tbuckley/cabot-search huggingface dataset:
Correlates of and interrelationships among social stressors, relationship quality, and family functioning among informal cancer caregivers.
Authors: Erin E. Kent, Kristin Litzelman, Julia Howe Rowland
Journal: Journal of Clinical Oncology (2015)

230 Background: Informal/family caregivers play a critical role in supporting cancer patients and are often an important part of the palliative care team. To better understand how informal caregivers are influenced by their role and inform future interventions, this study sought to evaluate the distribution and correlates of social and family factors among caregivers of cancer patients. Methods: This cross-sectional study used data from the Cancer Care Outcomes Research &amp; Surveillance Consortium (CanCORS). Lung and colorectal cancer patients nominated an informal caregiver to participate in a caregiving survey. Caregivers reported their sociodemographic and caregiving characteristics, social stress, relationship quality with the patient, and family functioning. Descriptive statistics were used to assess the distribution of caregivers’ social factors. Multivariable linear regressions were used to examine the independent correlates of each social factor. Results: Most caregivers reported low-to-moderate levels of social stress and good relationship quality and family functioning. In multivariable analyses older age was associated with lower social stress and better family functioning, but worse relationship quality, with effect sizes (Cohen’s D) up to 0.40 (p &lt; 0.05). Caring for a female patient was associated with lower social stress and better relationship quality, but worse family functioning (effect sizes up to 0.16, p &lt; 0.05). Few caregiving characteristics were associated with social stress, while several were significant independent correlates of relationship quality. Finally, social factors were important independent correlates of one another. Conclusions: The results highlight the importance of personal and caregiving-related characteristics and the broader family context to social factors. As social factors may play an important role in the health, quality of life, and caregiving efficacy of informal caregivers, future work is needed to better understand these pathways and assess whether interventions targeting social factors can improve caregiver well-being, thereby potentially improving patient-centered palliative care.
Abstract 2549: Familial risk of upper gastrointestinal cancers by tumor location
Authors: Elham Kharazmi, Masoud Babaei, Mahdi Fallah, Thianhui Chen, Kristina Sundquist, Kari Hemminki
Journal: Cancer Research (2016)

Abstract Background: Upper gastrointestinal (UGI) cancers are within the most common malignancies worldwide. Familial clustering of UGI cancers and the significance of family history have been addressed in the past. We aimed to further elucidate the familial risk based on specified tumor locations. Methods: Using the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed between 1958 and 2012. Standardized incidence ratio (SIR) was used for calculating concordant and discordant familial cancers risks, stratified by tumor locations. All results were adjusted for sex, age group, period, and socioeconomic status. Results: Risk of esophageal cancer in first-degree relatives (FDRs) of esophageal cancer patients was 2•4-fold higher than that in those without such a family history. Familial risk for concordant cancer in upper and middle third of esophagus was 3•2- and 5•6-fold, respectively. Family history of esophageal cancer in lower part was associated with increased risk of gastric cardia cancer in FDRs and vice versa. Family history of both adenocarcinoma and SCC of esophageal cancer increased the familial risk of concordant (similar) and discordant subtypes. Occurrence of gastric cancer in the body and the antrum of stomach in a FDR were associated with an increased risk of gastric cancer 6- to 7-fold in the same location in family members, respectively. Conclusion: Family history of UGI cancers in some specific locations like upper and middle third of esophagus, body and antrum of stomach can be considered as an important predictive evidence for the same cancers in relatives. Citation Format: Elham Kharazmi, Masoud Babaei, Mahdi Fallah, Thianhui Chen, Kristina Sundquist, Kari Hemminki. Familial risk of upper gastrointestinal cancers by tumor location. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2549.
Eltrombopag effect on the engraftment efficiency of human hematopoietic stem cells in a NOD/SCID xenotransplant model.
Authors: Y. Chen, Y. Tsai, R. Hu, J. Pietrusz, O. Hyrien, K. L. Dawson, C. L. Erickson-Miller, J. Liesveld, H. Sun
Journal: Journal of Clinical Oncology (2010)

6603 Background: Eltrombopag is a nonpeptide small molecule, agonist of the thrombopoietin receptor (c-Mpl), expressed on hematopoietic stem cells and progenitor/precursor cells involved in thrombopoiesis. Eltrombopag binds to the transmembrane domain of the c-Mpl receptor and has strict species specificity for only humans and chimpanzees. The species specificity limits the options for in vivo investigation of eltrombopag effects on the hematopoietic system. We describe the investigation of eltrombobag on engraftment efficiency of human hematopoietic stem cells and effect on in vivo human thrombopoiesis and WBC production in a human xenotransplant model using non-obese diabetic, severe combined immunodeficient (NOD/SCID) mice. Methods: NOD/SCID mice received 3.5 Gy total body irradiation for myeloablation followed by (≤24hrs) IV injection of human cord blood CD34+ cells. The following day transplanted mice started daily gavage of 50mg/kg eltrombopag vs. sterile water for 28 days. Mice were euthanized at 1, 2, 3, 4, 5, and 9 weeks after transplantation. Peripheral blood (PB) was analyzed for human platelets and CD45+ cells. Bone marrow (BM) was extracted from femurs and tibia and analyzed for human CD34+, CD 41+, and CD45+ cells. Results: PB platelets and PB-CD45+ cells, as well as BM-CD 34+, BM-CD 41+ and BM-CD45+ cells increased by week (wk) 2 after transplantation. Comparing the eltrombopag group with vehicle control using baseline wk 2 levels showed: platelet increase of 5.6 fold vs. 2.6 fold by wk 5; PB-CD 45+ cell increase of 16 fold vs. 9 fold by wk 9; BM-CD34+ cell increase of 102 fold vs. 62 fold by wk 9; BM-CD 45+ cell increase of 300 fold vs. 170 fold by wk 9 and BM-CD 41+ cell increase of 43 fold vs. 38 fold by wk 9. Eltrombopag group showed overall significantly higher levels of PB-platelets, PB-CD 45+, BM-CD34+, BM-CD45+, and BM-CD41+, with p-values significant at the 0.05 level. Conclusions: Eltrombopag treatment significantly improved human cord blood stem cell transplant efficiency as measured by engrafted human CD45+ cells, the expression of a CD34+ progenitor cell population, and thrombopoiesis (CD41+ cells & platelets) in the NOD/SCID human bone marrow xenotransplant model. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Abstract 5177: RNAseq and FACS profiling of syngeneic mouse models treated with immune checkpoint inhibitors enable biomarker discovery and model selection for cancer immunotherapy
Authors: Lan Zhang, Juan Zhang, Sheng Guo, Wubin Qian, Zhensheng Wang, Qian Shi
Journal: Cancer Research (2016)

Abstract Background: Syngeneic tumor models have long been used in cancer research. Recently, the clinical success of anti-CTLA4 and anti-PD1 antibodies resulted in increased interests in using syngeneic models to evaluate cancer immunotherapeutics. Furthermore, as researchers discovered chemo, radio and targeted therapies of cancer may interact or change tumor immune environment, they are looking for suitable models that may evaluate the combination of those therapies. More importantly, in the clinic it is still unknown why some patients respond to certain immunotherapies while others do not. We set out to utilize syngenetic models to address those questions. Material and methods: Syngeneic cell line models were used to evaluate anti-PD1, PD-L1 and CTLA4 antibodies efficacies. 13 tumors from different syngeneic models were collected before the treatment for RNAseq analysis. Tumors were also collected after treatment for immune cell analysis with FACS for PD response. Biomarkers were analyzed with the RNAseq data to predict treatment response to different immune checkpoint inhibitors. Results: Crown has established the largest collection of syngeneic models with well characterized immunotherapy data. Those models have a diverse response to anti-PD1, PD-L1 and CTLA4 antibodies, ranging from close to 100% inhibition to inducing tumor growth upon antibody treatment. Mostly recently, we have generated detailed maps of the expressional and mutational profiles of those models. Mutational analysis indicated a number of syngeneic models harbor mutations that may be useful for combination studies of targeted and immuno-therapy. Chemo and targeted therapy in combination with immunotherapy in syngeneic models suggested potential strategies that may be successful in the clinic. Analysis of RNAseq and FACS analysis data indicated markers that may be useful to predict immunotherapy response. Conclusions: These data will enable selection of models for chemo or targeted therapies in combination with immunotherapy. In addition, predictive biomarkers obtained from the analysis may be useful in understanding patient response in the clinic. Citation Format: Lan Zhang, Juan Zhang, Sheng Guo, Wubin Qian, Zhensheng Wang, Qian Shi. RNAseq and FACS profiling of syngeneic mouse models treated with immune checkpoint inhibitors enable biomarker discovery and model selection for cancer immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5177.
Abstract 2611: Effects of chalcones, nicotinamide, and resveratrol on PPAR gamma activation in oral cancer cells
Authors: Jennifer Diaz, Beverly Wuertz, Art Galbraith, Frank G. Ondrey
Journal: Cancer Research (2016)

Abstract Several classes of natural products have cancer prevention potential and PPAR gamma is an intriguing chemoprevention target as a nuclear receptor that controls multiple growth and differentiation processes. We have previously tested many classes of natural products in A/J mice and have found that the following chemoprevention compounds had no significant dietary toxicities: inositol, eucalyptol, chalcones, nicotinamides, and resveratrol. We tested these compounds for their capacity to activate PPAR gamma reporter genes in CA-9-22 oral cancer cells. In several repeated experiments we found that Inositol hexaphosphate did not activate PPAR gamma reporter genes at high concentrations of 1-4 mM. We found that eucalyptol, trans-Chalcone, 4 methoxy chalcone, Nicotinic Acid, and Nicotinamide had the capacity for statistically significant activation of PPAR gamma reporter genes in oral cancer cells from 20-60% at concentrations of 1-100 uM. We found that resveratrol was the most potent agent and could activate PPAR gamma reporter genes 2 fold. As a reference, this was about half the activity of the prototypic PPAR gamma activator pioglitazone. We performed additional experiments with resveratrol and found that it could activate the PPAR gamma dependent squamous differentiation gene Involucrin in oral cancer cells and BEAS 2B cells. Additionally, resveratrol significantly decreased BEAS 2 B proliferation from 48-96 hours at concentrations of 10 uM. From this data we conclude that resveratrol has the capacity to activate PPAR gamma in vitro and resveratrol and its derivatives may also function as PPAR gamma activators as an additional mechanism of action. We also conclude that inositol, eucalyptol, chalcones, and nicotinamides do not activate PPAR gamma. Citation Format: Jennifer Diaz, Beverly Wuertz, Art Galbraith, Frank G. Ondrey. Effects of chalcones, nicotinamide, and resveratrol on PPAR gamma activation in oral cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2611.
Abstract 3241: M1 macrophages promote ovarian cancer metastasis through NF-κB/TWIST axis signaling pathway
Authors: Un-Tek Jo, YongSang Song.
Journal: Cancer Research (2016)

Abstract The importance of tumor microenvironment in cancer progression has been recognized recently. However, factors associated with the tumor microenvironment are diverse and the molecular mechanisms are needed to be further defined for therapeutic intervention. Here we focused on the interaction between obesity related inflammatory cell, macrophage type 1 (MФ-1), and ovarian cancer cells in relation to metastasis. Two types of ovarian cancer cell lines; PA-1 and SKOV3, and monocyte-derived macrophages were used in this study. In the treatment with MФ-1 conditioned media, only SKOV3 cells were affected in proliferation activity. However migration and invasion were promoted by treatment with MФ-1 conditioned media in both ovarian cancer cells. In parallel, MФ-1 conditioned media treatment increased TWIST, EMT related gene. Interestingly, TWIST expression was correlated with protein expression levels of nuclear NF-κB (p65 and p50). Upon MФ-1 conditioned media treatment, nuclear translocation level and transcriptional activity of the NF-κB increased. Also, TPCK, NF-κB inhibitor suppressed invasion activity by MФ-1 conditioned media, in parallel with down-regulation of TWIST expression. Taken together, MФ-1 promoted EMT related metastatic potential in ovarian cancer cells through NF-κB signaling pathway. These results provide a new insight into the obesity related tumor microenvironment in ovarian cancer cell progression. Citation Format: Un-Tek Jo, YongSang Song. M1 macrophages promote ovarian cancer metastasis through NF-κB/TWIST axis signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3241.
Abstract 4233: Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small lung cancer with FLT-PET imaging
Authors: Xiao Chen, Ian Berger, Urooj Khalid, Jenny Cai, Akash Patel, Sharyn I. Katz
Journal: Cancer Research (2016)

Abstract Introduction: Successful inhibition of thymidylate synthase (TS) can be imaged with FLT ([18F]thymidine)-positron emission tomography (PET) thereby providing a measure of therapy response on day 1 of therapy. Here we characterize this imaging strategy for implementation into 1st line therapy with pemetrexed and cisplatin for NSCLC. Materials and Methods: The kinetics of pemetrexed-mediated TS inhibition mediated DNA salvage pathway “flare” in DNA was first characterized in vitro using 3H-thymidine DNA incorporation assays, analysis of TK1 protein expression and mobilization of the equilibrative nucleoside transporter 1 to the cell surface membrane. Kinetics of the pemetrexed-mediated “flare” in the salvage pathway was then confirmed in an in vivo mouse model of NSCLC. Finally, a proof-of-principle clinical trial was performed to demonstrate feasibility of imaging of pemetrexed-mediated TS inhibition in human subjects with NSLC. Results: In vitro examination of pemetrexed-induced changes in the salvage pathway revealed a burst in DNA activity that peaked at 2 hrs following the administration of pemetrexed. The addition of cisplatin did not impact the amplitude or timing of the pemetrexed-induced “flare” in the salvage pathway. In vivo imaging of TS inhibition with FLT-PET confirmed a peak in salvage pathway activity at 2 hrs. Imaging of pemetrexed-induced TS inhibition in a human clinical trial demonstrated feasibility with imaging at the 2 hr time point. Conclusion: FLT-PET measured efficacy of pemetrexed-induced TS inhibition is optimal at 2 hrs from the start of therapy. This timing of FLT-PET imaging is feasible in human clinical trials. Citation Format: Xiao Chen, Ian Berger, Urooj Khalid, Jenny Cai, Akash Patel, Sharyn I. Katz. Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small lung cancer with FLT-PET imaging. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4233.
Abstract 451: Large-scale evaluation of SLC18A2 in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels
Authors: Christa Haldrup, Anne-Sofie Lynnerup, Tine M. Storebjerg, Søren Vang, Peter Wild, Tapio Visakorpi, Christian Arsov, Wolfgang A. Schulz, Johan Lindberg, Henrik Grönberg, Lars Egevad, Michael Borre, Torben F. Ørntoft, Søren Høyer, Karina D. Sørensen
Journal: Cancer Research (2016)

Abstract Limitations of current diagnostic and prognostic tools for prostate cancer (PC) contribute to over-diagnosis and over-treatment. Here, we investigate the biomarker potential of the SLC18A2 (VMAT2) gene for PC at three molecular levels. Thus, SLC18A2 promoter methylation was analyzed in 767 malignant and 78 benign radical prostatectomy (RP) samples using methylation-specific qPCR and Illumina 450K methylation microarray data. SLC18A2 transcript levels were assessed in 412 malignant and 45 benign RP samples using RNAseq data. SLC18A2 protein was evaluated by immunohistochemistry in 502 malignant and 305 benign RP samples. Cancer-specificity of molecular changes was tested using Mann-Whitney U tests and/or receiver operating characteristic (ROC) analyses. Log rank, uni- and multivariate Cox regression tests were used for survival analyses. We found that SLC18A2 promoter hypermethylation was highly cancer-specific (area under the curve (AUC): 0.923-0.976) and associated with biochemical recurrence (BCR) after RP in univariate analyses. SLC18A2 transcript levels were reduced in PC and had independent prognostic value for BCR after RP (multivariate HR 0.13, P&amp;lt;0.05). Likewise, SLC18A2 protein was down-regulated in PC (AUC 0.898) and had independent prognostic value for BCR (multivariate HR 0.51, P&amp;lt;0.05). Reduced SLC18A2 protein expression was also associated with poor overall survival in univariate analysis (HR 0.29, P&amp;lt;0.05). Our results highlight SLC18A2 methylation as a new promising biomarker candidate for PC diagnosis. Furthermore, both SLC18A2 RNA and protein expression showed promising prognostic potential beyond routine clinicopathological variables. Thus, novel SLC18A2-based molecular tests could have useful future applications for PC detection and identification of high-risk patients. Citation Format: Christa Haldrup, Anne-Sofie Lynnerup, Tine M. Storebjerg, Søren Vang, Peter Wild, Tapio Visakorpi, Christian Arsov, Wolfgang A. Schulz, Johan Lindberg, Henrik Grönberg, Lars Egevad, Michael Borre, Torben F. Ørntoft, Søren Høyer, Karina D. Sørensen. Large-scale evaluation of SLC18A2 in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 451.
Comparison of Iron Load of the Liver and Gum of Patients with Thalassemia Major.
Authors: Umran Caliskan, Duran Canatan, Metin Ciris, Yesim Bozkurt, Gurhan Caglayan, Mine Kuran, Sevgi Kosaci, Nurgul Oguz, Cavidan Karadogan, Nihal Balta, Ruya Cosan
Journal: Blood (2005)
Abstract 4432: Targeted TET oxidase activity through methyl-CpG binding domain extensively suppresses cancer cell proliferation
Authors: Shinichi Fukushige, Yasuhiko Mizuguchi, Kanchan Chakma, Yuriko Saiki, Akira Horii
Journal: Cancer Research (2016)

Abstract DNA demethylating agents are useful therapeutic drugs for human cancer; 5-aza-2’-deoxycytidine and 5-azacytidine for myelodysplastic syndrome are good examples. They not only induce DNA demethylation but also have significant cytostatic and cytotoxic effects. However, precise mechanisms for anticancer activity of these demethylating reagents have yet to be established, mainly due to the lack of method to induce only DNA demethylation. Here we show that a fusion protein comprising the methyl-CpG binding domain (MBD) and the catalytic domain of Ten-eleven translocation protein 1 (TET1-CD) globally demethylates and upregulates a number of methylated genes. Gene expression microarray analyses using human embryonic kidney cell line 293T indicate that cells expressing wild-type (wt) TET1 catalytic domain with MBD (MBD-TET1-CDwt) upregulates more genes than ones expressing TET1-CDwt without MBD (TET1-CDwt) or catalytically inactive TET1-CD mutant (mut) with MBD (MBD-TET1-CDmut) and their upregulated genes frequently contained CpG islands (CGIs) within ± 1,000-bp of the transcription start site (TSS). Interestingly, 65% of genes upregulated 5-fold or more by MBD-TET1-CDwt were also reactivated after treatment with 5-azacytidine, DNA demethylating agent. These results suggested a fact that gene reactivation by both methods was primarily based on DNA demethylation. In order to examine growth inhibitory effects of DNA demethylation to cancer cells, we utilized a tetracycline inducible system to regulate the expression of MBD-TET1-CDwt using a prostate cancer cell line. Induction of MBD-TET1-CDwt demethylated and upregulated the glutathione S-transferase pi 1 (GSTP1), one of the hypermethylated genes in prostate cancer. In accordance with reactivation of methylated genes, induction of MBD-TET1-CDwt extensively suppressed the growth of LNCaP cells. Flow cytometry analysis showed decreased cells in S phase and increased cells in G1 phase by MBD-TET1-CDwt expression. Our present results clearly indicate that TET oxidase activity recruited at methyl-CpG sites through MBD induces reactivation of hypermethylated genes by DNA demethylation, and that our methods allow us to analyze the effects of global DNA demethylation in a wide variety of cancer cells. Citation Format: Shinichi Fukushige, Yasuhiko Mizuguchi, Kanchan Chakma, Yuriko Saiki, Akira Horii. Targeted TET oxidase activity through methyl-CpG binding domain extensively suppresses cancer cell proliferation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4432.
Cancer of unknown primary
Authors: Michael S Lee, Hanna K Sanoff
Journal: BMJ (2020)

Cancers of unknown primary (CUPs) are histologically confirmed, metastatic malignancies with a primary tumor site that is unidentifiable on the basis of standard evaluation and imaging studies. CUP comprises 2-5% of all diagnosed cancers worldwide and is characterized by early and aggressive metastasis. Current standard evaluation of CUP requires histopathologic evaluation and identification of favorable risk subtypes that can be more definitively treated or have superior outcomes. Current standard treatment of the unfavorable risk subtype requires assessment of prognosis and consideration of empiric chemotherapy. The use of molecular tissue of origin tests to identify the likely primary tumor site has been extensively studied, and here we review the rationale and the evidence for and against the use of such tests in the assessment of CUPs. The expanding use of next generation sequencing in advanced cancers offers the potential to identify a subgroup of patients who have actionable genomic aberrations and may allow for further personalization of therapy.