tbuckley/cabot-search huggingface dataset:
Abstract 721: Opposite roles of CD11b+ myeloid cells in primary and recurrent brain tumors
Authors: Wu Sheng-Yen
Journal: Cancer Research (2016)

Abstract Malignant glioma is one of the toughest tumors to be treated at present due to the complexity of the tumor microenvironment and the intrinsic resistant to irradiation. Previous studies have shown that CD11b+ myleoid cells play essential role in brain tumor recurrence following radiation therapy. Here we used the CD11b-diphtheria toxin receptor (CD11b-DTR) transgenic mouse model to evaluate the role of CD11b+ myleoid cells in TK/GCV suicide gene therapy for brain tumor in a murine astrocytomal tumor model, ALTS1C1-TK. Using this transgenic mouse model, the depletion of peritoneal macrophages (CD11b+F4/80+) and blood monocyte (CD11b+Ly6G−Ly6c−) could be achieved after two injections of DT, but the neutrophil (CD11b+Gr-1+) were increased transiently. Results found that the depletion of CD11b+ myleoid cells enhanced the efficacy of TK/GCV therapy as shown by the increase of median surviving time of GCV-treated ALTS1C1-TK tumor-bearing mice from 30.6 days to 37.5 days. Interestingly, the depletion of CD11b+ myleoid cells enhanced tumor growth as shown that tumor-bearing mice had shorter surviving days and larger tumor size after receiving two doses of DT injections compared to the control PBS group (22.4 days vs 25.0 days, respectively). This indicates that depleted CD11b+ myleoid cells might have anti-tumor function for control tumor, but have pro-tumor activity during TK/GCV therapy. This study also found the effect of CD11b+ myleoid cells was only seen when the depletion was performed during the administration of GCV, but not before or after GCV treatment. Collectively, above findings suggest that CD11b+ myleoid cells might have different roles on primary and recurrent brain tumors. Citation Format: Wu Sheng-Yen. Opposite roles of CD11b+ myeloid cells in primary and recurrent brain tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 721.
Abstract 3250: Caspase-1 from MDSC promote MyD88 dependent carcinogenesis that is T-cell independent
Authors: Qi Zeng, Jesse R. Qualliotine, Lee Blosser, Drew Pardoll, Young J. Kim
Journal: Cancer Research (2016)

Abstract Myeloid-derived-suppression cells (MDSC) are functionally defined to suppress T-cells in their primary means of immune evasion mechanism in cancer. However, we have discovered that MDSC can have direct, T-cell independent pro-carcinogenic effect on tumor cells. Sorted monocytic CD14+/CD11b+/HLA-DRlow MDSCs from head and neck squamous cell carcinoma (HNSCC) patients were found to increase the proliferation index of HNSCC cells. This induction of tumor proliferation was not dependent on MDSC-tumor cell contact. Exome analysis showed that these human MDSC from cancer patients expressed high levels of inflammasome complex, and supernatant from the MDSCs were found to secrete IL-1b and IL-18. When we probed the functional significance of these inflammasome complex, we found that MDSC's promotion of tumor proliferative index of the tumor was found to be Caspase-1 dependent. To test this in vivo, T-cell depleted caspase-1 null mice showed significant decrease in tumor growth rate. To confirm the importance of myeloid inflammasome signaling in carcinogenesis, we suppressed MyD88 gene in tumor cell line Cal27 and found that the ability of MDSC to promoting tumor proliferation is diminished. Taken together, our findings demonstrate that tumor infiltrating MDSCs may play a prominent role in chronic inflammation associated carcinogenesis. Citation Format: Qi Zeng, Jesse R. Qualliotine, Lee Blosser, Drew Pardoll, Young J. Kim. Caspase-1 from MDSC promote MyD88 dependent carcinogenesis that is T-cell independent. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3250.
Tumor-infiltrating CD204+ M2 macrophages compared to T cells as a prognosticator for patients with uterine cervical adenocarcinoma.
Authors: Asuka Kawachi, Hiroshi Yoshida, Shigehisa Kitano, Nobuyoshi Hiraoka
Journal: Journal of Clinical Oncology (2016)

5527 Background: Uterine cervical adenocarcinoma is rare but its incidence has been increasing gradually, which has a poor prognosis despite early detection. The tumor microenvironment plays important roles in the biological behavior of cancer. The host immune reaction contributes to the characteristics of the tumor microenvironment, which is represented by tumor-infiltrating immune cells. In this study, we analyzed the tumor-infiltrating immune cells in cervical adenocarcinoma and evaluated their clinicopathological impact. Methods: 148 patients with cervical adenocarcinoma surgically resected in National Cancer Center Hospital were investigated. None of the patients had received any therapy before surgery. For a representative tumor tissue section, immunohistochemical staining was performed for CD3, CD4, CD8, FOXP3 and PD-1 for tumor-infiltrating lymphocytes (TILs), CD68, CD163 and CD204 for tumor associated macrophages (TAMs), PD-L1and p16 for tumor cells. The density of TILs or TAMs was evaluated in intraepithelial and tumor stromal areas separately. For survival and correlation analyses, the patients were divided into two groups showing high and low cell infiltration, using the median value as a cut-off. Results: Most of cases (54.7%) were classified in stage 1b and 26 (17.6%) had recurrent disease. The density of stromal infiltrating CD4+, CD8+, FOXP3+, or PD-1+ lymphocytes, or CD68+ or CD204+ macrophages that had infiltrated invasive adenocarcinoma (n = 127) was significantly higher than in adenocarcinoma in situ (n = 27). Expression of PD-L1 on tumor cells was found in 17.3% of invasive adenocarcinoma and was not associated with HPV infection status. Kaplan–Meier survival analyses revealed that a higher density of tumor-infiltrating CD204+ M2 macrophages was significantly associated with shorter disease-free survival (P = 0.0027). Conclusions: It is suggested that tumor-infiltrating CD204+ M2 macrophages is a prognosticator for patients with cervical adenocarcinoma. Host immune reaction changed from immune reactive to immune tolerant during progression of cancer.
THE INTERNATIONAL CONGRESS OF ARTS AND SCIENCE.
Journal: JAMA (1904)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 562: Dinaciclib induces immunogenic cell death and enhances anti-PD-1 mediated tumor suppression
Authors: Dewan Mohammed Sakib Hossain, Fernando Ugarte, Anandi Sawant, Mingmei Cai, Venkataraman Sriram, Elaine Pinheiro, Svetlana Sadekova, Alissa Chackerian
Journal: Cancer Research (2016)

Abstract Blockade of the checkpoint inhibitor PD-1 has demonstrated remarkable success in the clinic for the treatment of a growing list of different cancers. However, several tumor types are resistant to anti-PD-1 monotherapy. This observation has spurred numerous combination studies to reveal what additional therapeutic interventions may complement anti-PD1 blockade. Recently it has been shown that immunogenic cell death (ICD), induced by radiation and/or chemotherapy, improves T cell responses against different tumor types. ICD is characterized by damage-associated molecular patterns (DAMPs) including surface expression of calreticulin, and release of ATP and HMGB1. Recognition of DAMPs triggers dendritic cell maturation and functions that are critical for tumor antigen-specific T cell activation. Thus therapies that evoke ICD may further augment anti-tumor immunity elicited by anti-PD-1. In mouse syngeneic tumor models, we observed combinatorial anti-tumor activity of anti-PD1 and the cyclin-dependent kinase inhibitor, dinaciclib. We hypothesized that dinaciclib potentiates the effects of anti-PD-1 by eliciting ICD. Indeed, tumor cells treated with dinaciclib express the hallmarks of ICD including HMGB1 and ATP release and surface expression of calreticulin. Dinaciclib treatment also increases tumor cell phagocytosis and induces dendritic cell maturation. Furthermore, mice immunized with dinaciclib-treated tumor cells are resistant to subsequent tumor challenge. Tumors from mice receiving anti-PD1 and dinaciclib have increased T cell infiltration and dendritic cell activation, indicating the overall quality of the immune response generated may be improved with the combo. Taken together, these findings suggest a potential mechanism for the observed synergy between dinaciclib and anti-PD1. Dinaciclib induces immunogenic cell death, converting the tumor cell into an endogenous vaccine and thereby boosting the effects of anti-PD-1. Citation Format: Dewan Mohammed Sakib Hossain, Fernando Ugarte, Anandi Sawant, Mingmei Cai, Venkataraman Sriram, Elaine Pinheiro, Svetlana Sadekova, Alissa Chackerian. Dinaciclib induces immunogenic cell death and enhances anti-PD-1 mediated tumor suppression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 562.
Clinical, Immunologic, and Genetic Features of an Autoimmune Lymphoproliferative Syndrome Associated With Abnormal Lymphocyte Apoptosis
Authors: Michael C. Sneller, Jin Wang, Janet K. Dale, Warren Strober, Lindsay A. Middelton, Youngnim Choi, Thomas A. Fleisher, Megan S. Lim, Elaine S. Jaffe, Jennifer M. Puck, Michael J. Lenardo, Stephen E. Straus
Journal: Blood (1997)
Breast cancer in the “very elderly”: Staging, treatment, and outcomes in patients over age 80.
Authors: D. M. Mintzer, B. Lim, D. M. Sataloff
Journal: Journal of Clinical Oncology (2010)

e11000 Background: Although the incidence of breast cancer increases with age, there is little data on treatment and outcomes in the increasing population of the “very elderly.” We retrospectively reviewed data from our urban, community setting to evaluate this population. Methods: Records from 99 newly diagnosed breast cancer patients age 80+ treated at the Joan Karnell Cancer Center of Pennsylvania Hospital from 2000-2009 were reviewed. Results: Median age at diagnosis was 84 (range 80-104). 21 patients had stage 0 (DCIS), 39 stage I, 23 stage II, 8 stage III and 8 stage IV. 77% were ER+ and/or PR+. 24% were HER2+ by IHC or FISH. Of 89 patients undergoing surgery, 20 had mastectomy and 69 had breast conservation. Of six patients who did not undergo potentially curative breast surgery, 3 refused and in 3 surgery was deferred due to comorbidities. 47/78 patients with invasive breast cancer had sentinel node sampling or axillary node dissection performed; 16 had positive nodes. 58 patients received post-operative radiotherapy (9 post-mastectomy; 49 post-lumpectomy). Eight patients requiring radiation therapy per NCCN guidelines had it deferred due to co-morbidities. Among 77 ER+ patients, 58 received hormonal therapy (25 an aromatase inhibitor, 10 tamoxifen, and 5 both in sequence). Only 3/18 patients meeting criteria for adjuvant chemotherapy per NCCN guidelines received chemotherapy. As of this report, of 70 patients diagnosed with stage I-III disease, there have been 8 local recurrences (2 after lumpectomy/XRT, 5 after lumpectomy alone, and 1 post-mastectomy). 2 patients developed distant metastasis. There have been 3 deaths from breast cancer and 4 deaths from other causes. 6 patients are lost to follow-up. Conclusions: Of our patients ages 80+, the majority are eligible for and opt for breast conservation therapy. Standard loco-regional and adjuvant hormonal therapies have been utilized in about 2/3 of patients, but about one third have modifications based on either patient or physician choice. Standard adjuvant chemotherapy was provided in only a minority of patients. Overall outcomes in this population to date have been relatively good, with only a minority suffering recurrence of disease or death from breast cancer. No significant financial relationships to disclose.
Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy
Authors: Manlio Cipriani, Maurizio Lunati, Maurizio Landolina, Alessandro Proclemer, Giuseppe Boriani, Renato P. Ricci, Roberto Rordorf, Maria Vittoria Matassini, Luigi Padeletti, Saverio Iacopino, Giulio Molon, Giovanni B. Perego, Maurizio Gasparini
Journal: European Journal of Heart Failure (2016)
Abstract 3852: U3-1784, a human anti-FGFR4 antibody for the treatment of cancer
Authors: Rene Bartz, Keisuke Fukuchi, Tanja Lange, Katrin Gruner, Toshiaki Ohtsuka, Ichiro Watanabe, Shinko Hayashi, Mauricio Redondo-Müller, Mizuki Takahashi, Toshinori Agatsuma, Johannes Bange, Reimar Abraham
Journal: Cancer Research (2016)

Abstract Fibroblast Growth Factor Receptor 4 (FGFR4) is the fourth member of the Fibroblast Growth Factor Receptor (FGFR) family of receptor tyrosine kinases. All of the FGFR's have been implicated in cancer development due to increased activation of their enzymatic activity either by gene mutation, over-expression or inadvertent ligand-mediated stimulation. One important alteration that may lead to FGFR4 activation in cancer is the overexpression of its ligand FGF19 in 20-40% of primary liver cancer. Here, we report the development of U3-1784, a phage display-derived fully human antibody that specifically binds to FGFR4 but not to isoforms of FGFR1-3. The antibody binds to an epitope in the putative ligand binding domain of the receptor and consequently inhibits ligand binding and downstream signaling. In a panel of 10 tumor models derived from hepatocellular carcinoma, U3-1784 significantly inhibits the growth of FGF19-expressing models up to 90% whereas models without FGF19 expression are insensitive. These results strongly suggest that the FGFR4/FGF19 axis is an oncogenic driver in hepatocellular carcinoma. U3-1784 is currently in phase I clinical trials. Citation Format: Rene Bartz, Keisuke Fukuchi, Tanja Lange, Katrin Gruner, Toshiaki Ohtsuka, Ichiro Watanabe, Shinko Hayashi, Mauricio Redondo-Müller, Mizuki Takahashi, Toshinori Agatsuma, Johannes Bange, Reimar Abraham. U3-1784, a human anti-FGFR4 antibody for the treatment of cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3852.
Dietary therapy for irritable bowel syndrome
Authors: Benjamin Lebwohl, Peter H R Green
Journal: BMJ (2016)

High expectations for low FODMAP diets

Irritable bowel syndrome (IBS) is a common disorder of the digestive system, affecting about 10% of the global population. The condition has no definitive biomarker or cure, but various drug treatments have been introduced in recent years, including antibiotics (to treat presumed small intestinal bacterial overgrowth) and agents that affect motility through fluid secretion or the enteric nervous system. Despite these advances, perhaps the most popular option among patients in recent years has been a dietary approach, the “low FODMAP diet.”

The term FODMAP was first coined by Gibson and Shepherd in 2005, referring to a new dietary class comprising fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. The authors identified a list of foods that are highly fermented but poorly absorbed, leading to the expansion of ileocolonic bacteria. This broad dietary class includes fructose (in fruits and sweeteners), lactose (in dairy products), fructans (wheat based products), galacto-oligosaccharides (legumes), and polyols such as xylitol and mannitol (fruits and artificial sweeteners). The authors first proposed FODMAPs as a potential trigger for inflammatory bowel disease (Crohn’s disease …
New radioligand therapy with 177Lu-PSMA-617 in men with metastatic prostate cancer: Initial clinical experience after 50 therapy cycles.
Authors: Martin Boegemann, Axel Bode, Matthias Weckesser, Nemanja Avramovic, Michael Claesener, Michael Schaefers, Lars Stegger, Kambiz Rahbar
Journal: Journal of Clinical Oncology (2016)

e16575 Background: Despite several new treatment options in metastatic castration resistant prostate cancer (mPCa), especially in castration resistant PCa (mCRPC), eventual resistance to approved treatment is common. Therefore, new therapy approaches are much-needed. Recently developed theranostic concepts using prostate specific membrane antigen (PSMA) are of increasing importance in diagnosis and treatment of mPCa. We report our initial experience with the radioligand therapy (RLT) with 177Lu-PSMA-617 concerning tolerability, response and survival. Methods: We administered 50 cycles of 177Lu-PSMA-617 in 28 patients. We analyzed safety-relevant toxicities and response and did exploratory overall survival analysis using Kaplan Meier estimates. The extent of metastases and PSMA expression was evaluated using 68Ga-PSMA-PET/CTs. Results: Twenty-two men received two and 6 men only one cycle of 177Lu-PSMA-617 therapy. The mean applied activity during the first cycle was 5,92±0,44 GBq and 5,86±0,73 GBq during the second cycle. In 59% and 75% of the men a decline of prostate specific antigen (PSA) was observed. A PSA decline ≥ 50% was seen in 32% and 50% of the men. There were no relevant changes in security relevant laboratory parameters and no permanent xerostomia. Overall survival was 29.4 weeks compared to a matched historic cohort prior to availability of 177Lu-PSMA-617 RLT with 19.7 weeks (hazard ratio: 0.44; 95% confidence interval: 0.20–0.95; P = 0.031). Conclusions: After 50 cycles applied, RLT with 177LuPSMA-617 in patients with mPCa and mCRPC seems to be safe and tolerable. In a large proportion of the heavily pretreated men, promising responses and overall survival could be seen.
AB0901 Trends in Paediatric Rheumatology Referral Times and Disease Activity Indices over A Ten-Year Period among Children with Juvenile Idiopathic Arthritis: Results from the Childhood Arthritis Prospective Study (CAPS): Table 1
Authors: F. McErlane, H.E. Foster, R. Carrasco, E.M. Baildam, A.S.E. Chieng, J.D. Davidson, Y. Ioannou, L.R. Wedderburn, W. Thomson, K. Hyrich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>ABSTRACT</h3> Traditionally, in <i>normal</i> case-control studies of disorder A, individuals with disorder A are screened-out of controls. However, in genome wide association (GWA) studies, controls are sometimes <i>unscreened</i> or screened for disorder A and disorder B, producing <i>super-normal</i> controls. Using simulations, we examine how the observed genetic correlations between two disorders (A and B) are influenced by the use of unscreened, normal, and super-normal controls. Normal controls produce unbiased estimates of the genetic correlation. However, unscreened and super-normal controls both bias upward the genetic correlations. The strength of the bias increases with increasing population prevalences for the two disorders. With super-normal controls, the magnitude of bias is stronger when the true genetic correlation is low. The opposite is seen with the use of unscreened controls. Adding screening of first-degree relatives of controls substantially increases the bias in genetic correlations with super-normal controls but has minimal impact when normal controls are used.
Abstract 904: Heterozygous ATG7 inhibition enhances endocrine therapy responsiveness through regulation of damage associated molecular patterns and priming the immune system in ER+ breast tumors
Authors: Robert Clarke, Pamela A.G. Clarke, Anni Wärri, Katherine L. Cook
Journal: Cancer Research (2016)

Abstract Breast cancer is the most prevalent cancer in women, with over 230,000 new cases diagnosed annually. The most common type of breast cancer, comprising over 70% of all cases, express the estrogen receptor (ER); these tumors are usually treated with an endocrine therapy such as an antiestrogen or aromatase inhibitor. Unfortunately, many of these tumors develop resistance, or in some instances express de novo resistance, which limits the curative potential of these therapies. Autophagy, a cellular process of “self-eating”, is implicated as possible contributor to endocrine therapy resistance in breast cancer. We previously showed that inhibiting autophagy through low-dose chloroquine treatment reversed antiestrogen therapy resistance in ER+ orthotopic breast tumors. We now show that heterozygous deletion of ATG7 decreased breast tumor multiplicity and increased endocrine targeting therapy sensitivity in a DMBA-model of ER+ mammary carcinogenesis. Knockdown of ATG7 through RNAi increased cytoplasmic to nuclear high-mobility group binding protein B1 (HMGB1) protein ratio, suggesting targeting ATG7 promotes damage associated molecular patterns (DAMP) signaling. Heterozygous deletion of ATG7 also increased cytoplasmic HMGB1 protein expression in tumor epithelial cells indicating targeting ATG7 promotes DAMP signaling in vivo. Furthermore, tumors from ATG7 heterozygous mice displayed increased CD68 staining indicating elevated macrophage infiltration. Corroborating previous literature showing the critical role of autophagy in T-cell maturation, splenic CD8+ T-cells were significantly reduced in tumor bearing ATG7 heterozygous mice. However, ATG7 heterozygous mice displayed increased tumor CD8+ T-cell population. These data suggest that while targeting ATG7 reduces overall circulating T-cell populations, inhibiting ATG7 enhances tumoral cytotoxic T-cell recruitment. Tumors from ATG7 heterozygous mice also showed a significant decrease in foxp3+ cells, indicating targeting ATG7 reduces immuno-suppressive T-reg population. Serum from ATG7 heterozygous mice showed increased circulating MDC, MCP-1, IL-6, and eotaxin cytokines. Taken together, these data suggests that ATG7 inhibition promotes an anti-tumor pro-inflammatory cytokine profile to enhance tumoral immune cell recruitment and promote endocrine therapy responsiveness. Citation Format: Robert Clarke, Pamela A.G. Clarke, Anni Wärri, Katherine L. Cook. Heterozygous ATG7 inhibition enhances endocrine therapy responsiveness through regulation of damage associated molecular patterns and priming the immune system in ER+ breast tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 904.
RETRACTED ARTICLE: NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages
Authors: Jong-Seok Moon, Kiichi Nakahira, Kuei-Pin Chung, Gina M DeNicola, Michael Jakun Koo, Maria A Pabón, Kristen T Rooney, Joo-Heon Yoon, Stefan W Ryter, Heather Stout-Delgado, Augustine M K Choi
Journal: Nature Medicine (2016)