tbuckley/cabot-search huggingface dataset:
Everolimus plus aromatase inhibitors vs aromatase inhibitors as maintenance therapy after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Final results of the phase III randomized MAIN-A trial
Authors: V. Guarneri, S. Cinieri, L. Orlando, C. Bengala, G. Mariani, G. Bisagni, A. Frassoldati, C. Zamagni, G. De Salvo, P.F. Conte
Journal: Annals of Oncology (2019)

Hormonal therapy is the mainstay of treatment for HR+/HER2- metastatic breast cancer (MBC). However, patients (pts) presenting with aggressive disease are generally offered first-line chemotherapy (CT), followed by maintenance hormonal therapy. This study is aimed to evaluate whether maintenance everolimus (EVE) combined with aromatase inhibitors (AI) can prolong progression free survival (PFS) over AI alone in pts with disease control after first-line CT. The Main-A trial is an investigator driven, randomized Phase III study. Postmenopausal pts achieving disease control (stable disease, partial response or complete response) after first-line CT were randomly assigned to EVE 10 mg po daily plus AI or to AI alone. Primary aim is PFS. We estimated a sample size of 54 pts per arm to detect an improvement from 6 to 11 months in the median PFS (Hazard Ratio 0.55). 110 pts were randomized to EVE+AI (n = 52) or to AI (n = 58). Median age was 58 yrs. Fifty% of the pts had liver metastases. Median interval from the time of primary diagnosis to first metastasis was 11.2 mos (9.1 mos in the EVE+AI arm and 16.0 months in the AI arm). A total of 88 PFS events were recorded, 40 in the EVE+AI arm and 48 in the AI arm. Median PFS was 9.9 mos (95%CI: 7.4-13.8) in the EVE+AI arm vs 7.2 mos (95%CI: 4.7-10.9) in the AI arm (HR 0.764, 95%CI: 0.501-1.164). EVE dose reductions were reported for 28 pts. Treatment related adverse events (AEs) were reported for 45 (87%) pts in the EVE+AI arm and for 15 (26%) pts in the AI arm. In the EVE-AI arm, 16 pts discontinued EVE because of AEs or non-compliance. In the AI arm one pts only discontinued therapy because of AE. Most common G>/=2 AEs in the EVE-AI arm were stomatitis (19.2%), neutropenia (9.6%), interstitial pneumonia (7.7%) and skin toxicity (7.7%). At our knowledge, this is the first randomized trial of maintenance endocrine therapy after CT for HR+/HER2- MBC. In these high risk MBC pts deemed suitable for first-line CT, maintenance therapy with AI resulted in a median PFS of 7.2 mos only. Adding EVE resulted in a 2.7 mos non significant PFS prolongation. No new safety signals emerged from this study.
THE PREVALENCE OF GASTRIC NEOPLASIA IS INCREASED IN PATIENTS WITH CHRONIC LIVER DISEASE COMPARED TO A HEALTHY SCREENING POPULATION
Authors: R Morais, M Marques, R Gaspar, R Alves, J Silva, E Dias, J Antunes, P Pereira, S Lopes, H Cardoso, R Liberal, G Macedo
Journal: Endoscopy (2019)

The standard paradigm of screening varices in patients with cirrhosis has for the greater part involved esophagogastroduodenoscopy (EGD). More recently, however, the Baveno VI criteria were proposed to identify patients who could safely avoid screening EGD. Epidemiological studies have suggested that patients with cirrhosis have an increased risk for gastric cancer.
Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis
Authors: Deepak Kumar Kaushik, Anindita Bhattacharya, Reza Mirzaei, Khalil S. Rawji, Younghee Ahn, Jong M. Rho, V. Wee Yong
Journal: Journal of Clinical Investigation (2019)

The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). This penetration likely utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of post-capillary venules are highly glycolytic as manifested by strong expression of lactate dehydrogenase A (LDHA) that converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4) specialized in secreting lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (CD147) as determined through co-expression/co-immunoprecipitation studies, and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4/EMMPRIN interaction was affirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor, α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identifies CHCA and diet as potential modulators of neuro-inflammation in MS.
A Microfluidic Chip Enables Isolation of Exosomes and Establishment of Their Protein Profiles and Associated Signaling Pathways in Ovarian Cancer
Authors: Kalpana Deepa Priya Dorayappan, Miranda L. Gardner, Colin L. Hisey, Roman A. Zingarelli, Brentley Q. Smith, Michelle D.S. Lightfoot, Rajan Gogna, Meghan M. Flannery, John Hays, Derek J. Hansford, Michael A. Freitas, Lianbo Yu, David E. Cohn, Karuppaiyah Selvendiran
Journal: Cancer Research (2019)

Abstract Because of limits on specificity and purity to allow for in-depth protein profiling, a standardized method for exosome isolation has yet to be established. In this study, we describe a novel, in-house microfluidic-based device to isolate exosomes from culture media and patient samples. This technology overcomes contamination issues because sample separation is based on the expression of highly specific surface markers CD63 and EpCAM. Mass spectrometry revealed over 25 exosome proteins that are differentially expressed in high-grade serous ovarian cancer (HGSOC) cell lines compared with normal cells—ovarian surface epithelia cells and fallopian tube secretory epithelial cells (FTSEC). Top exosome proteins were identified on the basis of their fold change and statistical significance between groups. Ingenuity pathway analysis identified STAT3 and HGF as top regulator proteins. We further validated exosome proteins of interest (pSTAT3, HGF, and IL6) in HGSOC samples of origin-based cell lines (OVCAR-8, FTSEC) and in early-stage HGSOC patient serum exosome samples using LC/MS-MS and proximity extension assay. Our microfluidic device will allow us to make new discoveries for exosome-based biomarkers for the early detection of HGSOC and will contribute to the development of new targeted therapies based on signaling pathways that are unique to HGSOC, both of which could improve the outcome for women with HGSOC. Significance: A unique platform utilizing a microfluidic device enables the discovery of new exosome-based biomarkers in ovarian cancer.
SURVIVAL OF PATIENTS WHO UNDERWENT PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE PLACEMENT IN THE INTENSIVE CARE UNIT: FOUR YEARS OF FOLLOW-UP
Authors: K Grammatikos, G Tziatzios, D Lygkos, M Panoutsakou, E Koukoulioti, K Miltiadou, P Gatos-Gatopoulos, LD Lazaridis, P Gkolfakis, K Triantafyllou
Journal: Endoscopy (2019)

We compared Intensive Care Unit (ICU) patients' survival to the survival of patients hospitalized in the General Medical Ward (GMW) after percutaneous endoscopic gastrostomy (PEG) tube placement in a tertiary hospital in Athens, Greece.
Preventing, recognising, and responding to fear of childbirth and birth trauma
Authors: Maeve Anne O'Connell
Journal: BMJ (2019)

Mothers share and compare their birth stories on social media through Twitter, Facebook groups, and online forums.1 Previously, they did not have the opportunity to discuss their stories,2 and social media seems to be giving women a voice. Some mothers compare their obstetric experience with that of violence or abuse.3 They use the hashtag #metoointhebirthroom with connotations of validating each other’s experience of abuse, …
Abstract #2186: Macrophage migration inhibitory factor (MIF) plays a role in proliferation and survival of Ewing tumor cells through the activation of Jak/Stat, Src and Rac1
Authors: Hyung-Gyoo Kang, Xian Liu, Poul Sorensen, Timothy Triche
Journal: Cancer Research (2009)

Cytokines and chemokines are important regulators of cell signaling networks, which control cell growth, proliferation, differentiation, and survival. In normal cells, expression of cytokines and their mediated cell signaling pathways are tightly and accurately regulated. In contrast, it has been shown that cytokine signaling pathways are deregulated in many tumors. Thus, identification and understanding of deregulated cytokines and their related pathways can provide the unique and promising opportunity for better-targeted therapies of cancer. In this study, we investigated cytokines expression in Ewing tumor cell lines using Human cytokine protein array and we found Macrophage migration inhibitory factor (MIF) is a predominant cytokine in Ewing tumor cells. MIF has been known to be a proinflammatory cytokine but recently it was shown that MIF plays roles in several tumors such as proliferation, survival and apoptosis. To study the effects and molecular mechanisms of MIF on Ewing tumor cell growth and survival we established MIF deficient Ewing tumor cell lines using shRNA method. In our study it was found that the decreased MIF expression is significantly correlated to morphological change, deregulation of differentiation, decrease of proliferation and increase of apoptosis in Ewing tumor cells. Then several signal pathways were investigated to elucidate the molecular mechanism of MIF functions in Ewing tumor cells. It has been found that MIF is involved in the activation of Jak/Stat and Src pathways that regulate activation of Akt and Erk, which play key roles in the cell survival and proliferation. Related to the morphological change in MIF-deficient cells it was found that Rac1 activation is highly regulated by MIF. In general it is known that Rac1 is an essential regulator of cellular morphology and movement related to proliferation, differentiation and migration. Therefore our data implies that MIF might functionally contribute to Ewing tumor cell growth and metastasis. In conclusion, coupled with earlier studies about MIF-dependent effects on tumor growth our data suggested that MIF might be a promising target of Ewing tumor cells therapy.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2186.
Molecular Residual Disease and Adjuvant Trial Design in Solid Tumors
Authors: Maria Coakley, Isaac Garcia-Murillas, Nicholas C. Turner
Journal: Clinical Cancer Research (2019)

Advances in diagnosis and treatment have resulted in a high rate of survival for many patients with early-stage cancers. However, identifying who is at ongoing risk of relapse remains of high priority to direct subsequent adjuvant therapy. Multiple recent retrospective studies have shown that detection of tumor-derived materials in blood, in particular with circulating tumor DNA (ctDNA) analysis, can identify patients with residual disease before clinical or radiological evidence of metastatic disease, anticipating relapse with relatively high sensitivity and high specificity. We discuss how these emerging technologies are defining new subgroups of patients with "Molecular Residual Disease" and "Molecular Relapse." We outline how novel clinical trials in the adjuvant setting designed for these new subgroups of patients may improve selection for adjuvant therapies, and provide new surrogate endpoints that may allow for early registration of adjuvant therapies and novel clinical trial designs in the adjuvant setting. We discuss the current limitations of these techniques and the routes to clinical implementation.
Combined Analysis of Whole Exome Sequencing Data in Philadelphia-Negative Myeloproliferative (Ph-negative MPNs) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs) Reveals Novel Recurrently Mutated Genes
Authors: Fabio P S Santos, Raquel Ma Paiva, Renato D Puga, Giulliana Ar Goncalves, Tarcila Santos Datoguia, Welbert Oliveira, Bianca Lisboa, Ricardo Helman, Guilherme Perini, Nelson Hamerschlak, Paulo Vidal Campregher
Journal: Blood (2017)
The outcome of patients with metastatic breast cancer with lung metastasis treated with fulvestrant is superior to that of those with liver metastasis
Authors: M. He, J.-J. Li, W.-J. Zuo, L. Ji, X.-C. Hu, Z.-H. Wang, Z.-M. Shao
Journal: Annals of Oncology (2019)

Background: Endocrine therapy is the preferred treatment for patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). While visceral metastasis is a negative prognostic factor, few studies have distinguished between the prognoses of metastases at different visceral sites. Methods: In total, 398 patients receiving fulvestrant 500 mg at a single center over a 6-year period were analyzed. Logistic regression models identified the prognostic factors associated with progression-free survival (PFS). Kaplan-Meier analysis compared the PFS of patients with lung and liver metastases. Results: Baseline visceral metastases were present in 233 patients, including 138 with lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/o lung metastases (liver metastases without lung involvement) and 41 with lung and liver metastases. The median PFS was 6.8 months (5.6 and 9.2 months for visceral and nonvisceral metastases, respectively, P = 0.028). Patients with lungw/o liver metastases had longer PFS than those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P < 0.001; liverw/o lung versus lungw/o liver hazard ratio (HR) 1.70; lung and liver versus lungw/o liver HR 2.85). Patients with liver metastases experienced significantly worse PFS than those without liver involvement (3.7 versus 9.2 months, P < 0.001). PFS benefits were observed in patients with longer disease-free intervals, no liver metastases, and no previous chemotherapy. Conclusions: Fulvestrant treatment benefitted patients with lungw/o liver or nonvisceral metastases. It is important to differentiate liver from lung metastases when treating HR-positive/HER2-negative MBC with endocrine therapy. Legal entity responsible for the study: Fudan University Shanghai Cancer Center. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Perforating Papules in a Patient With Acute Myeloid Leukemia
Authors: Dana Malajian, Sameera Husain, Stephanie Gallitano
Journal: JAMA Dermatology (2019)

A woman in her 50s with refractory acute myeloid leukemia and a history of breast cancer presented with new pulmonary nodules, elevated serum β-D-glucan levels, and subsequent pink papules on trunk and extremities. What is your diagnosis?
In Vitro and In Vivo Antimicrobial Activity of Antibiotic‐Conjugated Carriers with Rapid pH‐Responsive Release Kinetics
Authors: Sunyoung Kang, Gee Ho Park, Seulah Kim, Jungah Kim, Yoonhwa Choi, Yan Huang, Yan Lee, Tae Hyun Choi
Journal: Advanced Healthcare Materials (2019)

Abstract Two representative antibiotics, cephradine (CP) and moxifloxacin (MX), are covalently conjugated with a β‐cyclodextrin (β‐CD)‐based carrier via pH‐responsive 1‐methyl‐2‐(2′‐carboxyethyl) maleic acid amide (MCM) linkers with excellent conjugation efficiency via simple mixing. At pH 5.5, 90% and 80% of the CP and MX, respectively, are released from the carriers within 30 min, in contrast with the much‐delayed release profile at pH 7.4. The in vitro inhibitory effect of β‐CD–MCM–CP on the growth of Staphylococcus aureus is significantly lower than that of free CP at pH 7.4, but it reaches the level of free CP at pH 5.5. Moreover, S. aureus develops significant CP resistance after pretreatment with free CP, whereas the initial CP sensitivity is maintained after pretreatment with β‐CD–MCM–CP at pH 7.4. However, β‐CD–MCM–MX exhibits no such pH‐responsive activity against Bacteroides fragilis , probably due to the insufficient stability of the MX conjugation at pH 7.4. In nondiabetic and diabetic mouse models, β‐CD–MCM–CP significantly reduces the subcutaneous abscess scores and the bacterial counts in the abscess, although this represents only a marginal improvement in antimicrobial activity compared to free CP.
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY – “REMOVAL UNEXPECTED COMPLICATION”
Authors: J Fernandes, T Araújo, R Ramos, C Vicente, T Teles, R Cunha, C Azevedo, F Lucas, J Canena, L Lopes, C Casteleiro
Journal: Endoscopy (2019)

Percutaneous endoscopic gastrostomy (PEG) tube removal is recommended after patients resume oral intake.
Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes
Authors: Ruidong Xue, Lu Chen, Chong Zhang, Masashi Fujita, Ruoyan Li, Shu-Mei Yan, Choon Kiat Ong, Xiwen Liao, Qiang Gao, Shota Sasagawa, Yanmeng Li, Jincheng Wang, Hua Guo, Qi-Tao Huang, Qian Zhong, Jing Tan, Lisha Qi, Wenchen Gong, Zhixian Hong, Meng Li, Jingmin Zhao, Tao Peng, Yinying Lu, Kiat Hon Tony Lim, Arnoud Boot, Atushi Ono, Kazuaki Chayama, Zemin Zhang, Steve George Rozen, Bin Tean Teh, Xin Wei Wang, Hidewaki Nakagawa, Mu-Sheng Zeng, Fan Bai, Ning Zhang
Journal: Cancer Cell (2019)
MUCOSAL ENDOSCOPIC RESECTION OF LARGE LESIONS OF THE UPPER DIGESTIVE TRACT
Authors: E Brunet Mas, E Martínez Bauer, P Garcia Iglesias, L Hernández, J Da Costa, G Llibre, A Soria, J Vives, P Pedregal, G Grau, A Lira, ST Machlab, L Melcarne, V Puig Diví, E Brullet, R Campo, F Junquera
Journal: Endoscopy (2019)

Endoscopic mucosal resection (EMR) of upper digestive tract (UDT) lesions presents a good success rate and an excellent safety profile.
Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope
Authors: Goran Bajic, Max J. Maron, Yu Adachi, Taishi Onodera, Kevin R. McCarthy, Charles E. McGee, Gregory D. Sempowski, Yoshimasa Takahashi, Garnett Kelsoe, Masayuki Kuraoka, Aaron G. Schmidt
Journal: Cell Host & Microbe (2019)
Circulating miRNAs as diagnostic tool for discrimination of respiratory disease: Asthma, asthma‐chronic obstructive pulmonary disease (COPD) overlap and COPD
Authors: Jose M. Rodrigo‐Muñoz, Manuel J. Rial, Beatriz Sastre, Jose A. Cañas, Ignacio Mahíllo‐Fernández, Santiago Quirce, Joaquin Sastre, Borja G. Cosío, Victoria Del Pozo
Journal: Allergy (2019)

JS reports having served as a consultant to Thermo Fisher, Novartis, Sanofi, Leti, FAES FARMA, Mundipharma and GSK; having been paid lecture fees by Novartis, GSK, Stallergenes, LETI and FAES FARMA; and received grant support for research from Thermo Fisher and ALK. VDP reports having served as a speaker/consultant to Astra-Zeneca. BGC reports personal fees and/or grants from AstraZeneca, Boehringer, Novartis, Chiesi, Rovi, Menarini, Esteve, outside the submitted work. The rest of the authors declare no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
18F-FACBC PET/MRI in Diagnostic Assessment and Neurosurgery of Gliomas
Authors: Anna Karlberg, Erik Magnus Berntsen, Håkon Johansen, Anne Jarstein Skjulsvik, Ingerid Reinertsen, Hong Yan Dai, Yiming Xiao, Hassan Rivaz, Per Borghammer, Ole Solheim, Live Eikenes
Journal: Clinical Nuclear Medicine (2019)

Purpose This pilot study aimed to evaluate the amino acid tracer 18 F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas. Materials and Methods Eleven patients with suspected primary or recurrent low- or high-grade glioma received an 18 F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference. Results Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRI CE ), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRI CE and combined PET/MRI ( P = 0.031). TBRs increased with tumor grade ( P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRI CE volumes (&gt;98%) and were generally larger (1.5–2.8 times) than the MRI CE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRI CE (26.3%). Conclusions Low- versus high-grade glioma differentiation may be possible with 18 F-FACBC using TBR. 18 F-FACBC PET/MRI outperformed MRI CE in lesion detection and in detection of glioma tissue. More research is required to evaluate 18 F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.
Differential allergen expression in three <i>Tyrophagus putrescentiae</i> strains inhabited by distinct microbiome
Authors: Jan Hubert, Marta Nesvorna, Pavel Klimov, Scot E. Dowd, Bruno Sopko, Tomas Erban
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency
Authors: Qingle Liang, Nana Bie, Tuying Yong, Ke Tang, Xiaolong Shi, Zhaohan Wei, Haibo Jia, Xiaoqiong Zhang, Haiyan Zhao, Wei Huang, Lu Gan, Bo Huang, Xiangliang Yang
Journal: Nature Biomedical Engineering (2019)