GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (10)
  • 1
    Online Resource
    Online Resource
    Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 23 ( 2020-12-01), p. 5216-5230
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 23 ( 2020-12-01), p. 5216-5230
    Abstract: SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2+ tumor behavior, Snai2-deficient mice were crossed with a mouse line carrying the ErbB2/Neu protooncogene to generate HER2+/ERBB2+ breast cancer. Tumors generated in this model expressed SNAI2 in the stroma but not the epithelium, allowing for the role of stromal SNAI2 to be studied without interference from the epithelial compartment. The absence of SNAI2 in the stroma of HER2+/ERBB2+ tumors is associated with: (i) lower levels of cyclin D1 (CCND1) and reduced tumor epithelium proliferation; (ii) higher levels of AKT and a lower incidence of metastasis; (iii) lower levels of angiopoietin-2 (ANGPT2), and more necrosis. Together, these results indicate that the loss of SNAI2 in cancer-associated fibroblasts limits the production of some cytokines, which influences AKT/ERK tumor signaling and subsequent proliferative and metastatic capacity of ERBB2+ breast cancer cells. Accordingly, SNAI2 expression in the stroma enhanced the tumorigenicity of luminal B HER2+/ERBB2+ breast cancers. This work emphasizes the importance of stromal SNAI2 in breast cancer progression and patients' prognosis. Significance: Stromal SNAI2 expression enhances the tumorigenicity of luminal B HER2+ breast cancers and can identify a subset of patients with poor prognosis, making SNAI2 a potential therapeutic target for this disease.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-20-0278
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Screen to Save: Results from NCI's Colorectal Cancer Outreach and Screening Initiative to Promote Awareness and Knowledge of Colorectal Cancer in Racial/Ethnic and Rural Populations
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 5 ( 2020-05-01), p. 910-917
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 5 ( 2020-05-01), p. 910-917
    Abstract: The Center to Reduce Cancer Health Disparities (CRCHD), National Cancer Institute (NCI), launched Screen to Save, NCI's Colorectal Cancer Outreach and Screening Initiative to promote awareness and knowledge of colorectal cancer in racial/ethnic and rural populations. Methods: The initiative was implemented through CRCHD's National Outreach Network (NON) and Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) programs. NON is a national network of Community Health Educators (CHEs), aligned with NCI-designated Cancer Centers (CCs). CPACHE are partnerships between a CC and a minority-serving institution with, among other components, an Outreach Core and a CHE. In phases I and II, the CHEs disseminated cancer-related information and implemented evidence-based educational outreach. Results: In total, 3,183 pre/post surveys were obtained from participants, ages 50 to 74 years, during 347 educational events held in phase I. Results demonstrated all racial/ethnic groups had an increase in colorectal cancer-related knowledge, and each group agreed that the educational event increased the likelihood they would engage in colorectal cancer-related healthful behaviors. For phase II, Connections to Care, participants were linked to screening. Eighty-two percent of participants who were screened during the follow-up period obtained their results. Conclusions: These results suggest that culturally tailored, standardized educational messaging and data collection tools are key elements that can serve to inform the effectiveness of educational outreach to advance awareness and knowledge of colorectal cancer. Impact: Future initiatives should focus on large-scale national efforts to elucidate effective models of connections to care related to colorectal cancer screening, follow-up, and treatments that are modifiable to meet community needs.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-19-0972
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Deregulated Activity of Akt in Epithelial Basal Cells Induces Spontaneous Tumors and Heightened Sensitivity to Skin Carcinogenesis
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Research Vol. 67, No. 22 ( 2007-11-15), p. 10879-10888
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 22 ( 2007-11-15), p. 10879-10888
    Abstract: Aberrant activation of the phosphoinositide-3-kinase (PI3K)/PTEN/Akt pathway, leading to increased proliferation and decreased apoptosis, has been implicated in several human pathologies including cancer. Our previous data have shown that Akt-mediated signaling is an essential mediator in the mouse skin carcinogenesis system during both the tumor promotion and progression stages. In addition, overexpression of Akt is also able to transform keratinocytes through transcriptional and posttranscriptional processes. Here, we report the consequences of the increased expression of Akt1 (wtAkt) or constitutively active Akt1 (myrAkt) in the basal layer of stratified epithelia using the bovine keratin K5 promoter. These mice display alterations in epidermal proliferation and differentiation. In addition, transgenic mice with the highest levels of Akt expression developed spontaneous epithelial tumors in multiple organs with age. Furthermore, both wtAkt and myrAkt transgenic lines displayed heightened sensitivity to the epidermal proliferative effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and heightened sensitivity to two-stage skin carcinogenesis. Finally, enhanced susceptibility to two-stage carcinogenesis correlated with a more sustained proliferative response following treatment with TPA as well as sustained alterations in Akt downstream signaling pathways and elevations in cell cycle regulatory proteins. Collectively, the data provide direct support for an important role for Akt signaling in epithelial carcinogenesis in vivo, especially during the tumor promotion stage. [Cancer Res 2007;67(22):10879–88]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-07-2564
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Akt Activation Synergizes with Trp53 Loss in Oral Epithelium to Produce a Novel Mouse Model for Head and Neck Squamous Cell Carcinoma
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 3 ( 2009-02-01), p. 1099-1108
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 3 ( 2009-02-01), p. 1099-1108
    Abstract: Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia with poor prognosis and survival that frequently displays Akt overactivation. Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC. The myrAkt mice develop oral lesions, making it a possible model of human oral dysplasia. The malignant conversion of these lesions, which is hampered due to the induction of premature senescence, is achieved by the subsequent ablation of Trp53 gene in the same cells in vivo. Importantly, mouse oral tumors can be followed by in vivo imaging, show metastatic spreading to regional lymph nodes, and display activation of nuclear factor-κB and signal transducer and activator of transcription-3 pathways and decreased transforming growth factor-β type II receptor expression, thus resembling human counterparts. In addition, malignant conversion is associated with increased number of putative tumor stem cells. These data identify activation of Akt and p53 loss as a major mechanism of oral tumorigenesis in vivo and suggest that blocking these signaling pathways could have therapeutic implications for the management of HNSCC. [Cancer Res 2009;69(3):1099–108]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-08-3240
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract PD4-08: Breast cancer clinical subtypes in brain metastases patients from a prospective registry of advanced breast cancer, GEICAM/2014-03 (RegistEM)
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD4-08-PD4-08
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD4-08-PD4-08
    Abstract: Background: The incidence of breast cancer brain metastases (BCBM) is estimated to be around 5-15%, but necropsies show a much higher incidence (30-50%). Frecuency of BCBM has gradually increase likely as a result from advances in systemic treatment that allow more patients to live long enough to develop BCBM. In general, outcome for patients with BCBM is poor, with 1-year survival of approximately 20%, but some patient and tumor characteristics are associated with improved behaviour. The RegistEM study is a non-interventional cohort study providing prospective data from around 1,867 advanced breast cancer (ABC) patients (pts.). This study offers a unique opportunity to assess the incidence, potential risk factors, and outcomes for patients with BCBM. Methods: In this analysis (cut-off date 26/April/2021 and ongoing database), we describe the features of 218 pts. with BCBM included in the RegistEM study, which represent the 11% of current total number of pts. in the study. BC clinical subtypes are based on the most recent tumor lesion (distant metastasis or primary BC). The most frequent therapies by BC subtypes are detailed in the table below. At the database cut-off date, death had been reported in 74% pts with BCBM. Results: All pts. were female, 97% caucasian, and at ABC diagnosis, 66% were postmenopausal and their median age was 55 years. The subtype distribution was: Luminal (ER+/HER2-) 41%, HER2+ 35%, Triple Negative (TN) 19%, unknown 5%. Eighty pts. (37%) had BM at diagnosis of ABC, and in 17 of them BM was the only site of relapse. The median time from diagnosis of primary BC to BM at initial diagnosis of ABC was 34 months (mo), being shorter for TN (18 mo). In patients without BM at diagnosis of ABC, the median time from ABC diagnosis to onset of BM for de novo metastatic disease was: Luminal 27 mo, HER2+ 28 mo, TN 10 mo; while for EBC disease was: Luminal 18 mo, HER2+ 14 mo, TN 10 mo. De novo metastatic BC was associated with longer time to BM appearance (HR:0.527, CI 95%: 0.358-0.776) while TN subtype with shorter time (HR:4.122, CI 95%: 2.318-7.329) compared to Luminal subtype. The median survival from the onset of BM, according to BC subtype was: Luminal 6 mo, HER2 11 mo and TN 4 mo. Risk factors for worse survival were: BM at ABC (HR:1.677, CI 95%:1.169-2.406) and TN subtype (HR:3.631, CI 95%: 2.353-5.603) compared to Luminal subtype. Conclusions: TN breast cancer is associated with a shorter time to brain metastases and poorer outcome than other breast cancer subtype. Patients with de novo metastatic BC develop metastases later than patients with metastatic recurrence after primary BC. New treatment approach to avoid the onset of brain metastases in patients with ABC warrants further research. Luminaln=90 (41%)HER2+n=77 (35%)Triple Negativen=41 (19%)HRHER2+-Any+–First BC diagnosis, nEBC (stages I-III)ULABC or de novo metastatic65. 2555. 2227. 14Only CNS metastases at ABC diagnosis584Number of line (L)1L2L3L1L2L3L1L2L3Ln877158745936352515Type of therapy, nET/BT26167443---ET239531----CT/BT/ET58-15-----CT/BT10924014211331CT/ET623------CT172635321222214BT1693811---Most frequent therapies by mechanism of action, nAI/CDK4/6i 20SERD 12CT single agent 12AI single agent 11CT + antiangiogenic 9CT single agent 24SERD +/- CDK4/6i 8AI + CDK4/6i 7CT + antiangiogenic 7CT single agent 27CT combination 8SERD +/- CDK4/6i 6CT + dual anti-HER2 blockade 46CT + anti-HER2 blockade single agent 7Anti-HER2 single agent 35CT + anti-HER2 blockade single agent 12CT + anti-HER2 blockade single agent 18Anti-HER2 blockade single agent 9CT combination 12CT + antiangiogenic 12CT single agent 10CT single agent 16CT combination 6CT + antiangiogenic 4CT single agent 9CT combination 5Median Treatment duration, months (range)7 (0-31)6 (0-41)4 (0-16)12 (0-43)5 (0-47)3 (0-17)5 (0-18)3 (0-7)2 (0-6)TTP in months, median (range)8 (2-35)--12 (3-46)--6 (2-19)--Death, n635139Abbreviations: HR=hormone receptor; HER2=human epidermal growth factor receptor 2; BC=breast cancer; EBC=early breast cancer; ULABC=unresectable locally advanced breast cancer; ET=endrocrine therapy; BT=biological therapy; CT=chemotherapy; TTP=time to progression; AI=aromatase inhibitor; SERD=selective estrogen receptor degrader; CDK4/6i=cyclin dependent kinases 4 and 6 inhibitor Citation Format: Sara López-Tarruella, Ángel Guerrero-Zotano, César A Rodríguez, Josefina Cruz, María Hernández, Encarna Adrover, Álvaro Rodríguez-Lescure, Catalina Falo, Purificación Martínez, Ana Miguel, Raquel Andrés, Silvia Antolín, J. Ignacio Chacón, Jose Luis Alonso Romero, Rafael Villanueva Vázquez, Ana Isabel Ballesteros García, María Galán Gramaje, Diego Malón Jiménez, Silvia Varela Ferreiro, Diana Moreno Muñoz, Ruth Campo, María José Escudero, Susana Bezares, Federico Rojo, Isabel Alvarez. Breast cancer clinical subtypes in brain metastases patients from a prospective registry of advanced breast cancer, GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-08.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-PD4-08
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract CT107: Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. CT107-CT107
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. CT107-CT107
    Abstract: Background: There is a lack of predictive biomarkers for immunotherapy in melanoma. In terms of IHC, there is no strong rational to support the use of PD-L1 expression. BRAF mutations occur in 40-50% of melanomas and the MAPK pathway may also be activated by NRAS mutations. Patients harboring these mutations face usually a worse prognosis. BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI) that, by mimicking the effect of a viral infection, mobilizes the immune system. Prior data from a phase I trial (NCT02828098) suggest that, when administered intratumorally, it causes an increase in CD8 infiltration and PD-L1 expression. The role of these and other biomarkers is being explored in the present phase II clinical trial. Study Design: Single arm study with BO-112 plus pembrolizumab (NCT04570332) in patients with advanced melanoma in progression to anti-PD1 therapy. Tumors were genotyped by next generation sequencing, whole exome sequencing and tumor mutation burden. Antitumor and immunological effects of the treatment in the tumor microenvironment were assessed by PDL1 and CD8 immunohistochemistry with a paired biopsy performed after 21 days of treatment. Results: A preliminary analysis has been performed, based on patients evaluable for clinical benefit (defined as response or stable disease & gt;16 weeks). Samples from 35 patients have been analyzed, with 24 patients paired biopsies available. Patients with “cold” tumors (PD-L1 negative and CD8 low) at baseline had a trend to lack of clinical benefit. Only basal PD-L1 in the inflammatory component showed a statistically significant correlation with clinical outcome (4/20 (25%) tumors PDL1 IC negative had benefit versus 10/15 (67%) positive), p=0.0053. Fifteen patients had an increase in PD-L1 and 14 patients had increase in CD8 infiltrate after BO-112 treatment; the lack of increase in PDL1 and CD8 after treatment was also predictive of lack of response (p=0.04). BRAF/NRAS driver mutations correlated with positive outcome. Clinical benefit was observed in 4 of 17 (24%) patients not carrying activating mutations whereas 11 out of 18 (61%) patients with BRAF/NRAS activating mutations had clinical benefit (p=0.02), mainly in cutaneous histology (14% versus 65%, p=0.02). Mucosal melanoma patients (n=3) achieved an ORR 66.7% and DCR 100%. The two mucosal melanoma patients with partial response harbored SETD2 mutations and one of them showed extensive cyclic nucleotide-gated (CNGs), indicative of defects in DNA repair pathways. Regarding acral melanoma patients (n=9), no responses were observed, even in the single case with a NRAS mutation. The only patient achieving clinical benefit, with stable disease & gt;16 weeks; had a unique mutation profile, with TP53 (inactivating) and KIT (activating) mutations. Conclusions: Patients basal mutant BRAF/NRAS could have more probability of benefit from BO-112 and pembrolizumab combination. PD-L1 and/or CD8 increase is an early marker of response. These findings could help to select patients in future clinical trials. Further investigation into predictive biomarkers is warranted. Citation Format: Ruth Roman, Philippe Saiag, Caroline Dutriaux, Luis de la Cruz Merino, Eduardo Castanon, Miguel F. Sanmamed, Caroline Robert, Juan F. Rodríguez-Moreno, Pablo Cerezuela-Fuentes, Ana M. Arance, María González Cao, Henry Montaudié, María Pilar López Criado, Julie Charles, Alfonso Berrocal, María del Carmen Álamo de la Gala, Enrique de Miguel, Elisa Funk-Brentano, Sorilla Prey, Eva Muñoz-Couselo, Delvys Rodríguez Abreu, Juan Martín-Liberal, Helena Escuin-Ordinas, Mark Branum, Sonia Macia, Marisol Quintero, Javier Sánchez López, Marya F. Chaney, Beatriz García-Peláez, Marta Vives-Usano, Miguel Ángel Molina, Stéphane Dalle, Iván Márquez-Rodas. Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma [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 CT107.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-CT107
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract P1-17-11: Sexual function in Mexican patients with breast cancer receiving active oncological treatment
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-17-11-P1-17-11
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-17-11-P1-17-11
    Abstract: Background: It is widely recognized that women's sexuality can be particularly complex during the treatment of breast cancer. This, in turn, has physical, emotional and psychological consequences throughout the life of these patients. However, there is limited information regarding sexual health in Hispanic women with breast cancer. The objective of this study was to evaluate sexual dysfunction in Mexican women with breast cancer who were receiving active treatment against cancer. Methods: We prospectively evaluated sexual dysfunction among Mexican patients with breast cancer receiving active oncological treatment at a single institution in Mexico City using the Spanish language version of the Female Sexual Function Index (FSFI). FSFI is graded as a continuous scale from 2-36, and is formed of 6 subscales (desire, arousal, lubrication, orgasm, satisfaction, and pain) with a maximal score of 6 each. Sexual dysfunction was defined as an FSFI & lt;26.55 points. Demographic and clinical data were collected from the clinical record and analyzed using descriptive statistics. Fisher's exact tests were used for comparisons among groups. Results: 84 women with breast cancer undergoing active treatment completed the FSFI. Median age was 57 years (range 25-87), 59.2% were postmenopausal, and 46.4% were married. Median body mass index (BMI) was 25.2. 60% of patients had early stage breast cancer (Stage 0-II), 64% were receiving hormonal treatment (average duration of 28.3 months), and 25% were undergoing treatment with chemotherapy. 42% had undergone breast conserving surgery, while 28% had received a mastectomy. 51 patients (60.7%) reported absence of sexual activity during the previous four weeks. Patients who reported sexual activity in the previous four weeks had a mean FSFI score of 23 points (range 15.7-44) and 63.6% had sexual dysfunction. Subscale scores were as follows: desire 1.7 (range 1.2-2.4), arousal 2.9 (range 1.5-5.1), lubrication 3.1 (range 1.5-4), orgasm 3.6 (range 1.1-4.8), satisfaction 4.0 (range 1.2-5.6), and pain 2.5 (range 1.2-5.2). Premenopausal women were more likely than postmenopausal women to report sexual dysfunction (85% vs. 44%, p = 0.02) with a mean FSFI score of 20.9 and 17.3 respectively. Among postmenopausal women with sexual dysfunction, the lowest scores were found in the desire (1.72) and pain domains (2.5). Desire (3.2) and lubrication (3.27) were the domains with the lowest scores among premenopausal patients. Sexual dysfunction was not related to the type of breast surgery (mastectomy vs breast conserving, p = 0.26). Conclusions: Our study shows a significant proportion of Mexican women with breast cancer have sexual dysfunction and absence of sexual activity. Premenopausal patients were more frequently affected, particularly in the desire and lubrication domains, while postmenopausal women reported poor desire and pain. This provides valuable information to design innovative strategies aimed at improving the sexual health and quality of life of patients diagnosed with breast cancer undergoing active oncological treatments. Citation Format: Mónica Lily Cordón-Paz, Luis Lara-Mejía, Ana Olvera-Cruz, Lorelí Mejía-Fernández, Pilar Milke-Garcia, Yanin Chavarri-Guerra. Sexual function in Mexican patients with breast cancer receiving active oncological treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-11.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-P1-17-11
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 560: High levels of baseline ctDNA constitute a poor prognostic factor in progression-free survival in patients receiving neo-adjuvant chemo-immunotherapy: Results from NADIM clinical trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 560-560
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 560-560
    Abstract: There is growing evidence supporting that long-term survival of neoadjuvant chemo-immunotherapy for locally advanced NSCLC patients can be achieved. However, some patients invariably progress within the short-term. Identification of patients at high risk of progression is needed to achieve a better control of the disease. Concentrations of baseline ctDNA have been shown to be of prognostic significance. Patients and methods 42 pre-treatment plasma samples from the NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab, were analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). Variant calling, annotation and filtering were performed on the Ion Reporter (v5.14) platform using the OncomineTagSeq Pan-Cancer Liquid Biopsy workflow (v2.3). The final variant matrix was obtained from vcf files as generated from Ion Reporter (v5.14) platform and applying an internal pipeline (R-code is available upon request). Progression disease was evaluated by RECIST criteria V1.1. Results A total of 116 variants were detected in 88.10% (N=37) of the plasma samples collected before neoadjuvant treatment. The average number of variants detected per sample was 3.13. The most frequently mutated genes were TP53, which accounts for 59.52% of the detected variants, followed by PIK3CA (30.95%), MAP2K1 (30.95%), APC (23.81%), MTOR (9.52%) and KIT (9.52%). Patients in whom a GNA11 mutation was detected in the plasma sample by NGS showed worsen progression free survival (PFS) (HR: 14. 95%; CI: 2.6-71, P-value with Fold Discovery Rate correction: 0.019). Finally, ctDNA levels at Mutant Allele Frequency (MAF) below 1% at baseline were associated with improved PFS (P=0.025). At 30 months, PFS was 80.30% for these patients compared with 58.33% in patients with ctDNA levels ≥ 1%. Conclusions Molecular profiling of liquid biopsies collected before neoadjuvant chemo-immunotherapy using NGS can identify patients at high risk of progression who might require more aggressive adjuvant treatment in order to achieve a better control of the disease. Citation Format: Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, Amelia Insa, M. Rosario Garcia-Campelo, Diego Pereiro Corbacho, Manuel Domine, Margarita Majem, Delvys Rodriguez-Abreu, Alex Martinez-Marti, Javier de Castro, Manuel Cobo, Guillermo Lopez-Vivanco, Edel del Barco, Reyes Bernabe, Nuria Viñolas, Isidoro Barneto, Santiago Viteri, Eva Pereira, Ana Royuela, Marta Casarrubios, Clara Salas, Edwin R Parra, Ignacio Wistuba, Virginia Calvo, Raquel Laza-Briviesca, Bartomeu Massuti, Alberto Cruz-Vermudez, Atocha Romero. High levels of baseline ctDNA constitute a poor prognostic factor in progression-free survival in patients receiving neo-adjuvant chemo-immunotherapy: Results from NADIM clinical trial [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 560.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-560
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 2553: Immune and malignant cell phenotypes of ovarian cancer are determined by distinct mutational processes
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 2553-2553
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 2553-2553
    Abstract: High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, a high degree of tumor heterogeneity and intraperitoneal spread. As immunotherapies have thus far proven ineffective in this disease, we sought to establish the determinants of immune recognition, avoidance and evasion in disease natural history to gain insight into the co-evolutionary processes underlying malignant progression and host immunity. Accordingly we linked mutational processes and anatomic sites of tumor foci as determinants of tumor microenvironment (TME) cellular phenotypes within and between patients using genome-based stratification of homologous recombination proficient (HRP) and deficient (HRD) disease subtypes, and profiling single cell phenotypes from ~1 million cells including cancer cells, T cells, myeloid cells and fibroblasts derived from single cell RNA sequencing, and in situ spatial profiling of histopathology, cancer cell, T cell and macrophage states of 160 tumor sites obtained from 42 treatment-naive patients. Mutational processes in HRD-Dup (BRCA1 mutant-like) tumors were associated with cancer cell-intrinsic JAK/STAT signaling and predominance of highly-differentiated dysfunctional CD8+ T cells in the TME; HRD-Del (BRCA2 mutant-like) tumors were associated with cancer cell-intrinsic NF-κB and TNFα signaling and expansion of M2-type macrophages; and foldback inversion (FBI, HRP) tumors were associated with cancer cell-intrinsic TGFβ signaling and overall immune exclusion, with a predominance of naive/central memory-like T cells. Increased neoantigen burden and HLA loss of heterozygosity (LOH) were defining genomic features of the HRD, but not FBI tumors. These mechanisms of escape from immune predation, with distinct signalling activity and losses of HLA allelic diversity in HRD tumors, connect evolutionary selection with immunological phenotypic states. Multi-region sampling revealed substantial spatial variation, highlighting site-specific properties of the ovary and fallopian tube as putative “immune-privileged” sites. These results establish that in patients with widespread intraperitoneal disease, the local properties of organ sites may determine malignant cell selection and immune pruning. Furthermore, we observed that spatial cellular topology is a major determinant of tumor-immune interactions by in situ protein measurements, revealing ubiquitous PD1-PDL1 interactions in HRD tumors. Together, our findings yield mechanistic insights for how distinct mutational processes in HGSOC lead to diverse patterns of within- and between- patient variation in immune resistance, which can be exploited to optimize future immuno-therapeutic treatment strategies. Citation Format: Ignacio Vázquez-García, Florian Uhlitz, Nicholas Ceglia, Jamie L. Lim, Michelle Wu, Neeman Mohibullah, Arvin Eric B. Ruiz, Kevin M. Boehm, Viktoria Bojilova, Christopher J. Fong, Tyler Funnell, Diljot Grewal, Eliyahu Havasov, Samantha Leung, Arfath Pasha, Druv M. Patel, Maryam Pourmaleki, Nicole Rusk, Hongyu Shi, Rami Vanguri, Marc J. Williams, Allen W. Zhang, Vance Broach, Dennis S. Chi, Arnaud Da Cruz Paula, Ginger J. Gardner, Sarah H. Kim, Matthew Lennon, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Ritika Kundra, Agnes Viale, Yonina Bykov, Fatemeh N. Derakhshan, Luke Geneslaw, Ana Maroldi, Andrea Schietinger, Travis J. Hollmann, Samuel F. Bakhoum, Robert A. Soslow, Lora H. Ellenson, Nadeem Abu-Rustum, Carol Aghajanian, Claire F. Friedman, Andrew McPherson, Britta Weigelt, MSK SPECTRUM Consortium, Dmitriy Zamarin, Sohrab P. Shah. Immune and malignant cell phenotypes of ovarian cancer are determined by distinct mutational processes [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 2553.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-2553
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Spontaneous Squamous Cell Carcinoma Induced by the Somatic Inactivation of Retinoblastoma and Trp53 Tumor Suppressors
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Research Vol. 68, No. 3 ( 2008-02-01), p. 683-692
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 3 ( 2008-02-01), p. 683-692
    Abstract: Squamous cell carcinomas (SCC) represent the most aggressive type of nonmelanoma skin cancer. Although little is known about the causal alterations of SCCs, in organ-transplanted patients the E7 and E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved. Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that p53 is the predominant tumor suppressor acting in mouse epidermis. Although the simultaneous inactivation of pRb and p53 does not aggravate the phenotype observed in Rb-deficient epidermis in terms of proliferation and/or differentiation, spontaneous SCC development is severely accelerated in doubly deficient mice. The tumors are aggressive and undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the epidermal growth factor receptor/Akt pathway, resulting in increased proliferation in normal and dysplastic hair follicles and augmented tumor angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer. [Cancer Res 2008;68(3):683–92]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-07-3049
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...