tbuckley/cabot-search huggingface dataset:
Nonmediated, Label‐Free Based Detection of Cardiovascular Biomarker in a Biological Sample
Authors: JuKyung Lee, SuRyon Shin, Anna Desalvo, Geonhui Lee, Jeong Yoon Lee, Alessandro Polini, Sukyoung Chae, Hobin Jeong, Jonghan Kim, Haksoo Choi, HeaYeon Lee
Journal: Advanced Healthcare Materials (2017)

Direct electrochemical (EC) monitoring in a cell culture medium without electron transporter as called mediator is attractive topic in vitro organoid based on chip with frequently and long-time monitoring since it can avoid to its disadvantage as stability, toxicity. Here, direct monitoring with nonmediator is demonstrated based on impedance spectroscopy under the culture medium in order to overcome the limitation of mediator. The applicability of EC monitoring is shown by detecting alpha-1-anti trypsin (A1AT) which is known as biomarkers for cardiac damage and is widely chosen in organoid cardiac cell-based chip. The validity of presented EC monitoring is proved by observing signal processing and transduction in medium, mediator, medium-mediator complex. After the observation of electron behavior, A1AT as target analyte is immobilized on the electrode and detected using antibody-antigen interaction. As a result, the result indicates limit of detection is 10 ng mL-1 and linearity for the 10-1000 ng mL-1 range, with a sensitivity of 3980 nF (log [g mL])-1 retaining specificity. This EC monitoring is based on label-free and reagentless detection, will pave the way to use for continuous and simple monitoring of in vitro organoid platform.
Molecular analysis of <i>Kras</i> and <i>Nras</i> mutations in a series of 720 patients for guiding the treatment of metastatic colorectal cancer in Turkey.
Authors: Huseyin Karadayi, Cigdem Aktas, Mert Alkac, Yavuz Hakan Ozon, Hakan Berkil
Journal: Journal of Clinical Oncology (2016)

e13115 Background: Mutations in Kras and Nras genes in primary colorectal tumors are the reasons for nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). Results of the molecular analysis guides the treatment decision-making in mCRC. The aim of this study was to evaluate the Kras and Nras mutation data from 720 patients with mCRC between 01 January 2015 and 31 January 2016 using minisequencing method. Methods: We performed a two round nested PCR for the amplification of Exons 1, 2, 3 of Kras and Nras genes harbouring codons 12, 13, 59, 61, 117, and 146 followed by a multiplex minisequencing reaction for the detection of potential mutations. Results: A total of 720 patients were analysed for the mutations in codons 12, 13, 59, 61, 117, and 146 of Kras and Nras genes. Results were obtained from 718 out of 720 (99,72%) patients and no results were obtained from 2 (0,28%) of the cases. 400/718 (55,71%) patients were wild-type for Kras mutations while 318 of them carried a Kras mutation (44,29%). 8 of 318 (2,52%) patients carried two mutations which made totally 326 Kras mutations. Kras mutation rates were 192/326 (58,90%), 98/326 (30,06%), 3/326 (0,92%), 8/326 (2,45%), 3/326 (0,92%), 22/326 (6,75%) in codons 12, 13, 59, 61, 117, 146 respectively. Additional Nras mutation testing was performed for 400 patients which were found to be wild-type for Kras mutations. 31/400 (7,75%) patients were found to carry Nras mutations while 369 (92,25%) of them were wild-type for Nras mutations. 1 of 31 (3,23%) patients carried two mutations which made totally 32 Nras mutations. Mutation distribution was 10/32 (31,25%), 4/32 (12,50%), 4/32 (12,50%), 11/32 (34,38%), 2/32 (6,25%), 1/32 (3,13%) in codons 12, 13, 59, 61, 117, 146 respectively. Conclusions: High rate (349/718, 48,61%) of mutation finding in Kras and Nras testing makes mutation profiling in Kras and Nras genes an effective approach to select patients who are more likely to respond to anti-EGFR immunotherapy or rule out this treatment for those who are not likely to respond, and predict patient outcomes using minisequencing reaction which is a highly sensitive and cost effective method.
Exploration de l'intestin grêle par l'entéroscope à double ballon: Résultats de notre expérience préliminaire
Authors: G Gay, M Delvaux, I Fassler
Journal: Endoscopy (2005)

Les progrès réalisés dans l'exploration de l'intestin grêle par la capsule endoscopique se heurtent à l'absence de biopsie et de possibilité de traitement des lésions observées.
Re: Per-Uno Malmström, Richard J. Sylvester, David E. Crawford, et al. An Individual Patient Data Meta-Analysis of the Long-Term Outcome of Randomised Studies Comparing Intravesical Mitomycin C versus Bacillus Calmette-Guérin for Non–Muscle-Invasive Bladder Cancer. Eur Urol 2009;56:247–56
Authors: Mustafa Aldemir, Abdullah Erdem Canda, Mevlana Derya Balbay
Journal: European Urology (2010)
High throughput proteome screening for novel drug targets
Authors: Canhua Huang, Zhengyu Li, Zhi Wang, Lantu Gou, Aiping Tong, Rui Liu, Yuquan Wei
Journal: Clinical Cancer Research (2007)

C56  Identification of novel drug targets plays vital role for the development of new classes of drugs to overcome drug resistance and replace less efficacious treatments. Recent advances in genomics and proteomics in combination with modern approaches, such as structure-based drug design and combinatorial chemistry to biology-based targets open opportunities for the high throughput identification of novel cellular targets for rational drug development. Toward this goal, multiple proteomic approaches are undertaken in our group, which includes, (I) Comprehensive annotation of various cancer cell membrane proteome and membrane-associated microdomains. (II) Quantitative proteomic analysis of differentially expressed cellular factors during carcinogenesis. (III) Combination of immunoprecipitation and mass spectrometry screening for novel cancer antigens. (IV) Signaling proteomic approach identifying distinct signaling cascades for multiple diseases.
Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma
Authors: Anna Laurell, Maria Lönnemark, Einar Brekkan, Anders Magnusson, Anna Tolf, Anna Carin Wallgren, Bengt Andersson, Lars Adamson, Rolf Kiessling, Alex Karlsson-Parra
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs. <h3>Methods</h3> Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5–20&nbsp;×&nbsp;10<sup>6</sup> DCs (INTUVAX) was injected into the renal tumor twice with 2&nbsp;weeks interval before planned nephrectomy and subsequent standard of care. <h3>Results</h3> No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5&nbsp;months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy. <h3>Conclusions</h3> Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated. <h3>Trial registration</h3> Clinicaltrials.gov identifier: NCT01525017.
Comparison of high dose methotrexate treatments in CNS lymphoma patients: The Henry Ford experience.
Authors: Ranya Selim, Joyce Philip, Vijaya Donthireddy
Journal: Journal of Clinical Oncology (2017)

2028 Background: The main backbone of therapy for CNS lymphoma involves systemic treatment with high dose methotrexate (HDMTX)-based regimens,with radiotherapy reserved only for cases that fail systemic therapy due to the significant cognitive toxicity of radiation. Over the last decade, rituximab and subsequently temozolomide were added to HDMTX chemotherapy regimens. Methods: Patients diagnosed with CNS lymphoma between 2009 and 2015 were identified. A retrospective cohort study was conducted of patients who received HDMTX alone (Cohort A), HDMTX and rituximab (Cohort B) and HDMTX, rituximab and temozolomide (Cohort C). Data collected included treatment related adverse events along with OS and PFS. Results: 31 patients were diagnosed with CNS lymphoma. 11, 10 and 6 patients were in cohorts A, B and C respectively. Median PFS and OS for the entire cohort were 14 and 25 months respectively. Cohort results were compared to the respective reference trials published in the literature. Cohort A had a PFS of 11 months and OS of 12 months compared to 12.8 months and 22.8+ months in the reference Phase II trial. Cohort B had a median PFS of 25+ months and OS of 41 months compared to 21 months and 33.5 months in the reference trial. Cohort C had a 2-year PFS of 0.50 compared to 0.57 in the reference trial. 3 (9.6%), 5 (16.1%), and 2 (6.4%) patients developed renal dysfunction in cohorts A, B and C respectively. 4 (12.9), 2 (6.4%), and 0 patients developed leukopenia in cohorts A, B and C respectively. 3 (9.6), 2 (6.4%), and 1 (3.2%) patients developed anemia in cohorts A, B and C respectively. 1 (3.2%), 1 (3.2%) and 1 (3.2%) patient developed thrombocytopenia in cohorts A, B and C respectively. Conclusions: The addition of Rituximab to HDMTX treatment for the treatment of CNS lymphoma increased the PFS and OS compared to HDMTX alone and is in concordance with the reference phase II trials reported in the literature if not better. In addition, our data at HFH shows no increased risk of adverse events with combination therapies compared to HDMTX alone. The addition of Temozolomide to Rituximab and High Dose methotrexate treatment showed a median 2 year PFS of 0.50 which is comparable to published reports of a 2-year PFS of 0.59.
Total estrogen blockade and chemotherapy in high-risk premenopausal early breast cancer (BC): Long-term follow-up of a phase II study.
Authors: Francesco Recchia, Giampiero Candeloro, Alisia Cesta, Stefano Necozione, Silvio Rea, Massimo Bratta, William Soo Hoo, Thomas Cantor
Journal: Journal of Clinical Oncology (2014)

537 Background: Estradiol (E2) mediates two important functions of premenopausal patients with BC: the induction of vascular endothelial growth factor (VEGF) and the expansion of T-Regulatory cells (T-Regs). Both these functions are fundamental for breast cancer development. We hypothesized that, decreasing plasma E2, we could reduce VEGF and T-regs, and therefore, we could decrease the recurrence rate in premenopausal patients with high risk early breast cancer. Primary endpoint of this study was the evaluation of VEGF and T-Regs; secondary end points were the 5 and 15-year disease-free survival (DFS) and overall survival (OS) rates. Methods: Between June 1997 and June 2007, 200 premenopausal high risk early BC patients were entered into the study. After surgery and before starting the chemotherapy, an LH-RH analogue was administered to all patients. Chemotherapy was tailored to the biological characteristics of each patient, followed by radiation therapy, and by an aromatase inhibitor in ER+ patients. Results: Median patient’s age was 43 years (range 26-45). Mean number of positive axillary nodes was 3.2 (range 1-25). Seventy-one percent of patients were ER+, 29% were ER -, and median KI-67 was 30% (range 15% -100%). After a median follow-up of 104 months (range 63-180), E2 was suppressed to values < 40 ng/ml. A statistically significant decrease of VEGF (P<0.0001) and T-Regs (P<0.0001) were observed. Five-year DFS and OS rate were 89% and 96%, respectively, while the 15-year DFS and OS rate were 62%, and 73%, respectively. ER+ patients had a better DFS (P<0.05) with respect to ER- patients, while no difference was observed in OS. No recurrence after 5 years was observed in ER- patients who had late new primaries. ER+ patients had recurrences even after 15 years. The standard pattern of toxicity of chemotherapy was observed, while hot flashes and G1 osteopenia occurred after LH-RH analogue administration. Conclusions: E2 deprivation with an LH-RH analogue is able to decrease T-Regs and VEGF and to improve the expected DFS and OS rate in premenopausal high risk ER+ and ER- BC patients, at the price of a moderate toxicity.
Prognosis of leptomeningeal metastases from melanoma: A case series of 28 patients.
Authors: Sarah Oinino, Isabelle Rodrigues, Thomas Boulanger, Charles Andre, Jacques Bonneterre, Fahed Zairi, Laurent Mortier, Eve Desmedt, Carole Templier, Emilie Le Rhun
Journal: Journal of Clinical Oncology (2017)

e13550 Background: Leptomeningeal metastasis (LM) are reported in 5-25% of patients with melanoma. However, only very few large contemporary cohorts of melanoma patients with LM have been published. Methods: We report on a case series of 28 consecutive patients with LM from melanoma (BRAF mutated in 14 cases, of 19 tested) diagnosed between April 2007 and April 2016, and treated for LM using a combination of systemic treatment, intra-cerebrospinal fluid (CSF) therapy and radiotherapy according to prior treatments and the presentation of LM. Results: The median age at LM diagnosis was 49.5 years (range 27-73). Median ECOG-performance status was 2 (0-4). Concomitant brain metastases were present in all but 4 patients at LM diagnosis. LM was the first site of metastatic disease for only 2 patients. Median time from melanoma diagnosis to LM diagnosis was 0.33 years in patients with metastatic disease at melanoma diagnosis (4 patients) and 4.5 years in patients without metastatic disease at melanoma diagnosis (24 patients). First line treatment for LM was a combination of intra-CSF (liposomal cytarabine) and systemic treatments in 25 cases, and systemic treatment alone in 3 cases. Systemic treatments include chemotherapy (n = 18), targeted therapy (BRAF inhibitor n = 9; MEK inhibitor, n = 3) and immunotherapy (n = 4). No radiotherapy was performed. Ten patients received more than one line of treatment for LM. Median progression-free survival with first line treatment was 1.75 months. Responses or stabilization (for at least 2 months) were observed in only 7 patients. Median overall survival (OS) for the whole cohort was 3.08 months. Conclusions: The prognosis of patients with LM from melanoma remains poor. The role of new agents such as targeted therapies and immunotherapy for the treatment of LM is still not well defined. Adequate use of intrathecal chemotherapy, targeted therapy and immunotherapy could improve the survival of these patients.
The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection
Authors: Parag Mahale, Eric A Engels, Ruosha Li, Harrys A Torres, Lu-Yu Hwang, Eric L Brown, Jennifer R Kramer
Journal: Gut (2017)

Background and aim Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. Methods We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models. Results Of the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin’s lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke. Conclusions Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.
Two Fatal Cases of Adenovirus-Related Illness in Previously Healthy Young Adults—Illinois, 2000
Authors: Margaret A. Ryan, Gregory C. Gray, Marietta D. Malasig, Dean D. Erdman, Leonard N. Binn, Ludmila V. Asher, David C. Cute, Susan C. Kehl
Journal: JAMA (2001)

Abstract : Deaths from adenovirus infection are considered rare. Fatal cases are most often reported in children with chronic disease, but they have also been reported in previously healthy young adults. We report the first two adenovirus-related deaths identified in military recruits since vaccination became unavailable.
Triple negative breast cancer: Demographic and clinicopathological properties.
Authors: Gul Sema Yildiran Keskin, Arzu Oguz, Dilsen Colak, Zafer Akcali, Ozden Altundag, Mustafa Kadri Altundag
Journal: Journal of Clinical Oncology (2016)

e12572 Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype and accounts for %15-20 of all breast cancer cases. Since the clinical course is characterised by early relapses and poor survivals, still it represents an unmet clinical need. The aim of this study was to evaluate some conventional clinicopathologic and demographical parameters of patients with TNBC. Methods: The files of 4715 breast cancer patients were retrospectively evaluated and the ones with TNBC were identified. The demographical features of the TNBC patients, tumor features, stage at diagnosis and the treatments were noted. For all patients overall survival (OS) and in early stage patients disease free survival (DFS) values were calculated. Results: There were 414 TNBC patients and it was 8.7% of whole breast cancers. Median age was 48 years. Breast conserving surgery and sentinel lymph node were performed for 162 (39.1%) and 89 (21.5%) patients respectively. . Multicentricity and multifocality were detected in 24 (5.8%) of the cases. At diagnosis 26 (6.3%) patients were in metastatic stage, whereas neoadjuvant and adjuvant treatments were given to 53 (12.8%) and 328 (79.2%) patients respectively. Most of the tumors (75.7%) were grade 3. pCR (ypT0N0) was obtained in approximately 57% of patients. Lymphovascular space invasion and extracapsular extension were determined in 165 of all patients and were present in 118 (71.5%) and 55 (33.3%) of them respectively. Antracyclines and taxanes were used in the treatment of 77.3% and 43.7% of the patients that were not metastatic at diagnosis. During median 37 months follow-up period 94(22.9%) patients had recurrences; most common being visceral metastases (in 36 patients) and brain metastases comprising 17.8% of all recurrences. Median DFS was 117months. 3 year OS was %46.9 for all patient group and 48 patients died during this period. Median OS was not reached yet for the whole group. Conclusions: Studies relevant with molecular biology characteristics of TNBC, evaluating its gene expression profiles and mechanisms at molecular level should focus on effective targeted therapies according to these pathways to improve prognosis.
Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes.
Authors: Angela Santonja, Alfonso Sanchez-Muñoz, Yessica Plata Fernández, Jose Miramon, Irene Zarcos, Casilda Llacer Perez, Vanessa de Luque, Cristina Fernandez-Sousa, Jose Manuel Jerez, Martina Alvarez, Luis Vicioso, Emilio Alba
Journal: Journal of Clinical Oncology (2016)

1585 Background: Male breast cancer (MBC) is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry (IHQ) as a luminal disease. In this study, we use for the first time the PAM50 signature to unravel the molecular genetic heterogeneity in MBC. Methods: We collected surgical specimens of invasive MBC from four different Spanish pathology laboratories. IHQ staining for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR) and Ki-67 was performed on tissue microarrays composed of 3 cores sized 0.6 mm per case by standard methods. Breast cancer molecular subtypes were classified according to Cheang et al. (2009). Gene-expression profiling was performed on a research-use-only (RUO) nCounter Analysis System using the RUO PAM50 assay analyzed with the Prosigna algorithm. We explored the association of IHQ and PAM50 subtypes using Fisher’s exact test. Results: From the 78 selected patients, 59 (76%) had enough tumor tissue to be classified by both IHQ and PAM50 approaches. The characteristics of our cohort are the following: mean age 63, tumor-size > 2cm 54%, grade 1 46%, positive lymph nodes 44%, adjuvant chemotherapy (CHT) 51%, hormonotherapy (HT) 80%, CHT+HT 41%. By IHQ these samples are mainly RE, RP and RA positive (97%, 86%, and 90% respectively); HER2, CK5/6 and EGFR negative (100%, 97% and 80%) and with a balanced Ki67 expression (Ki67 > 14 56%). When subtyping by IHQ and PAM50, the majority of samples are luminal B (54 and 63%, respectively) followed by luminal A (43% and 32%). Only 3% by IHQ and 5% by PAM50 are non-luminal (1 basal-like and 1 non-basal triple negative by IHQ and 3 Her2-enriched by PAM50). We found a strong association between both IHQ and PAM50 classifications (p-value = 0.007). Conclusions: In contrast with female breast cancer in which a third of the cases are non-luminal, our findings suggest that MBC is mainly a genomic luminal disease. More research is needed to identify the reason for the scarcity of non-luminal subtypes in MBC and the predominance of the luminal B subtype.