tbuckley/cabot-search huggingface dataset:
Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation
Authors: Bianca Harris, Sejal M. Morjaria, Eric R. Littmann, Alexander I. Geyer, Diane E. Stover, Juliet N. Barker, Sergio A. Giralt, Ying Taur, Eric G. Pamer
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.To investigate whether changes in gut microbiota are associated with PCs after HCT.A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and γ-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas γ-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009).This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and γ-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.
PWE-350 Resilience and protection against the dose-related toxicity of hydrogen sulphide
Authors: D Sawbridge, J Wilson, C Probert
Journal: Gut (2015)

<h3>Introduction</h3> Hydrogen sulphide (H2S) is thought to have a biphasic effect on cells leading to cellular proliferation at “low” doses (micromolar) and cell death in “high” doses (millimolar). It is unclear how this is related to colonic physiology and in-vivo concentrations. H2S is cytotoxic by inhibiting cytochrome c, while genotoxicity may be mediated by free radicals of uncertain origin. We tested the effect of sub-physiological and physiological concentration of H2S on epithelial cell lines to identify proliferative/cytotoxic effects and whether a free radical scavenger could be protective. <h3>Method</h3> Cell lines were seeded at a concentration of 2.5 × 10<sup>4</sup>per well and cultured until 70–80% confluency. NaHS was dissolved in distilled water at 0, 100 μM, 500 μM, 1 mM, 2.5 mM and 5 mM and added to the culture. The number of surviving cells was counted after 24 h. In the protection experiments 1mM Tiron, a free radical scavenger, dissolved in distilled water was added concurrently. <h3>Results</h3> H2S proved considerably cytotoxic to CACO2 cells at even physiological doses (100 μM, 76.7% death), while at the higher end of the claimed physiological range (2.5 mM) 98.8% cell death was noted). Similar findings occurred with HCT116, though increased survival was noted with HT29 cells compared to the other colorectal cell lines (100 µM 43.9% death). Tiron was protective in all cell lines, especially in the CACO2 cells, with 100 μM + 1 mM Tiron mitigating cell death at 20% and 2.5 mM at 68.8%. P-values were significant at p &lt; 0.001 for all the above results. HELA and A549 cells were more resilient (100 μM, 7.6%, 2.5 mM, 37.6%) or A549 cells (100 μM, 5.2%, 2.5 mM, 22.6%), though these data were non-significant. <h3>Conclusion</h3> H2S is cytotoxic to cell lines, especially colonic lines, at estimated physiological doses. Tiron, a free-radical scavenger, increases cell survival after H2S exposure. This implicates excess free radicals in cytotoxicity. HT29 cells, with intact mismatch repair, were more resilient than other colorectal lines with mismatch deficiency. Contrary to some published research, this experiment suggests that H2S is cytotoxic, even at physiological levels, via a free radical mechanism, rather than protective against such insults. Colonic H2S may potentiate the risk of colorectal cancer. Steps to reduce its production or inhibit its action may reduce the risk of progression to cancer and reduce the chance of recurrence after surgery. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Szabo C, <i>et al</i>. Tumor-derived hydrogen sulfide, produced by cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. Proc Natl Acad Sci USA. 2013;110(30):12474–9 Deplancke B, Gaskins HR. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 2003;17(10):1310–2
Chronic Esophageal Perforation With Periesophageal Abscess Mimicking Malignancy on FDG PET/CT
Authors: Aisheng Dong, Ling Zhang, Yang Wang, Changjing Zuo
Journal: Clinical Nuclear Medicine (2016)

A 53-year-old man was admitted because of progressive dysphagia and retrosternal pain for 20 days. Esophagogastroduodenoscopy showed an irregular submucosal bulge on the distal esophageal wall. A barium swallow showed a triangular-shaped outpouching of contrast material with minimal contained extravasation into the periesophageal area. Enhanced CT showed thickening of the distal esophagus with an area containing air and septa. FDG PET/CT showed intense FDG uptake of the thickened esophageal wall mimicking malignancy. Endoscopic ultrasonography-guided biopsy of the submucosal mass revealed granulation tissue. The imaging and pathologic findings were consistent with chronic esophageal perforation with periesophageal abscess.
Histopathology of the Adrenal Glands of Rats Fed a Low-Protein, Low-Riboflavine Diet Alone, or with &lt;italic&gt;p&lt;/italic&gt;-Dimethylaminoazobenzene&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: A. Symeonidis, A. S. Mulay
Journal: JNCI Journal of the National Cancer Institute (1956)

Journal Article Histopathology of the Adrenal Glands of Rats Fed a Low-Protein, Low-Riboflavine Diet Alone, or with p-Dimethylaminoazobenzene Get access A. Symeonidis, A. Symeonidis National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. S. Mulay A. S. Mulay National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 5, April 1956, Pages 1163–1179, https://doi.org/10.1093/jnci/16.5.1163 Published: 01 April 1956 Article history Published: 01 April 1956 Received: 13 September 1965
Augmented Berlin-Frankfurt-Muenster Based Therapy For Young Adults With Acute Lymphoblastic Leukemia (ALL)
Authors: Michael E. Rytting, Deborah A. Thomas, Susan O'Brien, Kurt Schroeder, Rebecca Garris, Jorge E. Cortes, Farhad Ravandi, Naveen Pemmaraju, Naval Daver, Stefan H. Faderl, Anna R. K. Franklin, Gautam Borthakur, Steven M. Kornblau, Hagop M. Kantarjian
Journal: Blood (2013)
Combination of trastuzumab, oxaliplatin, and docetaxel as first-line treatment in HER2-positive metastatic breast cancer patients: First-step results of a phase II trial (HOT trial)
Authors: D. Amoroso, S. Donati, C. Valsuani, C. Puccetti, M. Rondini, O. Siclari, G. Tartarelli, P. Giannessi, A. Falcone, A. Camerini
Journal: Journal of Clinical Oncology (2009)

1132 Background: The addiction of trastuzumab to standard chemotherapy has improved the outcome of HER-2-positive metastatic breast cancer (MBC) pts. Oxaliplatin and docetaxxel are among the most active agents in MBC pts pretreated with anthracyclines. In vitro studies showed synergistic effect of the combination. We investigated the feasibility and the safety of the 3-drug combination given as first line chemotherapy (CT) in HER-2-positive MBC. Methods: HER-2-positive MBC pts were prospectively enrolled to receive a first-line treatment consisting of trastuzumab 8 mg/kg loading dose iv (followed by 6 mg/kg) on day 1, docetaxel 75 mg/sqm iv on day 1, and oxaliplatin 70 mg/sqm on day 2 every 21 days. All pts received peg-filgrastim 6 mg on day 3 to prevent bone marrow toxicity. Pts received up to 9 cycles of CT. Primary end points were overall response rate (ORR) (according to RECIST criteria), clinical benefit (CB), and tolerability. Cardiac function was evaluated by echocardiography at baseline, each 3 courses and at the end of treatment. Results: To date, 13 pts have been enrolled (median age 59 yrs [range 34–70]; ECOG PS 0) representing the first-step accrual according to Minimax design. Ten pts had previously received anthracyclines as adjuvant treatment and 11 pts presented with visceral metastasis. All pts received at least 6 cycles of treatment with 7 pts continuing up to 9 cycles. Response and toxicity data are available for all pts. Two pts experienced CR, 7 pts PR, and 4 pts showed SD (lasting more than 6 months in 3 cases) with an ORR of 70% and a CB of 100%. No pts progressed during treatment. No grade 4 toxicity was observed. Most common grade 3 toxicities were diarrhea (18%), nausea/vomiting (22%), mucositis (11%). In particular, 2 episodes of febrile neutropenia were reported and no grade 4 haematologycal toxicity was observed. No significative reduction of LVEF were reported. Conclusions: The combination of trastuzumab, oxaliplatin, and docetaxel (HOT combination) showed promising activity and was well tolerated as first-line treatment in pts with HER-2-positive MBC. Peg-filgrastim profilaxis improved safety profile. No significant financial relationships to disclose.
Reaching Millennium Development Goal 4
Authors: Malcolm Molyneux, Elizabeth Molyneux
Journal: The Lancet Global Health (2016)

2015 has come to an end, and with it the opportunity for countries—and the world—to reach the Millennium Development Goals (MDGs). Here we look at how close the world has come to achieving MDG 4—ie, to reduce by two-thirds, between 1990 and 2015, the under-5 mortality rate.
Lymphocyte surface markers in orbital lymphoid neoplasms.
Authors: D C Harmon, A C Aisenberg, N L Harris, R L Dallow, R M Linggood, B M Wilkes
Journal: Journal of Clinical Oncology (1984)

Since the malignant nature of many orbital lymphoid infiltrates is difficult to assess from pathologic examination alone, over the past four years lymphocyte surface marker studies have been added to the evaluation of 23 such cases. Only 10 of the 23 could be confidently classified as malignant lymphoma by histology alone. However, monoclonal surface immunoglobulin was found in 15, supporting the pathologic diagnosis of malignancy in eight and adding seven that could not have been diagnosed otherwise. Clinical evaluation, including a median follow-up of 18 months, revealed manifestations of systemic lymphoma in six of those 15; two had been diagnosed only by surface markers. In contrast, only one of eight cases lacking monoclonal surface immunoglobulin exhibited clinical evidence of malignancy (that case was also indeterminate by histologic criteria). The addition of surface marker analysis permits more accurate diagnosis of orbital lymphoma than is possible from pathologic study alone. This technique can suggest the subtype of lymphoma.
<i>Response to</i>“From histology to neurocognition: the influence of tumor grade in glioma of the left temporal lobe on neurocognitive function”
Authors: Kyle R. Noll, Jeffrey S. Wefel
Journal: Neuro-Oncology (2015)

The authors appreciate Dr Kane's commentary on our efforts to delineate relationships between histologic tumor grade and neurocognitive functioning (NCF) in patients with glioma of the left temporal lobe.1 In addition to lending support to our work, his letter offers us an opportunity to elaborate upon possibilities for further investigation. As Dr Kane noted, we demonstrated that patients with glioblastoma exhibited more frequent and severe NCF impairment than those with lower-grade tumors. Importantly, this finding was independent of lesion size, suggesting that differences in NCF across tumor grades relate to variation in growth characteristics, which we refer to as “lesion momentum.” More specifically, we proposed that the more aggressive nature of glioblastoma limits neuroplastic reorganization of brain networks underlying NCF to a greater extent than slower growing tumors of lower grades.
ERCC1 mRNA-based randomized phase III trial of docetaxel (doc) doublets with cisplatin (cis) or gemcitabine (gem) in stage IV non-small-cell lung cancer (NSCLC) patients (p)
Authors: R. Rosell, M. Cobo, D. Isla, B. Massuti, A. Montes, L. Paz-Ares, M. A. Munoz, N. Vinolas, G. L. Vivanco, E. Felip
Journal: Journal of Clinical Oncology (2005)

7002 Background: ERCC1 is a leading component of NER in repairing cis damage. Increased ERCC1 mRNA levels have been related to resistance to platinum-based chemotherapy. We hypothesized that p with high tumor ERCC1 levels would have a significantly better response with a non-cis combination. Methods: Stage IV NSCLC p with available tumor biopsy samples were randomized 1:2 to the control arm (A) or the genotypic arm (B). Arm A received doc/cis. In arm B, ERCC1 expression was examined by TaqMan assay (Response Genetics, Los Angeles, CA); p with low levels received doc/cis (arm B1) and p with high levels received doc/gem (arm B2). ERCC1 expression was examined retrospectively in arm A. At September 2004, 342 of a projected 440 p were included. Results: Data on 192 p are available: 80% male; 33% PS 0. Logistic regression of response showed that arm B1 had better response than A (P=0.04) and than B2 (P=0.02). Median ERCC1 levels were lower in responders in arms A and B1, but higher in responders in arm B2. When ERCC1 mRNA levels were divided into quartiles, p in the lowest quartile attained 70% response in arm B1, while the highest response in arm B2 was observed in the highest quartile (43%). Median ERCC1 levels were lower in adenocarcinomas (adeno) than in squamous cell carcinomas (SCC) (P=0.03). Median survival (MS) in arms A and B1 was 14 months (m) for 49 p in the lowest quartile vs 8 m for 19 p in the highest quartile (P=0.03). MS in arm B2 was 9.5 m in the two highest quartiles. Conclusions: Lower ERCC1 mRNA levels confer better response to doc/cis, while there is a tendency for p with higher levels to respond better to doc/gem than those with lower levels. Complete data on 300 p will be presented. No significant financial relationships to disclose.
Dose escalation and pharmacodynamic study of intravenous adminstration of Reolysin, a live replication competent RNA virus in patients with advanced solid tumors
Authors: M. H. Ghalib, K. K. Desai, R. Gollamudi, I. Chaudhary, M. Einstein, M. Coffey, K. Mettinger, S. Mani, S. Goel
Journal: Journal of Clinical Oncology (2009)

3583 Background: Reolysin is reovirus serotype 3 - Dearing strain, a double-stranded replication- competent RNA non-enveloped icosahedral virus. It induces cytopathic and anti-cancer effects in cells with an activating mutation in the ras proto-oncogene. Methods: This was a single center dose escalation trial of Reolysin administered intravenously every four weeks in doses ranging from 1X10 8 to 3X10 10 tissue culture infective dose (TCID) 50 . Serum for neutralizing antibody, and serum, stool, saliva, and urine for viral shedding were collected. Tumor samples were analyzed for activating mutations in the ras and braf oncogenes. Results: Eighteen patients received 27 doses of Reolysin in 6 dose cohorts accomplishing a 300 fold dose escalation without a protocol-defined dose limiting toxicity. Drug related grade 2 toxicities included fatigue and fever (1 patient each). All patients developed neutralizing antibody during the course of the study. Viral shedding was observed in 6 patients [urine (5), serum (4), saliva (3), and stool (2)]. One patient with anthracycline and taxane refractory breast cancer experienced a partial response (PR) and her tumor had a mutation in the ras oncogene. Biopsy from a chest wall mass showed evidence of necrosis and viral replication by electron microscopy. The overall clinical benefit rate was 45% and appeared higher in patients with viral shedding (67%) than those without (33%). Conclusions: Reolysin administered as a one hour infusion on a monthly schedule is safe and well-tolerated even in multiple doses. Reolysin has anti-tumor activity as a single agent warranting further evaluation, including in combination with chemotherapy. Viral shedding may suggest intrapatient replication yielding a benefit and should be studied carefully in future studies. [Table: see text]
A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling
Authors: Clíona Ní Cheallaigh, Frederick J. Sheedy, James Harris, Natalia Muñoz-Wolf, Jinhee Lee, Kim West, Eva Palsson McDermott, Alicia Smyth, Laura E. Gleeson, Michelle Coleman, Nuria Martinez, Claire H.A. Hearnden, Graham A. Tynan, Elizabeth C. Carroll, Sarah A. Jones, Sinéad C. Corr, Nicholas J. Bernard, Mark M. Hughes, Sarah E. Corcoran, Mary O’Sullivan, Ciara M. Fallon, Hardy Kornfeld, Douglas Golenbock, Stephen V. Gordon, Luke A.J. O’Neill, Ed C. Lavelle, Joseph Keane
Journal: Immunity (2016)

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-γ) receptor signaling. Mal-dependent IFN-γ receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-γ signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-γ-related diseases including autoimmunity and cancer.
Efficacy of opioid analgesics and effect on functional status of pain caused by radiation-induced mucositis among patients with head and neck cancer
Authors: A. Barasch, F. Spijkervet, A. Garden, M. R. Kudrimoti, D. Brachman, M. Brennan, R. B. Tishler, L. Elting, D. Keefe, S. Sonis
Journal: Journal of Clinical Oncology (2008)

6019 Background: Radiation (RT) to the oral cavity (OC), oropharynx (OP), larynx (L), or hypopharynx (HP) causes severe and debilitating mucositis in most patients (pts), particularly when chemotherapy (CT) is administered concomitantly. There are no available agents to prevent mucositis in pts with these cancers, thus, the standard of care is pain control, using opioids when pain is severe. We prospectively studied the risk and severity of mucositis during RT, its impact on daily activities, and analgesic use. Methods: The Triad Burden of Illness study is an international, 41-center, prospective study of the risks for and outcomes of RT- and CT-induced mucositis. At baseline and daily during RT, pts with L/HP or OC/OP cancers completed a previously validated survey describing severity of mouth and throat soreness (MTS) measured from 0 (“no soreness”) to 4 (“extreme soreness”), its interference with drinking, eating, talking, and sleeping measured from 0 (“not limited”) to 4 (“unable to do”), and use of analgesics. Results: To date, 191 evaluable pts have completed RT; 77% were males, and 88% were non-Hispanic whites. All received single daily fractions of RT; 60% had concomitant CT, 57% had intensity modulated RT, and 34% had concomitant boost. Most pts (98%) developed mucositis; 82% reported severe pain (MTS 3–4). Despite regular analgesic use (> 4 days per week) by 83%, and opioid use by 65%, mean MTS remained >2 from weeks 5 - 7 of RT. Use of analgesics, opioids and limitations to daily activities were significantly associated with mucositis severity. Conclusions: The pain caused by radiation-induced mucositis is severe, debilitating and poorly controlled by analgesics among pts with head and neck cancers. Preventive strategies are needed. Maximum MTS 0–2 N=34 % of total (CI) Maximum MTS 3–4 N=157 % of total (CI) P value Regular analgesic use 65 (49-81) 87 (82-92) 0.001 Opioid use 44 (27-62) 70 (62-77) 0.004 Activity limited a lot or unable to do Drinking 6 (1-20) 92 (87-96) <0.001 Eating 21 (9-38) 97 (93-99) <0.001 Talking 24 (11-41) 83 (77-89) <0.001 Sleeping 21 (9-38) 71 (63-78) <0.001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen
<i>Drosophila</i> Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport
Authors: Subhas Mukherjee, Carol Tucker-Burden, Changming Zhang, Kenneth Moberg, Renee Read, Costas Hadjipanayis, Daniel J. Brat
Journal: Cancer Research (2016)

Abstract Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable. Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443–52. ©2016 AACR.
Erratum to ‘Is aortoiliac calcification linked to colorectal anastomotic leakage? A case-control study’ [Int. J. Surg. 25 (2016) 123–127]
Authors: G.S.A. Boersema, K.A. Vakalopoulos, M.C.J.M. Kock, P.M.A. van Ooijen, K. Havenga, G.J. Kleinrensink, J. Jeekel, J.F. Lange
Journal: International Journal of Surgery (2016)