bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGA Molecules in Neuroblastic Tumors
Authors: CERIGNOLI F , AMBROSI C , MELLONE M , ASSIMI I , Di MARCOTULLIO LUCIA , GULINO A , GIANNINI G
Published: January 2005

Abstract: The high mobility group A (HMGA) proteins are thought to work as ancillary transcription factors and to regulate the expression of a growing number of genes through direct binding to DNA or via protein‐protein interactions. Both HMGA1 and HMGA2 are important regulators of basic biological processes, including cell growth, differentiation and transformation. Their qualitatively or quantitatively altered expression has been described in a number of human tumors. We studied and review here their expression in neuroblastic tumors. HMGA2 is expressed only in a subset of ex vivo neuroblastoma (NB) tumors and in the embryonic adrenal gland, but it is undetectable in the adult adrenal gland, suggesting that its anomalous expression might be associated with NB tumorigenesis and/or tumor progression. In vitro, its expression is easily detectable in retinoic acid (RA)‐resistant cell lines. The exogenous expression of HMGA2 is sufficient to convert RA‐sensitive SY5Y NB cells into RA‐resistant cells, thus suggesting that HMGA2 might be a relevant player in determining NB cell responses to endogenous or therapeutically important growth inhibitory substances. In contrast, HMGA1 expression is readily detectable in all NB cell lines and tumors, but its expression is consistently higher in less differentiated NBs compared with ganglioneuromas and ganglioneuroblastomas. Interestingly, RA increases HMGA1 expression in RA‐resistant NB cells but inhibits it in cells undergoing RA‐induced growth inhibition and neuronal differentiation. Our studies indicate that HMGA molecules might be biologically and pathologically relevant factors in neuroblastic tumor development and progression.
Angiogenesis in Neuroblastoma
Authors: RIBATTI DOMENICO , MARIMPIETRI DANILO , PASTORINO FABIO , BRIGNOLE CHIARA , NICO BEATRICE , VACCA ANGELO , PONZONI MIRCO
Published: January 2005

Abstract: Angiogenesis is a biological process by which new capillaries are formed from preexisting vessels. It occurs in physiological and pathological conditions, such as tumors, where a specific turning point is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells able to stimulate the growth of the host's blood vessels. In neuroblastoma, the most common extracranial solid tumor of infancy and childhood, angiogenesis also appears to play an important role in determining tumor phenotype. The nature of the angiogenic balance in neuroblastoma is complex, and a spectrum of angiogenesis stimulators, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor‐2 (FGF‐2), and inhibitors, such as tissue inhibitors of matrix metalloproteinases (MMPs), have been detected in neuroblastoma tumors. Moreover, an increased production of MMP‐2 and ‐9 has been also observed in advanced stages of tumor, favoring degradation of extracellular matrix and enhancing tumor dissemination. High tumor vascularity is correlated with widely disseminated disease, MYCN amplification, unfavorable histology, and poor outcome. In contrast, low tumor vascularity is associated with prognostically favorable features, such as a localized disease and favorable histology. It is becoming increasingly evident that agents that interfere with blood vessel formation also block tumor progression. Preclinical studies suggest that antiangiogenic strategies may be effective in the treatment of neuroblastoma. A major goal is the determination of whether inhibition of angiogenesis is a realistic way of inhibiting tumor cell dissemination and formation of metastasis in neuroblastoma.
Mechanism of Induction of Apoptosis by p73 and Its Relevance to Neuroblastoma Biology
Authors: ROSSI MARIO , SAYAN A EMRE , TERRINONI ALESSANDRO , MELINO GERRY , KNIGHT RICHARD A.
Published: January 2005

Abstract: TP73, as a TP53 homologue, drew the attention of tumor biologists because it is rarely mutated in human cancers and can induce cell cycle arrest and apoptosis by activating genes also regulated by p53. However, TP73 harbors an additional promoter that produces a dominant negative p73 protein (ΔNp73) having the opposite effect of the TAp73 protein. Thus, the regulation of p53 responsive genes in the absence of p53 relies on a critical balance between different p73 gene‐derived proteins. Recent reports have described additional complexity in the mechanism of action of transcriptionally active p73 (TAp73) in the induction of cell death. The molecular mechanism through which p73 induces apoptosis involves (i) expression and changes in subcellular localization of scotin, producing an endoplasmic reticulum (ER) stress; and (ii) transactivation of PUMA and Bax, thus determining cell fate. On the contrary, ΔNp73 inhibits apoptosis, thus contributing to the oncogenic potential of neuroblastoma cells.
Caspase‐8 Gene Expression in Neuroblastoma
Authors: CASCIANO IDA , BANELLI BARBARA , CROCE MICHELA , DE AMBROSIS ALESSANDRO , Di VINCI ANGELA , GELVI ILARIA , PAGNAN GABRIELLA , BRIGNOLE CHIARA , ALLEMANNI GIORGIO , FERRINI SILVANO , PONZONI MIRCO , ROMANI MASSIMO
Published: January 2005

Abstract: Neuroblastoma (NB) is a solid tumor of infancy that presents a high rate of spontaneous regression, a phenomenon that likely reflects the activation of an apoptotic/differentiation program. Indeed, the level of expression of molecules involved in the regulation of apoptosis, such as p73 or survivin, is a prognostic factor in NB patients. The caspase‐8 gene (CASP8) encodes a key enzyme at the top of the apoptotic cascade. Although methylation of a putative regulatory region of the CASP8 gene reportedly inhibits its transcription in some MYCN‐amplified NB, our results indicate that the transcriptional inactivation of caspase‐8 occurs in a subset of primary NB independently of MYCN amplification or CpG methylation. In addition, the apoptotic agent fenretinide (4HPR) and interferon‐γ (IFN‐γ) induce caspase‐8 expression without modifying the methylation status of this gene. Nevertheless, the methylation level of CASP8 intragenic and promoter regions is higher in MYCN‐amplified tumors as compared to nonamplified samples. This phenomenon might reflect the existence of distinct DNA methylation errors in MYCN‐amplified and MYCN‐single copy tumors. To gain information on the mechanisms that regulate the expression of this crucial apoptotic gene, we searched for potential CASP8 regulatory regions and cloned a DNA element at the 5′ terminus of this gene that functionally acts as a promoter only in NB cell lines that express caspase‐8. The retinoic acid analogue 4HPR, IFN‐γ, and the demethylating agent 5‐aza‐cytidine activate this promoter in NB cells that lack endogenous caspase‐8, indicating that this element may regulate both constitutive and inducible CASP8 expression. These results indicate also that demethylation of the cellular genome may upregulate CASP8 through the action of trans‐acting factors. Our results provide new insights to the regulation of CASP8, a gene with an essential role in a variety of physiologic and pathologic conditions.
Oncogenic Kinase Signaling in Human Neoplasms
Authors: TSATSANIS CHRISTOS , SPANDIDOS DEMETRIOS A.
Published: January 2005

Abstract: Oncogenic proteins participate in cellular functions that involve transduction of signals from the extracellular environment, through the membrane, into the cytoplasm towards the nucleus, where transcription is initiated to generate proteins that will eventually contribute to the oncogenic phenotype. The wild‐type homologues of cellular oncoproteins (proto‐oncoproteins) frequently participate in signal transduction mechanisms that regulate cell and tissue homeostasis. Deregulation of proto‐oncoprotein expression or function results in altered cellular signaling, oncogenic transformation, and inhibition of apoptosis. Oncogenic signals initiated from mutant proteins can override endogenous homeostasis control mechanisms such as anoikis and apoptosis and result in anchorage‐independent growth, uncontrolled proliferation, and metastasis.
Ignored Hallmarks of Carcinogenesis: Stem Cells and Cell‐Cell Communication
Authors: TROSKO JAMES E. , CHANG CHIA‐CHENG , UPHAM BRAD L. , TAI MEI‐HU
Published: January 2005

Abstract: Hanahan and Weinberg (2000, Cell 100: 57‐70) listed “hallmarks” of cancer that must be considered in order to understand the underlying determinants of carcinogenesis: (a) self‐sufficiency in growth signals; (b) insensitivity to growth‐inhibitory (antigrowth) signals; (c) evasion of programmed cell death (apoptosis); (d) limitedless replicative potential; (e) sustained angiogenesis; and (f) tissue invasion and metastasis. While these are important phenotypic markers, important concepts—the role of pluripotent stem cells and gap junctional intercellular communication (GJIC)—must be brought into this analysis of carcinogenesis. Carcinogenesis is a multistage, multimechanism process consisting of a single cell that has been irreversibly blocked from terminal differentiation (the initiation stage). The promotion phase is a potentially reversible or interruptible clonal expansion of the initiated cell by a combination of growth stimulation and inhibition of apoptosis. When the expanded initiated cells accrue sufficient mutations and epigenetic alterations to become growth stimulus independent and resistant to growth inhibitors and apoptosis, to have unlimited replicative potential and invasive and metastatic phenotypes, then the progression phase has been achieved. The hypothesis that integrates these hallmarks is that the stem cell and its early progenitor cell are the target cells for the initiation event. These cells are naturally immortal and become mortal only when they are induced to terminally differentiate and lose their telomerase activity. These two types of initiated cells are suppressed by either secreted negative growth regulators (the stem cells) or GJIC (the early initiated progenitor cells). Promoters inhibit either the secreted growth inhibitor to initiated stem cells or GJIC between the initiated progenitor cells and the normal progenitor cells. When a stable resistance to the secreted negative growth regulator or permanent downregulation of GJIC has occurred, the cell has entered the progression phase. These two new concepts contradict the current paradigm that the first phase of carcinogenesis is the immortalization of a normal cell followed by its neoplastic transformation. Our hypothesis is that the first stage of carcinogenesis must prevent the “mortalization” or terminal differentiation of a naturally immortal cell. Chemoprevention and chemotherapeutic implications suggest that one must induce connexin genes in initiated stem cells and restore GJIC in initiated early progenitor cells.
Intercellular Communication and Human Hepatocellular Carcinoma
Authors: CARRUBA GIUSEPPE , COCCIADIFERRO LETIZIA , BELLAVIA VINCENZO , RIZZO SERGIO , TSATSANIS CHRISTOS , SPANDIDOS DEMETRIOS , MUTI PAOLA , SMITH COLIN , MEHTA PARMENDER , CASTAGNETTA LUIGI
Published: January 2005

Abstract: We have previously reported that gap junction‐mediated intercellular communication (GJIC) can be restored in junctionally deficient human prostate epithelial cells, also suggesting that GJIC activity is regulated by estrogen. In the present work, we report studies on sex steroid regulation of GJIC and proliferative activity in both nontumoral (Chang liver, CL) and malignant (HepG2, Huh7) human liver cells. Junctional activity and liver cell growth were measured using the scrape‐loading/dye‐transfer (SL/DT) and the MTS assay, respectively. Using the SL/DT, only Huh7 cells exhibited a moderate degree of junctional activity in basic conditions, while neither CL nor HepG2 cells showed functional GJIC. Under exactly the same experimental approach used for prostate studies, we observed that, once again, both estrogen (either estradiol or estrone) and FK induce a significant increase of GJIC in Huh7 cells, while exposure of HepG2 cells to FK produces only a limited rise of junctional activity in this cell line. However, estrogen induced a significant increase and reduction of the proliferative activity of CL and Huh7 cells, respectively, while growth of HepG2 cells was not affected. While the above evidence suggests that estrogens are primarily implicated in growth regulation and communication of both prostate and liver epithelial cells, it also implies that compounds able to restore GJIC in junctionally deficient cells or prevent its disruption in junctionally proficient cells may be used for development of new strategies in the prevention and/or treatment of several human malignancies, including hepatocellular carcinoma (HCC).
Steroids as Procarcinogenic Agents
Authors: BRADLOW H LEON , SEPKOVIC DANIEL W.
Published: January 2005

Abstract: Although hormones produced in the body are normally considered to be beneficial in such matters as life, male and female development, fertility, and blood pressure regulation, these same compounds can act in some circumstances as carcinogens or carcinogen facilitators, In some such cases increased amounts of the hormone or changes in the formation of its metabolites might be responsible. In other cases the timing of hormone release plays a critical role. In some cases the hormone acts independently, while in others two or more compounds act in concert to promote cancer. The various compounds will be discussed separately, since they usually cause different kinds of cancer. Of the various hormones produced in the body, only aldosterone does not cause any cancers, although excess aldosterone can cause Conn's syndrome, which may be detected by the resultant hypertension.
A Unifying Mechanism in the Initiation of Cancer and Other Diseases by Catechol Quinones
Authors: CAVALIERI ERCOLE L. , ROGAN ELEANOR G.
Published: January 2005

Abstract: The first step in cancer initiation is the reaction of chemical carcinogens with DNA to form stable adducts, which remain in DNA unless removed by repair, and depurinating adducts, which detach from DNA following destabilization of the glycosyl bond. Depurinating DNA adducts of polycyclic aromatic hydrocarbons play a major role in the initiation of cancer, as shown by the correlation between depurinating adducts and oncogenic mutations of the H‐ras oncogene in mouse skin. Following these results, experiments on the metabolism of estrogens, formation of depurinating DNA adducts, carcinogenicity, mutagenicity, and cellular transformation have led us to the hypothesis that certain metabolites of endogenous estrogens—in particular, estradiol(estrone)‐3,4‐quinones—can react with DNA to form depurinating adducts at the N‐3 of Ade and the N‐7 of Gua. Depurination of these adducts can generate critical mutations by error‐prone repair to initiate breast, prostate, and other cancers. The oxidation mechanism of catechols to quinone compounds includes not only natural estrogens, but also synthetic estrogens, such as hexestrol and the human carcinogen diethylstilbestrol, which react with DNA to form N3Ade and N7Gua adducts, presumably to initiate cancer. Furthermore, the initiating mechanism of the leukemogen benzene involves oxidation of catechol to catechol quinone, which reacts with DNA to form N3Ade and N7Gua adducts. The quinone of the neurotransmitter dopamine can also react with DNA to form N3Ade and N7Gua adducts. The subsequent mutations could be at the origin of Parkinson's and other neurodegenerative diseases. In summary, the apurinic sites produced in DNA from the loss of these depurinating adducts can be converted into mutations by error‐prone repair, which may initiate cancer and other diseases.
Expression of IAPs and Alternative Splice Variants in Hepatocellular Carcinoma Tissues and Cells
Authors: NOTARBARTOLO MONICA , CERVELLO MELCHIORRE , GIANNITRAPANI LYDIA , MELI MARIA , POMA PAOLA , DUSONCHET LUISA , MONTALTO GIUSEPPE , D'ALESSANDRO NATALE
Published: January 2005

Abstract: IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.
Virokines in the Pathogenesis of Cancer: Focus on Human Herpesvirus 8
Authors: KLOUCHE MARIAM , CARRUBA GIUSEPPE , CASTAGNETTA LUIGI , ROSE‐JOHN STEFAN
Published: January 2005

Abstract: During evolution, DNA viruses have captured a broad array of cellular genes involved in immune recognition and growth control that are nonessential for viral replication. The encoded virokines and viroceptors may act as mimetics or antagonists of their cellular homologues, altering signal transduction and cell communication towards survival of virus‐infected cells. Human herpesvirus type 8 (HHV8) is the most recently identified human oncogenic herpesvirus. It is associated with Kaposi's sarcoma and lymphoproliferative diseases, such as pleural effusion lymphomas and multicentric Castleman's disease. HHV8 has captured a unique number of cellular regulatory genes, which redirect gene expression and cell growth, prevent apoptosis and immune recognition, and interfere with tumor suppressor gene function. HHV8 encodes a unique virokine, viral interleukin‐6, which is particularly relevant for the pathogenesis of HHV8‐associated tumors, since it participates in transformation and mediates autocrine and paracrine mitogenic and proinflammatory effects. Viral IL‐6 differs fundamentally from human IL‐6 in receptor engagement for signal transduction and thus constitutes a singular model to understand the facets of human and viral cytokine biology. We provide an overview of the role of virokines in cancer, with a particular focus on the differences of human and viral IL‐6 in the pathophysiology of HHV8‐associated tumors.
Transdisciplinarity: A Scientific Essential
Authors: HAMBERGER ERICH
Published: January 2005

Abstract: Transdisciplinarity in science is necessary to counteract the rapid growth of scientific results and information, the elimination of logical inconsistencies, and the effect of specialization whereby uncomparable disciplines develop. A correspondence is drawn between the uncontrolled growth, immune system malfunction, repression/expansion, and isolation that are characteristic of cancer and of the scientific concept of modernity. Suggestions are presented regarding the promotion of healing in both of these realms.
Immunotherapy of Melanoma Targeting Human High Molecular Weight Melanoma‐Associated Antigen: Potential Role of Nonimmunological Mechanisms
Authors: CHANG CHIEN‐CHUNG , CAMPOLI MICHAEL , LUO WEI , ZHAO WANZHOU , ZAENKER KURT S. , FERRONE SOLDANO
Published: January 2005

Abstract: Induction of humoral anti‐human high molecular weight melanoma‐associated antigen (anti‐HMW‐MAA) immunity following active specific immunotherapy is associated with a statistically significant prolongation of survival in patients with melanoma. This association does not appear to be mediated by immunological mechanisms because anti‐HMW‐MAA antibodies are poor mediators of complement‐ and cell‐mediated cytotoxicity of melanoma cells. Therefore, we have been investigating nonimmunological mechanisms by which anti‐HMW‐MAA antibodies (Abs) affect the biology of melanoma cells. We have demonstrated that anti‐HMW‐MAA mAbs interfere with the interaction of HMW‐MAA with extracellular matrix (ECM) components, a process known to be crucial in the early phase of melanoma metastasis. Furthermore, anti‐HMW‐MAA mAbs appear to block the series of signal transduction events triggered by the interaction of HMW‐MAA with ECM. They include the activation of the family of Rho GTPases, p130cas, and focal adhesion kinase (FAK). These findings parallel the inhibition of the rat homologue of HMW‐MAA NG2 function by anti‐NG2 antibodies. Taken together, all these results provide a mechanistic explanation not only for the therapeutic effect of anti‐HMW‐MAA antibodies in the treatment of melanoma, but also for the function of HMW‐MAA in the biology of melanoma cells. This information is expected to serve as a useful background to design effective HMW‐MAA‐targeted immunotherapy in patients with melanoma.
Expression of WISPs and of Their Novel Alternative Variants in Human Hepatocellular Carcinoma Cells
Authors: CERVELLO MELCHIORRE , GIANNITRAPANI LYDIA , LABBOZZETTA MANUELA , NOTARBARTOLO MONICA , D'ALESSANDRO NATALE , LAMPIASI NADIA , AZZOLINA ANTONINA , MONTALTO GIUSEPPE
Published: January 2005

Abstract: WISPs (Wnt‐induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine‐rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT‐PCR in four human HCC cell lines (HepG2, HuH‐6, HuH‐7, HA22T/VGH). Our results show for the first time that WISP1, WISP1v, and WISP3 are expressed in HCC cell lines. Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1Δex3‐4 and WISP3vL. Overall, our study suggests that WISP transcripts may have a role in the development of HCC, although further studies are necessary to clarify the relative importance of the expression of wild‐type WISPs, as well as of their novel variants, in this tumor type.
Expression Levels and Clinical‐Pathological Correlations of HER2/neu in Primary and Metastatic Human Breast Cancer
Authors: STEFANO ROSALBA , AGOSTARA BIAGIO , CALABRÒ MAURIZIO , CAMPISI ILDEGARDA , RAVAZZOLO BARBARA , TRAINA ADELE , MIELE MONICA , CASTAGNETTA LUIGI
Published: January 2005

Abstract: In this retrospective study we assessed the expression of the HER2/neu oncogene product in a series of 574 consecutive breast cancer cases, all recruited at the Maurizio Ascoli Cancer Center of Civico Hospital, in Palermo, between January 1998 and June 2003. The HER2/neu expression was evaluated using immunohistochemistry and scored from 0 to +3 as per FDA recommendations. The HER2/neu expression levels were related to the clinical‐pathological features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors, and hormonal or chemotherapeutic treatment. In 108 patients with a follow‐up period of 3 years or more, the HER2/neu expression was also related to their survival characteristics. A significant correlation (P= 0.011) between HER2/neu +3 and estrogen receptor‐negative cases was observed in the 487 M0 patients. In addition, HER2/neu +3 cases were associated with a positive nodal status (57.4%), although this association was not quite significant (P= 0.06). More importantly, follow‐up data revealed that, in the 91 M0 patients with an average follow‐up period of 37 months, the percentage of HER2/neu +3 patients who relapsed was remarkably greater (54.8%) than that observed for the HER2/neu +1/0 cases when combined (34.2%). Furthermore, the disease‐free interval (DFI) was 47 months in the HER2/neu +1/0 group, while it dropped to 45 months in c‐HER2/neu +3 cases. Although the limited number of cases does not allow us to draw any definitive conclusions, our data suggest that high expression levels of HER2/neu +3 are associated with an early relapse and a shorter disease‐free interval in M0 breast cancer patients.
Antioxidant Betalains from Cactus Pear (Opuntia ficus‐indica) Inhibit Endothelial ICAM‐1 Expression
Authors: GENTILE C , TESORIERE L , ALLEGRA M , LIVREA M A , D'ALESSIO P
Published: January 2005

Abstract: It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress‐correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine‐induced redox state alteration, through ICAM‐1 inhibition.
Glypicans shunt the Wingless signal between local signalling and further transport
Authors: Franch-Marro Xavier , Marchand Oriane , Piddini Eugenia , Ricardo Sara , Alexandre Cyrille , Vincent Jean-Paul
Published: January 2005

The two glypicans Dally and Dally-like have been implicated in modulating the activity of Wingless, a member of the Wnt family of secreted glycoprotein. So far, the lack of null mutants has prevented a rigorous assessment of their roles. We have created a small deletion in the two loci. Our analysis of single and double mutant embryos suggests that both glypicans participate in normal Wingless function, although embryos lacking maternal and zygotic activity of both genes are still capable of transducing the signal from overexpressed Wingless. Genetic analysis of dally-like in wing imaginal discs leads us to a model whereby, at the surface of any given cell of the epithelium, Dally-like captures Wingless but instead of presenting it to signalling receptors expressed in this cell, it passes it on to neighbouring cells, either for paracrine signalling or for further transport. In the absence of dally-like, short-range signalling is increased at the expense of long-range signalling (reported by the expression of the target gene distalless) while the reverse is caused by Dally-like overexpression. Thus, Dally-like act as a gatekeeper, ensuring the sharing of Wingless among cells along the dorsoventral axis. Our analysis suggests that the other glypican, Dally, could act as a classical co-receptor.
“Mechanics” of Molecular Assembly: Real-Time and In-Situ Analysis of Nano-to-Mesoscopic Scale Hierarchical Structures and Nonequilibrium Phenomena
Authors: Hashimoto Takeji
Published: January 2005

We have presented studies of the mechanics of molecular assembly for multicomponent molecular systems in the context of nonlinear and nonequilibrium phenomena. The studies cover the following three themes: (i) elucidation of space-time self-assembly of hierarchical structures, in the length scale ranging from nm to μm, of binary molecular mixtures via phase transition by means of real-time and in-situ analyses with various scattering methods and microscopy methods; (ii) elucidation of self-assembly of molecular mixtures under shear flow in the context of open nonequilibrium phenomena by means of newly developed rheo-optical methods, leading us to discover new dissipative structures as well as shear-induced phase transitions both from single-phase to two-phase and from two-phase to single-phase; (iii) elucidation of the influences of chemical bonds between different component polymers in block copolymers on microphase transition and ordered microdomain structures with nano-scale periodicity and various space-group symmetries and exploration of nano-fabrication methods of microdomain structures as templates in the context of nano-science and nano-technology of block copolymers. In each of the three themes, we highlight and emphasize the fact that polymer systems provide very good model systems for basic studies of nonlinear and nonequilibrium phenomena because of the fact that large structures evolve very slowly in polymer systems. The studies may give perspectives for creating advanced soft materials responsive to environmental stimuli and for understanding activities, adaptation, and evolution of living organisms.
Synthesis and Characterization of New Metal–Metal Bonded Heptabromo Porphyrin
Authors: Takagi Shigeru , Furuta Hiroyuki , Yagi Toshitaka , Yamada Hiroyuki
Published: January 2005

A new metal–metal bonded porphyrin [(hbtbpp)In–Mn(CO)5], where hbtbpp is the dianion of 2,3,7,8,12,13,17-heptabromo-5,10,15,20-tetrakis(3,5-di-t-butylphenyl)porphyrin, has been synthesized. In our attempt to synthesize the indium complex of octabromo porphyrin using the DMF method, we found that Br atom loss occurred in the process of metal insertion. When having synthesized the metal–metal bonded porphyrin by using a mixture of (heptabromoporphyrinato)indium and (octabromoporphyrinato)indium as the starting material, only heptabromo M–M bonded porphyrin was obtained. A large ring deformation of octabromo porphyrin disturbed the formation of the M–M bond. This heptabromo M–M porphyrin has shown high stability against electroreduction or photo-irradiation.
Synthesis, Characterization, and Thermal Stability of New Mononuclear Hydrogenperoxocopper(II) Complexes with N3O-Type Tripodal Ligands Bearing Hydrogen-Bonding Interaction Sites
Authors: Yamaguchi Syuhei , Kumagai Akinori , Nagatomo Shigenori , Kitagawa Teizo , Funahashi Yasuhiro , Ozawa Tomohiro , Jitsukawa Koichiro , Masuda Hideki
Published: January 2005

In order to understand the effect of an oxygen-containing ligand on the physico-chemical properties and reactivities of hydrogenperoxocopper complexes, new copper(II) complexes with the N3O-type tripodal ligand bearing pivalamido groups, N,N-bis(6-pivalamido-2-pyridylmethyl)glycine (Hbpga), and N,N-bis(6-pivalamido-2-pyridylmethyl)-β-alanine (Hbpaa), have been designed and synthesized. Copper(II) complexes without any external ligand and those with a monodentate ligand, such as azido and chloro, have been prepared and characterized with the aid of electronic absorption and ESR spectroscopic, cyclic voltammetric, and X-ray structure analytical methods. The redox potential values of the Cu(II) complexes, when they were compared with the Cu(II) complex of bis(6-pivalamido-2-pyridylmethyl)(2-pyridylmethyl)amine (bppa), reported previously, shifted toward the negative side upon the introduction of a carboxylate group in the place of one pyridine of bppa. Reactions of [Cu(bpga)]ClO4 (1a) and [Cu(bpaa)]PF6 (2a) with hydrogen peroxide in the presence of triethylamine in both MeCN and MeOH solutions gave mononuclear copper(II) complexes with hydrogenperoxide(1−), Cu–bpga–OOH (1d) and Cu–bpaa–OOH (2d) systems, respectively. The intense absorption bands, assignable to LMCT (HOO− → Cu(II)) and d–d bands, and ESR and resonance Raman spectra have revealed that they form trigonal bipyramidal copper complexes with OOH− in an end-on fashion. The thermal stabilities of 1d and 2d have also been studied by following the reduction rate of the LMCT bands at 283 K. Those of copper(II) complexes with hydrogenperoxide(1−) have been reduced in the order 1d > 2d >> [Cu(bppa)(OOH)]+ (3d), all of which are rather stable compared with that of Cu(II)–tpa–OOH (tpa = tris(2-pyridylmethyl)amine). These findings indicate that the hydrogenperoxocopper(II) complexes are activated by introducing carboxylate coordination, although they are stabilized by hydrogen-bonding interactions.
An Alkoxide-Bridged Dinuclear Zinc(II) Hexaazacryptate: A Novel Phosphate Capture Molecule in Aqueous Solution
Authors: Kinoshita Eiji , Ishikawa Kouhei , Kinoshita-Kikuta Emiko , Ohtani Kazuhiro , Shiro Motoo , Koike Tohru
Published: January 2005

A novel dinuclear zinc(II) hexaazacryptate (Zn2L3+) has been synthesized as a phosphate capture molecule in aqueous solution (L = an alkoxide form of 4,16-(2-hydroxypropano)-1,4,7,13,16,19-hexaazacyclotetracosane). Potentiometric pH titration study disclosed a 1:1 phenyl phosphate complexation with Zn2L3+. The dissociation constant, Kd ( = [Zn2L3+][PhOPO32−]/[Zn2L3+–PhOPO32−]) is a small value of 6 × 10 − 7 M at 35 °C with I = 0.10 (NaNO3). The X-ray crystal analysis of the p-nitrophenyl phosphate complex with Zn2L3+ showed that the phosphate dianion binds as a bridging ligand to the two zinc(II) ions. The analogous 1:1 CH3COO−-bound Zn2L3+ complex was isolated and characterized by X-ray analysis.
Selective Nitration of Thiacalix[4]arene and an Investigation of Its Acid–Base Properties with a Chemometric Method
Authors: Hu Xiaojun , Shi Huijie , Shi Xianfa , Zhu Zhongliang , Sun Qiuhong , Li Yong , Yang Haijun
Published: January 2005

The selective dinitro-substituted derivative of thiacalix[4]arene was synthesized by a three-step route and characterized. Its acid–base properties in a water solution were studied by UV–vis spectroscopy. Its four pKa values were determined by Target Testing Factor Analysis (TTFA).
Synthesis and Structural Analysis of Oligo(naphthalene-2,3-diyl)s
Authors: Motomura Takahisa , Nakamura Hideko , Suginome Michinori , Murakami Masahiro , Ito Yoshihiko
Published: January 2005

Oligo(naphthalene-2,3-diyl)s are synthesized by the palladium-catalyzed cross-coupling reactions of 2-naphthylzinc compounds with 2-bromonaphthalene derivatives. An NMR analysis together with an X-ray diffraction study supports the conjecture that the helical secondary structure is a common feature of the assemblies in which naphthalene-like aromatic units are linked together between the β-positions in series.
Aqueous Ammonia as a New Activator for Sonogashira Coupling
Authors: Mohamed Ahmed Mohamed S , Sekiguchi Akitoshi , Masui Kentaro , Mori Atsunori
Published: January 2005

Sonogashira coupling, which is a coupling reaction of terminal alkynes with organic halides, takes place with dilute aqueous ammonia as an activator. The reaction of several terminal alkynes and aryl iodides in the presence of small excess of aqueous ammonia at room temperature furnishes the cross-coupling product in good-to-excellent yields. A water-soluble amine with a high boiling point is alternatively employed for reactions at higher temperatures. A related coupling reaction in the presence of carbon monoxide also proceeded at room temperature and under ambient pressure to afford α,β-alkynyl ketones efficiently.
Formation of Active Sites for the NO + CO Reaction over Palladium Catalysts Supported on Mesoporous Silica
Authors: Yamaguchi Aritomo , Hayashi Takamitsu , Oyaizu Kenichi , Yuasa Makoto
Published: January 2005

The catalytic activities and structural changes of Pd containing mesoporous silica (Pd/MCM-41) catalysts for the NO + CO reaction were investigated. Pd/MCM-41 after calcination in air showed a very high catalytic activity for the NO + CO reaction because Pd metal particles with an appropriate size for the reaction were formed by the reaction gases.
Synthesis, Structures, and Reactions of Coordinatively Unsaturated Trinuclear Ruthenium Polyhydrido Complexes, [{Ru(C5Me5)}3(μ-H)6](Y) (Y = BF4, CF3SO3, 1/2(SO4), C6H5CO2, CH3CO2, B(C6H5)4, PF6) and [{Ru(C5Me5)}3(μ-H)3(μ3-H)2]
Authors: Suzuki Hiroharu , Kakigano Takeaki , Tada Ken-ichi , Igarashi Minoru , Matsubara Kouki , Inagaki Akiko , Oshima Masato , Takao Toshiro
Published: January 2005

Cationic triruthenium hexahydrido complexes, [{Ru(C5Me5)}3(μ-H)6](Y) (Y = BF4, CF3SO3, 1/2(SO4), C6H5CO2, CH3CO2), have been synthesized by the reaction of diruthenium tetrahydride [{Ru(C5Me5)}2(μ-H)4] with the corresponding acid, HBF4, CF3CO2H, H2SO4, C6H5CO2H, and CH3CO2H. The trimeric structure of these complexes has been confirmed by a crystallographic study of [{Ru(C5Me5)}3(μ-H)6](PF6). The treatment of [{Ru(C5Me5)}3(μ-H)6](Y) with CH3ONa in methanol selectively afforded a neutral trinuclear pentahydrido complex, [{Ru(C5Me5)}3(μ-H)3(μ3-H)2], which underwent an intermolecular H/D exchange reaction with benzene-d6, toluene-d8, or o-xylene-d10 to give [{Ru(C5Me5)}3(μ-D)3(μ3-D)2] as the result of arene C–H bond activation via an η2-arene intermediate complex. A cationic hydrido complex, [{Ru(C5Me5)}3(μ-H)6](Y), having a carboxylate as a counter anion was equilibrated with [{Ru(C5Me5)}3(μ-H)3(μ3-H)2] in solution, and the equilibrium constant depended on the counter anion. An X-ray diffraction study showed that [{Ru(C5Me5)}3(μ-H)3(μ3-H)2] has a triangular reaction field surrounded by three C5Me5 ligands. The reaction of [{Ru(C5Me5)}3(μ-H)3(μ3-H)2] with 1 equiv of O2 proceeded with the retention of the Ru3 framework to yield an 80/20 mixture of a mono-μ3-oxo complex [{Ru(C5Me5)}3(μ-H)3(μ3-O)] and a di-μ3-oxo complex [{Ru(C5Me5)}3(μ-H)3(μ3-O)2]. A novel trinuclear μ3-iodo-tetra-μ-hydrido complex, [{Ru(C5Me5)}3(μ3-H)(μ-H)3(μ3-I)] was formed upon the treatment of [{Ru(C5Me5)}3(μ-H)3(μ3-H)2] with 1 equiv of CH3I in tetrahydrofuran. The treatment of [{Ru(C5Me5)}3(μ-H)3(μ3-H)2] with carbon monoxide generated a paramagnetic trinuclear tetracarbonyl complex, [{Ru(C5Me5)}3(μ-CO)3(μ3-CO)].
Effective scCO2-ionic Liquid Reaction System Based on Symmetric Aliphatic Ammonium Salts for the Rapid CO2 Fixation with Aziridine to 2-Oxazolidinone
Authors: Kawanami Hajime , Matsumoto Hajime , Ikushima Yutaka
Published: January 2005

The hybrid reaction system composed of supercritical carbon dioxide and room temperature ionic liquid based on symmetric tetraalkyl ammonium salts can effectively promote the carbon dioxide fixation from aziridine to 2-oxazolidinone in the presence of iodine in high yield of 98% within 5 min. The TOF value under this condition is 254 times larger than that using conventional organic solvent.
Thiocyanate-selective PVC Membrane Electrode Based on Tricoordinate Schiff Base Copper(II) Complex
Authors: Dai Jian-Yuan , Chai Ya-Qin , Yuan Ruo , Zhang Yi-Sen , Liu Yan , Zhong Xia , Tang Dian-Ping
Published: January 2005

A new thiocyanate selective PVC membrane electrode was prepared by using a tricoordinate dimethylaminobenzaldehyde Schiff base copper(II) complex as neutral carrier, which demonstrates highly selectivity response to thiocyanate with substantially improved performance such as long lifetime, wide potentiometric response range, and low detection limit.
One Pot Synthesis of Photochromic Maleic Anhydride Derivatives
Authors: Yamaguchi Tadatsugu , Irie Masahiro
Published: January 2005

Photochromic 2-aryl-3-(1-propenyl)maleic anhydride derivatives were synthesized by one pot synthesis and their photochromic performance was examined in solution.
Temperature Dependence on the Activation Energy of Dechlorination in Thermal Degradation of Polyvinylchloride
Authors: Yoshioka Toshiaki , Saitoh Nobuo , Okuwaki Akitsugu
Published: January 2005

The dechlorination of polyvinylchloride (PVC) powder initially progressed on an apparent zero order reaction, and proceeded in higher dechlorination range by an apparent first order reaction. The apparent activation energies indicate that the rate of the dehydrochlorination is controlled by the chemical reaction at low temperature, but that from 300 to 400 °C is controlled by heat transfer rate.
A Novel Patterning Method of Low-resistivity Metals
Authors: Noh Chang-Ho , Son Hae-Jung , Kim Jin-Young , Hwang Ok-Chae , Song Ki-Yong , Byk T V , Sokolov V G , Kim Jin-Baek
Published: January 2005

Photocatalytic layers of amorphous TiO2 and polyvinyl alcohol were used for the patterning of low-resistivity metals such as copper and silver without using high cost materials and equipment.
When the Boards Fail Us—Structural Bias in Certification Examinations
Authors: Kuruvilla Pramita
Published: February 2024

This essay shines a light on structural bias inherent to the board certification examination process, sharing the author's experience preparing and sitting for the examination while contending with co-occurring challenging life events.
Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis
Authors: Huang Huei-Kai , Chuang Albert Tzu-Ming , Liao Tzu-Chi , Shao Shih-Chieh , Liu Peter Pin-Sung , Tu Yu-Kang , Lai Edward Chia-Cheng
Published: February 2024

Importance

Denosumab, a humanized monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is a widely used antiresorptive medication for osteoporosis treatment. Recent preclinical studies indicate that inhibition of RANKL signaling improves insulin sensitivity, glucose tolerance, and β-cell proliferation, suggesting that denosumab may improve glucose homeostasis; however, whether denosumab reduces the risk of incident diabetes remains unclear.

Objective

To evaluate whether denosumab use is associated with a lower risk of developing diabetes in patients with osteoporosis.

Design, Setting, and Participants

This nationwide, propensity score–matched cohort study used administrative data from Taiwan’s National Health Insurance Research Database. Adult patients who received denosumab for osteoporosis therapy in Taiwan between 2012 and 2019 were included. To eliminate the inherent bias from confounding by indication, the patients were categorized into a treatment group (34 255 patients who initiated denosumab treatment and adhered to it) and a comparison group (34 255 patients who initiated denosumab treatment but discontinued it after the initial dose) according to the administration status of the second dose of denosumab. Propensity score matching was performed to balance patient characteristics and to control for confounders.

Exposure

Treatment with denosumab.

Main Outcomes and Measures

The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. A Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident diabetes. Data were analyzed from January 1 to November 30, 2023.

Results

After propensity score matching, 68 510 patients were included (mean [SD] age, 77.7 [9.8] years; 57 762 [84.3%] female). During a mean (SD) follow-up of 1.9 (1.6) years, 2016 patients developed diabetes in the treatment group and 3220 developed diabetes in the comparison group (incidence rate, 35.9 vs 43.6 per 1000 person-years). Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90). Several sensitivity analyses also demonstrated similar results of lower diabetes risk associated with denosumab treatment.

Conclusions and relevance

The results from this cohort study indicating that denosumab treatment was associated with lower risk of incident diabetes may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering the risk of diabetes.
Revisiting the Emergency Department
Authors: Thomson Blake
Published: February 2024

This essay describes the author’s first time in an emergency department since accompanying his mother for neurologic evaluation.
Shifting Carotid Web Due to a Wandering and Rotating Carotid Artery
Authors: Mutlu Unal , Fokkink Willem Jan R. , van Kooten Fop
Published: February 2024

This case report describes the finding of a carotid web in combination with a wandering and rotating carotid artery, resulting in a stroke.
Merging MOF Chemistry & Biocatalysis: A Perspective for Achieving Efficient Organic Synthetic Processes and Applications in the Chemical Industry?
Authors: Gröger Harald , Allahverdiyev Adil , Yang Jianing , Stiehm Johannes
Published: February 2024

Biocatalysis has emerged in recent decades toward a widely applied catalysis technology in the chemical industry. In particular the fine chemicals and pharmaceuticals industries benefit from the advantages of biocatalysis, which made its way to a dominating industrial core technology for manufacturing chiral molecules. However, often biocatalysis is still to a certain extent away from having solved all challenges being needed for a “perfect industrial process technology”. Among existing challenges are, e.g., stability under process conditions and easy separation of the catalyst from the reaction mixture with the additional option of recyclability. Here metal‐organic framework (MOF) structures offer unique advantages, which can be beneficial for biocatalysis. A particular valuable option is integration of enzymes into MOF‐subunits, thus having a potential positive impact on stability (by reducing the tendency of unfolding) and enabling compartmentalization as a beneficial strategy in, e.g., chemoenzymatic synthesis. In this “Perspective”‐article, first the state of the art in biocatalysis is briefly summarized together with current challenges. Then, a short overview about current research achievements in “merging” MOF chemistry and biocatalysis is given as well as an outlook written from a biocatalysis practitioner's view, how MOF‐enzyme hybrid systems can play a major role in future process development to overcome existing hurdles of enzymatic catalysis.
Tempospatially Confined Catalytic Membranes for Advanced Water Remediation
Authors: Lu Na , Liu Fu
Published: February 2024

The application of homogeneous catalysts in water remediation is limited by their excessive chemical and energy input, weak regenerability, and potential leaching. Heterogeneous catalytic membranes (CMs) offer a new approach to facilitate efficient, selective, and continuous pollutant degradation. Thus, integrating membranes and continuous filtration with heterogeneous advanced oxidation processes (AOPs) can promote thermodynamic and kinetic mass transfers in spatially confined intrapores and facilitate diffusion‐reaction processes. Despite the remarkable advantages of heterogeneous CMs, their engineering application is practically restricted due to the fuzzy design criteria for specific applications. Herein, the recent advances in CMs for advanced water remediation are critically reviewed and the design flow for tempospatially confined CMs is proposed. Further, state‐of‐the‐art CM materials and their catalytic mechanisms are reviewed, after which the tempospatial confinement mechanisms comprising the nanoconfinement effect, interface effect, and kinetic mass transfer are emphasized, thus clarifying their roles in the construction and performance optimization of CMs. Additionally, the fabrication methods for CMs based on their catalysts and pore sizes are summarized and an overview of their application and performance evaluations is presented. Finally, future directions for CMs in materials research and water treatment, are presented.
Dilute Nanocomposites: Tuning Polymer Chain Local Nanostructures to Enhance Dielectric Responses
Authors: Rui Guanchun , Bernholc Jerzy (Jerry) , Zhang Shihai , Zhang Qiming
Published: February 2024

Dielectric polymers possessing high energy and low losses are of great interest for electronic and electric devices and systems. Nanocomposites in which high dielectric constant (high‐K) nanofillers at high loading (>10 vol%) are admixed with polymer matrix have been investigated for decades, aiming at enhancing the dielectric performance, but with limited success. In 2017, it is discovered that reducing nanofiller loading to less than 0.5 vol% in polymer matrix can lead to marked enhancement in dielectric performance. Here, we reviewed the discoveries and advances of this unconventional approach to enhance dielectric performance of polymers. Experimental studies uncover that nanofillers lead to interfaces changes over distances larger than 100 nm. Experimental and modeling results show that introducing free volume in polymers reduces the constraints of glass matrix on dipoles in polymers, leading to enhanced K without affecting breakdown. Moreover, low‐K nanofillers at low‐volume loading serve as deep traps for charges, lowering conduction losses and increasing breakdown strength. The dilute nanocomposites provide new avenues for designing dielectric polymers with high K, minimal losses, and robust breakdown fields, thus achieving high energy and power density and low loss for operation over a broad temperature regime.