tbuckley/cabot-search huggingface dataset:
Abstract 884: Associations of intakes of magnesium and calcium and survival among women with breast cancer: Results from Western New York Exposures and Breast Cancer (WEB) Study
Authors: Menghua Tao, Qi Dai, Amy E. Millen, Jing Nie, Stephen B. Edge, Maurizio Trevisan, Peter G. Shields, Jo Freudenheim
Journal: Cancer Research (2015)

Abstract Background: Magnesium (Mg) and calcium (Ca) antagonizes each other in (re)absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between Mg and Ca intakes and breast cancer survival, and the interaction between Ca and Mg intake. Method: In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total Ca, higher dietary intake of Mg was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Mg intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total Mg intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (&amp;gt;2.59). There were no clear associations for prognosis with intake of Ca. Conclusion: We found that Mg intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio. Citation Format: Menghua Tao, Qi Dai, Amy E. Millen, Jing Nie, Stephen B. Edge, Maurizio Trevisan, Peter G. Shields, Jo Freudenheim. Associations of intakes of magnesium and calcium and survival among women with breast cancer: Results from Western New York Exposures and Breast Cancer (WEB) Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 884. doi:10.1158/1538-7445.AM2015-884
Abstract LB-065: Mutational and functional analysis of the tumor suppressor PTPRD in human melanoma
Authors: Vijay Walia, Todd Prickett, Jung-Sik Kim, Jared J. Gartner, Jimmy C. Lin, Steven A. Rosenberg, Randolph C. Elble, David A. Solomon, Todd Waldman, Yardena Samuels
Journal: Cancer Research (2015)

Abstract Protein tyrosine phosphatases (PTPs) tightly regulate tyrosine phosphorylation essential for cell growth, adhesion, migration, and survival. We performed a mutational analysis of the PTP gene family in cutaneous metastatic melanoma and identified 23 phosphatase genes harboring somatic mutations. Among these, receptor-type tyrosine-protein phosphatase delta (PTPRD) is one of the most highly mutated genes, harboring 17 somatic mutations in 79 samples, a prevalence of 21.5%. Functional evaluation of six PTPRD mutations show enhanced anchorage-dependent and anchorage-independent growth. Interestingly, melanoma cells expressing mutant PTPRD are significantly more migratory than cells expressing wild-type PTPRD or vector alone, indicating a novel gain-of-function associated with mutant PTPRD. To understand the molecular mechanism of PTPRD, we searched for its binding partners by converting the active PTPRD enzyme into a ‘‘substrate trap’’ form. Using mass spectrometry and co-immunoprecipitation, we report desmoplakin, a desmosomal protein that is implicated in cell-cell adhesion, as a novel PTPRD substrate. Further analysis showed reduced phosphatase activity of mutant PTPRD against desmoplakin. Thus our study has established a novel link between PTPRD and desmoplakin and identified a phosphatase implicated in desmosome formation, which is disrupted in melanoma. As both Met and EGFR signaling have been shown to be involved in desmoplakin phosphorylation and their respective inhibitors, SU11274 and Gefinitib reduce its phosphorylation; melanoma cells harboring PTPRD mutations may be selectively sensitive to these two inhibitors. Moreover, because PTPRD is also mutated in glioblastomas and adenocarcinoma of the colon and lung, our data might be applicable to a number of human cancers. Note: This abstract was not presented at the meeting. Citation Format: Vijay Walia, Todd Prickett, Jung-Sik Kim, Jared J. Gartner, Jimmy C. Lin, Steven A. Rosenberg, Randolph C. Elble, David A. Solomon, Todd Waldman, Yardena Samuels. Mutational and functional analysis of the tumor suppressor PTPRD in human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-065. doi:10.1158/1538-7445.AM2015-LB-065
Abstract PL02-04: Drastically reducing HPV-associated cancers through etiologically-based primary and secondary prevention
Authors: Douglas R. Lowy
Journal: Cancer Research (2015)

Abstract HPV infection causes more than 25,000 anogenital and oropharyngeal cancers annually in US men and women and is responsible for about 10% of all female cancers worldwide. In the developing world, where cervical cancer is the main HPV-associated cancer, a woman's lifetime risk of dying from this cancer is estimated to be about 1%. Persistent infection by more than 10 HPV types can lead to cervical cancer; HPV16 and HPV18 account for about 70% of these tumors. These two HPV types account for more than &amp;gt;90% of the HPV-positive non-cervical cancers. Primary prevention by the FDA-approved HPV vaccines has the potential to reduce the incidence and mortality attributable to the HPV-positive anogenital and oropharyngeal cancers, while secondary prevention through HPV-based screening for cervical cancer can lower the incidence and mortality for this cancer. The first generation virus-like particle HPV vaccines, which target HPV16 and HPV18, can prevent more than 90% of new persistent infections attributable to these HPV types. These vaccines are already having an impact on HPV-induced early disease markers in vaccinated populations, including evidence of herd immunity. The high immunogenicity of these vaccines suggests that it should be possible to safely reduce the number of recommended vaccine doses from three to two - and perhaps eventually even to one dose - in young adolescents, who represent the main target group for the vaccine. A second generation vaccine, which targets the seven most oncogenic HPV types and has the potential to prevent ∼90% of cervical cancer, was recently approved by the FDA. HPV-based testing was recently approved by the FDA for primary cervical cancer screening in women 25 or older. Compared to cytology-based screening, HPV-based testing has higher sensitivity for detecting infections that may lead to squamous cell carcinoma and adenocarcinoma. It is predicted that the greater sensitivity of HPV-based testing will be even more important for cervical cancer screening of vaccinated women. Citation Format: Douglas R. Lowy. Drastically reducing HPV-associated cancers through etiologically-based primary and secondary prevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr PL02-04. doi:10.1158/1538-7445.AM2015-PL02-04
Proteomics To Identify Novel Immune-Targeted CML Stem Cell Antigens.
Authors: Melinda A. Biernacki, Ovidiu Marina, Liu Fenglong, Ingmar Bruns, David Zahrieh, Wandi Zhang, Christine Canning, Edwin P. Alyea, Robert J. Soiffer, Jerome Ritz, Catherine J. Wu
Journal: Blood (2007)
A Report of the Event-Free Survival (EFS) and Neurotoxicity for Children with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL) on Pediatric Oncology Group (POG) Protocol 9405.
Authors: Stephen Rodes, Beverly A. Bell, Sharon B. Abish, Jeanette Pullen, Allen Chauvenet, Joanne Kurtzberg, Meenakshi Devidas, Jonathan Shuster, Bruce M. Camitta
Journal: Blood (2005)
Abstract 4515: A phase 1 randomized, open-label, fixed-sequence, 2-period study of the effect of multiple doses of rifampin on palbociclib (PD-0332991) pharmacokinetics in healthy volunteers
Authors: Justin T. Hoffman, Anna Plotka, Melissa O'Gorman, Andrew Chang, Maha Kosa, Cho-Ming Loi, Corrado Gallo-Stampino, Diane D. Wang
Journal: Cancer Research (2015)

Abstract Background Rifampin is a strong inducer of multiple Phase 1 and Phase 2 metabolic enzymes including cytochrome (CYP) P450 3A4 and sulfotransferases (SULT). In vitro, the metabolism of palbociclib occurs primarily through CYP3A4 and SULT2A1; thus, coadministration of rifampin and palbociclib could result in decreased exposure of palbociclib. Methods This open-label, 2-period, fixed-sequence study assessed the effect of multiple oral doses of rifampin on single-dose palbociclib pharmacokinetics (PK) in 15 healthy volunteers (ClinicalTrials.gov; NCT01953731). Each subject received the following treatments: Period 1, oral palbociclib 125 mg on day 1; Period 2, oral rifampin 600 mg for 12 days and oral palbociclib 125 mg on day 8 (washout of ≥12 days between the 2 palbociclib doses). Serial blood sampling for palbociclib PK was performed predose and up to 120 hours post-palbociclib dose in both periods. Plasma concentrations of palbociclib were measured using validated high-performance liquid chromatography tandem mass spectrometry methods. Palbociclib plasma PK parameters were estimated using standard non-compartmental methods. Results Median time to maximum plasma concentration (Tmax) and mean half-life (t1/2) were shorter with palbociclib plus rifampin relative to palbociclib alone. Adjusted geometric mean palbociclib AUCinf (area under the curve from time zero to infinity) and Cmax (maximal plasma concentration) following treatment with rifampin (242.5 ng•h/mL and 15.52 ng/mL, respectively) were considerably lower relative to palbociclib administered alone (1568 ng•h/mL and 51.42 ng/mL). Generally, study treatments were well tolerated with no reported serious adverse events; 1 subject discontinued due to liver function test abnormalities after receiving rifampin alone for 7 days in Period 2. Conclusions Treatment with multiple doses of rifampin with palbociclib decreased total (AUCinf) and peak (Cmax) palbociclib exposure by approximately 85% and 70%, respectively, versus palbociclib alone. Palbociclib was well tolerated when administered alone or in combination with rifampin. Based on these results, concurrent administration of palbociclib with strong CYP3A inducers should be avoided. Citation Format: Justin T. Hoffman, Anna Plotka, Melissa O'Gorman, Andrew Chang, Maha Kosa, Cho-Ming Loi, Corrado Gallo-Stampino, Diane D. Wang. A phase 1 randomized, open-label, fixed-sequence, 2-period study of the effect of multiple doses of rifampin on palbociclib (PD-0332991) pharmacokinetics in healthy volunteers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4515. doi:10.1158/1538-7445.AM2015-4515
A randomized phase II study of bone-targeted therapy in advanced androgen-dependent prostate cancer.
Authors: M. A. Bilen, D. Liu, P. Mathew, L. C. Pagliaro, C. Logothetis, J. C. Araujo, A. Aparicio, P. G. Corn, J. Hajdenberg, S. R. Dakhil, S. Tu
Journal: Journal of Clinical Oncology (2011)

4649 Background: Bone is the most common site of progression in prostate cancer and the development of bone-targeted therapy may benefit such patients The aim of this phase II randomized controlled trial was to determine the progression-free survival of hormonal ablative therapy, combined with zoledronic acid and doxorubicin, with or without strontium-89, for patients with androgen-dependent prostate cancer and bone metastases. Methods: A total of 80 patients were enrolled on this study; 79 patients were randomized: 40 to the arm without and 39 to the arm with Sr-89 treatment. Eligible patients also received after randomization LHRH agonists of choice AND doxorubicin (20 mg/m2 on days 1, 8, and 15 q 4 weeks x2 cycles) AND zoledronic acid (4 mg IV q 4 weeks x6). Kaplan-Meier methodology was used to evaluate the primary outcome, which was progression-free survival (PFS). In addition, multivariate Cox proportional hazards regression was used to evaluate the effects of strontium-89 after controlling for the number of bone metastases. Results: The median follow-up time for the 44 of 79 randomized patients that were alive at the last follow-up, was 44.5 (range: 0.07–72.8) months. There was no statistical significance for PFS between the Sr-89 arm and no Sr-89 arm. Thirty-four of 72 (45.2%) patients died, 17 of 35 (48.6%) patients on the no Sr-89 treatment arm and 17 of 37 (45.9%) patients in the Sr-89. Median time to death was 46.5 months (95% CI: 32.3, not attained) in the no Sr-89 arm compared to 49.5 months (95% CI: 35.9, not attained). However, the Kaplan-Meier curves of overall survival for the evaluable population did not show any statistical significance. Unplanned subgroup analysis suggests that bone-targeted therapy may be more efficacious for patients with greater extent of bone involvement (ie, >6 vs <6 bone metastases on the bone scan). Conclusions: These preliminary data suggest that bone-targeted therapy using one dose of Sr-89 combined with chemohormonal ablative therapy did not improve the PFS of patients with androgen-dependent prostate cancer with bone metastases. Whether this bone-targeted therapy provided a favorable outcome for patients with greater tumor burden in the bone requires further investigation.
Bosutinib (BOS) as third-line therapy for chronic phase (CP) chronic myeloid leukemia (CML) following failure with imatinib (IM) and dasatinib (DAS) or nilotinib (NIL).
Authors: T. H. Brummendorf, J. E. Cortes, H. Kantarjian, C. Gambacorti-Passerini, M. Baccarani, D. Kim, A. Zaritskey, J. Navarro, A. Rapoport, P. E. Dorlhiac-Llacer, J. Milone, M. Zanichelli, N. Besson, E. Leip, V. Kelly, H. J. Khoury
Journal: Journal of Clinical Oncology (2011)

6535 Background: BOS is an orally active, dual Src/Abl tyrosine kinase inhibitor (TKI). Methods: This open-label, phase 1/2 trial evaluated safety and efficacy of BOS as 3rd-line therapy in patients (pts) with Philadelphia chromosome–positive CP CML. Pts with prior IM failure who were resistant (R)/intolerant (I) to DAS (n = 37/n = 50) or NIL-R (n = 27) received oral BOS starting at 500 mg/d. Results: 114 pts were evaluated (45% male; median age, 56 y [range 20-79 y]; median time from CML diagnosis, 6.3 y [range 0.6-18.3 y]). Median follow-up was 26.4 mo (range 0.3-54.0 mo); median BOS dose, 476 mg/d (range 185-563 mg/d). Of 82 (73%) evaluable pts achieving complete hematologic response (CHR; Table), 41% retained their response and are still on therapy. Of 31 (32%) evaluable pts achieving major cytogenetic response (MCyR), 39% retained their response and are still on therapy; 11 pts achieved complete response (CCyR). Major molecular response (MMR) was achieved in 22% of pts. MCyR and CHR were observed across 11 different Bcr-Abl kinase domain mutations, but not T315I. Non-hematologic treatment-emergent adverse events (TEAEs) seen in ≥20% of pts (all grades/grade ≥3) were diarrhea (83%/9%), nausea (46%/1%), vomiting (40%/1%), rash (27%/4%), headache (25%3%), fatigue (21%/1%), and abdominal pain (20%/1%). TEAE incidence was similar for DAS-R, DAS-I, and NIL-R pts. Gastrointestinal events were predominantly grade 1/2, early in onset, and usually subsided within a month. 2 DAS-I pts had grade 3 pleural effusions; both had these events on prior DAS and were grade 1 on study entry. No grade 3/4 QTc prolongation was observed. Grade 3/4 lab abnormalities (≥10%) included thrombocytopenia (26%), neutropenia (18%), and hypermagnesemia (12%). Conclusions: 3rd-line BOS therapy demonstrated acceptable toxicity and promising activity, emphasizing the therapeutic potential of BOS in CP CML pts with resistance/intolerance to other 2nd-generation TKIs. n/n evaluable (%) IM + DAS-R IM + DAS-I IM + NIL-R CHR 23/37 (62) 39/49 (80) 20/26 (77) MCyR 11/35 (31) 13/37 (35) 7/24 (29) CCyR 4/35 (11) 12/37 (32) 5/24 (21) MMR 3/32 (9) 17/46 (37) 1/19 (5)
A phase II study with perioperative modified docetaxel, cisplatin, and capecitabine (mDCX) in resectable gastroesophageal adenocarcinoma.
Authors: P. J. Fonseca, J. M. Vieitez, E. Turienzo, L. Sanz, G. Perez, M. Izquierdo, P. Pardo-Coto, M. Frunza, E. Gutierrez Restrepo, A. J. Lacave
Journal: Journal of Clinical Oncology (2011)

e14554 Background: DCF is associated with a high response rate in gastroesophageal cancer (GE), fact that makes it an interesting schedule in the neoadjuvant treatment. We developed a modified DCX (mDCX) regimen trying to minimize toxicity without compromising efficacy. We report the initial results of pathological response and toxicity. Methods: Patients (pts) with resectable adenocarcinoma of the stomach, gastroesophageal junction (GEJ) or lower esophagus (T3, T4 or N+) assessed by echoendoscopy and CT received 3 pre and 3 postoperative cycles of mDCX (docetaxel 70 mg/m2 day 1, cisplatin 70mg/m2 day 1 and capecitabine 1,500 mg/m2/day x 14 days, q21 days) with 3 doses of prophylactic GCSF (Neopugen 300mg) on day 4, 6 and 8 of every cycle. Results: Between July 2007 and July 2010, 26 pts (17 male/9 female) were treated in a Spanish centre. Median age: 54 years (range, 44-72). KPS: 80% (70-90%). Site of tumor: 15 stomach/8 GEJ/3 esophagus. Clinical stage of tumor: 2 (II)/ 12 (IIIA)/12 (IIIB). Surgery was curative in all patients and took place 8 weeks after completing the 3rd cycle; postoperative chemotherapy was initiated in 7 weeks (range: 5-10) after surgery. 22 (85%) pts of the 25 ones that had completed preoperative chemotherapy received surgery (1 pt requested to interrupt the treatment). The incidence of postoperative complications was 23% (6 pts) and there were 2 deaths (9%) within 10 days due to sepsis and esophageal fistula (graft necrosis). 3 of the 22 pts (14%) did not complete three postoperative cycles due to toxicity. The incidence of grade 3-4 pre and postoperative toxicity was 19% and 67%, respectively and 27% needed a dose reduction. Grade 3/4 adverse events: nausea/vomiting (40%), neutropenia (27%), diarrhea (19%), skin effects (8%). Toxicity-related hospitalizations: 27%. There were 2 (9%) complete pathological responses, 12 (54%) downstaging and 2 progressive diseases. Conclusions: Modified DCX seems to be tolerable, feasible and efficient. This regimen warrants further development in the neoadjuvant setting of GE cancer.
Abstract 5106: Influence of chloride flux on cell motility in head and neck squamous cell carcinoma
Authors: Nayel Khan, Kevin Steehler, Carolyn Kemp, Sucheta Kulkarni, Kara Davis, Umamaheswar Duvvuri
Journal: Cancer Research (2015)

Abstract Purpose: To assess the specific involvement of chloride flux through TMEM16A in the regulation of tumor cell motility. Background: Head and neck squamous cell carcinoma (HNSCC) often features tumor metastases and is associated with decreased patient survival. A key feature of the metastatic process is the ability of the cancer cells to migrate. TMEM16A, a calcium-activated chloride channel (CaCC), has been shown to play a role in cell migration and tumor metastasis, most recently as a potential node between cell proliferation versus cell migration. However, the role of chloride flux in this phenomenon has yet to be elucidated. Methods: HNSCC cell lines were engineered to stably overexpress or knock-down TMEM16A. Cell migration was assessed via wound healing and transwell migration assays in cell culture media with varying chloride concentrations and in the presence of a TMEM16A specific inhibitor. The impact of chloride manipulation on EMT markers (E-cadherin, vimentin, ZO-1) was assessed using immunoblotting. Results: Data obtained by both cell migration assays showed that in conditions of physiologically normal chloride, OSC19 TMEM16A overexpressors migrated less when compared to OSC19 vector controls. However, in conditions of low chloride, the migration rates between both cell lines were similar. Furthermore, inhibition of chloride flux using chloride depleted media, or pharmacologic inhibition of TMEM16A lead to a decrease in cell motility. As expected, an increase in markers of epithelial phenotype (i.e., Zo-1) and decrease in markers of mesenchymal phenotype (i.e., alpha-smooth muscle actin) in cells incubated in low chloride media was observed. Conclusion: This data further supports the evidence that increased TMEM16A expression is correlated with decreased cell motility and therefore potential for cell metastasis. In addition, we have shown a role of chloride flux in TMEM16A's ability to modulate cell motility with a correlated change in EMT. Citation Format: Nayel Khan, Kevin Steehler, Carolyn Kemp, Sucheta Kulkarni, Kara Davis, Umamaheswar Duvvuri. Influence of chloride flux on cell motility in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5106. doi:10.1158/1538-7445.AM2015-5106
659. Oncolytic Adenovirus Loaded with Bioactive Modified Peptide as a Novel Approach to Treat Cancer
Authors: Mariangela Garofalo, Barbara Iovine, Lukasz Kuryk, Cristian Capasso, Mari Hirvinen, Andrea Vitale, Marjo Yliperttula, Maria Assunta Bevilacqua, Vincenzo Cerullo
Journal: Molecular Therapy (2016)

Cancer is still a leading cause of death worldwide. Although many kinds of treatment have been developed during the past decades, there is still a lack of effective therapy for advanced cancer. Currently treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase patient life expectancy. Therefore new treatment strategies against cancer are in high demand. Efficient anticancer agent and its targeted delivery into the tumor mass is a key prerequisite for the successful cancer therapy. Oncolytic virotherapy is emerging as a potential approach to treat cancer, using viruses, which are specifically engineered to selectively infect, replicate in and kill cancer cells without causing damage to normal cells. Their combination with chemotherapeutic agents have shown promising results due to the synergistic effect of viruses and drugs; therefore the combinatorial therapy is considered a beneficial approach for cancer treatment. Taken into account these considerations we optimized a strategy to conjugate peptides on the viral capsid, based on electrostatic interaction and used this strategy to deliver an active anti-tumor dipeptide. We used L-carnosine, a naturally occurring histidine dipeptide with anti-proliferative activity. A modified L-carnosine, positively charged was absorbed onto the viral capsid of an oncolytic adenovirus to generate a virus-carnosine complex. The complex showed enhanced anti tumor efficacy in vitro and in vivo and higher infectious titer compared to a naked oncolytic adenovirus in colorectal and lung cancer cells. The in vivo efficacy of the complex was analyzed in lung and colon cancer xenograft models, displaying a significant reduction in tumor growth and synergistic effect between virus and dipeptide. Moreover, we studied the molecular mechanisms underlying the effects of complex on tumor growth reduction. Complex can induce apoptosis in both cells lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in further studies also for specific delivery of other active drugs.