bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnicity in Child Maltreatment Research: A Replication of Behl et al.'s Content Analysis
Authors: Miller Alisa B. , Cross Theodore
Published: December 2005

This study examines the use of ethnicity in 489 empirical research articles published in three major child maltreatment specialty journals from 1999 to 2002. Of the American samples, 12.5% focus on ethnicity, 76.2% report the ethnic composition of participants, and 33.8% use ethnicity of participants in analyses. Ethnicity has a significant effect in 52.3% of articles in which it was used in analyses, suggesting its importance as a variable in a wide range of studies. African Americans and Native Americans are underrepresented in research samples. These findings indicate more attention to ethnicity in American research than Behl, Crouch, May, Valente, and Conyngham's 2001 study might suggest but also highlight the need for continued expansion in focusing on, reporting, and using ethnicity in research.
The Relations Between Family Environment and Violence Exposure Among Youth: Findings From the National Survey of Adolescents
Authors: Hanson Rochelle F. , Self-Brown Shannon , Fricker-Elhai Adrienne E. , Kilpatrick Dean G. , Saunders Benjamin E. , Resnick Heidi S.
Published: December 2005

A national household probability sample of 4,023 adolescents (ages 12 to 17) completed telephone interviews assessing demographics, adverse family environment, and violence exposure. Logistic regressions examined relations among family environment and each violence exposure type, controlling for demographics and other violence exposures. Relationships between family environment and violence exposure varied, depending on type of violence reported, most notably between intrafamilial versus extrafamilial violence. After controlling for family environment, exposure to one violence type significantly increased the likelihood of other violence exposures. Family substance use and not always living with a natural parent were significantly associated with all three types of violence exposure. Findings indicate that clinical assessments should include a thorough evaluation of family environment and violence exposure and also highlight the need for treatment to focus on the adolescent and broader family unit. Future research is needed to further examine these complex interrelationships and their associations with adolescent outcomes.
Weekly Problems Scales: Instruments for Sexually Abused Youth and Their Nonoffending Parents in Treatment
Authors: Sawyer Genelle K. , Tsao Eugenia Hsu , Hansen David J. , Flood Mary Fran
Published: December 2005

This study's purpose was to determine if efficient measures could be created to assess multiple problematic behaviors identified in youth who were sexually abused and in treatment. Because of the lack of easily administered brief instruments that assess multiple domains of interest in this population, complementary parent and child assessment measures were developed. The Weekly Problems Scale–Child Version (WPSC) and the Weekly Problems Scale–Parent Version (WPS-P) were created to monitor the weekly progress of the child and family in treatment and focus specifically on common areas of difficulties in this population. Exploratory factor analysis was conducted to assist in identifying the number of underlying dimensions in the scales. Results indicate that the WPS-C and WPS-P demonstrate adequate internal consistency, temporal stability, and construct validity. The WPS-C and WPSP display significant promise as research and clinical assessment tools for use with youth who are sexually abused and their nonoffending parents in treatment.
Report of the APSAC Task Force on Attachment Therapy, Reactive Attachment Disorder, and Attachment Problems
Authors: Chaffin Mark , Hanson Rochelle , Saunders Benjamin E. , Nichols Todd , Barnett Douglas , Zeanah Charles , Berliner Lucy , Egeland Byron , Newman Elana , Lyon Tom , Letourneau Elizabeth , Miller-Perrin Cindy
Published: December 2005

Although the term attachment disorder is ambiguous, attachment therapies are increasingly used with children who are maltreated, particularly those in foster care or adoptive homes. Some children described as having attachment disorders show extreme disturbances. The needs of these children and their caretakers are real. How to meet their needs is less clear. A number of attachment-based treatment and parenting approaches purport to help children described as attachment disordered. Attachment therapy is a young and diverse field, and the benefits and risks of many treatments remain scientifically undetermined. Controversies have arisen about potentially harmful attachment therapy techniques used by a subset of attachment therapists. In this report, the Task Force reviews the controversy and makes recommendations for assessment, treatment, and practices. The report reflects American Professional Society on the Abuse of Children's (APSAC) position and also was endorsed by the American Psychological Association's Division 37 and the Division 37 Section on Child Maltreatment.
At the Anthropology Meetings
Authors: Campbell Howard
Published: December 2005

This short story uses satire to depict political and cultural posturing at the American Anthropological Association annual meetings. The story describes the encounter of a female working-class Mexican American graduate student with upper-middle-class Anglo professors and the miscommunications that ensue. The story illustrates and parodies Anglo-Mexican ethnic relations within the academy and along the U.S. Mexico border from the standpoint of a Chicana graduate student. The underlying theme of the work is the attraction (and repulsion) Mexican Americans feel for Anglo culture and vice versa as well as the need for intellectuals to take themselves less seriously.
Painting a Landscape of Abortion
Authors: Minge Jeanine Marie
Published: December 2005

This article explores the author's journey through the right to choose. The author fuses her experience in this text so the reader may visualize and reexperience the emotional tensions involved in her decision to have an abortion. She envisions forms of inquiry as atoms in constant motion. She borrows the concept of fusion, understanding the process as two lighter nuclei colliding to form a heavier particle—atoms change, fusion creates energy, energy radiates. The fusion of embodied art is the process of combining art forms as inquiry to illuminate different corners of understanding. The author is the nuclear reactor, forcing elements to collide to see what is illuminated. She invites others to combine and connect different modes of inquiry together. This fusion of embodied art uses painting, writing, and performance to re-create and offer a space that might connect, perhaps even through intense disconnect, ideas, feelings, responses, and knowing about abortion.
Negotiating Myself
Authors: Wesely Jennifer K.
Published: December 2005

This article grows from research in the form of in-depth interviews with female exotic dancers but foregrounds the ways that the author's lived experiences were informed by the interviewees and other aspects of the project. While engaging and then complicating feminist theory and methodology, this article focuses on howthe authorwas drawninto this research in variousways, including conversations, observations, and confrontations. Narratives outline the process of her disillusionment about her own safety as a woman. Overall, this piece challenges the notion of any one, fixed identity as the author negotiates meanings of herself related to objectification and privilege.
“You Can't Cross a River Without Getting Wet”
Authors: Shope Janet Hinson
Published: December 2005

This article discusses the knotty methodological and epistemological issues raised while doing research in rural communities in South Africa. Using entries from the author's field journal and conversations with rural Black women, this article explores the tensions between theory and experience, insiders and outsiders, and writing and orality. Rather than reconciling these tensions, feminist method resides amid the contradictions, wedged in the methodological and epistemological between spaces that open up the possibility of multiple interpretations and dialogue.
The Dancing Body without Organs
Authors: Markula Pirkko
Published: December 2005

This article deals with the process of using dance performance as a way of representing feminist research. It aims to document this process through the author's own experiences of choreographing and performing a solo contemporary dance piece that embraced feminist agenda of representing a positive feminine identity. The article derives from Gilles Deleuze's theoretical concept of Body without Organs in an attempt to disread the dancing body and inhabit an alternative molecular femininity. The article concludes that a dance performance has potential to succeed as a research presentation. However, the researcher needs to proceed cautiously by retaining a close connection to the audience's experiences yet assuming a clear theoretical vision.
Man-to-Man
Authors: Brooks Matthew
Published: December 2005

In this article, the author discusses friendship as a method of qualitative inquiry and howthis method informed research on the social construction of masculinity in male-male friendships. First, a narrative account of a first meeting with a participant is given. Next, the discursive aspect of fieldwork is considered where the author's ideas about friendship as method and “the reach of dialogue” are outlined. Finally, the article focuses on the role of autoethnography in conducting and representing qualitative work on masculinity.
Nurturing Dialogic Hermeneutics and the Deliberative Capacities of Communities in Focus Groups
Authors: Freeman Melissa
Published: December 2005

Dialogue is a central feature of focus groups. It is also a primary component of philosophical hermeneutic theories of understanding. Using a focus group with parents on the topic of state standardized testing in New York State, the author explores the process of creating focus group settings that nurture their relational and hermeneutic qualities and actively engage participants in the coconstruction of meaning and understanding. Central to this discussion is the use of alternative elicitation strategies such as using poetic displays of previous focus group transcripts to engage the participants.
Violence Against American Indian Women and the Services-Training-Officers-Prosecutors Violence Against Indian Women (STOP VAIW) Program
Authors: Luna-Firebaugh Eileen M.
Published: December 2005

When Congress appropriated funds to developways to reduce violence against American Indianwomen, tribal elders faced a challenging task: findways to cooperate with various tribal and nontribal criminal justice agencies and navigate the maze of law enforcement authority. An evaluative study was conducted of these programs and the different approaches used to help keep women safe by American Indian tribal governments. This study found that the tribes rose to the challenge; the moneywas making a difference. The grants to stop violence against Indian women have made a significant impact in the 134 native communities that received awards.
“Homeland” Insecurities?
Authors: Graham Stephen
Published: December 2005

This intervention explores the paradox that although the Bush administration has repeatedly stressed the purported insecurity of U.S. urbanites to “terroristic” threats since 9/11, it has simultaneously undermined the preparedness and resilience of U.S. cities in the face of catastrophic weather and seismic events. Arguing that Katrina needs to be seen as an event that unerringly exposes the politics of urban security in post-9/11 U.S. cities, the piece explores the relationships between neoconservative, antiurban ideology; the “homeland security” drive; and climate change, catastrophic weather events, and oil geopolitics.
Those Who Overstate the Lessons of the Past Are Condemned to Draw Erroneous Conclusions
Authors: Kich Martin
Published: December 2005

In many of the editorial commentaries on the disaster in New Orleans, references have been made to the only other comparable natural disaster to strike a major American city, the great earthquake that struck San Francisco in 1906. There are in fact many striking parallels between the two disasters. But, like most analogous events, these two disasters have as many significant differences as similarities, differences that have been largely ignored.
“Mise en Fiction du Monde”
Authors: Harvey Daina Cheyenne
Published: December 2005

The recent urban trauma in New Orleans has given rise to a series of questions on how to rebuild the city. Absent from the discussion has been an analysis of the collective memory of New Orleans and the mnemonic tropes that might be used in its reconstruction.
Noticing Design/Recognizing Failure in the Wake of Hurricane Katrina
Authors: Brabham Daren C.
Published: December 2005

If good design strives to be invisible, then the aftermath of Hurricane Katrina is a warning to act on the visible flaws in design before they erupt. Knowing that poverty, poor race relations, and more existed in New Orleans before the disaster was to see the flaws in a larger social design.
The Shock of a Social Disaster in an Age of (Nonsocial) Risk
Authors: Burgess Adam
Published: December 2005

The distinctly socially differentiated impact of the New Orleans flood stands in marked contrast to the nonsocial character of disasters and inquiries we have become accustomed to in the “risk society.”
The Buoyancy of Failure
Authors: Lavin Chad , Russill Chris
Published: December 2005

New Orleans and the Mississippi River are often described as a battleground in the war between man and nature. The authors argue that crisis displacement strategies disincline reflection on how this characterization contributes to catastrophic events. The authors outline three sites of crisis displacement: the Army Corps of Engineers, media coverage, and the philosophy of war of the United States government.
What Makes a Disaster “Natural”?
Authors: Alagona Peter S.
Published: December 2005

Natural disasters differ from unnatural disasters not so much in their causes or in their effects but primarily in our reaction to them. In natural disasters nature plays the role of a catalyst. Yet nature does not provide a convenient enemy to rally against and attack in retribution. This in part explains why, unlike the social and political unity that followed the terrorist attacks of September 11, 2001, violence and political turmoil ensued in the immediate aftermath of Hurricane Katrina.
In the Dark All You Have Left Is Architecture
Authors: Lara Fernando
Published: December 2005

This short essay was inspired by the blackout of August 14, 2003, which left a large portion of the Northeast and the Great Lakes (including Canada) without electricity. The author makes the point that without power, we are forced to have a much deeper engagement with the physical reality of our built environment.
The Drowned World
Authors: Gandy Matthew
Published: December 2005

J. G. Ballard’s fictional depiction of a future London under water bears a striking similarity with the actual experience of New Orleans. In reality, however, the impact of racism and “disaster capitalism” on both relief efforts and urban reconstruction have added a disturbing new dimension to Ballard’s neo-Hobbesian evocation of the collapse of the late modern public realm.
A Rhetorical Response to Hurricane Katrina
Authors: Dawkins Marcia Alesan
Published: December 2005

This essay is a rhetorical response to Hurricane Katrina. It begins with a reaction to the initial depictions of Katrina, continues with a discussion of the use of symbols to socially construct its aftermath, and concludes with key questions that the strengths of rhetorical theory allow the critic to ask and answer.
On Flexible Urbanism
Authors: Manaugh Geoff , Twilley Nicola
Published: December 2005

The Atlantean fate of New Orleans was, in large part, a factor of its architecture. Through an over-reliance on urban fortifications—levees, bulwarks, and other rigid, literally military defenses built by the U.S. Army Corps of Engineers—New Orleans lost all flexibility to act as its surrounding landscape returned to a state of hydrological dynamism.
Offering
Authors: Clark Nigel
Published: December 2005

Steering away from the more obvious concern with the breakdown of social order following Hurricane Katrina, this article draws on weblogs and bulletin boards to highlight acts of generosity and hospitality provoked by the disaster and poses some questions about what disasters might tell us about the emergence of the “social.”
The Position of the Theorist in the Lower Ninth Ward
Authors: Fisher C. Tabor
Published: December 2005

A too-easy equation of race and poverty with the Lower Ninth Ward of New Orleans can spatially contain our responses to the social inequities that contributed to the disaster wrought by Hurricane Katrina. This containment reproduces abstract space and inhibits movements for social change.
Disastrous Social Theory—Lessons From New Orleans
Authors: Van Loon Joost , Charlesworth Simon
Published: December 2005

Contemporary social theory struggles to deal with disasters not just because of epistemological shortcomings regarding the continued dualistic nature of its dealings with social phenomena and events, relegating disasters to the real of “extraordinary events,” but also because it has effectively foreclosed on its ability to deal with social reality. The latter is less the consequence of epistemic shortcomings but itself a social by-product of the institutionalization of social thought in the academy. Divorced from an ability to come to terms with social reality, because it lacks both an empirical grounding and a sense of urgency to understand that which lies outside the comfort zone of academic life, social theory is left rather aimlessly afloat amid a sea of debris that signals that the apocalypse has already happened.
Visualizing the Corrosive Community
Authors: Miller DeMond Shondell
Published: December 2005

After visiting his home in the wake of Hurricane Katrina, the author is confronted with a newly configured landscape and a new social reality marked by a culture of distrust and a decline in social capital among residents. The comments here view one aspect of the corrosive community impact: the decline in civic trust, more specifically, trust and interaction among neighbors. One indicator of this distrust is evidenced by signs posted to limit illegal activity. These signs are posted throughout New Orleans and the surrounding areas to deter looters from the outside and looters from “within.”
Urban Calamities
Authors: Anjaria Jonathan Shapiro
Published: December 2005

One month prior to Hurricane Katrina, the city of Mumbai, India, experienced similar unprecedented and disastrous flooding. In contrast to New Orleans, however, the Mumbai floods were not marked by social disorder and violence but by widespread acts of generosity and altruism. The author argues that, paradoxically, it was the very “Third World-ness” of Mumbai that prevented the city from experiencing the chaos witnessed in New Orleans.
Creole Urbanism
Authors: Wagner Jacob A.
Published: December 2005

The destruction of New Orleans will be met with many acts of (re)creation that will help not only to mend the physical city but also the very soul of the people and the place. This essay introduces the concept of “creole urbanism” to describe the city’s unique urban culture and built environment.
Site and Situation
Authors: Paleo Urbano Fra
Published: December 2005

When a site is highly exposed to hazards, choices for mitigation are much more complex. The location of cities, towns, and settlements in general has been guided by economic and resource opportunities, translated as situation. However this is a multifaceted concept that also comprises relationships with distant environments and their changing conditions.
The Relevance of Human Geography for Studying Urban Disasters
Authors: Fraser James C.
Published: December 2005

The purpose of this article is to make a case for the centrality of geography in studying human dimensions of urban environmental change. The author undertakes this task by highlighting two potential areas of inquiry that need further attention: (a) the creation of sociospatial identities and (b) urban governance as it relates to disasters. For each area of inquiry, the author provides a conceptual statement and a brief illustration.
Resounding Silence in the Streets of a Musical City
Authors: Sakakeeny Matt
Published: December 2005

New Orleans is a musical city where sound is inextricable from the experience of place. Sound has played a defining role in distinctive cultural practices such as jazz funerals and parades called “second lines,” in which African Americans have made claims on the contested city streets for over a century. How will New Orleans re-sound after extraordinary forces claimed those same streets?
National Human Resource Development: A Focused Study in Transitioning Societies in the Developing World
Authors: McLean Gary N.
Published: December 2005

The problem and the solution. The world continues to be one that is marked by incredible disparities in wealth, education, employment, health, technology, infrastructures, safety, and other factors that contribute to one’s sense of well-being. The renewed interest in national human resource development may be an effective, systematic approach to assisting in reducing these disparities and in reaching the United Nation’s target to accomplish the Millennium Development Goals by 2015. Such developments make it increasingly important for human resource development professionals to understand and contribute to this broader context of human resource development. This issue of Advances in Developing Human Resources fills one more niche in the growing literature related to national human resource development.
National Human Resource Development in Transitioning Societies in the Developing World: Introductory Overview
Authors: Paprock Kenneth E.
Published: December 2005

The problem and the solution. At present, there is no publication that brings together the experience of rapidly changing countries and their attempts at national human resource development. This issue explores different approaches to national human resource development in transitioning nations and highlights the forces working for and against their success. A review of related research, an informed theoretical framework, and a model for examining human resource development in transitioning societies in the developing world is presented and discussed in this article. Its purpose is to provide a basis for discussion and comparisons between the selected case examples in the developing world that make up this issue.
National Human Resource Development in Transitioning Societies in the Developing World: The People’s Republic of China
Authors: Ke Jie , Chermack Thomas J. , Lee Yi-Hsuan , Lin Jie
Published: December 2005

The problem and the solution. China has an excess of unskilled and semiskilled workers but a serious shortage of professionals and managers. Problematic education and training facilities are the main causes. Although higher education, which was interrupted throughout China during the Cultural Revolution (1966-1976), has been substantially expanded since 1978, it cannot keep pace with rapid economic development. As a result, China must reconsider the problems in developing its human resources and find innovative ways to solve them. This article reviews the historical and transitioning contexts of China with an eye on the evolving role of human resource development. Driving forces in the HRD environment are examined along with their potential impacts. Strategies for increasing the contribution of human resource development to economic, social, cultural, and political growth in China are suggested that are believed to have the potential to spark synergy between China’s booming economy and its need for human resource development.
National Human Resource Development in Transitioning Societies in the Developing World: Morocco
Authors: Cox J. Ben , Al Arkoubi Khadija , Estrada Samuel D.
Published: December 2005

The problem and the solution. As a transitioning society in the developing world, Morocco has made significant progress in improving human development and social conditions and has recently introduced a number of reforms that are intended to promote human rights and economic development. The national human resource development strategy has a large role to play in the success of these initiatives. Human resource development professionals and policy makers must implement and build on the current reform initiatives to overcome barriers between institutions, ineffective and corrupt business practices, disillusion among the disenfranchised, and the loss of strategic human capital to other countries.
National Human Resource Development in Transitioning Societies in the Developing World: Concept and Challenges
Authors: Lynham Susan A. , Cunningham Peter W.
Published: December 2005

The problem and the solution. Synthesizing findings from five selected case studies reflective of high-transitioning countries in the developing world, this article proposes a number of comparative discoveries about the necessary role and nature of national human resource development in this context. One such discovery is the influence of the political, economic, and sociocultural environments on the necessary nature and role of national human resource development in each country. A second is that context and intent shape and inform what makes for responsible human resource development. Another is that discoveries from this and other studies suggest emerging models and necessary attributes, components, and dimensions useful for informing an integrative and collaborative theoretical and sense-making framework for future study and practice of national human resource development. These and other discoveries pose numerous challenges to the human resource development profession—challenges that will require fundamental reperceiving by its professionals.
Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation
Authors: Lu Dao-Pei , Dong Lujia , Wu Tong , Huang Xiao-Jun , Zhang Mei-Jie , Han Wei , Chen Huan , Liu Dai-Hong , Gao Zhi-Yong , Chen Yu-Hong , Xu Lan-Ping , Zhang Yao-Chen , Ren Han-Yun , Li Dan , Liu Kai-Yan
Published: December 2005

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.
Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function
Authors: Catalano Alfonso , Caprari Paola , Moretti Simona , Faronato Monica , Tamagnone Luca , Procopio Antonio
Published: December 2005

An important aspect of tumor progression is the ability of cancer cells to escape detection and clearance by the immune system. Recent studies suggest that several tumors express soluble factors interfering with the immune response. Here, we show that semaphorin-3A (Sema-3A), a secreted member of the semaphorin family involved in axonal guidance, organogenesis, and angiogenesis, is highly expressed in several tumor cells. Conditioned media of Sema-3A-transfected COS-7 cells or human recombinant Sema-3A inhibited primary human T-cell proliferation and cytokines production under anti-CD3 plus anti-CD28 stimulating conditions. Sema-3A also inhibited the activation of nonspecific cytotoxic activity in mixed lymphocyte culture (MLC), as measured against K-562 cells. In contrast, suppression of Sema-3A in tumor cells with a small interfering RNA (siRNA) augmented T-cell activation. The inhibitory effect of Sema-3A in T cells is mediated by blockade of Ras/mitogen-activated protein kinase (MAPK) signaling pathway. The presence of Sema-3A increased the activation of the Ras family small GTPase Rap1 and introduction of the dominant-negative mutant of Rap1 (Rap1N17) blunted the immunoinhibitory effects of Sema-3A. These results suggest that Sema-3A inhibits primary T-cell activation and imply that it can contribute to the T-cell dysfunction in the tumor microenvironment.
NF-κB is essential for the progression of KSHV- and EBV-infected lymphomas in vivo
Authors: Keller Shannon A. , Hernandez-Hopkins Denise , Vider Jelena , Ponomarev Vladimir , Hyjek Elizabeth , Schattner Elaine J. , Cesarman Ethel
Published: December 2005

Activated NF-κB is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacologic inhibition of constitutive NF-κB activity induces apoptosis in KSHV- and EBV-infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-κB in vitro induced identical mitochondrially mediated apoptosis cascades. Assessment of gene regulation by microarray analysis revealed that the inhibition of NF-κB in tumor cells results in the down-regulation of a distinct group of prosurvival genes, including cIAP-1, cIAP-2, cFLIP, and IL-6. Using EBV- and KSHV-associated lymphomas in a murine system, we demonstrated that Bay 11-7082, a selective pharmacologic inhibitor of NF-κB, prevents or delays tumor growth and prolongs disease-free survival. Inhibition of NF-κB activity and tumor growth responses were further documented using a traceable reporter KSHV-positive cell line and in vivo imaging. These findings indicate that specific NF-κB-regulated survival factors work cooperatively to protect KSHV- and EBV-infected lymphoma cells from apoptosis such that they promote the establishment and progression of KSHV- and EBV-associated lymphomas in mice. They also support the use of selective NF-κB inhibitors in the treatment of herpesvirus-associated lymphomas.
A global role for EKLF in definitive and primitive erythropoiesis
Authors: Hodge Denise , Coghill Elise , Keys Janelle , Maguire Tina , Hartmann Belinda , McDowall Alasdair , Weiss Mitchell , Grimmond Sean , Perkins Andrew
Published: December 2005

Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and β-globin gene regulation but failure to rectify lethal fetal anemia upon correction of globin chain imbalance suggested additional critical EKLF target genes. We employed expression profiling of EKLF-null fetal liver and EKLF-null erythroid cell lines containing an inducible EKLF-estrogen receptor (EKLF-ER) fusion construct to search for such targets. An overlapping list of EKLF-regulated genes from the 2 systems included α-hemoglobin stabilizing protein (AHSP), cytoskeletal proteins, hemesynthesis enzymes, transcription factors, and blood group antigens. One EKLF target gene, dematin, which encodes an erythrocyte cytoskeletal protein (band 4.9), contains several phylogenetically conserved consensus CACC motifs predicted to bind EKLF. Chromatin immunoprecipitation demonstrated in vivo EKLF occupancy at these sites and promoter reporter assays showed that EKLF activates gene transcription through these DNA elements. Furthermore, investigation of EKLF target genes in the yolk sac led to the discovery of unexpected additional defects in the embryonic red cell membrane and cytoskeleton. In short, EKLF regulates global erythroid gene expression that is critical for the development of primitive and definitive red cells.
Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis
Authors: Pick Marjorie , Perry Chava , Lapidot Tsvee , Guimaraes-Sternberg Cinthya , Naparstek Elizabeth , Deutsch Varda , Soreq Hermona
Published: December 2005

To study the role of the stress-induced “readthrough” acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR). Increased AChE hydrolytic activity in the peripheral blood of TgR mice was associated with increased thrombopoietin levels and platelet counts. Bone marrow (BM) progenitor cells from TgR mice presented an elevated capacity to produce mixed (GEMM) and megakaryocyte (Mk) colonies, which showed intensified labeling of AChE-R and its interacting proteins RACK1 and PKC. When injected with bacterial lipopolysaccharide (LPS), parent strain FVB/N mice, but not TgR mice, showed reduced platelet counts. Therefore, we primed human CD34+ cells with the synthetic ARP26 peptide, derived from the cleavable C-terminus of AChE-R prior to transplantation, into sublethally irradiated NOD/SCID mice. Engraftment of human cells (both CD45+ and CD41+ Mk) was significantly increased in mice that received ARP26-primed CD34+ human cells versus mice that received fresh nonprimed CD34+ human cells. Moreover, ARP26 induced polyploidization and proplatelet shedding in human MEG-01 promegakaryotic cells, and human platelet engraftment increased following ex vivo expansion of ARP26-treated CD34+ cells as compared to cells expanded with thrombopoietin and stem cell factor. Our findings implicate AChE-R in thrombopoietic recovery, suggesting new therapeutic modalities for supporting platelet production.
Cytoplasmic/Nuclear Shuttling and Tumor Progression
Authors: WANG SHAO‐CHUN , HUNG MIEN‐CHIE
Published: December 2005

Abstract: Protein localization is a highly dynamic biological process. To ensure a proper cellular function, the spatial distribution of different proteins needs to be delicately regulated and coordinated. In cancer, this process is tightly correlated with the outcome of cell proliferation and the response to apoptotic stress. Here we summarize our recent studies regarding the role of subcellular trafficking on cancer cell growth through an AKT‐independent regulation of the forkhead transcription factor and, on cancer metastasis, through the regulated localization and subsequent protein degradation of the Snail protein, a key transcription factor involved in epithelial‐mesenchymal transition (EMT). In both cases, cellular signaling pathways mediated by distinct protein kinases modulate the appropriate protein localization and functioning. Finally, we address a novel translocation pathway for tyrosine kinase receptors between the cell membrane and the nucleus. We demonstrate that the ErbB family proteins are also expressed in the nucleus and can function as transcriptional regulators. Using a genomic approach, we have identified a number of the target genes regulated by this pathway that are closely related to cancer cell proliferation and metastasis. Our findings, together with the seminal discoveries by other groups, highlight the importance of protein localization in cancer biology and its potential to be a therapeutic target for cancer.
Targeting Intracellular Signaling Pathways as a Novel Strategy in Melanoma Therapeutics
Authors: SMALLEY KEIRAN S.M. , HERLYN MEENHARD
Published: December 2005

Abstract: Melanoma has been one of the fastest rising malignancies in the last four decades with cases increasing from below 3 per 100,000 people to above 13. Despite worldwide efforts in prevention, diagnosis, and treatment, cases of melanoma continue to rise at an alarming rate of 2.5% annually in the United States. Although early primary melanomas are curable through surgery, treatment of advanced disease remains difficult and the strategies employed in the last 30 years have not significantly improved cure rates, which are less than 5%. The recent identification of activating mutations in BRAF in over 60% of cases of melanoma has caused much excitement in the melanoma community and may offer the first opportunity for a rational treatment program. Combination therapy using the RAF inhibitor, BAY 43‐9006, and chemotherapy has led to impressive responses in some melanoma patients and provides a new paradigm for therapeutic intervention in this intractable disease. Besides activating mutations in BRAF, melanomas have constitutive activity in a number of other signaling pathways implicated in oncogenesis, including PI3 kinase/Akt, NFB, Src, and STAT3. With more and more selective small molecule inhibitors becoming available, there are good prospects for treating advanced melanoma using new combinations of signal transduction inhibitors and chemotherapy. In the current review, we discuss the role for these signaling pathways in melanoma and discuss the rationale for targeting signaling cascades using small molecule inhibitors.
Studies into the Anticancer Effects of Selenomethionine against Human Colon Cancer
Authors: NELSON MARK A. , GOULET ANNE‐CHRISTINE , JACOBS ELIZABETH T. , LANCE PETER
Published: December 2005

Abstract: Colorectal cancer is the third most frequent fatal malignant neoplasm in the United States and is expected to cause significant morbidity and mortality. The recent recall of cyclooxygenase‐2 inhibitors from clinical trials highlights the need to develop other agents for cancer chemoprevention trials. Intervention strategies with selenium compounds represent a viable option to reduce colon cancer. Here we discuss epidemiologic studies and ongoing clinical trials with selenium. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular bases for the anticancer effects of selenomethionine.
Mechanisms of Prostate Tumorigenesis: Roles for Transcription Factors Nkx3.1 and Egr1
Authors: ABDULKADIR SARKI A.
Published: December 2005

Abstract: Recent developments in the generation and analysis of transgenic mouse models have improved our understanding of the early stages of prostate tumorigenesis. Analysis of models based on the homeodomain protein Nkx3.1 and the zinc finger protein Egr1 suggests that these transcription factors play distinct roles in the initiation and progression of precursor prostatic intraepithelial neoplasia (PIN) lesions, respectively. Nkx3.1 is a candidate prostate tumor suppressor gene (TSG) that demonstrates haploinsufficiency. Disruption of one or both copies of the murine Nkx3.1 gene leads to the development of epithelial hyperplasia and PIN. This appears to be a consequence of delayed exit from the cell cycle by differentiating prostate luminal epithelial cells in Nkx3.1 mutant mice. Gene expression profiling has provided additional insight into the basis of haploinsufficiency in Nkx3.1 mutant mice. A reduction in Nkx3.1 dosage leads to dramatic alterations in the expression of a subset of genes by altering the probability of a target gene existing in the “on” or “off” state. The immediate early gene Egr1, on the other hand, is overexpressed in human and mouse prostate tumors and PIN lesions and regulates the expression of several genes implicated in prostate tumor progression, including platelet‐derived growth factor and insulin‐like growth factor II. Prostate cancer‐prone mice lacking Egr1 exhibit a significant delay in tumor progression. Specifically, Egr1 deficiency impairs the transition from PIN to invasive carcinoma. Thus, Nkx3.1 and Egr1 regulate gene programs involved in distinct aspects of prostate tumorigenesis.
Preclinical Modeling of Combination Treatments: Fantasy or Requirement?
Authors: DECKER SHANNON , SAUSVILLE EDWARD A.
Published: December 2005

Abstract: Combination chemotherapy is considered the “norm” in cancer chemotherapy. While the development of classical combination regimens took into account factors such as single‐agent activity, different toxicity profiles, and advantageous pharmacology of the component drugs, in the era of targeted therapies there are additional considerations such as new mechanisms of resistance due to modulation of pathway dependence. Since it is not feasible to test all of the possible combinations clinically, some method for preclinically identifying and prioritizing promising combinations is necessary. While in vivo animal models can be used for safety testing and some pharmacokinetics, even they can quickly become prohibitively resource intensive for the purpose of efficacy determinations. Therefore, factors such as biologic rationale, reliable in vitro results in more than one tumor type, achievable in vivo pharmacology, and selectivity of primary tumor cell activity become important in the evaluation of potential combination regimens.
The Proteasome Inhibitor Bortezomib (Velcade) Sensitizes Some Human Tumor Cells to Apo2L/TRAIL‐Mediated Apoptosis
Authors: BROOKS ALAN D. , RAMIREZ TERESA , TOH UHI , ONKSEN JENNIFER , ELLIOTT PETER J. , MURPHY WILLIAM J. , SAYERS THOMAS J.
Published: December 2005

Abstract: On testing a panel of different human cancer cell lines, we observed that the proteasome inhibitor bortezomib could dramatically sensitize some lines to the apoptotic effects of Apo2L/TRAIL. Certain renal, colon, or breast tumor cell lines were dramatically sensitized, whereas other tumor lines from the same tissue of origin remained resistant. This sensitization did not correlate with either the p53 status of the individual tumor cell lines or their intrinsic sensitivity to Apo2L/TRAIL. Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Although the molecular basis of bortezomib sensitization of tumor cells to Apo2L/TRAIL remains to be determined, this combination can have an enhanced apoptotic effect over either agent alone for certain human cancer cells.
A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma
Authors: LEOW CHING CHING , POLAKIS PAUL , GAO WEI‐QIANG
Published: December 2005

Abstract: A significant reduction or loss of goblet cells is often observed in clinical samples of colon adenocarcinomas, which is the predominant form of colon carcinoma. Mice lacking Math1, a bHLH transcription factor downstream of the Notch signaling pathway, demonstrates that Math1 is necessary for cell fate determination of the intestinal secretory cells, including goblet cells. Examination of Hath1, the human orthologue of Math1, expression in multiple colon tumor samples and colon cancer cell lines reveals a dramatic decrease in Hath1 expression in colon tumor samples and colon cancer cell lines. Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage‐independent growth both in vitro and in vivo. At the molecular level, Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway, which has been clearly implicated in colon tumorigenesis.
Alterations in DNA Repair Gene Expression under Hypoxia: Elucidating the Mechanisms of Hypoxia‐Induced Genetic Instability
Authors: BINDRA RANJIT S. , SCHAFFER PAUL J. , MENG ALICE , WOO JENNIFER , MÅSEIDE KÅRSTEIN , ROTH MATT E. , LIZARDI PAUL , HEDLEY DAVID W. , BRISTOW ROBERT G. , GLAZER PETER M.
Published: December 2005

Abstract: Hypoxia is a common feature of solid tumors and is associated with genetic instability and tumor progression. It has been shown previously that alterations in the expression of DNA repair genes in response to hypoxic stress may account for a proportion of such genetic instability. Here, we demonstrate that the expression of RAD51, a critical mediator of homologous recombination (HR), is repressed by hypoxia in numerous cell lines derived from a wide range of tissues. Repression of this gene by hypoxia occurs in a cell cycle‐ and hypoxia‐inducible factor (HIF)‐independent manner, and decreased RAD51 expression was observed to persist during the post‐hypoxic period. In addition, decreases in Rad51 expression were correlated with functional impairments in HR repair in hypoxic and post‐hypoxic cells. Based on these data, we propose a novel mechanism of hypoxia‐induced genetic instability via suppression of the HR pathway in cancer cells within the tumor microenvironment.
Single-Cycle Induction Chemotherapy Selects Patients With Advanced Laryngeal Cancer for Combined Chemoradiation: A New Treatment Paradigm
Authors: Urba Susan , Wolf Gregory , Eisbruch Avraham , Worden Francis , Lee Julia , Bradford Carol , Teknos Theodoros , Chepeha Douglas , Prince Mark , Hogikyan Norman , Taylor Jeremy
Published: December 2005

Purpose

Primary chemoradiotherapy in patients with advanced laryngeal cancer can achieve high rates of organ preservation without sacrificing survival compared with radiation alone or conventional laryngectomy. Appropriate selection of patients for organ preservation approaches could enhance overall treatment outcome and quality of life. We conducted a phase II organ preservation trial for patients with stage III and IV larynx cancer to determine whether late salvage surgery rates could be decreased and survival improved by selecting patients for organ preservation based on response to a single cycle of induction chemotherapy.

Patients and Methods

The chemotherapy was cisplatin 100 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d for 5 days. Patients who achieved less than 50% response had immediate laryngectomy. Patients who achieved more than 50% response went on to concurrent chemoradiotherapy. Histologic complete responders after chemoradiotherapy received two more cycles of chemotherapy. Patients with residual disease after chemoradiotherapy had planned salvage surgery.

Results

Of 97 eligible patients, 73 (75%) achieved more than 50% response and received chemoradiotherapy. A total of 29 patients (30%) had salvage surgery; 19 patients (20%) had early salvage surgery after the single cycle of induction chemotherapy, three patients (3%) had late salvage surgery after chemoradiotherapy, six patients (6%) eventually had salvage surgery for recurrence, and one patient had laryngectomy for chondroradionecrosis. The median follow-up time was 41.9 months. The overall survival rate at 3 years is 85%. The cause-specific survival rate was 87%. Larynx preservation was achieved in 69 patients (70%).

Conclusion

These results confirm excellent larynx preservation and improved overall survival rates compared with historical results.