bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the necrotic periodontal membrane in cementum resorption and ankylosis
Authors: Lindskog Sven , Pierce Angela M. , Blomlöf Leif , Hammarström Lars 
Published: April 2006

Abstract Teeth replanted with non‐vital periodontal membranes demonstrate a high incidence of root resorption and ankylosis. It has been suggested that necrotic periodontal membrane remnants actively stimulate resorption of the resistant cementum layer. The aim of this study was to examine resorption and ankylosis patterns following replantation of teeth with chemically denuded root surfaces and, by extrapolation from these data, to suggest a role for the necrotic periodontal membrane in resorption and ankylosis.Monkey incisors were replanted after endodontic therapy and immersion in 10% sodium hypochlorite. Teeth were either examined with scanning electron microscopy at intervals from 1 day to 8 wk, or subjected to light microscopic examination, using a morphometrical evaluation technique, at 8 wk post‐replantation.Only a few macrophage‐like cells, in relation to shallow resorption lacunae, were observed by 8 wk. Histologically, the alveolar bone had approached an apparently intact cementum surface in 93% of the morphometrically recorded points. This bone appeared to lie in close approximation to the cementum surface.Denuding the root surface of periodontal membrane prior to replantation demonstrated the resistance of the cementum to colonization and resorption in the absence of stimulation from necrotic periodontal membrane remnants. Furthermore, it revealed that bone replacing the periodontal membrane space grew from the alveolus towards the cementum, to which it appeared unable to fuse due to the absence of significant resorption. Thus, removal of a non‐vital periodontal membrane may result in slower destruction of tooth substance following replantation of teeth with severely damaged periodontal membranes.
Experimental internal resorption in monkey teeth
Authors: Wedenberg Cecilia , Lindskog Sven 
Published: April 2006

Abstract Internal resorption is a rare pathological finding except in pulpectomized deciduous teeth. Although its etiology is largely unknown, infection and trauma have been suggested in a number of cases. The aim of this study was to explore the possibility of provoking internal resorption in vivo, to study etiological factors such as trauma and infection, and to describe the cells colonizing the walls of the pulp chamber. Monkey incisors were opened, injected with Freund's complete adjuvant and sealed or left open to the oral cavity. After varying observation periods, the teeth were extracted and prepared for examination with scanning electron microscopy, microradiography, light microscopy and enzyme histochemistry. Colonization of the walls of the pulp chamber by macrophage‐like cells was observed in both experimental groups. However, it appeared to be transient in Unsealed, non‐infected teeth and more extensive and prolonged in the open, infected teeth. In sections of pulp tissue a tartrate‐resistant acid phosphatase activity characteristic of mineralized tissue resorbing cells was evident.It is suggested that internal resorption may be divided into a transient type and a progressive type, the latter requiring a continuous stimulation by infection.
Integrating data on DNA copy number with gene expression levels and drug sensitivities in the NCI-60 cell line panel
Authors: Bussey Kimberly J. , Chin Koei , Lababidi Samir , Reimers Mark , Reinhold William C. , Kuo Wen-Lin , Gwadry Fuad , Ajay  , Kouros-Mehr Hosein , Fridlyand Jane , Jain Ajay , Collins Colin , Nishizuka Satoshi , Tonon Giovanni , Roschke Anna , Gehlhaus Kristen , Kirsch Ilan , Scudiero Dominic A. , Gray Joe W. , Weinstein John N. 
Published: April 2006

AbstractChromosome rearrangement, a hallmark of cancer, has profound effects on carcinogenesis and tumor phenotype. We used a panel of 60 human cancer cell lines (the NCI-60) as a model system to identify relationships among DNA copy number, mRNA expression level, and drug sensitivity. For each of 64 cancer-relevant genes, we calculated all 4,096 possible Pearson's correlation coefficients relating DNA copy number (assessed by comparative genomic hybridization using bacterial artificial chromosome microarrays) and mRNA expression level (determined using both cDNA and Affymetrix oligonucleotide microarrays). The analysis identified an association of ERBB2 overexpression with 3p copy number, a finding supported by data from human tumors and a mouse model of ERBB2-induced carcinogenesis. When we examined the correlation between DNA copy number for all 353 unique loci on the bacterial artificial chromosome microarray and drug sensitivity for 118 drugs with putatively known mechanisms of action, we found a striking negative correlation (−0.983; 95% bootstrap confidence interval, −0.999 to −0.899) between activity of the enzyme drug l-asparaginase and DNA copy number of genes near asparagine synthetase in the ovarian cancer cells. Previous analysis of drug sensitivity and mRNA expression had suggested an inverse relationship between mRNA levels of asparagine synthetase and l-asparaginase sensitivity in the NCI-60. The concordance of pharmacogenomic findings at the DNA and mRNA levels strongly suggests further study of l-asparaginase for possible treatment of a low-synthetase subset of clinical ovarian cancers. The DNA copy number database presented here will enable other investigators to explore DNA transcript-drug relationships in their own domains of research focus. [Mol Cancer Ther 2006;5(4):853–67]
A T3587G germ-line mutation of the MDR1 gene encodes a nonfunctional P-glycoprotein
Authors: Mutoh Kazuyoshi , Mitsuhashi Junko , Kimura Yasuhisa , Tsukahara Satomi , Ishikawa Etsuko , Sai Kimie , Ozawa Shogo , Sawada Jun-ichi , Ueda Kazumitsu , Katayama Kazuhiro , Sugimoto Yoshikazu 
Published: April 2006

Abstract
The human multidrug resistance gene 1 (MDR1) encodes a plasma membrane P-glycoprotein (P-gp) that functions as an efflux pump for various structurally unrelated anticancer agents. We have identified two nonsynonymous germ-line mutations of the MDR1 gene, C3583T MDR1 and T3587G MDR1, in peripheral blood cell samples from Japanese cancer patients. Two patients carried the C3583T MDR1 allele that encodes H1195Y P-gp, whereas a further two carried T3587G MDR1 that encodes I1196S P-gp. Murine NIH3T3 cells were transfected with pCAL-MDR-IRES-ZEO constructs carrying either wild-type (WT), C3583T, or T3587G MDR1 cDNA and selected with zeocin. The resulting zeocin-resistant mixed populations of transfected cells were designated as 3T3/WT, 3T3/H1195Y, and 3T3/I1196S, respectively. The cell surface expression of I1196S P-gp in 3T3/I1196S cells could not be detected by fluorescence-activated cell sorting, although low expression of I1196S P-gp was found by Western blotting. H1195Y P-gp expression levels in 3T3/H1195Y cells were slightly lower than the corresponding WT P-gp levels in 3T3/WT cells. By immunoblotting analysis, both WT P-gp and H1195Y P-gp were detectable as a 145-kDa protein, whereas I1196S P-gp was visualized as a 140-kDa protein. 3T3/I1196S cells did not show any drug resistance unlike 3T3/H1195Y cells. Moreover, a vanadate-trap assay showed that the I1196S P-gp species lacks ATP-binding activity. Taken together, we conclude from these data that T3587G MDR1 expresses a nonfunctional P-gp and this is therefore the first description of such a germ-line mutation. We contend that the T3587G MDR1 mutation may affect the pharmacokinetics of MDR1-related anticancer agents in patients carrying this allele. [Mol Cancer Ther 2006;5(4):877–84]
Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering cell cycle kinetics and enhancing senescence
Authors: Yan Tao , Seo Yuji , Schupp Jane E. , Zeng Xuehuo , Desai Anand B. , Kinsella Timothy J. 
Published: April 2006

Abstract
We previously reported that methoxyamine (an inhibitor of base excision repair) potentiates iododeoxyuridine (IUdR)–induced radiosensitization in human tumor cells. In this study, we investigated the potential mechanisms of this enhanced cell death. Human colorectal carcinoma RKO cells were exposed to IUdR (3 μmol/L) and/or methoxyamine (3 mmol/L) for 48 hours before ionizing radiation (5 Gy). We found that IUdR/methoxyamine altered cell cycle kinetics and led to an increased G1 population but a decreased S population before ionizing radiation. Immediately following ionizing radiation (up to 6 hours), IUdR/methoxyamine–pretreated cells showed a stringent G1-S checkpoint but an insufficient G2-M checkpoint, whereas a prolonged G1 arrest, containing 2CG1 and 4CG1 cells, was found at later times up to 72 hours. Levels of cell cycle–specific markers [p21, p27, cyclin A, cyclin B1, and pcdc2(Y15)] and DNA damage signaling proteins [γH2AX, pChk1(S317), and pChk2(T68)] supported these altered cell cycle kinetics. Interestingly, we found that IUdR/methoxyamine pretreatment reduced ionizing radiation–induced apoptosis. Additionally, the extent of cell death through necrosis or autophagy seemed similar in all (IUdR ± methoxyamine + ionizing radiation) treatment groups. However, a larger population of senescence-activated β-galactosidase-positive cells was seen in IUdR/methoxyamine/ionizing radiation–treated cells, which was correlated with the increased activation of the senescence factors p53 and pRb. These data indicate that IUdR/methoxyamine pretreatment enhanced the effects of ionizing radiation by causing a prolonged G1 cell cycle arrest and by promoting stress-induced premature senescence. Thus, senescence, a novel ionizing radiation–induced tumor suppression pathway, may be effectively targeted by IUdR/methoxyamine pretreatment, resulting in an improved therapeutic gain for ionizing radiation. [Mol Cancer Ther 2006;5(4):893–902]
Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery
Authors: Visaria Rachana K. , Griffin Robert J. , Williams Brent W. , Ebbini Emad S. , Paciotti Giulio F. , Song Chang W. , Bischof John C. 
Published: April 2006

Abstract
Tumor necrosis factor-α (TNF-α) is a potent cytokine with anticancer efficacy that can significantly enhance hyperthermic injury. However, TNF-α is systemically toxic, thereby creating a need for its selective tumor delivery. We used a newly developed nanoparticle delivery system consisting of 33-nm polyethylene glycol–coated colloidal gold nanoparticles (PT-cAu-TNF-α) with incorporated TNF-α payload (several hundred TNF-α molecules per nanoparticle) to maximize tumor damage and minimize systemic exposure to TNF-α. SCK mammary carcinomas grown in A/J mice were treated with 125 or 250 μg/kg PT-cAu-TNF-α alone or followed by local heating at 42.5°C using a water bath for 60 minutes, 4 hours after nanoparticle injection. Increases in tumor growth delay were observed for both PT-cAu-TNF-α alone and heat alone, although the most dramatic effect was found in the combination treatment. Tumor blood flow was significantly suppressed 4 hours after an i.v. injection of free TNF-α or PT-cAu-TNF-α. Tumor perfusion, imaged by contrast enhanced ultrasonography, on days 1 and 5 after treatment revealed perfusion defects after the injection of PT-cAu-TNF-α alone and, in many regions, complete flow inhibition in tumors treated with combination treatment. The combination treatment of SCK tumors in vivo reduced the in vivo/in vitro tumor cell survival to 0.05% immediately following heating and to 0.005% at 18 hours after heating, suggesting vascular damage–mediated tumor cell killing. Thermally induced tumor growth delay was enhanced by pretreatment with TNF-α-coated gold nanoparticles when given i.v. at the proper dosage and timing. [Mol Cancer Ther 2006;5(4):1014–20]
Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer
Authors: Chun Jae Yeon , Nadiminty Nagalakshmi , Lee Soo Ok , Onate Sergio A. , Lou Wei , Gao Allen C. 
Published: April 2006

Abstract
Prevention trials showed that selenium reduced prostate cancer incidence by 50%, establishing selenium as a promising chemopreventive agent for prostate cancer. Selenium inhibited human prostate cancer cell growth, blocked cell cycle progression at multiple transition points, and induced apoptotic cell death. Previous studies showed a novel mechanism of selenium anticancer action in which selenium markedly reduces androgen signaling and androgen receptor (AR)–mediated gene expression, including prostate-specific antigen (PSA), in human prostate cancer cells. The molecular mechanisms of selenium-mediated down-regulation of AR signaling are not clear. In this study, a systemic approach was taken to examine the modification of androgen signaling by selenium in human prostate cancer cells. In addition to reduced AR mRNA expression, selenium was found to initially increase the stability of AR mRNA within 6 hours while decreasing the stability of AR mRNA after 8 hours. Selenium increased AR protein degradation and reduced AR nuclear localization. Scatchard analysis indicated that selenium did not affect ligand binding to AR in LNCaP cells. Chromatin immunoprecipitation analyses showed that DHT increased the recruitment of AR and coactivators, such as SRC-1 and TIF-2, to the promoter of the PSA gene, and that recruitment was greatly diminished in the presence of 5 μmol/L selenium. On the other hand, selenium enhanced the recruitment of corepressors, such as SMRT, to the promoter of the PSA gene. Taken together, these results suggest that selenium disrupts AR signaling at multiple stages, including AR mRNA expression, mRNA stability, protein degradation, nuclear translocation, and recruitment of coregulators. [Mol Cancer Ther 2006;5(4):913–8]
Sensitizing hormone-refractory prostate cancer cells to drug treatment by targeting 14-3-3σ
Authors: Han Baoguang , Xie Han , Chen Qun , Zhang Jian-Ting 
Published: April 2006

Abstract
Advanced and hormone-refractory prostate cancer has long been considered as a chemoresistant disease. Recently, it was found that 14-3-3σ expression increases as prostate tumor progresses, and that 14-3-3σ contributes significantly to drug resistance in breast cancers. We, thus, hypothesized that advanced and hormone-refractory prostate cancers may have an increased level of 14-3-3σ, which in turn may contribute to drug resistance in advanced and hormone-refractory prostate cancers. In this study, we tested this hypothesis and found that, indeed, the expression level of 14-3-3σ in androgen-independent prostate cancer cell lines DU145, PC3, and CWR22RV are much higher than that in the androgen-dependent cell line LNCaP, and that the androgen-independent cells are more resistant to mitoxantrone and Adriamycin than the androgen-dependent cells. Depleting 14-3-3σ expression in DU145 and CWR22RV by RNA interference significantly sensitized these cells to mitoxantrone and Adriamycin by abrogating G2-M checkpoint and increasing apoptosis, whereas restoring 14-3-3σ expression in LNCaP cells enhanced drug resistance. We also showed that 14-3-3σ deficiency caused nuclear localization of Cdc2 and dephosphorylation of the Tyr15 residue upon DNA damage. Based on these studies, we propose that therapeutic intervention targeting 14-3-3σ may be useful for sensitizing hormone-refractory prostate cancers to chemotherapy by both G2-M checkpoint abrogation and apoptosis enhancement. [Mol Cancer Ther 2006;5(4):903–12]
Effects of the farnesyl transferase inhibitor R115777 (Zarnestra) on mammary carcinogenesis: prevention, therapy, and role of HaRas mutations
Authors: Lubet Ronald A. , Christov Konstantin , You Ming , Yao Ruisheng , Steele Vernon E. , End David W. , Juliana M. Margaret , Grubbs Clinton J. 
Published: April 2006

Abstract
The ability of the farnesyl transferase inhibitor R115777 to act as a cancer therapeutic/preventive agent and to modulate proliferation/apoptosis markers was determined in the methylnitrosourea-induced model of mammary carcinogenesis. Female Sprague-Dawley rats were given methylnitrosourea at 50 days of age. In the prevention study, R115777 (5, 16, or 50 mg/kg body weight/d), beginning 5 days after methylnitrosourea treatment, decreased the formation of mammary cancers by 6%, 42%, and 75%, respectively. Approximately 50% of the mammary cancers that developed had HaRas mutations. Only 1 of 15 tumors that grew out in the presence of R115777 (16 or 50 mg/kg body weight/d) had a HaRas mutation. In the therapeutic study, a surgical biopsy of a mammary cancer was done to determine HaRas status, and growth of the cancer was then followed during treatment of the rat with R115777. Virtually every cancer with a HaRas mutation underwent complete regression within 3 weeks, whereas tumors without a HaRas mutation had variable responses to the inhibitor. Both of these studies implied a high sensitivity of tumors with HaRas mutations to the effects of R115777. In order to understand the preferential susceptibility of tumors with HaRas mutations, rats with a palpable cancer were treated with R115777 for a period of 36 or 96 hours prior to sacrifice, and the proliferation and apoptosis levels in the cancers were determined. The proliferative index was significantly (&gt;85%) decreased in all mammary cancers with HaRas mutations, whereas variable responses were observed in cancers without HaRas mutations. Apoptosis was also measured and a 5-fold increase was observed in HaRas mutant tumors, again with varying responses in the HaRas wild-type cancers. Thus, R115777 was active in the prevention and therapy of these chemically induced mammary cancers, but was strikingly more effective in cancers with HaRas mutations. [Mol Cancer Ther 2006;5(4):1073–8]
DNA adducts formed by a novel antitumor agent 11β-dichloro in vitro and in vivo
Authors: Hillier Shawn M. , Marquis John C. , Zayas Beatriz , Wishnok John S. , Liberman Rosa G. , Skipper Paul L. , Tannenbaum Steven R. , Essigmann John M. , Croy Robert G. 
Published: April 2006

Abstract
The multifunctional molecule 11β-dichloro consists of a ligand for the androgen receptor linked to a bifunctional alkylating group, permitting it to create DNA adducts that bind the androgen receptor. We propose that binding of the androgen receptor to 11β-DNA adducts acts to both shield damaged sites from repair and disrupt the expression of genes essential for growth and survival. We investigated the formation 11β-DNA adducts in tumor xenograft and nontumor tissues in mice. Using [14C]-11β-dichloro, we show that the molecule remains intact in blood and is widely distributed in mouse tissues after i.p. injection. Covalent 11β-guanine adducts identified in DNA that had been allowed to react with 11β-dichloro in vitro were also found in DNA isolated from cells in culture treated with 11β-dichloro as well as in DNA isolated from liver and tumor tissues of mice treated with the compound. We used accelerator mass spectrometry to determine the levels of [14C]-11β-DNA adducts in LNCaP cells treated in culture as well as in liver tissue and LNCaP xenograft tumors in treated mice. The level of DNA adducts in tumor tissue was found to be similar to that found in LNCaP cells in culture treated with 2.5 μmol/L 11β-dichloro. Our results indicate that 11β-dichloro has sufficient stability to enter the circulation, penetrate tissues, and form DNA adducts that are capable of binding the androgen receptor in target tissues in vivo. These data suggest the involvement of our novel mechanisms in the antitumor effects of 11β-dichloro. [Mol Cancer Ther 2006;5(4):977–84]
Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway
Authors: Chirnomas Deborah , Taniguchi Toshiyasu , de la Vega Michelle , Vaidya Ami P. , Vasserman Maria , Hartman Anne-Renee , Kennedy Richard , Foster Rosemary , Mahoney Jennifer , Seiden Michael V. , D'Andrea Alan D. 
Published: April 2006

AbstractCisplatin resistance occurs, at least in part, through the function of the Fanconi anemia (FA)/BRCA pathway, a DNA-damage response pathway required for repair of cisplatin cross-links. In the current study, we designed a cell-based screening strategy to identify small-molecule inhibitors of the FA/BRCA pathway with the hypothesis that such molecules could restore sensitivity to platinum agents. We identified four inhibitors, including three protein kinase inhibitors (wortmannin, H-9, and alsterpaullone) and one natural compound (curcumin) that inhibit the FA/BRCA pathway. We show that curcumin, a compound that is generally regarded as safe, inhibits the monoubiquitination of the FANCD2 protein as predicted by the screen and consequently sensitizes ovarian and breast tumor cell lines to cisplatin through apoptotic cell death. We believe that this study shows an efficient, high-throughput method for identifying new compounds that may sensitize cancer cells to DNA-damaging chemotherapy. [Mol Cancer Ther 2006;5(4):952–61]
Genesis xv
Authors: Schmidt Ludwig 
Published: April 2006

AbstractThe story of Abraham in Gen. xi 27-xxv 10 (11) is structured by two different literary layers in Gen. xv. The basic layer, consisting of V. 7-11, 17, 18, was originally connected with Gen. xiii 18. It must be assigned to the pentateuchal redaction, because it builds upon both Gen. xiii 14-17 and the priestly mentions of departure in xi 31; xii 4b, 5. The pentateuchal redaction wanted to demonstrate that Jahwe will not take back his promise of land for the descendants of Abraham, because he has obliged and laid upon himself a conditional curse in the presence of Abraham. Within the conception of the pentateuchal redaction Gen. xv 7ff.* has the function to finish the first part of the story of Abraham (xi 27-xiii 18; xv 7ff.*), which is dominated by the subject "the land for Abraham and his descendants". The subject of the second part (xv 1-xxv 11) can be described as "the descendants of Abraham and his life until his death".A later redactor integrated V. 1-6*, 12-16, 19-21. He wanted to emphasize that the faith of Abraham, trusting God to fulfill his promise of a physical heir and unnumbered descendants (V. 1-6*), gives Jahwe reason to lay upon himself a conditional curse in order to guarantee the promise of the land. This is furthermore the reason, why Jahwe told Abraham that the promise of land will only be fulfilled in a distant future (V. 12-16). In the view of the redactor Gen. xv is the starting point of the second part of the story of Abraham, in which he wanted to tell how Jahwe fulfills his promise of protection and of a physical heir for Abraham (xv 1bα, 4).
Choosing brides for the crown-prince. Matrimonial politics in the Davidic dynasty
Authors: Niemann Hermann Michael 
Published: April 2006

AbstractUntil now no one has outlined the matrimonial politics of the Davidic dynasty as a whole. A closer look reveals these policies to be a clear-cut means of stabilizing David's dynasty and expanding its territory and power. As far as we know, all of the marriages of Davidic crown-princes are comprehensible in the political and regional context of the time. In every case, choosing the bride for the crown-prince of Jerusalem and Judah was politically goal oriented. Selection of the royal bride throws light on the sometimes weaker, sometimes stronger (more independent) position of the kings as well as the possibilities and aims of Davidic politics. Mentioning the kings's mothers makes clear that the Bible can supply valuable information for the investigation of the history of Israel and Judah.
The enigmatic plurals like "one of us" (Genesis i 26, iii 22, and xi 7) in hyperchronic perspective
Authors: Eslinger Lyle 
Published: April 2006

AbstractThe enigma of the first person plural pronouns in Gen. i 26, iii 22, and xi 7 can be resolved by careful consideration of their rhetorical and hyperchronic contexts. All three instances emanate from the same speaker in similar situations. Their common rhetorical purpose is to mark out the ontological boundaries between gods and humans. The first person plurals schematize the "we," of "the gods," versus the "them," of "the humans."