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B cell responses to tumor antigens occur early in breast tumors and may identify immunogenic drivers of tumorigenesis. Sixty-two candidate antigens were identified prior to palpable tumor development in TgMMTV-neu and C3(1)Tag transgenic mouse mammary tumor models. Five antigens (VPS35, ARPC2, SERBP1, KRT8, and PDIA6) were selected because their decreased expression decreased survival in human HER2 positive and triple negative cell lines in a siRNA screen. Vaccination with antigen-specific epitopes, conserved between mouse and human, inhibited tumor growth in both transgenic mouse models. Increased IgG autoantibodies to the antigens were elevated in serum from women with ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). The autoantibodies differentiated women with DCIS from control with AUC 0.93 (95% CI 0.88–0.98, p

Mammography is essential to identify early breast cancer but the sensitivity is dependent on breast characteristics. A serum-based biomarker used along with mammography to identify lesions that need to be biopsied may improve the sensitivity of mammography and reduce the number of biopsies needed. We have identified a panel of autoantibodies found in early breast cancer. An autoantibody biomarker is ideal because antibody immunity can be detected with very low levels of antigen with direct antigen recognition by B cells resulting in clonal amplification of antigen specific plasma cells. Work in our laboratory has identified tumor-associated proteins present in pre-malignant tumors that are necessary for survival of human breast cancer cells across breast cancer subtypes. Increased autoantibodies to seven of these early tumor-associated proteins (PDIA6, KRT8, SERBP1, ARPC2, RRM2, AURKA, and NDC80) were present in the sera of women with DCIS and invasive breast cancer in two independent serum collections but not in control women with no known breast lesions. The presence of autoantibodies in the discovery set was evaluated in 185 individuals: 42 control women, 12 women with hyperplasia, 36 patients with fibroadenoma, 59 patients with ductal carcinoma in situ (DCIS), and 36 patients with invasive breast cancer (IBC). The validation set was evaluated in 228 individuals: 50 control patients, 50 patients with fibroadenoma, 18 patients with hyperplasia, 50 patients with DCIS, and 60 patients with IBC, 20 with hormone receptor positive (HR+) HER2 negative, 20 with HER2+, and 20 triple negative (TN). We defined a positive autoantibody response as over 2 standard deviations above the mean found in control women. All seven autoantibodies could predict patients with hyperplasia, fibroadenoma, DCIS, and IBC in both the discovery and validation sets. For example, the seven-antibody panel could identify DCIS from control women with AUC of 0.95 (95% CI 0.912 to 0.995, p Citation Format: Sasha Elizabeth Stanton, Jason Schlumbohm, Erik Ramos, Charles Drescher, Jeffrey Marks, Mary L. Disis. Seven autoantibody panel, validated in two independent patient serum collections, can detect women with DCIS and invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3380.

MUDI es un sistema reconocedor de gestos, capaz de detectar el acercamiento, rotación y cambiar de pieza arqueológica modeladas en 3D existentes en el MureH. El sistema está contextualizado para un museo interactivo en el que los usuarios puedan descubrir las características de las piezas de una forma entretenida y divertida. Para desarrollar el sistema se utilizó PSP, el cual es una metodología encaminada al proceso personal, establecido y regido por etapas bien establecidas, una de ellas es el diseño que permite tener una buena estructura del sistema traduciéndose en una fácil implementación y control de los errores de codificación, así como el manejo de los requerimientos. Para medir la interacción, efectividad y facilidad de uso de MUDI se usaron técnicas de usabilidad, obteniendo resultados favorables, específicamente el acercamiento tuvo una calificación de 4.8, rotación de 4.0 y cambiar pieza de 4.4 en una escala del 0 al 5. Los usuarios manifestaron gran aceptación y buenos comentarios puesto que con MUDI se olvidaban de las visitas tradicionales.

Although breast cancer tumors tend to have less tumor immune infiltration than immunogenic tumors such as melanoma and colon cancer, the prognostic importance of tumor immune infiltrates in breast cancer has confirmed the essential role of the immune response to the breast tumor. Increased tumor immune infiltrate, particularly antitumor type 1 (Th1) immune infiltrate, has been shown to predict improved disease-free and overall survival, particularly in triple-negative breast cancer, and to influence the response to chemotherapy. Furthermore, autoantibodies against tumor antigens are present in patients even before breast cancer development but not in women who will not develop breast cancer, and these autoantibodies may provide both early diagnosis and response to therapy biomarkers. Finally, the generation of clinical responses to emerging therapies including vaccines and immune checkpoint inhibitor monoclonal antibodies has clearly demonstrated that breast cancer is immunologically active. In the future, therapies that harness the immune system will be used in all stages of breast cancer treatment including the possibility of stimulating immunity for breast cancer prevention. This chapter provides an overview of current immunologic approaches to develop predictive and prognostic assays in breast cancer and novel, clinically effective immune therapy; it also provides an overview of considerations for new directions in breast immunooncology for the future.

Cervical cancer (CC) remains a challenging disease despite the approved preventive vaccines against HPV, which is the cause of this type of tumor. Immune-mediated treatments, or immuno-oncology, currently represent 6% of cancer therapies, and in the next 10 years, this percentage is expected to increase up to 70%. There are ongoing efforts to develop specific immunotherapies, such as immunomodulatory drugs and antibodies, to treat CC in combination with standard-of-care regimens. However, currently, there are no clinically available active antigen-specific immunotherapies that effectively treat CC, despite multiple studies in animal models that have mainly focused on the viral early proteins (E2, E5, E6, and E7). There are data from clinical trials using DNA, proteins, and peptide vaccines targeting these viral early proteins as treatments for CC, but there has been limited clinical success. It is clear that the adaptive immune system plays an important role in CC; multiple studies have shown that immune infiltration is related to prognosis. Non-viral targets are also potential candidates for targeting by next-generation immunotherapies for CC and vaccines to prevent relapse.

While mammography is essential to identify early breast cancer, the sensitivity is dependent on breast characteristics. Currently all breast masses identified by mammography have to be biopsied to determine if malignant. A serum-based biomarker used along with mammography to identify pre-malignant lesions to biopsy would both improve the sensitivity of mammography and reduce the number of biopsies needed. We have identified a panel of autoantibodies found in early breast cancer. An autoantibody biomarker is ideal because antibody immunity can be detected with very low levels of antigen with direct antigen recognition by B cells resulting in clonal amplification of antigen specific plasma cells. Work in our laboratory has identified tumor-associated proteins present in pre-malignant tumors that are necessary for survival of human breast cancer cells across breast cancer subtypes. We have found that increased autoantibodies to seven of these early tumor-associated proteins (PDIA6, KRT8, SERBP1, ARPC2, RRM2, AURKA, and NDC80) were present in the sera of women with pre-malignant breast atypia but not women with no breast atypia or benign breast atypia and may be a panel to increase sensitivity of mammography. The presence of autoantibodies was evaluated in 191 individuals, 36 women with no breast atypia, 12 women with benign breast atypia, 36 patients with fibroadenoma, 12 patients with hyperplasia, 59 patients with ductal carcinoma in situ (DCIS), and 36 patients with invasive breast cancer (IBC). We found more women with pre-malignant breast atypia had increased autoantibodies to at least one of the seven early tumor associated proteins as compared to women with either no breast atypia or benign breast atypia. For example, a positive autoantibody response is over 2 standard deviations above the mean found in women with no breast atypia. There were 2.9% of women with positive autoantibody response to RRM2 in women without breast atypia. However, in women with breast atypia, there was a positive antibody response in 41.7% of individuals with hyperplasia, 48.6% of individuals with fibroadenoma, 34.5% of individuals with DCIS, and 28.6% of individuals with IBC. All seven autoantibodies could predict patients with hyperplasia, fibroadenoma, DCIS, and IBC from both women with no atypia and women with benign breast atypia. For example, the seven-antibody panel could identify DCIS from women with no breast atypia with AUC of 0.95 (95% CI 0.912 to 0.995) and from women with benign breast atypia with AUC of 0.71 (95% CI 0.519 to 0.898). This is a better AUC than seen with previous published autoantibody profiles in DCIS. Future studies will validate these findings with the goal of developing a serum biomarker that will improve sensitivity of mammography. Citation Format: Sasha Elizabeth Stanton, Erik Ramos, Mary L. Disis. Panel of autoantibodies to seven early tumor-associated overexpressed proteins can identify women with DCIS from women with benign breast tumors detected by mammography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2224.

Vaccine therapy may be ideal to destroy ductal carcinoma in situ (DCIS) and prevent recurrence. A vaccine can induce type 1 T-cells against DCIS antigens that could migrate from the circulation to invade and destroy the tumor as well as generate immunologic memory to provide long lasting protective immunity. One of the limitations to developing a DCIS vaccine is identifying antigens that target all subtypes of DCIS. DCIS has many of the same molecular abnormalities as invasive breast cancer (IBC), including overexpressed proteins that may be drivers of progression to invasive disease. Eliminating cells that are overexpressing driver proteins by vaccination may prevent progression to IBC if such proteins could be determined. In this study, we identified proteins that were overexpressed from normal breast in both DCIS and IBC across fifteen Geo and Array Express data sets. From 68 candidate proteins, we identified twelve whose expression was necessary for cancer cell survival across breast cancer subtypes. We selected overexpressed proteins necessary for cancer survival using a high throughput siRNA screen and chose candidates that increased apoptosis and decreased cell survival in HER2 positive (HER2), triple negative (TN), and hormone receptor positive HER2 negative (HR) human breast cancer cell lines with decreased expression of the target protein. For example, decreased expression of NDC80 caused decreased cell survival to 56±3% in HR, 46±3% in TN, and 77±2% in HER2 breast cancer cell lines and increased apoptosis by 1.4±0.03 fold in HR and 1.2±0.03 fold in TN breast cancer cell lines. Decreased expression of RRM2 caused decreased cell survival to 66±3% in HR and 89±2% in HER2 breast cancer cell lines and increased apoptosis by 1.6±0.08 fold in HR, 1.4±0.07 fold in TN, and 2.4±0.3 fold in HER2 breast cancer cell lines. Twelve proteins (AURKA, KIF11, NDC80, RRM2, SDC1, UBE2C, HJURP, CENPA, CENPF, HIST2H2AA3, HIST1H2BD, and TOP2A) were essential for cancer cell survival in at least 2 breast cancer subtypes. These protein targets are immunogenic in patients with DCIS. In the sera of women without breast atypia (n=36), autoantibodies to NDC80 were detected with a mean of 5.3±1.8 ng/mL while in women with fibroadenoma (n=36) autoantibodies were detected with a mean of 8.3±1.5 (p=0.05). In the sera of women without breast atypia (n=36), autoantibodies to RRM2 were detected with a mean of 0.16±0.7 ng/mL while in women with fibroadenoma (n=36) autoantibodies were detected with a mean of 7.2±2.1 (p=0.05) and in women with DCIS (n=59) autoantibodies were detected with a mean of 2.6±0.6 ng/mL (p=0.0003). These proteins represent DCIS antigens of biologic importance in tumor growth and, potentially, progression to IBC and are candidate immunogens for a vaccine to treat DCIS. Citation Format: Sasha Elizabeth Stanton, Erik Ramos, James Annis, Andrew Timms, Tessa Rue, Mary L. Disis. Identifying candidate antigens for a ductal carcinoma in situ vaccine that are essential to breast cancer survival across multiple subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 623. doi:10.1158/1538-7445.AM2017-623

Background: Meloxicam and nimesulide have been studied as potential cancer immunomodulatory agents. Those drugs have been shown to have immune stimulatory effects on the tumor stroma and the microenvironment of several tumors including pancreatic ductal adenocarcinoma. They have several immune effects in vitro and in animal models. We compared the immunomodulatory activity of two preferential Cox-2 inhibitors drugs, meloxicam and nimesulide in advanced pancreatic cancer patient’s peripheral blood mononuclear cells (PBMCs) with good and poor Karnofsky. Materials and Methods: Repository PBMCs from advanced pancreatic patients with Karnofsky < 50% (n=10) and > 80% (n=10) were stimulated with different concentrations of meloxicam and nimesulide in vitro. We performed dose-response curve with concentrations of both drugs ranging from 0.5, 1, 10, 50 and 100 μM and we performed the ELISPOT assays for Interferon-gamma using human anti-CD3 and CMV whole lysate as basal T cell stimulation. Th2 cytokines were measured as well by ELISPOT and Cytokine ELISA. Results: In patients with Karnofsky > 80% both meloxicam and nimesulide were effective in promoting IFN-gamma production after stimulation with both drugs starting at 0.5 μM. The use of meloxicam was associated with significant production of IFN-gamma at 0.5 μM (p Meloxicam and nimesulide treatment resulted in different responses in PBMCs IFG-gamma production from pancreatic cancer patients that had a Karnofsky Additionally PBMCs treated with nimesulide in both groups were able to decrease Th2 cytokines such as IL-6, IL-18, TNF-alpha and IL-8 (statistical analysis in progress). Discussion: This preliminary data suggests that the use of meloxicam and nimesulide as putative immunomodulatory drugs may be less effective when pancreatic patients have a poor Karnosky although at high concentration they are effective. Also, the potent induction of IFN-gamma in patients with a good Karnofsky suggest synergy of these drugs in combination with standard of care treatment, immunogenic chemotherapy, anti-stroma strategies and active specific immunotherapy as a combinatorial approach to move forward into animal models of pancreatic cancer and eventually into the clinic. Grant Support: Junior Physician Scientist Fellowship Grant from CICS. Citation Format: Juan Marquez, Erik Ramos, Pedro Alejandro Lucero-Diaz, Fernando Durazo-Bustamante, Gerardo Palacios Diaz De Leon, Rosana Soto-Soto, Sara Carrillo-Marquez, Arturo Suplee-Rivera, Alejandro Camacho-Hernandez, Daniel Camacho-Gil.{Authors}. Meloxicam and nimesulide modulate immunity in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A75.

The present work is originated from the fact of low assistance of general population to the museums, particularly the school-age population as Conaculta reports. Experience shows that more interest is generated when interactive activities are offered. The present paper presents the development stages of an interactive guide using Augmented Reality for the “Museoregional de Huajuapan”. The goal of this project is to contribute towards spreading the rich cultural Mixteca heritage. We explore two different Augmented Reality libraries compatible with Android NyARToolKit and Vuforia. Augmented Reality is implemented by pattern recognition on special marks. Market share for smart phones are reviewed to make sure that Android is the most suited platform. We may conclude that smart phones are well suited to implement Augmented Reality in the museographic tourist guide as they are lightweight devices that can be carried and manipulated easily.

e22527Background: The potential clinical important targets for synovial sarcoma (SS) are mainly unknown. We performed a systematic review and we found eight potential proteins to be targeted in thi...

e15705Background: The discovery of biological relevant targets to design effective active antigen specific immunotherapy for pancreatic ductal adenocarcinoma (PDAC) is extremely important. In terms...

e17067Background: Some antibiotics have been studied as potential cancer immunomodulatory agents. We compared the ability of two commonly used antibiotics in human peripheral blood mononuclear cell...

Our understanding of the immune responses to pancreatic tumors is very limited. Analysis of the preexisting immune responses against a panel of tumor-associated antigens could help generate new immune-based therapies and diagnostic tools. Furthermore, the majority of the few studied tumor-associated antigens found in pancreatic cancer are not clinically relevant or important for cancer cell survival. Animal and clinical immunotherapeutic studies have demonstrated that there is immune selection and immune escape against most of these antigens. Overactivation of the epidermal growth factor pathway, apoptosis-related proteins and death resistance of cancer stem cells and tumor stroma have been observed in human pancreatic cancer and often are associated to overexpression or deregulation of several proteins including EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2. EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2 are implicated in tumor aggressiveness, progression, resistance, and metastasis. Overexpression of these proteins in the tumor cells and tumor stroma of advanced pancreatic cancer, and the lack of relevant mutations make them reliable targets for clinical immunotherapy trials. We designed long peptides representing immunogenic T helper and CTL epitopes for all these six proteins. The immune response was studied in pancreatic cancer (n=15), pancreatitis (n=17) and matched controls. PBMCs were analyzed to determine Th1 and Th2 immune response by production of IFN-γ and IL-10 respectively using an ELISPOT assay. Sera and ascites fluid were used for the study of the humoral immune response by ELISA using human anti-IgG and human anti-IgA. We detected significant preexisting humoral and cellular immune responses against these peptides in patients suffering from advanced pancreatic cancer. In this study, we demonstrated that this panel of proteins could be targets for humoral and cellular immune recognition in pancreatic cancer patients whereas no detectable responses were found in healthy patients. Our results suggest that a Th2 immune response is present more often in this cohort and that it could be associated with a poor prognosis measured by overall survival. In conclusion, Th2 and ascites IgA immune responses against proteins important for tumor survival that are overexpressed in cancer cells and tumor stroma were common in our cohort of pancreatic cancer patients. Some of these proteins could serve as broad-spectrum tumor antigens to target in peptide vaccine immunotherapy trials to achieve better clinically relevant responses in pancreatic cancer patients. Citation Format: Jose V. Torres, Gardner B. Murray, Ramon Cabello, Eduardo Flores, Alejandro Camacho, Pedro A. Lucero, Anton Ostashko, Roger Dela Cruz, Jr., Fernando Durazo, Xia Li, Lizette Rodriguez, Erik Ramos, Juan Pablo Marquez-Manriquez. Preexisting immune responses against EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2 in pancreatic cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A54.

Integrating CSCL activities is something that has been widely discussed in the CSCL community but as yet only implemented in a reduced set of domain specific tools. In this paper we propose the integration of a set of default and authoring CSCL tools into a standard LMS, as a complete sequence of learning activities based on a constructivist approach. An experiment was also carried out in order to verify the usability and extent of the collaborative work in a real context. Based on results of evaluation, we conclude that the integration of chat was a useful addition to the concept map building tool. This highlighted the professor role as a moderator entity maintaining a central role during the learning experience. The tests were carried out in presence of professors who felt that software would be useful to promote the participation of students and facilitate continuous assessment for this courses and other courses.

Over last years, Indoor Positioning and Navigation Systems (IPNS) has been subject of intense study and research ought to it has become a blind spot with regard to Positioning and Navigation Software. None of proposed indoor solutions has been as successful as outdoor systems like Global Position System (GPS). Our proposal presents the design and implementation on mobile device(the most common), of a 3D positioning and navigation system for indoor based on the use of Bluetooth (BT) radio technology and implemented using Java and J2ME, this implementation is adaptable to whatever indoor environment (commercial centers, offices, museums, etc.) previously modeled and loaded. This 3D model can be build using the most common 3D design tools with M3G formats support. Location is implemented on BT with distributed estimation (the mobile device performs it).

The emergence of networked computers has originated new technologies for teaching and learning, particularly, the technology of learning management systems. We have applied Erlang to deal with the concurrent part of a distributed system to support teaching and learning tasks. We have also employed declarative programming together with some formal tools to elaborate the specification and the conceptual model of the system and some extreme programming techniques to deal with some issues of software development. We show how Erlang supports the transition from the specification to the implementation, and the whole concurrent and computational process of our distributed system.

El presente estudio tuvo como propósito evaluar si las concentraciones naturales de fósforo y nitrógeno limitaban la biomasa fitoplanctónica en el Lago Alchichica. Se aplicaron tratamientos de enriquecimiento con nitrógeno, fósforo y nitrógeno + fósforo durante las dos etapas características de la hidrodinámica del lago: estratificación y mezcla. Se dio seguimiento al potencial de crecimiento algal mediante la evaluación fluorométrica in vivo de los cambios diarios de la concentración de clorofila a expresados como porcentaje de cambio relativo con respecto al testigo (T). Durante la época de mezcla la respuesta al enriquecimiento fue limitada y la comunidad de fitoplancton no modificó su composición ni abundancia. Contrariamente, durante la época de estratificación la adición de nutrimentos favoreció el crecimiento del fitoplancton modificando su composición y abundancia. Los resultados muestran que el nitrógeno es el nutrimento que principalmente podría limitar el crecimiento algal en el lago Alchichica como ha sido encontrado en otros lagos tropicales, a diferencia de los lagos templados en donde se ha encontrado que el nutriente limitante es el fósforo. La adición de un solo nutrimento produjo sólo un breve incremento en el crecimiento en tanto el otro nutrimento se agotó. Sin embargo, cuando ambos nutrientes fueron añadidos, el crecimiento fue sostenido y se produjo una respuesta importante y detectable.

Statistics show that attendance to culture and science promotion centers can be increased if interactive activities are offered. This paper presents the development of an application based on Kinect SDK which manipulates 3D models of archaeological pieces from the Museo Regional de Huajuapan (MureH). This manipulation is performed without controls, with only hand movements needed to interact with the application. The process and details of 3D models design highlighting the use of textures to add a more realistic appearance is presented, along with some details and tests about the development of the Kinect-based Application.