bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4045: Pediatric osteosarcoma lung metastasis: variations in clinical management
Authors: Vo Andrea T. , Bhattasali Onita , Roth Michael , Gill Jonathan , Geller David , Randall Lor , Gorlick Richard 
Published: May 2015

Abstract
Background: Nearly 20% of patients with newly diagnosed osteosarcoma have detectable metastatic disease at presentation, most of which is located in the lungs. These patients have a poor prognosis with survival of generally less than 30%. NCCN guidelines as well as many osteosarcoma clinical trials endorse resection of metastases as part of standard treatment. There are limited recommendations as to the timing or method of resection.
Methods: An anonymous online questionnaire was distributed to establish practice patterns among members of the Connective Tissue Oncology Society, a multi-disciplinary sarcoma focused organization. Participants were asked about management of lung metastases in 3 clinical scenarios (2 cm unilateral, 0.5 cm unilateral, and multiple bilateral lung nodules). Questions evaluated timing of management, decision to resect, technique of resection, and decision to explore the contralateral lung.
Results: 183 individuals completed the survey. Most report initiating nodule management after neoadjuvant therapy. If the nodule disappeared after neoadjuvant therapy or definitive surgery, most report not performing surgical resection. Among nodules resected after neodjuvant therapy or definitive surgery that were unchanged in size, thoracotomy is the most commonly reported surgical technique. When only unilateral nodules were present on imaging, few choose to explore the contralateral lung (11% in 2.0cm and 10% in 0.5cm, compared to 70% in multiple bilateral nodules). Pediatric Oncologists were more likely to initiate management earlier than Medical Oncologists for 2.0cm nodule (90% vs 63%, p&lt;0.001), 0.5 cm nodule (77% vs. 47%, p &lt;0.005), and multiple bilateral nodules (79% vs. 51%, p =0.008).
Conclusion: There is marked heterogeneity among treating clinicians in their management of pulmonary metastases in osteosarcoma. Variation was also noted between medical specialties. Prospective trials are needed to evaluate if these differences have significant implications on outcomes for patients with newly diagnosed metastatic osteosarcoma.
Citation Format: Andrea T. Vo, Onita Bhattasali, Michael Roth, Jonathan Gill, David Geller, Lor Randall, Richard Gorlick. Pediatric osteosarcoma lung metastasis: variations in clinical management. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4045. doi:10.1158/1538-7445.AM2014-4045
Abstract 4046: N-myc interactor impacts autophagy via modulation of GSK3β/mTOR signaling
Authors: Metge Brandon J. , Mitra Aparna , Shevde Lalita A. , Samant Rajeev S. 
Published: May 2015

Abstract
Autophagy is a cellular mechanism for removal of dysfunctional cellular organelles, large protein complexes. It drives a specialized form of program cell death termed as programmed cell death II. Recent studies have demonstrated a prominent role of the process of autophagy in cancer progression and drug sensitivity. Under conditions of stress, cancer cells try to utilize autophagy to leverage a survival advantage; however, excessive autophagy renders cells vulnerable.
Our previous work has demonstrated a pivotal role of N-myc interactor(NMI) in impeding breast cancer progression and metastasis. Loss of NMI is one of the key events that precedes and contributes to invasive progression of breast cancer. Here we provide evidence that NMI plays a crucial role in regulation of mTOR signaling ultimately impacting the autophagic response in breast cancer cells. Our initial observations showed that breast cancer cells restored for NMI expression contained more acidic vacuoles as determined by staining with Lysotracker. Further indication of autophagy was evidenced by the formation of distinct punctae in NMI cells upon transfection with GFP-LC3 which was ablated upon treatment with an autophagy inhibitor. Cells restored for expression of NMI showed decreased levels of p62 along with an increased LC3II processing. The mTOR signaling pathway plays a pivotal role in driving the autophagy. We found that p70S6K phosphorylation dramatically decreases in NMI expressing cells indicating an inhibition of mTOR signaling in these cells. Our observations show that active GSK3β, a negative modulator of mTOR, is responsible for mediating the effects of NMI. Conversely, NMI silenced cells showed indication of inactive GSK3β concomitant with activated mTOR signaling.
Functionally, NMI mediated sensitization of cells to autophagy rendered breast cancer cells incapable of sustaining stress of cisplatin treatment. The sensitivity of these cells to cisplatin was notably reduced upon inhibition of the autophagic process. This suggests a possible role for autophagy in NMI induced drug sensitivity. Collectively, our results suggest that NMI plays an important role in modulation of autophagy via activation of GSK3β and consequent inhibition of mTOR signaling.
Citation Format: Brandon J. Metge, Aparna Mitra, Lalita A. Shevde, Rajeev S. Samant. N-myc interactor impacts autophagy via modulation of GSK3β/mTOR signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4046. doi:10.1158/1538-7445.AM2014-4046
Abstract 4094: Identification of co-inhibitory receptor expression on T cells from gastric cancer patients
Authors: Zong Yunhui , Chu Fuliang , He Songbing , Jing Yu , Hunsucker Sally A , Yang Tina , Zhang Ming , Ye Sisi , Li Yafen , Liu Bin , Tang Jinle , Meng Huimin , An Gangli , Yang Lin 
Published: May 2015

Abstract
The critical role of tumour antigen-specific immune responses to restrain tumour growth in patients with gastric cancer furthers the need to dissect the co-inhibitory pathways involved in tumour infiltrating lymphocyte (TIL) exhaustion/dysfunction. It was previously reported that PD-1 expression was significantly increased on CD4+ and CD8+ T cells from patients with gastric cancer and in gastric cancer tissues, compared to normal donors. In this study, we observed up-regulation of TIM-3 and PD-1 expression on peripheral T cells and up-regulation of CTLA-4, TIGIT, TIM-3 and PD-1 expression on TILs from gastric cancer patients; however TIGIT was down-regulated on CD8+ TILs and TIM-3 up-regulation on CD8+ TILs was not statistically significant. Furthermore, the percentages of PD-1+/TIM-3+ and PD-1+/TIM-3- peripheral T cells was significantly higher in gastric cancer patients than normal donors, and the percentage of PD-1+/TIM-3+ TILs was significantly higher than the percentage of PD-1+/TIM-3+ peripheral T cells in gastric cancer patients. PD-1+/TIM-3+ cells represent the predominant fraction of TILs. PD-1 blockade enhanced cytokine production and the cytotoxicity of TILs and exhibited a synergistic effect with TIM-3 blockade. Collectively, our results suggest that the use of anti-PD-1 blockade in combination with anti-TIM-3 blockade could restore the cytotoxic activity of TILs in patients with gastric cancer.
Citation Format: Yunhui Zong, Fuliang Chu, Songbing He, Yu Jing, Sally A Hunsucker, Tina Yang, Ming Zhang, Sisi Ye, Yafen Li, Bin Liu, Jinle Tang, Huimin Meng, Gangli An, Lin Yang. Identification of co-inhibitory receptor expression on T cells from gastric cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4094. doi:10.1158/1538-7445.AM2014-4094
Abstract 4097: Vacuolar ATPase subunit a2 is associated with immunosuppression in cancer
Authors: Katara Gajendra K. , Kulshrestha Arpita , Jaiswal Mukesh , Gilman-Sachs Alice , Beaman Kenneth D. 
Published: May 2015

Abstract
Macrophage polarization contributes to distinct human pathologies. In tumors, a polarized M2 phenotype called tumor-associated macrophages (TAMs), are associated with promotion of invasion and angiogenesis. In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma/vesicular membranes and critically influences the metastatic behavior. In addition, the soluble, cleaved N-terminal domain of a2 isoform of V-ATPase (a2NTD) is associated with in vitro induction of pro-tumorigenic properties in monocytes. Monocytes induced with recombinant a2NTD showed polarization towards M2 macrophage subtype by expressing high levels of mannose receptor-1, Arginase-1, IL-10, MMP-9, VEGF and TGF-β. Additionally, co-culture of these macrophages enhances invasion and angiogenesis of tumor cells and suppression of T cell activation. This activity of the a2 isoform of V-ATPase (a2V) caused us to further investigate its role in cancer progression by evaluating the effects of a2V knock down on tumor cells. In this study, we have successfully deleted a2V gene in mouse 4T1 breast cancer cells using shRNA mediated knock down. These knock down cell lines are co-cultured with macrophages to evaluate previously observed immuno-modulatory effect of a2NTD. In addition, a2V knock down cells are injected into the Balb/c mice to generate tumors. The effect of a2V gene deletion on tumor progression and immune responses are evaluated in mice. We show that in the absence of a2V (finally a2NTD) growth and progression of tumor are suppressed by dominated host immune responses.
Citation Format: Gajendra K. Katara, Arpita Kulshrestha, Mukesh Jaiswal, Alice Gilman-Sachs, Kenneth D. Beaman. Vacuolar ATPase subunit a2 is associated with immunosuppression in cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4097. doi:10.1158/1538-7445.AM2014-4097
Abstract 4102: p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity
Authors: McCampbell Adrienne S. , Mittlestedt Megan L. , Dere Ruhee , Zhou Lijun , Djordjevic Bojana , Soliman Pamela T. , Zhang Qian , Wei Caimiao , Hursting Stephen D. , Lu Karen H. , Walker Cheryl L. , Broaddus Russell R. 
Published: May 2015

Abstract
Endometrial carcinoma exhibits the strongest association with obesity of any cancer. Tumor growth is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex (TSC) and p27, with inactivation of TSC2 and loss of cytoplasmic misloclization of p27 both being linked to PI3K/AKT signaling. However, little is known about the involvement of p27 in the development of endometrial carcinoma arising in the setting of obesity, expecially its role in early disease progression. We found that p27 was moderatley-to-severely reduced in both “normal” endometrial glands as well as endometrial hyperplasia of obese women. Obese Tsc-2-deficient Eker rats similarly developed endometrial hyperplasia with a high frequency and short latency, and like obese women, endometrial hyperplasia that developed in obese rats exhibited loss of p27. In Eker rats, even a short duration of caloric restriction (2-4 months of age) reduced weight, increased adiponectin and lowered leptin to produce favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, primarily in the nucleus, and significantly decreased endometrial hyperplasia incidence by up to 50%. These data demonstrate that in the setting of obesity, loss of p27 occurs very early in progression to carcinoma. Importantly, p27 can be modulated along with weight by diet, and perhaps other lifestyle interventions that decrease risk for development of carcinoma, suggesting it may be a useful biomarker, and possible determinant of risk for endometrial carcinoma in the setting of obesity.
Citation Format: Adrienne S. McCampbell, Megan L. Mittlestedt, Ruhee Dere, Lijun Zhou, Bojana Djordjevic, Pamela T. Soliman, Qian Zhang, Caimiao Wei, Stephen D. Hursting, Karen H. Lu, Cheryl L. Walker, Russell R. Broaddus. p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4102. doi:10.1158/1538-7445.AM2014-4102
Abstract 4106: Curcumin inhibit PhIP induced cytotoxicity by inhibiting ROS production, DNA strand breaks and DNA adducts formation in MCF 10A cells
Authors: Jain Ashok K. , Samykutty Abhilash , Jackson Carissa L. , Thangaraju Muthusamy , Browning Darren D. 
Published: May 2015

Abstract
PhIP is a known food carcinogen found in well done meat which causes several cancers including breast cancer. PhIP metabolites produce DNA adduct and DNA strand breaks. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity. So far none of the study demonstrates the inhibition of PhIP induced cytotoxicity by the co-treatment of Curcumin in normal breast epithelial cells in vitro. Therefore, we developed a model system using the MCF 10A normal breast epithelial cells to study the PhIP cytotoxicity and if cells are co-cultured with Curcumin and PhIP how it affects. Consequently, the core signaling pathways have been explored to evaluate the efficacy of Curcumin. In this study, the effectiveness of Curcumin was investigated in MCF 10A cells along with PhIP. The cytotoxic ability was detected with MTT assay, ROS activation by DCF, the influence of the cell cycle was checked with flow cytometry, DNA damage by comet assay, DNA adduct formation by anti-PhIP DNA primary, and apoptosis by Annexin-V-FITC staining. The influence of the core signaling pathways was evaluated by RT PCR and/or Western blotting which included Nrf2 (GSR, GPX, NQO1), FOXO (Catalase, GADD45, PRDX3) targets; DNA repair genes/proteins BRCA1, H2AFX and PARP-1; and tumor suppressor P16 gene expression. PhIP cytotoxicity induced the expression of various antioxidant and DNA repair genes on MCF-10A cells but co-treatment of Curcumin retained its expression level similar to untreated groups. Additionally, Curcumin co- treatment increased the expression level of tumor suppressor expression gene P-53. Expression of antioxidants genes was induced by PhIP whereas Curcumin significantly suppress the PhIP induced ROS activation, DNA strand breaks and DNA adduct formation and consequently inhibited the cell death. In conclusion, Curcumin appears to be effective to inhibit P450 mediated ROS production and PhIP-DNA adducts which consequently reduces DNA damage.
Citation Format: Ashok K. Jain, Abhilash Samykutty, Carissa L. Jackson, Muthusamy Thangaraju, Darren D. Browning. Curcumin inhibit PhIP induced cytotoxicity by inhibiting ROS production, DNA strand breaks and DNA adducts formation in MCF 10A cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4106. doi:10.1158/1538-7445.AM2014-4106
Abstract 4115: GS-19, a novel GSK inhibitor suppresses the growth of pancreatic cancer cells by inhibiting EGFR/AKT/STAT-3 signaling
Authors: Ranjan Alok , Birkenfeld Ashlee , Lu Jianyu , Hua Duy , Srivastava Sanjay K. 
Published: May 2015

Abstract
Pancreatic cancer remains the fourth leading cause of cancer related deaths in the United States. Therefore, identification of novel strategies to control and treat pancreatic cancer is of great importance. GS-19 is a novel compound recently found to be a GSK inhibitor. In this study, we determined the anti-cancer effects of GS-19 in pancreatic cancer cells. GS-19 treatment inhibited the growth of Panc-1 and BxPC-3 cells in a concentration-dependent manner. Both the cell lines treated with GS-19 exhibited G-1 cell cycle arrest as well as apoptosis. Western blot analysis of both BxPC-3 and Panc-1 cells treated with GS-19 inhibited the activation (phosphorylation) and expression of key survival signaling proteins such as EGFR, STAT3 and AKT. The apoptosis induced by GS-19 was associated with cleavage of caspase-3 and PARP. Taken together, our results suggest that GS-19 suppress pancreatic cancer cell growth by inhibiting EGFR/AKT/STAT-3 signaling. However, further mechanistic studies are in progress to establish the role of EGFR/AKT/STAT-3 signaling in pancreatic cancer cells. [The studies in part were supported by R01 grant CA129038 awarded by NIH to S.K.S.]
Citation Format: Alok Ranjan, Ashlee Birkenfeld, Jianyu Lu, Duy Hua, Sanjay K. Srivastava. GS-19, a novel GSK inhibitor suppresses the growth of pancreatic cancer cells by inhibiting EGFR/AKT/STAT-3 signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4115. doi:10.1158/1538-7445.AM2014-4115
Abstract 4120: Periodic fasting mimicking diet started late in life reduces and delays carcinogenesis
Authors: Brandhorst Sebastian , Wei Min , Navarre Gerrardo , Dubeau Louis , Conti Peter , Morgan Todd , Longo Valter D. 
Published: May 2015

Abstract
Nutrition can have profound effects on aging and age-related pathologies including cancer. As such, studies of fasting (the complete withdrawal of food) and dietary restriction (DR, generally described as a 20- 40% reduction in calories) have greatly contributed to the understanding of the relationship between nutrients, cellular aging, cancerogenesis and cancer cell survival. Our findings in yeast indicated that starvation decreases age-dependent mutations whereas our mouse xenograft tumor models indicate that fasting alone can be as effective as chemotherapy drugs in delaying the progression of certain tumor types, in part through the reduction of extracellular glucose and IGF-1 concentration/signaling. Here, we developed a fasting mimicking/enhancing diet (FMD) and tested its effects on cancerogenesis. In a cohort of female C57Bl6 mice, bi-monthly 4 day FMD feeding cycles followed by normal food intake, significantly improved survival in mice without causing excessive weight loss. Mice in the FMD cohort had a significantly reduced lifelong cancer incidence rate. Lymphoma was the most common cause of morbidity/mortality and affected ∼67% in the ad lib fed control group but only ∼40% of the FMD fed mice. In both cohorts lymphomas contributed to the great majority of all neoplasms found. Neoplasms were found in animals in the ad lib fed cohort starting 5 months after onset of our study, whereas no tumors occurred in the first 8 months in the FMD cohort. Furthermore, the FMD caused a shift from the presence of tumors in multiple organs (≥3) to tumors being either absent or present in 2 or less sites, thus indicating a potential shift to the development of benign tumors in the FMD group. In summary, the periodic FMD cycles had a significant impact on the development of cancer while allowing the preservation of lean body mass and animal weight until old age and extending longevity.
Citation Format: Sebastian Brandhorst, Min Wei, Gerrardo Navarre, Louis Dubeau, Peter Conti, Todd Morgan, Valter D. Longo. Periodic fasting mimicking diet started late in life reduces and delays carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4120. doi:10.1158/1538-7445.AM2014-4120
Abstract 4133: Disparities in colon cancer survival according to payer status: Findings from national cancer data bank
Authors: Devarakonda Srinivas S. , Shi Runhua , Neppalli Amarendra , Mills Glenn 
Published: May 2015

Abstract
BACKGROUND:
The objective of the current study was to examine the impact of payer status on relative survival outcomes in colon cancer patients.
METHODS:
A population-based analysis of National Cancer Data Bank (NCDB) records for invasive colon cancer was done using data from patients diagnosed between 1998 and 2006 and followed up to 2011. The cohort consisted of colon cancer patients of analytic stage I to stage IV. Information regarding age, race, gender, stage of cancer at the time of diagnosis, year of diagnosis, insurance status, income, treatment received and diagnostic facility, and type of treating facility were included in this study. Age, sex, race, calendar year specific US life table between 1970 and 2007 were used to compute expected survival. Multivariate Poisson modeling was used to estimate relative survival for payer status adjusting for other factors.
RESULTS:
436,235 colon cancer patients who met the inclusion criteria were included in the study. The mean age at diagnosis was 68.9 years. The stage distribution among the variables listed above is statistically significant. The 5-year cumulative relative survivals are 0.76, 0.84, 0.93, 1.74 and 1.10 for uninsured, Medicaid, private insurance, Medicare, and unknown payer status respectively. In multivariate analysis of relative survival, adjusting for other factors, the excess hazard ratios (EHR) were 1.74, 1.14, 0.89 and 1.29 for uninsured, Medicaid, Medicare, and unknown payer status versus private insurance respectively (P&lt;0.05). The EHRs for blacks and other races versus whites were 1.07 and 1.53 respectively (p&lt;0.05). The EHRs for follow-up year of 2, 3, 4, 5 versus year 1 were 1.17, 0.21, 0.18, and 0.54 respectively (P &lt;0.05). Compared to academic/research program facility type, the EHRs for community cancer program, comprehensive community cancer program, and other specified types of cancer programs were 1.02,0.77 and 25.9 respectively (P &lt;0.05). The relative survival rates for stage II, III, IV versus stage I were 0.95, 0.82, and 0.70 respectively (P&lt;0.05). Diagnosis before or after 2002 and the type of treatment facility lead to a marginal difference in the relative survival.
CONCLUSIONS:
Our study shows the impact of payer status on the relative survival of patients with colon cancer and demonstrated increased mortality for uninsured patients in contrast to survival benefit for patients with Medicare and private insurance.
Citation Format: Srinivas S. Devarakonda, Runhua Shi, Amarendra Neppalli, Glenn Mills. Disparities in colon cancer survival according to payer status: Findings from national cancer data bank. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4133. doi:10.1158/1538-7445.AM2014-4133