tbuckley/cabot-search huggingface dataset:
Recovery of the Upper Limb Function after Sentinel Lymph Node Biopsy or Axillary Dissection.
Authors: T. Utsumi, N. Kobayashi
Journal: Cancer Research (2009)

Abstract Introduction:Sentinel lymph node biopsy (SLNB) is widely accepted as an excellent method in the management of early breast cancer in patients with clinically negative axillary lymph nodes. The aim of this study was to evaluate the relationship between the type of breast cancer surgery and early postoperative arm mobility.Materials and methods:The study group consisted of 290 consecutive patients aged 30 to 86 years (median age 58) with breast cancer, operated upon in the Department of Breast Surgery and evaluated in Department of Rehabilitation Medicine afterward, between February 2005 and December 2008. Out of the 290 patients, 126 (43.4% - group 1) underwent breast conserving therapy with SLNB, 65 (22.4% - group 2) simple mastectomy with SLNB, 41 (14.1% - group 3) breast conserving therapy with axillary lymph node dissection (ALND) and 58 (20% - group 4) modified radical mastectomy. Shoulder mobility was evaluated after 1month and after 3 months.Results:After 1 month, patients in the ALND group (group 3 and 4) had more limitations in shoulder mobility than patients in the SLNB group (group1 and 2).After 3 months, shoulder mobility was not different between the ALND group (n=52) and the SLNB group (n=32) (shoulder flexion: 161.6±22.5 degree vs. 167.8±19.5 degree, abduction: 165.2±27.5 degree vs. 164.4±28.9 degree, respectively).Conclusion:In terms of upper limb functional status, the benefits of SLNB over ALND was observed at the early postoperative time. However, long-term effects have to be confirmed by further, larger series. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3118.
AB0120 Il-2 therapy results in intrarenal foxp3+ regulatory t cells expansion and decreased number of infiltrating cd4+ t cells in nzb/w mice
Authors: A. Rose, C. von Spee-Mayer, J. Humrich, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an acquired IL-2 deficiency, which leads to a homeostatic imbalance between regulatory T cells (Treg) and effector T cells (Tcon). Humrich <i>et al.</i> (2010) demonstrated that the IL-2 deficiency in diseased (NZBxNZW) F1 mice can be rebalanced in lymphoid organs using a treatment with recombinant IL-2 (IL-2) by promoting the homeostatic proliferation of regulatory T cells. <h3>Objectives</h3> The aim of this study was to investigate the impact of IL-2 therapy on intrarenal Foxp3+ Treg and kidney infiltrating CD4+ T cells in (NZBxNZW) F1 mouse model of lupus nephritis. <h3>Methods</h3> (NZBxNZW) F1 mice with active nephritis were treated with recombinant IL-2 either over a short period or for a total of 30 days. Absolute numbers, phenotype and proliferation of kidney infiltrating CD4+ T cells were determined by flow cytometry. <h3>Results</h3> (NZBxNZW) F1 mice treated over a short term with IL-2 showed an enhanced proliferation of Foxp3+ T cells and increased numbers and frequency of CD4+Foxp3+ T cells compared to untreated control mice. On the other hand, long term IL-2 treatment did not result in a persistent expansion of the intrarenal CD4+Foxp3+ T cell population. Nevertheless, total numbers of kidney infiltrating CD4+ T cells were diminished and the conventional T cells (Tcon) showed reduced signs of cellular activation. <h3>Conclusions</h3> Our data indicates that short term IL-2 treatment is able to expand the size of the intrarenal Treg pool. In contrast, long term IL-2 treatment decreases the numbers of kidney infiltrating CD4+ T cells. These results may in part explain the delay of disease progression induced by treatment with IL-2 and underline the important role of intrarenal Treg for the suppression of kidney disease in lupus mice. These results also provide additional rationales for an IL-2 based immunotherapy of human disease. <h3>References</h3> Humrich, JY et al, PNAS, 2010 <h3>Disclosure of Interest</h3> None Declared
Abstract B28: Mitochondrial dysfunction is associated with cancer progression in ulcerative colitis
Authors: Rosa Ana Risques, Cigdem Himmetoglu Ussakli, Anoosheh Ebaee, Teresa A. Brentnall, Peter S. Rabinovitch
Journal: Cancer Research (2011)

Abstract Ulcerative colitis (UC) is an inflammatory disease of the colon that predisposes to colorectal cancer. Dysplasia and cancer arise in pre-cancerous fields of inflammed epithelium, which harbor molecular alterations in spite of histologically normal appearance. We hypothesized that these pre-cancerous fields might contain dysfunctional mitochondria as a consequence of oxidative stress associated with the inflammatory environment. If so, mitochondrial alterations could be used to identify UC patients at risk for cancer progression. To test this hypothesis we stained colon biopsies with Cytochrome C oxidase subunit I (COX), a respiratory transport chain protein whose loss is attributed to mitochondrial DNA mutations. Four histologically normal biopsies randomly collected from the colon of 9 UC patients with high-grade dysplasia or cancer (Progressors) and 9 patients free of dysplasia (Non-progressors) were stained with COX and quantified using multispectral imaging. Low and high grade dysplasia (LGD, HGD) and cancer biopsies were also included in the analysis. Subsequent to COX staining, a subset of the biopsies were also stained for Prohibitin, Opal, and Mfn1, which are nuclear encoded mitochondrial proteins. On average, UC progressors had 40% less COX staining than UC non-progressors (p&amp;lt;0.0001). The mean COX staining intensity of 4 biopsies could distinguish UC progressors from non-progressors with 100% sensitivity and 77.8% specificity. Moreover, in UC progressors, the closer the biopsies were located to dysplasia the lower the amount of COX staining (p=0.003), suggesting that mitochondrial abnormalities increase progressively in more advanced preneoplastic fields. Complete COX loss was observed in some non-dysplastic biopsies &amp;lt;10cm to dysplasia and in LGD biopsies. Interestingly, HGD and cancer showed areas with very intense COX staining, suggesting a recovery of mitochondrial function later in neoplastic progression. Prohibitin, Opa1, and Mfn1 showed similar trends of loss in early progression and gain in later progression, although the patterns of staining did not always overlap with COX. Thus, we have shown that mitochondrial dysfunction, measured as the loss of COX staining, precedes the development of dysplasia and cancer and may be useful as a biomarker for cancer risk in UC patients. Intriguingly, mitochondrial function seems to be recovered in HGD and cancer, suggesting that epigenetic mechanisms underlie the pre-neoplastic loss of mitochondria. These results are currently under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B28.
Abstract 4784: Targeting NF-kappaB pathway with Bay11-7085 leads to inhibition of cell viability and induces apoptosis in primary effusion lymphoma cells
Authors: Azhar R. Hussain, Maqbool Ahmed, Saeeda O. Ahmed, Rong Bu, Omar S. Khan, Leonidas Platanias, Khawla S. Al-Kuraya, Shahab Uddin
Journal: Cancer Research (2011)

Abstract Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin's B cell lymphoma that mainly grows as a lymphomatous effusion in body cavities and is infected with Kaposi sarcoma-associated herpesvirus (KSVH/HHV8). A number of constitutively activated signaling pathways play critical role in the survival and growth of PEL cells including NF-kB. NF-κB is constitutively activated in a number of cancers including multiple myeloma, burkitt's lymphoma and diffuse large B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored. Therefore, in this study, we found that Bay11-7085, an inhibitor of NF-kB pathway inhibit cell viability and induce apoptosis in several PEL cell lines in a dose dependent manner. Such effects of Bay11-7085 result from its ability to in-activate p-IκBα leading to the inability of p65 subunit of NF-κB to enter the nucleus to assert its anti-apoptotic transcriptional activity. Our data demonstrate that Bay11-7085 treatment of PEL cell lines causes de-phosphorylation of Bad protein leading to conformational changes of Bax protein and subsequently translocation from cytosole to mitochondria causing loss of mitochondrial membrane potential with subsequent release of cytochrome c from the mitochondria. Released cytochrome c into the cytosole activates caspases-9 and -3, followed by polyadenosin-5’-diphosphate-ribose polymerase (PARP) cleavage. In addition, pretreatment of PEL cells with zVAD-fmk, a universal inhibitor of caspases prevents caspase-3 activation and abrogates cell death induced by Bay11-7085 treatment of PEL cells strongly suggesting that Bay11-7085-induced apoptosis is caspase dependent. Finally, treatment of PEL cells with Bay11-7085 down-regulates the expression of inhibitor of apoptosis proteins (IAP). Altogether, these data suggest that NF-κB plays an important role in PEL cell survival and targeting this pathway with Bay11-7085 induces caspase dependent apoptosis via disruption of mitochondrial pathway. This raises the possibility that this agent may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of the NF-κB pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4784. doi:10.1158/1538-7445.AM2011-4784
DNA adducts in human urinary bladder and other tissues.
Authors: D H Phillips, A Hewer
Journal: Environmental Health Perspectives (1993)

Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by 32P-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)
AB1292 Patological changes of shoulder joint in early phase of rheumatoid arthritis detected by ultrasound, magnetic resonance imaging and power doppler
Authors: P. Peric, D. Babic Naglic, B. Curkovic, N. Laktašic Žerjavic, I. Žagar, M. Pervan, M. Prutki, K. Kovac Durmiš
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The primary objective of the study was to establish the status of rotator cuff in the early rheumatoid arthritis (RA) using shoulders ultrasonography (US), Power Doppler (PD) and MRI. The other specific objective was to detect other inflammatory changes of shoulder joint such as erosions, synovitis, effusion, bursitis and humeral head bone oedema. <h3>Methods</h3> The prospective study was conducted at the Clinical Department of Rheumatology and Rehabilitation, Clinical Hospital Center Zagreb, in the group of 50 patient who fullfiled criteria for diagnosis of RA. The study was conducted by US machine Logiq 700, using 7-11 MHz high-resolution linear probe (General Electric). MRI of shoulder joints was performed using machine: Siemens Magnetom Trio, with 3T magnetic field. <h3>Results</h3> All three methods were effective in detecting early inflammatory changes. MRI of shoulder was the most accurate method in discovering the humeral head bone oedema. US and MRI of shoulders had very good results in detecting early rotator cuff changes. Rotator cuff tears were found in 7 patients (14%) using US and in 11 patients (24%) using MRI. The highest number of tears were found in the site of supraspinatus tendons (in 5 out of 7 patients using US and in 8 out of 11 patients by MRI). US and MRI showed the highest correlation between findings in the way of detecting rotator cuff tears (correlation index 88%, kappa value=0,598 which is the highest kappa value in the study). US and MRI are efficient in detecting effusions and bursitis. PD of shoulder was the superior method in detecting synovitis with the highest number of positive findings (90%) in comparison to standard US and MRI. <h3>Conclusions</h3> Those data emphasize the importance of US, PD and MRI of shoulder in detecting early inflammatory changes in the patients with RA, especially of rotator cuff tears using US and MRI and detecting humeral bone oedema using MRI. <h3>Disclosure of Interest</h3> None Declared
IMPS-27TARGETING GLIOBLASTOMA WITH BISPECIFIC ANTIBODY-ARMED ACTIVATED T CELLS
Authors: Sharon Michelhaugh, Anthony Guastella, Neil Klinger, Prahlad Parajuli, Archana Thakur, Lawrence Lum, Sandeep Mittal
Journal: Neuro-Oncology (2015)

BACKGROUND: The epidermal growth factor receptor (EGFR) is amplified and overexpressed in ∼40% of glioblastoma tumors. EGFR-mediated signaling leads to drug resistance, proliferation, migration and aggressiveness in cancer cells, all of which contribute to the limited treatment options and poor outcomes for GBM patients. A previous study (Nitta et al., 1990; PMID: 1968115) explored targeted T cell therapy with activated killer cells armed with a bispecific antibody (anti-CD3 × anti-glioma) with promising results. METHODS: To further expand the targeted T cell approach, we utilized anti-EGFR × anti-CD3 bispecific antibody (EGFRBi) to generate armed activated T cells (aATCs) to target GBM cells. EGFRBi-aATCs, unarmed-ATCs, or vehicle were co-injected with U87 GBM cells subcutaneously into the flank of immunocompromised mice to determine the ability of EGFRBi-aATCs to prevent tumor development. An orthotopic study was also performed by intracranial stereotactic co-injection of T cells with U87 cells as described for the flank study. RESULTS: In the flank study, mice co-injected with EGFRBi-aATCs had no palpable tumors 40 days post-injection, while mice co-injected with unarmed-ATCs or vehicle required euthanasia due to tumor burden between days 35-40. For the intracranial experiment, MRI scans 3 weeks post-injection revealed tumor volumes ranging from 50-100mm3 in the control mice, and mice co-injected with unarmed-ATCs, whereas there were no visible tumors in mice that were co-injected with EGFRBi-aATCs. All mice in the control and unarmed-ATC groups died or required euthanasia within 30 days post-injection, but mice co-injected with EGFRBi-aATCs were healthy and asymptomatic for over 128 days. CONCLUSIONS: Targeted T cell therapy using bispecific antibodies may provide a new avenue for the treatment of GBM.
Persistent and Fatal Central-Nervous-System ECHOvirus Infections in Patients with Agammaglobulinemia
Authors: Catherine M. Wilfert, Rebecca H. Buckley, T. Mohanakumar, John F. Griffith, Samuel L. Katz, John K. Whisnant, Peyton A. Eggleston, Marcie Moore, Edward Treadwell, Michael N. Oxman, Fred S. Rosen
Journal: New England Journal of Medicine (1977)

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.
The Production of Extracellular Matrix Proteins by Human Passively Sensitized Airway Smooth-Muscle Cells in Culture
Authors: PETER R. A. JOHNSON, JUDITH L. BLACK, STEPHEN CARLIN, QI GE, P. ANNE UNDERWOOD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Airway remodeling is a key feature of persistent asthma. Part of the remodeling process involves the laying down of extracellular matrix (ECM) proteins within the airways. In this study we compared the production of ECM proteins by human airway smooth-muscle (ASM) cells in culture after exposure to 10% serum from an asthmatic individual or 10% serum from a nonasthmatic individual with or without beclomethasone (0.01 to 100 nM). Enzyme-linked immunosorbent assays were done with antibodies to human fibronectin; perlecan; elastin; the laminin beta(1), gamma(1), beta(2), alpha(1) chains; thrombospondin; chondroitin sulfate; collagen types I, III, IV, and V; versican; and decorin. Serum from the asthmatic individual, when compared with that from the nonasthmatic individual, caused a significant increase in the production of fibronectin, perlecan, laminin gamma(1), and chondroitin sulfate. Beclomethasone caused a significant reduction in the number of cells exposed to serum from either the asthmatic or nonasthmatic individual, but did not reverse the increase in ECM protein induced by the former. These results suggest an interaction between the ASM and the allergic process that may alter components of the airway wall in asthma, and that corticosteroids may not prevent the fibrosis induced by resident cells within the airways.
Megestrol Acetate for the Prevention of Hot Flashes
Authors: Charles L. Loprinzi, John C. Michalak, Susan K. Quella, Judith R. O'Fallon, Alan K. Hatfield, Robert A. Nelimark, Ann Marie Dose, Tammy Fischer, Claudia Johnson, Nancy E. Klatt, Walter W. Bate, Raylene M. Rospond, Joseph E. Oesterling
Journal: New England Journal of Medicine (1994)

Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients.
HOXB9 Promotes the Acquisition of Tumorigenic Phenotypes in Mammary Epithelial Cells.
Authors: T. Hayashida, T. Hayashida, F. Takahashi, N. Chiba, E. Brachtel, H. Jinno, Y. Kitagawa, S. Maheswaran
Journal: Cancer Research (2009)

Abstract Background:The class I HOX gene family consists of 39 members with a shared highly conserved 61-amino acid homeodomain motif. HOX genes are important regulators of developmental processes, and their role in neoplastic transformation and tumor progression is increasingly recognized (Abate-Shen et al., Nat Rev Cancer, 2002; Cantile et al., Eur J Cancer, 2003). However, the molecular mechanisms by which HOX proteins promote tumorigenesis is not well understood. We recently, observed that HOXB9, a 9th HOX gene paralogue involved in mouse mammay gland development, is deregulated in breast cancer and enhanced expression correlated with high tumor grade. A role for elevated HoxB9 expression in breast tumor progression is demontrated by its ability to activate the ErbB and TGF-B pathways which influence tumor-associated phenotypes in cells.Methods and results:Overexpression of HOXB9 was found in 43% of primary breast cancer by RT-PCR and in situ hybridization (Figure 1A) and correlated with high tumor grade. Ectopic expression of HOXB9 in MCF10A mammary epithelial cells induced EMT, cell migration, invasion (Figure 1B, and 1C). It also increased the expression of angiogenic factors, which enhance the formation of new vessels in mouse dorsal air sac model. Conversely, genetic ablation of endogenous HOXB9 in MDA-MB-231 breast cancer cells suppresses their motility and angiogenic potential. Further, we confirmed that HOXB9-induced tumor phenotypes arise through the activation of both ErbB-AKT and TGFß signaling pathways. Finally, in mouse xenograft model, we observed that HOXB9 cooperates with activated H-Ras to transform mammary epithelial cells leading to large, vascularized and invasive tumors (Figure 2).Discussion:Our findings imply that overexpression of HOXB9 in human breast cancer contributes to tumor progression through activation of signaling pathways that alter both tumor-specific cell fates and tumor-stromal microenvironment, leading to increased invasion and metastasis. It is suggested that combined suppression of ErbB and TGFß signaling pathways to target breast cancers overexpressing HOXB9 may be effective in tumor inhibition. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6145.