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  • American Association for Cancer Research (AACR)  (6)
  • 1
    Online-Ressource
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    Abstract 4204: CDK4/6 inhibition mitigates chemotherapy-induced immunosuppression and enhances the efficacy of chemo- immunotherapy in small cell lung cancer models
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 4204-4204
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 4204-4204
    Kurzfassung: Small cell lung cancer (SCLC) is an aggressive form of lung cancer with a notably low survival rate. Chemotherapy and more recently its combination with immunotherapy are the standard of care for extensive stage SCLC. Although this combinatorial treatment provides clinical benefit, it can be hampered by the effect of chemotherapy on inducing immunosuppression. Cyclin dependent kinases 4/6 (CDK4/6) phosphorylate retinoblastoma (Rb) protein and promote proliferation of Rb-intact hematopoietic stem progenitor cells (HSPCs) by allowing cells to progress through S phase. Rb loss is a signature mutation in SCLC tumors, making these tumor cells unresponsive to CDK4/6 inhibition. Therefore, we hypothesized that CDK4/6 inhibitors could be utilized to block the proliferation of Rb-intact HSPCs and protected them from chemotherapy without altering the effect of chemotherapy on Rb-deficient SCLC cells. We treated Rb-deficient SCLC cancer cells and Rb-intact NK and T cells with increasing concentrations of cisplatin, etoposide and topotecan with or without the CDK4/6 inhibitor G1T28. Cell proliferation, apoptosis and cell cycle were analyzed using CellTiter-Glo, Annexin V staining, and PI-based cell cycle analysis. In vitro, CDK4/6 inhibition did not alter the impact of chemotherapy on Rb-deficient SCLC cell viability, whereas with Rb-intact NK and T cells, CDK4/6 inhibitor treatment induced cell cycle arrest and prevented apoptosis induced by chemotherapeutic agents. In the TKOTmG Rb-deficient mouse model of SCLC, CDK4/6 inhibition improved the efficacy of cisplatin plus etoposide. In vivo studies using the KP-1 syngeneic mouse models showed that treatment with a CDK4/6 inhibitor improved the efficacy of chemotherapy and immunotherapy individually or chemo-immunotherapy combinations by reducing the tumor growth rate and prolonging animal survival. CDK4/6i treatment prior to chemotherapy preserved white blood cell counts in comparison to chemotherapy alone. Tissue and blood immune marker analysis showed that CDK4/6 inhibitor treatment increased both the circulating and tumor-resident NK cells. Collectively, we demonstrated that CDK4/6 inhibition does not antagonize the therapeutic impact of chemotherapy on Rb-deficient SCLC cells but enhances the efficacy of chemotherapy and immunotherapy in KP-1 syngeneic SCLC mouse model. CDK4/6i also at least partially abrogated the chemotherapy-induced reductions in subpopulatons of immune cells. CDK4/6 inhibition may be considered as a therapeutic strategy for mitigating chemotherapy-induced immunosuppression and enhance antitumor immunity in SCLC patients. Citation Format: Thiruvengadam Arumugam, Irene G. Muñoz, Alissa Poteete, Fahoa Zhang, Monique Nilsson, John S. Yi, Jessica A. Sorrentino, Andrew P. Beelen, John V. Heymach. CDK4/6 inhibition mitigates chemotherapy-induced immunosuppression and enhances the efficacy of chemo- immunotherapy in small cell lung cancer models [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 4204.
    Materialart: Online-Ressource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-4204
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2022
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Abstract A58: Adaptation of a Spanish-language educational DVD about biobanking for Hispanics in Puerto Rico and Florida
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 23, No. 11_Supplement ( 2014-11-01), p. A58-A58
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11_Supplement ( 2014-11-01), p. A58-A58
    Kurzfassung: Introduction: Biobanks are repositories that store biospecimens and health information for research. Healthy control samples from diverse racial/ethnic groups must be represented in biobanks to better examine genetic and environmental risk factors for diseases such as cancer.1 However, the general public appears to be skeptical about the purpose of these repositories, with minority populations being less likely to donate samples. 2,3 Specific media approaches have shown improved efficacy for communicating health information to minority audiences, including Hispanics. Audiovisual materials offer advantages to Hispanic populations including: high acceptability4; broad dissemination; appealing to individuals with low literacy5; and can be viewed with family.4 Recently, the Tampa Bay Community Cancer Network (TBCCN) developed an educational biobanking DVD in Spanish (“Biobancos: Una esperanza de cura para el cáncer”) for the Tampa community. In preparation for a study conducted by the Ponce School of Medicine-Moffitt Cancer Center Partnership examining communication channels for delivering biobanking education to healthy Hispanics, TBCCN's Spanish-language DVD was tested among Hispanic populations in Tampa, FL and Ponce, PR to assess acceptability among a diverse, yet predominantly Puerto Rican Hispanic population. Methods: The existing Spanish-language biobanking DVD was reviewed by 18 Hispanic community members from Tampa, FL (n=9) and Ponce, PR (n=9) to assess acceptability of content, delivery, tone, and message. Community members from Tampa represented diverse Hispanic sub-groups, while those in Ponce were all Puerto Rican. Feedback from both groups was compared and revisions were made based on common themes. Results: Participants responded favorably to several aspects of the DVD including: the format, Spanish language, visual attractiveness and use of color, description of biobanking procedures and biospecimens, and the use of community member interviews. However, they also identified several areas for enhancement including: shortening the video, slowing down the narration, and reducing the use of scientific language and images. They also reported that the video would be improved by adding an emotional connection that would trigger desire to participate as a healthy donor. Based on these data and preferences, a derivative DVD was developed that maintained the core informational content elements while incorporating community member feedback. New footage was filmed in PR and incorporated into the final version. Edits included shortening and re-narrating the script; replacing scientific/technical language and imagery with lay terms and family images; and including survivor testimonials to build on the emotional connection and importance of biobanking as a healthy individual. Conclusion: Although the original DVD was in Spanish and created for the Tampa community, some elements did not resonate well when tested with a different Hispanic population (predominantly Puerto Rican), highlighting the importance of adapting Spanish educational materials across Hispanic sub-ethnicities. The newly derived DVD discussing biobanking and its importance in cancer research may present an effective way to recruit Hispanics as healthy controls. Future plans include utilizing this DVD in a RCT to examine the most effective communication channel for delivering cancer prevention and biobanking education to Hispanics. Citation Format: Yonaira M. Rivera, Jessica McIntyre, Daianna Adams, Julio Jiménez, Clement Gwede, Susan Vadaparampil, Vani Simmons, Thomas H. Brandon, Cathy D. Meade, Wendy E. González, Himilce Vélez, Gloria Asencio, Cruz M. Nazario, Eida Castro, Teresita Muñoz-Antonia, Gwendolyn P. Quinn. Adaptation of a Spanish-language educational DVD about biobanking for Hispanics in Puerto Rico and Florida. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A58. doi:10.1158/1538-7755.DISP13-A58
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1538-7755.DISP13-A58
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2014
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Abstract CT004: Adjuvant therapy with nivolumab (NIVO) combined with ipilimumab (IPI) vs NIVO alone in patients (pts) with resected stage IIIB-D/IV melanoma (CheckMate 915)
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. CT004-CT004
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. CT004-CT004
    Kurzfassung: Background: NIVO has demonstrated significant benefit over IPI as adjuvant treatment in pts with resected stage IIIB–C or stage IV melanoma (AJCC v7). Combination NIVO + IPI has shown numerically longer survival than NIVO alone in pts with metastatic melanoma. CheckMate 915 evaluated adjuvant NIVO + IPI 1 mg/kg Q6W vs NIVO. Methods: Pts aged ≥ 12 y with completely resected stage IIIB–D or stage IV melanoma (AJCC v8) were stratified by tumor PD-L1 expression and stage and treated with NIVO 240 mg Q2W + IPI 1 mg/kg Q6W (NIVO + IPI1) or placebo-controlled NIVO 480 mg Q4W alone for ≤ 1 y (NIVO + IPI were to be discontinued together). Dual endpoints were recurrence-free survival (RFS) in the PD-L1 & lt; 1% and intent-to-treat populations. Distant metastasis-free survival (DMFS) in pts with stage III disease was an exploratory endpoint. Results: Of 920 pts randomized to NIVO + IPI1 and 924 to NIVO alone, most had stage IIIB (31% vs 31%) or IIIC (53% vs 52%) disease and had undergone complete lymph node dissection (64% vs 64%). Pts treated with NIVO + IPI1 vs NIVO alone had a shorter median duration of therapy (7.6 vs 11.1 mo) and therefore, a lower median cumulative NIVO dose (3840 vs 6240 mg). At a minimum follow-up of 24 mo, RFS and DMFS did not differ between treatment groups (table). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 33% of pts treated with NIVO+IPI1 and 13% with NIVO alone; any-grade TRAEs led to discontinuation of therapy in 32% vs 10% of pts, respectively. There were 4 treatment-related deaths (all with NIVO + IPI1). Conclusions: The NIVO + IPI1 regimen did not result in RFS or DMFS improvement vs NIVO in stage IIIB–D/IV resectable melanoma; safety profiles were consistent with previous studies. NIVO 480 mg Q4W outcomes in CheckMate 915 were similar to previous NIVO results and reinforce NIVO as an adjuvant standard of care in a study population that included pts with and without complete lymphadenectomy. NIVO 240 mg Q2W + IPI 1 mg/kg Q6W (ITT)NIVO 480 mg Q4W (ITT)NIVO 240 mg Q2W + IPI 1 mg/kg Q6W (tumor PD-L1 & lt; 1%)NIVO 480 mg Q4W (tumor PD-L1 & lt; 1%)RFS24-mo rate64.6% (95% CI, 61.3-67.7)63.2% (95% CI, 59.9-66.4)53.6% (95% CI, 48.0-58.8)52.4% (95% CI, 46.8-57.7)Median, mo (events/pts)Not reached (327/920)Not reached (347/924)33.2 (159/349)25.3 (166/351)HR, NIVO + IPI1 vs NIVO0.92 (97.295% CI, 0.77-1.09); P = 0.2690.91 (95% CI, 0.73-1.14)DMFS in pts with stage III disease24-mo rate75.4% (95% CI, 72.1-78.4)77.4% (95% CI, 74.1-80.3)67.9% (95% CI, 61.9-73.1)68.4% (95% CI, 62.5-73.7)Median, mo (events/pts)Not reached (195/797)Not reached (194/798)Not reached (92/305)Not reached (96/307)HR, NIVO + IPI1 vs NIVO1.01 (95% CI, 0.83-1.23)0.94 (95% CI, 0.70-1.25) Citation Format: Georgina V. Long, Dirk Schadendorf, Michele Del Vecchio, James Larkin, Victoria Atkinson, Michael Schenker, Jacopo Pigozzo, Helen J. Gogas, Stéphane Dalle, Nicolas Meyer, Paolo A. Ascierto, Shahneen Sandhu, Thomas Eigentler, Ralf Gutzmer, Jessica C. Hassel, Caroline Robert, Matteo Carlino, Anna Maria Di Giacomo, Marcus O. Butler, Eva Muñoz-Couselo, Michael P. Brown, Piotr Rutkowski, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Alexander Menzies, Sandra Re, Tuba O. Bas, Veerle de Pril, Daniel Tenney, Hao Tang, Jeffrey S. Weber. Adjuvant therapy with nivolumab (NIVO) combined with ipilimumab (IPI) vs NIVO alone in patients (pts) with resected stage IIIB-D/IV melanoma (CheckMate 915) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT004.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-CT004
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2021
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Abstract 1033: Evaluation of HER2 status in circulating tumor cells isolated using the Parsortix® system
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1033-1033
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1033-1033
    Kurzfassung: Background: Evaluation of HER2 status in tissue from breast cancer patients is a standard test for clinical diagnosis and treatment. However, tissue biopsy is invasive and repeated testing is generally not possible. Liquid biopsy allows minimally invasive, repeat sample collection for regular monitoring. This study combined ANGLE’s Parsortix® PR1 Research System*, an epitope-independent microfluidic device that isolates and harvests rare cells from blood based on size and deformability, with two downstream assays: an Immunofluorescence (IF) assay for HER2 protein detection and an IF assay combined with FISH targeting HER2 gene amplification, to determine HER2 status on circulating tumor cells (CTCs). Methods: Blood was collected from healthy volunteers into Streck Cell-Free DNA tubes. Two aliquots of blood from each donor were spiked with cultured SKBR3 (HER2+) and Hs 578T (HER2-) breast cancer cells and then processed using Parsortix® PR1 instruments. Captured cells were harvested and spun onto positively charged slides. One slide per donor was stained using ANGLE’s IF panel for CTC detection, consisting of a nuclear dye, antibodies targeting epithelial and mesenchymal markers, and antibodies targeting blood cell markers. After imaging, slides were de-stained and processed using a commercially available HER2 FISH kit. Cancer cells identified by the IF panel were re-imaged to examine FISH signal. Cells were considered HER2+ if the ratio of HER2 foci to CEP17 foci was ≥2. The second slide was stained using the same IF CTC panel in combination with an antibody targeting HER2 protein. HER2 expression was analyzed based on intensity of fluorescence signal. Same workflow was implemented in a small cohort of breast cancer patients with blood processed 72-144 hours post-draw using Parsortix® PC1 Clinical System. Results: The numbers of epithelial and mesenchymal CTCs detected on each slide were comparable in both assays. In HER2 FISH-stained samples, 97.3% of the SKBR3 cells and 13.3% of the Hs 578T cells harvested showed HER2 amplification. This data was consistent with the literature (~20% of Hs 578T cells tend to form isochromosomes, altering the HER2/CEP17 ratio). In IF-only stained samples, 96.8% of the SKBR3 cells and 0% of the Hs578T cells harvested overexpressed HER2 protein. In patient samples, CTCs were identified in 80% of the donors (mean: 21; median: 6; range: 0-200), with 17% of the CTC-positive donors having ≥1 CTC overexpressing HER2 protein. Conclusions: This study demonstrates the feasibility of HER2 evaluation using IF for protein expression and HER2 FISH for gene amplification on CTCs enriched from blood using the Parsortix® systems. It also demonstrates that blood collection in Streck tubes is suitable for both assays, with the advantage of allowing longer blood sample storage and facilitating batch shipping and processing of clinical samples. *Research Use Only. Not for use in diagnostic procedures. Citation Format: Nerea Borreguero-Munoz, Alex Young, Jessica Kimber, Mariacristina Ciccioli, Anne-Sophie Pailhes-Jimenez. Evaluation of HER2 status in circulating tumor cells isolated using the Parsortix® system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1033.
    Materialart: Online-Ressource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-1033
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2023
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 5
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    Abstract A54: Reaching the Hispanic community via ¡Salud! Serie de Charlas
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 23, No. 11_Supplement ( 2014-11-01), p. A54-A54
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11_Supplement ( 2014-11-01), p. A54-A54
    Kurzfassung: Background: Racial and ethnic minority populations have additional and unique barriers to cancer care services than majority populations. Knowledge and language barriers are particularly prevalent among Hispanic populations. Results from our team's previous work and other public health research indicate that face-to-face health communication efforts are the most revered and preferred communication style for health messages within the Hispanic community. In addition, the success of the messages can be further enriched by increasing interpersonal communication; that is, by moving from the formal health education context to an informal context, such as neighborhood and community gatherings . Consistent with this notion, the impact of respected health advisors from the community has been studied and results suggest improved behavior or attitude changes. Recent studies report community-based programs developed for Hispanic populations incorporating health advisors (i.e. health workers, outreach educators, community health advocates) have been successful in increasing cancer screening behaviors. Methods: ¡Salud! Serie de charlas (Health! A series of meetings) is a free, quarterly community gathering focused on reducing cancer health disparities in the Hispanic community of Tampa Bay, FL. These two-hour charlas, led by a community health educator and a panel of Spanish-speaking physicians, healthcare professionals and cancer survivors, encourage audience interaction as various topics are presented. A ¡Salud! Serie de charlas centered on Cancer Prevention was offered to the Hispanic Community in August 2013 at Ana G. Méndez University System, Tampa Bay Campus. Forty individuals participated in discussions regarding cancer prevention and screening guidelines. At the end of the event participants completed an evaluation survey. Results: The majority of participants were Puerto Rican, Mexican or Venezuelan. 63% were between the ages of 35-64; 66% female and 65% married. 54% preferred receiving health information in Spanish, while 40% said either English or Spanish was acceptable. 100% believed they learned something new and felt confident in their ability to make good decisions about their health based on the information they learned. 98% reported increased awareness about cancer prevention. The participant's questions centered on nutrition, skin cancer protection and breast cancer screening. Most participants enjoyed the event and requested extended length of time for future presentations. Conclusion: Charlas conducted in the community may present an effective interpersonal communication channel for increasing knowledge and affecting health behavior change among Hispanic populations. Future ¡Salud! Serie de charlas events will take place at Moffitt Cancer Center to demystify the hospital and increase comfort levels with choosing a cancer center for treatment. Citation Format: Jessica McIntyre, Yonaira M. Rivera, Wendy Gonzalez, Axel Ramos, Teresita Muñoz-Antonia, Julio Jimenez, Gwendolyn P. Quinn. Reaching the Hispanic community via ¡Salud! Serie de Charlas. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A54. doi:10.1158/1538-7755.DISP13-A54
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1538-7755.DISP13-A54
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2014
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Discovery Vol. 6, No. 8 ( 2016-08-01), p. 900-913
    Details
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 6, No. 8 ( 2016-08-01), p. 900-913
    Kurzfassung: CRISPR/Cas9 has emerged as a powerful new tool to systematically probe gene function. We compared the performance of CRISPR to RNAi-based loss-of-function screens for the identification of cancer dependencies across multiple cancer cell lines. CRISPR dropout screens consistently identified more lethal genes than RNAi, implying that the identification of many cellular dependencies may require full gene inactivation. However, in two aneuploid cancer models, we found that all genes within highly amplified regions, including nonexpressed genes, scored as lethal by CRISPR, revealing an unanticipated class of false-positive hits. In addition, using a CRISPR tiling screen, we found that sgRNAs targeting essential domains generate the strongest lethality phenotypes and thus provide a strategy to rapidly define the protein domains required for cancer dependence. Collectively, these findings not only demonstrate the utility of CRISPR screens in the identification of cancer-essential genes, but also reveal the need to carefully control for false-positive results in chromosomally unstable cancer lines. Significance: We show in this study that CRISPR-based screens have a significantly lower false-negative rate compared with RNAi-based screens, but have specific liabilities particularly in the interrogation of regions of genome amplification. Therefore, this study provides critical insights for applying CRISPR-based screens toward the systematic identification of new cancer targets. Cancer Discov; 6(8); 900–13. ©2016 AACR. See related commentary by Sheel and Xue, p. 824. See related article by Aguirre et al., p. 914. This article is highlighted in the In This Issue feature, p. 803
    Materialart: Online-Ressource
    ISSN: 2159-8274 , 2159-8290
    URL: Article
    DOI: 10.1158/2159-8290.CD-16-0178
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2016
    ZDB Id: 2607892-2
    Standort Signatur Einschränkungen Verfügbarkeit
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