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Research shows utilizing pre-employment tests leads to improved job performance and satisfaction, and decreased turnover in hospitality industry. However, employers have been slow to embrace pre-employment testing due to concerns regarding validity, potential for discrimination, and heavy administration costs. Using focus groups, this study examined hospitality hiring managers' perceptions of pre-employment testing's value, barriers to adoption, and the relationship between testing, organizational commitment, and job performance in both the United States and Australia. Results showed opposing viewpoints between participants. Research results may enable hiring managers to justify the implementation of pre-employment testing, select which tests to use, and revise current assessment practices. [ABSTRACT FROM AUTHOR]

The purpose of this article is to analyze the production of space in "agrovila" Calúcia and the role that it plays within the urban dispersal of Castanhal, Pará. The methodological procedures carried out consisted in bibliographical revision; documentary survey; exploratory approach of the study area, with data collection by observation addressed; semi-structured interviews with residents of Calúcia and with public managers. Through the analysis of the data collected were found to this space, even keeping certain content related to the field, has evidenced the logic of urban dispersal, serving as residences for social groups included, which was poorly denied the right to town. [ABSTRACT FROM AUTHOR]

As restaurants are the primary hospitality business represented on flash-sale sites, this study examined motivations of restaurant managers when choosing whether to utilize the promotional mediums of flash-sales. Interviews were administered as a measurement instrument. Results demonstrated restaurants which have employed flash-sales are weary of the likelihood of success and believe the flash-sales brought in established customers. Non-users indicated hesitation towards adoption of flash-sales related to low profit margins per item in their operation and the percentage split of the sale price between the firm and flash-sale provider. Findings provide keen foundational insight into the flashsale phenomenon. [ABSTRACT FROM AUTHOR]

Previous research has indicated that gender is an imperative factor that influences consumers’ online purchasing behavior. The traditional view of gender differences in consumer behavior states that females are influenced by emotional gratification and seek promotions more frequently than males. This study aimed to investigate whether gender differences existed in deal-hunting behavior during the hotel booking process. The research model was structured to understand the factors that influence consumers to search and book hotel deals. A total of 603 completed online questionnaires were collected. Results showed there were significant differences between females’ and males’ deal-searching behavior and purchase intentions. Male consumers were likely influenced by emotional gratification, such as feeling excited about finding a good deal online. Alternatively, female consumers were not influenced by affection but by their cognitive evaluation. In addition, male and female consumers demonstrated different preferences in types of promotion utilized by travel websites. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the factors that influence travelers’ decision-making process while searching and booking hotel deals. This study indicated that consumers’ cognition directly and significantly influenced their intent to book hotel deals. Although consumers’ affection did not have a positive and significant influence on booking intentions in general, consumers’ tendency toward being a market maven moderated the effect in consumers’ emotions of deal-searching. The findings suggested that hospitality marketers should develop promotional messages that are tailored to evoke consumers’ cognitive and affective states in terms of their tendency to be a market maven. [ABSTRACT FROM PUBLISHER]

Amidst a growing industry, foodservice professionals are seeking certifications to differentiate themselves from the competition. The American Culinary Federation (ACF) provides the most comprehensive culinary certification program in the United States, promoting professional development through specialized training in the culinary arts. Proponents of the ACF certification program boast benefits such as increased pay and prestige. However, there has been limited research focusing on the relationship between professional foodservice certifications and perceived career success. This study examined the relationships between culinary certifications and objective (i.e. salary) and subjective (i.e. job satisfaction, self-efficacy) indicators of career success. [ABSTRACT FROM PUBLISHER]

This study aims to identify the representativeness of hospitality and service industry firms on flash-sale sites such as Groupon and LivingSocial. Currently, academic findings related to the frequency of offerings from these firms are nonexistent. This research relied upon a content analysis rubric and daily measurement of offerings from randomly selected cities represented by Groupon and LivingSocial for a period of 6 weeks. The daily offerings for specific cities on the Groupon and LivingSocial sites were utilized as the primary data sources. Findings indicate firms in these industries, outside of restaurants, have shunned away from offering their services via flash-sale mediums. The research findings demonstrate restaurants frequently utilize flash sales as a promotional tool. However, the abundant representation of these types of firms has created a scenario in which operators are compelled to offer deep discounts to make their offers competitive with offers from competing firms in the same city. [ABSTRACT FROM AUTHOR]

Exponential growth in the Chinese hospitality industry has fueled an overabundance of hotel job opportunities. The unintended consequences of an untrained workforce have posed a serious challenge to hospitality managers. Western hotel managers are hired for their special knowledge and expertise, and due to a lack of preparation and cultural training, they experience high assignment failure rates. Using the leveraging leader–member exchange theory, this qualitative study collected data from primary sources and revealed key emergent issues facing Western expatriate hotel managers working in China today. Productive culture-specific tactics for Western expatriate managers were offered to enhance team performance. [ABSTRACT FROM AUTHOR]

Hospitality management programs, similar to other fields within higher education, are faced with numerous challenges including decreased funding and competition for students.In an effort to boost enrollment, researchers suggest a transformation of higher education, placing students at the center of these initiatives.With a focus on service, particularly student-staff interactions, knowledgeable and experienced faculty have been shown to increase perceived service quality. This research sought to quantify students’ perspectives regarding the importance of faculty members’ hospitality industry experience in an effort to meet expectations, which may translate into greater undergraduate enrollment, retention and graduation rates. A large sample (n = 1130) of undergraduates from the U.S. participated in the study from hospitality programs ranging under 500 to over 1000 students. [ABSTRACT FROM AUTHOR]

A substantial body of empirical research exists on the topic of online teaching and learning; however, few qualitative studies have been conducted examining the deeper reasons for teaching online and no studies of this type have been performed in the hospitality discipline. This research sought to understand the subjective norms influencing hospitality faculty to teach online. Data were coded according to TAM2 constructs and sub-coded revealing emergent themes. Findings demonstrated hospitality faculty’s propensity for blended learning as well as other strategies for improved online instruction. [ABSTRACT FROM PUBLISHER]

The authors explore the use of metaphors as a training tool for beginning counselors for enhancing client case conceptualization, counselor-client relationships, and intervention strategies. The history of the use of metaphors in counseling, several definitions, and a case study are presented. The authors discuss intentional use of metaphors with students in training and with clients. How to introduce the use of metaphors into counselor training and practice is also included. [ABSTRACT FROM AUTHOR]

This study examined the relationship between level of depression and level of psychological abuse in women. In addition, the relationship between the use of self-report and measured report of psychological abuse within an intimate relationship was assessed. One hundred women were surveyed using the Psychological Maltreatment of Women Inventory (PMWI) and the Beck Depression Inventory (BDI). Results form the PMWI, the BDI and self-report measures were compared and analyzed. Statistical results indicated that a significant relationship existed between level of depression and level of psychological abuse. In addition, self-report was not predictive of psychological abuse as measured by the PMWI. [ABSTRACT FROM AUTHOR]

A review of the research literature on the psychological abuse of women is presented including defining and measuring the construct. Implications for practice, research, and multiculturalism are explored. [ABSTRACT FROM AUTHOR]

Assesses a variety of variables for their potential effect on length of sobriety for female addicts. Women who had received chemical dependency treatment through the Women's Residential Addiction Program (WRAP) as participants to the study; WRAP's aftercare program and vocational and educational programming as significantly related to length of sobriety.

The authors assessed potential differences between children of alcoholics and children of nonalcoholics in depression and choice of coping strategies. Although significant group differences were detected for level of depression, mean depression scores for both groups fell within the no depression range on the Beck Depression Inventory, No significant differences in coping strategies were detected. [ABSTRACT FROM AUTHOR]

This exploratory study employed the values, attitudes, and behavior (VAB) framework to test Hofstede’s cultural values, state-level ethnocentrism (state brand consumption), and identity (state pride) on intent to support ag-related products in the context of a state operated agricultural marketing program (SOAMP). Results (N = 259) showed collectivism and long term orientation have a positive influence on consumers’ attitudes. State brand consumption was found to be the strongest predictor of intent to purchase local food products, while state pride had a mild level of predictability. Practical implications for food and beverage retailers, hospitality marketers and ag-related government agencies are provided. [ABSTRACT FROM AUTHOR]

The article discusses a study on the treatment of hepatitis C virus infection and mentions topics including adverse effects and dose adjustment during the treatment, use of interferon-free drugs for avoiding complications, and cooperation of public health authorities for the treatment.

The rapid expansion of the hotel industry in Mainland China has precipitated an increased need for hiring Western expatriate managers, especially among multinational brands. The consequences of expatriate failure are well studied and are of vital concern among stakeholders, necessitating a deeper understanding of Chinese norms. Prior justice research in China has recommended the inclusion of Chinese societal protocols, such as face protection and conflict avoidance, as predictors of Interactional Justice. The current study has added to the literature the importance of understanding face conflict avoidance styles as a precursor to Western expatriate managerial success. [ABSTRACT FROM AUTHOR]

This study proposes and tests the influence of the cruise ship brand equity model on behavioral intentions by utilizing the constructs of brand loyalty, image, awareness, message, and perceived quality. The study found overall that brand loyalty and perceived quality were most influential on the behavioral intentions of cruise passengers. Specifically, repeat purchase intentions, the likelihood of recommending the brand to others, and brand preference were found to be significant in the model. The finding is consistent with extant literature which credits brand loyalty with being the most influential variable on cruise passenger's behavioral intentions. Brand image was the most highly correlated construct with behavioral intentions and was found to lack discriminant validity although theory distinguishes the two as separate constructs. The results from this study may be useful to cruise line corporations, particularly in formulating successful marketing campaigns and in encouraging relationship building with customers. [ABSTRACT FROM AUTHOR]

The authors studied the relationships between adult workers' spiritual well-being and job satisfaction. Two hundred participants completed 2 instruments: the Spiritual Well-Being Scale (C. W. Ellison & R. F. Paloutzian, 1982) and the Minnesota Satisfaction Questionnaire Short Form (D. J. Weiss, R. V. Dawis, G. W. England. & L. H. Lofquist, 1967). A bivariate correlational analysis showed spiritual well-being, religious well-being. and existential well-being to be positively related to job satisfaction for this sample. With a forced-entry multiple regression analysis, overall spiritual well-being was found to have a moderate influence, existential well-being had a much stronger influence, and religious well-being had a minimal influence all on, general job satisfaction. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) is a risk factor for type 2 diabetes. In the era of interferon-based HCV therapy, type 2 diabetes was associated with decreased likelihood of sustained virologic response (SVR). Preliminary studies suggest that type 2 diabetes may not reduce the efficacy of regimens involving direct-acting antiviral (DAA) medications. We aimed to determine whether preexisting type 2 diabetes is associated with a reduced rate of SVR achieved 12 weeks after treatment of HCV with DAA-based regimens. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the usefulness of real-time molecular profiling through next-generation sequencing (NGS) in predicting the tumor biology of advanced pancreatic neuroendocrine tumors (panNETs) and in characterizing genomic evolution. Methods: Patients with metastatic panNETs were recruited in the routine clinical practice setting (between May 2014 and March 2017) for prospective NGS of their tumors as well as for germline analysis using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing platform. When possible, NGS was performed at multiple time points. Results: NGS was performed in 96 tumor samples from 80 patients. Somatic alterations were identified in 76 of 80 patients (95%). The most commonly altered genes were MEN1 (56%), DAXX (40%), ATRX (25%), and TSC2 (25%). Alterations could be defined in pathways that included chromatin remodeling factors, histone methyltransferases, and mammalian target of rapamycin pathway genes. Somatic loss of heterozygosity was particularly prevalent (55 of 95 tested samples [58%]), and the presence of loss of heterozygosity resulted in improved overall survival (P =.06). Sequencing of pre- and post-treatment samples revealed tumor-grade progression; clonal evolution patterns were also seen (molecular resistance mechanisms and chemotherapy-associated mutagenesis). Germline genetic analysis identified clinically actionable pathogenic or likely pathogenic variants in 14 of 88 patients (16%), including mutations in high-penetrance cancer susceptibility genes (MEN1 , TSC2 , and VHL). Conclusion: A clinical NGS platform reveals pertubations of biologic pathways in metastatic panNETs that may inform prognosis and direct therapies. Repeat sequencing at disease progression reveals increasing tumor grade and genetic evolution, demonstrating that panNETs adopt a more aggressive behavior through time and therapies. In addition to frequent somatic mutations in MEN1 and TSC2 , germline mutations in these same genes underlie susceptibility to panNETs and highlight the need to re-evaluate whether germline genetic analysis should be performed for all patients with panNETs. [ABSTRACT FROM AUTHOR]

Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ/γ isoforms currently in clinical development. PI3K-δ/γ inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a phase 1, open-label study of duvelisib in patients with relapsed or refractory PTCL (n = 16) and CTCL (n = 19), along with in vitro and in vivo models of TCL. The overall response rates in patients with PTCL and CTCL were 50.0% and 31.6%, respectively (P = .32). There were 3 complete responses, all among patients with PTCL. Activity was seen across a wide spectrum of subtypes. The most frequently observed grade 3 and 4 adverse events were transaminase increases (40% alanine aminotransferase, 17% aspartate aminotransferase), maculopapular rash (17%), and neutropenia (17%). Responders and nonresponders had markedly different changes in serum cytokine profiles induced by duvelisib. In vitro, duvelisib potently killed 3 of 4 TCL lines with constitutive phospho-AKT (pAKT) vs 0 of 7 lines lacking pAKT (P = .024) and exceeded cell killing by the PI3K-δ-specific inhibitor idelalisib. Administration of duvelisib to mice engrafted with a PTCL patient-derived xenograft resulted in a shift among tumor-associated macrophages from the immunosuppressive M2-like phenotype to the inflammatory M1-like phenotype. In summary, duvelisib demonstrated promising clinical activity and an acceptable safety profile in relapsed/refractory TCL, as well as preclinical evidence of both tumor cell-autonomous and immune-mediated effects. This trial was registered at www.clinicaltrials.gov as #NCT01476657. [ABSTRACT FROM AUTHOR]

Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-δ (PI3K-δ) and PI3K-γ in late-stage clinical development for hematologic malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the dose escalation phase (n = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as 75 mg twice daily. In the expansion phase (n = 179), patients with indolent non-Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma (TCL) were treated with 25 or 75 mg duvelisib twice daily continuously. Single-dose duvelisib was rapidly absorbed (time to maximum concentration, 1-2 hours), with a half-life of 5.2 to 10.9 hours. PD results showed inhibition of phospho-AKT (S473) in CLL tumor cells following a single dose and near-complete inhibition of CLL proliferation (Ki-67) by cycle 2. Clinical responses were seen across a range of doses and disease subtypes: iNHL overall response rate, 58% (n = 31) with 6 complete responses (CRs); relapsed/refractory CLL, 56% (n = 55) with 1 CR; peripheral TCL, 50% (n = 16) with 3 CR; and cutaneous TCL, 32% (n = 19). Median time to response was ∼1.8 months. Severe (grade ≥3) adverse events occurred in 84% of patients: neutropenia (32%), alanine transaminase increase (20%), aspartate transaminase increase (15%), anemia and thrombocytopenia (each 14%), diarrhea (11%), and pneumonia (10%). These data support further investigation of duvelisib in phase 2 and 3 studies. This trial was registered at clinicaltrials.gov as #NCT01476657. [ABSTRACT FROM AUTHOR]

Bosutinib is an oral, dual SRC/ABL tyrosine kinase inhibitor (TKI) with clinical activity in Philadelphia chromosome-positive (Ph+) leukemia. We assessed the safety and tolerability of bosutinib 500 mg per day in a phase 1/2 study in chronic-phase (CP) chronic myeloid leukemia (CIVIL) or advanced Ph+ leukemia following resistance/intolerance to imatinib and possibly other TKIs. Patient cohorts included second-line CP CML (n = 286), third-/fourth-line CP CML (n = 118), and advanced leukemia (n = 166). Median bosutinib duration was 11.1 (range, 0.03-83.4) months. Treatment-emergent adverse events (TEAEs) in each cohort were primarily gastrointestinal (diarrhea [86%/83%/74%], nausea [46%/48%/ 48%], and vomiting [37%/38%/43%]). Diarrhea presented early, with few (8%) patients experiencing grade 3/4 events; dose reduction due to diarrhea occurred in 6% of affected patients. Grade 3/4 myelosuppression TEAEs were reported in 41% of patients; among affected patients, 46% were managed with bosutinib interruption and 32% with dose reduction. Alanine aminotransferase elevation TEAEs occurred in 17% of patients (grade 3/4, 7%); among patients managed with dose interruption, bosutinib rechallenge was successful in 74%. Bosutinib demonstrated acceptable safety with manageable toxicities in Ph+ leukemia. [ABSTRACT FROM AUTHOR]

Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors. [ABSTRACT FROM AUTHOR]

Abstract: The increased survival associated with treatments for CML emphasize the importance of understanding the HRQOL of newly diagnosed and previously treated CML patients with all phases of disease. Functional Assessment of Cancer Therapy-Leukemia results from a phase 3 and a phase 2 trial are reported for over 900 1st, 2nd, 3rd line CP, AP, and BP patients. Physical Well-being and Leukemia symptoms were worse for patients in later lines of therapy. Individuals with AP and BP CML had poorer HRQOL than individuals with CP CML. HRQOL of CML patients was predominantly consistent with the longitudinal clinical trajectory of the disease. [Copyright &y& Elsevier]

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pre-treated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic résponse was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/ maintained in 73% of patients. On-treat-ment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhemato-logic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the impact of second-line tyrosine kinase inhibitor therapy on the health-related quality of life (HRQOL) of imatinib (IM)-resistant and IM-intolerant chronic phase chronic myeloid leukemia (CP CML) patients is important given the increased survival that comes with therapy. As part of a bosutinib single-arm phase 2 trial, 200 IM-resistant and 88 IM-intolerant CP CML patients’ HRQOL was assessed prior to and throughout treatment with the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Little HRQOL impairment was demonstrated at baseline. Over the course of 96weeks on bosutinib therapy, patients noted statistically significant and/or clinically meaningful improvements on several FACT-Leu scales. [Copyright &y& Elsevier]

Uranyl oxide hydrate minerals are common in the altered zones of U deposits and are expected to form where spent nuclear fuel is altered in an oxidizing environment. Consistent with all known uranyl oxide hydrate minerals, metaschoepite [(UO2)4O(OH)6](H2O)5, contains sheets of uranyl polyhedra with H2O groups located in the interlayer. Several crystals along the series from metaschoepite to Na-substituted metaschoepite (Na-MS), approximate formula Na[(UO2)4O2(OH)5](H2O)5, have been synthesized and their structures have been determined. Each contains sheets of uranyl pentagonal bipyramids that are topologically identical to those in metaschoepite, schoepite and fourmarierite. The sheets are electroneutral in metaschoepite, but substitution of O for OH located at the equatorial vertices of the uranyl polyhedra gives a charged sheet that is balanced by incorporation of Na in the interlayer. Synthesis of crystals of Na-MS from a solution containing ∼500 ppm Np5+, followed by analysis of the crystals using laser-ablation inductively coupled-plasma mass-spectroscopy, demonstrated that the crystals incorporate Np. This is in contrast to earlier studies that showed no incorporation of Np5+ in synthetic metaschoepite (which has electroneutral sheets), and supports the hypothesis that Np5+ incorporation is more likely in uranyl oxide hydrates with charged species in the interlayer. [ABSTRACT FROM AUTHOR]

The United States Forest Service promulgated new planning regulations under the National Forest Management Act in 2012 (i.e., the Planning Rule). These new regulations include the first requirements in U.S. public land management history for National Forests to evaluate, protect, and/or restore ecological connectivity as they revise their land management plans. Data and resource limitations make single‐species, functional connectivity analyses for the myriad species that occur within the 78 million ha the Forest Service manages implausible. We describe an approach that relies on freely available data and generic species, virtual species whose profile consists of ecological requirements designed to reflect the needs of a group of real species, to address the new Planning Rule requirements. We present high‐resolution connectivity estimates for 10 different generic species across a 379,000 ha study area centered on the Custer Gallatin National Forest (CGNF) in Montana and South Dakota under two different movement models. We identify locations important for connectivity for multiple species and characterize the role of the CGNF for regional connectivity. Our results informed the Plan Revision process on the CGNF and could be readily exported to other National Forests currently or planning to revise their land management plans under the new Planning Rule. [ABSTRACT FROM AUTHOR]

Pediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. In so doing we found that pediatric brain tumors were more sensitive to the viruses and expressed significantly more nectin-1 (CD111) than adult glioblastoma. Pediatric embryonal and glial tumors were 74-fold and 14-fold more sensitive to M002 and 16-fold and 6-fold more sensitive to G207 than adult glioblastoma, respectively. Of note, pediatric embryonal tumors were more sensitive than glial tumors. Differences in sensitivity may be due in part to nectin-1 expression, which predicted responses to the viruses. Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV. [ABSTRACT FROM AUTHOR]

Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma. [ABSTRACT FROM AUTHOR]