bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B9: Abnormalities in cellular and humoral immunity in breast cancer patients resistant to endocrine therapy.
Authors: Zavadova Eva , Konopasek Bohuslav , Vocka Michal , Miskovicova Michaela , Spacek Jan , Fucikova Terezie , Petruzelka Lubos
Published: August 2014

Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients.

Although more than 2/3 of treated patients respond to the endocrine therapy, most patients with metastatic breast cancer will develop resistance.. It appears that other factor contributing to the resistance may be a transforming factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endothelial growth factor /VEGF.

The purpose of the study was to monitor immune responses in patients with hormone receptor positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF beta, and VEGF production was monitored and we analyzed the changes during hormonal treatment.

Methods: 85 patients included in the research project were implemented routine cancer treatment with endocrine therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta, VEGF were measured by ELISA and anti-tumor cellular immunity (CD4, CD8, antigen presenting cells ) were measured by flow cytometry.

Results In patients with resistance to endocrine therapy mainly depression in cellular immunity was found. Immunglobulin plasma level was decreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particularly in those, involved into blood coagulation process/anti phospholipide and anti cardiolipin autoantibodies.

Conclusion Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the prediction of resistance to hormonal therapy and contribute to the selection of targeted immune therapy in cancer patients.

Dedication: This project was supported by grant IGA NT11168-3/2010.

Citation Format: Eva Zavadova, Bohuslav Konopasek, Michal Vocka, Michaela Miskovicova, Jan Spacek, Terezie Fucikova, Lubos Petruzelka. Abnormalities in cellular and humoral immunity in breast cancer patients resistant to endocrine therapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B9.
Abstract B90: Eribulin mesylate alters immune homeostasis in mice bearing syngeneic tumors.
Authors: Albu Diana I. , Kumar Namita , Kusnetzov Galina , Xu Shanqin , Littlefield Bruce , Woodall-Jappe Mary
Published: August 2014

Numerous studies indicate that certain tumor-infiltrating macrophage subsets can support neoplastic growth. Recent reports showed that spleen can serve as an important reservoir for macrophages and neutrophils that replicate in situ, then migrate to support tumor growth. Eribulin mesylate (Halaven®) is a microtubule-dynamics inhibitor approved for third line clinical use in patients with heavily pretreated metastatic breast cancer based upon statistically significant increase in median overall survival (OS) compared to treatment of physician's choice. In an effort to understand whether eribulin has additional effects beyond its anti-mitotic activity, the current study addressed the effects of eribulin mesylate on immune cells. Using the subcutaneous syngeneic murine tumor model Lewis lung carcinoma (LLC), we found that the tumor shrinking effect of eribulin correlated with increased extramedullary hematopoiesis observed in the spleens of treated mice. Eribulin was also found to inhibit the proliferation of M2 tumor-associated macrophages (TAMs) in the spleens of LLC-bearing mice. Early effects of eribulin were studied using the CT-26 colon tumor isograft model and included increased differentiation and death of CD4+ and CD8+ effector T cells. Furthermore, eribulin caused increased CD25 expression on CD4+ Foxp3- T cells but not on CD4+ Foxp3+ T regulatory cells. Finally, frequencies of exhausted CD8+ T cells were reduced following eribulin treatment. Taken together, these results suggest that eribulin-mediated modulation of immune homeostasis especially in the spleen, may contribute to its anti-tumor effect.

Citation Format: Diana I. Albu, Namita Kumar, Galina Kusnetzov, Shanqin Xu, Bruce Littlefield, Mary Woodall-Jappe. Eribulin mesylate alters immune homeostasis in mice bearing syngeneic tumors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B90.
Abstract B97: The role of JNK isoforms in adenovirus-induced autophagy: Implications for cancer immunotherapy using oncolytic adenoviruses.
Authors: Klein Sarah R. , Jiang Hong , Piya Sujan , Lu Zhimin , Gomez-Manzano Candelaria , Fueyo Juan
Published: August 2014

Glioblastoma multiforme is the most common and lethal form of primary brain tumor in adults. Targeted immunotherapy using recombinant oncolytic viruses is a promising strategy for the treatment of brain tumors. Delta-24-RGD is a highly selective and potent oncolytic adenovirus that induces autophagy in malignant gliomas. Data from our ongoing clinical trial suggested Delta-24-RGD initiated an anti-tumor immune response in patients. Importantly, autophagy promotes the presentation of viral antigens for activation of immune cells; therefore, we sought to elucidate the molecular mechanisms by which adenoviruses induce autophagy. Adenoviral replication induced phosphorylation of JNK that was required for autophagy. Our results indicated that JNK regulates autophagy through Bcl-2 phosphorylation and consequent dissociation of Bcl-2 and beclin 1. Contrary to starvation-induced autophagy, adenovirus-mediated autophagy was facilitated by both JNK1 and JNK2 isoforms of JNK. Moreover, our data indicated that adenoviral antigens were presented at the cell surface, which was ablated upon down-regulation of JNK or autophagy. We propose a JNK/autophagy-dependent mechanism for the immune presentation of viral antigens that can be leveraged when developing recombinant adenoviruses for the advancement of anti-tumor immunotherapy. Thus, we developed a genetically-modified Delta-24 adenovirus expressing an EGFRvIII epitope that is aberrantly expressed in gliomas. The majority (>80%) of cells infected with Delta-24-FvIII presented the fiber-bound EGFRvIII epitope on their surface, an effect that was diminished upon inhibition of autophagy. Our data demonstrated that oncolytic adenoviruses can be modified to present cancer antigens for an anti-tumor immune response that may be enhanced by positively regulating autophagy.

Citation Format: Sarah R. Klein, Hong Jiang, Sujan Piya, Zhimin Lu, Candelaria Gomez-Manzano, Juan Fueyo. The role of JNK isoforms in adenovirus-induced autophagy: Implications for cancer immunotherapy using oncolytic adenoviruses. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B97.
Abstract IA10: Tipping the balance from a procarcinogenic to anticancer response in pancreatic cancer.
Authors: Jaffee Elizabeth
Published: August 2014

Pancreatic cancer remains a “death sentence”, with the poorest survival rates reported for solid tumors. Escalating this problem is the fact that pancreatic cancer is among the most resistant cancers to traditional forms of therapy. But in this new era of targeted therapies, there is reason to hope that significant progress will be made in the development of new treatments in the near future.

Until recently, barriers to immunotherapy clinical successes for pancreatic cancer have been due to a lack of understanding of the immune pathways within the pancreatic tumor microenvironment that hinder successful immune responses. Recent advances in our understanding of its immunobiology has identified new targets for developing cancer specific vaccines and new targets for modulating the tumor microenvironment to allow more potent activation and improved access of vaccine induced immune responses. We are just learning that non-neoplastic cells, including cancer-associated myofibroblasts, regulatory T cells, dendritic cells, myeloid-derived suppressor cells, and tumor-associated macrophages, are hijacked by pre-invasive and invasive cancer cells to create a tolerogenic tumor microenvironment. Current research is focused on elucidating the mechanisms of this tolerogenic polarization within the tumor microenvironment with the goal of tipping the balance in favor of an anticancer immune response. With the recent advances in molecular technologies and the development of relevant pancreatic cancer mouse models, it is now within our reach to dissect the inhibitory pathways within the pancreatic tumor microenvironment. This will in turn, lead to new therapeutic opportunities that will eliminate these barriers and convert this deadly cancer into a treatable disease.

This presentation will provide new data in pre-clinical and clinical studies demonstrating mechanisms that convert procarcinogenic inflammatory responses into anticancer immunity.

Citation Format: Elizabeth Jaffee. Tipping the balance from a procarcinogenic to anticancer response in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA10.
Abstract IA12: Translation of an OX40 agonist: Putting a foot on an immunologic gas pedal.
Authors: Weinberg Andrew D.
Published: August 2014

Our group has focused on using agonists to the TNF-receptor, OX40, to enhance anti-tumor immunity/activity. OX40 agonists have T cell costimulatory activity and are known to increase CD4 and CD8 T cell proliferation, effector function, and memory T cell survival. Injecting OX40 agonists into cancer-bearing hosts leads to increased anti-tumor immunity, which has been observed in several different mouse tumor models. The OX40 agonist anti-tumor activity is dependent on both CD4 and CD8 T cells and mice cured via OX40 agonists are immune to tumor rechallenge, suggesting an enhanced tumor-specific memory T cell response. The preclinical data led to the development of a mouse anti-human OX40 agonist Ab that was recently tested in a phase I clinical trial. The phase I trial treated metastatic cancer patients from several different tumor types, which included melanoma, renal cell carcinoma, ovarian cancer, lung cancer, colon cancer, and prostate cancer. A dose escalation of the human OX40 Ab was well-tolerated and showed increased signs of T cell proliferation in both CD4/FoxP3neg and CD8 T cells (via Ki-67 staining) that peaked at the 0.4 mg/kg dose level. We also found that OX40-induced proliferating CD8 T cells showed increased levels of immune activation, as these cells had increased levels of CD38 and HLA-DR on their surface. One round of treatment led to regression of at least one metastatic lesion in 12/30 patients treated, however there were no partial or complete responses by RECIST criteria. In a select group of patients we were able to assess anti-tumor immune responses pre- and post-anti-OX40 treatment. We found in 3 of 4 patients that the anti-tumor immune responses were increased following anti-OX40 administration. In summary, OX40 agonist stimulation enhances anti-tumor immunity in cancer-bearing hosts and this activity was translated to late stage cancer patients. The human OX40 agonist used in these clinical studies was a mouse Ab. Hence it could only be administered once and had a relatively short half-life in vivo, therefore humanized versions of the OX40 agonists will be tested in future clinical trials.

Citation Format: Andrew D. Weinberg. Translation of an OX40 agonist: Putting a foot on an immunologic gas pedal. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA12.
Abstract IA7: Regulation of myeloid-derived suppressor cells in tumor micro-environment.
Authors: Gabrilovich Dmitry
Published: August 2014

Myeloid-derived suppressor cells (MDSC) is a major factor responsible for tumor escape. These cells accumulate in large numbers in tumor-bearing hosts and are characterized by their myeloid origin, immature state, and, most importantly, by their potent ability to suppress different aspects of immune responses, primarily T-cell proliferation and cytokine production. This heterogeneous group of cells, consists of immature myeloid cells (IMC) with morphological and phenotypic characteristics, similar to that of monocytes (M-MDSC) and polymorphonuclear neutrophils (PMN-MDSC). However, MDSC have a distinct gene expression profile and a number of biochemical, and functional, differences from monocytes (Mon) and neutrophils (PMN). In tumor-bearing hosts, there is a constant influx of myeloid cells from the bone marrow to other peripheral organs. Soluble growth factors and certain cytokines produced by tumor cells modulate, expand and differentiate these immature myeloid cells by interacting with the receptors on their surface and converting them to a suppressive phenotype. Recently, “two-signal” model of MDSC accumulation was proposed. This model suggests that accumulation of MDSC can be separated into two processes governed by different signal transduction pathways. One pathway is predominantly responsible for MDSC expansion and the second one for driving MDSC activation. The fate of MDSC remains poorly understood. We found, contrary to our initial expectations, that MDSC, in tumor-bearing mice and cancer patients, have a substantially lower survival than their control counterparts, Mon and PMN. We have identified possible mechanism of this phenomenon and suggested that it can be used for selective elimination of MDSC in tumor-bearing hosts.

Citation Format: Dmitry Gabrilovich. Regulation of myeloid-derived suppressor cells in tumor micro-environment. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA7.
DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation
Authors: Bakhoum Samuel F. , Kabeche Lilian , Murnane John P. , Zaki Bassem I. , Compton Duane A.
Published: August 2014

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore–microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN.

Significance: The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. Cancer Discov; 4(11); 1281–9. ©2014 AACR.

See related commentary by Jelluma and Kops, p. 1256

This article is highlighted in the In This Issue feature, p. 1243
Role of Two Types of Angiotensin II Receptors in Colorectal Carcinoma Progression
Authors: Zhou Linyan , Luo Yi , Sato Seiya , Tanabe Eriko , Kitayoshi Misaho , Fujiwara Rina , Sasaki Takamitsu , Fujii Kiyomu , Ohmori Hitoshi , Kuniyasu Hiroki
Published: August 2014

Angiotensin II (Ang-II) is a bioactive peptide associated closely with the progression and metastasis of colorectal cancer (CRC). We examined the expression and role of 2 Ang-II receptor types in 20 cases of CRC. Ang-II type 1 receptor (AT1R) protein was localized to the plasma membrane, whereas Ang-II type 2 receptor (AT2R) protein was localized to the nuclei. AT1R expression showed a direct correlation with tumor stage and liver metastasis, whereas AT2R expression showed an inverse correlation. A knockdown study of the AT1R or AT2R with Ang-II treatment was performed to reveal their individual roles in a mouse rectal cell line CMT93, which expresses both Ang-II receptor types. AT2R knockdown showed that the AT1R was associated with tumor growth, survival, invasion and VEGF-A secretion in CMT93 cells in a dose-dependent manner. In contrast, AT1R knockdown showed that the AT2R was associated with increased VEGF-A secretion at low Ang-II concentrations, whereas high concentrations of Ang-II inhibited tumor growth, survival, invasion and VEGF-A secretion. Thus, the AT1R showed a monophasic protumoral effect, while the AT2R showed a biphasic amphitumoral effect. Our findings suggest that a high angiotensinogen condition in the liver might evoke the antitumoral role of the AT2R in CRC cells.
Long-Term Observation of the Vitreomacular Relationship in Normal Fellow Eyes of Patients with Unilateral Idiopathic Macular Holes
Authors: Otsuji Futoshi , Uemura Akinori , Nakano Tetsuro , Sakamoto Taiji
Published: August 2014

Purpose: To describe long-term changes in the vitreomacular relationship in normal fellow eyes of patients with unilateral idiopathic macular holes (MHs). Methods: This is a retrospective, observational case series. The medical records of patients who underwent surgery for idiopathic MHs between May 2000 and December 2010 were reviewed. Patients who had clinically normal fellow eyes and underwent 12 months or more of follow-up were included. The vitreomacular relationship in the fellow eyes was evaluated using optical coherence tomography (OCT) and slit-lamp biomicroscopy. Results: The study included 153 patients with a mean age of 65.5 years and a mean follow-up of 33.5 months (range, 12-121). The incidence of vitreomacular attachments evaluated by OCT was 52% (80 eyes) at initial examination, which decreased to 41, 37 and 23% at 1, 2 and 3 years after the initial examination, respectively. Of the 80 eyes with vitreomacular attachments at initial examination, 40 (50%) still had vitreomacular attachments at the final visit. Of the remaining 40 eyes in which vitreomacular separation occurred during follow-up, 11 (28%) developed an MH, with a mean interval of 45 months. None of the eyes with vitreomacular separation at presentation developed an MH. Conclusion: This largest series of fellow eyes of MHs followed by OCT shows that, at presentation, about half of the patients already have premacular vitreous detachment and therefore no risk of MH, and that second MH develops in about 30% in the process of vitreomacular separation, which evolves over a prolonged period.
Impact of Advanced Hearing Aid Technology on Speech Understanding for Older Listeners with Mild to Moderate, Adult-Onset, Sensorineural Hearing Loss
Authors: Cox Robyn M. , Johnson Jani A. , Xu Jingjing
Published: August 2014

Background: Hearing loss is one of the most common chronic health conditions of older people. Hearing aids are the customary treatment and they improve quality of life in older adults. Even so, relatively few older adults with uncomplicated, mild to moderate, adult-onset, sensorineural hearing loss use hearing aids. One reason for this is a belief that hearing aids do not provide sufficient value to justify their expense. Although modern hearing aids are available at several price points, there is minimal evidence about the relative benefits of premium-level versus basic-level hearing aid technologies. Objective: This research was designed to demonstrate the relative effectiveness of premium hearing aids compared with basic hearing aids in improving speech understanding and quality of life. Methods: 25 participants, including both new and experienced hearing aid users, completed blinded month-long field trials with each of four pairs of hearing aids: two basic and two premium level. Outcomes were laboratory speech understanding tests, standardized questionnaires and open-ended diary items. Results: Participants reacted very positively to all the hearing aids. Both everyday speech understanding and quality of life were substantially improved with hearing aids. Results for both new and experienced users were consistent with a conclusion that there were no statistically significant or clinically important differences in improvement between the premium- and basic-level hearing aids. Conclusions: It should not be assumed that more costly hearing aids always produce better outcomes. With contemporary hearing aids from two major manufacturers, the subjects obtained as much improvement in speech understanding and quality of life from lower-cost basic-level instruments as from higher-cost premium-level instruments. Regardless of technology level, comprehensive best-practice fitting protocols should be followed to optimize results for every patient. © 2014 S. Karger AG, Basel
Prevalence of Methicillin-Resistant Staphylococcus aureus: Effect of Different Criteria for Elimination of Duplicates
Authors: Álvarez-Paredes Ledicia , López-Riquelme Natividad , Rodríguez Juan Carlos , Santibañez Miguel , Belda Sofía , Galiana Antonio , López Pilar , Ruiz-García Montserrat , Royo Gloria
Published: August 2014

Background: The purpose of this study is to compare the effect of different systems for eliminating duplicates in order to optimize the calculation of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection. Methods: We compare the Clinical and Laboratory Standards Institute (CLSI) criterion, time criteria and the criterion recommended by the European Antimicrobial Surveillance System (EARSS). Results: Multiple isolates of MRSA are frequently recovered from successive cultures from the same patient (the average isolation rate of MRSA is 2.72), which demonstrates the importance of eliminating duplicates. When CLSI criterion data are compared to those obtained using other criteria, a significant increase in the number of S. aureus isolates was found applying time criteria (up to 36%) or the EARSS criterion (13%). There is also an increase in the methicillin resistance rate (between 3.31 and 3.96%; p < 0.01). Conclusions: We believe that the EARSS method, with the proper quality controls and latest software tools available, is the best for determining the true situation of MRSA.
Cytological Features of Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland: A Case Report
Authors: Ishikura Naoyo , Kawada Takako , Mori Masaki , Maegawa Hideki , Ohta Makoto , Imamura Yoshiaki
Published: August 2014

Background: Carcinosarcoma of the salivary gland is an extremely rare tumor composed of carcinomatous and sarcomatoid components. This report describes the cytological and pathological findings of a case of carcinosarcoma ex pleomorphic adenoma arising in the right parotid gland. Case: A 47-year-old female visited a hospital with swelling of the right parotid region, slight pain and facial palsy. Fine-needle aspiration smears showed both clustered epithelium-like cells and singly scattered cells in a necrotic background. The cells, especially the latter, exhibited significant cellular pleomorphism and had irregularly shaped nuclei. Myxoid stroma-like cell clusters without cellular atypism were also seen. The right parotid gland was resected, and the tumor tissue was histologically diagnosed as carcinosarcoma ex pleomorphic adenoma. Conclusion: The cytological findings of carcinosarcoma ex pleomorphic adenoma have been reported in very few cases. In the present case, various components, including the presence of atypical epithelium-like cell clusters and singly scattered atypical cells with stromal components on cytological specimens, led to consideration of the diagnosis of carcinosarcoma ex pleomorphic adenoma.
Is There Any Evidence for a Role of Local Treatment in Cholangiocarcinoma?
Authors: Vogel Arndt , Dudeck Oliver
Published: August 2014

Background: Most cholangiocarcinomas (CCA) are locally advanced and unresectable at the time of diagnosis. Currently, chemotherapy combining gemcitabine with a platinum agent is the recommended first-line treatment regimen for advanced biliary tract cancer. However, median overall survival is only approximately 1 year. As the hepatic tumor burden is the limiting factor for the prognosis of these patients, local tumor control is essential. Methods: We present and discuss the current evidence for such therapy options for patients with CCA. Results: Local and locoregional therapies have been shown to be well tolerated and can contribute to tumor control in the context of a comprehensive oncologic treatment strategy, and may prolong survival of patients with advanced CCA. Unfortunately, only few high-quality clinical trials are available. Conclusion: Randomized prospective clinical trials enrolling larger numbers of patients need to be carried out to elucidate the precise value of these treatments alone as well as in combination with systemic chemotherapy.
A Vanishing Lymphoma in the Cheek
Authors: Farquhar Douglas , Sobanko Joseph , Williams Kimberly , Newman Jason G.
Published: August 2014

Background: We describe the unusual case of a 66-year-old woman who presented with a cheek mass that completely abated with oral steroids. Case Report: Multiple separate biopsies of the mass were negative or inconclusive. MRI revealed a large mass, yet after a short steroid course, this mass was completely undetectable on clinical examination. A repeat biopsy eventually revealed follicular lymphoma. Discussion: Lymphomas are known to be steroid sensitive; the medication is an essential component of the common CHOP therapy. While known to occur in the central nervous system, to the best of our knowledge, the presence of a ‘vanishing' lymphoma has not been documented in the head and neck. We discuss the likely physiology of the vanishing lymphoma, and the diagnostic difficulty it presents. Conclusion: When a lymphoma is suspected, patient care may be optimized if biopsy is delayed until steroids have been discontinued.
Metabolic Syndrome and Breast Cancer: Is There a Link?
Authors: Hauner Dagmar , Hauner Hans
Published: August 2014

Summary Epidemiological data suggest a close link between obesity and breast cancer, the most frequently occurring cancer in women. The metabolic syndrome is typically associated with abdominal obesity and comprises disturbances in glucose and/or lipid metabolism and/or hypertension. Recent studies have established a specific association between the metabolic syndrome - as well as its components - and breast cancer, indicating both an increased risk of developing breast cancer and a poorer prognosis. In premenopausal women, obesity might have a protective effect only on receptor-positive tumors, whereas a positive association was observed between obesity/abdominal obesity and an increased risk of triple-negative breast cancer (TNBC). Overall survival and disease-free survival were reported to be significantly shorter in premenopausal obese women with TNBC compared to non-obese women, but these results are still inconsistent and need further research. The metabolic syndrome is characterized by a state of insulin resistance/hyperinsulinemia and subacute chronic inflammation, with both conditions offering a plausible mechanistic link towards breast cancer. Thus, in addition to their increased risk of cardiovascular morbidity and mortality, women with this syndrome represent a group at elevated risk of developing breast cancer and with poorer prognosis.
Impact of Acetylsalicylic Acid on the Clinicopathological Characteristics and Prognosis of Patients with Invasive Breast Cancer
Authors: Sendur Mehmet A.N. , Aksoy Sercan , Ozdemir Nuriye Y. , Zengin Nurullah , Altundag Kadri
Published: August 2014

Background: The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. Patients and Methods: Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). Results: The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). Conclusion: Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.
Cardiac-Specific Overexpression of Human Stem Cell Factor Promotes Epicardial Activation and Arteriogenesis After Myocardial Infarction
Authors: Xiang Fu-Li , Liu Yin , Lu Xiangru , Jones Douglas L. , Feng Qingping
Published: August 2014

Background—

The adult epicardium is a potential source of cardiac progenitors after myocardial infarction (MI). We tested the hypothesis that cardiomyocyte-specific overexpression of membrane-associated human stem cell factor (hSCF) enhances epicardial activation, epicardium-derived cells (EPDCs) production, and myocardial arteriogenesis post MI.

Methods and Results—

Wild-type and the inducible cardiac-specific hSCF transgenic (hSCF/tetracycline transactivator) mice were subjected to MI. Wilms tumor-1 (Wt1)–positive epicardial cells were higher in hSCF/tetracycline transactivator compared with wild-type mice 3 days post MI. Arteriole density was significantly higher in the peri-infarct area of hSCF/tetracycline transactivator mice compared with wild-type mice 5 days post MI. In cultured EPDCs, adenoviral hSCF treatment significantly increased cell proliferation and growth factor expression. Furthermore, adenoviral hSCF treatment in wild-type cardiomyocytes significantly increased EPDC migration. These effects of hSCF overexpression on EPDC proliferation and growth factor expression were all abrogated by ACK2, a neutralizing antibody against
c-kit
. Finally, lineage tracing using ROSA
mTmG
;Wt1
CreER
mice showed that adenoviral hSCF treatment increased Wt1
+
lineage–derived EPDC migration into the infarcted myocardium 5 days post MI, which was inhibited by ACK2.

Conclusions—

Cardiomyocyte-specific overexpression of hSCF promotes epicardial activation and myocardial arteriogenesis post MI.
Diagnostic Concordance of Echocardiography and Cardiac Magnetic Resonance–Based Tissue Tracking for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy
Authors: Amaki Makoto , Savino John , Ain David L. , Sanz Javier , Pedrizzetti Gianni , Kulkarni Hemant , Narula Jagat , Sengupta Partho P.
Published: August 2014

Background—

Variations in longitudinal deformation of the left ventricle have been suggested to be useful for differentiating chronic constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). We assessed left ventricular mechanics derived from cardiac magnetic resonance (CMR) cine–based and 2-dimensional echocardiography–based tissue tracking to determine intermodality consistency of diagnostic information for differentiating CP from RCM.

Methods and Results—

We retrospectively identified 92 patients who underwent both CMR and 2-dimensional echocardiography and who had a final diagnosis of CP (n=28), RCM (n=30), or no structural heart disease (n=34). Global longitudinal strain from long-axis views and circumferential strain from short-axis views were measured on 2-dimensional echocardiographic and CMR cine images using the same offline software. Logistic regression models with receiver operating characteristics curves, continuous net reclassification improvement, and the integrated discrimination improvement (IDI) were used for assessing the incremental predictive performance. Global longitudinal strain was higher in patients with CP than in those with RCM (
P
<0.001), and both techniques were found to have similar diagnostic value (area under the curve, 0.84 versus 0.88 for CMR and echocardiography, respectively). For echocardiography, the addition of global longitudinal strain to respiratory septal shift and early diastolic mitral annular velocity resulted in improved continuous net reclassification improvement (
P
<0.001 for both) and integrated discrimination improvement (
P
=0.005 and 0.024) for both models. Similarly, for CMR, the addition of global longitudinal strain to septal shift and pericardial thickness resulted in improved continuous net reclassification improvement (
P
<0.001 for both) and integrated discrimination improvement (
P
=0.003 and <0.001).

Conclusions—

CMR and echocardiography tissue tracking–derived left ventricular mechanics provide comparable diagnostic information for differentiating CP from RCM.
Could You Please Look into the Camera?
Authors: Al Attar Mohammad , Ziter Edward , Wedeen Lisa
Published: August 2014

Are theatre texts documents of rapidly changing events in times of extreme complexity? If so, then what kind of documents are they? These questions provided the first motivation for writing Could You Please Look into the Camera? The second motivation was purely personal: the Assad regime’s program of arbitrary detention had stepped up the frequency of arrests, creating a republic of fear. This ugly fear that Syrians now share—whether arrested or not—had to be exposed in public.
Genomics Governance in the United States and the United Kingdom
Authors: Ireni-Saban Liza
Published: August 2014

Technological innovation in the area of personalised genetic data poses novel regulatory concerns for state governance. Since personalised genetic data reveals highly sensitive and private information about a person’s susceptibility to illness, it may lead to stigmatisation, discrimination, and breach of privacy. Although legal arrangements for personal or medical data have always been governmental and legal concerns, the introduction of genetic technologies over the past two decades has breathed new life into the idea of privacy and non-discrimination protection for individuals and communities, leading to possible new types of social relationships that circulate in a global biomedical arena. Thus, our analysis of genetic information regulation is based on a comparative analysis of policy instruments by examining the appropriateness of various policy instrument choices made in the United States and in the United Kingdom for securing the rights for privacy, non-discrimination, and access to research benefits for individuals and communities.
Transoral Resection of Stylopharyngeus Calcification
Authors: Kamil Rebecca J. , Gonik Nathan J. , Lee Jimmy S. , Shifteh Keivan , Smith Richard V.
Published: August 2014

Background:

Eagle syndrome is often considered in the work-up of odynophagia and neck pain. Classically, this is manifested by ossification or calcification of the stylohyoid ligament or styloid process. There are no reported cases of stylopharyngeal calcification leading to these symptoms.

Case:

We describe a patient with a suspected submucosal pharyngeal foreign body who was found to have a calcified stylopharyngeus muscle and tendon during surgery. The patient experienced full resolution of symptoms after transoral robotic resection. This diagnosis was initially missed because the radiology was inconsistent with Eagle syndrome.

Conclusion:

This is the first report of isolated stylopharyngeal calcification, and this unique manifestation of a stylohyoid complex syndrome should be considered in patients with symptoms of Eagle syndrome without styloid elongation.
The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: Trauma and early psychotic mania
Authors: Daglas Rothanthi , Conus Philippe , Cotton Sue M , Macneil Craig A , Hasty Melissa K , Kader Linda , Berk Michael , Hallam Karen T
Published: August 2014

Objective:

Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania.

Methods:

Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point.

Results:

Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania ( p=0.02), depression ( p=0.03) and psychopathology ( p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant ( p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning ( p=0.04) at the 12-month assessment with medium effect.

Conclusions:

Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.
Theory of Mind and attachment styles in people with psychotic disorders, their siblings, and controls
Authors: Pos Karin , Bartels-Velthuis Agna A , Simons Claudia JP , Korver-Nieberg Nikie , Meijer Carin J , de Haan Lieuwe ,   for GROUP, Bruggeman Richard , Cahn Wiepke , de Haan Lieuwe , Kahn René S , Meijer Carin J , Myin-Germeys Inez , van Os Jim , Wiersma Durk
Published: August 2014

Objective:

Impaired Theory of Mind (ToM) and insecure (adult) attachment styles have been found in persons with schizophrenia as well as in their healthy siblings. ToM refers to the ability to infer mental states of self and others including beliefs and emotions. Insecure attachment is proposed to underlie impaired ToM, and comprises avoidant (discomfort with close relationships, high value of autonomy) and anxious (separation anxiety, dependency on others) attachment. Insight into the association between attachment style and ToM is clinically relevant, as it enhances our understanding and clinical approach to social dysfunction in schizophrenia. Therefore, we studied the association between insecure attachment styles and ToM in patients with schizophrenia, their siblings, and healthy controls.

Methods:

A total of 111 patients with a diagnosis in the schizophrenia spectrum, 106 non-affected siblings and 63 controls completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions, a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma Questionnaire-Short Form. Severity of symptoms was assessed with the Community Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale.

Results:

After controlling for sex, intelligence, history of trauma and symptom severity, avoidant attachment was significantly associated with cognitive as well as with affective ToM, showing U-shaped associations, indicating better ToM performance for patients with lower or higher levels of avoidant attachment compared to medium levels. Anxious attachment in patients was associated with more problems in cognitive ToM.

Conclusion:

The results from this study support the idea that an anxious attachment style is associated with worse ToM performance in patients. Results also suggested a potential protective role of higher levels of avoidant attachment on ToM. These findings bear clinical relevance, as activation of (insecure) attachment mechanisms may affect interpersonal relations, as well as therapeutic working alliance. Further clarification is needed, especially on associations between ToM and avoidant attachment.
The Ties That Bind
Authors: Charnysh Volha , Lucas Christopher , Singh Prerna
Published: August 2014

At the psychological level, ethnic conflict can be seen as an extreme result of normal group identification processes. Bridging perceived intergroup boundaries is therefore key to improving intergroup relations. In contrast to the dominant association of nationalism with racism, chauvinism, xenophobia, and intolerance, we highlight the constructive potential of national identification. In a survey experiment, we find that the increased salience of a shared (Indian) national identity increases donations by members of a dominant ethnic group (Hindus) to members of a rival, minority group (Muslims). This effect is moderated by social status (caste). We suggest that national identification leads to a greater transformation in the behavior of low-status members of an ethnic group because they are more likely to be drawn to national identity as an enhancement of their social standing. Our study has implications for theories of social identity and interethnic cooperation, as well as for the literature on nationalism.
Urban School Choice and Integration
Authors: Ritter Gary W. , Jensen Nathan C. , Kisida Brian , Bowen Daniel H.
Published: August 2014

We examine the impact of charter schools on school integration in the Little Rock, Arkansas metropolitan area. We find that charters are less likely to be hyper-segregated than traditional public schools (TPS), but TPS have compositions more closely reflecting the region. However, differences in each case are slight. Using student-level data to follow students who left TPS for charters, we find that most transfers improve integration levels at the schools they left. This finding is attributed to the fact that most transfers involve minority students leaving predominately minority schools or White students leaving predominantly White schools.
Effects of Carrying a Backpack in an Asymmetrical Manner on the Asymmetries of the Trunk and Parameters Defining Lateral Flexion of the Spine
Authors: Drzał-Grabiec Justyna , Snela Sławomir , Rachwał Maciej , Podgórska Justyna , Rykała Justyna
Published: August 2014

Objective:

The aim of this study was to examine changes in the body posture parameters defining asymmetry of the trunk and lateral flexion of the spine in children while carrying a backpack weighing 10% of a child’s weight.

Background:

Carrying a backpack may negatively affect the posture of schoolchildren and contribute to spinal pain.

Method:

The study involved 162 primary school students ages 11 to 13 years. The parameters describing body posture were assessed with a backpack carried on the right or left shoulder as well as without a load. To assess the predefined parameters, we used the CQ Elektronik System, employing the photogrammetric method.

Results:

Trunk inclination shifted significantly in the opposite direction to the shoulder the backpack was carried on, and an increase in shoulder asymmetry was also found. We also observed a more pronounced right-side lateral flexion of the spine when the backpack was carried on the right shoulder and an analogous relationship for the left side.

Conclusion:

The results of this study show that carrying a backpack in an asymmetrical manner negatively affects spine, even if the backpack weight constitutes 10% of the child’s weight, which has been previously recommended as a safe load for a child’s shoulders.

Application:

We suggest that the issue of safe backpack weight be reassessed and that students be taught basic ergonomic principles on how to carry loads. Changes to the management pattern of carrying textbooks to and from school also should be considered.
Audience Costs, Information, and Credible Commitment Problems
Authors: Moon Chungshik , Souva Mark
Published: August 2014

Leaders who can accumulate audience costs can send costly signals that may help alleviate information problems associated with crisis escalation. We argue that research examining the effect of audience costs fails to appreciate the theoretical context in which audience costs matter. Audience costs may help alleviate information problems associated with international conflict. However, credible commitment problems are more central than information problems for some international conflicts. Theory does not expect audience costs to matter in this context; as a result, extant tests, and many criticisms, of the effect of audience costs on crisis escalation are flawed. We offer a more appropriate test of the effect of audience costs on crisis escalation. Consistent with extant theoretical arguments, we find that audience costs only reduce the likelihood of conflict when credible commitment problems are not the dominant concern motivating a dispute or crisis.
Facing Your Opponents
Authors: Mago Shakun D. , Samak Anya C. , Sheremeta Roman M.
Published: August 2014

We experimentally investigate the effect of social identification and information feedback on individual behavior in contests. In all treatments, we find significant overexpenditure of effort relative to the standard theoretical predictions. Identifying subjects through photo display decreases wasteful effort. Providing information feedback about others’ effort does not affect the aggregate effort, but it decreases the heterogeneity of effort and significantly affects the dynamics of individual behavior. A behavioral model that incorporates a nonmonetary utility of winning and relative payoff maximization explains significant overexpenditure of effort. It also suggests that decrease in “social distance” between group members through social identification promotes prosocial behavior and decreases overexpenditure of effort, while improved information feedback decreases the heterogeneity of effort.