bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 15: Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma
Authors: Masuda Muneyuki , Toh Satoshi , Rikimaru Hidefumi , Kunitake Naonobu , Higaki Yuichiro 
Published: December 2017

Abstract
Background: Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. We have developed a “chemoradioselection” protocol with minimal toxicity using initial response to CRT as a biomarker for patient selection.
Materials and Methods: From 2000 to 2012, 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol. Two cycles of split (15 mg/m2 x 5 days, 2000-2008) or bolus (80 mg/m2, 2009-present) CDDP was concurrently administered.
Results: Tumor responses were evaluated after 40 Gy of CRT and 64 responders (i.e., chemoradioselected, CRS) received further CRT up to 70 Gy, while radical surgery was recommended for the 59 non-responders (N-CRS), and 34 underwent surgery (N-CRS-ope). The remaining 25 patients who refused surgery (N-CRS-refu) were treated with continuous CRT. The 5-yr overall survival (OS) and disease-specific survival (DSS) were 67% and 77%, respectively. The CRS demonstrated quite favorable 5-yr OS (73%) and 5-yr laryngo-esophageal dysfunction-free survival (LEDFS, 69%). In contrast, the N-CRS-refu showed significantly (P = 0.0193) lower 5-yr OS (47%) than CRS (73%) and N-CRS-ope (70%), and significantly (P &lt; 0.0001) lower 5-yr LEDFS (20%) than the CRS (69%). On multivariate analyses including T, N, primary site, and planned treatment (CRS + N-CRS-ope) or not (N-CRS-refu), unplanned treatment alone showed a significant correlation with poor OS (Hazard ratio [HR]: 2.584, 95% CI: 1.313–4.354, P = 0.007).
Conclusions: Chemoradioselection reflects the biological aggressiveness of each tumor, and can segregate patients for functional laryngeal preservation with moderate intensity CRT (150-160 mg/m2 of CDDP) from those who would be better treated with surgery. This strategy may be useful for the optimization of the therapeutic intensity.
Citation Format: Muneyuki Masuda, Satoshi Toh, Hidefumi Rikimaru, Naonobu Kunitake, Yuichiro Higaki. Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 15.
Abstract 61: Overcoming acquired resistance to PI3K inhibitors in head and neck squamous cell carcinoma with combination treatment
Authors: Mizrachi Aviram , Dunn Lara , Ho Alan , Scaltriti Maurizio 
Published: December 2017

Abstract
Purpose: Activating mutations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in both HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC). These mutations are therapeutic targets and selection for PIK3CA mutations leads to superior activity of PI3K inhibitors. However, early clinical trials have been disappointing, mainly because the durability of activity of these drugs is limited. Recent preclinical data suggest that acquired resistance to PI3K inhibition is a result of activation of alternative pathways such as mTORC1 and the Cyclin D1 complex.
Experimental Design: We challenged two different mechanisms by which PIK3CA-mutated tumors develop resistance to PI3K inhibitors by combining PI3K inhibitors with either mTORC1 inhibitor or CDK 4/6 inhibitor. Using patient-derived xenograft models of HNSCC, we tested whether these therapeutic strategies can overcome drug resistance and result in durable response.
Results: Administration of the PI3K inhibitor BYL719 together with the mTORC inhibitor RAD001 delayed tumor growth in comparison with either of these drugs alone. Similarly, treatment with another PI3K inhibitor GDC-0032 and the CDK4/6 inhibitor abemaciclib was superior to single-agent treatments.
Conclusions: Co-suppression of PI3K and either mTORC1 or CDK4/6 is effective in preclinical models of HNSCC. These results may provide the rationale to test these therapeutic strategies in the clinic.
Citation Format: Aviram Mizrachi, Lara Dunn, Alan Ho, Maurizio Scaltriti. Overcoming acquired resistance to PI3K inhibitors in head and neck squamous cell carcinoma with combination treatment [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 61.
Abstract 62: Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence
Authors: Simmons Amanda , Kong Christina , Eyben Rie von , Attardi Laura , Ma Xiaohui , Le Quynh-Thu , Nathan Cherie-Ann 
Published: December 2017

Abstract
Objectives: PERP (p53 apoptosis effector related to PMP22) localizes to the desmosomal adhesion complexes and is involved in suppressing squamous cell carcinoma (SCC) development. Loss of PERP expression leads to destabilization of desmosome complexes, resulting in enhanced tumor aggressiveness and worse local control in head and neck SCC (HNSCC). We had previously examined PERP loss at surgical margins in a small cohort of HNSCC patients. Results suggested that the loss of PERP may serve as a marker for persistent tumor and predictive of local relapse. Here we validate these findings in an independent patient cohort and report on the combined results of both groups.
Materials and Methods: We previously examined the PERP protein expression by immunohistochemistry (IHC) in the surgical mucosal margins of 17 HNSCC patients. The validation cohort consists of 31 patients (15 oral cavity, 11 hypopharynx, 5 larynx). PERP expression was similarly assessed by IHC in the surgical margins of these patients. Finally, we combined the results of both groups to yield 48 patients with HNSCC (18 oral cavity, 12 hypopharynx, 4 oral pharynx, 14 larynx) for competing risk analysis. The relationship between local relapse and PERP expression (positive or negative) was analyzed in a competing risk model with death as a competing risk.
Results: In the initial cohort, the 2-year cumulative incidence rate of local relapse was 37.5% for the negative PERP group compared to a 20% for the positive PERP group (p = 0.177). In the validation cohort, the 2-year cumulative incidence rate of local relapse was 50% for the negative PERP group compared to a 15% for the positive PERP group (p = 0.063). Since the results were similar between two groups, we combined them together for additional analyses. In this combined dataset, PERP expression was negative in 18, positive in 26, and not assessable in three patients. Of the 45 analyzable patients, the 2-year cumulative incidence rate of local relapse was 44.4% for the negative PERP group compared to a 16.4% for the positive PERP group (p = 0.010). There was also a trend for worse progression-free survival (p = 0.059) and overall survival (p = 0.085) with the loss of PERP.
Conclusions: PERP loss at the surgical margins appears to be associated with a higher risk of local recurrence in HNSCC. These promising results need to be tested in a larger prospective study.
Citation Format: Amanda Simmons, Christina Kong, Rie von Eyben, Laura Attardi, Xiaohui Ma, Quynh-Thu Le, Cherie-Ann Nathan. Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 62.
Abstract 64: Abnormal splicing events in adenoid cystic carcinoma
Authors: Leonard Brandon , Humtsoe Joseph O. , Kim Hyun-Su , Ling Shizhang , Marchionni Luigi , Fertig Elana J. , Considine Michael , Ha Patrick 
Published: December 2017

Abstract
Salivary gland adenoid cystic carcinoma (ACC) is a relatively rare and understudied malignancy. While this disease can often be controlled locally by surgery and radiation therapy, distant metastases occur in nearly 50% of cases. Interestingly, these metastases can remain asymptomatic for several years, and there are currently no factors that are known to contribute to their dormancy or aggressiveness. Furthermore, there are no targeted chemotherapeutic agents available to treat any stage of this disease.
To identify aberrations that contribute to ACC tumorigenesis, we performed whole genome methylation profiling, RNA sequencing, and exome sequencing on 18 primary ACC tumors and matched normal salivary gland tissue. A novel analysis methodology of Splice Expression Variability Analysis (SEVA) coupled with outlier statistical analyses of mRNA splice junctions revealed the presence of several abnormal splicing events (ASEs) in the studied tumors. Interestingly, the ASEs were significantly overrepresented in tumors as compared to matched normal salivary gland tissue. In vitro analyses found that many of the ASEs are also expressed in the only validated ACC cell line, MDA-ACC01, and multiple patient-derived xenograft (PDX) models of ACC. Overall, these studies have identified an unanticipated aberration in ACC and developed a model in which to study ASEs. Future work will be aimed at determining the functional impact that ASEs have on tumor initiation and growth.
Citation Format: Brandon Leonard, Joseph O. Humtsoe, Hyun-Su Kim, Shizhang Ling, Luigi Marchionni, Elana J. Fertig, Michael Considine, Patrick Ha. Abnormal splicing events in adenoid cystic carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 64.
Abstract 73: Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cell by targeting forkhead transcription factors FOXO3a and FOXM1
Authors: Tanaka Noriaki , Zhao Mei , Zhang Jiexin , Wang Jing , Zhou Ge , Myers Jeffrey N. 
Published: December 2017

Abstract
Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties in promoting cancer cell invasive growth and metastasis, but the mechanisms mediating these functions largely remain elusive. We show here that overexpression of the GOF mutant p53 G245D and other GOF p53 mutants enhances invasive cell growth of p53-deficient head and neck squamous cell carcinoma (HNSCC) UM-SCC-1 cells both in vitro 3D culture and in vivo orthotopic tumor mouse model. We demonstrate that the expression of the oncogenic forkhead transcription factor FOXM1 is upregulated by GOF mutant p53s in UM-SCC-1 cells and tumors. Moreover, we show that overexpression of GOF mutant p53 G245D decreases the inhibitory phosphorylation of FOXO3a, a tumor suppressive forkhead transcription factor, leading to its cytoplasmic accumulation. Consistent with the observation that FOXO3a negatively regulates FOXM1 expression, we demonstrate that overexpression FOXO3a decreases GOF mutant p53-mediated FOXM1 expression, whereas downregulation of FOXO3a partially restores decreased FOXM1 expression due to loss of GOF mutant p53. In support of the roles of FOXO3a-FOXM1 signaling axis in mutant p53's GOF signaling, we further show that overexpression of FOXO3a or downregulation of FOXM1 impairs GOF mutant p53-mediated cell invasion, whereas downregulation of FOXO3a, in part, rescues impaired cell invasion due to downregulated GOF mutant p53. Finally, given that AMP-activated protein kinase (AMPK) directly phosphorylates and promotes FOXO3a function, and that our prior demonstration that GOF mutant p53s inhibit AMPK, our current study establishes that GOF mutant p53-AMPK-FOX3a-FOXM1 signaling is one of important mechanisms through which mutant p53s gain oncogenic functions in HNSCCs.
Citation Format: Noriaki Tanaka, Mei Zhao, Jiexin Zhang, Jing Wang, Ge Zhou, Jeffrey N. Myers. Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cell by targeting forkhead transcription factors FOXO3a and FOXM1 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 73.
Abstract IA10: Integrated omics analyses identify prognostic biomarkers of oral cavity squamous cell carcinoma in Taiwan
Authors: Chang Kai-Ping , Chen Ting-Wen , Pickering Curtis R. , Myers Jeffrey N. , Chang Yu-Sun 
Published: December 2017

Abstract
To uncover genomic alterations that can be used as molecular markers for oral cavity squamous cell carcinoma (OSCC) in Taiwan, we recruited patients who were ethnically Taiwanese and admitted to Chang Gung Memorial Hospital at Taipei. We performed whole-exome sequencing (WES) of matched tumor/PBMC DNAs from 50 OSCC patients (75-Mbp target region, mean depth = 244 ± 54), and RNA sequencing of matched tumor/adjacent normal tissues from 39 of the 50 patients (mean read count = 38.7 ± 15.2 million). A subset of the identified somatic mutations was validated in 49 tumor tissues using an IonAmpliSeqTM Comprehensive Cancer Panel (CCP; 409 cancer-related genes). In total, our exome sequencing analyses uncovered 33,160 somatic single nucleotide variants (SNVs) and InDels. The targeted approach of CCP enabled us to independently validate 84.91% of the SNVs identified by our whole-exome sequencing. We cross-referenced our data with that of 172 oral cavity cancer samples (OSCC-TCGA) from the Head-Neck Squamous Cell Carcinoma (HNSC) project of TCGA (HNSC-TCGA) and 106 from India (OSCC-India), as annotated in the International Cancer Genome Consortium (ICGC). We found that our patient cohort was characteristic of OSCC with regard to frequently mutated genes, such as CDKN2A, TP53, and NOTCH1. Interestingly, however, our analysis further identified mutations in seven other genes that turned out to be unique, locally prevalent (&gt;10% of patients) alterations. We further used our exome sequencing data to examine copy number alterations in our samples and our findings largely recapitulated the profile found in OSCC-TCGA, which included significantly amplified/deleted regions encompassing genes such as EGFR, FGFR1, FADD, FAT1 and CDKN2A. Comparative analysis of the transcriptomes of tumor and normal tissues allowed us to identify 3,548 genes as being differentially expressed in OSCC-Taiwan; these included 1,220 up-regulated and 2,328 down-regulated genes. Notably, 91.3% of these differentially expressed genes were similarly identified in the OSCC-TCGA data, indicating that the overall expression profile of OSCC is highly similar across ethnic groups. In the meeting, I will report the unique genomic alterations with the potential biomarkers in OSCC, and these findings might introduce a hitherto unknown genetic component of this disease.
Citation Format: Kai-Ping Chang, Ting-Wen Chen, Curtis R. Pickering, Jeffrey N. Myers, Yu-Sun Chang. Integrated omics analyses identify prognostic biomarkers of oral cavity squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA10.
Report on the Third FDA–AACR Oncology Dose-Finding Workshop
Authors: Emens Leisha A. , Bruno Rene , Rubin Eric H. , Jaffee Elizabeth M. , McKee Amy E. 
Published: December 2017

Abstract
The FDA–AACR Oncology Dose-Finding Workshop, Part 3, was held in Washington, DC, on July 20, 2017, as a continuation of the previous two collaborative dose-finding and optimization workshops presented by the FDA and AACR. This year's workshop focused on combination therapy with immune-oncology agents and best practices regarding patient and dose selection, predictive biomarkers, and novel clinical endpoints. This summary highlights viewpoints that emerged during the workshop. Cancer Immunol Res; 5(12); 1058–61. ©2017 AACR.
<b>Small carnivores of the montane forests of Eravikulam National Park in the Western Ghats, India</b>
Authors: Nikhil S. , Nameer P. O. 
Published: November 2017

The study of small carnivores of the montane forests of Eravikulam National Park in the southern Western Ghats, India recorded nine species of small carnivores using the camera trapping technique. These include three species of Mongoose (Herpestidae), two species each of lesser cats (Felidae) and civets (Viverridae), one species each of Otter and Marten (Mustelidae). They are Stripe-necked Mongoose Herpestes vitticollis, Brown Mongoose Herpestes fuscus, Indian Grey Mongoose Herpestes edwardsii, Jungle Cat Felis chaus, Leopard Cat Prionailurus bengalensis, Common Palm Civet Paradoxurus hermaphrodites, Small Indian Civet Viverricula indica, Asian Small-clawed Otter Aonyx cinereus, and Nilgiri Marten Martes gwatkinsii. It is interesting to note that the felines (lesser cats) are the more common small carnivores in the montane forests. Felis chaus was the most abundant small carnivore, which is followed by Prionailurus bengalensis and Herpestes vitticollis. Two species are Vulnerable as per the IUCN Red List, viz., Martes gwatkinsii and Aonyx cinereus.
<b>Population size, herd structure and sex ratio of the Blackbuck <I>Antilope Cervicapra</I> (Mammalia: Cetartiodactyla: Bovidae) in a human dominated area in Odisha, India</b>
Authors: Debata Subrat 
Published: November 2017

Blackbuck Antilope cervicapra in human dominated landscapes are vulnerable to poaching, habitat loss and competition with livestock for forage. I estimated population sizes and age structure of Blackbucks in an unprotected site of 61.21km² in Odisha over a period of one year (October 2012 to October 2013). A total of 7,134 individuals in 366 herds were documented ranging from a single individual to the largest herd of 51 animals. Average herd size was 19.49±0.03 (SE) and ranged from 13.34±0.06 in summer to 31.86±0.07 during the monsoon. Sex ratio was skewed towards females by 3:1. The young constituted 16% of the population. This indicates that a healthy population of blackbuck is surviving in this area; therefore measures need to be taken to conserve this site and manage the area as a Blackbuck reserve.
<b>Flies matter: a study of the diversity of Diptera families (Insecta: Diptera) of Mumbai Metropolitan Region, Maharashtra, India, and notes on their ecological roles</b>
Authors: Dhamorikar Aniruddha H 
Published: November 2017

Diptera is one of the three largest insect orders, encompassing insects commonly known as ‘true flies’. They are one of the most important in terms of their interactions with humans. Family-level diversity of Diptera was studied in the Mumbai Metropolitan Region (MMR)—50 families were recorded in four protected areas—Sanjay Gandhi National Park, Tungareshwar Wildlife Sanctuary, Karnala Bird Sanctuary, and Matheran Eco-Sensitive Zone, of which 24 were also found in urban areas of Mumbai and Thane City. The MMR’s family-level dipteran diversity constitutes 78% of families documented in the Western Ghats and 57% of India’s known families of Diptera. The recorded Diptera families were segregated into two groups based on their habits - beneficial and pestiferous. Of the 50 families, 66% comprised members which were beneficial in terms of flower visitations (28%), decomposition (24%), and predators and parasitoids of pest insects (14%), whereas 34% comprised members that were pestiferous in nature in terms of posing a threat to human health and causing nuisance (11%), causing crop and food damage (12%), posing a threat to animal health (8%), and as parasitoids of beneficial insects (3%). In terms of their feeding preferences, the majority of the adults were flower visitors (26%), 24% were saprophagous, followed by members that were frugivorous, fungivorous, coprophagous, and predatory in nature. Among larval feeding habits, 31% were detritivorous, 18% phytophagous, and 13% predatory in nature. In terms of their habitat preferences, 24 families were found in dense undergrowth, 12 in mountainous forests, and 11 in fruit gardens. This study establishes that Diptera is more diverse in natural areas than urban areas, and emphasizes the need for further exploration in terms of taxonomic and ecological studies, and economic benefits vis-à-vis the losses they incur in the region.
<b>First records of two Ginger Lilys <I>Hedychium</I> (Zingiberaceae) species from the Western Ghats, India</b>
Authors: Thomas Sinjumol , Brittto Susai John , Mani Bince 
Published: November 2017

Hedychium forrestii Diels and H. spicatum Sm. (Zingiberaceae) are new distribution records from the Western Ghats, India, extending their range up to southern India. Detailed taxonomic descriptions are provided for the species along with photographs.
<b>Detection of <I>Artyfechinostomum sufrartyfex</I> - a zoonotic parasite from the Small Indian Mongoose <I>Herpestes auropunctatus</I> (Mammalia: Carnivora: Herpestidae) in Jammu & Kashmir, India</b>
Authors: Borkataki Sanku , Goswami Pankaj , Katoch Rajesh , Kumar Shahil , Raghuvanshi Pratiksha 
Published: November 2017

The treamatode Artyfechinostomum sufrartyfex was identified from the small intestine of the Indian Mongoose and the morphological identification of the parasites was described. The fluke A. sufrartyfex is important considering its significant zoonotic potential, and the present study highlights the first report of occurrence of the parasite in a newer wild host, the mongoose from India.
<b>Roadkill records of Lowland Tapir <I>Tapirus terrestris</I> (Mammalia: Perissodactyla: Tapiridae) between kilometers 06 and 76 of highway BR-163, state of Pará, Brazil</b>
Authors: De Freitas Marco A. , Printes Rodrigo C. , Motoyama Eric K. , Fucks Assor E. , Veríssimo Diogo 
Published: November 2017

Fifteen Lowland Tapirs Tapirus terrestris were found road killed between kilometer six and 76 of the BR-163 highway, in the state of Pará, Brazil. The findings took place during two periods, May/July 2016, and June 2017. This highway is internationally known for its environmental impact and here we present additional evidence of its impact on the population of a threatened species.
<b>A first record of the Smallfin Gulper Shark <I>Centrophorus moluccensis</I> Bleeker, 1860 (Chondrichthyes: Squaliformes: Centrophoridae) from the Andaman & Nicobar waters, Indian EEZ</b>
Authors: Pradeep H. D. , Shirke Swapnil S. , Nashad M. , Sukham Monalisha Devi 
Published: November 2017

The Smallfin Gulper Shark Centrophorus moluccensis is reported for the first time from the Andaman & Nicobar waters of the Indian EEZ. A male specimen of 785mm total length and weighing 2.34kg was landed by a motorized longliner at Burmanallah, South Andaman District. The specimen was caught off Chidiyatapu, South Andaman at a depth of 250m. A detailed morphological description of the specimen and comparison with previous literature is provided.