tbuckley/cabot-search huggingface dataset:
Association of germ-line single nucleotide polymorphisms (SNPs) with pathologic response to neoadjuvant cisplatin-based chemotherapy in patients with resectable non-small cell lung cancers.
Authors: Jamie E. Chaft, Sohela Shah, Esther N. Drill, Camelia S. Sima, Vijai Joseph, Ana Virginia Calogeras Dutra-Clarke, Jason Littman, Mark G. Kris, William D. Travis, Naiyer A. Rizvi, Kenneth Offit
Journal: Journal of Clinical Oncology (2013)

7558 Background: Pathologic response to neoadjuvant chemotherapy correlates with survival in resected lung cancers. Predictive biomarkers of response are needed. Tumor-specific biomarkers have been hindered by reproducibility and specimen adequacy. Genome-wide association studies (most in SE Asia) have identified candidate SNPs that correlate with clinical outcomes after cisplatin-based chemotherapy. We evaluated whether these candidate SNPs are predictive of pathologic response to neoadjuvant chemotherapy in a US population. Methods: We aimed to correlate SNPs with near complete PR (ncPR) to neoadjuvant cisplatin + docetaxel in patients with resectable lung cancers. ncPR was defined as 90% necrosis, inflammation and fibrosis across serial 1cm sections of the resected tumor. Germline DNA was extracted and 50 candidate SNPs were genotyped by Sequenom Mass ARRAY iPLEX. SNPs were analyzed for correlation with ncPR using recessive (aa vs AA/aA) , dominant (AA vs aa/aA) and log-additive (linear increase in risk with each additional allele) genetic models. In this exploratory dataset, a p-value &lt;0.1 was considered worthy of further study. Results: 60 patients were treated and had sufficient DNA for analysis. Nine patients had a ncPR. 7 of 50 SNPs (table) correlated with pathologic response in one of the three models. Conclusions: Of the candidate SNPs identified from the literature, 7 showed a promising correlation to ncPR to neoadjuvant chemotherapy. This expands upon the experience evaluating SNPs and chemotherapy sensitivity into a North American population. Study of these 7 SNPs is ongoing in our current multimodality trial as a validation cohort. This study was funded by the Lung Cancer Research Foundation. [Table: see text]
Recombinant Adenovirus Expressing a Soluble Fusion Protein PD-1/CD137L Subverts the Suppression of CD8+ T Cells in HCC
Authors: Yonghui Zhang, Hailin Zhang, Mei Wei, Tao Mou, Tao Shi, Yanyu Ma, Xinyu Cai, Yunzheng Li, Jie Dong, Jiwu Wei
Journal: Molecular Therapy (2019)

Oncolytic viruses are an excellent platform for developing effective strategies in cancer immunotherapy. Several challenges remain in the use of viro-immunotherapy for cancer, such as the lack of costimulatory signals and negative regulation of immune checkpoints. In this study, we designed a novel adenovirus expressing a soluble fusion protein, programmed cell death protein 1 (PD-1)/CD137L, which contains the extracellular domains of PD-1 and CD137L at each terminus (Ad5-PC). Ad5-PC preserved the costimulatory activity of CD137L and facilitated the persistence of activated CD8+ T cells. Ad5-PC induced strikingly increased antitumor activity in both ascitic and subcutaneous hepatocellular carcinoma (HCC) tumor models, with 70% and 60% long-term cure rates, respectively. The improved antitumor effect of Ad5-PC was attributed to the sustained high-level lymphocyte activation and interferon (IFN)-γ production in the tumor microenvironment, and was essentially dependent on CD8+ T cells rather than natural killer (NK) cells. Moreover, Ad5-huPC-expressing human soluble PD-1/CD137L fusion protein was effective in suppressing tumor growth and improving survival in a humanized mouse model. We confirmed that Ad5-PC induced tumor-specific and systematic protection against tumor rechallenges at both in situ and distant sites. Thus, Ad5-PC harnesses several distinct functions to efficiently overcome several major hurdles of viro-immunotherapy.
Abstract 13111: Determinant of Sucessful Implantation of a Novel Autologous Valve Substitute (Biovalve) with Transcatheter Technique
Authors: Yoshiaki Takewa, Yasuhide Nakayama, Satoru Kishimoto, Kazuma Date, Hirohito Sumikura, Keiichi Kanda, Tsutomu Tajikawa, Takaharu Tanaka, Yoshiyuki Taenaka, Eisuke Tatsumi
Journal: Circulation (2014)

Introduction: There are some attempts to use tissue-engineered materials for heart valvular substitutes, but it is not clear what is determinant of successful implantation of the substitutes. It is generally thought that appropriate cell migration into an implanted graft tissue is essential in order to sufficiently exert the functions as a native valve. Hypothesis: We are developing a novel autologous aortic valve (Biovalve), using simple, safe and economical in-body tissue engineering which is based on a tissue encapsulation phenomenon in the living body. In this study, we investigated key factors in hitogenesis when the Biovalve was implanted in a large animal model with transcatheter technique. Methods: Biovalves were prepared by 2-month embedding of the molds, assembled using plastic rods in the subcutaneous spaces of goats. After extracting the molds and removing the plastic rods only, Biovalve were constituted from completely autologous connective tissues. We combined the Biovalve with a metaric stent for transcatheter implantation. Twenty Biovalve Stents were implanted in the aorta (n=16) and the pulmonary artery (PA) (n=4) in situ with transcatheter apical approach technique. Results: The Biovalve Stents were successfully implanted in both aortic and PA postion. They were extracted every month (maximum 6 months) after implantation to observe their cell migration process. The leaflets of the Biovalve kept their shape and elasticity even after 6 months and neither calcification nor thrombi were observed. Histological examination showed the cell migration inside the Biovalve body and laminar endothelialization on the surface of the valve leaflets even in 1 month after implantation. Their histogenesis have gradually advanced in 6 months without any hyperplasia, but were interrupted when the Biovalve tissues were not attached enough on the native vascular wall surface. Conclusions: The Biovalve satisfied the higher requirements of systemic and pulmonary circulation in goats for 6 months with the histogenic potential that was mainly induced by cell migration from the native vascular tissues contacting with the Biovalve.
Choice of sequential biologic therapies in metastatic colorectal cancer (mCRC): A cost comparison analysis for wild-type KRAS mCRC patient population in Brazil.
Authors: Rui Weschenfelder, Caio Timko Buschinelli
Journal: Journal of Clinical Oncology (2013)

e14679 Background: Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in Brazil. Metastatic disease affects up to 50% of patients resulting in 5-year survival of less than 10%. Therefore, there is an increasing interest about the best treatment options, mainly regarding biologics and their sequencing across first line (1L) and second line (2L) treatment of mCRC. Modern series show that the probability of a patient receives 1L, 2L and a third line (3L) therapy is approximately 99%, 70% and 40%, respectively. In addition, in 2012, the ML 18147 study demonstrated the benefit of sequential use, 1L and 2L, of bevacizumab (bev) based combination in mCRC and considering this emerging data, it is important to understand the implications in terms of costs for the Brazilian private healthcare system. Methods: A costing tool was developed to compare the sequencing costs of 1L → 2L regimens used for treatment of wild-type KRAS mCRC patients. Dosing schedules were derived from labels, clinical trials and expert opinion. Analysis was performed from a private payer perspective and included drug-acquisition and administration costs only. Sequences in the ML18147 study (1L bev 5mg/kg+FOLFOX → 2L bev 5mg/kg+FOLFIRI and 1L bev 5mg/kg+FOLFIRI→2L bev 5mg/kg+FOLFOX) were compared to another frequently used sequence in Brazil where bev is replaced by cetuximab(cet) in 1L (1L cet 400-250mg/m 2 + FOLFIRI → 2L bev 5 mg/Kg + FOLFOX). Results: Average costs per patient per month were Brz 21,285.50 for sequences with bev in 1L and 2L and Brz 24,191.68 when bev is replaced by cet in 1L. The average cost savings per patient for the entire treatment were Brz 28,767 (1L bev 5mg/kg + FOLFOX → 2L bev 5mg/kg + FOLFIRI vs 1L cet + FOLFIRI → 2L bev + FOLFOX) and Brz 29,938 (1L bev 5mg/kg + FOLFIRI → 2L bev 5mg/kg + FOLFOX vs1L cet + FOLFIRI → 2L bev + FOLFOX). Conclusions: Sequential use of bev in 1L and 2L mCRC according to the ML18147 study protocol is less costly compared to another sequence of biologics that starts with cet in 1L followed by bev in 2L. Resources savings with sequential bev have the potential to optimize 3L treatment strategy for wild-type kras mCRC patients in Brazil.
Expression of epidermal growth factor receptor (EGFR) associates with proliferation, apoptosis, and histologically aggressive features in hepatocellular carcinoma
Authors: S. Morinaga, Y. Nakamura, N. Sugano, K. Tsuchida, M. Shiozawa, Y. Miyagi, M. Akaike, Y. Sugimasa, S. Takemiya
Journal: Journal of Clinical Oncology (2006)

14039 Background: Epidermal growth factor receptor (EGFR) is over-expressed in many types of cancers, plays an important role in the tumorigenesis, and is indicated to be a promising target for cancer therapy. Hepatocellular carcinoma (HCC) is a cancer with one of the worst prognosis, and new therapeutic approaches are required. The aim of this study was to clarify a possible role of EGFR expression on clinico-pathology of HCC. Methods: HCC tissues were obtained from 36 HCC patients (23 men and 13 women, range 45–80 years old) who underwent curative surgery. EGFR status of the tumors was assessed by immunohistochemical (IHC) analysis on formalin-fixed paraffin-embedded tissue. The percentage of positive tumor cells was scored as follows: 0+, no positive tumor cells; 1+, 1–10% positive cells; 2+, 10–50% positive cells; 3+, &gt;50% positive cells. The staining intensity of membrane was evaluated as follows: 0+, negative; 1+, weak; 2+, moderate; 3+, strong. A composite score (EGFR score) was obtained by calculating the sum of these two scores. The tumor cell proliferation and apoptosis were assessed with Ki-67 labeling and ssDNA labeling, respectively. Results: EGFR expression was detected in 33 (91.7%) of 36 tumors. EGFR score ranged from 0 to 6. Higher EGFR score was related with poorer histologic grade (P = 0.005 by Kruskal-Wallis) and advanced pathologic stage (P = 0.038 by Kruskal-Wallis). EGFR score correlated positively with Ki-67 labeling indices (r = 0.358 and P = 0.032 by Spearman), and correlated negatively with apoptosis indices (r = −0.388 and P = 0.019 by Spearman). EGFR score did not affect disease free survival (DFS) or over all survival (OS), after curative surgery. Conclusions: Higher expression of EGFR, assessed with IHC, associates with more aggressive pathologic features, increased tumor cell proliferation, and reduced tumor cell apoptosis. However, further examination is needed to clarify its predictive significance. No significant financial relationships to disclose.
The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
Authors: Anna Karnkowska, Sebastian C Treitli, Ondřej Brzoň, Lukáš Novák, Vojtěch Vacek, Petr Soukal, Lael D Barlow, Emily K Herman, Shweta V Pipaliya, Tomáš Pánek, David Žihala, Romana Petrželková, Anzhelika Butenko, Laura Eme, Courtney W Stairs, Andrew J Roger, Marek Eliáš, Joel B Dacks, Vladimír Hampl
Journal: Molecular Biology and Evolution (2019)

Abstract The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less “reduced” than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe–S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
Automated home-based symptom monitoring coupled with centralized telecare management in a statewide trial involving rural and urban community-based oncology practices
Authors: D. E. Theobald, K. Kroenke, K. A. Iseminger, R. Sanders, K. Norton, S. McCalley, P. Harvey, D. Butler, W. M. Dugan, N. Bechar
Journal: Journal of Clinical Oncology (2007)

9089 Background: Pain and depression are two of the most prevalent and treatable cancer-related symptoms, each present in at least 20–30% of oncology patients. Therefore, we are conducting the NCI-funded Indiana Cancer Pain and Depression (INCPAD) study, a randomized clinical trial conducted in a statewide network of 13 community-based cancer clinics located in both rural and urban oncology practices. Methods: Patients are screened at the local clinics followed by telephone-based enrollment and informed consent, depression and pain care management, and serial research outcome assessments over a 12-month period. Patients randomized to the intervention complete automated home-based symptom monitoring by interactive voice-recorded phone calls or by internet on a tapering schedule (twice a week tapering to monthly), allowing a single nurse care manager to centrally monitor treatment of patients asynchronously and efficiently. Results: Of the first 1,612 patients screened for the trial, 820 (51%) screened positive for depression and/or pain. Of these screen-positive patients, 760 (93%) were successfully contacted by telephone, of whom 203 were ineligible (most often because of symptoms that did not reach severity thresholds), 299 refused, and 163 were enrolled. Reasons that patients refused included lack of interest in trial participation (n=176), the belief their symptoms were not cancer-related (n=35), too sick (n = 30), too busy (n = 21), or other reasons (n = 36). Conclusions: INCPAD demonstrates the feasibility of enrolling cancer patients from multiple geographically-dispersed practices and providing centralized symptom care management. The fact that two-thirds of eligible patients still refuse to participate in a relatively “low burden” trial focused on alleviating bothersome symptoms and conducted almost exclusively by telephone highlights the need for additional strategies to facilitate enrollment in cancer trials. In particular, specific approaches to overcome low enthusiasm for trial participation need to be developed. No significant financial relationships to disclose.
Influence of age on receipt of chemotherapy for adult Medicaid beneficiaries with metastatic colorectal cancer
Authors: H. D. Klepin, E. Y. Song, A. M. Geiger, J. A. Tooze, K. L. Foley
Journal: Journal of Clinical Oncology (2009)

9548 Background: Although advances in systemic treatment for metastatic colorectal cancer (CRC) have improved survival, it is unclear if this treatment is administered routinely among vulnerable individuals. Our objective was to describe treatment patterns for low income individuals with metastatic CRC and evaluate the influence of age on delivery of treatment in the context of patient, community, and health care setting characteristics. Methods: Matched North Carolina Cancer Registry and Medicaid claims data were used to identify a cohort of 390 patients with metastatic CRC diagnosed between 1999 and 2002. We assessed the relationship between treatment delivered within one year of diagnosis and characteristics of the patient (age, gender, race/ethnicity, comorbidity), community (percent poverty, percent rural), and health care setting (academic medical center, surgery volume). Treatment delivery was categorized into: 1) receipt of any chemotherapy, 2) local therapy only, and 3) no treatment. We fit a logistic regression model comparing receipt of any chemotherapy to local treatment only and another comparing receipt of any chemotherapy to no treatment. Results: Patients' mean age was 65.1±14.6 years; 56.0% were female and 45.5% were non-white. Only 27.7% received chemotherapy, while 50.3% received local therapy only and 22.0% received no treatment. After adjusting for comorbidity and all other covariates, patients aged &lt;75 years were more likely to receive chemotherapy than patients ≥75 (versus local treatment only, OR=3.2, 95% CI=1.7–6.1; versus no treatment, OR=3.9, 95% CI=1.9–8.3). Absence of significant comorbidity was associated with use of chemotherapy only when compared to those who received no treatment (OR=3.1, 95% CI=1.6–5.9). Race/ethnicity, community, and health care setting characteristics were not associated with treatment. Conclusions: Use of chemotherapy in this low income cohort was low compared to published reports in other populations. Younger age was the only characteristic in this analysis which was consistently associated with receipt of chemotherapy. These results suggest that older low income patients may represent a particularly vulnerable population with regard to treatment disparity. No significant financial relationships to disclose.
Risk of Venous Thrombotic Events (VTE) in Patients with Myelodysplastic Syndromes with 5q Deletion during Lenalidomide Therapy: Single Institution Experience
Authors: Omar Alkharabsheh, Darci Zblewski, Naseema Gangat, Kebede H. Begna, Michelle A. Elliott, Hassan B. Alkhateeb, Mrinal M. Patnaik, William J. Hogan, Mark R. Litzow, Aref Al-Kali
Journal: Blood (2017)
Body Mass Index Influences the Salutary Effects of Metformin on Survival After Lobectomy for Stage I NSCLC
Authors: Sai Yendamuri, Joseph Barbi, Sarabjot Pabla, Cara Petrucci, Achamaporn Punnanitinont, Mary Nesline, Sean T. Glenn, Paul Depietro, Antonios Papanicalou-Sengos, Carl Morrison, Grace K. Dy, Peter L. Elkin
Journal: Journal of Thoracic Oncology (2019)
The IgG-degrading enzyme of Streptococcus pyogenes causes rapid clearance of anti-glomerular basement membrane antibodies in patients with refractory anti-glomerular basement membrane disease
Authors: Inga Soveri, Johan Mölne, Fredrik Uhlin, Thomas Nilsson, Christian Kjellman, Elisabeth Sonesson, Mårten Segelmark
Journal: Kidney International (2019)
Temozolomide (TMZ) in combination with pegylated interferon alfa-2b for stage IV metastatic melanoma: A multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)
Authors: K. Spieth, R. Dummer, U. Leiter, C. Garbe, J. Gille, J. C. Becker, A. Hauschild, W. Tilgen, R. Kaufmann, D. Schadendorf
Journal: Journal of Clinical Oncology (2006)

8017 Background: Modifying the pharmacokinetic profile of IFN alfa-2b (PegIFN) may improve its activity and tolerability. Specifically, the conjugation of recombinant IFN alfa-2b with a 12 kDa polyethylene glycol (Peg) chain results in a prolonged half-life and has been previously demonstrated to increase efficacy in hepatitis C patients compared to nonpegylated IFNs. We therefore evaluated the combination of TMZ with PegIFN in stage IV metastatic melanoma. Methods: This open-label, phase II study was conducted by the DeCOG at 10 study sites. Eligible pts were between 18 and 75 yrs, had a histologically confirmed diagnosis of metastatic melanoma (stage IV AJCC), no brain metastases and no prior chemotherapy. Pts were required to have a Karnofsky score of &gt; 60% as well as adequate renal, liver and bone marrow function. Informed consent from all participants and approval from the corresponding ethic committees was provided. The regimen (28 d cycles) consisted of TMZ (200 mg/m 2 d 1–5) in combination with PegIFN (100 μg sc d 1, 8, 15 and 21). Patients received 2 cycles before reevaluation (WHO response criteria). OR and OS were primary and TTP and toxicity were secondary endpoints of the trial. Results: 124 pts were accrued between 10/02 and 7/04, 8 pts were ineligible or withdrew consent, and thus 116 pts were treated per protocol. At the time of data analysis, 81.0% of pts had died from melanoma and median follow up time was 9.4 months. OR was 18.1% (2 CR, 1.7%; 16 PR; 16.4%); 25.0% of pts presented with SD and 54.3 % progressed (2.6% not evaluable). Median TTP was 2.8 months, median OS 9.0 months (95% CI 7,4;10,6). Grade (gr) 3/4 leucopenia occurred in 22.8% and gr 3/4 thrombocytopenia in 20.3%. Gr 1/2 nausea and emesis experienced 37.5% of the pts; severe nausea (gr 3/4) was rare (1.7%). Liver enzyme elevation occurred in 30.5 % (26.3% gr 1/2; 4.2% gr 3). Conclusions: Combination therapy with TMZ and pegylated interferon alfa-2b constitutes a manageable treatment option in the outpatient setting for advanced metastatic melanoma. Its primary advantage is an increased patient convenience as a result of oral intake of TMZ and once weekly application of PegIFN. [Table: see text]
Nodal positivity between &lt;12 and &gt;12 lymph nodes harvested in colorectal cancer undergoing SLNM compared with conventional surgery
Authors: D. Wiese, M. Soni, A. Gayer, A. Korant, S. Sirop, B. Chakravaty, S. Arora, D. Iddings, S. Saha
Journal: Journal of Clinical Oncology (2009)

4048 Background: Sentinel Lymph Node Mapping (SLNM) upstages significantly more patients (pts) than conventional surgery (Conv Sx) in Colon Cancer (CCa). According to current guidelines, the examination of 12 or more LNs are required to ensure accurate staging. Our study compares the rates of nodal positivity between differing numbers of total Lymph Nodes (LNs) harvested to see if the nodal positivity of &lt;12 LN harvested by SLNM is equivalent to &gt;12 LN obtained by Conv Sx. Methods: Of 951 pts with CCa, 545 pts underwent SLNM and standard oncological resection; 406 pts received Conv Sx without SLNM. The total number of LNs harvested for each pt as well as number of pts with metastatic LNs were recorded. Pts were grouped according to 2–11 LNs, 12–25 LNs and &gt;25 LNs. Results: Of 951 pts, 81 pts in SLNM group and 6 in Conv Sx group were excluded due to benign disease. Average (avg) total nodes harvested in 2–11 node group for SLNM and Conv Sx was 7.9 vs 6.8 nodes respectively. Overall nodal positivity for SLNM pts and Conv Sx pts in the 2–11 node groups was 48% vs. 33% (p=.02). In the 12–25 node group, avg total number of LNs harvested was 17.23 and 16.32 respectively. In the 12–25 node group, 53% of pts in the SLNM arm had +ve nodes vs 44% (p=0.17) in the Conv Sx group. In pts with &gt;25 nodes harvested avg nodal positivity was 33.78% vs 32.38% for SLNM and Conv Sx. Overall nodal positivity was 55% for SLNM vs 37% for Conv Sx group. When SLNM pts with 2–11 LN harvested were compared to Conv Sx pts with 12–25 LN harvested, nodal positivity was 48% vs 44% (p=0.55). Conclusions: Increased survival has been shown when &gt;12 nodes are harvested in CCa. On avg SLNM identified a higher number of total nodes than conventional surgery. In addition, SLNM pts had higher nodal positivity with &lt;12 LNs harvested compared to the nodal positivity of &gt;12 nodes harvested in the Conv Sx group. A higher number of LN harvested coupled with a greater nodal positivity with less LNs make SLNM a more accurate way to stage CCa. [Table: see text] No significant financial relationships to disclose.