bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4053: A unique nutrient mixture suppresses ovarian cancer growth of A-2780 by inhibiting invasion and MMP-9 secretion
Authors: Roomi M. Waheed , Rath Matthias , Niedzwiecki Aleksandra 
Published: July 2016

Abstract
Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. The American Cancer Society estimated that it would claim 14,250 lives in 2013. Despite the advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a unique nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were inoculated by I.P. with 2×106 cells in 0.1ml PBS and randomly divided into two groups. Group A (n = 6) was fed a regular diet and group B (n = 6) a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed and processed for histology. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with NM in triplicate at concentrations between 0-1000 μg/ml. Cell proliferation was measured by MTT assay, MMP-9 secretion by gelatinase zymography, invasion through Matrigel and morphology by H&E staining. All control mice (Group A) developed large ovarian tumors, whereas 5 out of 6 mice in group B developed no tumors, and one, a small tumor. Zymography demonstrated only MMP-9 expression, which NM inhibited in a dose dependent fashion, with virtual total block at 250 μg/ml concentration. NM significantly inhibited invasion through Matrigel with total block at 250 μg/ml concentration. MTT showed dose dependent inhibition of cell proliferation with NM and H&E staining showed no morphological changes below 500 μg/ml NM. These results suggest that NM has therapeutic potential in treatment of ovarian cancer by significantly suppressing tumor growth and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.
Citation Format: M. Waheed Roomi, Matthias Rath, Aleksandra Niedzwiecki. A unique nutrient mixture suppresses ovarian cancer growth of A-2780 by inhibiting invasion and MMP-9 secretion. [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 4053.
Abstract 4062: Human mammary tumor virus (HMTV) is a breast cancer pathogen
Authors: Holland James F. , Melana Stella , Nartey Teiko , Tripodi Joseph , Jaffer Shabnam , Nayak Anupna , Pogo Beatriz GT 
Published: July 2016

Abstract
Human mammary tumor virus (HMTV) a betaretrovirus 90-98% homologous to Mouse Mammary Tumor Virus (MMTV), the causative agent for breast cancer in mice, has been detected in approximately 40% of American women's breast cancers. Mouse DNA contamination has been definitively excluded by contamination-free guarantee techniques. In Western European countries and their former colonies, age standardized rates (ASR) of breast cancer incidence (47 to 92 per 100,000 per year) are higher than Asian incidence (29 to 43 ASR/y). This difference could be explained by excess HMTV-related breast cancer incidence. In 7 West European, American and Oceania countries, 30 to 60% contain HMTV, while in 5 Asian nations HMTV associated breast cancers range from 0 to 22%. Different indigenous murine species with disparate MMTV burdens parallel these findings: mus domesticus in the West with much MMTV in its genome, and mus castaneus or mus musculus in the East with less. HMTV is found in cells in milk of 8% of unselected American mothers and in milks of 21% of women previously biopsied for unconfirmed cancer suspicion.
HMTV isolated from primary cultures of metastatic breast cells is able to infect In vitro, human mammary epithelial cells, B and T lymphocytes and dendritic cells. MCF10A breast cell line infected with HMTV shows molecular changes associated with epithelial-mesenchymal transition, such as up-regulation of vimentin, and down-regulation of E-cadherin.
HMTV sequences were also shown to be more prevalent in inflammatory, gestational and familial breast cancers than in unselected sporadic samples, consistent with association with more aggressive breast cancer phenotypes. To establish a direct connection between the presence of HMTV sequences and metastatic breast cancer, we have found HMTV sequences in 94% of primary cultures of metastatic breast cells obtained directly from effusion fluids. HMTV present in primary breast tumors has been demonstrated in their metastatic axillary nodes.
Taken together the results suggest an association between the presence of HMTV sequences and breast cancer aggressiveness. HMTV poses a new and challenging dimension in breast cancer research involving causation, diagnosis, molecular mechanisms, epidemiology, therapy and prevention.
Citation Format: James F. Holland, Stella Melana, Teiko Nartey, Joseph Tripodi, Shabnam Jaffer, Anupna Nayak, Beatriz GT Pogo. Human mammary tumor virus (HMTV) is a breast cancer pathogen. [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 4062.
Abstract 423: Toxicity and efficacy probability intervals design for phase I dose-finding in oncology trials
Authors: Li Daniel H. , Whitmore Jim , Ji Yuan 
Published: July 2016

Abstract
We propose a toxicity and efficacy probability interval (TEPI) design for dose-finding in phase I oncology studies. This approach incorporates efficacy outcomes to inform dosing decisions to optimize both efficacy and safety. Decision rules can be prespecified, allowing for transparency to clinicians and non-statisticians. The TEPI design is an extension over the modified toxicity probability interval (mTPI) design, which uses only dose-limiting toxicity (DLT) data for dose escalation. The TEPI method is motivated by recent promising data from cancer immunotherapies, for which response or a biomarker for response can be observed in the same interval as a DLT.
The TEPI method is based on a two-way decision table constructed by combining the target probability intervals of DLT and efficacy. It uses a beta/binomial hierarchical model to compute the posterior probabilities of intervals for toxicity and efficacy. The dosing decision depends on the joint unit probability mass of toxicity and efficacy data, which follows the Bayes rule under independent beta prior distributions. TEPI can pre-calculate all dosing actions for any possible combination of toxicity and efficacy outcome at a certain time point during a trial. For example, dose escalation or de-escalation decisions at time of 6, 9, and 12 treated patients are provided in Table 1.
In the current era of potent novel agents in oncology, phase I trials that simultaneously optimize antitumor activity and safety may accelerate development of these therapies. The proposed TEPI method recognize this needs, and is appealing to clinicians because all dose escalation or de-escalation can be prespecified. Simulation studies have been performed to evaluate the performance of TEPI, and compared to other designs. No. of RespondersNo. of Treated Patients at Current Dose LevelNo. of DLTs01-45-660-1EUES2-3SSS4-6DUDUDU01-67-990-2EUES3-4SSS5-9DUDUDU0-12-78-12120-3EUES4-6SSS7-12DUDUDU
Table 1. The letters in cells are computed based on the decision rules under the TEPI method and represent different dose-finding actions. EU: Unacceptable efficacy; DU: Unacceptable safety. Target toxicity probability = 0.3 and target response rate probability = 0.5.
Citation Format: Daniel H. Li, Jim Whitmore, Yuan Ji. Toxicity and efficacy probability intervals design for phase I dose-finding in oncology trials. [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 423.
Abstract 4350: Human oral microbiome and prospective risk for pancreatic cancer: a population based, nested case control study
Authors: Fan Xiaozhou , Alekseyenko Alexander V. , Wu Jing , Jacobs Eric J. , Gapstur Susan M. , Purdue Mark P. , Abnet Christian C. , Stolzenberg-Solomon Rachael , Miller George , Ravel Jacque , Hayes Richard B. , Ahn Jiyoung 
Published: July 2016

Abstract
Background: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer in prospective studies; however, relationships of oral microbes with pancreatic cancer have not been directly evaluated. We conducted a prospective study to examine the relationship of oral microbiota with subsequent risk of pancreatic cancer.
Methods: We selected 361 incident pancreatic cancer cases and 371 matched controls from two prospective cohort studies, the ACS Cancer Prevention Study (CPS) II and the NCI Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). From pre-diagnostic oral wash samples, we characterized the composition of the oral microbiota using bacterial 16S rRNA gene amplification and sequencing. Logistic regression analysis was used to examine the association between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, age, race, sex, smoking status, alcohol consumption, body mass index, and history of diabetes.
Findings: Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted Odds Ratio [OR]p.g = 1·59 and 95% confidence interval [CI] = 1·15-2·20; ORa.a = 2·19 and 95%CI = 1·15-4·15, respectively). Greater relative abundance of phylum Fusobacteria was associated with decreased pancreatic cancer risk (OR per percent increase of abundance = 0·92, 95%CI = 0·87-0·98). Risks related to these phylotypes remained after exclusion of cases that developed within two years of sample collection, reducing the likelihood of reverse causation in this prospective study.
Interpretation: The study provides evidence that the oral mcirobiota plays a role in the etiology of pancreatic cancer and may point to accessible means for prevention of this disease.
Citation Format: Xiaozhou Fan, Alexander V. Alekseyenko, Jing Wu, Eric J. Jacobs, Susan M. Gapstur, Mark P. Purdue, Christian C. Abnet, Rachael Stolzenberg-Solomon, George Miller, Jacque Ravel, Richard B. Hayes, Jiyoung Ahn. Human oral microbiome and prospective risk for pancreatic cancer: a population based, nested case control study. [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 4350.
Abstract 436: Glycodelin expression in endometrial carcinoma
Authors: Koistinen Hannu , Pasanen Annukka , Hautala Laura 
Published: July 2016

Abstract
Glycodelin is a lipocalin protein mainly expressed in well-differentiated epithelial cells in reproductive tissues, including endometrium and seminal vesicles. Previously, glycodelin has been shown to induce differentiation of endometrial carcinoma cells, which was associated with reduced xenograft tumor growth. Glycodelin is highly expressed in secretory endometrium, but not in proliferative or postmenopausal endometrium. While glycodelin is weakly, if at all, expressed in cancer tissues and, when expressed, associated with better prognosis, results regarding the expression of glycodelin in endometrial carcinoma are discordant. Therefore, we studied the expression of glycodelin in endometrial carcinoma and hyperplasia by immunohistochemical staining using highly validated antibody developed in house. Furthermore, the levels of mRNA were addressed utilizing in silico transcriptomics databases.
Glycodelin transcripts were more abundant in normal uterus than in uterine carcinomas. Glycodelin staining in endometrial carcinoma sections was also much lower than that in secretory phase endometrium. Interestingly, in some endometrial hyperplasia samples glycodelin levels were much lower in hyperplastic regions of the sample as compared to those having normal histology.
In conclusion, our data show that glycodelin is not highly expressed, if at all, in endometrial carcinoma tissues. This is in keeping with the reduced expression of glycodelin in postmenopausal endometrium and association of glycodelin in epithelial differentiation.
Citation Format: Hannu Koistinen, Annukka Pasanen, Laura Hautala. Glycodelin expression in endometrial 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 436.
Abstract 4569: Use of ACPD and ICA-1 as inhibitors of atypical proteinkinase C-zeta (ζ) and iota (ι) in metastasized melanoma cells
Authors: Ratnayake Wishrawana S. , Acevedo-Duncan Mildred 
Published: July 2016

Abstract
The number of melanoma cases report is increased every year. Malignant melanoma is very common among all Caucasian populations worldwide. New cases in these populations are expected to be doubled every 10-20 years. According to the NIH Surveillance, Epidemiology and End Results (SEER) program, 73,870 new cases and 9,940 deaths were reported in 2015 in USA [http://seer.cancer.gov/statfacts/html/melan.html (11/10/2015)]. It is not totally understood which intracellular chemicals are involved in certain signaling pathways and which governs the metastasis of melanoma cancer cells. Even though PKC- iota (ι) was not reported in normal melanocytes, it was detected in high amounts in both transformed melanocytes and melanoma metastases. PKC- zeta (ζ) was also reported in both normal melanocytes and melanoma metastases [Melanoma Res. 12:201-209 (2002)]. We believe these atypical PKCs play an important role in cell motility of melanoma therefore we tested two inhibitors for them. The objective of this study was to test the inhibition effectiveness of ACPD [Diabetes. 63:2690-2701 (2014)] on both PKC-ι and PKC-ζ and ICA-1 [Int. J. Biochem. Cell Biol.43:784-794(2011)] as an inhibitor of PKC-ι. SK-MEL-2 metastasis melanoma cells and PCS-200-013 normal melanocyte cells were cultivated and treated with ACPD and ICA-1 in separate sets of flasks for three consecutive days while taking the cell count for every 24 hrs. Preliminary results of this experiment shows statistically significant decrease in cell number in SK-MEL-2 cells while no change in PCS-200-013. Future investigations will involve examining the effects of ACPD and ICA-1 on cell motility. Our preliminary results confirms the cell population of melanoma cells have an inversely proportional relationship with the drug concentrations. In conclusion, ACPD and ICA-1 are capable of decreasing the cell proliferation of melanoma cancer cells.
Citation Format: Wishrawana S. Ratnayake, Mildred Acevedo-Duncan. Use of ACPD and ICA-1 as inhibitors of atypical proteinkinase C-zeta (ζ) and iota (ι) in metastasized melanoma 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 4569.
Abstract 4586: FGFR2 amplification in serous ovarian cancer
Authors: Tyulyandina Alexandra , Tsimafeyeu Ilya , Demidova Irina , Gikalo Marina , Tjulandin Sergei 
Published: July 2016

Abstract
Fibroblast growth factor receptor (FGFR) signaling pathway plays an important role in biology of cancer. Approximately 7% of ovarian cancer (OC) exhibits FGFR1 amplification. Recently the overexpression of FGFR2 was found in 95% of clear cell OC. Up to date there is no data about FGFR2 status in OC. 54 paraffin-embedded blocks from 18 patients with serous OC were analyzed by FISH to identify FGFR2 amplification. Scoring for amplification and polysomy level was adopted from previous studies for gastric cancer (Su X, et al. BJC 2014). Material from each patient had 3 samples: from primary tumor, from primary metastatic lesions, and from relapse. Intratumoral FGFR2 amplification heterogeneity was assessed in sections from all cases with FGFR2 amplification, and was defined as the presence of areas with different FISH scores within the same tumor in full sections.
Amplification was observed in 3 patients (15.7%). Interestingly, in one case amplification was observed in primary ovarian tumor but not in the metastatic nor in relapse samples. In two other cases the FGFR2 amplification was detected in relapse samples and in primary metastatic samples but not in ovary. High-level polysomy (HLP) was observed in 10 patients (55.5%). In all of those patients HLP was revealed in the samples of relapse. In 3 patients HLP was found in all 3 samples, in 3 cases HLP was observed only after relapse, in 4 cases HLP in metastasis sample was the same as in relapse sample, but it wasn't observed in ovary samples. Eight of 13 FGFR2 amplified ovarian cancers or tumors with HLP (61.5%) displayed intratumoral heterogeneity within full sections. In 5 (27.8%) cases neither amplification nor high level polysomy was observed. In conclusion, this is the first study of FGFR2 FISH in serous ovarian adenocarcinoma, demonstrating a FGFR2 amplification and HLP in primary tumor, primary metastases and relapse. Furthermore, we found evidence for intratumoral heterogeneity of FGFR2 amplification and HLP in about 61.5% of ovarian cancers. This study was supported by grant from the “Oncoprogress Foundation”. FGFR2 amplification and high-level polysomy in patients with serous cancer (13 patients)N (%), patientsPrimary tumor (N samples)Primary metastasis (N samples)Relapse (N samples)Amplification3 (15.7%)122High level polysomy10 (55.5%)3410
Citation Format: Alexandra Tyulyandina, Ilya Tsimafeyeu, Irina Demidova, Marina Gikalo, Sergei Tjulandin. FGFR2 amplification in serous ovarian 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 4586.
Abstract 4615: eIF4B is a key effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways during Abl-mediated cellular transformation
Authors: Chen Ke , Li Jianning , Chen Jilong 
Published: July 2016

Abstract
Abl oncoproteins, including v-Abl, Bcr-Abl and Tel-Abl, are activated non-receptor tyrosine kinases that are associated with various malignant transformations of hematopoietic cells. Expression of Abl kinase constitutively activates multiple signaling pathways that are critically involved in the regulation of cell proliferation and survival. Despite extensive studies, the precise mechanism by which these Abl oncoproteins induce hematopoietic malignances is not fully elucidated. eIF4B plays a critical role in Abl-mediated cellular transformation, but the precise mechanisms are largely unknown. Here we show that eIF4B is a convergent substrate of JAK/STAT/Pim and PI3K/Akt/mTOR pathways in Abl transformants. Both pathways regulated the phosphorylation of eIF4B in Abl-transformed cells, and such redundant regulation was responsible for the limited effect of single inhibitor on Abl oncogenicity. Surprisingly, persistent inhibition of one signaling pathway induced the activation of the other pathway and thereby restored the phosphorylation levels of eIF4B. Simultaneous inhibition of the two pathways impaired eIF4B phosphorylation more effectively, and synergistically induced apoptosis in Abl transformed cells and inhibited the growth of engrafted tumors in nude mice. Similarly, the survival of Abl transformants exhibited a higher sensitivity to the pharmacological inhibition, when combined with the shRNA-based silence of the other pathway. Interestingly, such synergy was dependent on the phosphorylation status of eIF4B on Ser422, as overexpression of eIF4B phosphomimetic mutant S422E in the transformants greatly attenuated the synergistic effects of these inhibitors on Abl oncogenicity. In contrast, eIF4B knockdown sensitized Abl transformants to undergo apoptosis induced by the combined blockage. Collectively, the results indicate that eIF4B integrates the signals from Pim and PI3K/Akt/mTOR pathways in Abl-expressing leukemic cells, and is a promising therapeutic target for such cancers.
Citation Format: Ke Chen, Jianning Li, Jilong Chen. eIF4B is a key effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways during Abl-mediated cellular transformation. [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 4615.
Abstract 4652: Effects of anti-DLL4 treatment on non-small cell lung cancer (NSCLC) human xenograft tumors
Authors: Brunner Alayne , Cattaruzza Fiore , Yen Wan-Ching , Yeung Pete , Fischer Marcus , Cancilla Belinda , O’Young Gilbert , Tam Raymond , Liu Yu-Wang , Gurney Austin , Lewicki John , Hoey Tim , Wang Min , Kapoun Ann M. 
Published: July 2016

Abstract
Background: Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancers, the leading cause of cancer-related deaths. Notch signaling has been shown to play an important role in lung cancer initiation and progression. Delta-like ligand 4 (DLL4) activates the Notch pathway and is important for cancer stem cell (CSC) survival. Demcizumab (OMP-21M18) is a humanized IgG2 anti-DLL4 antibody currently being tested in a Phase 2 trial in combination with pemetrexed and carboplatin for first-line treatment of patients with NSCLC. Previously, OMP-21M18 in combination with its mouse anti-DLL4 surrogate has been shown to inhibit tumor growth, decrease cancer stem cell frequency, and cause dysfunctional sprouting of new vessels resulting in an anti-angiogenic effect in patient-derived tumor xenograft (PDX) models in breast, colon, ovarian, and pancreatic cancers. Here we show results from NSCLC PDX models.
Methods and Results: Anti-DLL4 treatment was tested in a series of NSCLC PDX models. Because DLL4 inhibition has been shown to have effects on the tumor as well as the vasculature, the combination of OMP-21M18 (targeting human DLL4) and 21R30 (antibody targeting mouse DLL4) treatment in the PDX models was used to model demcizumab treatment in humans. Treatment with anti-DLL4 in combination with chemotherapy inhibited tumor growth in a series of NSCLC PDX models. Additionally, a tumorigenicity assay showed a decrease in the frequency of tumor-initiating cells following treatment with anti-DLL4 and chemotherapy. Gene expression analysis of tumor samples provided insights into the mechanism of action.
Conclusions: Anti-DLL4 treatment in a panel of NSCLC PDX tumor models in vivo showed inhibition of tumor growth and a decrease in the frequency of tumor-initiating cells. Mechanism of action and gene expression analysis of these models treated with anti-DLL4 will be presented. These findings provide additional evidence supporting demcizumab as an effective treatment for NSCLC patients.
Citation Format: Alayne Brunner, Fiore Cattaruzza, Wan-Ching Yen, Pete Yeung, Marcus Fischer, Belinda Cancilla, Gilbert O’Young, Raymond Tam, Yu-Wang Liu, Austin Gurney, John Lewicki, Tim Hoey, Min Wang, Ann M. Kapoun. Effects of anti-DLL4 treatment on non-small cell lung cancer (NSCLC) human xenograft tumors. [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 4652.