bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3279: Circulating inflammatory biomarker C-reactive protein and radiotherapy-related pain in breast cancer patients
Authors: Lee Eunkyung , Nelson Omar L. , Puyana Carolina , Takita Cristiane , Wright Jean L. , Zhao Wei , Reis Isildinha M. , Lin Rick , Hu Jennifer J. 
Published: July 2017

Abstract
Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes. However, many patients develop treatment-related pain that negatively impacts quality of life.
Methods: We evaluated an inflammatory biomarker, C-reactive protein (CRP) in RT-associated pain in a prospective study of 366 breast cancer patients (64% Hispanic whites, 20% African Americans, 16% non-Hispanic whites) undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly-sensitive ELISA kit. Pain score was assessed at pre- and post-RT as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were considered clinically-relevant pain. Association between pain and CRP levels was evaluated using logistic regression models after adjusting for potential confounders.
Results: Overall, 16% patients at pre-RT and 31% patients at post-RT had pain. In multivariable analyses, RT-related pain score change &gt;4 was significantly associated with CRP change &gt;1 mg/L (OR=3.24, 95%CI=1.33, 7.88), age &lt;50 (OR=3.27, 95%CI=1.20, 8.92), and 3+ comorbidity conditions (OR=5.91, 95%CI=1.33, 26.82).
Conclusion: This is the first study to suggest that increased inflammatory biomarker, CRP level was associated with RT-related pain. Impact: Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect patients from RT-related pain and improve quality of life in breast cancer patients undergoing RT.
Citation Format: Eunkyung Lee, Omar L. Nelson, Carolina Puyana, Cristiane Takita, Jean L. Wright, Wei Zhao, Isildinha M. Reis, Rick Lin, Jennifer J. Hu. Circulating inflammatory biomarker C-reactive protein and radiotherapy-related pain in breast cancer patients [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 3279. doi:10.1158/1538-7445.AM2017-3279
Abstract 3289: Cutaneous melanocytic nevi and risk of melanoma deaths in women and men: a prospective study
Authors: Li Wen-Qing , Geng Hao , Cho Eunyoung , Qureshi Abrar 
Published: July 2017

Abstract
Background: Increased number of common acquired melanocytic nevi (moles) has been associated with an increased risk of melanoma. It is unclear whether melanocytic nevi may predict melanoma deaths. We prospectively examined the association between number of melanocytic nevi and risk of melanoma deaths based on 77316 women from the Nurses’ Health Study (NHS) and 32454 men from the Health Professionals Follow-up Study (HPFS).
Methods: In both cohorts, diagnosis of melanoma was reported biennially and pathologically confirmed. Deaths were confirmed by next of kin or the National Death Index. Information on the number of moles with ≥3 mm diameter on the upper extremity was collected in 1986. We used Cox regression models to evaluate the associations between number of melanocytic nevi and risk of melanoma deaths in the overall cohorts as well as only among melanoma cases.
Results: A total of 2450 cases of melanoma were documented (1545 in NHS and 905 in HPFS), out of which we identified 192 incident deaths due to melanoma (87 in NHS and 105 in HPFS) during the follow-up (1986-2012). Increased number of melanocytic nevi was associated with melanoma deaths; the multivariate-adjusted hazard ratio (HR) for 3 or more melanocytic nevi compared with no nevi on the upper extremity was 2.55 (95% confidence interval (CI): 1.52-4.28) for women and 3.97 (95% CI: 2.54-6.22) for men. A secondary analysis further found that increased number of melanocytic nevi was associated with both lethal melanoma (melanoma cases that died of melanoma) and non-lethal melanoma. Among melanoma cases, increased number of melanocytic nevi was independently associated with risk of melanoma deaths in men, with a HR of 1.89 (95% CI: 1.17-3.05) for 3 or more melanocytic nevi. The association persisted even after adjusting for Breslow thickness of melanoma and appeared particularly stronger among those with lower Breslow thickness (P for interaction=0.03). However, number of melanocytic nevi was not significantly associated with risk of melanoma deaths among melanoma cases in women (HR=1.03, 95% CI: 0.61-1.76 for 3 or more nevi).
Conclusion: Increased number of melanocytic nevi was significantly associated with risk of melanoma deaths in our cohorts of women and men. A high number of melanocytic nevi may independently predict the risk of melanoma deaths among men with melanoma.
Citation Format: Wen-Qing Li, Hao Geng, Eunyoung Cho, Abrar Qureshi. Cutaneous melanocytic nevi and risk of melanoma deaths in women and men: a prospective study [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 3289. doi:10.1158/1538-7445.AM2017-3289
Abstract 3294: Breast cancer extent and survival in diabetic women in a Finnish population based cohort
Authors: Murto Mika , Artama Miia , Visvanathan Kala , Murtola Teemu 
Published: July 2017

Abstract
Introduction: Breast cancer and diabetes are two major health problems for women. Around 1.7 million new breast cancer cases are diagnosed each year, making breast cancer the most common cancer type in women. Number of people with diabetes is estimated to be 415 million worldwide, thus one in 11 adults have diabetes. However, evidence on the association between diabetes and breast cancer prognosis is controversial. We estimated breast cancer extent at diagnosis and survival in a Finnish population-based cohort of female breast cancer patients.
Materials and methods: All newly diagnosed breast cancer cases among women in Finland between 1995 and 2013 were identified from comprehensive national Finnish Cancer Registry. To minimize possible bias due to differing participation in cancer screening the study population was limited to women with at least one mammography screening before the diagnosis. In total 45,786 cases were included in our study cohort. Information on recorded diagnoses of diabetes, hypertension, hypercholesterolemia and obesity from in- and outpatient hospital visits during 1995-2013 were obtained from national Care Register for Health Care maintained by National Institute for Health and Welfare. Logistic regression was used to evaluate the risk of having cancer extended to axillary lymph nodes or beyond at diagnosis. Cox regression was used to evaluate risk of breast cancer death and overall mortality after the diagnosis. Analyses were adjusted for age, comorbidities and number of mammography screens before the diagnosis. Survival analyses were further adjusted for tumor extent and primary treatment.
Results: In total 1,419 women had diabetes. Compared to non-diabetic women, breast cancer was more often advanced to axillary lymph-nodes (OR 1.19; 95% CI 1.05-1.34) or metastatic at diagnosis (OR 1.58; 95% CI 1.26-1.97) in diabetic women. Nevertheless, during the median follow-up of 6.9 year after the diagnosis, risk of breast cancer death did not differ between diabetic and non-diabetic women (0.99; 95% CI 0.81-1.21). Overall risk of death was elevated among diabetic women (HR 1.34; 95% CI 1.19-1.51).
Conclusion: Diabetic women have more often advanced tumor extent at diagnosis compared to non-diabetic women. However, diabetes did not affect disease-specific survival within 6.9 years after the diagnosis.
Citation Format: Mika Murto, Miia Artama, Kala Visvanathan, Teemu Murtola. Breast cancer extent and survival in diabetic women in a Finnish population based cohort [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 3294. doi:10.1158/1538-7445.AM2017-3294
Abstract 3298: Diindolylmethane and its halogenated analogues induce autophagy in human prostate cancer cells via induction of the astrocyte-elevated gene-1 (AEG-1)
Authors: Draz Hossam , Goldberg Alexander , Sanderson Thomas , Safe Stephen 
Published: July 2017

Abstract
3,3’-diindolylmethane (DIM) and its halogenated derivatives (ring-DIMs) are recently shown to induce protective autophagy in human prostate cancer cells. The mechanism of induction of autophagy by DIM has not been elucidated. As DIM is a mitochondrial ATP synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of AMP/ATP ratio and activation of AMPK signaling in prostate cancer cells. Autophagic activity was monitored by LC3B-I to LC3B-II conversion in LNCaP and C42B prostate cancer cells. Autophagic vacuoles were examined using Cyto-ID autophagy detection kit and transmission electron microscope (TEM). Protein levels for AMPK, pAMPK, acetyl-CoA carboxylase (ACC), pACC, AEG-1, pULK-1 and β-actin were measured by western blot. AMPK and AEG-1 gene expression was downregulated using siRNA. DIM and ring-DIMs induced autophagy by increasing autophagic vacuoles and LC3B-I to LC3B-II conversion in LNCaP and C42B cells. These compounds also induced AMPK, ULK-1 and ACC phosphorylation in a time dependent manner. Interestingly, DIM, 4,4’ dibromoDIM and 7,7’ dichloroDIM induced the oncogenic protein AEG-1 time dependently in LNCaP and C42B cells. Downregulation of AEG-1 or AMPK inhibited DIM- and ring-DIM-induced autophagy. Pretreatment with ULK1 inhibitor MRT 67307 or siRNAs targeting AEG-1 or AMPK potentiated the cytotoxicity of DIM and ring-DIMs. Interestingly, downregulation of AEG-1 induced senescence in cells treated with toxic concentrations of DIM or ring-DIMs, and inhibited the onset of apoptosis in response to DIM or ring-DIMs. In summary, we identified a novel mechanism for DIM- and ring-DIM-induced protective autophagy, via induction of AEG-1 and activation of AMPK. Our findings could help towards the development of novel drug therapies for prostate cancer that include selective autophagy inhibitors as adjuvants.
Citation Format: Hossam Draz, Alexander Goldberg, Thomas Sanderson, Stephen Safe. Diindolylmethane and its halogenated analogues induce autophagy in human prostate cancer cells via induction of the astrocyte-elevated gene-1 (AEG-1) [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 3298. doi:10.1158/1538-7445.AM2017-3298
Abstract 3303: Survivin negatively-regulates autophagy through interference with the formation of Atg5-Atg12-Atg16L complex in breast cancer cells
Authors: Chan Hsiu-Han , Coumar Mohane Selvaraj , Cheng Siao-Muk , Tsai Shing-Ling , Lin Chun-Hui , Chen Shang-Hung , Leung Euphemia , Cheung Chun Hei Antonio 
Published: July 2017

Abstract
Survivin, a member of the inhibitors-of-apoptosis proteins family, is highly expressed in different cancers and its expression is correlated with tumorigenesis and tumor metastasis. At the cellular and molecular levels, Survivin is a dual functions protein that promotes mitosis and also inhibits apoptosis. In this study, we found that Survivin is a novel negative-regulator of autophagy. Molecular analysis and computational modeling revealed that Survivin negatively regulates the formation of Atg5-Atg12 conjugates, which plays important roles in the process of autophagosome elongation, in breast cancer cells. It also negatively regulates the expression and activity of cathepsin L in cells. Interestingly, we found that Survivin binds to p62/SQSTM1 and LC3B and is also an autophagic substrate protein, in which its expression is in part directly regulated by autophagy at the protein level. Finally, mechanistic study revealed YM155, a Survivin inhibitor that was originally developed to inhibit Survivin gene transcription, downregulates Survivin expression in part through autophagic protein degradation. Taken together, findings of this study provide new mechanistic insights into both molecular functions and regulations of Survivin and the molecular mechanism of actions of YM155, a drug currently undergoing clinical trials for cancer treatment.
Citation Format: Hsiu-Han Chan, Mohane Selvaraj Coumar, Siao-Muk Cheng, Shing-Ling Tsai, Chun-Hui Lin, Shang-Hung Chen, Euphemia Leung, Chun Hei Antonio Cheung. Survivin negatively-regulates autophagy through interference with the formation of Atg5-Atg12-Atg16L complex in breast cancer cells [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 3303. doi:10.1158/1538-7445.AM2017-3303
Abstract 3310: Atg7 overexpression promotes bladder cancer invasion via autophagic removal of AUF1 protein and subsequently increased RhoGDI2 mRNA stability in vitro and in vivo
Authors: Zhu Junlan , Li Yang , Huang Chuanshu , Huang Haishan 
Published: July 2017

Abstract
Autophagy is the basic catabolic mechanism regulating degradation of unnecessary or dysfunctional cellular components and is regulated by the autophagy-related gene 7 (Atg7). Since invasive bladder cancer (BC) can progress to life threatening metastases, understanding the molecular mechanisms underlying BC invasion is of tremendous importance for potentially reducing the mortality of this disease. In the present study, we for the first time found that the Atg7 was remarkably upregulated in human BC cell lines and the BBN-induced mouse invasive BCs, which is consistent with our most recent finding in human BCs. The knockdown of Atg7 in human BC cells dramatically inhibited cancer cell invasion, suggesting that Atg7 is a key player in regulation of BC invasion. Mechanistic studies revealed that Atg7 overexpression was mediated by miR-190, which was highly upregulated at transcriptional level in BC tissues and cell lines, and was able to bind to 3’-UTR of atg7 mRNA for its stabilization. Moreover, Atg7-mediated autophagic mechanism could remove AUF1 protein and in turn reduced AUF1 interaction with rhogdi2 mRNA, resulting in elevation of rhogdi2 mRNA stability, and subsequently leading to BC cell invasion. Remarkably, inhibition of Atg7-mediated autophagy led to AUF1 protein accumulation, RhoGDI2 downregulation and BC cell invasion attenuation. Collectively, our results demonstrate that overexpressed Atg7 mediates BC cell autophagy, which removes AUF1 protein, thereby reducing its binding with rhogdi2 mRNA and subsequently leading to elevation of rhogdi2 mRNA stability and protein expression, further promoting BC invasion. The identification of miR-190/Atg7 autophagic mechanism regulating AUF1/RhoGDI2 expression provides a significant insight into understanding the nature of BC invasion, and is also highly potential for developing autophagy-based-specific therapeutic strategy for treatment of human BC patients.
Citation Format: Junlan Zhu, Yang Li, Chuanshu Huang, Haishan Huang. Atg7 overexpression promotes bladder cancer invasion via autophagic removal of AUF1 protein and subsequently increased RhoGDI2 mRNA stability in vitro and in vivo [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 3310. doi:10.1158/1538-7445.AM2017-3310
Abstract 3313: Autophagic ovarian cancer cells exhibit substantially enhanced sensitivity to Crizotinib
Authors: Blessing Alicia M. , Wang Yan , Mao Weiqun , Pang Lan , Lu Zhen , Bast Robert C. 
Published: July 2017

Abstract
One of the major factors contributing to poor outcomes for patients with ovarian cancer is the persistence of dormant, drug resistant cancer cells after primary surgery and chemotherapy. Recurrent, progressively growing ovarian cancer metastases are generally well vascularized and may only have a small fraction of cancer cells undergoing autophagy. By contrast, the persistent, drug resistant, dormant cancer cells that remain on the peritoneal cavity after conventional treatment tend to be poorly vascularized. In this nutrient-poor, avascular microenvironment autophagy is widespread and can be found in more than 80% of cases. Drugs that regulate survival in autophagic cancer cells may be much more active when administered as maintenance therapy than when used to treat gross primary or recurrent disease. Using unbiased siRNA screens, we have identified target genes that regulate the survival of ovarian cancer cells that are undergoing autophagy that has been induced by the re-expression of DIRAS3 or by amino acid starvation. Knockdown of the anaplastic lymphoma kinase (ALK) significantly reduced survival of ovarian cancer cells that were undergoing autophagy. Importantly, the FDA-approved ALK inhibitor, Crizotinib, exhibited significantly greater toxicity after induction of autophagy by upregulation of DIRAS3 (ARHI) in OVCAR8, CAOV3, and SKOv3 ovarian cancer cells. Induction of autophagy by upregulation of DIRAS3 in SKOv3 ovarian cancer cells reduced the IC50 of Crizotinib from 7.44µM ± 0.04708 to 2.129µM ± 0.06152 (P&lt;0.05). Conversely, siRNA knockdown of DIRAS3 in CAOV3 cells with endogenously high DIRAS3 expression and baseline autophagy increased the IC50 of Crizotinib from 204 nM ± 0.01265 to 267 nM ± 0.01715 (P&lt;0.05). Our studies in cell culture suggest that Crizotinib might provide an effective agent to eliminate autophagic, dormant drug resistant ovarian cancer cells that remain after conventional cytoreductive surgery and combination chemotherapy. Subsequent studies will evaluate the effect of Crizotinib in xenograft models of DIRAS3-induced ovarian cancer dormancy.
Citation Format: Alicia M. Blessing, Yan Wang, Weiqun Mao, Lan Pang, Zhen Lu, Robert C. Bast. Autophagic ovarian cancer cells exhibit substantially enhanced sensitivity to Crizotinib [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 3313. doi:10.1158/1538-7445.AM2017-3313
Abstract 3323: Anticancer activity of medicinal plant and neuroglioma
Authors: Shivers Michael Quincy 
Published: July 2017

Abstract
Neuroglioma, also called gliocytoma, is one of the common malignant tumors in central nervous system at present. Neuroglioma can make aggressive growth around brain tissue, so complete radical treatment can be realized by single excision. Nutritional and botanical treatments have been found useful in treating neuroglioma and other types of cancers. Vernonia amygdalina (VA) is a valuable medicinal plant that is widespread in East and West Africa. It has been reported to have not only diverse therapeutic effects for many tropical diseases, but has recently been shown to possess anti-cancer properties. Therefore, the goal of this research was to determine the therapeutic mechanisms of VA leaf extracts in the management of brain tumor. To achieve this goal, Human H4 neuroglioma cells were treated with different concentrations of Vernonia Amygdalina for 24 hr. Cell survival was determined by MTs assay. The extent of oxidative cell/tissue damage was determined by measuring malondialdehyde (lipid peroxidation biomarker) concentrations by spectrophotometry. Cell apoptosis was measured by flow cytometry assessment (Annexin V/PI assay). Data obtained from the MTS assay indicated that VA significantly (p &lt; 0.05) reduced the viability of in H4 cells in a concentration-dependent manner. We detected a significant (p &lt; 0.05) increase in malondialdehyde (MDA) concentrations in VA-treated glioblastoma cells compared to the control. Flow cytometry data showed a strong concentration-response relationship between VA exposure annexin V/PI positive cells. Taken together, our finding indicates that VA induced cytotoxicity and apoptosis in H4 cells is associated with the formation of MDA, a by-product of lipid peroxidation and biomarker of oxidative stress. At therapeutic concentrations, VA-induced cytotoxic and apoptotic effects in H4 cells is mediated by oxidative stress.
Note: This abstract was not presented at the meeting.
Citation Format: Michael Quincy Shivers. Anticancer activity of medicinal plant and neuroglioma [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 3323. doi:10.1158/1538-7445.AM2017-3323
Abstract 3324: FATE1 promotes mitochondrial hyperfusion and supports maintenance of mitochondrial networks following apoptosis stimulation
Authors: Hamacher-Brady Anne , Lang Verena , Brady Nathan R. 
Published: July 2017

Abstract
FATE1 (fetal and adult testis expressed 1), also known as the cancer-testis antigen BJ-HCC-2, is expressed in testis and tumor tissues. FATE1 was recently described as a major survival factor in tumor cells of various origins, by mediating the degradation of the pro-apoptotic BH3-only protein Bik (Maxfield et al., in Nat Commun 2015 Nov 16;6:8840) and through ER-mitochondrial uncoupling (Doghman-Bouguerra et al., in EMBO Rep 2016 Sep;17(9):1264-80). Interestingly, FATE1 shares high sequence homology with the mitochondrial Drp1 receptor MFF (mitochondrial fission factor). We thus investigated a possible role of FATE1 impact on mitochondrial morphology following the stimulation of apoptosis in cancer cells. We found that, similar to MFF, FATE1 is localized to outer mitochondrial membranes and, unlike MFF, additionally localized to the endoplasmic reticulum. Importantly, in contrast to MFF, FATE1 overexpression does not recruit Drp1 to mitochondria, and instead promotes hyperfusion of mitochondrial networks. Co-immunoprecipitation experiments and reconstitution of Mfn2 or Mfn1 in double knockout mouse embryonic fibroblasts indicate a role for the mitochondrial fusion protein Mfn2, but not Mfn1. As FATE1 overexpressing cancer cells were more resistant to mitochondrial fragmentation in response to TNF and valinomycin treatments, we propose FATE1 as a novel regulator of mitochondrial morphology changes occurring during apoptosis, with possible implications in FATE1-mediated resistance of cancer cells to chemotherapy.
Citation Format: Anne Hamacher-Brady, Verena Lang, Nathan R. Brady. FATE1 promotes mitochondrial hyperfusion and supports maintenance of mitochondrial networks following apoptosis stimulation [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 3324. doi:10.1158/1538-7445.AM2017-3324