tbuckley/cabot-search huggingface dataset:
Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development
Authors: Sabine Bartel, Stefania La Grutta, Giovanna Cilluffo, Giovanni Perconti, Antonella Bongiovanni, Agata Giallongo, Jochen Behrends, Jochen Kruppa, Stefanie Hermann, Dapi Chiang, Michael W. Pfaffl, Susanne Krauss‐Etschmann
Journal: Allergy (2019)

miRNAs are master regulators of signaling pathways critically involved in asthma and are transferred between cells in extracellular vesicles (EV). We aimed to investigate whether the miRNA content of EV secreted by primary normal human bronchial epithelial cells (NHBE) is altered upon asthma development.NHBE cells were cultured at air-liquid interface and treated with interleukin (IL)-13 to induce an asthma-like phenotype. EV isolations by precipitation from basal culture medium or apical surface wash were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blot, and EV-associated miRNAs were identified by a RT-qPCR-based profiling. Significant candidates were confirmed in EVs isolated by size-exclusion chromatography from nasal lavages of children with mild-to-moderate (n = 8) or severe asthma (n = 9), and healthy controls (n = 9).NHBE cells secrete EVs to the apical and basal side. 47 miRNAs were expressed in EVs and 16 thereof were significantly altered in basal EV upon IL-13 treatment. Expression of miRNAs could be confirmed in EVs from human nasal lavages. Of note, levels of miR-92b, miR-210, and miR-34a significantly correlated with lung function parameters in children (FEV1 FVC%pred and FEF25-75%pred ), thus lower sEV-miRNA levels in nasal lavages associated with airway obstruction. Subsequent ingenuity pathway analysis predicted the miRNAs to regulate Th2 polarization and dendritic cell maturation.Our data indicate that secretion of miRNAs in EVs from the airway epithelium, in particular miR-34a, miR-92b, and miR-210, might be involved in the early development of a Th2 response in the airways and asthma.
Profile of multiple myeloma in the inner city: Disease presentation and clinical course.
Authors: Adam Goldrich, Andriane Melanthiou, Anuja Kriplani, Elizabeth Helzner, Arvind Babu, Daniel Fein, Juhee Sidhu, Jason Parker Gonsky, Olcay Batuman
Journal: Journal of Clinical Oncology (2013)

8594 Background: Multiple myeloma (MM) is the most common hematologic neoplasm in blacks in the US. Based on SEER data of all Americans, the disease is more common in men, has a median diagnosis age of 70 and median survival of 3-6 years. The subclinical syndrome MGUS precedes MM, and blacks have a 2-3-fold higher risk of developing MGUS and MM. Further, recent improvements in survival observed for white patients are not observed in blacks. To gain new insight into pathogenesis and to optimize patient care, we characterized our inner city, largely Caribbean-African population in Brooklyn, NY, in terms of disease presentation and course. Methods: MM patients were identified by tumor registries based on histopathology. Data including survival were collected from records of patients diagnosed between 2001-2011 (n=242). Data analysis was performed using SPSS Advanced Statistics. Results: Median age was 64 (range 35-91), male: female ratio was 0.70. The most common presenting pathology was the presence of multiple skeletal lesions with fractures (67% of patients). Spinal cord compression and spinal compression fractures occurred in 33% and 32% of patients, respectively. Renal disease was present in 26%, indicated by serum creatinine &gt;2 mg/dL. Consistent with advanced stage and renal failure, median serum beta-2 microglobulin was 4.25 (range 0.96-82.8). Chromosome banding and FISH was available on 133 patients and showed no cytogenetic abnormalities in 53%; hyperdiploidy (30.4%). Common trisomies included chr 1, 5, 15 and 19. Other abnormalities were del 13 (13%) and chr 14 translocations (11%). Comorbidities include hypertension (65%), diabetes (35%) and obesity (BMI over 30 in 24%). While recent improvements in acquiring health insurance have improved access, less than 10% of patients received HDCT and ASCT. As of October 1, 2012, 36% of all patients are living. Survival analyses are underway. Conclusions: MM presents at an advanced stage and affects younger AA’s in the Downstate community. Strategies for identifying and treating patients with progressive MGUS and at earlier disease stages may enhance survival.
RSF-1/HBXAP to predict prognosis in HBV-related hepatocellular carcinoma patients after curative resection.
Authors: Yang Xu, Jia Fan, Robert Anders, Bin Guan, Qingfeng Zhu, Le-Ming Shih
Journal: Journal of Clinical Oncology (2012)

e14538 Background: Remodeling and spacing factor 1(Rsf1, or HBXAP) was demonstrated consistent overexpression in several solid tumors and could be a prognostic marker, while its role in hepatocellular carcinoma (HCC) is still unclear. We try to illustrate the prognostic significance of RSF1 and its mechanism in HBV related HCC patients. Methods: RSF1 expressions were detected in tumor tissue microarrays of 254 HCC patients who underwent curative surgical resection during 2/2004 to 12/2005. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. The effects of RSF1 on cell proliferation and migration were tested in RSF1 knockdown and inducible HCC cells. Related genes were screened by cDNA Microarray and then confirmed by qRT-PCR and werstern blot. Results: RSF1 expression in HCC tissues was significantly related to replase of tumor in HCC patients after curative resection, and significantly related to MMP9 and HBV infection. Knockdown (or over-express) of RSF1 in HCC cells significantly inhibited (or enhanced) HCC proliferation and invasion in vitro. RSF1 controlled the expression of MMP9 in HCC cells. Conclusions: RSF1 up-regulates MMP9 and predicts poor prognosis in HBV related HCC patients after curative resection.
Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond
Authors: Maria E Cabanillas, Mabel Ryder, Camilo Jimenez
Journal: Endocrine Reviews (2019)

Abstract The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.
Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization
Authors: Simon P. Jochems, Karin de Ruiter, Carla Solórzano, Astrid Voskamp, Elena Mitsi, Elissavet Nikolaou, Beatriz F. Carniel, Sherin Pojar, Esther L. German, Jesús Reiné, Alessandra Soares-Schanoski, Helen Hill, Rachel Robinson, Angela D. Hyder-Wright, Caroline M. Weight, Pascal F. Durrenberger, Robert S. Heyderman, Stephen B. Gordon, Hermelijn H. Smits, Britta C. Urban, Jamie Rylance, Andrea M. Collins, Mark D. Wilkie, Lepa Lazarova, Samuel C. Leong, Maria Yazdanbakhsh, Daniela M. Ferreira
Journal: Journal of Clinical Investigation (2019)

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.
Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Authors: I. Tsimafeyeu V., A. Madzhuga, L. Demidov
Journal: Journal of Clinical Oncology (2009)

e16134 Background: In experimental systems, interference with coagulation can affect tumor biology. We suggested that abnormal coagulation could be a negative predictor for response to immunotherapy and survival among patients with metastatic renal cell carcinoma (MRCC). Methods: To address this issue, retrospective analysis of 289 previously untreated MRCC patients entering on institutional review board-approved clinical trials was conducted between 2003 and 2006. In addition, two groups of MRCC patients with (n = 28) or without (n = 28) hypercoagulability were compared in a case-control study. Baseline and treatment characteristics were well balanced. Results: Hypercoagulability was present at treatment start in 40% of patients. Median baseline fibrinogen was 6.2 mg/dl. Serious disorders were found in 68% of patients. Abnormal coagulation was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0–1 (p = 0.001). Patients with high extent of hypercoagulability had significantly higher number of metastatic sites (p = 0.02). On univariate analysis, patients with hypercoagulability had significantly shorter overall survival than patients with normal coagulation; median survivals of 8.9 and 16.3, respectively (p = 0.001). Short survival and low response rate also were significantly associated with hypercoagulability in a case-control study. Median cancer-specific survival was 8.2 months and 14.6 months, respectively (p = 0.0011). Disease control rate (overall response + stable disease) was significantly higher in patients with normal coagulation: 71.4 versus 42.9% (p = 0.003). We did not reveal VTE-related deaths. Conclusions: Hypercoagulability disorders were found to be prognostic factor for response rate to systemic therapy and survival in patients with MRCC. No significant financial relationships to disclose.
Correction: Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenström Macroglobulinemia
Authors: Aldo M. Roccaro, Xavier Leleu, Antonio Sacco, Anne-Sophie Moreau, Evdoxia Hatjiharissi, Xiaoying Jia, Lian Xu, Bryan Ciccarelli, Christopher J. Patterson, Hai T. Ngo, Domenico Russo, Angelo Vacca, Franco Dammacco, Kenneth C. Anderson, Irene M. Ghobrial, Steven P. Treon
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), Fig. 5B contains incorrect blots for beta-catenin (whole-cell lysate) and nucleolin panels. These errors have been corrected with original data in the latest online HTML and PDF versions of the article. The authors regret these errors.
Pegfilgrastim (N) induced bone pain (NIBP): Incidence, risk factors and management in a community practice
Authors: J. J. Kirshner
Journal: Journal of Clinical Oncology (2006)

8598 Background: In the early clinical trials, the incidence of NIBP was 15–30%, with ‘severe‘ pain in less than 8% of patients (pts). The incidence in clinical practice may be higher and contribute to a significant decrease in quality of life (QOL) for pts undergoing chemotherapy(Ch). Methods: In our large oncology practice (HOACNY), pts were surveyed following their initial injection of N. Pain was graded on a scale of 1–10. Pts were divided into 3 groups: no pain (1), pain 1–5 (2) and pain 6–10(3). Pts recorded the day of onset, duration of pain and its location. Information was obtained as to how the pts treated their pain and how effective the treatment was.Data was collected re: age, sex, disease,and Ch and whether pts were already on analgesics/steroids. All pts received 10–20 mg of IV dexamethasone pre-Ch. N was administered 24–72 h post chemotherapy. Differences among the groups were analyzed using the t-test. Results: To date, surveys have been analyzed from 75 pts, with results tabulated below. Dose dense AC for adjuvant breast ca was the most common Ch (44%). There were no significant differences among the groups when analyzed by pt age, sex, disease, or Ch, although there was a higher % of lung ca pts in Gp 3 (treated with carboplatin/paclitaxel). On average, the onset of pain was within the first 2 days &amp; lasted 2–3 days(Gp2) and an additional day (Gp 3). Gp 2 pts had more localized pain than Gp 3 pts &amp; responded very well to APAP or NSAID’s. Gp 3 pts had more diffuse pain and 50% had minimal or no relief with OTC analgesics. Conclusions: NIBP is a significant problem in clinical practice, interfering with pt QOL. It is unpredictable and often severe &amp; may be refractory to OTC analgesia. It may be more common in lung ca pts treated with carboplatin/paclitaxel. A prospective randomized trial is planned (URCC CCOP Research Base) to further define the problem and determine if daily ‘premedication‘ with NSAIDS could reduce or eliminate NIBP. [Table: see text] [Table: see text]
The assessment of randomized double blind clinical trial of Shugan-liangxue prescription used for the treatment of hot flashes in breast cancer patients
Authors: P. Li
Journal: Journal of Clinical Oncology (2006)

8584 Background: Hot flashes are a common side effect for breast cancer (BC) pts with TAM treatment. Traditional Chinese medicine (TCM) is typically given to BC pts in China. This trial is to assess the effects of TCM for relieving hot flashes. TCM oral solution is prescribed for clearing heat and cooling blood. The compound was tested and contained no phytoestrogen. A randomized, double blind clinical trial was designed to examine the effects of TCM over a 3-week period. Methods: From October 2004 to October 2005, 49 BC pts undergoing treatment with TAM who having hot flashes at least 3 times a day involved the study. Daily average of hot flashes was recorded by the pts for a week as a baseline. TCM or placebo liquid (100 ml) was administered orally three times a day for 3 weeks by a randomized double-blind method. The number of hot flashes and quantity of sleep disturbance in the two groups were evaluated. Results: 45 pts were evaluated in TCM group (n = 22) and the placebo group (n = 23). The severity of the hot flash symptoms was evaluated according to the Kupperman menopausal index (KI). Pts were distributed approximately equally between the two groups. There were 31% (7/22) and 26% (6/23)pts with mild hot flashes in TCM and placebo groups, and 68% (15/22) and 73% (17/23) with severe hot flashes in TCM and placebo groups. Hot flash relief was described as either symptom disappearing, a decrease from severe to mild symptoms, or no change. In TCM group, 50% showed no change, 27% decrease and 23% symptoms disappearing. In the placebo group, 70% no change, 30% decrease and no pts reporting symptoms disappearing. A statistically significant difference exists between the two groups (P &lt; 0.05). In TCM group, 73% of pts sleep improvement compared to 35% in the placebo group (P &lt; 0.05). No adverse events or any side effects were reported. Conclusion: The oral solution of TCM is effective in alleviating tamoxifen-induced hot flashes and sleep disturbance. The study of the drug’s mechanism and an expanded clinical trial are underway. No significant financial relationships to disclose.
Functional reprogramming of regulatory T cells in the absence of Foxp3
Authors: Louis-Marie Charbonnier, Ye Cui, Emmanuel Stephen-Victor, Hani Harb, David Lopez, Jack J. Bleesing, Maria I. Garcia-Lloret, Karin Chen, Ahmet Ozen, Peter Carmeliet, Ming O. Li, Matteo Pellegrini, Talal A. Chatila
Journal: Nature Immunology (2019)
Multicenter phase II study of cetuximab plus docetaxel in 84 patients with recurrent or metastatic, platinum-pretreated SCCHN
Authors: M. K. Knoedler, T. Gauler, A. Matzdorff, O. Jordan, M. Schroeder, V. Gruenwald, A. Dietz, D. Arnold, B. Hennemann, U. Keilholz
Journal: Journal of Clinical Oncology (2009)

6048 Background: Cetuximab and docetaxel are both active in squamous cell carcinoma of the head and neck (SCCHN). We investigated the efficacy of cetuximab plus docetaxel as second-line treatment in platinum-pre-treated patients with recurrent and or metastatic SCCHN. Methods: 84 patients were enrolled and received cetuximab (initial dose of 400 mg/m2, followed by subsequent weekly doses of 250 mg/m2) and docetaxel (35 mg/m2 on days 1, 8, 15 of a 4-week cycle) for a maximum of 6 cycles. Patients with stable disease continued to receive cetuximab until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate according to RECIST criteria. Secondary endpoints were response rate in relation to platinum sensitivity, progression-free survival, overall survival, and toxicity. Results: According to RECIST there were 10 PR (12%) and 23 SD (27%), resulting in a disease control rate of 39%. Response to protocol treatment was unrelated to previous platinum sensitivity. Median progression-free survival was 4 months (95% CI, 2.9 to 5.1) and median overall survival was 7 months (95% CI, 5.5 to 8.5). The duration on protocol treatment exceeded 12 months in 6 (8%) patients. Grade III/IV toxicities included gastric perforation (n = 1), pneumonia (n = 7), mucositis and skin toxicities. Conclusions: Cetuximab plus docetaxel was an active second-line treatment regimen with acceptable toxicity in patients with platinum-pretreated SCCHN. The responsiveness was independent of previous platinum sensitivity. [Table: see text]
Suboptimal SVR rates in African patients with atypical genotype 1 subtypes: Implications for global elimination of hepatitis C
Authors: Kate Childs, Christopher Davis, Mary Cannon, Sarah Montague, Ana Filipe, Lily Tong, Peter Simmonds, Donald Smith, Emma C. Thomson, Geoff Dusheiko, Kosh Agarwal
Journal: Journal of Hepatology (2019)

Highlights•Unusual genotypes (G1 non 1a/1b or G4 non 4a/4d) were common in African patients.•11 previously unclassified HCV subtypes were represented including novel G1p.•Patients with unusual G1 subtypes had a lower SVR rate than any other genotype.•Failures were driven by patients treated with a first generation NS5A inhibitor.•The majority of unusual G1 subtypes had baseline NS5A resistance mutations.Graphical abstractAbstractBackground & AimsHCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients.MethodsWe identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen next-generation sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences.ResultsOf 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%).ConclusionsMost individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination.Lay summaryDirect-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these genotypes. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.
Comparison of engraftment in patients undergoing peripheral blood stem call transplantation (PBSCT) with or without support of G-CSF on day +5: A prospective cohort study results
Authors: F. Arpaci, K. Baskoy, S. Ataergin, A. Ozet, S. Komurcu, B. Ozturk
Journal: Journal of Clinical Oncology (2006)

17521 Background: The role of G-CSF administration on day +5 after PBSCT in terms of hematologic engraftment and supportive treatment need has been evaluated. Methods: Forty-two consecutive patients with solid and hematological malignancies were enrolled in two cohort groups depending on G-CSF administration. Twenty-seven patients were given G-CSF (5 μg/kg/day) from day +5 after the transplantation until the achievement of neutrophil engraftment. Posttransplant G-CSF was not given to the control arm of 15 patients. A number of at least 2 × 10 6 CD34+ cells per kilogram collected by cytapheresis were given to all patients. Results: A significant difference was found between the two groups in favor of G-CSF receiving group, in terms of neutrophil engraftment time (10.56 ± 1.22 vs 11.93 ± 2.89 day; p = 0.04), number of days with fever (3.33 ± 2.66 vs 5 ± 2.95 day; p = 0,03) and number of the days requiring antibiotic therapy (7.07 ± 3.46 vs 11.87 ± 3.74 day; p &lt; 0,001); whereas, no statistically significant difference was noted in terms of hospitalization period (13.30 ± 4.79 and 13.53 ± 2.56 day; p = 0.26), platelet engraftment time (12.22 ± 2.79 and 13.40 ± 3.89 day; p = 0.26) and erythrocyte transfusion need; however, platelet transfusion need was statistically significant between the groups with and without G-CSF support (1.27 ± 0.96 vs 0.56 ± 0.75, p = 0.01) Conclusions: This study reveal that starting G-CSF on day +5 may fasten the neutrophil engraftment, decrease the number of days with fever, as well as a the need for antibiotic therapy in posttransplant period. No significant financial relationships to disclose.