tbuckley/cabot-search huggingface dataset:
Retrospective Analysis of Pathologic Criteria in 446 Patients with pT1a and pT1b Breast Cancer: A Study from Two French Anti-Cancer Centers.
Authors: F. Dalenc, B. Comet, M. Lacroix-Triki, H. Charytanski, M. Chauvet, L. Ceugnart, Y. Belkacemi
Journal: Cancer Research (2009)

Abstract Background: To assess the risk of recurrence and survival after locoregional and systemic treatment regarding biological features among women with a 1cm-maximal size of breast cancer.Material and Methods: Individual clinicopathological data were collected from 446 patients, treated in the Oscar Lambret and Claudius Regaud centers between 2003 and 2006. 5 patients had bilateral breast cancer. Median age was 59y (range: 26-92). None of the patient had node involvement, but patients could have isolated cells. Surgery consisted of lumpectomy, quadrantectomy or total mastectomy in 95%, 1%, 4% of the patients respectively. Sentinelle node biopsy and axillary dissection were performed in 87% and 13% of the patients, respectively. Estrogen receptor (ER, n=447) and Progesterone receptor (PR, n=448) were determined from tumor tissue microarrays using immunohistochemistry (IHC). Cut-off used for ER and PR positivity was 10% of stained cells. Radiation therapy was delivered to 432 breasts (96%; 45-50Gy) and a boost to 296 (69%; 6-16Gy). Nodal RT was delivered in 29% of the patients. Systemic therapy consisted of hormonotherapy in 380 (85%) including aromatase inhibitors in 38%. Chemotherapy was administered in 18 patients. Only two patients received 1 year of trastuzumab.Results:Pathological tumor size was ranged between 1.0 and 10.0 mm (median: 8.0 mm). The majority of tumors (n= 383 or 85%) were ductal infiltrant carcinoma and 42 (9%) were lobular infiltrant. 189 tumors (48%) contained a ductal carcinoma in situ component. 11/381 (3%) presented lymphovascular invasion. The majority were grade III (n=194 or 45%). Only 53 tumors (12%) were ER negative and 129 (28.8%) were PR negative. Nineteen (5.2%) tumors and 4 (0.9%) patients presented tumors with Her 2 overexpression or gene amplification, respectively.After a median survival of 26 months, 8 patients presented locoregional or distant recurrence. Local, locoregional, and distant metatstases were observed in 3, 2 and 4 patients. Among these 8 patients ¾ were aged more than 50y, all of them had tumors &amp;gt; 5mm and grade II or III. 6 out of the 9 patients were HR+. Presences of lymphovascular invasion and Her2+ status were not correlated to recurrence.ConclusionMammographic screening increased the rate of small tumors diagnosed and reduces mortality in breast cancer. It is not known if this reduction is more pronounced in certain groups of patients. In the new era of tumor biology new markers that could predict the sensitivity of tumours to local and systemic therapy have to be determined in further studies for more tailored treatments in small tumors. Further pathologic analyses are ongoing and will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6026.
Psoriasis Flare from Koebner's Phenomenon after Acupuncture
Authors: Jashin J Wu, Caroline Caperton
Journal: New England Journal of Medicine (2013)

A 73-year-old man who had had plaque psoriasis for more than 20 years on the arms, legs, and scalp presented for consultation on a new rash. He had been using topical steroid creams and shampoos to control occasional flares.
Decreased Hepatic Uroporphyrinogen Decarboxylase Activity in Porphyria Cutanea Tarda
Authors: Bertram F. Felsher, Noemi M. Carpio, David W. Engleking, Allan T. Nunn
Journal: New England Journal of Medicine (1982)

To test whether reduced hepatic uroporphyrinogen decarboxylase activity is a specific and intrinsic defect in porphyria cutanea tarda, we measured enzymatic activity in the livers of 17 patients with porphyria cutanea tarda, 12 "normal" control patients without liver disease, and 41 patients with other forms of porphyria, alcoholic liver disease, hemochromatosis, or chronic hepatitis. Enzyme activity in all the patients with porphyria cutanea tarda was lower than in the patients without this disease, except for one patient with alcohol-induced fatty liver. Reduction of hepatic iron stores by phlebotomy did not alter the enzymatic activity in porphyria cutanea tarda. We conclude that reduced hepatic uroporphyrinogen decarboxylase activity is a specific and intrinsic hepatic defect in porphyria cutanea tarda, but modulation of uroporphyrinogen synthesis by extrinsic factors is required for the full biochemical expression of the disease. (N Engl J Med. 1982; 306: 766–9.)
OC-052 Combined EMR and Radio Frequency Ablation Leads to High Barrett’S Eradication Rates following Structured Training Programme
Authors: J Faulkner, R Ley Greaves, J Hoare
Journal: Gut (2013)

<h3>Introduction</h3> EMR and Radio Frequency Ablation (RFA) have recently been combined to treat dysplastic Barrett’s oesophagus (1). These are complex techniques and require a high level of endoscopic skill and published reports show a range of success. The Academic Medical Centre (AMC) in Amsterdam is a high volume tertiary centre for these procedures and has established expertise in providing structured teaching (2). After attending a structured teaching programme at the AMC a service was established at a London teaching hospital to treat patients with dysplastic Barrett’s oesophagus. We wanted to know if high quality results could be reproduced in this setting. <h3>Methods</h3> We retrospectively analysed all cases of dysplastic Barrett’s referred for treatment at our centre since the introduction of RFA (Barryx), following structured training at the AMC. Decision for endoscopic therapy was made at a multidisciplinary meeting involving surgeons, radiologists, oncologists and gastroenterologists. Published protocols for treatment with EMR/RFA were closely followed (1), although argon plasma coagulation was used to remove residual islands less than 5mm in the interests of cost, rather than RFA. All procedures were carried out by one of two senior endoscopists. <h3>Results</h3> Over 30 months 33 patients were referred for endoscopic therapy. Following initial EMR of visible lesions 3were found to have cancer extending beyond the first 1/3 of the sub-mucosa and were offered alternative therapy. 24have finished therapy and 1 is lost to follow up. Mean age was 70 years (53–89) and mean Barrett’s length 5.4cm (&lt;1–10 cm). Therapy was applied as follows: 2 patients had only EMR, 4 only RFA, 1 EMR + APC, 6 EMR + RFA, 5 RFA +APC, 6 EMR + RFA + APC. 24/24 have had eradication of high grade dysplasia or intra-mucosal cancer (100%). 21/24(87.5%) have had complete eradication of Barrett’s by endoscopic and histological criteria. Mean follow up is 9.8 months(1.5–25). There were no perforations. 3 strictures were treated endoscopically. <h3>Conclusion</h3> Following a comprehensive structured teaching programme in the treatment of dysplastic Barrett’s with combined RFA and EMR, results comparable to published studies are achievable in lower volume centres treating approximately only one new patient per month. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Radiofrequency ablation for total Barrett’s eradication: a description of the endoscopic technique, itsclinical results and future prospects. Pouw RE <i>et al.</i> Endoscopy. 2008 Dec; 40(12):1033–402. Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications evenwithin a structured training programme. Van Vilsteren FG <i>et al.</i> Endoscopy. 2012 Jan; 44(1):4–12.
P44 Maintenance of space for COPD (A Self-management Programme of Activity, Coping &amp; Education): a six month qualitative study
Authors: LD Apps, SL Harrison, KE Mitchell, M Steiner, M Morgan, SJ Singh, SJ Singh
Journal: Thorax (2013)

<h3>Introduction &amp; Objectives</h3> Few self-management interventions for COPD have conducted qualitative interviews on completion of such a programme and none have followed participant’s longer term. This study conducted interviews with participants allocated to the SPACE FOR COPD self-management programme as part of an RCT. We aimed to gain insight into how the programme was utilised over a 6 month period. Earlier analysis of interviews carried out at 6 weeks highlighted the value of the education material<sup>1</sup>. <h3>Method</h3> Semi-structured interviews were carried out with participants (n = 24) receiving SPACE for COPD six months after receiving the intervention. Interviews were transcribed verbatim and a constant comparison approach was taken to analysis supported by NVivo software (Version 10) by 2 researchers with experience in qualitative methods. <h3>Results</h3> Following preliminary analysis, four main themes describe the challenges and conducive behaviours that influenced participant’s self-management behaviours during 6 months of using SPACE FOR COPD - <i>continuing to utilise the manual, establishing an exercise routine, social support &amp; multiple burdens. </i>Many participants describe continuing to use the SPACE FOR COPD manual (e.g. for breathing control techniques and to refresh memory) and establishing an exercise routine early on with the intervention. Social support was utilised for informational (advice), instrumental (help with tasks) and emotional reasons and largely consisted of family members. Challenges to continued regular exercise at home included barriers of time and weather and wider ranging burdens (e.g. other family member’s ill-health, life events, such as moving house). <h3>Conclusion</h3> Participants reported continued use of the manual and acknowledged thatestablishing a regular exercise routine was instrumental to encouraging continued exercise and this behaviour may have increased feelings of personal control over their disease.However, the challenges identified could disrupt these patterns of self management and further healthcare professional support may be required to help participants cope with these. Participants viewed the telephone support they had had favourably. <h3>References</h3> L Apps, S Harrison, J Williams, M Steiner, M Morgan &amp; S Singh. (2012). A self-management programme of activity, coping &amp; education (SPACE) for COPD: Patients perspective. ERS Annual Conference 2012
Abstract 872: Identification of romidepsin (FK228) and its analogs as HDAC/PI3K dual inhibitors
Authors: Ken Saijo, Tadashi Katoh, Hideki Shimodaira, Akifumi Oda, Ohgi Takahashi, Chikashi Ishioka
Journal: Cancer Research (2012)

Abstract Activation of phosphatidylinositol 3-kinase (PI3K) signaling is involved in carcinogenesis and cancer progression. Therefore, inhibitors targeting PI3K are considered to be candidate drugs for cancer therapy. Indeed, some PI3K inhibitors have entered clinical trials, but efforts are still underway to develop new PI3K inhibitors. To discover novel PI3K inhibitors, we took advantage of a drug screening system by using the yeast Saccharomyces cerevisiae with deleterious mutations in ATP-binding cassette transporter genes. This is because wild-type yeast employs drug efflux pumps for reducing intracellular drug concentrations. The screening system is based on growth inhibition induced by overexpression of membrane localized p110α in yeast, in which no endogenous p110 homolog is expressed. However, compounds with the ability to inhibit PI3K can rescue cells from p110α induced growth inhibition. Using this system, we screened the deposited chemical library of the Screening Committee of Anticancer Drugs (SCADS). As a result, the histone deacetylase (HDAC) inhibitor romidepsin (FK228) and its novel analogs were isolated. In vitro PI3K activity assays confirmed that these compounds directly inhibit PI3K activity at μM-range concentrations. FK-A5 analog was the most potent inhibitor. Western blotting revealed that these compounds inhibit phosphorylation of v-akt murine thymoma viral oncogene homolog (AKT) and downstream signaling components. Molecular modeling of the PI3K-FK228 complex indicated that FK228 binds to the ATP binding pocket of p110α. At µM range concentrations, FK228 and FK-A5 exhibit potent cytotoxicity even in HDAC inhibitor-resistant cells. Fluorescence activated cell sorting (FACS) and western blotting indicated apoptosis as the cause of cell death. Furthermore, it was suggested that HDAC/PI3K dual inhibitory activity of FK228 and FK-A5 at µM range concentrations contributed to the induction of potent apoptosis because of the following reasons. 1) FK228 or FK-A5 within µM range inhibited AKT phophorylation and acetylated histones simultaneously. 2) The apoptosis induction by FK228 or FK-A5 at µM range concentrations was mimicked by combination of HDAC inhibitor and PI3K inhibitor. In conclusion, we demonstrated that FK228 and its analogs directly inhibited PI3K activity and induce potent apoptosis exhibiting HDAC/PI3K dual inhibition at µM range concentrations. In future, optimizing potency of FK228 and its analogs against PI3K may contribute to the development of novel HDAC/PI3K dual inhibitors for cancer treatment. 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 872. doi:1538-7445.AM2012-872
Reduced Langerhans’ Cell Ia Antigen and ATPase Activity in Patients with the Acquired Immunodeficiency Syndrome
Authors: Donald V. Belsito, Miguel R. Sanchez, Rudolf L. Baer, Fred Valentine, G. Jeanette Thorbecke
Journal: New England Journal of Medicine (1984)

We investigated the possible role of a defect in antigen-presenting cells in the acquired immunodeficiency syndrome (AIDS), by enumeration of Langerhans' cells, the epidermal antigen-presenting cells. These cells were stained for the characteristic markers, surface Ia antigen and surface ATPase activity. A significant reduction was observed in the number of stained cells per square millimeter of body-surface area in 24 patients with AIDS and either opportunistic infections (Ia, 258 +/- 34, and ATPase, 274 +/- 46) or Kaposi's sarcoma (Ia, 378 +/- 100, and ATPase, 530 +/- 26), as compared with 38 appropriate controls (Ia, 721 +/- 13, and ATPase, 693 +/- 12). Examination of six patients with an "AIDS-related complex" revealed significantly reduced numbers of Langerhans' cells per square millimeter; this reduction was more pronounced in staining for Ia antigen (306 +/- 69) than in staining for ATPase activity (517 +/- 101). Given the known role of Ia expression in antigen presentation, we suggest that functional alterations in Langerhans' cells, and perhaps also in antigen-presenting cells in tissues other than skin, may be involved in the pathogenesis of AIDS.
1.64 Interleukin-33 suppresses experimental arthritis through promoting Foxp3<sup>+</sup>regulatory T-cells and type-2 immune responses in mice
Authors: Jérôme Biton, Allan Thiolat, Sara Khaleghparast Athari, Delphine Lemeiter, Roxane Hervé, Stéphane Rogas, Anais Levascot, Patrice Decker, Jean-Philippe Girard, André Herbelin, Marie-Christophe Boissier, Natacha Bessis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Interleukin (IL)-33 is a new member of the IL-1 family that exerts pleiotropic activities in innate and adaptive immunity. With its receptor ST2, they have newly emerged as key molecules strongly involved in several inflammatory and autoimmune disorders. Recent evidence suggests that the IL-33/ST2 axis is strongly involved in the pathophysiology of rheumatoid arthritis (RA). However in RA models, the role of IL-33 and its receptor is still controversial. We aimed at deciphering IL-33 mode of action after administration in an experimental model of RA, namely collagen-induced arthritis (CIA). <h3>Material and Methods</h3> CIA was induced by immunisation of C57Bl/6 mice with type 2 collagen. IL‑33 was ip administrated in CIA mice and cells were analysed by flow cytometry on day 28 after CIA induction. <h3>Results</h3> We show a previously unshown dramatic inhibition of mouse collagen-induced arthritis (CIA) development after repeated administration of IL-33. This therapeutic effect was related to an enhanced type-2 immune response, including the expansion of eosinophils, Th2 cells, innate type 2 lymphoid cells (ILC2, defined as CD25<sup>+</sup> c-Kit<sup>+</sup> Lin<sup>-</sup> Sca-1<sup>+</sup>ST2L<sup>+</sup>) and an increase in Th2 cytokines levels in the serum of treated mice. Moreover, our work brings out the interplay between Treg and IL-33. Since IL-33 acts directly on Treg via ST2L, we showed that IL-33 treatment of CIA majors Treg frequency and increases the suppressive capacities of those cells. IL-33 also induces the emergence of a CD39<sup>+/high</sup> Treg population in a ST2L dependant manner. <h3>Conclusions</h3> In the light of our present study, IL-33 can exert powerful anti-inflammatory properties in CIA, integrating the establishment of a type-2 immune response, the expansion and the activation of Treg. Our study reveals an undescribed mechanism by which IL-33 inhibits arthritis development, thus updating and strengthening the crucial role of IL-33 in RA.
Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases
Authors: Hans Reiser, Miguel J. Stadecker
Journal: New England Journal of Medicine (1996)

Most immune responses depend on the activation of T cells. This class of lymphocytes consists of functionally and phenotypically distinct populations, the best characterized of which are helper T cells and cytotoxic T cells. Distinctive molecules on the cell surface provide markers of these populations: CD4 for helper T cells and CD8 for cytotoxic T cells. CD4 and CD8 T cells recognize antigens through a T-cell antigen receptor composed of an α chain and a β chain. Other T cells bearing γ- and δ-chain receptors have been identified, but their function is less clear.CD4 helper T cells can be . . .
Abstract LB-131: Mathematical model for tumor growth
Authors: Jiang ji, Guangde tu, Mei zou
Journal: Cancer Research (2010)

Abstract Cancer is a leading cause of morbidity and mortality among humans worldwide. Theoretical studies could provide biologists with complementary and valuable insight into the mechanisms that may control the development of solid tumors. Based on our studies on membrane formation kinetics, a novel growth model is established for solid tumor development, which is consistent with the experimental data. According to the concept of the proliferation-active cells in the tumor tissue, two parameters, the effective cell division cycle for mitosis and the effective infiltration distance relevant to the nutrient support, are introduced in the model. The two parameters introduced can be further applied when the drug effects were considered. We have reviewed over 200 literatures and selected more than 50 of them having experimental data from different cell lines for theoretical studies. The growth curves generated by our model are consistent with many experimental data including lung cancer, breast cancer, liver cancer, ovarian cancer and colon cancer. Thus, the model obtained is very important not only for cancer research but also for searching anti-cancer drug and therapies. In the figure below, we have displayed growth curves for colon carcinoma cell line. The dash lines are simulation curves of the model and the dots are the corresponding experimental data. 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 LB-131.
How do cancer physicians say they discuss prognosis with their terminally-ill patients? A survey of ASCO members
Authors: C. K. Daugherty, F. J. Hlubocky
Journal: Journal of Clinical Oncology (2005)

8005 Background: Information is lacking about how physicians discuss prognosis (prog) with terminally-ill cancer patients (tcp). Methods: We surveyed medical oncologists’ (med oncs) self-reported behaviors and attitudes regarding prog communication (comm) with their tcp. Following a pre-notification letter, surveys were mailed to a systematic sample of 1,222 med oncs with U.S. addresses listed in the 2004 ASCO Members Directory. Results: Surveys were mailed with a $25 gift card in November, 2004. With completed surveys still arriving, 559 surveys have been completed and returned (46% response rate). A second mailing for non-responders is planned. Median age of respondents (res) is 52 (34–80); 84% men; 54% in group private practice; 12% practice solo; 22% practice in a medical school. Res have practiced a median 19 years (2–50) and see a median 60 (0–250) patients/week. Answering yes or no, 98% of res say their usual practice is to tell their tcp they will eventually die of their disease. Choosing from closed-ended responses: 43% say they always discuss prog, 32% discuss prog only after asking their tcp if they want the information, and 14% discuss it only if their tcp ask for the information. 43% say they always or usually communicate a timeframe as to when death may occur and 57% sometimes, rarely, or never give a timeframe. If they do not tell a tcp their prog, 21% always, 27% usually, 20% sometimes, and 19% rarely or never tell family or friends. 93% are always or usually satisfied with their prog comm. 92% say their tcp are always or usually satisfied with the comm. 97% believe prog comm education should be part of cancer-care training. 66% say such education was either absent or inadequate during their training. Qualitative data has also been collected about: clinical factors influencing med oncs’ prog comm, associated emotions, and examples of recent prog comm. Conclusions: Most med oncs say they do not communicate an estimated survival time to their tcp. However, they believe in the need to either discuss the terminal nature of their tcp’ prog or at least respect tcp’ preferences for such information. While nearly all believe prog comm education is needed, the vast majority say they are satisfied with their own comm practices. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vitas Hospice
Use of Fusion Images of I-131 Metaiodobenzylguanidine, SPECT, and Magnetic Resonance Studies to Identify a Malignant Pheochromocytoma
Authors: A Fujita, H Hyodoh, Y Kawamura, K Kanegae, M Furuse, K Kanazawa
Journal: Clinical Nuclear Medicine (2000)

Pheochromocytoma is a chromaffin tumor in which 10% are extra-adrenal and 10% are malignant. I-131 metaiodobenzylguanidine (MIBG) scintigraphy has an important role in the identification of these tumors and investigation of metastatic lesions. The authors describe a 36-year-old woman who underwent resection of a malignant left adrenal pheochromocytoma who was thought to have metastases in the liver and para-aortic lymph nodes. Fusion images of I-131 MIBG SPECT and magnetic resonance studies were obtained to properly identify the metastatic lesions. These fusion images helped greatly in subsequent surgery.