Exploration of Textile-Silicone Composites and Materials for Personal Impact-Resistant Protection.

Conventional cushioning materials such as silicone sheets which have been recommended for resisting impact generally cause discomfort to the wearer from heat and perspiration. With the increasing need for personal protective equipment, textile-silicone composite structures are proposed in this study to reduce acute impact and moisture while enhancing thermal comfort. The influence of the composite structure and thickness on the mechanical and thermal properties of textile-silicone materials are systematically investigated. The results show that an additional knitted powernet fabric as a composite material can significantly improve the tensile properties of silicone rubber by up to 315%. However, only a slight improvement is found in the thermal conductivity (up to 16%), compression elasticity (up to 18%) and force reduction performance (up to 3.6%). As compared to inlaid spacer fabric, which has also been used for cushioning and preserving thermal comfort, the textile-silicone composites have higher tensile and compression elasticity, exhibit force reduction with the largest difference of 43% and are more thermally conductive, with increases more than 38%. The findings of this study introduced a cost-effective new silicone-textile composite for optimal impact protection and wear comfort for protective applications.

A Scientometric Analysis and Visualization of Prosthetic Foot Research Work: 2000 to 2022.

This study aims to highlight recent research work on topics around prosthetic feet through a scientometric analysis and historical review. The most cited publications from the Clarivate Analytics Web of Science Core Collection database were identified and analyzed from 1 January 2000 to 31 October 2022. Original articles, reviews with full manuscripts, conference proceedings, early access documents, and meeting abstracts were included. A scientometric visualization analysis of the bibliometric information related to the publications, including the countries, institutions, journals, references, and keywords, was conducted. A total of 1827 publications met the search criteria in this study. The related publications grouped by year show an overall trend of increase during the two decades from 2000 to 2022. The United States is ranked first in terms of overall influence in this field (n = 774). The Northwestern University has published the most papers on prosthetic feet (n = 84). Prosthetics and Orthotics International has published the largest number of studies on prosthetic feet (n = 151). During recent years, a number of studies with citation bursts and burst keywords (e.g., diabetes, gait, pain, and sensor) have provided clues on the hotspots of prosthetic feet and prosthetic foot trends. The findings of this study are based on a comprehensive analysis of the literature and highlight the research topics on prosthetic feet that have been primarily explored. The data provide guidance to clinicians and researchers to further studies in this field.

Associations of School Diversity with Students' Race-based Victimization and School Connectedness: A Combined Influence of Student and Teacher Racial/Ethnic Diversity and Socioeconomic Diversity.

School diversity has been shown to be associated with students' school experiences. However, most studies have focused solely on student racial/ethnic diversity, in spite of the multifaceted nature of diversity. This study assessed how the combined influence of student and teacher racial/ethnic diversity and socioeconomic diversity were related to race-based victimization, school connectedness, and racial/ethnic disparities of these outcomes. The participants were Asian, Black, Latinx, and White students (n = 100,408; 46.2-53.5% female) in Grade 7 to Grade 12 attending 278 public schools in California. The participating schools' diversity contexts were categorized into four latent profiles differentiated by varying levels of student and teacher racial/ethnic diversity and socioeconomic diversity. Race-based victimization was the least prevalent in schools with low student racial/ethnic diversity, low socioeconomic diversity, and moderate teacher racial/ethnic diversity. The magnitude of racial/ethnic disparities in race-based victimization differed across the four latent profiles; racial/ethnic disparities were minimal when there were similar numbers of students in each racial/ethnic group. School diversity's relation with school connectedness was minimal. White students perceived higher school connectedness than other racial/ethnic groups across profiles, but the White-Latinx gap was smaller in profiles with schools having a homogeneous Latinx student population. The findings underline the importance of understanding school diversity's interaction with students' characteristics, particularly racial/ethnic identity, on students' school experiences.

Teacher victimization and teachers' subjective well-being: Does school climate matter?

Guided by the job demands-resources model, we examined the multilevel associations between victimization experience with student violence directed against teachers, school climate, and teachers' subjective well-being (i.e., school connectedness and teaching efficacy) among 1711 teachers (7th-12th grade) from 58 middle and high schools in China. Hierarchical linear modeling analyses revealed that teachers who reported more frequent teacher victimization perceived a lower level of teaching efficacy; however, teachers in schools with a higher level of teacher victimization scores at the school level perceived a higher level of teaching efficacy. Although school climate was positively related to teacher well-being at both teacher and school levels, the negative association between teacher victimization and teachers' subjective well-being at the teacher level was exacerbated in schools with a more positive school climate at the school level. The significant cross-level moderating effect of school-level school climate in the association between teacher-level victimization and subjective well-being was consistent with the "healthy context paradox" but contradicted with the "emotion contagion hypothesis." Our findings support the risk influence of teacher victimization and the promotive role of positive school climate on teachers' subjective well-being. Our results also indicate that teachers in schools with a more positive and collective perception of school climate tend to be more attuned to the negative influences of teacher victimization on their subjective well-being than teachers in schools with a less positive and collective perception of school climate.

Social support profiles associations with adolescents' psychological and academic functioning.

Social support is empirically linked to improved adolescent psychological and academic functioning. This study explored typologies characterized by family, peer, and school support among students in early (Grade 7; n = 27,399) and late (Grade 11; n = 27,984) adolescence. We assessed how each latent profile related to key aspects of psychological and academic functioning and the moderation of gender in these associations. Three convergent profiles (i.e., High, Moderate, and Low Support) and two divergent profiles (i.e., Minimum Peer Support and Minimum Family Support) were found in both grade levels, with psychological and academic functioning differentiated by the profiles. The Minimum Peer Support and Minimum Family Support profiles showed the lowest functioning in all domains across grade levels. The High Support profile showed the highest psychological health and academic performance. Gender moderation was observed in the associations between social support profiles and psychological functioning and was more prominent among 7th graders than 11th graders. Findings suggest that social support's impact is determined by combinations of various support sources, age, and gender. The social support profiles and their associations with students' characteristics and outcomes may inform practitioners in supporting vulnerable groups and planning interventions.

Heterogeneity Among Moderate Mental Health Students on the Mental Health Continuum-Short Form (MHC-SF).

Measures of positive well-being are needed to support the shift away from a deficit-based approach to mental health. This study examined one measure, the Mental Health Continuum-Short Form (MHC-SF), as a measure of positive well-being used in school-based mental health monitoring efforts. This study used latent profile analysis (LPA) to explore the mental health classifications of 10,880 California high school students' responses to MHC-SF emotional, psychological, and social well-being items. Five latent mental wellness profiles emerged, including two ordered profiles (i.e., High Well-Being and Low Well-Being) and three profiles spanning the two ordered profiles. The High Well-Being profile had the most favorable psychological adjustment, and the three moderate well-being range profiles had differentiated functioning. Informing the utility of the MHC-SF, this study also compared the MHC-SF categorical diagnostic criteria with the LPA's empirical classification approach and found the two classification approaches to be congruent. The findings provide an impetus for educators to attend to students in moderate well-being ranges and emphasize promoting positive mental well-being as an essential component of school-based mental health services.

Elementary school teacher well-being and supportive measures amid COVID-19: An exploratory study.

As frontline education providers, teachers have encountered many challenges since the outbreak of the COVID-19 pandemic. To better understand teacher well-being during this crisis and inform practices to support them, this study employed an online survey with a mixed-methods approach to assess teacher well-being and the support they need to work effectively. A sample of 151 elementary school teachers in the United States was recruited in summer 2020 to complete an online survey through emails and social media outlets. Participants were asked to provide retrospective reports of their experiences teaching in spring 2020 after schools closed due to COVID-19. The majority of participants reported feeling emotionally exhausted and high levels of task stress and job ambiguity. Consistent with hypotheses, path analysis testing a model informed by the job demand-resources framework indicated that task stress and job ambiguity were robustly related to teacher well-being. Moreover, three job resources (i.e., teaching efficacy, school connectedness, and teaching autonomy) were related to job satisfaction. A moderation finding revealed that teachers who reported high teaching efficacy felt emotionally exhausted when they were unclear of their job duties. Thematic analysis of responses to an open-ended question found that teachers would feel supported if provided resources to develop competence in distance learning, workplace emotional support, and flexibility during COVID-19. The findings identified a critical need to allocate more attention and resources to support teacher psychological health by strengthening emotional support, autonomy, and teaching efficacy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

School-wide social emotional learning (SEL) and bullying victimization: Moderating role of school climate in elementary, middle, and high schools.

Guided by the school-wide social-emotional learning framework and social-ecological model, in this study we examined the associations between students' perceptions of four core social emotional learning (SEL) competencies (i.e., responsible decision-making, social awareness, self-management, and relationship skills) and school climate and their experience with bullying victimization through a multilevel framework. We also examined the multilevel moderating effects of students' perceptions of school climate, gender, and school levels (elementary, middle, and high schools) on the association between SEL competencies and bullying victimization. Participants were 23,532 students (4th to 12th grade) from 90 schools in Delaware. Using hierarchical linear modeling and controlling for demographic factors and school climate at both student and school levels, we found that three of the four core SEL competencies (i.e., social awareness, relationship skills, and self-management) and student-level school climate perceptions had significant associations with students' bullying victimization experiences. Moreover, the positive association between social awareness and bullying victimization and the negative association between self-management and bullying victimization were both mitigated in schools with more positive school climate at the student level. The association between some of the SEL competencies and bullying victimization varied depending on students' gender and grade levels. The findings highlight the unique and differentiated relations among the four core SEL competencies and students' bullying victimization experiences; they also suggest the importance of including school climate assessment and applying gender- and grade-level-specific efforts in bullying prevention programs with an SEL focus.

Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.

OBJECTIVE: To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service. METHODS: Five cases with secondary findings were reviewed. RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which was supported by arrayCGH of amniocyte DNA, with final karyotype showing mosaic tetrasomy 18p. In Case 2, a deletion in the proximal long arm of chromosome 18 of maternal origin was suspected and confirmed by arrayCGH of maternal white cell DNA. In Case 3, NIPT was negative for trisomies 21 and 18. In-depth analysis for deletions/duplications was requested when fetal structural anomalies were detected at routine scan. A deletion in the proximal long arm of chromosome 3 was found and confirmed by karyotyping. In Case 4, NIPT correctly predicted confined placental mosaicism with triple trisomy involving chromosomes X, 7 and 21. In Case 5, NIPT correctly detected a previously unknown maternal mosaicism for 45X. CONCLUSION: Non-invasive prenatal testing is able to detect a wide range of fetal, placental and maternal chromosomal abnormalities. This has important implications on patient counseling when an abnormality is detected by NIPT.

Non-invasive prenatal screening of fetal Down syndrome by maternal plasma DNA sequencing in twin pregnancies.

Non-invasive prenatal screening for fetal Down syndrome (NIFTY) by maternal plasma sequencing was performed in 12 subjects with twin pregnancies, including 11 with normal fetuses and 1 with discordant fetal Trisomy 21. For every sample, it was processed, sequenced and reported as soon as it was collected as other clinical samples for singleton pregnancies. The NIFTY test was negative in the 11 pregnancies carried normal fetuses, and was positive (high risk) in the case with discordant fetal Trisomy 21. The sensitivity and specificity were both 100%. This small case series suggested the NIFTY as a screening test for fetal Trisomy 21 is feasible in twin pregnancies.

Non-invasive prenatal screening of fetal sex chromosomal abnormalities: perspective of pregnant women.

OBJECTIVE: To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test. METHODS: Two hundred and one patients carried a singleton pregnancy requesting the NIFTY test were invited to give their preferences if there was suspicion of SCA by the NIFTY test. RESULTS: Over 93.5% were ethnic Chinese, with a mean age of 36. Prior Down screening was positive in 66 (32.8%). Over 50% of subjects considered SCA to be better in terms of disability compared to Down syndrome, and only 5.2% considered SCA to be worse. Yet, the majority (198, 98.5%) indicated that they wanted to be informed if there was suspicion of SCA. Of whom 34.8% would have an amniocentesis for confirmation, while 57.1% were not certain, indicating the possibility of accepting these conditions. CONCLUSION: Besides screening Down syndrome by NIFTY, most pregnant women would also like to be informed if there was suspicion of SCA. Those screened positive should be counseled by those with experience in genetics to avoid unnecessary pregnancy termination.

Clinical utility of noninvasive fetal trisomy (NIFTY) test--early experience.

OBJECTIVE: To report the initial experience of noninvasive prenatal diagnosis of fetal Down syndrome (The NIFTY test) in a clinical setting. METHODS: The NIFTY test was offered as a screening test for fetal Down syndrome to pregnant women with a singleton pregnancy at 12 weeks of gestation or beyond. A satisfaction questionnaire was sent to the first 400 patients. RESULTS: During a 6-month period, 567 NIFTY tests were performed. Over 90% of those studied were ethnic Chinese, and the mean age of the women studied was 36 years. The test was performed at 12-13 weeks of gestation in 49.21%. The median reporting time was 9 days. The test was positive for trisomy 21 in eight cases, and for trisomy 18 in 1 case; all were confirmed by fetal karyotyping. There was no false-positive result. Of the questionnaires, 182 completed responses were received. Over 95% had complete or almost complete resolution of anxiety. Except for one, all were satisfied with the NIFTY test, and all indicated that they would recommend the test to their friends. CONCLUSION: The NIFTY test was a highly specific test. Unnecessary invasive tests and associated fetal losses could be avoided in almost all women who have a normal fetus.

Fluorescence-assisted cytological testing (FACT): Ex Vivo viral method for enhancing detection of rare cancer cells in body fluids.

Cytological analysis of body fluids is currently used for detecting cancer. The objective of this study was to determine if the herpes virus carrying an enhanced green fluorescent protein (EGFP) could detect rare cancer cells in body fluids against millions of normal cells. Human cancer cells suspended with normal murine cells were infected with NV1066 at a multiplicity of infection (MOI) of 0.5 and 1.0 for 18 h. Fluorescent microscopy and flow cytometry were used for EGFP detection of cancer cells. EGFP-expressing cells were confirmed as cancer cells with specific markers by immunohistochemistry staining. Limits of detection of cancer cells in body fluid were measured by serial dilutions. Applicability of technique was confirmed with samples from patients with malignant pleural effusions. NV1066 expressed EGFP in 111 human cancer cell lines detected by fluorescent microscopy at an MOI of 0.5. NV1066 selectively infected cancer cells and spared normal cells as confirmed by immunohistochemistry. Sensitivity of detecting fluorescent green cells was 92% (confidence interval [CI] 83% to 97%) at a ratio of 1 cancer cell to 1 million normal cells. EGFP-positive cells were detected by fluorescent microscopy in patients' malignant pleural effusion samples. Our data show proof of the concept that NV1066-induced EGFP expression allows detection of a single cancer cell against a background of 1 million normal cells. This method was demonstrated to be a reliable screening tool for human cancer cells in a suspension of normal murine cells as well as clinical specimens of malignant pleural effusions.

Hyperthermia potentiates oncolytic herpes viral killing of pancreatic cancer through a heat shock protein pathway.

BACKGROUND: Oncolytic herpes simplex virus-1 (HSV-1) is designed to specifically infect, replicate in, and lyse cancer cells. This study investigates a novel therapeutic regimen, combining the effects of NV1066 (a recombinant HSV-1) and hyperthermia in the treatment of pancreatic cancer. METHODS: NV1066 is an attenuated HSV-1 that replicates in cells resistant to apoptosis. Heat shock protein 72 (Hsp72) is a member of a family of proteins that is upregulated after hyperthermic insult, lending cellular protection by inhibiting apoptosis. In these experiments, we test the hypothesis that increased Hsp72 expression in response to hyperthermia enhances anti-apoptotic mechanisms, thereby increasing viral replication and tumor cell kill. Hs 700T pancreatic cancer cells were treated with hyperthermia alone (42 degrees C), NV1066 alone, and combination therapy. Cell survival and viral growth were measured. The effect of siRNA-directed Hsp72 knockdown was also measured. RESULTS: Combining hyperthermia and viral treatment produced a synergistic effect on cell kill. Viral growth increased greater than 6-fold in the presence of hyperthermia (P < .05). Hyperthermia alone showed minimal cytotoxic activity against Hs 700T cells, while NV1066 infection resulted in approximately 50% cell kill. The combination of hyperthermia and viral infection significantly increased cell kill to approximately 80% (P < .01). Hsp72 knockdown attenuated this synergistic effect. CONCLUSION: Hyperthermia enhances NV1066 replication, thereby potentiating the viral oncolytic response against pancreatic cancer cells. This finding has potential clinical application in the use of heated perfusion or permissive hyperthermia for delivery of oncolytic viral therapies.

Radiation-induced cellular DNA damage repair response enhances viral gene therapy efficacy in the treatment of malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) treated with radiotherapy (RT) has incomplete responses as a result of radiation-induced tumoral stress response that repairs DNA damage. Such stress response is beneficial for oncolytic viral therapy. We hypothesized that a combination of RT and NV1066, an oncolytic herpes virus, might exert an additive or synergistic effect in the treatment of MPM. METHODS: JMN, a MPM cell line, was infected with NV1066 at multiplicities of infection of .05 to .25 in vitro with and without radiation (1 to 5 Gy). Virus replication was determined by plaque assay, cell kill by lactate dehydrogenase assay, and GADD34 (growth arrest and DNA damage repair 34, a DNA damage-repair protein) by real-time reverse transcriptase-polymerase chain reaction and Western blot test. Synergistic cytotoxicity dependence on GADD34 upregulation was confirmed by GADD34 small inhibitory RNA (siRNA). RESULTS: Synergism was demonstrated between RT and NV1066 across a wide range of doses. As a result of such synergism, a dose-reduction for each agent (up to 5500-fold) can be accomplished over a wide range of therapeutic-effect levels without sacrificing tumor cell kill. This effect is correlated with increased GADD34 expression and inhibited by transfection of siRNA directed against GADD34. CONCLUSIONS: RT can be combined with oncolytic herpes simplex virus therapy in the treatment of malignant pleural mesothelioma to achieve synergistic efficacy while minimizing dosage and toxicity.

Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus.

OBJECTIVES: Lymph node status is the most important prognostic factor determining recurrence and survival in patients with mesothelioma and other thoracic malignancies. Accurate localization of lymph node metastases is therefore necessary to improve selection of resectable and curable patients for surgical intervention. This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell-specific expression of green fluorescent protein. METHODS: After infection with NV1066, a herpes simplex virus carrying green fluorescent protein transgene, human mesothelioma cancer cell lines were assessed for cancer cell-specific infection, green fluorescent protein expression, viral replication, and cytotoxicity. Murine models of lymphatic metastasis were established by means of surgical implantation of cancer cells into the preauricular (drainage to cervical lymph nodes) and pleural (mediastinal and retroperitoneal lymph nodes) spaces of athymic mice. Fluorescent thoracoscopy, laparoscopy, and stereomicroscopy were used to localize lymph node metastases that were confirmed by means of immunohistochemistry. RESULTS: In vitro NV1066 infected, replicated (5- to 17,000-fold), and expressed green fluorescent protein in all cancer cells, even when infected at a low ratio of one viral plaque-forming unit per 100 tumor cells. In vivo NV1066 injected into primary tumors was able to locate and infect lymph node metastases producing green fluorescent protein that was visualized by means of fluorescent imaging. Histology confirmed lymphatic metastases, and immunohistochemistry confirmed viral presence in regions that expressed green fluorescent protein. CONCLUSIONS: Herpes virus-guided cancer cell-specific production of green fluorescent protein can facilitate accurate localization of lymph node metastases. Fluorescent filters that detect green fluorescent protein can be incorporated into operative scopes to precisely localize and biopsy lymph node metastases.

Real-time intraoperative detection of breast cancer axillary lymph node metastases using a green fluorescent protein-expressing herpes virus.

OBJECTIVE: To investigate the use of a green fluorescent protein (GFP)-expressing oncolytic herpes virus to enable real-time intraoperative detection of breast cancer lymph node metastases. SUMMARY BACKGROUND DATA: Axillary lymph node status is the most important factor determining treatment, recurrence, and overall survival for women with breast cancer. The current methods of determining nodal status, however, have limitations. NV1066 is a novel oncolytic herpes viral strain that specifically infects cancer cells and expresses GFP. METHODS: Seven human breast cancer cell lines were infected in vitro with NV1066 and assessed for GFP expression, viral replication, and cytotoxicity. An in vivo model of breast cancer lymphatic metastasis was established in mice. Tumor-bearing mice were treated with NV1066 via injection into the primary tumor. Axillary lymph nodes were analyzed using an in vivo fluorescent imaging system. Histologic and molecular assessment of lymph nodes were performed using immunohistochemistry and reverse transcriptase PCR and operating characteristics were determined. RESULTS: NV1066 infected, expressed GFP, replicated within, and killed all human breast cancer cell lines in vitro. Injection of NV1066 into primary breast tumors resulted in viral transit to axillary lymph nodes, infection of lymphatic metastases, and GFP expression that was visualized with in vivo fluorescent imaging. Histologic and molecular confirmation demonstrated favorable operating characteristics of this method (sensitivity 80%; specificity 96%). CONCLUSIONS: We introduce a novel, sensitive, and specific method of lymphatic mapping that utilizes NV1066-guided cancer cell-specific viral production of GFP to enable real-time intraoperative detection of lymphatic metastases.

Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer.

Oncolytic herpes simplex virus-1 (HSV-1) mutants selectively replicate in and lyse tumor cells. Viral replication is dependent on the cellular proliferative mechanism. Estrogen increases cellular proliferation and decreases apoptosis in estrogen receptor-positive (ER+) human breast cancer cells. We hypothesize that the cellular changes produced by estrogen may enhance oncolytic viral replication and improve the treatment of ER+ breast cancer cells. Estrogen increased proliferation and replication of the HSV-1 mutant, NV1066, in ER+ breast cancer cells. Additionally, cells grown with estrogen had lower rates of apoptosis and higher bcl-2 levels at baseline and after infection. Estrogen enhanced the oncolytic effect of NV1066, with cell kills of 95% and 97% at MOIs of 0.1 and 0.5, compared to 53 and 87% respectively without estrogen (p<0.001). Therapy of ER+ human breast cancer cells with a replication-competent HSV-1 mutant is improved in the presence of estrogen, in contrast to more standard therapies, such as chemotherapy and radiation, which demonstrate decreased efficacy in similar conditions. These data provide the mechanistic basis for the use of oncolytic HSV-1 in patients with hormone receptor-positive breast cancer, particularly if the disease progresses with conventional therapies.

Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery.

Current efforts on expanding minimally invasive techniques into the realm of oncological surgery are hindered by lack of accurate visualization of tumor margins and failure to detect micro metastases in real time. We used a systemic delivery of a herpes viral vector with cancer-selective infection and replication to precisely differentiate between normal and malignant tissue. NV1066 is a genetically modified, replication-competent herpes simplex virus carrying a transgene for enhanced green fluorescent protein (GFP). We tested the potential of NV1066 in delineating tumor tissue in vitro and in vivo in a wide range of cancers and whether NV1066-induced GFP expression can detect small foci of tumors and metastases in in vivo models using an operating endoscope with fluorescent filters. Our findings indicate that NV1066 can be used for real-time intraoperative imaging and enhanced detection of early cancers and metastases. We demonstrate that a single dose of NV1066, administered either locally (intratumoral or intracavitary) or systemically, will detect loco-regional and distant disease throughout the body. Such cancer selectivity is confirmed in 110 types of cancer cells from 16 different primary organs. Fluorescence-aided minimally invasive endoscopy revealed microscopic tumor deposits unrecognized by conventional laparoscopy/thoracoscopy. Furthermore, NV1066 ability to transit and infect tumor and metastases is proven in syngenic and transplanted tumors in different animal models, both immunocompetent and immunodeficient. Cancer-selective GFP expression is confirmed by histology, immunohistochemistry, and qRT-PCR. These studies form the basis for real-time, intraoperative diagnostic imaging of tumor and metastases by minimally invasive endoscopic technology.

Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. METHODS: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. RESULTS: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. CONCLUSION: These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.