tbuckley/cabot-search huggingface dataset:
Plasma exosome microRNA-155 expression in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors: A potential biomarker of response to systemic therapy.
Authors: Maryam Soleimani, Marisa Thi, Neetu Saxena, Bernhard J. Eigl, Daniel Joseph Khalaf, Kim N. Chi, Christian K. Kollmannsberger, Lucia Nappi
Journal: Journal of Clinical Oncology (2021)

4570 Background: The search for a reliable predictive biomarker of response to immune checkpoint-based therapy (ICBT) remains a critically unmet need in the management of metastatic renal cell carcinoma (mRCC). We sought to evaluate the biomarker potential of plasma exosome microRNAs (miRNAs) implicated in RCC and in augmentation of the tumour microenvironment (TME) for such a role. Methods: Eleven miRNAs that are over-expressed in RCC and/or immune-associated were evaluated in 40 patients with mRCC (prior to initiating ICBT) and in 30 healthy volunteers. Exosomes were extracted from 500 uL of plasma and were used for miRNAs extraction. MiRNAs expression was evaluated by RT-PCR. Cycle threshold values were normalized to miR-30-3b, and the relative quantity of the expression (RQ) was compared to those of healthy volunteers and calculated using the 2 ΔΔ Ct method. Mann-Whitney U test was used to evaluate the expression of miRNAs between mRCC pts and healthy volunteers according to best response to first line ICBT between responders (n = 27) v non-responders (n = 13). The cut-off value of significant expression was established by Youden’s index. Responders were defined as those patients experiencing complete response, partial response or stable disease and non-responders were those who experienced progressive disease. Results: The most common first line ICBT was nivolumab + ipilimumab (n = 32), followed by pembrolizumab + axitinib (n = 5), and avelumab + axitinib (n = 3). A significantly higher expression of miRNA-1233 (median 1.85 v 0.81 p = 0.008) and miRNA-155 [miR-155] (3.69 v 0.21 p = 0.006) were found in patients compared to healthy volunteers. Higher miR-155 expression was associated with higher Fuhrman grade (p = 0.002). There was no association with other clinical prognostic factors. MiR-155 was expressed at a significantly lower level in responders than in non-responders (median 0.61 v 35.29, p = 0.042). Response rate amongst patients with low and high expression of miR-155 (RQ ≤ 2.5) was statistically different (p = 0.042) and 84.2% of the pts with low miR-155 expression responded to the treatment. Conclusions: Lower expression of miR-155 was associated with response to ICBT in patients with mRCC. Functionally, miR-155 is involved in regulation and modulation of the TME. These results underscore the need for further work in this area to elucidate the role of this and other miRNAs as biomarkers of response in mRCC.
ベルギーにおけるヒトおよび下痢子牛から分離された新興血清型O80:H2の志賀毒素産生および腸病原性大腸菌の特性【JST・京大機械翻訳】
Authors: K De Rauw, D Thiry, B Caljon, M Saulmont, J Mainil, D Pierard
Journal: Clinical Microbiology and Infection (2019)
Designing Inherently Photodegradable Cell‐Adhesive Hydrogels for 3D Cell Culture
Authors: Alisa Rosenfeld, Tobias Göckler, Mariia Kuzina, Markus Reischl, Ute Schepers, Pavel A. Levkin
Journal: Advanced Healthcare Materials (2021)

Abstract Light‐based microfabrication techniques constitute an indispensable approach to fabricate tissue assemblies, benefiting from noncontact spatially and temporarily controlled manipulation of soft matter. Light‐triggered degradation of soft materials, such as hydrogels, is important in tissue engineering, bioprinting, and related fields. The photoresponsiveness of hydrogels is generally not intrinsic and requires complex synthetic procedures wherein photoresponsive crosslinking groups are incorporated into the hydrogel. This paper demonstrates a novel biocompatible and inherently photodegradable poly(ethylene glycol) methacrylate (PEGMA)‐based gelatin‐methacryloyl (GelMA)‐containing hydrogel that can be used to culture cells in 3D for at least 14 d. These gels are conveniently and quickly degraded via UV irradiation for 10 min to produce structured hydrogels of various geometries, sizes, and free‐standing cell‐laden hydrogel particles. These structures can be flexibly produced on demand. In particular, photodegradation can be temporarily delayed from photopolymerization, offering an alternative to hydrogel array production via photopolymerization with a photomask. The paper investigates the influences of hydrogel composition and swelling liquid on both its photodegradability and biocompatibility.
E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non–small cell lung cancer
Authors: Ke Li, Xufen Zheng, Hua Tang, Yuan-Sheng Zang, Chunling Zeng, Xiaoxiao Liu, Yanying Shen, Yuzhi Pang, Simin Wang, Feifei Xie, Xiaojing Lu, Yuxiang Luo, Zhang Li, Wenbo Bi, Xiaona Jia, Tao Huang, Rongqiang Wei, Kenan Huang, Zihao Chen, Qingchen Zhu, Yi He, Miaoying Zhang, Zhizhan Gu, Yichuan Xiao, Xiaoyang Zhang, Jonathan A. Fletcher, Yuexiang Wang
Journal: The Journal of Experimental Medicine (2021)

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non–small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell–specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry–based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.
External validation of a radiomic signature to predict HPV (p16) status from standard CT images of anal and vulvar cancer patients.
Authors: Ralph T.H. Leijenaar, Sean Walsh, Akshayaa Vaidyanathan, Fadila Zerka, Mariaelena Occhipinti, Denis Danthine, Frederic Kridelka, Roland Hustinx, Wim Vos, Julien Guiot, Michelle Leech, Charles Gillham, Ciara A. Lyons, Aileen Flavin, Philippe Lambin, Pierre Lovinfosse
Journal: Journal of Clinical Oncology (2021)

e15502 Background: HPV status of anal and vulvar cancers cannot be predicted by visual inspection as well as for oropharyngeal cancers. Radiomics applied on computed tomography images can extract features that may better characterize the structure and the underlying biology of the tumor. Methods: In this multi-center study, we validated a CT based radiomic signature to predict HPV (p16) status, developed in head &amp; neck cancer, in anal and vulvar cancer patients. The patients cohort was composed of 68 anal cancer patients and 7 vulvar cancer patients, with p16 status determined by immunohistochemistry, while a control cohort was composed of 422 lung cancer patients. The patient cohorts come from 4 different centers (Maastro Clinic - the Netherlands, CHU Liege – Belgium, St Luke’s Hospital – Ireland, Cork University Hospital - Ireland). The primary tumor volume was manually delineated for each patient on axial CT images. Prior to analysis, all images were resampled to isotropic voxels of 2 mm, using linear interpolation. A total of 37 radiomics features were calculated from five groups: tumor intensity, shape, texture, Wavelet and Laplacian of Gaussian. The signature was built using regularized logistic regression [1]. The signature was evaluated according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) and the Radiomics Quality Score (RQS). Results: The signature classified anal and vulvar cancers based on their HPV status (positive or negative), with an AUROC of 0.760 comparable to the performance of the original signature developed in oropharyngeal squamous cell carcinomas (AUROC of 0.764) [1]. The model, tested in the control cohort of lung cancer patients, predicted the HPV positive status of 1% of the patients which is in line with expected European prevalence (0 – 10%). This signature is TRIPOD level 4 (57%) with an RQS of 61%. Conclusions: This study supplies an additional insight into HPV imaging phenotype, providing a proof of concept that molecular information can be inferred from standard medical images by means of radiomics. These preliminary but encouraging results may pave the road for further generalization of CT image features of HPV-related tumors and aid in the optimization of future therapy developments [2]. Reference [1] Ralph TH Leijenaar et al., The British Journal of Radiology 2018 91:1086 [2] Immunotherapy Drug with Two Targets Shows Promise against HPV-Related Cancers - accessed on 12/02/2021 - https://www.cancer.gov/
Feasibility of ovarian preservation as a stage in correcting the quality of life in young patients after gynecologic surgeries.
Authors: Natalia V. Chernikova, Ekaterina V. Verenikina, Yuriy A. Poryvaev, Tatiana Yu. Myagkova, Anna P. Menshenina
Journal: Journal of Clinical Oncology (2021)

e17560 Background: The purpose of the study was to analyze the structure and activity of the blood flow in the preserved ovaries after gynecologic surgeries. Methods: We monitored 50 patients (mean age 35.8±0.5 years) using sonography after ovary-sparing hysterectomy for benign, precancerous and preinvasive malignant uterine diseases. For revascularization, the preserved ovaries were attached to the lateral wall of the small pelvis or to the base of round ligaments of the uterus. Results: Ovarian hypertrophy was recorded in 3 women during the first year of the follow-up; the ovaries returned to the initial size without correction by 24 months. By the third year of observation, 94% of women had normal gonadal sizes, and only 2 women had ovarian hypoplasia. During the entire observation period (3 years), in 91% of cases, we could visualize the regular maturation of follicles in the preserved ovaries, which indicated the preservation of ovulatory function. The use of Doppler techniques during 24 months of the follow-up demonstrated that the blood circulation in the attached ovaries after hysterectomy was decreased on the average by 20.3%, compared to the intact ovaries. Conclusions: After the critical period of hysterectomy, the blood flow in the ovaries in almost all patients remains sufficient during the first 2-3 years, stimulating the regular growth of follicles and maintaining the gonadal activity. The quality of life of the operated patients during the first three years of follow-up remains optimal without additional correction with hormone replacement therapy.
An Open-Label Study of the Safety and Efficacy of Morotocog Alfa (AF-CC) in Previously Untreated Patients Aged <6 Years in Usual Care Settings
Authors: Kaan Kavakli, James Baumann, Francois Pierre Huard, Lynne Smith, Christine Alvey, Joan Korth-Bradley, Pablo Rendo, Jeremy Rupon
Journal: Blood (2017)
Обоснование выбора метода операции в хирургическом лечении осложненных форм хронического панкреатита
Authors: I.Ya. Budzak
Journal: GASTROENTEROLOGY (2013)

В клинике института за период 2010–2012 гг. оперировано 43 пациента по поводу осложненных форм хронического панкреатита. На основании данных компьютерной томографии и эндоскопической ретроградной панкреатохолангиографии выделялись значимые для выбора метода операции варианты патологии поджелудочной железы. Оценка интраоперационных биопсий показала, что основным проявлением хронического панкреатита во всех случаях выступал выраженный фиброз ткани железы. При этом, если у больных с III степенью фиброза фиброзная ткань составляла 68,2–76,4 % площади поджелудочной железы, а экзокринная — 16,2–24,8 %, у больных с IV степенью фиброза соответственно 79,5–95,5 и 2,3–10,8 %. Выделены показания для выполнения органосохраняющих резекционных, резекционно-дренирующих вмешательств и изолированных, дренирующих протоковую систему поджелудочной железы операций. Удельный вес комбинированных резекционно-дренирующих вмешательств с сохранением двенадцатиперстной кишки составил 30,2 %, общая летальность — 2,3 %, количество послеоперационных койко-дней — (9,1 ± 0,8).
Propping up the parents: An environmental scan of childcare programs available to cancer patients in North America.
Authors: Katherine Preston, Mackenzie MacDonald, Meredith Elana Giuliani, Barbara L. Melosky, Bonnie Leung, Paris-Ann Ingledew
Journal: Journal of Clinical Oncology (2021)

e18805 Background: Approximately 20% of newly diagnosed cancer patients are between the ages of 20 and 54, and many of these patients are also the primary caregivers of children. Qualitative studies focusing on this demographic indicate that patients who are parents struggle to balance their own care needs with those of their children. Further, a lack of childcare support during cancer treatments can negatively impact compliance and increase existing psychological stress for patients. In the efforts to establish a child-minding program at a major Canadian cancer centre, we carried out an environmental scan to evaluate the current state of childcare support for cancer patients. Methods: Firstly, a literature scan was conducted in order to assess current knowledge about childcare and cancer patients, which included the use of search engines, directed internet searches, a review of oncology conference proceedings and websites of oncology associations. Literature was selected based on pre-determined criteria. Secondly, 12 representatives from major Canadian cancer centres (CCC) completed a questionnaire assessing current childcare strategies at their respective institutions. Finally, a broad scan of the grey literature was conducted by investigating 161 Canadian and American hospitals for on-site childcare services, using lay-accessible searching techniques (hand-searching hospital websites, phone and email correspondences). Results: The literature scan identified seventeen primary articles, which focused largely on exploring the role strain faced by patients who are also parents. A single study explored the instrumental challenges of being a parent with cancer, and formally assessed the childcare needs of these patients. The questionnaire results indicated that only two of the twelve investigated CCCs had established an approach to child-minding for patients. The grey literature scan identified twenty-six on-site, patient-accessible child-minding centres at hospitals in Canada and the US based on pre-determined inclusion criteria. Of these, 76.9% of centres were associated with pediatric hospitals, and 69.2% were located in the United States. Most centres (76.9%) were open for over 30 hours per week, and 88.5% of centres were free of charge to users. Conclusions: These findings generally indicate that a minority of Canadian and American hospitals and cancer centres have formal childcare services in place to support patients who are also parents. As cancer patients are at increased risk for financial toxicity, they may be particularly in need of this kind of instrumental support. This highlights the importance of carrying out a targeted needs assessment in order to fully elucidate the need for patient-accessible childcare services at CCCs.
Association of HIV infection with survival and cancer-specific death in cancer patients in Louisiana.
Authors: Suki Subbiah, Shelby Meckstroth, Yong Yi, Lauren Maniscalco, Xiao-Cheng Wu, Karlie Plaisance-Bonstaff, Christopher Parsons
Journal: Journal of Clinical Oncology (2021)

e18630 Background: Studies have reported elevated mortality in HIV patients (pts), including cancer-specific mortality, compared to non-HIV pts. However, many of these studies did not include data from Louisiana. Louisiana has among the highest HIV and AIDS case rates in the country, but there is no available large-scale data regarding cancer outcomes in HIV pts in the state. We compared our data in Louisiana to the largest known study to date over an expanded time period to evaluate for disparities. Methods: Following linkage of Louisiana Tumor Registry data from 1995-2016 and Louisiana Office of Public Health, STD/HIV Program database, we identified a total of 435,478 cancer cases, of which 2,949 were HIV-positive (0.67%). Analyses of categorical variables were performed using Pearson’s chi-squared test. Cause of death was extracted from death certificate or autopsy report. Survival analyses were performed utilizing SEER*Stat. Results: Despite the higher proportion of HIV in cancer pts in Louisiana, demographics are similar to previously published data in that cancer pts with HIV tended to be male, black, and younger than their HIV-negative counterparts (p&lt;0.001). However, although 5-year survival was substantially decreased in HIV-cancer pts in congruence with other studies, cancer-specific mortality was lower than non-HIV pts in all cohorts, including both AIDS-defining cancers (ADC) and non-AIDS-defining cancers (non-ADC). Conclusions: HIV infection in cancer pts in Louisiana is associated with lower survival but not increased cancer-specific death, independent of race, gender, age, ADC vs non-ADC, and viral vs non-viral etiology. HIV-related deaths still comprise a substantial cause of death in this population.[Table: see text]
Impact of clinical trial enrollment on episode costs in the Oncology Care Model (OCM).
Authors: Garrett Young, Larry Edward Bilbrey, Edward Arrowsmith, L. Johnetta Blakely, Davey B. Daniel, Andrew Yue, Basit Iqbal Chaudhry, David R. Spigel, Aaron J. Lyss, Natalie R. Dickson, John Fox, Stephen Matthew Schleicher, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2021)

6513 Background: Clinical trials are critical for improving outcomes for patients with cancer. However, there is some concern from health insurers that clinical trial participation can increase total cost of care for cancer patients. We investigated the impact of clinical trial participation on total costs paid by Medicare during the OCM program in a large community-based practice. Methods: Tennessee Oncology (TO) is a community oncology practice comprising over 90 oncologists across 30 sites of care. We linked TO trial data and electronic medical record data with OCM data for episodes of care from 2016-2018. To assess the impact of trial participation on total cost relative to routine care, we created matched comparator groups for each OCM episode based on cancer type, metastatic status, number of comorbidities, performance status, and age. Patients with breast cancer receiving hormone therapy only were excluded. Absolute and percent cost differences between groups were calculated for episodes that had a comparator group size of five or greater. Differences in total cost for trial episodes were compared to non-trial episodes, and significance was assessed using the Mann–Whitney U test. We also studied the impact of trial participation on receipt of active treatment in the last 14 days of life (TxEOL), hospice use, and hospitalizations. Results: During the study period, 8,026 completed OCM episodes met study criteria. Patients were enrolled in a clinical trial for 459 of these episodes. On average, episodes during which patients were on trial cost $5,973 less than matched non-trial episodes (Table), independent of early versus late-phase trial. Most savings resulted from decreased drug costs. There were no differences in rates of TxEOL (15% vs. 14% p=1.0), rates of hospitalizations (31% vs. 30% p=0.54), or hospice use (52% vs. 62% p=0.08) between trial and non-trial episodes. Median difference from comparator group average cost was significantly lower for clinical trial episodes (-18% vs. -6%, p&lt;0.01). Conclusions: In the community setting, total costs paid by Medicare for patients participating in clinical trials during OCM episodes were lower than costs for similar patients receiving routine care. Clinical trial participation did not adversely impact end-of-life care or likelihood of hospitalization. These findings suggest that patient participation in clinical trials does not increase total cost of care nor enhance financial risk to payers.[Table: see text]
Streamlining the Path to Endovascular Reperfusion in Stroke
Authors: Bruce C. V. Campbell
Journal: JAMA Neurology (2021)

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