tbuckley/cabot-search huggingface dataset:
Genomic history of the origin and domestication of common bean unveils its closest sister species
Authors: Martha Rendón-Anaya, Josaphat M. Montero-Vargas, Soledad Saburido-Álvarez, Anna Vlasova, Salvador Capella-Gutierrez, José Juan Ordaz-Ortiz, O. Mario Aguilar, Rosana P. Vianello-Brondani, Marta Santalla, Luis Delaye, Toni Gabaldón, Paul Gepts, Robert Winkler, Roderic Guigó, Alfonso Delgado-Salinas, Alfredo Herrera-Estrella
Journal: Genome biology (2017)

Modern civilization depends on only a few plant species for its nourishment. These crops were derived via several thousands of years of human selection that transformed wild ancestors into high-yielding domesticated descendants. Among cultivated plants, common bean (Phaseolus vulgaris L.) is the most important grain legume. Yet, our understanding of the origins and concurrent shaping of the genome of this crop plant is limited. We sequenced the genomes of 29 accessions representing 12 Phaseolus species. Single nucleotide polymorphism-based phylogenomic analyses, using both the nuclear and chloroplast genomes, allowed us to detect a speciation event, a finding further supported by metabolite profiling. In addition, we identified ~1200 protein coding genes (PCGs) and ~100 long non-coding RNAs with domestication-associated haplotypes. Finally, we describe asymmetric introgression events occurring among common bean subpopulations in Mesoamerica and across hemispheres. We uncover an unpredicted speciation event in the tropical Andes that gave rise to a sibling species, formerly considered the “wild ancestor” of P. vulgaris, which diverged before the split of the Mesoamerican and Andean P. vulgaris gene pools. Further, we identify haplotypes strongly associated with genes underlying the emergence of domestication traits. Our findings also reveal the capacity of a predominantly autogamous plant to outcross and fix loci from different populations, even from distant species, which led to the acquisition by domesticated beans of adaptive traits from wild relatives. The occurrence of such adaptive introgressions should be exploited to accelerate breeding programs in the near future.
Analysis of the prognostic impact of Treg-related genes in tumor and stroma in resectable NSCLC.
Authors: Marta Usó, Eloisa Jantus-Lewintre, Rafael Sirera, Sandra Gallach, Ana Blasco, Nieves Martinez, Cristina Hernando, Ricardo Guijarro, Carlos Camps
Journal: Journal of Clinical Oncology (2013)

11073 Background: Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed the expression of 11 genes related to Tregs in both tumor and stroma samples of resectable NSCLC patients. Methods: Primary tumor tissues of FFPE samples from 125 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a as well as CD4 and CD8. Relative gene expression was assessed using GAPDH and CDKN1B as endogenous controls and results were normalized against a human cDNA (Clontech) as a reference. All statistical analyses were considered significant at p&lt; 0.05. Results: In both tumor and stroma, we found over-expression of CD25 (5.40X and 7.95X, respectively) and down-expression of CD127 (0.28X and 0.37X, respectively). There was a tendency toward higher expression of FOXP3 (1.67X and 2.01X, respectively) and CTLA-4 (1.92X and 1.76X, respectively) as well. Paired Wilcoxon test showed significant gene expression differences between tumor and stroma in FOXP3 (p=0.006), CD25 (p&lt;0.0001), CD4 (p&lt;0.0001), CD8 (p=0.028), IL-10 (p&lt;0.0001) and TGFB-1 (p&lt;0.0001). Kruskal-Wallis test showed that FOXP3 expression was higher in adenocarcinoma than in SCC samples (2.56X vs 1.79X, p=0.002). Survival analyses revealed that patients with a “Treg profile” (↑CD25 and ↓CD127) had a reduced overall survival (OS) (median 29.90 vs 74.33 months, p=0.003). We also found that those patients with higher levels of the ratio FOXP3 stroma/tumor had worse time to progression (TTP) (median 32.50 vs NR, p=0.04). Conclusions: Treg markers in the tumor microenvironment seem to play an important prognostic role in early-stage NSCLC patients. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII.
Impact of sarcopenia on survival outcomes in patients (pts) with metastatic gastric cancer (mGC).
Authors: Keiji Sugiyama, Yukiya Narita, Seiichiro Mitani, Kazunori Honda, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Takashi Ura, Masashi Ando, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2017)

141 Background: Sarcopenia is a poor prognostic factor in several cancers. This study aimed to assess the predictive value of sarcopenia on survival outcomes among pts with mGC. Methods: We retrospectively analyzed 170 consecutive pts with mGC starting first-line chemotherapy at the single institution during January 2013–December 2014. Inclusion criteria were as follows: treatment with fluoropyrimidine plus platinum-based regimen, ECOG PS 0–2, and adequate organ function. Skeletal muscle index (SMI) was calculated from cross-sectional area of muscle at L3 using CT scan divided by the square of the height. Baseline sarcopenia (S) was defined as 53.4 cm 2 /m 2 for men and 38.5 cm 2 /m 2 for women. Muscle loss after chemotherapy (L) was defined as 10% ≤ reduction in SMI. Univariate and multivariate analyses were conducted to identify whether S and L were independent prognostic factors of time to treatment failure (TTF) and overall survival (OS). Multivariate analysis included variables with p values ≤ 0.1 in univariate analyses. Results: Ninety-seven pts met the inclusion criteria; 83 (86%) were classified with S, and 39 (31%) with L. PS (0 vs. 1 and 2) and ALP (ULN&gt; vs. ULN≤) were significantly associated with L. Overall response rate for S, non-S, L, and non-L was 60%, 63%, 63%, and 61%, respectively. S was not associated with TTF or OS. However, L was significantly associated with a shorter TTF (4.7 vs. 7.3 m, HR=1.82; 95% CI: 1.16-2.85, p=0.009) and tended toward worse OS (14.2 vs. 19.7 m, HR=1.31; 95% CI: 0.78-2.20, p=0.29). Variables with p values ≤ 0.1 in univariate analyses for TTF were L, LDH (ULN≤), ALB (ULN&gt;), and histology (poorly differentiated). Histology was only variables with p values ≤ 0.1 for OS (p=0.002). As per multivariate analyses, only L was a significant prognostic factor of TTF. Conclusions: L is an independent negative prognostic factor of TTF in pts with mGC. Intervention for muscle loss can be a therapeutic approach for mGC. [Table: see text]
Five-year overall survival among patients with metastatic renal cell carcinoma: Results of Russian population-based study RENSUR5.
Authors: Ilya Tsimafeyeu, Tatiana Zolotareva, Sergey Varlamov, Ruslan Zukov, Liubov Yu Vladimirova, Vladislav Petkau, Mikhail Mazhbich, Galina Statsenko, Sufia Safina, Igor Zaitsev, Dina Sakaeva, Alexander Popov, Pavel Borisov
Journal: Journal of Clinical Oncology (2017)

20 Background: The results of the 5-year overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) has been reported rarely. The aim of the RENSUR5 registry study was to obtain real-world data on the use of therapies in mRCC and assess 5-year OS in Russian population. Methods: Patients were retrospectively identified at 11 cancer centers in different regions of Russia (Astrakhan, Barnaul, Ekaterinburg, Kazan, Krasnoyarsk, Obninsk, Omsk, Rostov-on-Don, Samara, St.Petersburg, Ufa). Patients were included if mRCC was diagnosed from January 2010 to January 2011. Anonymised data were collected through an online registry covering demographics, treatments and outcomes. Results: 439 adult mRCC patients were included in the study for analysis. Mean age at diagnosis of mRCC was 60.9 (33-90) years (with 9% of patients aged 3 75 years). Patients were predominantly male (70.2%), 67.7% had nephrectomy; clear-cell and non-clear cell tumors were detected in 61.1% and 7.7% of patients, respectively. 271 (62%) patients received systemic therapy. Median duration of therapy was 11 months (95% CI 9.5-12.5). The majority of treatment was with interferon only (n=145). 105 (23.9%) patients were treated with targeted therapy. 69 (15.7%) patients received 3 2 treatment lines. Survival outcomes are listed in Table. Conclusions: RENSUR5 is a large 'real-world' database assessing mRCC treatment patterns and 5-year OS in Russia. Based on results of this study, we assume that 5-year OS is poor and should be improved on novel therapies. [Table: see text]
Natural history of malignant bone disease in non-small cell lung cancer: Preliminary results of a multicenter bone metastasis survey.
Authors: Daniele Santini, Salvatore Intagliata, Toni Ibrahim, Francesco Ferraù, Sandro Barni, Luca I. Moscetti, Giovanni Mansueto, Francesca Comito, Francesco Pantano, Flavia Longo, Antonio Russo, MAntonietta Satolli, Vincenzo Adamo, Nicla Maria La Verde, Giuseppe Badalamenti, Davide Ottaviani, Antonella Ferzi, Raffaele Addeo, Enrico Vasile, Giuseppe Tonini
Journal: Journal of Clinical Oncology (2013)

e19084 Background: Bone metastases represent an increasing clinical problem in advanced non-small cell lung cancer (NSCLC) as disease-related survival improves. This is a multicenter, retrospective survey aimed to explore the impact of bone involvement in this severe, life-threatening disease. Methods: Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 421 deceased NSCLC patients (48.6% aged &gt;66 years) with evidence of bone metastasis were statistically analyzed. Results: ECOG performance status at diagnosis of NSCLC was 0 in 41.4% of patients, 1 in 42.8% and 2 in 13.9%. The most frequent stage at diagnosis was IV (76.8%). Adenocarcinoma was the commonest histotype (70.3%) and EGFR status was unknown in 77.7%. Chemotherapy was the preferred I line treatment in 82.2%. Lung cancer frequently spreaded to bone, with metastases evident at diagnosis in up to 57.2% of patients. In the remaining cases median time to bone metastases was 9 months. Patients ECOG performance status when bone metastases were detected was 1 in 46.6% and 2 in 22.9%. In our sample multiple bone metastases were detected in 82.5% of patients and 71.2% were osteolitic. Axial skeleton was interested in 74.6% of cases, pelvic bones in 46.7% and limb bones in 29.3%. Bone metastases related pain was reported by 84% of patients. Median Verbal Numerical Rating Scale (VNRS) for pain was 4 and it measured &gt;4 in 47.2% of cases. Bisphosphonates was administered in 65.6% of patients; zoledronic acid was mainly used (61.1%). Osteonecrosis of the jaw was reported in only 1.1 % of cases. Median number of SREs/patient was one, less than half of the patients (41.7%) experienced at least one SRE, 21.2% experienced at least two SREs, and only 2.1% experienced at least three SREs. The most common SRE was the need of radiotherapy (73.8%). Median time to first SRE was 3 months. Median survival after bone metastases diagnosis was 8 months and after first SRE was 6 months. Conclusions: These preliminary data suggest that bone metastases are a relevant clinical event in the natural history of patients affected by NSCLC. Final results will be available next ASCO meeting.
Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.
Authors: Joseph Sung, Kelvin Kf Tsoi
Journal: Journal of Clinical Oncology (2017)

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]
Ex vivo expansion of CTCs in culture isolated by size from patients with melanoma.
Authors: Naoual Benali-Furet, Janine Wechsler, Fei Ye, Sarah Ezaoui, Marie-Françoise Avril, Francoise Boitier, Agnes Carlotti, Isbou Paraiso, Yvon E Cayre
Journal: Journal of Clinical Oncology (2012)

e21046 Background: To date there are no studies demonstrating the ability of circulating tumor cells (CTCs) isolated from patients to grow ex-vivo in culture. Most of our knowledge on the mechanisms of cancer metastasis has been obtained from CTCs of mouse models. In human, a main issue for studying circulating melanoma cells subpopulations and constructing tumor models is to be able to grow CTCs from patients. Here we defined optimized conditions to isolate CTCs alive and to culture them using the ScreenCell technology. Methods: CTCs were isolated alive by size using a ScreenCell device from 6 ml blood of 11 patients with melanoma at diagnosis and before surgical excision. Cells were cultured directly on a porous and high adhesion filter with optimized culture conditions. The filter was also used as a crossing barrier for cell invasion assay. After 15 days culture, cells were fixed and immunohistochemically stained for proliferative, hypoxia and invasive phenotype markers. Results: After 5 daysunder specific culture conditions, CTCs were adherent to the filter with several shapes and size in all patients, while no cells were found in blood of healthy donors. After proximately 10 days in culture, a population of small cells started to growth while a subpopulation of large cells migrated through the pores of the filter to form spheroids into the Matrigel ® located under the filter. After 15 days in culture the non-invasive and invasive cells were positively immunostained for expression of the Melan-A proliferative phenotype marker and for the Glut-1 and Wnt5A hypoxia and invasive phenotype markers, respectively. In parallel, the corresponding primary melanoma lesions were immunostained and compared to immunostaining data of CTCs. Conclusions: TheScreenCell technology preserves the viability, proliferative and invasion potentials of CTCs. Furthermore, CTCs can be maintained in culture allowing ex vivo expansion and characterization of subpopulations of CTCs with proliferative and invasive characteristics. Using the ScreenCell devices we have defined optimal technical and microenvironment conditions for CTCs isolation and culture. We are currently exploring the ability of CTCs to xenoengraft and develop tumor in immunocompromized mice.
Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients with induced immune responses and a prolonged OS.
Authors: Yoshihiro Yoshitake, Daiki Fukuma, Akira Yuno, Masatoshi Hirayama, Hideki Nakayama, Takuya Tanaka, Masashi Nagata, Kenta Kawahara, Yoshihiro Nakagawa, Ryoji Yoshida, Hidenao Ogi, Akimitsu Hiraki, Hirofumi Jono, Akinobu Hamada, Koji Yoshida, Takuya Tsunoda, Yasuharu Nishimura, Yusuke Nakamura, Masanori Shinohara
Journal: Journal of Clinical Oncology (2014)

3094 Background: The peptides derived from ideal cancer-testis antigens, including LY6K, CDCA1 and IMP3 (identified using genome-wide cDNA microarray analyses), were utilized in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy. Methods: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS and immunological response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated based on differences between HLA-A*2402-positive (A24(+)) patients treated with peptide vaccine therapy and –negative (A24(-)) patients treated without peptide vaccine therapy among those with advanced HNSCC. Results: Our cancer vaccine therapy was well tolerated. The OS of the A24(+)vaccinated group (n = 37) was statistically significantly longer than that of the A24(-) group (n=18) (MST 4.9 vs. 3.5 month, respectively, p<0.05). One of the patients exhibited a complete response. In the A24(+) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1- and IMP3-specific CTL responses in 85.7%, 64.3% and 42.9% of the patients, respectively. The patients showing LY6K- and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses. Conclusions: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC. Clinical trial information: 000008379.
Safety and tolerability in patients over age 75 included in phase I: The Institut Gustave Roussy experience.
Authors: Carole Helissey, Florian Roquet, Emilie Lanoy, Andrea Varga, Christophe Massard, Anas Gazzah, Vincent Ribrag, Rastislav Bahleda, Eric Angevin, Eric Deutsch, Jean-Charles Soria, Antoine Hollebecque
Journal: Journal of Clinical Oncology (2013)

9556 Background: Safety and tolerability of anti-cancer therapy in elderly people (&gt;=75 years, EP) is of major interest since they represent 31% of US patients diagnosed with cancer. However proportion of EP recruited is only 9% in clinical trials and probably less in phase I trials, which aim to determine the recommended phase II dose. Our objective was to evaluate the safety of phase I trials in EP. Methods: Patients treated from 2007 to 2012 at Institut Gustave Roussy in phase I trials, in which patients aged over 75 years had been included. Population was divided into two groups: EP or patients aged &lt; 75 years (YP). Time to occurrence of first high toxicity (any grade 3-4 adverse event (AE) or dose-limiting toxicity DLT) and overall survival were estimated using Kaplan-Meier method. Conditional Cox proportional hazards model was used to compare occurrence of AE in a sub population of patients aged &gt;= 75 years matched with patients aged &lt;75 years of same Royal Marsden Hospital (RMH) score (Albumin, LDH, Number of metastatic site) and protocol. Results: In the 33 EP and the 161 YP, 20(60%) and 100(62%) grade 3-4 AEs and 1(3%) and 18(11%) DLTs occurred. The median time to occurrence of high toxicity were 2 months (95%CI=1-4) and 2 months (95%CI=1-2). The median overall survival were 22 months (95%CI=11-non estimable) (EP) and 13 months (95%CI =10-16) (YP). Twenty-seven patients aged &gt;=75 years could be matched: age over 75 years was not associated with higher risk of neither high toxicity (HR=0.85, 95%CI=[0.45 ; 1.61], p=.62) nor death (HR=1.03, 95%CI=[0.47;2.24], p=.94). Conclusions: No impact of age over 75 years on occurrence of neither high toxicity nor death was identified. Patients above 75 years are good candidates for phase I trials.
Meat and fish consumption and risk of colorectal adenomas in Korea.
Authors: Sun Young Yang, Eun Young Doo, Young Sun Kim, Jung Eun Lee, Jiyoung Youn, Ji Hyun Song, Jeong Yoon Yim, Sun Hee Lim
Journal: Journal of Clinical Oncology (2017)

559 Background: Consumption of red meat and alcohol are known risk factors for colorectal cancer. Colorectal adenomas are considered precursors to colorectal cancer through adenoma-carcinoma sequence. The identification of modifiable risk factors for colorectal adenoma contributes to prevent colorectal cancer from progressing. Many studies have suggested that high red meat or processed meat intake is associated with an increased risk of colorectal adenoma. However, the effect of high fish intake on colorectal adenoma has been insufficient in epidemiological studies. The aim of this study is examine the relationship between meat and fish intake and the risk of colorectal adenoma. Methods: The study enrolled participants who visited Seoul National University Hospital Healthcare System Gangnam Center from May to December, 2011. All participants underwent screening colonoscopy and completed validated food frequency questionnaire. The study sample included 414 adenoma patients, 142 advanced adenoma patients and 1160 polyp-free controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat and fish and colorectal adenoma using multivariate logistic regression. Results: The intake of total meat, red meat, poultry or processed meat showed no clear association with risk of colorectal adenoma or advanced adenoma. A significant negative association between fish intake and risk of advanced adenoma (OR = 0.51, 95% CI = 0.27 – 0.95, p for trend = 0.0281) after adjusting for confounders such as age, BMI, family history of colorectal cancer, alcohol consumption, smoking status, diabetes, total energy intake, fiber, vegetable/fruit and red meat intake. Conclusions: In conclusion, this study showed no clear relationship between the incidence of colorectal adenoma/advanced adenoma and meat intake. Although, high fish intake and incidence of advanced adenoma showed a significant inverse association in Korean.