tbuckley/cabot-search huggingface dataset:
Abstract 3656: Cooperation of Rab25 loss with oncogenes in breast cancer
Authors: Krishna A. Rao, Pooja S. Joshi
Journal: Cancer Research (2016)

Abstract Breast cancer is the most common type of cancer in females worldwide. A number of genes such as BRCA1, BRCA-2, Hras, and p53 undergo mutations and contribute to tumorigenesis of the mammary tissue. The RAB guanosine triphosphates (RAS-related in brain) belong to the Ras superfamily of GTPases. The human RAS family consists of 3 proto oncogenes - H-ras, K-ras, N-ras. Rab 25 belongs to the Rab11 subfamily and plays an important role in vesicular trafficking. The Rab proteins are ubiquitously expressed. Loss of Rab 25 expression has been reported in a number of breast cancer cases and in transformed mammary cell lines containing H-ras point mutations. Human Mammary Epithelial Cells (HMEC) were obtained from healthy individuals undergoing reduction mammoplasty. The cells were immortalized by transducing with LXSN CDK4 R24C. This was followed by transduction with hTERT, catalytic subunit of the telomerase enzyme. In this study, we are trying to understand if loss of Rab25 expression in HMEC co-operates with wild and mutant H-ras as well as other oncogenes and contributes to tumorigenesis. HMEC lines in which Rab25 has been knocked down were transduced with various oncogenes, including wild type and mutant H-ras, Her-2, and IGFR1. We examined the co-operativity between loss of Rab25 and these oncogenes in migration, anchorage independent growth, stem cell marker expression, and also in vivo tumorigenesis and metastasis in nude mice. Citation Format: Krishna A. Rao, Pooja S. Joshi. Cooperation of Rab25 loss with oncogenes in breast cancer. [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 3656.
Abstract 1327: Gold nanorods based hypoxia-targeted photothermal cancer therapy
Authors: Huan Xie, Sunil Krishnan
Journal: Cancer Research (2016)

Abstract PURPOSE: Tumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. Gold nanorods (GNR), with unique dimension and optical properties, have shown superior capability for tumor photothermal ablation. This study aimed to develop a new nanoconstruct composed of gold nanorods (GNRs) conjugate to anti-carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. METHODS: GNR were synthesized according to the seed-mediated growth method with modification. Transmission electron microscopy (TEM) were used to characterize the size and shape of the particles. The GNR/anti-CAIX conjugates were prepared through a bifunctional polyethylene glycol (PEG). The conjugates were characterized by UV-Vis spectra, particle sizes and zeta potentials. The binding affinity and specificity of the GNR/anti-CAIX were evaluated with ELISA, cell adhesion assay and cell photothermal treatment. HT29 colon cancer cell line (overexpressing CAIX) and NIH3T3 cell line (no expressing CAIX) were used in our study. Near-infrared (NIR) ablation was performed on HT29 tumors in mice that treated with PBS, GNR-PEG and GNR/anti-CAIX. Biodistribution were conducted on the latter two groups. RESULTS: TEM images showed that the synthesized GNR had an aspect ratio of about 3 (8 × 24 nm). The changes of UV-vis spectra, particle sizes and zeta potentials confirmed the success of the conjugation. ELISA suggested that the number of anti-CAIX per GNR was 4.8 ± 0.3. In the cell binding assay, GNR/anti-CAIX only showed specific and high degree binding to HT29 cells but not to NIH3T3 cells. NIR laser treatment of HT29 cells resulted in significantly higher killing of GNR/anti-CAIX-targeted cells than of controls. NIR ablation of HT29 tumors in mice showed no tumor regression in the sham-treated group, regression but recurrence in the non-targeted-GNR group, and complete tumor regression in the targeted-GNR group. Biodistribution study showed significant higher accumulation in tumor in the targeted-GNR group. CONCLUSIONS: GNR/anti-CAIX nanoconstructs show promise as highly efficient targeting and photothermal ablation agents for cancer treatment. GRANT SUPPORT: This work was performed under funding from NIH/NIGMS grant (1SC3GM102018-01) and NIH/NIMHD/RCMI grant (5G12RR003045-21). Citation Format: Huan Xie, Sunil Krishnan. Gold nanorods based hypoxia-targeted photothermal cancer therapy. [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 1327.
First report of a North American invasive mosquito species Ochlerotatus atropalpus (Coquillett) in the Netherlands, 2009
Authors: E J Scholte, W Den Hartog, M Braks, C Reusken, M Dik, A Hessels
Journal: Eurosurveillance (2009)

In late August and early September 2009, numerous larvae, pupae, and actively flying adult specimens of Ochlerotatus atropalpus were discovered in the Province of Brabant, southern Netherlands, during surveillance activities for Aedes albopictus at two trading companies that import used tires. No Ae. albopictus were found. Both companies mainly import used tires from countries in Europe, but also from North America. Oc. atropalpus is endemic to North America and has so far only been found outside of its endemic range in Europe, namely France and Italy, where it was subsequently eradicated. A preliminary modelling study shows that the weather conditions in the Netherlands are unlikely to prevent establishment of Oc. atropalpus. This species has so far only been shown to serve as a vector for virus transmission under laboratory conditions. Studies on potential human and veterinary health risks, as well as possible control strategies are currently ongoing.
Use and outcomes of metastasectomy in older patients with urothelial cancers.
Authors: Bishoy Faltas, Renee L. Gennarelli, Daniel P. Nguyen, Scott T. Tagawa, Elena B. Elkin
Journal: Journal of Clinical Oncology (2015)

e15506 Background: Small single-institution series suggest that some patients with advanced urothelial cancer (UC) who have metastasectomy may have long-term survival. However, this procedure may also be associated with morbidity and mortality. Our objective was to examine use and outcomes of metastasectomy in older patients with UC in a large population-based dataset. Methods: We identified all patients with UC of the bladder, ureter and renal pelvis diagnosed 2001-2009 in the population-based SEER-Medicare dataset. Patients with a history of another solid tumor were excluded. Metastasectomy, identified in inpatient, outpatient and physician claims, was defined as resection of a metastatic lesion in a distant organ (brain, lung or liver) at any time after diagnosis or pelvic exenteration more than 6 months after first cystectomy. We examined hospital readmissions within 7 days of the procedure, 30-day mortality, and overall survival from first metastasectomy. Results: Of 70,648 patients with UC, 1,725 had at least one metastasectomy during a median follow-up of 4.8 years from diagnosis, including 162 patients who had more than one procedure. In a total of 1,924 metastasectomies, 63% were resections of lesions in the brain, 33% lung, 2% liver, and 2% pelvic exenteration. Metastasectomy was more common among younger patients and those diagnosed earlier in the study period. Patients diagnosed with stage T2 or less disease at presentation were more likely to have a metastasectomy at any point during the follow-up period. After metastasectomy, 30-day mortality was 4%, and 6% of patients required hospital readmission within 7 days of discharge. Median overall survival after first metastasectomy was 55 months (interquartile range: 14-113 months). Conclusions: In this population of older adults, metastasectomy was uncommon. However, in a selected patient population, hospital readmissions and 30-day mortality were acceptably low following resections of predominantly visceral disease, and overall survival exceeded 4 years. In well-selected UC patients with reasonable life expectancy and resectable lesions, metastasectomy appears safe, and the benefits may outweigh the risks.
Abstract 5163: Mitochondrial mutations and gene expression analysis in colorectal adenopolyps
Authors: LaShanale M. Wallace, Sharifeh Mehrabi, Xuebiao Yao, Felix Aikhionbare
Journal: Cancer Research (2016)

Abstract Colorectal cancer (CRC) is the third most common diagnosed and cause of cancer related deaths in both men and women in the United States. Numerous studies have analyzed mitochondria DNA mutations in CRC and other tumors. Results from these studies have detected high mutation rates which may lead to mitochondrial deregulation and tumor progression. Most CRCs develop from adenopolyps via the adenoma-carcinoma sequence. Therefore, analysis of mitochondrial mutations and gene expression may provide a mechanism for inhibition of this tumoral sequence in individuals with a high risk of developing CRC. In the present study, PCR based sequencing and reverse transcription-quantitative PCR (RT-qPCR) were used to determine if mutations in mitochondrial encoded genes and levels of expression of these genes could influence the progression of the adenoma- carcinoma tumoral sequence. Genes analyzed included MT-RNR1, MT-COI, MT-ATP6, MT- MT-CYB, and mitochondrial ND genes that are involved in the normal metabolism of mitochondria. Measurements were made for 34 tissue sample pairs obtained from various types of colorectal adenomas and corresponding normal surrounding tissues. Additionally, mitochondrial complexes I (NADH: ubiquinone oxidoreductase) and III (CoQH2-cytochrome c reductase) protein was analyzed. There was progressive differential expression of mt-genes and complexes I and III proteins among the colorectal tumor stages relative to their paired normal samples. The level of complexes I and III were higher in tumor tissues relative to normal surrounding tissues. Noticeably, the expression of MT-COI was higher in late stage carcinomas among; all studied transcripts. We detected 54 point mutations in one region ranging from 11871-11877. The frequency of these mutations in all stages was as followed; 71.5% in tubular adenoma, 57% tubulovillous, and 43% in villous and carcinoma. Our results suggest that alterations in mt-gene expression play a role in the transformation of the colorectal tumoral stages. Citation Format: LaShanale M. Wallace, Sharifeh Mehrabi, Xuebiao Yao, Felix Aikhionbare. Mitochondrial mutations and gene expression analysis in colorectal adenopolyps. [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 5163.
GRN163L, a Novel and Potent Telomerase Inhibitor, Inhibits Myeloma Cell Growth In Vitro and In Vivo.
Authors: Masood A. Shammas, Hemanta Koley, Pierfrancesco Tassone, Paola Neri, Alexei Protopopov, Sergei Gryaznov, Allison Chin, Robert C. Bertheau, Constantine Mitsiades, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Abstract 4668: Silencing PTGER3 enhances chemotherapeutic responses
Authors: Emine Bayraktar, Cristian Rodriguez-Aguayo, Junhua Mai, Cristina Ivan, Cristina Ivan, Arturo Chavez-Reyes, Anil K. Sood, Mauro Ferrari, Haifa Shen, Gabriel Lopez-Berestein
Journal: Cancer Research (2016)

Abstract Inflammation is involved in the pathogenesis of cancer and inflammatory mediators such as prostaglandins (PGs) are abundantly present in the tumor microenvironment. Prostaglandin E(2) (PGE(2))-prostaglandin E2 receptor (EP)3 (PTGER3) signaling appears critical for tumor-associated angiogenesis, tumor growth and chemoresistance. However, the precise mechanism of this phenomenon in ovarian cancer remains unknown. In this study we hypothesized that down modulation of PTGER3 regulates drug resistance through the regulation of Ras-MAPK/Erk-Est-ELK1 axis in OC cells, resulting in decreased migration, proliferation and increased apoptosis. We analyzed a PTGER3 data set of OC patients from the Cancer Genome Atlas. Furthermore, the analysis of a panel of ovarian cancer cell lines showed that PTGER3 at mRNA and protein levels were higher in cisplatin-resistant cells when compared with their cisplatin sensitive counterparts. In vitro cell viability, growth, cell-cycle progression, migration, invasion and apoptosis, as well as in vivo therapeutic effectiveness in murine xenograft models, were also assessed following siRNA-mediated PTGER3 silencing in cisplatin-resistant ovarian cancer cells. The experimental validation identifies PTGER3 associated with OC survival. Significant inhibition of cell growth and viability, cell-cycle arrest, and activation of apoptosis were observed upon siRNA-mediated PTGER3 suppression. Furthermore, combination treatment with MSV/DOPC-siRNA-PTGER3 and cisplatin inhibited growth of A2780-CP20 tumors, which were otherwise resistant to cisplatin treatment. These findings identify PTGER3 as a potential therapeutic target in ovarian chemo-resistant cancers expressing high levels of this oncogenic protein. Citation Format: Emine Bayraktar, Cristian Rodriguez-Aguayo, Junhua Mai, Cristina Ivan, Cristina Ivan, Arturo Chavez-Reyes, Anil K. Sood, Mauro Ferrari, Haifa Shen, Gabriel Lopez-Berestein. Silencing PTGER3 enhances chemotherapeutic responses. [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 4668.
Abstract 288: Low-dose cabazitaxel inhibits the growth of prostate cancer cells and enhances the anti-tumor properties of PEDF with greater efficacy than docetaxel
Authors: Courtney L. Jarvis, Thomas Nelius, Dalia Martinez-Marin, Srirupa Cheerla, Stéphanie Filleur.
Journal: Cancer Research (2016)

Abstract Despite recently approved novel agents, taxane-based chemotherapy remains the major therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC). Still mCRPC continues to be incurable. Furthermore, patients often experience severe side effects, prompting a re-evaluation of conventional regimen. Past studies have demonstrated promise for Low-Dose Metronomic (LDM) chemotherapy; schedule defined as the frequent administration of low doses of chemotherapeutic drugs with no prolonged drug-free breaks. Yet relative activities of LDM taxanes and combinations with known anti-neoplasic agents have to be investigated. Using CRPC cell lines (PC3, Du145 and the LNCaP-derivative CL1), we have shown that cabazitaxel-treated cells have a significantly lower EC50 compared to docetaxel, with Du145 cells presenting the greatest differences. In cell cycle analysis, both low-dose taxanes increased the sub-G1 cells population. However, the sub-G1 increase was significantly greater in cabazitaxel- than in docetaxel-treated Du145 cells, but not in PC3 and CL1. Accordingly, plasma membrane Annexin V elevation occurred in Du145 cells at lower doses of cabazitaxel than docetaxel validating a higher efficacy due to increased apoptosis. As other possible cell death mechanisms, autophagy and necrosis were investigated. Beclin1 expression levels remain unchanged in all three cell lines. In contrast, necrosis was stimulated in all the taxanes-treated cell lines in a dose dependent manner. In vivo, LDM cabazitaxel was significantly more efficient in delaying tumor growth than docetaxel. This effect was markedly increased when cabazitaxel was combined with the angio-inhibitor and anti-tumor Pigment Epithelium-Derived Factor (PEDF). Other results showed that PEDF and LDM chemotherapy combination induces more phagocytosis of CRPC cells when compared to single treatments. In conclusion, our data demonstrate a higher efficacy of cabazitaxel on CRPC both in vitro and in vivo, and suggest that LDM taxane chemotherapy/PEDF combination could be used as a novel therapeutic strategy for CRPC. Citation Format: Courtney L. Jarvis, Thomas Nelius, Dalia Martinez-Marin, Srirupa Cheerla, Stéphanie Filleur. Low-dose cabazitaxel inhibits the growth of prostate cancer cells and enhances the anti-tumor properties of PEDF with greater efficacy than docetaxel. [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 288.
Abstract 3636: Improved clinical variant calling and HLA genotyping with GRCh38
Authors: Brad Chapman, Alison Meynert, Deanna Church, Justin Johnson, Oliver Hofmann
Journal: Cancer Research (2016)

Abstract The Genome Reference Consortium released human genome build 38 (hg38, GRCh38) two years ago and it offers major improvements over the six year old previous build, 37 (hg19, GRCh37). The new build reflects our increased understanding of the heterogeneity within human sub-populations, contains a large number of alternative genomic loci that better capture our knowledge of genome structure, and includes highly diverse human leukocyte antigen (HLA) regions enabling HLA typing. To help with the migration of clinical sequencing workflows we provide support for variant calling on build 38, validate methods using truth sets from the Genome in a Bottle consortium and Illumina's Platinum Genome and show that feature projection approaches are a viable intermediate approach to port existing annotation resources. We show how the refined genomic representation improves mapping and variant calling by reducing the number of false positive SNP calls and improving InDel detection, and how post-processing of sequence reads mapping to HLA regions enables accurate HLA genotyping from targeted panels, exome- and WGS data. Using Omixon HLA validation data, integrated OptiType HLA calling achieved 100% accuracy on 8 targeted panels and better than 90% accuracy on 1000 genome exome samples. This work provides a freely available, validated, ready to run pipeline making use of the improved heterogeneity representation in build 38 and demonstrating the value of moving towards a more accurate, graph-based representation of human genomes. Citation Format: Brad Chapman, Alison Meynert, Deanna Church, Justin Johnson, Oliver Hofmann. Improved clinical variant calling and HLA genotyping with GRCh38. [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 3636.
Abstract 3664: RARRES2 functions as a direct tumor suppressor by promoting beta-catenin phosphorylation and degradation independent of CMKLR1 and CMKLR1-mediated antitumor immune response in adrenocortical carcinoma
Authors: Yi Liu-Chittenden, Kelli Gaskins, Sophie Wang, Electron Kebebew
Journal: Cancer Research (2016)

Abstract Tumor suppressors and the immune system are critical players in tumor suppression. However, little is known about whether a tumor suppressor can function through both immune-dependent and immune-independent mechanisms. RARRES2 is a small secreted protein that is down-regulated in multiple human cancer types such as adrenocortical carcinoma (ACC), hepatocellular carcinoma (HCC) and melanoma. It has been shown that RARRES2 can play an indirect tumor-suppressive role by acting as a chemoattractant to recruit anti-cancer immune cells expressing its receptor CMKLR1 to sites of tumor. In this study, we show that epigenetic CpG hypermethylation of RARRES2 in vivo and in vitro in ACC causes RARRES2 down-regulation. We also found that RARRES2 can function as a direct tumor suppressor and that its tumor suppressive effect does not depend on the recruitment of CMKLR1-expressing immune cells. We show that although exogenous treatment of cultured cells with recombinant human RARRES2 protein did not show any tumor-suppressive effect, transient overexpression of RARRES2 significantly inhibited cellular invasion. Stable overexpression of RARRES2 in ACC cell line NCI-H295R led to significantly reduced cell proliferation, cell invasion, and tumorigenecity in a RARRES2 dose-dependent manner. Using xenografts of stable NCI-H295R cell lines in two immunodeficient mouse models (athymic nude mice and NSG mice), we found that in the absence of functional immune cells, stable RARRES2 overexpression can still significantly suppress tumor growth in vivo. RARRES2 overexpression promoted beta-catenin phosphorylation and degradation, reduced the phosphorylation of p38 MAP kinase and inhibited the secretion of matrix metalloprotease protein 10 (MMP10) from cancer cells in a RARRES2 dose-dependent manner. Taken into account that CMKLR1 expression is barely detectable in all the cell lines tested, our results present the first evidence that RARRES2 can function as a direct tumor suppressor independent of CMKLR1 and CMKLR1-mediated anti-tumor immune response. Citation Format: Yi Liu-Chittenden, Kelli Gaskins, Sophie Wang, Electron Kebebew. RARRES2 functions as a direct tumor suppressor by promoting beta-catenin phosphorylation and degradation independent of CMKLR1 and CMKLR1-mediated antitumor immune response in adrenocortical carcinoma. [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 3664.