tbuckley/cabot-search huggingface dataset:
Molecularly annotation of mouse avatar models derived from patients with colorectal cancer liver metastasis
Authors: Jingyuan Wang, Baocai Xing, Wei Liu, Jian Li, Xicheng Wang, Juan Li, Jing Yang, Congcong Ji, Zhongwu Li, Bin Dong, Jing Gao, Lin Shen
Journal: Theranostics (2019)

Background: Liver is the most common metastatic site in advanced colorectal cancer. Most patients with colorectal cancer liver metastasis (CRLM) do not benefit from current treatment. Patient-derived xenografts (PDXs) with defined molecular signatures are attractive models for preclinical studies. Methods: Successfully established PDXs were evaluated to elucidate their fidelity of patients' biologic characteristics (pathologic, genetic and protein properties, together with chemosensitivity). The genomic variations of PDXs were analyzed by next-generation sequencing to explore the underlying molecular mechanism of metastasis and potential therapeutic targets. Results: CRLM (N=73) showed a significantly higher successful PDX establishment rate than primary specimens (N=26; 76.7% vs. 57.7%). CRLM PDXs recapitulated the pathologic, genetic and protein properties of parental tumors, as well as chemosensitivity. Frequent altered genes in PDXs showed high consistency compared to patients' genomic alterations and were enriched in MAPK, ErbB, cell cycle, focal adhesion pathways for CRLM PDXs, whereas primary tumor-derived PDXs only exhibited genomic variations involving ErbB and cell cycle. The genetic alterations showed high concordance between paired PDXs from primary and metastatic tissues, except for recurrent gene mutations (ARID1A, CDK8, ETV1, STAT5B and WNK3) and common copy number gains in chromosomes 20q (e.g., SRC/AURKA). Several potential drug targets such as KRAS, HER2, and FGFR2 were validated using corresponding inhibitors. Additionally, PDX models could also be used in screening efficient regimens for patients with no druggable alterations. Conclusion: This study has successfully established and validated a large panel of molecularly annotated platforms from patients with CRLM for preclinical studies.
The management of dysphagia in esophageal adenocarcinoma patients undergoing neoadjuvant chemotherapy: Can invasive tube feeding be avoided?
Authors: Jonathan Cools-Lartigue, Daniel Jones, Taline Zourikian, Mathieu Rousseau, Jonathan Spicer, Eleanor Eckert, Thierry Alcindor, Lorenzo Ferri
Journal: Journal of Clinical Oncology (2013)

e15034 Background: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophago-gastric adenocarcinoma. However the dysphagia frequently associated with this condition may interfere with patient tolerance of neoadjuvant chemotherapy. Surgical or endoscopic invasive tube feeding (ITF), including stents, is a commonly employed strategy to maintain nutritional support however it can cause significant morbidity in its own right. We sought to determine if an approach of careful dietary counseling and fast-tracked neoadjuvant chemotherapy can obviate the need for ITF. Methods: Pts undergoing neoadjuvant chemotherapy (DCF or ECF Q3 weeks x3 or FLOT Q2weeks x4) for locally advanced (cT3 and/or N+) esophageal or EGJ adenocarcinoma at a single institution from 3/07-9/12 were identified from a prospective database. All received dietary counseling and were closely monitored for signs/ symptoms of malnutrition with serial (baseline/pre-surgery) Body Mass Index (BMI), albumin, dysphagia scores (DS: 0 best - 4 worse), and quality of life (FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant treatment and the need for ITF. Data presented as median (Interquartile Range) or median (±SD), paired t-test or Wilcoxon signed ranks test determined significance (*p=0.05). Results: Of 130 patients undergoing neoadjuvant chemotherapy 78 had dysphagia scores of 2 or greater, most of whom received DCF (91%). Overall the dysphagia improved in 75/78 (96%) from a DS of 3 (2-4) to 0 (0-1)*. This was associated with an increase in FACT-E QoL scores (117±23 to 140±20)*. Weight (Kg)(70±22:69±24), BMI (24.5±8 to 23.9±7), and Albumin (40±5 to 37±4) were maintained. Only one patient required a stent, and none a jejunostomy, or gastrostomy. Conclusions: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for stenting or invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.
Abstract #5332: Adiponectin-mediated inhibition of metastatic properties of breast cancer cells involves upregulation of tumor suppressor gene, LKB1 and modulation of AMPK-S6K axis.
Authors: LaTonia Taliaferro-Smith, Arumugam Nagalingam, Diansheng Zhong, Wei Zhou, Brandi Knight, Elaine Oberlick, Neeraj Saxena, Dipali Sharma
Journal: Cancer Research (2009)

Adiponectin is one of the most important adipocytokines secreted from adipose tissue. It is widely known as an adipocytokine with therapeutic potential for its markedly protective role in the pathogenesis of obesity-related disorders, metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Several recent clinical studies have reported that low serum levels of adiponectin are associated with increased risk and a more aggressive phenotype (large size of tumor and increased metastasis) of breast cancer but the complex underlying molecular mechanisms have remained largely unknown. In the present study, we investigated the molecular mechanisms by which adiponectin inhibits metastatic properties of breast cancer cells. Our results showed that adiponectin efficiently inhibited growth and migration potential of breast cancer cells. Further analysis revealed that adiponectin treatment increased AMP-activated protein kinase (AMPK) phosphorylation and activity as evident by increased phosphorylation of downstream target of AMPK, Acetyl CoA Carboxylase (ACC). Upregulation of AMPK in response to adiponectin treatment also resulted in inhibition of mTOR activity. Intriguingly, we discovered that adiponectin up-regulates the expression of tumor suppressor gene, LKB1 in breast cancer cells. Overexpression of LKB1 in breast cancer cells further increased adiponectin-mediated phosphorylation of AMPK. Using isogenic LKB1 knockdown cell line pair, we found that LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, inhibition of metastatic properties of breast cancer cells. Taken together these data suggest a novel mechanism involving LKB1-AMPK-S6K axis by which adiponectin inhibits growth and migration of breast cancer cells. Our findings indicate the possibility of using adiponectin analogues to inhibit the metastatic properties of breast cancer cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5332.
Paradoxical effects of medical reassurance in patients with breast cancer
Authors: C. G. Shields, K. Corbin, M. Weiss, D. M. Lambert, J. J. Griggs
Journal: Journal of Clinical Oncology (2007)

11018 Objective: The purpose of this study was to investigate the impact of medical reassurance on distress and fear of recurrence in women with ductal carcinoma in situ (DCIS) and early stage invasive breast cancer. Methods: We conducted an anonymous survey on the website of breastcancer.org, a non-profit organization. Recruitment to the survey was through a general invitation to “Tell us about your breast cancer experience.” The survey inquired about disease and treatment characteristics and contained the Positive and Negative Affect Scale (PANAS) and the Concerns about Recurrence Scale. Participants were also asked if they had been told by any of their medical providers that they had a “good cancer,” “favorable cancer,” or “better kind of cancer.” Analyses were performed to investigate the impact that being told one has or had a “good cancer” and feelings of reassurance, isolation, distress, and guilt. Results: A total of 362 participants with breast cancer completed the survey, 143 of whom had DCIS. Of these, 147 (41%) reported having been told that they had a “good cancer” by one or more of their medical providers, most often by their surgeon (83%) and/or their medical oncologist (61%). Among those told they had a good cancer, 67% reported that being told this led to their feeling moderately-to-extremely “reassured.” Many respondents, however, also reported moderate-to-severe negative responses to being told that they had a good or favorable cancer_feeling “isolated” (38%), “distressed” (43%), “scared” (61%), and “guilty” (30%). Conclusions: Although telling patients they have a “good” or “favorable” cancer leads to feelings of being reassured in the majority of women, such terms may also contribute to distress, feelings of isolation, and guilt among many patients who otherwise might enjoy a good prognosis quality of life. Providing reassurance is a complex process. Further research into effective ways of communicating reassurance is warranted in order to minimize distress and enhance quality of life. No significant financial relationships to disclose.
Abstract #2510: Gamma-tocotrienol, a vitamin E isomer from palm oil, suppresses prostate cancer cell growth through multiple signaling pathways
Authors: Y. Wong, Wei Yap, Piek Chang, M Ling, Yee Yap
Journal: Cancer Research (2009)

It has been demonstrated that tocotrienol-rich-fraction (TRF) from palm oil has suppressive effect on proliferation of prostate cancer (PCa) cells. To examine this anti-proliferative effect on PCa cells, this study targeted on two aspects. First, to identify the most potent isomer against PCa cells and second, to examine the molecular mechanisms involved. The studies showed that the inhibitory effect of gamma-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of pro-caspases and the presence of sub-G1 cell population. To confirm this, we examined the effects of gamma-tocotrienol on the activities of several pro-survival genes. The results revealed that the tocotrienol-induced cell death was associated with suppression of NF-\#954;B, EGF-R and Id family proteins (Id1 and Id3). Gamma-tocotrienol treatment also resulted in the induction of JNK signaling pathway while inhibition of JNK activity by specific inhibitor (SP600125) was able to partially block the effect of gamma-tocotrienol. In the meantime, gamma-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and gamma-catenin expression together with the suppression of cell invasion capability of PCa cells. Furthermore, a synergistic effect was observed when PCa cells were treated with a combination of gamma-tocotrienol and Docetaxel, the only chemotherapeutic drug which has been shown to have effect on hormone refractory prostate cancer. These results suggested that the gamma-tocotrienol suppresses cell proliferation and invasion ability of PCa cells through multiple signaling pathways. The study further suggested that tocotrienol could act synergistically with Docetaxel to suppress the growth of PCa cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2510.
Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council
Authors: Bruce Strober, Caitriona Ryan, Peter van de Kerkhof, Joelle van der Walt, Alexa B. Kimball, Jonathan Barker, Andrew Blauvelt, Marc Bourcier, Andre Carvalho, Arnon Cohen, Peter Foley, Colby Evans, Paolo Gisondi, Chris Griffiths, Mahira Hamdy El-Sayed, Cristina Eschevarria, Andrew Finlay, Robert Kalb, Craig Leonardi, Chuck Lynde, Ruth Murphy, Masamoto Murakami, Yukari Okubo, Errol Prens, Lluís Puig, Marieke Seyger, Lone Skov, Tadashi Terui, Fernando Valenzuela, Nicole Ward, Jashin Wu, Min Zheng
Journal: Journal of the American Academy of Dermatology (2019)

Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well as to determine eligibility criteria for clinical studies. However, owing to the heterogeneity of severity classifications and their lack of consideration for the impact of psoriasis involvement of special areas or past treatment history, patients may be miscategorized, which can lead to undertreatment of psoriasis.To develop a consensus statement on the classification of psoriasis severity.A modified Delphi approach was developed by the International Psoriasis Council to define psoriasis severity.After completion of the exercise, 7 severity definitions were preferentially ranked. This most preferred statement rejects the mild, moderate, and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: (1) body surface area >10%, (2) disease involving special areas, and (3) failure of topical therapy.This effort might have suffered from a lack of representation by all relevant stakeholders, including patients.The consensus statement describes 2 categories of psoriasis severity, while accounting for special circumstances where patients may require systemic therapy.
Latin American consensus on the supportive management of patients with severe combined immunodeficiency
Authors: Juan Carlos Bustamante Ogando, Armando Partida Gaytán, Juan Carlos Aldave Becerra, Aristóteles Álvarez Cardona, Liliana Bezrodnik, Arturo Borzutzky, Lizbeth Blancas Galicia, Diana Cabanillas, Antonio Condino-Neto, Agustín De Colsa Ranero, Sara Espinosa Padilla, Juliana Folloni Fernandes, Jorge Alberto García Campos, Héctor Gómez Tello, María Edith González Serrano, Alonso Gutiérrez Hernández, Víctor Manuel Hernández Bautista, Gabriele Ivankovich Escoto, Alejandra King, Juliana Lessa Mazzucchelli, Beatriz Adriana Llamas Guillén, Saul Oswaldo Lugo Reyes, Sarbelio Moreno Espinosa, Matías Oleastro, Francisco Otero Mendoza, María Cecilia Poli Harlowe, Oscar Porras, Nideshda Ramirez Uribe, Lorean Regairaz, Francisco Rivas Larrauri, Federico José Saracho Weber, Anete S. Grumach, Tamara Staines Boone, Beatriz Tavares Costa-Carvalho, Marco Antonio Yamazaki Nakashimada, Francisco Javier Espinosa Rosales
Journal: Journal of Allergy and Clinical Immunology (2019)
Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-ofseason results
Authors: R Pebody, F Warburton, J Ellis, N Andrews, A Potts, S Cottrell, J Johnston, A Reynolds, R Gunson, C Thompson, M Galiano, C Robertson, R Byford, N Gallagher, M Sinnathamby, I Yonova, S Pathirannehelage, M Donati, C Moore, S de Lusignan, J McMenamin, M Zambon
Journal: Eurosurveillance (2016)

© 2016 Eurosurveillance. All right reserved. The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season’s adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.
Novel prognosis prediction model for human breast cancer patients based on a heterologous tissue culture gene expression signature
Authors: Eun Sung Park, Ju-Seog Lee, Hyun Goo Woo, Fenghuang Zhan, Joanna Shih, John Shaughnessy, J. Mushinski
Journal: Cancer Research (2007)

2706  Patients with cancer have highly variable clinical outcomes owing to many factors, among which are genes that determine the likelihood of invasion and metastasis. This genetic predisposition may be reflected in the gene expression pattern of the primary tumor, which has the potential to predict outcomes and guide the choice of treatment better than traditional clinical predictors. We developed an mRNA expression-based model that can predict prognosis/outcomes of human breast cancer patients regardless of microarray platform and patient group. Our model was developed using genes differentially expressed in mouse plasma cell tumors growing in vivo versus those growing in vitro. The prediction system was validated using published data from three cohorts of patients for whom microarray and clinical data had been compiled. The model stratified patients into four independent survival groups (BEST, GOOD, BAD, and WORST: log-rank test p=1.7 x 10-8). Our model significantly improved the survival prediction over other expression-based models and permitted recognition of patients with different prognoses within the estrogen receptor-positive group and within a single pathological tumor class. Basing our predictor on a dataset that originated in a different species and a different cell type may have rendered it less sensitive to proliferation differences and endowed it with wide applicability. It also avoids overfitting, which has made it successful in analyzing patients from three different institutions.
Chemoradiotherapy in anal carcinoma using cisplatin and 5FU
Authors: G. Calderillo, C. Cano, J. M. Ruiz, J. Zamora, H. Lopez, J. Martinez, D. Gallardo
Journal: Journal of Clinical Oncology (2006)

14128 Background: Chemoradiation (CRT) is now established as the primary treatment for anal carcinoma. The original combination was 5Fu and mitomycin C, but the cisplatin may offer better local control than the standar of MMC with toxicity more tolerable. Methods: Between March 2000 and January 2005, 25 patients with anal carcinoma advanced with non pre-treated were enrolled. Eligible patients had an ECOG PS 0–2. They received cisplatin 80–100 mg/m 2 day 1 and 5FU 800–1000 mg/m 2 day 1–4 every 4 weeks and radiotherapy &gt;45 Gys. Results: 25 patients, 12 male and 13 female, median age 63 (range 36–83 y). 22 with squamous cell carcinoma and 3 adenocarcinoma. (A) 11 patients recieved QT concurrente with RT, median cycles 2 and median of RT 50 Gys and (B) 14 patients recieved QT follow QT-RT concurrent, median cycles 3.5 and median of RT 48 Gys. The toxicity 3–4 were: neutropenia 23%, anaemia 4%, trombocytopenia 8%, diarrhea 15%, vomiting and nausea 19%. The evaluation: (RC) (64%), (RP) (28%) and PD (8%). The median survival 15.5 m (9–42 m), 12 m group A vs 16 m group B. Conclusions: The combination RT-QT with cisplatin and 5FU is feasible and tolerable, and may offer more the secuencie QT follow CRT. No significant financial relationships to disclose.
LAT1‐specific inhibitor is effective against T cell‐mediated allergic skin inflammation
Authors: Keitaro Hayashi, Osamu Kaminuma, Tomoe Nishimura, Mayumi Saeki, Kunie Matsuoka, Takachika Hiroi, Promsuk Jutabha, Yohei Iwata, Kazumitsu Sugiura, Takayoshi Owada, Kazuhiro Kurasawa, Isao Okayasu, Motoshi Ouchi, Tomoe Fujita, Yoshikatsu Kanai, Hitoshi Endou, Naohiko Anzai
Journal: Allergy (2019)

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Assessment of Patient Nondisclosures to Clinicians of Experiencing Imminent Threats
Authors: Andrea Gurmankin Levy, Aaron M. Scherer, Brian J. Zikmund-Fisher, Knoll Larkin, Geoffrey D. Barnes, Angela Fagerlin
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Patient disclosure to their clinician about experiencing an imminent threat is a critical step toward receiving support or assistance. <h3>Objective</h3> To examine the frequency of patients not disclosing their experience of imminent threats to their clinician and their reasons for doing so. <h3>Design, Setting, and Participants</h3> Survey study incorporating results from 2 national, nonprobability samples of 2011 US adults recruited from Amazon's Mechanical Turk (MTurk) from March 16 to 30, 2015, and 2499 recruited from Survey Sampling International (SSI) from November 6 to 17, 2015. Data analysis was conducted from December 20 to 28, 2018. <h3>Main Outcomes and Measures</h3> Self-reported nondisclosure of 4 types of imminent threats (depression, suicidality, abuse, and sexual assault) to their clinician and reasons for nondisclosure. <h3>Results</h3> There were 2011 participants in the MTurk sample (1210 [60.3%] female; 1696 [60.2%] white; mean [SD] age, 35.7 [12.4] years; age range, 18-79 years) and 2499 participants (1273 [51.0%] female; 1968 [78.8%] white; mean [SD] age, 61.0 [7.6] years; age range, 50-91 years) in the SSI sample. Among those who reported experiencing at least 1 of the 4 imminent threats, 613 of 1292 MTurk participants (47.5%) and 581 of 1453 SSI participants (40.0%) withheld information from their clinician. The most commonly endorsed reasons for withholding this information included being embarrassed (MTurk: 72.7%; SSI: 70.9%), not wanting to be judged or lectured (MTurk: 66.4%; SSI: 53.4%), and not wanting to engage in a difficult follow-up behavior (MTurk: 62.4%; SSI: 51.1%). Respondents who experienced at least 1 of the 4 imminent threats had significantly higher odds of nondisclosure in both samples if they were female (MTurk: odds ratio [OR], 1.66 [95% CI, 1.30-2.11]; and SSI: OR, 1.33 [95% CI, 1.07-1.67]) or younger (MTurk: OR, 0.99 [95% CI, 0.98-1.00]; and SSI: OR, 0.98 [95% CI, 0.97-1.00]). Worse self-rated health was also associated with nondisclosure, but only in the SSI sample (OR, 0.85 [95% CI, 0.74-0.96]). <h3>Conclusions and Relevance</h3> This study suggests that many people withhold information from their clinicians about imminent health threats that they face. A better understanding of how to increase patients' comfort with reporting this information is critical to allowing clinicians to help patients mitigate these potentially life-threatening risks.