss, Inc
Mutational spectra in the lacl gene in skin from 7, 12‐dimethylbenz[a]anthracene‐treated and untreated transgenic mice
Authors: Gorelick Nancy J. , Andrews Julie L. , Gu Marie , Glickman Barry W.
Published: February 2007

Transgenic mice carrying the bacterial lacl gene in a lambda shuttle vector were used to isolate and characterize background and 7, 12‐dimethylbenz[a]anthracene(a) ‐induced mutations in skin. Adult male mice were treated once topically with either DMBA or acetone or were left untreated. Seven days later, DMBA treatment had significantly increased the mutant frequency in the skin(mean ± SEM, 36 ± 3 × 10−5) versus in vehicle‐treated(6.4 ± 1.2 × 10−5) and untreated mice(7.1 ± 1.0 × 10−5). At least 10 mutants from each of three DMBA‐treated and three untreated mice were selected for DNA sequence analysis. In each case, the entire 1080‐bp target gene was sequenced. Base‐pair substitutions predominated(86 of 96 mutations), although frameshift and deletion mutations were also detected. Twelve percent of the mutants carried more than one mutation. In controls, the mutations were predominantly GC → AT transitions(26 of 42), and no AT → TA transversions were recovered. In contrast, in the DMBA‐treated mice, AT → TA transversions represented 42% of the mutations(23 of 54) and GC → AT transitions accounted for only 11%. The AT → TA transversions occurred mostly at 5′‐CA sites. This class of mutation has been recovered frequently in ras genes from DMBA‐treated mice and probably represents an early event in carcinogenesis(Nelson MA et al., Proc Natl Acad Sci USA 89:6398–6402, 1992). Our present results are consistent with the types of DNA damage induced by DMBA. The observation of different mutant frequencies and spectra in treated and control mice demonstrates the utility of this approach in the study of mutagenesis in vivo.© 1995 Wiley‐Liss, Inc
Delay of dimethylbenz[a]anthracene‐induced mammary tumorigenesis in transgenic mice by apoptosis induced by an unusual mutant p53 protein
Authors: Li Baolin , Kittrell Frances S. , Medina Daniel , Rosen Jeffrey M.
Published: February 2007

Murine p53 containing an Arg → Leu substitution at amino acid 172 possesses many properties characteristic of wild‐type p53, including the ability to induce p21/WAF/Cip1 and apoptosis. To determine if p53–dependent apoptosis plays a critical role in mammary tumorigenesis, transgenic mice were generated in which the expression of this mutant p53 protein was targeted to the mammary gland by using the rat whey acidic protein gene promoter. Mice bearing pituitary isografts were treated with 7,12–dimethylbenz[a]anthracene (a) and examined for mammary tumor development. Mice overexpressing the p53 transgene exhibited a statistically significant increase in apoptosis in the mammary gland and a statistically significant decrease in the incidence of DMBA‐induced mammary tumors. No difference in tumor incidence was observed in mice without pituitary isografts who were treated with DMBA, because the transgene is not overexpressed in the absence of hormone stimulation provided by the pituitary isograft. The unexpected wild‐type properties of the 172Arg→Leu mutant p53, including its ability to stimulate apoptosis, make it a possible candidate for use in gene therapy protocols. ©1995 Wiley‐Liss, Inc.
Frameshift mutation in codon 176 of the p53 gene in rat esophageal epithelial cells transformed by benzo[a]pyrene dihydrodiol
Authors: Wang Dian , You Liang , Sneddon Jeff , Cheng Shu‐Jun , Jamasbi Roubadeh , Stoner Gary D.
Published: February 2007

Mutations in the p53 tumor suppressor gene have been associated with exposure to environmental chemical carcinogens. Cultured rat esophageal epithelial cells were transformed in vitro by treatment with benzo[a]pyrene dihydrodiol (BP‐DHD). A BP‐DHD‐transformed cell line and control cell lines were analyzed for mutations in the p53 gene and in the Ha‐ras gene by single‐strand conformation polymorphism analysis of polymerase chain reaction‐amplified products and direct DNA sequencing. The deletion of one cytosine in codons 174–176 (TGCCCCCAC → TGCCCCAC) of the p53 gene was found only in the BP‐DHD‐transformed cell line. The BP‐DHD‐transformed cells were highly invasive and tumorigenic when transplanted into syngeneic rats, whereas control lines either were nontumorigenic or formed epithelial cysts. BP‐DHD‐transformed cells and control lines were negative for mutations in the Ha‐ras gene. Our results suggest that the tumorigenic potential of the BP‐DHD‐transformed cell line is associated with a frameshift mutation in codon 176 of the p53 gene but not with mutations in the Ha‐ras gene. The G/C‐rich codons 174–176 in the ratp53 gene may be specific targets for BP‐DHD. ©1995 Wiley‐Liss, Inc.
Expression of c‐myc in altered hepatic foci induced in rats by various single doses of diethylnitrosamine and promotion by 0.05% phenobarbital
Authors: Deguchi Takeshi , Pitot Henry C.
Published: February 2007

Among the proto‐oncogenes examined by northern blot analysis, c‐myc, c‐Ha‐ras, c‐fos, and c‐raf‐1 have been reported to be activated in rat liver cell carcinomas. However, there are relatively few reports on proto‐oncogene expression in altered hepatic foci (a) early during hepatocarcinogenesis in the rat. In this study, diethylnitrosamine (a) at doses ranging from 10 to 200 mg/kg was used to initiate and phenobarbital (0.05%) to promote AHF in rats. AHF were detected by the presence of the marker enzymes glutathione s‐transferase, placental form (GST‐P); γ‐glutamyltranspeptidase (a); glucose‐6‐phosphatase (G6Pase); and canalicular ad‐enosine triphosphatase (a). Proto‐oncogene expression in individual AHF was investigated by in situ hybridization (a). ISH for the mRNAs of c‐Ha‐ras, c‐fos, and c‐raf‐1 revealed little or no expression in AHF. However, the levels of c‐myc mRNA were increased in about 10% of the AHF initiated by the highest dose of DEN (200 mg/kg). Thus, altered expression of proto‐oncogenes was not seen in AHF initiated by nonnecrogenic doses of DEN and promoted by phenobarbital. However, at the necrogenic dose of 200 mg/kg DEN, c‐myc expression was found mostly in AHF in which abnormal expression of GST‐P, GGT, G6Pase, and ATPase was also present, indicating that c‐myc expression is correlated with phenotypically greater complexity of the AHF, a characteristic of malignant hepatic neoplasms in the rat. © 1995 Wiley‐ Liss, Inc.
Distribution of the DNA adducts of 2‐amino‐3–methylimidazo[4,5–f]quinoline and 2–amino‐1–methyl‐6–phenylimidazo[4,5–b]pyridine in the supF gene as determined by polymerase arrest assay
Authors: Endo Hisashi , Schut Herman A. J. , Snyderwine Elizabeth G.
Published: February 2007

The distribution of the adducts of the cooked meat‐derived heterocyclic amines 2–amino‐3–methylimidazo 4,5–flquinoline (a) and 2–amino‐1–methyl‐6–phenylimidazo[4,5–b]pyridine (a) was examined in the supF gene of PSP 189 by a polymerase‐arrest assay using thermal‐cycle sequencing. The reactive N‐acetoxy metabolites of both compounds showed an overwhelming preference for reacting with guanine residues in the supF gene of the shuttle vector pSP189. The distribution of the IQ and PhIP guanine adducts was not random; instead, patterns of adduct hot‐spots and cold‐spots were observed. There was a striking similarity between both compounds in their preferred sites of adduct formation. The finding that IQ and PhIP adducted to guanine concurred with previous results showing that the target sites for IQ and PhIP mutations in supF were also at guanine. However, the adduct hot‐spot sites were not predictive of the known sites of mutation hot‐spots. In addition, despite the similarity in adduct hot‐spots for IQ and PhIP, their reported mutation spectra in the supF gene were different. Factors in addition to adduct location therefore appear to play a role in the mutation spectra induced by the heterocyclic amines in the supF gene. © 1995 Wiley‐ Liss, Inc.
Molecular analysis of a family of cyclin‐dependent kinase inhibitor genes (p15/MTS2/INK4b and p18/INK4c) in non‐small cell lung cancers
Authors: Kawamata Norihiko , Miller Carl W. , Koeffler H. Phillip
Published: February 2007

Cyclin and cyclin‐dependent kinase (a) complexes play important roles in modulating the cell cycle. The CDK inhibitors (a) inhibit the kinase activities of these complexes and block the cell cycle. The p16/multiple tumor suppressor (MTS) 1/inhibitor of CDK4 (INK4) a/CDKN2 gene, a CDKI, is frequently deleted in a variety of human cancers. Recently another CDKI gene, p15/MTS2/INK4b, was cloned and localized to within 20kb of the p16 gene. Moreover, a third CDKI gene, named p18/INK4c and having a high degree of protein homology to p16, has now been cloned. To elucidate the importance of these CDKI genes in non‐small cell lung cancers (a), we examined DNAs from 34 NSCLC samples for alterations in these genes by Southern blot and polymerase chain reaction (a) ‐single‐strand conformational polymorphism (a) analyses. Matched control normal tissues from the same individuals were also examined. Homozygous deletions of the p15 gene were found in three cases. Furthermore, comparative PCR analysis confirmed these deletions and suggested that one additional case had an abnormality of the p15 gene. Neither rearrangements nor deletions of the p18 gene were detected. By PCR‐SSCP and direct sequencing of the aberrantly migrating bands, we detected only polymorphic nucleotide substitutions in both the p15 and p18 genes. In summary, the frequency of deletions of the p15 gene was 12% (four of 34 cases), and no point mutations in the p15 gene were detected in the NSCLCs. For the p18 gene, no abnormalities were detected. A previous analysis of these NSCLC samples for p16 gene alterations revealed that the three cases with homozygous deletions of the p15 gene also have homozygous deletions of the p16 gene. © 1995 Wiley‐ Liss, Inc.
Infrequent Ha‐ras mutations and absence of Ki‐ras, N‐ras, and p53 mutations in 4‐nitroquinoline 1‐oxide‐induced rat oral lesions
Authors: Suzui Masumi , Yoshimi Naoki , Tanaka Takuji , Mori Hideki
Published: February 2007

The alkylating agent 4‐nitroquinoline 1‐oxide (4‐NQO) is a powerful carcinogen and induces squamous cell hyperplasia, squamous cell dysplasia, papilloma, and squamous cell carcinoma (a) in rat oral epithelia. Oral cancers induced by a single application of 4‐NQO develop through a multistage process in a way similar to the development of this cancer in humans. In this study, mutations in exons 1 and 2 of Ki‐ras, N‐ras, and Ha‐ras and exons 4–7 of p53 were examined by polymerase chain reaction (a) ‐single strand conformation polymorphism (a) analysis, followed by PCR‐direct sequencing for the confirmation of mutations. Samples for the mutation analysis were obtained from dysplasias, papillomas, and SCCs on the tongue epithelia induced in F344 rats by adding 4‐NQO (20 ppm) to their drinking water for 8 wk. The Ha‐ras mutations (61A→T transversions in the second position) were found in five of 29 (17%) samples (one dysplasia and four SCCs). However, no mutations were detected in either Ki‐ras, N‐ras, or p53 under two different conditions of PCR‐SSCP analysis. We suggest that some neoplasms in oral carcinogenesis induced by 4‐NQO may involve Ha‐ras mutations but not mutations in Ki‐ras, N‐ras, or p53. The 4‐NQO‐induced rat oral carcinogenesis model may provide a system for evaluation of the mechanisms of multistage oral carcinogenesis associated with Ha‐ras mutation without Ki‐ras, N‐ras, or p53 mutation. © 1995 Wiley‐ Liss, Inc.
Bladder diary measurements in asymptomatic females: functional bladder capacity, frequency, and 24‐hr volume
Authors: Amundsen Cindy L. , Parsons Matthew , Tissot Bill , Cardozo Linda , Diokno Ananias , Coats Alfred C.
Published: February 2007

Aims

To study the effects of age and 24‐h volume (V24) on bladder diary measurements of voiding frequency (F24) and functional bladder capacity (FBC) from an asymptomatic female population. Also, to use these data to develop clinical reference values. (We use FBC as a generic term for bladder diary volume‐per‐void measurements.)

Materials and Methods

Computer‐processed 3‐day bladder diaries were collected from 161 females (median age: 46.6 years; range = 19.6–81.8 years) claiming no urological symptoms, previous pelvic surgery and diseases and medications effecting urologic function. Regression analysis was used to investigate relationships among age, FBC and V24.

Results

Both FBC and F24 increase as V24 increases (P < 0.0005). With aging, F24 increases (P = 0.026) and FBC may decrease slightly (P = 0.02–0.08). There is a concave downward, curvilinear relationship between age and V24. We used multiple regression to generate tables of FBC and F24 “normal limits” adjusted for these simultaneous influences of V24 and age. Removing their relationships to age reduces the variability of FBC and F24 reference values by 50% and 20%, respectively.

Conclusions

Our finding, supported by others, that, with increasing V24, FBC increases more than F24 suggests an adaptive mechanism that adjusts FBC to urine production to minimize changes in voiding frequency. We illustrate adjustment of reference values for age and V24 by calculating traditional clinical “normal limits.” However, the probable large overlap between “normal” and “abnormal” suggests that it may be more useful to report bladder diary measurements as reference population percentiles rather than to designate them “normal” or “abnormal”. Neurourol. Urodynam. 26:341–349, 2007. © 2007 Wiley‐Liss, Inc.
Comment on reinterpreting the pollen data from Dos Cabezas
Authors: Reinhard Karl J. , Bryant Vaughn M. , Vinton Sheila Dorsey
Published: February 2007

The published pollen analysis of the Dos Cabezas giants, Geyer et al. (2003), lists a variety of purported dietary pollen types. The paper also hypothesises that the giants were poisoned with plant toxins. We have severe reservations about the pollen evidence of diet and poisoning. We suggest that the analysts made several errors in their interpretation. Firstly, some of the discovered pollen types are not prehistoric endemics to the Dos Cabezas region of coastal Peru. These include the pollen of fava beans (cultivated in the Old World), and specified species of agave and sage. We believe that some or all of the identifications of pollen from arracacha, maca, yuca, oca, potato, peanut, ciruela and tarwi are in error based on the distance they grow from Dos Cabezas and/or their ecological/pollination requirements. We think that it is unlikely that the giants were poisoned because the poisons made from six poisonous plants are not made from the flowers and five of them grow on the opposite side of the Andes from Dos Cabezas. We present an alternative dietary interpretation of the Dos Cabezas giants and suggest methods by which palynological analysis could be improved. Copyright © 2007 John Wiley & Sons, Ltd.
Lipid‐ und Lipoproteinstoffwechsel: Physiologie und Pathophysiologie
Authors: Wächtershäuser Astrid , Stein Jürgen
Published: February 2007

Die im Blut vorkommenden Lipide, Cholesterolester, Triglyzeride und Phospholipide sowie die fettlöslichen Vitamine A, D, E und K sind weitgehend wasserunlöslich und müssen daher in eine wasserlösliche Form gebracht werden. Diesem Zweck dienen Proteine mit Lipid‐komplexierenden Eigenschaften, die als “Apolipoproteine”, kurz “Apoproteine”, bezeichnet werden. Die entstehenden Lipid‐Proteinkomplexe werden Lipoproteine genannt.
Synthesis of water‐dispersible, fluorinated particles with grafting sulfonate chains by the core crosslinking of block copolymer micelles
Authors: Matsumoto Kozo , Kage Shuji , Matsuoka Hideki
Published: February 2007

Fluorinated polymer particles with grafting sulfonate chains, which showed high dispersion stability in aqueous media, were synthesized by the crosslinking of block copolymer micelles. A crosslinkable block copolymer, poly[(2,3,4,5,6‐pentafluorostyrene)‐co‐4‐(1‐methylsilacyclobutyl)styrene]‐b‐poly(neopentyl 4‐styrenesulfonate), composed of a statistical copolymer segment of 2,3,4,5,6‐pentafluorostyrene with 4‐(1‐methylsilacyclobutyl)styrene and a neopentyl 4‐styrenesulfonate segment, was prepared by the nitroxy‐mediated living radical polymerization of a 2,3,4,5,6‐pentafluorostyrene/4‐(1‐methylsilacyclobutyl)styrene mixture and neopentyl 4‐styrenesulfonate. The block copolymer formed micelles with a poly[(2,3,4,5,6‐pentafluorostyrene)‐co‐4‐(1‐methylsilacyclobutyl)styrene] core in acetonitrile, which were crosslinked via the ring‐opening reaction of silacyclobutyl groups in the core by a treatment with a platinum catalyst. The deprotection of sulfonate groups in the micelle corona by exposure to trimethylsilyl iodide and a treatment with aqueous HCl, followed by neutralization with aqueous NaOH, provided a polymer particle with polymer chains of sodium 4‐styrenesulfonate grafted on its surface. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1316–1323, 2007
Electrical DC conduction mechanism in some newly synthesized nylon 6/12 copolymers
Authors: Rusu Gheorghe , Rusu Elena , Leontie Liviu , Rusu Gheorghe I.
Published: February 2007

The synthesis and the study of DC electrical transport properties (electrical conductivity, σ, and Seebeck coefficient,S) as a function of temperature of some recently synthesized nylon 6/12 copolymers with 0, 5, 10, 20, 30, and 50 wt % laurolactam (LL), respectively, are reported. Nylons were obtained by rotational molding via the anionic activated copolymerization of ε‐caprolactam and LL. As evidenced by XRD analyses, they are semicrystalline. The temperature dependences of σ andSare typical for polycrystalline semiconducting (p‐type) materials. The activation energy of electrical conduction lay in the range 0.79–1.22 eV, while the ratio of charge carrier mobilities ranged between 0.53 and 0.77. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 794–799, 2007
A qualitative analysis of acidic proteins associated with regressing, growing, or dividing rat ventral prostate cells
Authors: Anderson K. M. , Baranowski J. , Rubenstein M. , Economou S. G.
Published: February 2007

A qualitative analysis of Coomassie blue R‐250‐stained acidic proteins from normal, regressing, growing or dividing rat ventral prostate cells was performed. Four prostates from each of five groups of animals that included normal, and short (3‐day) or longer‐term (6‐day) castrates, some of which received pharmacologic amounts of testosterone propionate for 3 subsequent days to induce cellular hypertrophy or hyperplasia respectively, were solubilized. Proteins were separated in the first dimension by their isoelectric points from pI 3 to 10, and in the second according to molecular weights, using SDS polyacrylamide gel electrophoresis. Composite “normograms” of protein distribution were developed, based on four different samples from each of the five groups, and 17 out of 31 possible subsets defined. Two major conclusions resulted: 1) The physiologic state of the organ could be identified by its distribution of stained proteins, reflected in the composite “normogram” for each of the five groups and 2) twelve of the seventeen identified patterns of protein distribution were provisionally correlated with the physiologic state of the sample. Excluding the trivial category of “ubiquitous” proteins, subsets including androgen‐dependent and androgen‐inhibited proteins, putative cell number or cell type‐dependent changes, proteins associated with cellular hypertrophy, hyperplasia, and short or long‐term castration and protein synthesis that may have been affected by nonandrogen‐dependent gonadal factors could provisionally be delineated. Most of these categories would not have been evident without the use of two‐dimensional protein analysis. It will be understood that these subsets, predicated upon the apparent presence or absence of proteins detected with a stain of limited sensitivity, would probably be markedly altered if a more sensitive means of protein detection were used. However, within the sensitivity provided by the dye, these conclusions are warranted.
Proteolytic fragmentation of rat prolactin by the rat ventral prostate gland
Authors: Compton Mark M. , Witorsch Raphael J.
Published: February 2007

Homogenates of rat ventral prostate diminished the immunoreactivity of rat prolactin (PRL) in a fashion dependent on time and tissue concentration, suggestive of hormone degradation. Direct evidence of PRL proteolysis was demonstrated by subjecting ventral prostate homogenates and cell fractions that were incubated with 125I‐labeled rat PRL to SDS‐PAGE and radioautography. Heat‐labile PRL proteolysis predominated in the crude homogenate, the 3,300g pellet and the 100,000g (100 K g) supernatant of rat ventral prostate. The degradation of PRL by the 100 K g supernatant led to the formation of two stable peptide fragments weighing approximately 16,000 and 12,000 daltons. PRL proteolysis was negligible in 100 K g supernatants of the liver, salivary gland, testis, epididymis, vas deferens, seminal vesicle, and dorsolateral prostates of male rats. On the other hand, 100 K g supernatants of rat spleen, lung, and kidney did degrade rat PRL, although the patterns of peptide fragment formation differed from that of ventral prostate. Enzyme inhibitor analysis suggested that PRL degradation by the 100 K g supernatants of rat ventral prostate was due to sulfhydryl and serine proteases and not due to metalloenzyme or aspartate proteases. The functional significance of PRL fragmentation by rat ventral prostate cytosol remains to be determined.
Localization of acid phosphatase activity in testosterone‐treated prostatic urethra of human fetuses
Authors: Kellokumpu‐Lehtinen P.
Published: February 2007

Androgens accelerated differentiation of human fetal urethral epithelial cells into secretory prostatic cells in organ culture. These epithelial cells contained supranuclear Golgi complexes in which acid phosphatase enzyme activity could be demonstrated by an electron microscopic histochemical technique. Most of the acid phosphatase activity was localized in lysosomes. Some apical precipitates could also be seen. This apical activity might be in secretory granules. Also, mesenchymal cells contained this enzyme.
Are fluorescein‐conjugated androgens appropriate for a histochemical detection of prostatic androgen receptors?
Authors: Lämmel Andreas , Krieg Michael , Klötzl GÜNther
Published: February 2007

Histochemical fluorescence techniques could be of great value in order to assay androgen receptors (AR), particularly in punch biopsies from human prostatic carcinoma (PCA). Therefore, prostatic tissue was examined for specific binding of fluorescein‐labeled Sα‐ dihydrotestosterone derivatives (FDHT) to AR.

Using a 17β‐fluoresceinated DHT derivative (17‐FDHT), variable fluorescence was found in human and rat prostates at high 17‐FDHT concentrations. This fluorescence could be blocked by unlabeled DHT in 11 and 73% of human and rat prostatic tissue, respectively. Control studies of receptor and organ specificity were conducted and showed that preheated slices from rat prostates displayed no decrease of fluorescent staining. No difference in fluorescence intensity could be seen between prostates from castrated and uncastrated rats. Unstained tissue slices frequently showed a considerable intensity of autofluorescence. An appreciable amount of fluorescence in both rat liver and spleen was found. From these results and various general methodical problems inherent in fluorescent receptor assays, we conclude that the fluorescence techniques described are inappropriate for demonstration of AR.
Growth responses of the guinea pig seminal vesicle epithelium and muscle to long‐term treatment with dihydrotestosterone and/or estradiol benzoate
Authors: Mariotti Angelo , Duremdes Gene , Mawhinney Michael
Published: February 2007

The three‐month treatment regimen with dihydrotestosterone (DHT) and estradiol (E2B) which was capable of producing a supranormal growth of the canine prostate gland equal to that occurring in spontaneous canine benign prostatic hypertrophy, failed to produce similar changes in either the epithelium or smooth muscle of the guinea pig seminal vesicle. The factor limiting the growth response in the seminal vesicle epithelium and muscle of the castrate guinea pig proved to be the lack of a DHT‐estradiol benzoate (E2B) synergism, since the growth responses in seminal vesicle tissues to the three‐month treatment with DHT alone were similar to that previously recorded for the canine prostate. The lack of a DHTE2B synergism in the guinea pig seminal vesicle may be responsible for the absence of spontaneous hypertrophy of this organ and other organs such as the human seminal vesicle with advancing age.
Protease inhibitors: Possible anticarcinogens in edible seeds
Authors: Troll Walter , Wiesner Rakoma
Published: February 2007

Protease inhibitors, which are common constituents of seeds (rice, beans, and maize) have been shown to inhibit breast, colon, and skin cancers in animal experiments. Epidemiological studies have shown that diets rich in these components (ie seed proteins) decrease the occurrence of prostatic, breast, and colon cancers in man. We have demonstrated that a typical purified inhibitor from soybeans, the Bowman‐Birk inhibitor, is excreted in the feces complexed with digestive proteases from the duodenum. This results in greater excretion of proteins, thus effectively decreasing the amount of protein available for digestion.

Excess protein in the diet in addition to fats may contribute to increased cancer. Thus, the addition of seeds (chick‐peas, beans, etc) to the diet rather than removal of meat or fat offers the opportunity of preventing these cancers, because the protease inhibitors present would effectively remove a portion of the proteins being consumed.

Protease inhibitors also act directly as antioxidants in relation to tumor promoters and ionizing radiation. To what extent this contributes to the nutritional effects of eating seeds containing protease inhibitors remains to be determined.
Circadian variation of different fractions of serum acid phosphatase
Authors: Schmeller Nikolaus T. , Bauer H. W.
Published: February 2007

The circadian variation of different fractions of serum acid phosphatase was determined in two men with a normal prostate, two men with benign prostatic hyperplasia, and four men with prostatic cancer. Serum samples were obtained every 2 hours from 8:00 a.m. until 6:00 a.m. the following day. An overall sample standard deviation of 1.98 U/liter was calculated for total acid phosphatase, 0.4 U/liter for tartrate‐labile acid phosphatase, and 0.13μg/liter for prostatic acid phosphatase as determined by immunoenzyme assay.
The patient, disease status, and treatment options for prostate cancer: Stages B1 and B2
Authors: Herr Harry W.
Published: February 2007

Prostatic adenocarcinoma palpably confined to the prostate is clinically defined as stage B. Although potentially curable in many, if not most, instances, there is no disputing that the optimal management of patients with stage B neoplasms is one of the most uncertain and controversial issues in modern urologic oncology. The present uncertainty can be related to three major factors: 1) competing causes of death in patients commonly older than 50 years of age; 2) the variable and unpredictable natural course of localized prostatic cancer as reflected by the three, at least in part. independent variables of growth rate, metastatic potential, and therapeutic responsiveness; and 3) the multiplicity and effectiveness of a variety of treatments in producing effects on the tumor favorable to the patient. The relative effectiveness of different treatments has been and remains clouded by a constantly changing array of clinical staging techniques, selection criteria for treatment, and definitions of response, and by the general absence of satisfactory control data. Experiences with patients receiving no treatment, various forms of irradiation, and radical excision have indicated a general similarity in at least 10‐year survival rates and clinically manifest local failure rates among comparable substages of stage B prostatic cancer. Since suitable control data are lacking, one may conclude that a variety of treatments offer similar prospects of benefit or that none of the treatments is producing significant beneficial effect and that survivals are a consequence of the natural history of stage B disease. A possibility that has yet to be evaluated is that different treatments produce benefit in different segments of the stage B prostatic cancer population, and the challenge today is to recognize and define such neoplasms that may respond most appropriately to one form of therapy or another.
Treatment of prostatic cancer with LH‐RH analogues
Authors: Borgmann V. , Nagel R. , Al‐Abadi H. , Schmidt‐Gollwitzer M.
Published: February 2007

Twenty‐one of 32 patients with locally advanced prostatic cancer (stage C) were treated with the LH‐RH analogue Buserelin for 7‐19 months. After an initial sequence of subcutaneous injections, treatment was continued with intranasal spray application (three daily doses of 400 μg each) which ensured maintenance of serum testosterone within the range seen in castrated men.

To evaluate the response of the primary tumor to Buserelin, cytological regression was established for all patients by fine‐needle aspiration biopsy every 3 months. The cytological results corresponded with those of DNA analyses of single‐cell cytophotometry showing a statistically significant drop of the grade of aneuploidy or polyploidy when the prostatic carcinoma responded positively to Buserelin therapy.

Seventeen of 21 patients treated with the potent LH‐RH analogue showed good therapy response. Four patients with no cytological signs of tumor regression received secondary treatment with estramustin phosphate because of hormone resistence. One patient had to be crossed over to cyclophosphamide, the third drug, for clinical progression after 15 months. Essential side effects have not been observed.

Continuous treatment of locally advanced prostatic cancer with Buserelin, combined with close control of the patient, offers not only a real alternative to surgical castration–as the patient is spared the psychical stress of orchiectomy–but also to estrogen therapy with its risk of cardiovascular side effects.
Transabdominal ultrasonography in the evaluation of patients with advanced prostatic carcinoma: Effects of castration and of chronic administration of a gonadotropin releasing hormone agonistic analogue
Authors: Tolis G.
Published: February 2007

Twenty‐two patients with advanced prostatic carcinoma were subjected either to orchiectomy (group 1, n=5) or to chronic administration of a gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly‐NH210 LHRH nonapeptide (HOE 766) (group 2, n=17).

Plasma testosterone was similar in both groups prior to treatment (group 1: 636 ± 129.29, group 2: 580.85 ± 37.57; × ±SE). The levels attained in group 1 were significantly lower (P <.05) than those of group 2 through eight weeks of follow‐up but were similar by the third month.

Prostatic size (cm2) as estimated by transabdominal ultrasonography did not differ between the two groups prior to treatment (group 1: 23.6 + 3.35, group 2: 21.4 ± 1.97; × ± SE). Both therapies resulted in a decrease of prostatic size that was significantly more pronounced (P <.05) in group 1 compared with group 2 by the first and third month; by the six month, there was no statistical difference in the prostatic size attained with either therapeutic modality. Persistant suppression of prostatic size was documented in all patients of group 2 chronically (up to 24 months) treated with HOE 766 even when there was evidence of uninhibited or progressive bony metastases.

The above data 1) indicate the efficacy of the HOE 766 in inducing medical castration and prostatic shrinkage in advanced carcinoma of the prostate, 2) document the usefulness of transabdominal ultrasound in the follow‐up of such patients, and 3) suggest a relationship between the rapidity of tumor shrinkage and Leydig cell suppression.
Effect of castration on experimental bacterial prostatitis in rats
Authors: Kaplan Les , Lee Chung , Schaeffer Anthony J.
Published: February 2007

Inoculation of Escherichia coli into the ventral lobe of the rat prostate produced positive bacterial cultures in the expressed fluid of all three lobes of the rat prostate for a prolonged period of time. Orchiectomy at the time of bacterial inoculation significantly shortened the interval of positive bacterial cultures in the prostate expressate.
Ultrastructural localization of zinc in the hyperplastic prostate
Authors: Okada Kiyoki , Morita Hirohito , Arai Ritsuo , Kishimoto Takashi
Published: February 2007

The localization of zinc was investigated in specimens of hyperplastic prostate by means of light microscopy, electron microscopy, and x‐ray microanalysis. After fixation in glutaraldehyde plus hydrogen sulfide, representative sections were developed with sulfide‐silver while, for comparison, other sections were not developed. Aggregation of the silver precipitation was seen on the secretory vacuoles of the developed sections. None of the deposits were detected on the nucleus, lysosomes, Golgi apparatus, or other cytoplasmic organelles. X‐ray microanalysis was performed on these sections of hyperplastic prostate. X‐ray energy spectrum analysis of the undeveloped sections revealed that the concentration of zinc on the electrondense materials in the secretory vacuoles corresponded to the deposits of silver granules. The present investigation provides direct proof of the localization of ionized zinc in the cytoplasm of the hyperplastic prostate.
The timing of androgen ablation therapy and/or chemotherapy in the treatment of prostatic cancer
Authors: Isaacs John T.
Published: February 2007

The effect of varying the timing of androgen ablation alone and in combination with chemotherapy on tumor growth rate and host survival has been studied using the serially transplantable Dunning R‐3327 H rat prostatic adenocarcinoma as a model. These studies have demonstrated three basic points: 1) When either androgen ablation or Cytoxan chemotherapy are given as a single agent treatment, they are both most effective when given as early as possible; 2) when androgen ablation is combined with Cytoxan chemotherapy, it is most effective when both therapies are begun simultaneously and as early as possible; and 3) when androgen ablation and Cytoxan treatment are begun simultaneously and early, it is possible to increase survival above that found for either treatment when given optimally as single modalities (ie, such simultaneous early treatment enhances the individual therapeutic effectiveness of both treatments).
Rationale for chemotherapeutic approaches to prostate cancer
Authors: Creaven Patrick J.
Published: February 2007

The problems of curing tumors with a low growth fraction with cytotoxic chemotherapeutic agents include 1) the fact that such agents attack biochemical pathways common and vital to all cells, 2) the existence in a tumor of cells with both temporary and permanent resistance to specific agents, and 3) the exponential nature of cell kill, which necessitates a much more intensive treatment to effect cure than to effect remission. The possible bases for selectivity of anticancer drugs include those factors that affect the concentration of the active form of the drug at the active site, those that affect the drug receptor interaction and those that determine whether this interaction will lead to cell death. Possible ways of overcoming resistance include combination chemotherapy, more intensive chemotherapy, adjuvant chemotherapy, and maneuvers leading to recruitment of cells into cycle. Because of tumor cell heterogeneity a different approach may be needed to effect cure from that required to induce complete remission.
Treatment of prostatitis in the rat
Authors: Lundgren Rolf , Holmquist Bo , Hesselvik Margareta , Müntzing Jonas
Published: February 2007

A spontaneous, nonacute, age‐dependent prostatitis was found in a high incidence in the lateral prostatic lobes of Lewis rats. Such rats were treated with methylprednisolone, indometacin, testosterone, hexyloxyphenylproprionate, polyestradiol phosphate, various antibiotics, or were caged together with female rats. The effect of the different treatment modalities was evaluated microscopically by blind observation of the degree of inflammatory reaction in the lateral prostate. Methylprednisolone and the testosterone ester caused a reduction of the inflammatory reactions and so did caging with female rats. The similarity of the rat prostatitis to the human condition may suggest the possibility of using corticosteroids or androgens for the treatment of patients with nonacute prostatitis.
Biochemical difference between ventral and dorsolateral prostates: Effects of castration and administration of the antiandrogen 16β‐ethyl‐17β‐hydroxy‐4‐oestren‐3‐one on SDS‐electrophoretic patterns of subcellular proteins from rat prostates
Authors: Wada Fumio , Nishi Nozomu , Matuo Yuhsi
Published: February 2007

Protein species in the cytosol, postnuclear particulate, and nuclear fractions from the ventral and dorsolateral prostates of rats castrated or injected with antiandrogen, 16β‐ethyl‐17β‐hydroxy‐4‐oestren‐3‐one (EHOO), were analzyed by SDS‐polyacrylamide gel electrophoresis. The effects of EHOO injection on the contents of the most abundant species in all three fractions of ventral prostate were similar to the effects of castration, but the effects of EHOO and castration were only similar on the nuclear fraction in the dorsolateral prostate. The most sensitive species to castration in the three subcellular fractions of dorsolateral prostate were the same as those to EHOO injections; this was not the case for the cytosol and nuclear fractions in the ventral prostate.
Involution of spontaneous benign prostatic hyperplasia in the dog under the influence of chronic treatment with a LHRH agonist
Authors: Dubé J. Y. , Frenette G. , Tremblay R. R. , Tremblay Y. , Bélanger A.
Published: February 2007

Eight dogs with spontaneous benign prostatic hyperplasia were treated with daily subcutaneous injections of 25 μg of Buserelin, (D‐Ser(TBU)6, des‐Gly‐NH210)ethylamide during 3 months. Prostate weight before treatment was estimated by tridimensional measurements during open surgery. After 3 months of treatment, prostate weight was decreased by 50–60%. In two castrated control animals, prostate weight decreased about 70% after 3 months. Histological pattern in prostates from castrated or Buserelin‐treated animals was similar and indicated considerable atrophy of glandular epithelium and predominance of stroma. At the same time, testes weight decreased with complete disappearance of spermatogenic activity. Acid phosphatase and arginine esterase activity levels, two markers of androgenic action in the prostate, were similar after Buserelin or castration. Steroid receptors for androgens, estrogens, and progesterone also behaved similarly under the influence of Buserelin and castration.
Antigrowth effect of polyamine biosynthesis inhibitors on the dunning R 3327‐G prostatic tumor
Authors: Herr Harry W. , Kleinert Edward L.
Published: February 2007

α‐Difluoromethylornithine (DFMO) and methylglyoxal‐bis‐guanylhydrazone (MGBG), when administered simultaneously, inhibited growth and were highly toxic to the Dunning R 3327‐G hormone‐resistant prostatic adenocarcinoma transplanted into Copenhagen rats. Neither DFMO (2%) nor MGBG at a nontoxic dose (15 mg/kg) inhibited tumor growth, but total (47% early cure rate) or near total suppression of growth of established tumors was observed in rats receiving both treatments.
Prostatic adenocarcinoma PC EW, a new human tumor line transplantable in nude mice
Authors: Hoehn W. , Wagner M. , Riemann J. F. , Hermanek P. , Williams E. , Walther R. , Schrueffer R.
Published: February 2007

A serially transplantable human prostatic carcinoma line, PC EW, has been developed through heterotransplantation of tumor tissue from a lymph node metastasis. PC EW is androgen dependent and is similar to the original tumor in terms of histological pattern, amounts of prostatic acid phosphatase secreted, and absence of a hormonally independent subline. This line is thus similar to PC 82, and we herein report the first results of comparative treatment trials conducted on PC EW.
Transrectal ultrasonotomography of the canine prostate
Authors: Miyashita Hiroaki , Watanabe Hiroki , Ohe Hiroshi , Saitoh Masahito , Oogama Yasuhiro , Iijima Syohgo
Published: February 2007

We developed a new scanner for transrectal ultrasonotomography of the canine prostate. Using this scanner, a clear horizontal tomogram of the canine prostate was obtained for cross sections at every 2 mm. Prostatic volume was estimated as the sum of the volume of each section. Accordingly, the weight of the canine prostate could be accurately calculated from the volume and the specific gravity of the prostate.
Clinical applications and value of receptor levels in treatment of prostate cancer
Authors: Connolly J. G. , Mobbs B. G.
Published: February 2007

Factors affecting the validity and interpretation of androgen receptor (AR) assays on prostatic carcinoma tissue are discussed, and attempts to relate AR concentration with response of the patient to hormonal manipulation are reviewed. It is concluded that nuclear AR content may be useful in evaluating prognosis and likely response to hormonal therapy, and that, owing to the heterogeneity of many prostatic carcinoma specimens, a reliable histochemical method for the assessment of androgen sensitivity would be a valuable supplement to the biochemical assay.
Single case report of prostate adenocarcinoma in a dog castrated three months previously. Morphological, biochemical, and endocrine determinations
Authors: Dubé J. Y. , Frenette G. , Tremblay Y. , Bélanger A. , Tremblay R. R.
Published: February 2007

During the course of another investigation, three dogs had been castrated 3 months previously. Upon completion of the experiment, it was discovered that one dog presented a spontaneous prostatic adenocarcinoma of intraalveolar proliferative type at histology. Prostate weight of this dog before castration was estimated to be 22 g by tridimensional measurement at laparotomy and remained relatively constant (19 g) 3 months after castration. These results indicate that if regression had occurred in some cell populations (androgen‐dependent) it was only partial and masked by growth of androgen‐independent cells. Analysis of 12 individual steroids in peripheral blood and in prostatic tissue attested of a normal adrenal secretory activity. A series of 15 hydrolytic enzymes along with receptors for androgen, estrogen, and progesterone, were determined in prostatic tissue obtained at sacrifice. Enzymatic activities were those of typical epithelial cells, and most of them remained relatively high despite low levels of circulating testosterone. However, two markers of androgen action in dog prostate, acid phosphatase and arginine esterase, were significantly reduced. Receptor levels were similar to those of castrated animals. Thus, cancer cells had probably retained some androgen sensitivity.