bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-04-01: β2-adrenergic receptor signaling regulates metabolic pathways critical for the function of myeloid-derived suppressor cells
Authors: Mohammadpour Hemn 
Published: March 2022

Abstract
Summary Nerve-driven chronic adrenergic stress can suppress anti-tumor immunity. However, details are still missing or poorly understood. Catecholamines (epinephrine, norepinephrine) released by sympathetic nerves can activate adrenergic receptors present on nearly every cell type including myeloid derived suppressor cells (MDSCs). MDSCs are increasingly recognized as critical players in tumor immunology because, in addition to their fundamental roles in suppressing effector NK cells, CD8+ T cells and CD4+ T cells, they also play a direct role in tumor growth, differentiation and metastasis. Recently, we have shown that β2 adrenergic receptor signaling activated by chronic stress increases the immunosuppressive function of MDSCs, but the precise mechanisms remain unresolved. Building upon our earlier work, we now have discovered that the beta-2 adrenergic receptor (β2-AR) stress pathway drives the immune suppressive activity of MDSCs through altering their metabolism. First, we found that the expression of surface β2-AR on MDSCs increases with tumor growth in 4T1 breast cancer model and patients with breast cancer. We also found that β2-AR signaling decreases glycolysis, while increasing oxidative phosphorylation and fatty acid oxidation (FAO). β2-AR signaling also increased mitochondrial intensity and mitochondrial potential of MDSCs both in vitro and in vivo. β2-AR signaling in MDSCs also increased the expression of Carnitine Palmitoyltransferase 1A (CPT1A) necessary for the FAO-mediated immunosuppressive function of MDSCs. Blocking CPT1A using etomoxir decreased tumor growth and immunosuppressive function of MDSCs in Wild Type (WT) mice but not β2-AR-/- mice or severe combined immunodeficient mice (SCID) mice. Moreover, we found that β2-AR signaling increases autophagy and activates the arachidonic acid cycle, both required for increasing the release of the immunosuppressive mediator, PGE2 in both mouse MDSCs and. PBMCs derived MDSCs. Together, our data reveal that stress-driven β2-AR signaling is an important physiological determinant that regulates key metabolic pathways in MDSCs enabling their immunosuppressive function. These data reveal a major, physiologically relevant role for nervous activity and adrenergic stress in MDSC-tumor biology. Keywords: β2 adrenergic receptor, stress, MDSC, Metabolism, Breast Cancer,
Citation Format: Hemn Mohammadpour. β2-adrenergic receptor signaling regulates metabolic pathways critical for the function of myeloid-derived suppressor cells [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 P4-04-01.
Abstract P4-07-12: An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer
Authors: Nishimura Reiki , Osako Tomofumi , Okumura Yasuhiro , Nakano Masahiro , Otsuka Hiroko , Fujisue Mamiko , Arima Nobuyuki 
Published: March 2022

Abstract
Background: Lymphovascular invasion (LVI) is associated with a poor outcome in breast cancer. The purpose of this study was to evaluate the clinical significance of LVI in primary breast cancer and to investigate disease-free survival (DFS) as a prognostic marker according to the breast cancer subtypes. The clinical significance of LVI was analyzed to investigate the biology and prognosis. Patients and Methods: This study examined 4,652 consecutive invasive breast cancer cases excluding the patients with non-invasive cancer, Stage IV and neo-adjuvant therapy from February 2002 to February 2021. Clinicopathological characteristics and prognosis of LVI positive and negative tumors were compared. LVI was evaluated in hematoxylin and eosin staining specimen from surgically resected samples. The ER, PgR, Ki-67, p53, HER2 status were evaluated using immunohistochemistry (IHC). Breast cancer subtypes were categorized based on the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff point: 20%) in invasive tumors. The median follow-up period was 95 months. Results: The LVI expression rates were 29.2%(low: 19.7% and high: 9.5%)in all primary cases. The LVI positive rate significantly correlated with ER/PgR negative, HER2 positive, p53 overexpression, higher Ki-67 index values, higher nuclear grade, positive nodes, and larger tumor. Moreover, the subtypes significantly correlated with LVI positivity; 20% in Luminal A, 34.6% in Luminal B, 40.9% in Lumina/HER2, 38.1% in HER2 enriched, and 29.8% in Triple Negative (TN). There were significant differences in DFS between LVI status in Luminal A, Luminal B, and TN subtypes, but there were no difference in the Luminal/HER2 and HER2 enriched subtypes. A multivariate analysis revealed that LVI was a significant factor in Luminal B and TN subtypes. Conclusion: LVI significantly correlated with the advanced and aggressive characteristics in breast cancer. Luminal A type had a lower LVI rate and HER2 type had a higher rate. Moreover, LVI was a significant prognostic factor in Luminal B and TN subtypes. These data suggest that the LVI status was useful in predicting the prognosis in HER2 negative breast cancer.
Citation Format: Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Hiroko Otsuka, Mamiko Fujisue, Nobuyuki Arima. An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer [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 P4-07-12.
Abstract P4-09-07: Psychological impact of type of breast cancer surgery: A national cohort study
Authors: Ahn Soo Kyung , Oh Sohee , Kim Jongjin , Choi Jung-Seok , Hwang Ki-Tae 
Published: March 2022

Abstract
Background Type of breast surgery and breast reconstruction after mastectomy may affect the psychological well-being of breast cancer patients. The present study assessed the impact of different types of breast surgery on rates of psychological disorders in breast cancer patients. Patients & Methods This nationwide cohort study, based on Korean Health Insurance Review and Assessment Service (HIRA) claims data, included 26,259 patients who were diagnosed with invasive breast cancer and underwent surgery from June 1, 2017, to December 31, 2018. Associations between the incidence of psychological disorders and variables such as type of breast cancer surgery, patient age, and insurance type were evaluated by univariable and multivariable time dependent Cox regression analyses. Results Of the 26,259 patients, 9,394 (35.8%) underwent total mastectomy (TM) and 16,865 (64.2%) underwent partial mastectomy (PM); of the former, 4,056 (43.2%) underwent breast reconstruction surgery (RS). The median follow-up time for all patients was 194 days (interquartile range 74-334 days). A total of 4685 patients (17.84%) were newly diagnosed with psychological disorders after breast cancer surgery. Multivariable analysis showed that axillary lymph node dissection (ALND) was significantly associated with increased rates of overall psychological disorders (hazard ratio [HR] 1.337 p&lt;0.0001), depression (HR 1.124 p=0.0462), anxiety (HR 1.459, p&lt;0.0001) and insomnia (HR 1.238, p&lt;0.0001). The rates of overall psychological disorders (HR 0.889, p=0.0002) and insomnia (HR 0.897, p=0.01) were significantly lower in patients who underwent TM than PM. The rates of overall psychological disorders (HR 0.837, p=0.0001) and insomnia (HR 0.831, p=0.0021) were also significantly lower in patients who underwent TM followed by RS than in patients who underwent PM. RS tended to reduce the rate of overall psychological disorders in patients who underwent TM. Subgroup analysis showed that, compared with PM, RS after TM significantly reduced the incidence of insomnia in younger patients (&lt;50 years) and those who underwent sentinel lymph node biopsy (SLNBx). Conclusion In contrast to general belief, rates of overall psychological disorders and insomnia were higher in patients who underwent PM than TM. Compared with PM, RS after TM resulted in significantly lower rates of psychological disorders and insomnia in younger patients (age &lt;50 years) and those who underwent SLNBx at a median &lt; 1 year postoperatively. ALND was associated with increased rates of overall psychological disorders, depression, anxiety and insomnia.
Citation Format: Soo Kyung Ahn, Sohee Oh, Jongjin Kim, Jung-Seok Choi, Ki-Tae Hwang. Psychological impact of type of breast cancer surgery: A national cohort study [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 P4-09-07.
Abstract P5-05-08: CXCL16 as a potential therapeutic target of triple-negative breast cancer
Authors: Cho Sun Wook , Jang Mi Gyeong , Sun Hyun Jin , Lee Han Sai , Song Young Shin , Kim Seong Keun 
Published: March 2022

Abstract
CXCL16, as a chemotactic cytokine, promotes cancer proliferation, migration, and immune cell infiltration in tumor microenvironment. However, CXCL16 has been shown to play a conflicting role in breast cancer. The aim of this study was to investigate the therapeutic potential of CXCL16 in breast cancer. Breast cancer patients (n=1097) from the TCGA dataset were divided into two group according to the CXCL16 expressions, the CXCL16low (n=548) and the CXCLhigh (n=549) groups. Mean diagnostic ages were similar between groups (59 ± 13.5 vs 58 ± 12.9 years, P=0.233). The ratio of triple-negative breast cancer (TNBC) was significantly higher in the CXCLhigh than that of the CXCL16low groups (24.8 vs 6.8%, P&lt;0.001), while the presence of distant metastasis or overall survivals were not different between groups. Interestingly, gene scoring analysis showed that oncogenic molecules including M2-macrophage- (r=0.36, P&lt;0.001), efferocytosis- (r=0.42, P&lt;0.001), and chemokine- (r=0.46, P&lt;0.001) related gene sets showed significantly strong positive relations with the CXCL16 expressions in all patients including both TNBC (n=924) and non-TNBC (n=173). Additionally, the gene set score from PI3K/Akt pathway showed positive relation with the CXCL16 expressions in the non-TNBC (r=022, P&lt;0.001) but not in the TNBC group. Next, a xenograft mouse model of TNBC was established with MDA-MB-231 cells, and anti-mouse CXCL16 antibody (designated as aCXCL16 group) or control IgG (designated as control group) were intravenously injected (25µg/100µl), twice per week. During 3 weeks, tumor growth was significantly delayed in the aCXCL16 than the control group by 37%. In conclusion, CXCL16 is highly expressed in TNBC and positively correlates with M2-macrophage related genes. Neutralizing CXCL16 by anti-CXCL16 shows therapeutic effects on the xenograft model of TNBC, suggesting that CXCL16 can be a potential therapeutic target for breast cancer.
Citation Format: Sun Wook Cho, Mi Gyeong Jang, Hyun Jin Sun, Han Sai Lee, Young Shin Song, Seong Keun Kim. CXCL16 as a potential therapeutic target of triple-negative breast cancer [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 P5-05-08.
Abstract P5-14-15: Examining inequities related to inpatient hospital length of stay for breast cancer patients: A retrospective study during the COVID-19 pandemic
Authors: Kamaraju Sailaja , Canales Bethany , Wright Tamiah , Charlson John , Szabo Aniko , Wetzel Thomas , Power Steve , Campbell Grace 
Published: March 2022

Abstract
Purpose: In the state of Wisconsin, breast cancer patients from African American (AAs) communities have lower survival rates compared to their Caucasian counterparts. Multiple inequities related to sociodemographic factors, delays in diagnosis, advanced disease stage at presentation and presence of comorbidities including higher body mass index (BMI) contribute to these disparities, many of which have only widened during the COVID-19 pandemic. This study examined specific factors related to prolonged hospital length of stay (LOS) for breast cancer patients admitted to inpatient units during the pandemic. Methods: This analysis includes initial CY20 LOS medical record data for hospitalized patients 18 years and older with a diagnosis of breast cancer from 1/1/2020-12/31/2020. Supplemental data included disease registry and diagnostic data, and SES data determined by patient zip code. Poisson regression models with robust standard errors were used to compare the LOS index (LOSi) between groups of patients based on race, SES group, primary payer, and BMI. Results: A total of 272 patients with breast cancer that were admitted to inpatient oncology units were identified. Demographics included White (72.4%), Black (22.4%), and others (5.1%). Other characteristics included: low SES (8.8%), medium- low (9.5%), medium (15.4%), medium-high (11.0%), high SES (4.4%), and others (non-Milwaukee county) (50.7%),Medicaid (8.8%), Medicare (61.3%), Managed care (29.0%), and others (0.73%). Body mass varied among the patients; underweight (0.36%), overweight (30.8%), obese (41.5%). There were significant differences in LOSi: Black (LOSi=1.24, p=0.01), medium-low SES (LOSi=1.46, p=0.02), Medicaid (LOSi=1.40, p=0.00), underweight (LOSi=1.66, p=0.00), and overweight (LOSi=1.23, p = 0.01) patients had slightly longer LOSi, with LOSi ratio above 1. Conclusion: This study shows how patient-specific factors such as race, SES, primary payer, and BMI contribute to inpatient LOS for breast cancer patients. Healthcare systems may benefit by addressing indicators and patients’ factors to reduce hospital LOS, and ultimately healthcare costs.
Citation Format: Sailaja Kamaraju, Bethany Canales, Tamiah Wright, John Charlson, Aniko Szabo, Thomas Wetzel, Steve Power, Grace Campbell. Examining inequities related to inpatient hospital length of stay for breast cancer patients: A retrospective study during the COVID-19 pandemic [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 P5-14-15.
Abstract P5-17-10: Anti-progranulin (GP88) antibody AG01 inhibitory effect on the growth of triple negative breast cancer cells
Authors: Serrero Ginette , Guha Rupa , Dong Jianping , Yue Binbin 
Published: March 2022

Abstract
Background: Triple negative breast cancer (TNBC) is characterized by invasiveness and short survival. Identifying novel TNBC targeted therapies to potentiate standard of care (SOC) therapy, is an unmet need. Progranulin (PGRN/GP88) is a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC). PGRN/GP88 tissue expression is an independent prognostic factor of recurrence while elevated serum PGRN/GP88 level is associated with poor outcomes such as progression of disease and shortened survival. Since PGRN/GP88 expression is elevated in 30% TNBC, we investigated the effect of inhibiting PGRN/GP88 effect on the proliferation and tumor growth of triple negative breast cancer cells. Methods: For this purpose, we have developed a neutralizing anti-human PGRN/GP88 monoclonal antibody AG01 and examined its effect on the proliferation, migration, signaling pathway activation and biomarker expression of two TNBC cell lines MDA-MB-231 and HS578-T expressing PGRN/GP88, both in vitro and in vivo. Results: The inhibition of PGRN/GP88 action by AG01 treatment reduced proliferation and migration in a dose-and time-dependent fashion in MDA-MB-231 and HS578-T cells. Western blot analysis showed decreased expression of phosphorylated protein kinases p-Src, p-AKT and p-ERK involved in proliferation and survival upon AG01 treatment for both cell lines. Transwell assay showed that AG01 treatment inhibited migration and invasion in a dose-dependent fashion. Microarray analysis of several oncoproteins in cells treated with AG01 or control antibody demonstrated the inhibition of the expression of several markers of migration and angiogenesis. In vivo xenograft studies with MDA-MB-231 cells injected in athymic nude mice showed that AG01 treatment inhibited tumor growth as well as Ki67 expression, mitotic index and microvessel counts when compared to antibody control treated mice. In vivo dose response of AG01 in MDA-MB-231 tumor bearing mice will be provided. Conclusion: TNBC is a disease with poor prognosis in need of novel targeted therapeutic solutions. PGRN/GP88 represents a therapeutic target for TNBC with two companion diagnostics (tissue test and ELISA to measure GP88 circulating levels). Blocking PGRN/GP88 with AG01 antibody treatment will provide novel targeted therapeutic option for TNBC which could address the issue of toxicity, and unresponsiveness associated with SOC. This work is supported by a grant CA 224718 from the National Cancer Institute to GS.
Citation Format: Ginette Serrero, Rupa Guha, Jianping Dong, Binbin Yue. Anti-progranulin (GP88) antibody AG01 inhibitory effect on the growth of triple negative breast cancer cells [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 P5-17-10.
Abstract PD3-09: Cd73 may influence zoledronate-induced b- and t-cell accumulation into triple-negative breast tumors
Authors: Petruk Nataliia , Siddiqui Arafat , Määttä Jorma , Sandholm Jouko , Selander Katri 
Published: March 2022

Abstract
Background: CD73 is an ecto-5′-nucleotidase, which converts AMP to adenosine. In breast cancer, CD73 expression is associated with prognosis, treatment responses to anthracyclines and tumor immunity. Bisphosphonates (BP) inhibit osteoclast-mediated bone resorption. When given in the adjuvant setting, BPs increase survival among post-menopausal breast cancer patients. Since BPs also affect cells of the immune system, we hypothesized that CD73 expression may affect BP responses in triple negative breast cancer cells. Methods: Cell viability and IC50 BPs doses were determined by WST-8 kit. Apoptotic rate and cell cycle arrest were showed by FACS. The number of caspase3/7- positive cells was accessed by a red fluorescence emission via IncuCyteS3. The apoptosis-associated genes mRNA expression was determined by qPCR. To compare BP effect on TNBC tumoral responses in vivo, we used immune-competent mouse models of breast cancer. Tumors were stained by immunofluorescence and immunohistochemically.Results: Suppression of CD73 expression, but not of enzymatic activity significantly sensitized TNBC cells to nitrogen-containing BPs (n-BPs), especially to zoledronate in vitro. The stronger growth inhibitory effects of n-BPs in CD73-suppressed cells were associated with G1 cell cycle arrest and increased apoptosis, as compared with representative control cells in vitro. Zoledronate similarly inhibited both control and CD73-suppressed TNBC tumor growthin immune-competent mice. CD73 suppression in tumors led to the lower lung metastatic burden and metastases size. Zoledronate effect on increased apoptosis was similar in both groups, but significant in CD73-suppressed tumors. Impaired angiogenesis was shown by decreased CD34-positive cell number in CD73-suppressed tumors. Zoledronate significantly increased infiltration of CD45R/B220+ B cells and cytotoxic CD8+ T cells into CD73-suppressed tumors.Conclusions: Suppressed CD73 sensitizes TNBC cells to n-BP treatment, resulting inapoptosis activation and delayed proliferation in vitro. Zoledronate induces a more profound accumulation of CD45R/B220+ B cells and CD8+ T cells into TNBC tumors with the lack of CD73. Since tumor B-cell infiltration has been associated with favourable patient prognosis in breast cancer, the significance of this B-cell effect of zoledronate warrants further investigation.
Citation Format: Nataliia Petruk, Arafat Siddiqui, Jorma Määttä, Jouko Sandholm, Katri Selander. Cd73 may influence zoledronate-induced b- and t-cell accumulation into triple-negative breast tumors [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 PD3-09.
Immediate Recanalization of Large‐Vessel Occlusions by Tissue Plasminogen Activator Occurs in 28% of Patients Treated in a Mobile Stroke Unit
Authors: Czap Alexandra L. , Parker Stephanie , Yamal Jose‐Miguel , Wang Mengxi , Singh Noopur , Zou Jinhao , Phan Kenny , Rajan Suja S. , Grotta James C. , Bowry Ritvij 
Published: March 2022

Background
Recanalization of cerebral large‐vessel occlusions (LVOs) by intravenous thrombolysis is infrequent but has been relatively unexplored with ultraearly treatment. We evaluated prehospital treatment with tissue plasminogen activator (tPA) in a mobile stroke unit to explore the recanalization rate in patients with LVOs and its effect on early clinical improvement and long‐term disability.

Methods
Prospectively collected data were analyzed from Houston mobile stroke unit patients who were treated with tPA and had LVOs identified by either hyperdense arteries on computed tomography or arterial occlusion on computed tomography angiography while on board the mobile stroke unit. The primary outcome was immediate recanalization (IRC), categorized as resolution of LVO on repeat vascular imaging in the emergency department (ED) or on emergent angiography. The secondary outcome was change in National Institutes of Health Stroke Scale from baseline and modified Rankin score at 90 days.

Results

Sixty‐nine patients with anterior or posterior circulation LVOs were enrolled; the median time from last known normal to tPA bolus was 64.0 minutes (interquartile range, 52.0–89.0). Nineteen patients (28%) had IRC, with 11 based on computed tomography angiography on ED arrival and 8 based on first run of emergent angiography. Median time from tPA bolus to documentation of IRC was 61.0 minutes (interquartile range, 42.0–111.0). IRC was associated with improvement in median National Institutes of Health Stroke Scale from baseline (17.0 [14.0–22.0]) to ED arrival (10.0 [5.5–16.5]) and to 24 hours (4.0 [0.5–10.5]). Of the non‐IRC patients, 41 had recanalization after endovascular thrombectomy and 9 did not receive recanalization. The IRC group, earlier last known normal to tPA bolus, greater baseline National Institutes of Health Stroke Scale, and M1 and M2 middle cerebral artery occlusion locations were independently associated with greater improvement in National Institutes of Health Stroke Scale from baseline to ED arrival. The 90‐day modified Rankin score distribution was best in the IRC group, followed by the delayed recanalization group, and both had significantly less disability than the no recanalization group (
P
=0.002).

Conclusions
Recanalization by ED arrival occured in 28% of patients with LVO who received tPA treatment in a mobile stroke unit and results in early clinical improvement and less disability at 90 days.