bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 99: Wnt signaling promotes tumor propagation in a mouse model of lung adenocarcinoma
Authors: Tammela Tuomas , Kerper Natanya , Xue Wen , Joshi Nikhil , Katajisto Pekka , Jacks Tyler 
Published: May 2015

Abstract
The considerable variability within tissue microenvironments as well as the multiclonality of cancers leads to heterogeneity within tumors, increasing the probablility of cellular states that promote resistance to therapy and eventually lead to reconstitution of the tumor by treatment-resistant cancer cells, which in some case have properties of normal tissue stem cells. Wnt signals are important in the maintenance of stem cells in various epithelial tissues, including in lung development and regeneration. We hypothesized that Wnt signals would also contribute to hierarchial organization of KrasG12D and KrasG12D; tp53Δ/Δ mouse lung adenocarcinomas. Indeed, rare cells with nuclear βeta-catenin were detected in mouse tumors in vivo. Stimulating KP mouse lung adenocarcinoma cells with recombinant Wnt3a promoted their spheroid-forming ability in a 3-dimensional Matrigel culture system, whereas RNAi or small-molecule inhibitors targeting Porcupine, an enzyme required for post-translational palmitoylation of Wnt, suppressed tumor initiation in vitro and in vivo. Interestingly, either the stimulation or inhibition of the Wnt signaling pathway had no effect on growth of KP lung cancer cells in standard 2-dimensional cell culture, suggesting that Wnt signaling qualitatively modulates the cellular phenotype instead of controlling cell proliferation. We propose that targeting the Wnt signaling pathway can stimulate re-differentiation of lung adenocarcinoma cells, which may render them more sensitive to conventional anti-tumor therapies.
Citation Format: Tuomas Tammela, Natanya Kerper, Wen Xue, Nikhil Joshi, Pekka Katajisto, Tyler Jacks. Wnt signaling promotes tumor propagation in a mouse model of lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 99. doi:10.1158/1538-7445.AM2014-99
Abstract CT223: Dendritic cells pulsed with Wilms′ tumor gene 1 (WT1)-specific and MHC class I and II-restricted epitopes with gemcitabine induce antitumor immune responses in patients with advanced pancreatic cancer
Authors: Koido Shigeo , Homma Sadamu , Okamoto Masato , Mori Masako , Yoshizaki Shinji , Takakura Kazuki , Hayashi Kazumi , Kan Shin , Ishidao Takafumi , Yusa Sei-ichi , Shimodaira Shigetaka , Uchiyama Kan , Kajihara Mikio , Imazu Hiroo , Arakawa Hiroshi , Ohkusa Toshifumi , Tajiri Hisao 
Published: May 2015

Abstract
Wilms' tumor gene 1 (WT1) protein is an attractive target for cancer immunotherapy. To evaluate whether dendritic cells (DCs) pulsed with WT1-specific and MHC class I and II-restricted epitopes in combination with gemcitabine induce antitumor immune responses and improve clinical outcome in patients with advanced pancreatic cancer, we investigated the clinical and immunologic responses to the chemoimmunotherapy. Ten pancreatic cancer patients with stage IV and HLA positive for HLA-A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:02, DRB1*15:01, DPB1*09:01, or DPB1*05:01 were enrolled in this study. Patients first received gemcitabine on days 1, 8, and 15, followed by intradermal vaccinations with DCs pulsed with MHC class I or II alone (n=3), or MHC-I/II-restricted WT1 peptides (n=7) depending on their HLA biweekly and gemcitabine on days 1, 8, and 15 of a 28-day cycle. In 4 of 7 patients vaccinated with MHC-I/II pulsed DCs and none of 3 patients vaccinated with MHC-I or -II pulsed DCs, we detected WT1 peptide-specific delayed-type hypersensitivity (DTH). Among ten enrolled patients, DTH-positive patients showed significantly improved clinical outcome, compared with negative patients. Moreover, longer survivors featured a higher frequency of memory-phenotype in WT1-specific cytotoxic T-lymphocytes after vaccination with MHC-I/II pulsed DCs. In conclusion, the combination therapy was well-tolerated and activation of WT1-specific immune responses may be associated with improved clinical responses for patients with advanced pancreatic cancer.
Citation Format: Shigeo Koido, Sadamu Homma, Masato Okamoto, Masako Mori, Shinji Yoshizaki, Kazuki Takakura, Kazumi Hayashi, Shin Kan, Takafumi Ishidao, Sei-ichi Yusa, Shigetaka Shimodaira, Kan Uchiyama, Mikio Kajihara, Hiroo Imazu, Hiroshi Arakawa, Toshifumi Ohkusa, Hisao Tajiri. Dendritic cells pulsed with Wilms′ tumor gene 1 (WT1)-specific and MHC class I and II-restricted epitopes with gemcitabine induce antitumor immune responses in patients with advanced pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT223. doi:10.1158/1538-7445.AM2014-CT223
Abstract CT302: A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic or recurrent breast cancer patients with triple negative disease
Authors: Cowherd Stacy , Melin Susan , Akman Steven , Cole John , Lawrence Julia 
Published: May 2015

Abstract
Purpose: Metastatic triple negative breast cancer is an unmet need in oncology. A targeted therapy for triple negative breast cancer has not been found so metastases are treated with chemotherapy as a single agent or in combination. The epidermal growth factor receptor (EGFR) is frequently over-expressed in triple negative breast cancer. This EGFR receptor can be targeted with agents such as cetuximab or panitumumab. We designed a single-arm clinical trial to investigate the activity of panitumumab in combination with carboplatin and paclitaxel in women with triple negative breast cancer.
Patients and Methods: Patients with metastatic disease and who had received no greater than one prior chemotherapy regimen were eligible for the study. Patients received paclitaxel 80mg/m^2 and carboplatin with AUC 2 on days 1, 8, and 15. In addition they received panitumumab 6mg/kg on days 1 and 15. The primary endpoint was overall response rate. We evaluated patients for toxicity prior to each cycle. We also subtyped the breast tumor specimens using microarray into basal-like, Her-2 enriched, luminal A, luminal B, and normal-like to assess for differential response to therapy among these subtypes.
Results: We enrolled 14 patients into the study at two sites (Wake Forest University Baptist Medical Center and Ochsner Medical Center). The average age of enrolled patients was 54.1 years. Nine out of the 14 women were African American and 5 patients were Caucasian. The median number of cycles received by the cohort was 3.5 (1-9) with median time to progression of 98 days. Common grade 3 and 4 adverse events included lymphopenia in 5 patients and neutropenia in 9 patients. Seven participants experienced grade 1/2 mucositis and two participants had grade 3 mucositis. Seven patients experienced grade 1/2 acneiform rash. Response to therapy based on tumor subtype (basal-like, Her-2 enriched, luminal A, luminal B, or normal-like) will also be presented, data in progress.
Conclusion: Adding the EGFR inhibitor panitumumab to carboplatin/paclitaxel was a well-tolerated and effective therapy for metastatic triple negative breast cancer. This combination could be most appropriate for certain subtypes of triple negative disease.
Citation Format: Stacy Cowherd, Susan Melin, Steven Akman, John Cole, Julia Lawrence. A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic or recurrent breast cancer patients with triple negative disease. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT302. doi:10.1158/1538-7445.AM2014-CT302
Abstract CT318: FOLFOXIRI+B-mab showed powerful effect as preoperative chemotherapy for multiple liver metastases of colorectal cancer
Authors: Ichikawa Yasushi , Goto Ayumu , Kobayashi Noritoshi , Tokuhisa Motohiko , Ishikawa Takashi , Ishibe Atsushi , Watanabe Kazuteru , Nojiri Kazunori , Kumamoto Yoshibumi , Takeda kazuhisa , Ota Mitsuyoshi , Akiyama Hirotoshi , Tanaka Kuniya , Endo Itaru 
Published: May 2015

Abstract
Background; R0 resection for liver metastases of colorectal cancer is one of the promising treatment to improve prognosis of advanced colorectal cancer. Powerful regimen FOLFOXIRI including 3 cytotoxic drugs; 5FU, irinotecan and oxaliplatin was reported as promising treatment for advanced colorectal cancer (J Clin Oncol 2007; 25: 1670-76). In our department Phase I/II study of FOLFOXIRI+B-mab including fluoroiuracil/oxaliplatin/irinotecan/bevacizumab for advanced liver metastases of colorectal cancer as pre-operative chemotherapy has been conducted now, and Phase II was on going. In this study, we report effect and safety of FOLFOXIRI+B-mab.
Methods: The study was designed as a single-arm, open-label phase I/II trial. Phase I was conducted to decide tolerated dose (MTD) of irinotecan and 150 mg/m2 was decided as recommended dose. Patients who are colorectal cancer with 4 or more liver metastases and no other distant metastases are included. The regimen includes bevacizumab; 5 mg/kg, irinotecan; 150 mg/m2, oxaliplatin; 85 mg/m2, l-LV; 200 mg/m2, 5FU; 400 mg/m2 administered on day 1, followed by 5FU; 2400 mg/m2 continuously administered for 46 hours. R0 resection rate of liver metastases as primary endpoint will be evaluated.
Results: Currently, 16 patients were enrolled. Two patients dropped out because of grade 3 diarrhea and grade 3 thromboembolism. One patient is waiting for liver resection and R0 resection of liver metastases was performed for 9 patients. In the 14 patients excluding 2 drop out, 13 showed PR and average of reduction rate was 51%. There was no pathological CR in the 9 patients who was performed R0 resection. There was no severe postoperative complication in them.
Conclusion: This regimen is safe and shows high PR rate. So, the regimen is effective and improve R0 resection rate for multiple liver metastases of colorectal cancer. Further investigation of this study is still ongoing now.
Citation Format: Yasushi Ichikawa, Ayumu Goto, Noritoshi Kobayashi, Motohiko Tokuhisa, Takashi Ishikawa, Atsushi Ishibe, Kazuteru Watanabe, Kazunori Nojiri, Yoshibumi Kumamoto, kazuhisa Takeda, Mitsuyoshi Ota, Hirotoshi Akiyama, Kuniya Tanaka, Itaru Endo. FOLFOXIRI+B-mab showed powerful effect as preoperative chemotherapy for multiple liver metastases of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT318. doi:10.1158/1538-7445.AM2014-CT318
Abstract CT334: Pazopanib as third-line therapy for metastatic renal cell carcinoma: Clinical efficacy and temporal analysis of cytokine profile
Authors: Pal Sumanta K. , Hossain Dewan Md Sakib , Zhang Qifang , Gao Chan , Jones Jeremy O. , Frankel Paul H. , Figlin Robert A. , Kortylewski Marcin 
Published: May 2015

Abstract
Background: Pazopanib was assessed in a phase III study conducted in patients (pts) with mRCC who were either cytokine-refractory or treatment-naïve, and clinical outcomes with pazopanib have been associated with a specific immunologic profile (IP). The activity of pazopanib in the third-line setting and temporal changes in molecular profile during therapy are poorly understood, however.
Methods: Eligibility was limited to pts with 2 prior lines of therapy (including at least 1 VEGF-directed therapy), ECOG PS 0-2, and clear cell histology. Pts received pazopanib 800 mg/daily on a 28d cycle. A Simon MinMax 2-stage design was employed, with 80% power of declaring an encouraging overall response rate (ORR) of 23% (type I error=10%). IPs were assessed monthly on a Luminex platform using the Human Cytokine 30-plex Cytokine Immunoassay (Invitrogen).
Results: 28 pts were enrolled with a median age of 63 (range, 45-86). In the pre-specified intent-to-treat analysis, 12/28 pts (43%) had a confirmed response (1 CR, 11 PR), with 1 additional unconfirmed PR. Median progression-free survival for the cohort was 17.4 mos (95% CI 14.7-NR). No grade 4 treatment-related toxicities were observed. The most common grade 3 toxicities included hypertension (46%) and proteinuria (14%). Amongst patients still on therapy at 6 months and 12 months, responders had lower levels of HGF, VEGF, IL-6, IL-8 and soluble IL-2R (P&lt;0.05 for each). Non-responders also showed increased numbers of myeloid-derived suppressor cells (MDSCs) at both time intervals. Phenotypic and functional studies confirmed that MDSCs from these mRCC patients were granulocytic.
Conclusions: The ORR observed with pazopanib in the current study is the highest to date in a third-line trial in mRCC. Differences in cytokine profile and granulocytic MDSC quantity between responders and non-responders suggest that the mechanism of pazopanib resistance is at least partly related to generation of systemic tumor immune tolerance.
Citation Format: Sumanta K. Pal, Dewan Md Sakib Hossain, Qifang Zhang, Chan Gao, Jeremy O. Jones, Paul H. Frankel, Robert A. Figlin, Marcin Kortylewski. Pazopanib as third-line therapy for metastatic renal cell carcinoma: Clinical efficacy and temporal analysis of cytokine profile. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT334. doi:10.1158/1538-7445.AM2014-CT334
Abstract CT342: Phase I/II study of gefitinib in combination with vorinostat in patients with advanced non-small cell lung cancer (NSCLC) who progressed on prior chemotherapy
Authors: Han Ji-Youn , Lee Soo Hyun , Yun Tak , Lee Young Jooo , Hwang Kum Hui , Ryu Sunah , Kim Heung Tae , Lee Jin Soo 
Published: May 2015

Abstract
Background: Gefitinib has shown marked efficacy in EGFR-mutant NSCLC. However, the development of acquired resistance is inevitable. Additionally, its therapeutic effect in EGFR-wild type NSCLC is controversial. Vorinostat, a histone deacetylase inhibitor, has shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated patients with advanced NSCLC.
Methods: A 3+3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: gefitinib 250/day on days 1 through 28 and vorinostat on days 1-7 and 15-21 at 200, 300 and 400mg/day every 28 days. Phase II eligibility included advanced NSCLC, ≤2 line prior therapy, PS 0-2, adequate organ function. The primary endpoint was to determine the median progression-free survival (PFS) (null hypothesis 3.5 months, alternative hypothesis 6.5 months).
Results: Planned dose escalation was completed without reaching the MTD. The RP2D was gefitinib 250mg and vorinostat 400mg. Fifty-two patients were enrolled and treated in this study (43 in phase II). The median age was 59 years (range, 39 to 79 years), 30 were male, 48 had adenocarcinoma, 29 were never smokers, 31 had one prior regimen and 12 had two prior regimens; 21 had sensitive EGFR mutations, 3 had resistant exon 20 mutations and 5 had KRAS mutations. The most common adverse events were mild or moderate diarrhea, anorexia and anemia. In 43 assessable patients in phase II, there were 16 partial responses, 6 stable disease. The median PFS was 3.4 months; overall survival (OS) was 20.3 months. In patient harboring EGFR mutations, response rate (RR) was 88%, median PFS was 9.3 months and median OS was 22.6 months.
Conclusions Gefitinib 250mg daily with biweekly vorinostat 400 mg/day was feasible and well tolerated. In unselected patient population, this combination dose not improved PFS compared with historical control of single gefitinib. However, in EGFR-mutant NSCLC, this combination may improve RR and survival compared with historical control of gefitinib in previously treated EGFR-mutant NSCLC.
Citation Format: Ji-Youn Han, Soo Hyun Lee, Tak Yun, Young Jooo Lee, Kum Hui Hwang, Sunah Ryu, Heung Tae Kim, Jin Soo Lee. Phase I/II study of gefitinib in combination with vorinostat in patients with advanced non-small cell lung cancer (NSCLC) who progressed on prior chemotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT342. doi:10.1158/1538-7445.AM2014-CT342
Abstract CT407: Phase I study of preoperative continuous 5-fu and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma
Authors: Kim Richard , Jiang Kun , Zhao Xiuhua , Chen Dung-Tsa , Campos Tiffany , Hoffe Sara , Shridhar Ravi , Shibata David 
Published: May 2015

Abstract
Background: Preoperative treatment with fluoropyrimidine-based chemoradiotherapy is considered standard therapy for locally advanced rectal cancer( T3, T4 or N1). Sorafenib is an inhibitor of ras/raf, PDFGR and VEGFR with synergistic activity with radiation. The phase I trial evaluated the safety and efficacy of sorafenib in combination with infusional 5-FU and radiation
Methods: Patients with stage II or III patients confirmed by EUS and CT scan were recruited in cohorts of 3 patients per dose level (DL). A 3+3 dose escalation design was used. On all dose levels RT was given in 25 fractions at 1.8Gy (45Gy) day 1- 5. Surgery was done 6-10 weeks after the completion of neoadjuvant treatment.
Results: At Moffitt Cancer we enrolled 12 patients in 4 cohorts. 8 females(67%) and 4 males(33%); Median age is 55(range: 40-72). After observing toxicity in first cohort ( 2 pts with with G2 and G3 skin toxicity and 1 pt with G2 mucositis) which required dose interruptions, amendment was made to change the schedule of chemotherapy and sorafenib to days 1-5 instead of daily. After the amendment, hypertension was the only grade III toxicity observed. 2 patients had G3 hypertension at 200mg adjusted dose(day1-5); 1 patient had G3 hypertension at 400 mg PO BID dose level and no grade IV toxicities were seen. No perioperative complications related to the study drugs were seen. 2 patients never went to surgery due to patient refusal. KRAS testing information was available on 10 patients. pCR rate was 30 % and downstaging was observed in 80% of the patients. pCR was 50% in patients with Kras mutant tumors ( 2/4 pts)
Conclusion: After changing the schedule of the chemotherapy, the regimen was very well tolerated. pCR and downstaging rate of the tumor seems to be encouraging. Plan is to open up an expansion cohort at DL3 to gather more safety and efficacy data.
Schedule of sorafenib dose escalationDose level ( 3 patients each)Sorafenib5-FU infusion Rate (mg/m2/24hrsDL 1 before amendment200mg PO QD225 on day 1-7 for 5½ weeksDL 1 after amendment200mg PO QD( Day1-5)225 on day 1-5 for 5½ weeksDL 2 after amendment400mg PO QD( Day1-5)225 on day 1-5 for 5½ weeksDL 3 after amendment400mg PO BID( Day1-5)225 on day 1-5 for 5½ weeks
Citation Format: Richard Kim, Kun Jiang, Xiuhua Zhao, Dung-Tsa Chen, Tiffany Campos, Sara Hoffe, Ravi Shridhar, David Shibata. Phase I study of preoperative continuous 5-fu and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT407. doi:10.1158/1538-7445.AM2014-CT407
Abstract CT420: An open label pilot study of NovoTTF Therapy concomitant with gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma (NCT01971281)
Authors: Weinberg Uri , Kirson Eilon D. , Farber Ori , Giladi Moshe , Palti Yoram 
Published: May 2015

Abstract
Background: NovoTTF Therapy is a non-invasive, anti-mitotic treatment modality, based on low intensity alternating electric fields. Tumor Treating Fields (TTFields) interfere with two steps during mitosis: The formation of the mitotic spindle (metaphase), and the translocation of charged organelles (anaphase). TTFields inhibit proliferation of pancreatic cell lines in vitro, and inhibit pancreatic tumor growth in vivo, alone and in combination with gemcitabine. NovoTTF Therapy applied to the brain in recurrent GBM patients demonstrated an anti-tumoral effect with minimal toxicity and better quality of life, compared to chemotherapy (Stupp et al, 2012). Being a regional treatment, TTFields can potentially inhibit the primary tumor as well as major metastatic sites of pancreatic adenocarcinoma.
Objectives: the current trial is designed to study the safety, tolerability and efficacy of NovoTTF therapy applied to the abdomen concomitant to the standard care gemcitabine treatment, in patients suffering from advanced pancreatic adenocarcinoma.
Endpoints: severity and frequency of adverse events associated with the experimental treatment (primary), progression free survival (PFS), 6-month PFS rate, overall survival, overall response rate, compliance with NovoTTF Therapy (secondary)
Treatments: Gemcitabine 1000 mg/m^2 over 30 minute infusion once weekly for up to 7 weeks, followed by a week rest from treatment. Subsequent cycles will consist of once weekly infusions on days 1, 8, 15 every 28 days. Continuous NovoTTF Therapy at a frequency of 150 kHz will be administered to the abdomen, in order to cover the region of primary tumor and main metastatic sites. The fields will be applied in two perpendicular directions at a maximal intensity of 1414 mA RMS, using highly insulated Transducer Arrays connected to a portable, battery-operated electric field generator. TTFields will be administered for at least 18 hours a day until radiological disease progression.
Major eligibility criteria: unresectable, pathologically confirmed, locally advanced/metastatic pancreatic adenocarcinoma, measurable/assessable disease, ECOG score 0-1, no prior chemotherapy or radiation, no implantable electronic medical devices.
Citation Format: Uri Weinberg, Eilon D. Kirson, Ori Farber, Moshe Giladi, Yoram Palti. An open label pilot study of NovoTTF Therapy concomitant with gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma (NCT01971281). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT420. doi:10.1158/1538-7445.AM2014-CT420