tbuckley/cabot-search huggingface dataset:
Breast cancer instructs dendritic cells to express OX40 ligand and to prime pro-inflammatory type 2 CD4+ T cells that facilitate tumor development.
Authors: AK Palucka, A Pedroza, C Aspord, M Gallegos, E Burton, J Banchereau
Journal: Cancer Research (2009)

Abstract Abstract #1050 We found that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. CD4+ T cells infiltrating breast cancer tumors secrete type 1 (IFN-g), pro-inflammatory (TNF) as well as high levels of type 2 (IL-4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated STAT6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells.&amp;#x2028; To determine the link between breast cancer, DCs and CD4+ T cells, we implanted human breast cancer cell lines in NOD/SCID b2m-/- mice engrafted with human CD34+ hematopoietic progenitor cells (HPCs) and autologous T cells. There, CD4+ T cells promote early tumor development. This can be prevented by administration of IL-13 antagonists and is dependent on DCs. Furthermore, these humanized mice demonstrate a signature of IL-13.&amp;#x2028; Similarly to patient samples, in humanized mice breast cancer but not melanoma tumors are infiltrated with large numbers of human myeloid DCs. DC isolated from breast tumor and its draining lymph nodes induce the production of high level of IL4, IL13 and TNF by naive CD4 T cells further demonstrating that breast tumor modulates DC to induce an inflammatory Th2 response.&amp;#x2028; Accordingly, immunofluorescence staining of breast cancer tissue sections from patients shows high expression of OX40 ligand on DCs. This can be ascribed to activity of breast cancer cell-derived soluble factors. Finally, blocking OX40 ligand prevents generation of IL-13 secreting CD4+ T cells.&amp;#x2028; Thus, breast cancer targets DCs to generate pro-inflammatory type 2 immunity that promotes its development.&amp;#x2028; Supported by U19 AIO57234, RO-1 CA89440, CA78846, and CA85540. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1050.
OP0191 The Fecal Microbiota of Rheumatoid Arthritis Patients Differs from that of Healthy Volunteers and is Considerably Altered by Treatment with Biologics
Authors: Y. Maeda, M. Matsushita, A. Yura, S. Teshigawara, M. Katayama, M. Yoshimura, A. Watanabe, E. Tanaka, S. Tsuji, A. Kitatobe, Y. Harada, S. Ohshima, Y. Katada, J. Hashimoto, K. Ogata, T. Takahashi, H. Tsuji, K. Nomoto, A. Kumanogoh, K. Takeda, Y. Saeki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> New insights from DNA sequence-based analyses of gut microbial communities and the renewed interest in mucosal immunology suggest that the microbiome is an important environmental factor influencing autoimmune disease manifestations. <h3>Objectives</h3> To investigate the fecal microbiota of rheumatoid arthritis (RA) patients and healthy volunteers (HVs), we used the Yakult Intestinal Flora-SCAN (YIF-SCAN<sup>®</sup>), based on reverse transcription–quantitative polymerase chain reaction, with primers specific for target bacterial rRNA. We also investigated whether the fecal microbiota changed in RA patients due to biologic (Bio) treatment. <h3>Methods</h3> Fecal samples were collected from 55 RA patients and 77 HVs in NHO Osaka Minami Medical Center during 2011–2012. YIF-SCAN® was performed to quantify the bacterial count with 16S or 23S rRNA-targeted group-specific primers. 25 RA patients were re-examined after they underwent Bio treatment (tocilizumab, 10; infliximab, 9; etanercept, 3; adalimumab, 1; abatacept, 2) for 6 mo. Patients who had received antibiotic therapy were excluded. <h3>Results</h3> The mean age was 57.8 ± 14.5 and 36.3 ± 10.7 years; mean body weight, 54.5 ± 10.0 and 57.0 ± 9.0 kg; and the proportion of women, 72.7% and 90.9%, for the RA patients and HVs, respectively. From the facultative anaerobic groups, the total population levels of <i>Lactobacillus</i> (especially the <i>Lactobacillus gasseri, L. reuteri,</i> and <i>L. fermentum</i> subgroups) and <i>Enterococcus,</i><i>Enterobacteriaceae</i> were significantly higher in RA. These results support those of our 2012 study [1]. The background of the 25 RA patients reanalyzed after treatment is shown in Table 1. The DAS28CRP was 4.1 ± 1.1 at baseline and 2.5 ± 1.1 at 6 mo. 12 patients (48%)achieved remission (DAS28CRP &lt; 2.3) at 6 mo. The total bacterial count and total population levels of the Clostridium. coccoides group, Bifidobacterium, and the L. gasseri and L. plantarum subgroups significantly decreased at 6 mo (Table 2). <h3>Conclusions</h3> We confirmed the difference in the fecal microbiota of RA patients and HVs. Bio treatment considerably reduced commensal bacteria in RA patients. To our knowledge, this is the first study describing changes in fecal microbiota due to Bio treatment. Further studies are required to elucidate the clinical significance of these results. <h3>References</h3> Y.maeda, et al. Ann Rheum Dis 2012;71(Suppl3):496 <h3>Disclosure of Interest</h3> None Declared
Two papers in The BMJ with statin side effect errors shouldn't be retracted, independent panel concludes
Authors: N. Hawkes
Journal: BMJ (2014)

Two articles published in The BMJ that contained an error in reporting the side effects of statins should not be retracted, an independent panel set up by the journal has concluded.

The errors, which have been corrected, were not such as to justify retraction under the code adopted by the Committee on Publication Ethics (COPE), says the panel, chaired by Iona Heath, a former president of the Royal College of General Practitioners. Calls for retraction of the articles have been led by Rory Collins of Oxford University, who complained that by misrepresenting the side effects of statins the articles might discourage people from taking the drugs and cost lives.

But neither article, one by a team led by John Abramson of Harvard University and the other by the London cardiologist Aseem Malhotra,1 2 met the COPE criteria, which say that retraction should usually be reserved for publications that are so seriously flawed that their findings or conclusions cannot be relied on. The code says, “If only a small part of an article reports flawed data and especially if this is the result of genuine error then the problem is best rectified by a correction or erratum.”

In the case of both the articles in The BMJ the error was to claim, on …
Recanalized Umbilical Vein in a Patient with Multifocal Malignant Schwannoma
Authors: G C Kaya, M Yilmaz, E Derebek, M A Koçdor, O Dicle, H Durak
Journal: Clinical Nuclear Medicine (2000)

A 72-year-old man with symptoms of anemia underwent abdominal ultrasound and computed tomography (CT) during a clinical work-up. Multiple mass lesions thought to be intestinal lymphoma were found. In the meantime, the patient experienced melena and hematochezia, for which he was referred for Tc-99m–labeled red blood cell (RBC) scintigraphy to localize the active gastrointestinal bleeding site. Flow images showed increased perfusion to the masses, indicating that they were well vascularized. Focally increased activity in the midabdomen that persisted throughout the study with no distal movement was caused by the recanalized umbilical vein, which was also shown by CT. No active bleeding site was identified on scintigraphic images. Histopathologic examination revealed multifocal malignant schwannoma, a rare abdominal tumor.
Abstract 272: Direct binding of neuregulin-1 to integrins is involved in neuregulin-1/ErbB signaling
Authors: Katsuaki Ieguchi, Zi Ma, Yoko K. Takada, Yoshikazu Takada
Journal: Cancer Research (2010)

Abstract Crosstalk between growth factor receptors and integrins play a role in growth factor signaling. In current models of NRG/ErbB signaling, integrins and ErbB receptors transduce signals independently upon binding to their ligands (e.g., extracellular matrix and NRGs, respectively) and their signals are merged inside the cells. We discovered that the EGF-like domain of NRG1 binds directly to integrins αvβ3 and α6β4. Docking simulation predicted that three Lys residues at the amino terminus of NRG1 are involved in integrin binding. We mutated these residues to Glu (designated the 3KE mutant). Indeed the 3KE mutation markedly reduced the NRG1 binding to integrins, while the 3KE mutation did not affect the NRG1 binding to ErbB3. This is consistent with the prediction that the Lys residues critical for integrin binding are not involved in ErbB binding. We studied the effect of the 3KE mutation on NRG1/ErbB signaling in MCF-7 and T47D human breast cancer cells. The 3KE mutation markedly reduced the levels of ErbB3 phosphorylation, AKT and Erk1/2 activation, suggesting that direct integrin binding to NRG1 is critical for NRG1/ErbB signaling. Furthermore, stimulation of cells with WT NRG1 induced co-precipitation of ErbB3 with integrin α6β4. This suggests that WT NRG1 induces integrin-NRG1-ErbB3 ternary complex formation. WT NRG1 induced co-precipitation of ErbB3 with integrin αvβ3 to a less extent than with integrin α6β4. This probably reflects low levels of integrin αvβ3 expression compared to integrin α6β4 in these cells. In contrast, the 3KE mutation markedly reduced the levels of ternary complex formation, suggesting that this process depends on the ability of NRG1 to bind to integrins. Notably, the 3KE mutant acted as an antagonist to ErbB/NRG1 signaling in vitro and effectively suppressed proliferation of breast cancer cells in vivo. These results suggest that 1) NRG1-integrin interaction mediates crosstalk of integrins with ErbB receptors, 2) integrin α6β4 plays a major role in ErbB/NRG signaling in the cancer cells tested, and 3) the 3KE mutant has potential as a therapeutic in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 272.
Abstract 4851: Selective small molecule inhibition of anti-apoptotic MCL-1
Authors: Nicole A. Cohen, Michelle L. Stewart, Evripidis Gavathiotis, Jared L. Tepper, Joseph T. Opferman, Loren D. Walensky
Journal: Cancer Research (2012)

Abstract BCL-2 family proteins are key regulators of the mitochondrial apoptotic pathway in health and disease. Anti-apoptotic members such as BCL-2, BCL-XL, and MCL-1 have been implicated in the initiation, progression, and chemoresistance of human cancer. The anti-apoptotic BCL-2/BCL-XL groove that binds and sequesters pro-apoptotic BH3 death helices has been successfully targeted by small molecules and peptides. Such compounds induce tumor cell apoptosis and are being advanced in clinical trials as promising next-generation cancer therapeutics. Notably, selective antagonists such as ABT-737 are highly effective at inducing apoptosis in BCL-2/BCL-XL-dependent cancers, but are rendered inactive by overexpression of MCL-1, a formidable chemoresistance protein that lies outside the molecule's binding spectrum. By screening a library of Stabilized Alpha-Helix of BCL-2 domains (SAHBs), we previously discovered that the MCL-1 BH3 helix is itself a potent and exclusive MCL-1 inhibitor (Stewart et al., Nat Chem Biol, 2010). Here, we deployed this natural peptidic inhibitor of MCL-1 in a competitive binding screen to identify an MCL-1 inhibitor molecule (MIM) that displays exquisite selectivity in in vitro binding and functional assays. NMR analysis documented that MIM engages the canonical BH3-binding pocket of MCL-1. Importantly, MIM selectively triggers caspase 3/7 activation and apoptosis in a cancer cell line that is dependent on induced overexpression of MCL-1, but showed no activity in the isogenic cell line that is driven instead by overexpressed BCL-XL. Conversely, ABT-737 manifested activity in the BCL-XL-overexpressing cancer cells but had no effect on the corresponding MCL-1-dependent cells. Thus, we report the application of MCL-1 SAHB to identify a selective small molecule inhibitor of MCL-1 that exhibits pro-apoptotic activity in the specific context of MCL-1 dependence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4851. doi:1538-7445.AM2012-4851
Real-time histology of colon polyps – is it ready for prime time?
Authors: A. Rastogi
Journal: Endoscopy (2012)

Up until a few years ago, the idea of real-time histology of colon polyps might have sounded absurd to many. However, recent innovations in optical technologies have now afforded gastroenterologists the unique capability of in vivo identification of polyp histology, in real time during colonoscopy. These technologies work on different principles of optics. They can accentuate the contrast between the normal and abnormal tissue and highlight the surface patterns on polyps, for example with dyes (chromoendoscopy) or by varying the wavelength of light by filters (narrow-band imaging [NBI]) or by color enhancement methods (Fujinon Intelligent Chromoendoscopy [FICE], i-scan). Other technologies can increase the magnification (confocal endomicroscopy and endocytoscopy) or help to characterize polyp histology by quantifying the color and intensity of the reflected light (autofluorescence, spectroscopy). Broadly speaking, these technologies can be divided into “large-field” and “small-field” technologies depending upon the area of mucosa imaged. Large-field technologies include chromoendoscopy, electronic chromoendoscopy (NBI, FICE, i-scan), and autofluorescence, whereas the small-field technologies include confocal endomicroscopy, endocytoscopy, and spectroscopy.
Abstract 501: A novel PDT system consisting of a DDS-type photosensitizer and a newly developed fiber probe for homogenous irradiation
Authors: Kozo MIYAZAKI, Yuji MORIMOTO, Miho MURAOKA, Michiaki KUMAGAI, Souta HORIE, Shigeto FUKUSHIMA, Nariyoshi SHINOMIYA, Nobuhiro NISHIYAMA, Kazunori KATAOKA
Journal: Cancer Research (2010)

Abstract Introduction: Photodynamic therapy (PDT) has already been established as anti-cancer therapy. However, since some types of cancer proliferate multifocally and/or diffusely, topical irradiation of light by a conventional optical fiber results in an insufficient PDT effect. Moreover, using a conventional fiber, we cannot irradiate minimal tumors that escape from detection by conventional diagnostic approaches. When PDT is applied to the lesions of hollow organs, if we homogenously irradiate a wide area of the organ wall, undetectable minimal tumors and multifocally proliferating tumors can be treated simultaneously. In order to realize this concept, we have developed a novel fiber probe that provides homogenous light irradiation on the mucosa of hollow organs. In this study, we fabricated a homogenous irradiation fiber probe (HIFP) for illuminating the bladder by the use of state-of-the-art processing technology (torsional deformation of a fiber core, conical shaping of fiber tip, etc). We evaluated the PDT effect on a rat orthotopic bladder tumor model using the HIFP and a dendrimer phthalocyanine micelle (DPc/m) that we developed as a DDS-type photosensitizer. Materials and Methods: The property of spatial distribution of light emitted from the HIFP was measured. Using the HIFP, PDT was carried out on a rat orthotopic bladder tumor model 24 h after administration of a photosensitizer (Photofrin or DPc/M) and PDT effects were pathologically evaluated. Results: Preliminarily examination of ultrasonic imaging revealed that the shape of the rat bladder approximates an ellipsoidal body with a long radius of 7.5 mm and a short radius of 5 mm. Analysis of spatial distribution showed that the light emitted from the HIFP covered 90% of the whole luminal area of the approximate ellipsoidal body, while the light emitted from a control fiber (CF) (NA=0.41; flat cleaved end) covered only 15%. Pathological study of the PDT-treated rat using the CF revealed that an anti-tumor effect occurred only in the local area proximate to the focal point of the CF with no anti-tumor effect in tumors in other areas of the bladder wall. In contrast, pathological study of the PDT-treated rat using the HIFP revealed that light was distributed over 60 −80% of the mucosa of the bladder and tumor proliferation was widely suppressed. Conclusion: Widespread and homogenous irradiation in the mucosa of the bladder was achieved using the newly developed fiber probe. PDT using a combination of the fiber probe and DPc/M enhanced the anti-tumor effect without bladder shrinking. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 501.
Maintenance of Granuloma Formation in Pulmonary Sarcoidosis by T Lymphocytes within the Lung
Authors: Gary W. Hunninghake, James E. Gadek, Roscoe C. Young, Oichi Kawanami, Victor J. Ferrans, Ronald G. Crystal
Journal: New England Journal of Medicine (1980)

Pulmonary granulomata of sarcoidosis are composed primarily of mononuclear phagocytic cells that are probably derived from blood monocytes. To evaluate the concept that recruitment of blood monocytes to the sarcoid lung is mediated by chemoattractants produced by immune effector cells within the lung, we obtained mononuclear cells from lung and blood of six patients with active pulmonary sarcoidosis, six normal subjects, and six patients with active idiopathic pulmonary fibrosis and studied their ability to secrete a chemotactic factor for monocytes. Lung T lymphocytes from all sarcoidosis patients, but not from normal subjects or patients with idiopathic pulmonary fibrosis, spontaneously secreted such a mediator. Lung T lymphocytes from patients with sarcoidosis secreted more monocyte chemotactic factor than did blood T lymphocytes from the same patients. The accumulation of monocytes in the lung in patients with pulmonary sarcoidosis may be mediated by local production of monocyte chemotactic factor by lung T lymphocytes.
Abstract 4850: Sensitization to chemotherapy through interference with FOXO4 - a pivotal node between senescence and apoptosis
Authors: Peter L. j. de Keizer, Judith Campisi
Journal: Cancer Research (2012)

Abstract Malignant transformation of damaged cells is restricted through activation of potent tumor suppressive mechanisms as apoptosis and cellular senescence. While apoptotic cells are cleared from the organism, senescent cells are withdrawn from the cell cycle, remain present in the organism and accumulate with age. Senescent cells retain the capacity to become tumorigenic upon acquisition of additional mutations. Forcing a shift from the senescence program towards apoptosis may therefore prove clinically useful as treatment for senescence-escaped tumors. Unfortunately, it is still unclear why certain cells undergo apoptosis whereas others enter senescence in response to identical stimuli. We establish the transcription factor FOXO4 as a pivot in this decision process. FOXO4 expression is elevated in DNA-damaged cells, associated with its recruitment to focal sites of DNA damage. Treatment of primary cultures that would otherwise senesce in response to DNA-damaging insults could be pushed towards apoptosis by interference with FOXO4 expression. This formed the basis for a series of experiments addressing the potential role of FOXO4 in tumor survival. Recently, the BRAFV600E-specific drug Vemurafenib has been shown to significantly enhance tumor-free survival rates of malignant melanoma patients carrying this mutation, but in time recurrence tends to occur. Excitingly, we observed that interference with FOXO4 expression in BRAFV600E-driven malignant melanomas sensitized them to Vemurafenib as well as their “classical” chemotherapeutic agent Dacarbazine. Several NRAS-mutated melanoma lines could furthermore be spontaneously induced to apoptose by FOXO4 interference. Finally, these observations are not limited to melanoma and interference with FOXO4 also sensitized mammary carcinoma cells toward 5-fluorouracyl and prostate carcinoma cells towards Mitoxantrone. We are currently exploring the potential of targeted anti-FOXO4 therapy in vivo to see whether FOXO4 could provide a general Achilles’ heel in the survival of malignant carcinomas. This work is supported by post-doctoral fellowship Buit-4649 of the Dutch Cancer Society awarded to PLJDK and NIH grant AG017242 awarded to JC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4850. doi:1538-7445.AM2012-4850
MUCOSECTOMIA CON BANDAS: ¿UN TRATAMIENTO APROPIADO PARA LESIONES PRENEOPLÁSICAS O NEOPLASICAS PRECOCES?
Authors: J Espinel Díez, E Pinedo Ramos, B Alvarez Cuenllas, L Vaquero Ayala
Journal: Endoscopy (2013)

Introducción: La mucosectomía es una técnica alternativa a la quirúrgica, en el tratamiento de lesiones preneoplásicas y cáncer intramucoso. La mucosectomía con bandas (MB) permite resecciones secuenciales, sin necesidad de inyección submucosa ni de retirada del endoscopio. Objetivo: Valorar la eficacia y seguridad de la MB en el tratamiento de lesiones preneoplásicas o de cáncer intramucoso del TDS. Material y Método: Estudio de 24 pacientes sucesivos (15 hombres, 9 mujeres; edad media: 65,6 años; rango: 38 – 90 años) tratados mediante MB (mayo 2005-junio 2013). La MB se realizó según la técnica convencional, resecándose las lesiones con corriente de coagulación pura. Resultados: Lesiones esofágicas (12 pacientes): 10 pacientes con esófago de Barrett (8 con DAG, 1 con DBG, 1 con ADC intramucoso); 1 paciente con tumor de Abrikossoff, 1 paciente con DAG no relacionada con Barrett. La mucosectomía confirmó el diagnóstico de la biopsia inicial pero en 2 (16,6%), se advirtió una lesión degenerada no conocida. Una paciente (ADC con infiltración submucosa) fue operada no advirtiéndose en la cirugía tumor residual. Se precisaron una media de 1,8 mucosectomías (rango 1 – 4). Se advirtieron complicaciones (estenosis, HD leve) en 4 pacientes (33,3%). El seguimiento medio fue de 24 meses. Lesiones gástricas (12 pacientes): 4 pacientes con ADC intramucoso, 1 paciente con carcinoide, 7 pacientes con lesiones adenomatosas. La mucosectomía confirmó el diagnóstico de la biopsia inicial en 7 pacientes, pero en 5 (41,6%) se evidenció una lesión degenerada no advertida. Se precisaron una media de 1,08 mucosectomías (rango 1 – 2). Hubo complicaciones leves (sangrado) en 5 pacientes (41,6%). El seguimiento medio fue de 23,3 meses. Conclusiones: La MB constituye un eficaz método diagnóstico y terapéutico en el manejo de las lesiones preneoplásicas y cáncer intramucoso del TDS, obteniéndose muy buenos resultados a medio plazo.