tbuckley/cabot-search huggingface dataset:
Abstract 5119: Evaluation of Minnelide as potential targeted therapy for triple negative breast cancer
Authors: Mahendra K. Singh, Soham Shah, Nikita Satish Sharma, Bhuwan Giri, Sulagna Banerjee, Ashok Saluja
Journal: Cancer Research (2017)

Abstract Recent advances in diagnostics and better understanding of molecular mechanism underlying breast cancer has let to the better therapeutic options and disease outcome for majority of breast cancer patients. However, ~10 - 20% of all breast cancers often referred to as “triple negative” as they lack expression of the estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors convey a poor prognosis due in part to a lack of targeted therapies. The aim of the current study is to evaluate whether triptolide and its water soluble analog Minnelide is effective against triple negative breast cancer cells. We have previously shown that triptolide/Minnelide not only reduces tumor growth in various cancer models but it also regulates epithelial -mesenchymal transition (EMT), an important mechanism underlying metastasis. In our preliminary findings using three triple negative breast cancer (TNBC) cell lines, MDA-MB-231, MDA-MB-468, and MDA-MB-157, we demonstrate that triptolide not only inhibits the proliferation of TNBC cells but also regulates the protein levels of EMT markers including β-Catenin and Vimentin. In order to elucidate the mechanism underlying triptolide mediated inhibition of cellular proliferation and regulation of EMT markers in TNBC cells, we identified Src kinase and Aurora kinase A as two new targets for triptolide action in TNBC cells. By targeting Src and Aurora kinase, triptolide disrupts the integrity of focal adhesion structures and reduces cell spreading via regulating FAK activity. Our preliminary findings regarding potential use of triptolide/Minnelide in TNBC based on in vitro experiments are promising. However, considering the complex pathophysiology of breast cancer and other biological factors playing role in a disease setting, in-vivo experiments to test the efficacy of Minnelide in relevant mouse models for mammary cancers are currently underway. Citation Format: Mahendra K. Singh, Soham Shah, Nikita Satish Sharma, Bhuwan Giri, Sulagna Banerjee, Ashok Saluja. Evaluation of Minnelide as potential targeted therapy for triple negative breast cancer [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 5119. doi:10.1158/1538-7445.AM2017-5119
RAPID RESPONSES FROM BMJ.COM
Authors: Joanne Rule
Journal: BMJ (2004)

While we acknowledge the importance of qualitative research, we have some concerns about the Wright study.

The stated objective of the study was to determine how a small group of patients with breast cancer wanted their doctors to communicate with them. When this aim was addressed through a structured questionnaire, its findings “concurred with the current emphasis on information, choice and emotional discussion.” This should come as no surprise as this is the result of solid and substantial research showing how highly these three factors are valued by patients.

The …
Abstract 4850: Overexpression of P62/IMP2 promotes metastasis in hepatocellular carcinoma via inhibition of E-cadherin expression
Authors: Mengtao Xing, Pei Li, Jitian Li, Jianxiang shi, Liping Dai, Giulio Francia, Jianying Zhang
Journal: Cancer Research (2017)

Abstract Hepatocellular carcinoma (HCC) is one of the most common type of cancer and the third leading cause of cancer related death in worldwide. Insulin-like growth factor 2 mRNA binding protein 2 (p62/IMP2/IGF2BP2) was originally reported as an autoantigen in HCC which belongs to IMPs family. The IMPs family contains three members: IMP1, IMP2 and IMP3, which share similar protein structure. IMPs are oncofetal proteins, which are expressed during embryogenesis and lost in most tissues in adults. Therefore, p62/IMP2 can be used as a potential biomarker for early diagnosis of HCC. We have evaluated the expression of p62/IMP2 protein both in human tissues and HCC cell lines by immunohistochemistry and western blotting analysis, and found that p62/IMP2 protein is overexpressed in human HCC tissues compared with normal human liver tissues (score= 10.30, n=40 vs. score =5.23, n=30, p&amp;lt;0.05). The expression of p62/IMP2 was scored by immune-staining intensity and positively immune-staining cell numbers. At the same time, we found that p62/IMP2 was also overexpressed in several HCC cell lines. Stable p62/IMP2 overexpression and depletion SNU449 human HCC cell line was made by using p62/IMP2 cDNA transfection and lentivirus mediated knockdown approaches, and it was further confirmed by western blotting analysis. Wound healing assay has shown that overexpression of p62/IMP2 can significantly enhance the cell migration ability in SNU449 cells. On the contrary, the depletion of p62/IMP2 can reduce the migration ability in SNU449 cells (p&amp;lt;0.05). Moreover,MTT assay has also shown p62/IMP2 overexpressed cells may have a higher rate of proliferation at 72h(p&amp;lt;0.05). In addition, we have observed that overexpression of p62/IMP2 can significant inhibit the expression of E-cadherin in western blotting analysis. In summary, our data would suggest that overexpression p62/IMP2 may promote metastasis via inhibition of E-cadherin expression in HCC. Citation Format: Mengtao Xing, Pei Li, Jitian Li, Jianxiang shi, Liping Dai, Giulio Francia, Jianying Zhang. Overexpression of P62/IMP2 promotes metastasis in hepatocellular carcinoma via inhibition of E-cadherin expression [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 4850. doi:10.1158/1538-7445.AM2017-4850
Abstract 266: Trends in age distribution of breast cancer, in north east of Iran: Report of six thousand patients over 30 years
Authors: Maryam Salehi, Soodabeh Shahidsales, Mehdi Seilaniantousi, Gholamhosein Noferesti, Mahta Salehi, Amirhossein mohammadian bajgiran
Journal: Cancer Research (2017)

Abstract Aim: This study was aimed to evaluate the age at the time of diagnosis of breast cancer and it’s probably changes in distribution among patients during 30 years. Methods: This cross- sectional study was conducted in Mashhad, Iran from 1981 until 2011. The data of patients were obtained from case records. The duration of study was categorized into three periods: 1981-1990, 1991-2000 and 2001-2011. SPSS software was used for analyses. The difference was considered significant if P&amp;lt;0.05. Result: From 6274 breast cancer cases, 174 patients were male (2.5%) and the others 6100 were female (97.5%).Mean age at the time of diagnosis was 49.07 ± 12.07 years (male: 56.48 ± 14.14, female: 48.8 ±12.01). There was significant difference in age by sex (p &amp;lt;0.001). Table 1 presents the mean age of studied patients in each 10 years of study. ANOVA test showed that there was not statistical significant difference (P value= 0.1). DecadesFrequencyMean ageSDYoungestOldest1981-199046747.9712.04318882000-1991177149.0312.33820992001-2011394949.2211.9542098 The most histologic type of breast cancer was ductal carcinoma 65.6% others percent in order were: NOS 19.6%, lobular 3.7%, medullary 2.8%, adenocarcinoma 2.8%, tubular and papillary 0.2% and 5.1% of other types. Relative frequency of histologic types had significant differences among 3 intervals (p &amp;lt;0.001), the frequency of adenocarcinoma was decreasing but ductal carcinoma was increasing during 3 decades. Mean age of ductal carcinoma, lobular, medullary and adenocarcinoma was 48.9±11.8, 50.6±12.4, 46.4±11.4, 50.2±11.9, respectively. Mean age had significant differences among these main histologic types (p =0.002).98% of patients were urban and 2% were rural. Mean age of these 2 groups has statistical significant difference (P = 0.001) and is 10 years older in rural patients. Frequency of people who live in urban area was increased significantly (p&amp;lt;00.1) during these 30 years compare with rural area. Conclusion: breast cancer occurs in Iranian women at least one decade younger than women in developed countries we found no change in mean age of diagnosis of breast cancer during these 30 years from 1981 to 2011. . Note: This abstract was not presented at the meeting. Citation Format: Maryam Salehi, Soodabeh Shahidsales, Mehdi Seilaniantousi, Gholamhosein Noferesti, Mahta Salehi, Amirhossein mohammadian bajgiran. Trends in age distribution of breast cancer, in north east of Iran: Report of six thousand patients over 30 years [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 266. doi:10.1158/1538-7445.AM2017-266
Abstract 730: High sensitive detecting procedure of circulating repetitive RNA as novel early marker of pancreatic cancer
Authors: Takahiro Kishikawa, Motoyuki Otsuka, Kazuhiko Koike
Journal: Cancer Research (2017)

Abstract Pancreatic ductal adenocarcinoma (Pdac) is one of the most intractable malignancies due to difficulties in early detection. Although promising biomarkers are increasingly reported, such methods are not yet easy to apply clinically, mainly due to their low reproducibility or technical difficulties. In this study, we developed a convenient and sensitive method for quantifying aberrantly expressed satellite repeat RNAs in sera, which can be used to efficiently detect patients with Pdac. It is difficult to correctly quantitate repeat arrays because its repetitive nature makes it difficult to establish appropriate primers that amplify a single product using simple PCR procedures. Here, we introduce a Tandem Repeat Amplification by nuclease Protection (TRAP) method combined with droplet digital PCR (ddPCR) to detect human satellite II (HSATII) RNAs, which are specifically expressed in human Pdacs at greater levels than normal tissues. HSATII RNA core sequence levels in sera were significantly higher in Pdac patients compared with non-cancer patients (median copy number: 14.75 and 3.17 per µl in the training set and 17.35 and 2.9 in the validation set, respectively). In addition, patients with intraductal papillary mucinous neoplasm (IPMN), a precancerous lesion of Pdac, could also be efficiently detected. This method can be routinely applied to screen patients with Pdac and high-risk patients, facilitating the development of preventive medicine for this disease. Citation Format: Takahiro Kishikawa, Motoyuki Otsuka, Kazuhiko Koike. High sensitive detecting procedure of circulating repetitive RNA as novel early marker of pancreatic cancer [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 730. doi:10.1158/1538-7445.AM2017-730
Abstract 3267: Combined effect of multiple gene polymorphisms on cancer risk stratification
Authors: Radhika Gade Andavolu, Olivia Rodriguez, Anastasia Al Rubakovic, Catherine Stafford, Murthy V. Andavolu
Journal: Cancer Research (2017)

Abstract Cyclin D1 (CCND1) G870A polymorphism has been known to be a risk factor in multiple cancers. Cyclin D1 is a cell cycle regulator frequently mutated, amplified and overexpressed in a variety of tumors. Activation and over expression of CCND1 have been found in variety of tumors and alterations in CCND1 are thought to be involved in carcinogensis. CCND1 polymorphism A870G interferes with splicing and studies showed DNA damage in cells from subjects with ‘A’ allele to bypass G1/S check point of the cell cycle control mechanism more easily than damage in cells with G allele (wild type). A single base pair polymorphism (exon 4, G870A) in the CCND1 gene affects gene splicing. This identification and validation of contributing genetic factors such as single-nucleotide polymorphisms (SNPs) represents a critical step in the advance toward personalized medicine. Several gene expression correlation studies have been done but to our knowledge studies have not been reported on SNP’s of ERBB2 gene, ESR gene and CCND1 combined effect correlating with high risk. In this study, we examined the relationship between ERBB2 (codon 655), Estrogen receptor (ER Intron1 T&amp;lt;C) and cyclin D1 (Exon 4) polymorphic additive effect in cancers more specific to breast cancer. Genomic DNA was extracted from whole blood samples collected on study. The SNPs were tested by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Our results show individuals carrying CCND1 ‘A allele in combination with variant ERBB2/BsmAI uncut allele are significantly high (P&amp;lt;0.004) in cancer patients (N=232) as compared to controls. (N=222). Similarly individuals carrying CCND1 Variant ‘A ‘ allele in combination with ESR ‘C’ Allele showed high frequency with p&amp;lt;0.009. Both these combinations showed a strong and significant association with cancer but individually, ERBB2 variant did not show any significant association, ESR gene showed a borderline association and CCND1 showed strong association independent of these two gene polymorphisms. Earlier few studies have shown no association of ERBB2 mutation in agreement with the previous reports. In conclusion our data suggests that in complex diseases a single gene may not contribute to show its effect but in combination may show a profound effect in evaluating the risk. Citation Format: Radhika Gade Andavolu, Olivia Rodriguez, Anastasia Al Rubakovic, Catherine Stafford, Murthy V. Andavolu. Combined effect of multiple gene polymorphisms on cancer risk stratification [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 3267. doi:10.1158/1538-7445.AM2017-3267
Abstract 88: The role of RBPMS in cisplatin resistant ovarian cancer
Authors: Perla M. Báez-Vega, Fatma Valiyeva, Ginette Santiago, Pablo Vivas-Mejia
Journal: Cancer Research (2017)

Abstract Epithelial ovarian cancer is the fifth leading cause of cancer-associated deaths among women in the United States. High-grade serous ovarian cancer (HGSOC) is the most common type of epithelial ovarian cancer and accounts for 70-80% of ovarian cancer patient deaths. RNA-Binding Protein With Multiple Splicing (RBPMS) is a member of a family of proteins that bind to the nascent RNA transcripts and regulate their processing, including the pre-mRNA splicing and the transport, localization, and stability of the RNA molecules. However, little is known about the biological function of RBPMS family in ovarian cancer. We hypothesized that decreasing the expression of RBPMS in high-grade serous ovarian cancer increases ovarian cancer progression and platinum-based drug resistance. Quantitative real-time PCR (qPCR) and Western blot (WB) analysis were conducted to determine the basal mRNA and protein expression of RBPMS in ovarian cancer cells. The invasion ability of the ovarian cancer cells after targeting RBPMS with silencing RNA (siRNA) was determined by invasion assays. The proliferation rate of the ovarian cancer cells overexpressing RBPMS was determine by colony formation assay. RBPMS is highly expressed in A2780 cells when compared to the cisplatin resistance ovarian cancer cells and HGSOC cancer cells. Targeting RBPMS increased the invasion ability of the A2780 cells. Cisplatin resistant, A2780CP20 cells overexpressing RBPMS showed a decreased in cell proliferation when compared to the A2780CP20 empty vector clones. We described here for the first time the mRNA and protein expression profile of RBPMS in HGSOC and epithelial ovarian cancer cells. These studies will help to better understand the role of RBPMS in ovarian cancer and may support the use of RBPMS as an adjuvant treatment to overcome the platinum-based chemotherapy resistance characteristic of the high-grade serous ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Perla M. Báez-Vega, Fatma Valiyeva, Ginette Santiago, Pablo Vivas-Mejia. The role of RBPMS in cisplatin resistant ovarian cancer [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 88. doi:10.1158/1538-7445.AM2017-88
Abstract 3406: Hereditary risks of male breast cancer in a multi-gene panel testing cohort
Authors: Elizabeth C. Chao, Mary Pritzlaff, Summerour Pia, Rachel McFarland, Shuwei Li, Jill Dolinsky, David Goldgar, Hermela Shimelis, Fergus Couch, LaDuca Holly
Journal: Cancer Research (2017)

Abstract While the population-based risk for breast cancer in males remains relatively low (1:1000), inherited predisposition can significantly raise this to as high as 10%, in men who carry a mutation in the BRCA2 gene. Lifetime breast cancer risks of 1-2% have also been reported in men who carry a mutation in BRCA1. These risks, as well as elevated risks of prostate, pancreatic, and melanoma cancers, are important to discuss in families diagnosed with Hereditary Breast and Ovarian Cancer Syndrome, which is often viewed as being clinically relevant only to the women in an affected family. However, beyond the BRCA1/2 genes, limited data is available on hereditary predisposition to male breast cancer. We analyzed clinical histories and molecular results from multi-gene panel testing for hereditary cancer predisposition in a cohort of 715 men affected by breast cancer. A total of 708 male breast cancer patients were eligible for inclusion in the final analysis. Molecular testing included analysis of 5 to 59 genes for DNA coding sequence and copy number variants by next-generation sequencing and microarray. Genetic variants identified were classified according to a 5-tier system using previously validated algorithms1,2. Only those variants classified as pathogenic or likely pathogenic were included in the analyses as positive for a mutation. Overall, a mutation was detected in 18% of these men. Four subjects carried a mutation in two different breast cancer predisposition genes. BRCA2 and CHEK2 were the most frequently mutated genes. The risk of breast cancer was significantly elevated compared to public controls in individuals with a mutation in BRCA2 (odds ratio (OR)=13.9; p=1.92x10-16), CHEK2 (OR=3.8; p=6.24x10-24) and PALB2 (OR=6.6, p=0.01). Average age was similar amongst men with (63.5±2.7 years) and without (62.3±1.2 years) mutations, as were clinical and family histories of additional cancers. The high overall diagnostic yield suggests the utility of testing all male breast cancer patient regardless of age or family history by multigene panel testing, and provides data to support risk-based counseling and medical recommendations for screening and/or prevention in male mutation carriers. 1. 1. LaDuca et al. Genet Med. 2014 Nov;16(11):830-7 2. 2. Richards et al. Genet Med. 2015 May;17(5):405-24 Citation Format: Elizabeth C. Chao, Mary Pritzlaff, Summerour Pia, Rachel McFarland, Shuwei Li, Jill Dolinsky, David Goldgar, Hermela Shimelis, Fergus Couch, LaDuca Holly. Hereditary risks of male breast cancer in a multi-gene panel testing 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 3406. doi:10.1158/1538-7445.AM2017-3406
Infants discriminate number: Evidence against the prerequisite of visual object individuation and the primacy of continuous magnitude
Authors: Melissa E Libertus, Emily J Braham, Ruizhe Liu
Journal: Behavioral and Brain Sciences (2017)

Abstract Leibovich et al. hypothesize that the absence of visual object individuation limits infants' numerical skills and necessitates a reliance on continuous magnitudes. We argue that parallels between infants' numerical discrimination in the visual and auditory modalities, their abilities to match numerosities across modalities, and their greater ability to discriminate changes in number compared with continuous magnitudes contradict the authors' assumptions.
Abstract 642: Detection of circulating antibodies against KRAS in patients with advanced cancers
Authors: Ed Kheder, Helen J. Huang, Alice Wu, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Siqing Fu, Vivek Subbiah, Apostolia M. Tsimberidou, Aung Naing, Adi Diab, Milind Javle, Scott Kopetz, Anil K. Sood, Jonathan M. Kurie, Funda Meric-Bernstam, Martin Gleeson, Filip Janku
Journal: Cancer Research (2017)

Abstract Introduction: KRAS gene plays a major role in tumorigenesis, cell proliferation and survival. Yet, there has been no effective targeted therapy against KRAS mutation-mediated tumors. We hypothesized that KRAS can induce humoral-mediated immune response. Methods: Plasma or serum samples from patients with progressing advanced cancers with or without KRAS mutations were tested for the presence of circulating KRAS antibodies. We used the Maverick Detection System (Genalyte, San Diego, CA), which can perform real-time detection of macromolecules in crude samples using biologically functionalized silicon photonic biosensors lithographically printed on disposable silicon chips. Results: We collected serum or plasma samples from 213 patients with advanced cancers (KRAS-mutant, N=100; KRAS wild-type, N=113) and 50 (23%) were found to have circulating KRAS antibodies. There was no association between KRAS antibodies and tumor KRAS mutation status (21/100, 21% for KRAS-mutant vs. 29/113, 26% for KRAS wild-type; P=0.52). In addition, there was no difference in detection of KRAS antibodies in colorectal cancer (21/89, 24%) compared to other cancers (29/124, 23%; P=1.00). There was no difference in the median survival in patients with KRAS antibodies compared to patients without KRAS antibodies (9.0 months vs. 10.1 months; P= 0.825). Similarly, there was no difference in the median survival according to the presence of circulating KRAS antibodies in subgroups of patients with tumor KRAS mutations (P= 0.96) and without tumor KRAS mutations (P=0.63). On the contrary, the median survival of patients with tumor KRAS mutation was shorter compared to patients with KRAS wild-type (7.2 months vs. 11.5 months; P&amp;lt;0.001). Conclusion: Circulating KRAS antibodies can be detected in 23% of patients with advanced cancers. Biological implications of circulating KRAS antibodies remain to be understood. Citation Format: Ed Kheder, Helen J. Huang, Alice Wu, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Siqing Fu, Vivek Subbiah, Apostolia M. Tsimberidou, Aung Naing, Adi Diab, Milind Javle, Scott Kopetz, Anil K. Sood, Jonathan M. Kurie, Funda Meric-Bernstam, Martin Gleeson, Filip Janku. Detection of circulating antibodies against KRAS in patients with advanced cancers [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 642. doi:10.1158/1538-7445.AM2017-642