tbuckley/cabot-search huggingface dataset:
A Progress Report on the Treatment of 157 Patients with Advanced Cancer Using Lymphokine-Activated Killer Cells and Interleukin-2 or High-Dose Interleukin-2 Alone
Authors: Steven A. Rosenberg, Michael T. Lotze, Linda M. Muul, Alfred E. Chang, Fred P. Avis, Susan Leitman, W. Marston Linehan, Cary N. Robertson, Roberta E. Lee, Joshua T. Rubin, Claudia A. Seipp, Colleen G. Simpson, Donald E. White
Journal: New England Journal of Medicine (1987)

We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available. One hundred eight patients were treated with 127 courses of LAK cells plus interleukin-2, and 49 patients were treated with 53 courses of high-dose interleukin-2 alone. Of 106 evaluable patients receiving LAK cells plus interleukin-2, 8 had complete responses, 15 had partial responses, and 10 had minor responses. The median duration of response was 10 months among those with complete responses and 6 months among those with partial responses; the patient with the longest complete response was still in remission 22 months after treatment. Of 46 evaluable patients treated with high-dose interleukin-2 alone, 1 had a complete response (remission greater than 4 months), 5 had partial responses (2, greater than 3, greater than 5, 7, and greater than 11 months), and 1 had a minor response. Seven of the total of nine complete responses still remain in remission. Hypotension, weight gain, oliguria, and elevation of bilirubin and creatinine levels were common, but these side effects resolved promptly after interleukin-2 administration was stopped. There have been four treatment-related deaths among these 157 patients. This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present. Determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.
Follow-up study of gallbladder polyps diagnosed as benign with endoscopic ultrasonography
Authors: M Hattori, K Inui, J Yoshino, K Okushima, H Miyoshi, Y Nakamura, Y Nomura, T Chikaishi
Journal: Endoscopy (2006)

By EUS, we diagnosed 99 patients with benign gallbladder polyps between 1989 and 2004. We classified polyps morphologically into 3 groups based on surface structure, shape of the base, and internal echoes: group A, with flat or smooth surface structure, a thin stalk, and homogeneous echoes; group B, finely granular surface structure, and hyper-echoic echoes; and group C, granular surface structure, and coarse and scattered echoes. We looked for changes for over time in the 3 groups every 3 to 6 months. We calculated doubling time (DT) from initial observation for polyp size. Groups. A, B and C respectively consisted of 27, 28, and 99patients. Mean observation periods in groups A, B, and C were 3.4, 8.2, and 10.2 months respectively. In 3 group A patients, internal echoes changed from hyper-echoic and homogeneous to iso-echoic and heterogeneous. These polyps, showed rapid growth and were diagnosed pathologically as carcinoma in adenoma. The other 24 patients, who did not undergo surgery, did not show changes in internal echoes but 9 showed growth. Polyps showed growth in only 11 of 28 patients in group B. No patient in group B underwent surgery. In group C 12 of 99 patients underwent surgery, pathologic examinations disclosed cholesterol polyps. Twelve of the 87 patients, not undergoing surgery, showed growth of polyps and 4 showed an increase in number of polyps. DT in group A ranged from 10.3 to 408.8 days (mean, 198); in group B, 18.2 to 1587.2 days (mean, 789.3); and in group C 81.5 to 4102.9 days (mean, 1120.1). Based on DT, an appropriate observation period was considered to be 3 months for group A, 10 months for group B, and 12 months for group C. EUS is useful for diagnosis of gallbladder polyps. However, polyps with characteristics as in our group A should be followed up closely, that group B or C features can be followed up at longer interval.
Abstract 4216: Activation of Akt and β-catenin pathways are required for the sustention of cancer stem cell-like characteristics generated by epithelial-mesenchymal transition
Authors: Junlin Li, Mark B. Evers, Binhua P. Zhou
Journal: Cancer Research (2010)

Abstract Approximately 90% of cancer deaths are caused by metastasis. The increased motility and invasiveness of tumor cells is reminiscent of the processes at the epithelial-mesenchymal transition (EMT), which is essential for morphogenetic events in embryonic development, tissue remodeling, and wound healing. EMT not only confers tumor cells with a distinct advantage for metastatic dissemination but also provides cancer stem cell-like characteristics for their proliferation and survival. However, the molecular mechanism for maintenance of these cancer stem cell-like traits by EMT remains unclear. In this study, we generated two stable transfectants in breast cancer MCF7 and cervical cancer Hela cell lines with expression of Twist, a key transcriptional factor of EMT. We found that expression of Twist induced a morphological EMT changes in these cells by downregulating the expression of E-cadherin and ZO-1 and by increasing vimentin and N-cadherin expression. We also showed that the CD44highCD24low subpopulation in these stable transfectants, which is associated with cancer stem cells properties, was significantly increased. Consistent with these findings, expression of stem cell marker ALDH1 was also elevated in these cells. The increased stem cell-like traits in Twist expression clones correlated with the tumorsphere formation in these cells. Strikingly, we found that β-catenin and Akt pathways were activated in these Twist-expressing transfectants. The nuclear accumulation of β-catenin correlated with the expression of CD44. Knockdown of β-catenin expression or inhibition of the Akt pathway significantly decreased the expression of CD44. Together, our results indicate that the activation of β-catenin and Akt pathway are required for the sustention of cancer stem cell-like traits generated by EMT. 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 4216.
IT-28 * VACCINATION AGAINST EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT III IN GLIOBLASTOMA: THE RINDOPEPIMUT COMPASSIONATE USE EXPERIENCE
Authors: E. Razis, G. Vlahovic, L. Recht, H. Wheeler, D. Reardon, P. G. Fisher, S. Owen, K. Nicholas, E. Paradise, M. Yellin, T. Davis, M. Weller, R. Stupp, A. F. Hottinger
Journal: Neuro-Oncology (2014)

The tumor-specific epidermal growth factor receptor variant III mutation (EGFRvIII) is widely expressed in glioblastoma and thus represents an attractive target for immunotherapeutic approaches. The investigational vaccine rindopepimut is an EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin and is administered intradermally with GM-CSF. Previous single-arm studies of rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. This compassionate use program provided rindopepimut to 61 EGFRvIII+ glioblastoma patients who were ineligible for ongoing clinical trials. Data are currently available on 42 patients, 12 (29%) with newly diagnosed glioblastoma (resected or inoperable) and 30 (71%) with recurrent disease. MGMT methylation was seen in 9/17, while all tested patients were negative for IDH1 (12/12) and IDH2 (7/7). Median age was 53 years (15-70) and median time from diagnosis was 14.5 months (2.7-58.7). Rindopepimut, administered in combination with temozolomide (57%), bevacizumab (57%), and/or other (17%), was well tolerated, with frequent mild injection site reactions and one potentially treatment-related, serious event of cerebral edema. Median peak rindopepimut-induced anti-EGFRvIII titer was 1:1,200 (<1:100-1:6,553,600). Median treatment duration is currently 3.7 (0.03-60.1) months. Tumor response (>50% shrinkage in measurable disease) was observed in six patients receiving rindopepimut with other agents. One inoperable glioblastoma patient experienced a CR during treatment with rindopepimut, erlotinib, temozolomide, and bevacizumab, and has continued rindopepimut for >5 years without significant toxicity or disease recurrence. Biopsy at recurrence showed EGFRvIII was eliminated in a patient who received rindopepimut and temozolomide for ∼9 months. In patients with newly diagnosed and recurrent glioblastoma, respectively, median PFS was 9.1 and 2.5 months, and median OS was 15.7 and 8.7 months from first vaccination. In conclusion, rindopepimut in combination with various anticancer therapies resulted in robust anti-EGFRvIII humoral response with minimal toxicity. PFS and OS appear promising in this heterogeneous, poor prognosis population.
Study on the Diagnostic Yield and Correlated Factors of EUS-FNA in Pancreatic Masses
Authors: Zhu Qi, Zhang Yi, Gong Ting-ting, Sun Yun-wei, Tan Ji-hong, Xia Lu, Wu Wei, Chen Xi
Journal: Endoscopy (2011)

Aims: EUS-FNA has become an important tool in diagnosis of pancreatic masses. However, the diagnostic accuracy of the technology is influenced by many factors.
Administration of Nasal Nafarelin as Compared with Oral Danazol for Endometriosis
Authors: Milan R. Henzl, Stephen L. Corson, Kamran Moghissi, Veasy C. Buttram, Christer Berqvist, Jan Jacobson
Journal: New England Journal of Medicine (1988)

Treatment with nafarelin, a gonadotropinreleasing hormone agonist, reversibly inhibits ovarian function and induces hypoestrogenemia. To determine the efficacy of such hormonal manipulation in the treatment of endometriosis, we randomly assigned 213 patients with laparoscopically confirmed endometriosis to receive, for six months, either nafarelin by nasal spray (400 or 800 μg per day) or oral danazol (800 mg per day). Placebo nasal spray and placebo tablets were used to double blind the study. Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society's scoring system. More than 80 percent of the patients in each treatment group had a reduction in the extent of disease as assessed by laparoscopy. The mean laparoscopic scores decreased from 21.9 to 12.6 with 800 μg of nafarelin, from 20.4 to 11.7 with 400 μg of nafarelin, and from 18.4 to 10.5 with danazol (P = 0.0001 within each group; there were no statistically significant differences between the groups). The percentage of women with severely painful symptoms of endometriosis decreased from about 40 percent to 5 to 10 percent, whereas the percentage with no or minimal discomfort rose from 25 to 70 percent. Of the 149 patients who tried to become pregnant, 58 (39 percent) succeeded after the completion of treatment; similar rates of pregnancy applied to the three treatment groups. Danazol use decreased high-density lipoprotein levels and increased low-density lipoprotein levels. These changes were not observed in nafarelin users, but a higher percentage of them reported hot flashes and decreased libido. We conclude that nafarelin is an effective agent for treating endometriosis and has few side effects other than hypoestrogenism. (N Engl J Med 1988; 318:485–9.)
EUS-guided transluminal versus percutaneous transhepatic biliary drainage in malignant biliary obstruction after failed ERCP; an international multicenter controlled study
Authors: Park Do Hyun, Kitano Masayuki, KJ Chang, JG Lee, Lee Sang Soo, Seo Dong Wan, Lee Sung Koo, Kim Myung-Hwan, Kudo Masatoshi
Journal: Endoscopy (2011)

Background: Although endoscopic ultrasound-guided biliary drainage (EUS-BD) may be a useful alternative method for patients with biliary obstruction in whom endoscopic transpapillary biliary drainage fails, there is limited data on the outcomes and complications of EUS-BD with transluminal stent compared with those of percutaneous transhepatic biliary drainage (PTBD).
SP0053 Delays in Help Seeking and Referral: Problems and Potential Solutions in the Context of Inflammatory Arthritis
Authors: K. Raza
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Rheumatoid arthritis is a common disease associated with significant articular and extra-articular complications. Outcomes are improved if treatment is started early and the first three months after the onset of symptoms have been suggested to represent a therapeutic window of opportunity. Unfortunately many patients miss this window. Reasons for delayed treatment include delays on the part of the patient in seeking help, delays on the part of the primary care physician in referring the patient to a rheumatologist and delays on the part of the rheumatologist in assessing the patient and commencing therapy. The relative contributions of these levels of delay vary between different countries. Reasons underlying delays at each of these levels will be discussed and potential solutions will be reviewed. <h3>Disclosure of Interest</h3> None Declared
Abstract 2145: AR-42, a novel histone deacetylase inhibitor with selectivity against leukemia stem cell via apoptosis induction, inhibition of chaperone function of heat shock protein 90 in acute myeloid leukemia
Authors: Neng Yang, Duane C. Hassane, Marlene Balys, Cheryl A. Corbett, Craig T. Jordan, Monica L. Guzman
Journal: Cancer Research (2011)

Abstract AML is a fatal disease where most patients relapse and die of their disease. Increasing evidence indicates that disease relapse is driven by leukemia stem cells (LSCs). Thus, it is imperative to identify new therapies that can ablate LSCs. We have previously reported that screening the NCBI Gene Expression Omnibus (GEO) can accelerate the identification of anti-LSC compounds by searching for those mimicking the gene expression pattern of a known anti-LSC compound, parthenolide (PTL). One of our “hits” was the HDACi, AR-42 (Arno Therapeutics, Inc). This compound represents a novel class of HDACis that are structurally similar to phenylbutyrate, but with improved HDACi activity at sub-micromolar concentrations. At first, we investigated effects of AR-42 on growth and colony forming ability by using AML cell lines and primary human AML samples. AR-42 exhibits low micromolar potency in biochemical and cellular assays. AR-42 efficiently suppressed AML cell growth at a low dosage (1 μM) after 24 hours of treatment. Just like PTL, AR-42 preferentially targets AML progenitor and stem cell populations. More than 50% cell death was induced by AR-42 in phenotypically defined AML stem / progenitor. Colony forming capability of LSCs treated with 1 μM AR-42 for 24 hours was significantly diminished. Furthermore, 1 μM AR-42 significantly impaired the potential of LSCs in a nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenograft model. Surprisingly, even though AR-42 partially mimics the gene expression pattern of PTL, it does not activate Nrf2-controlled cytoprotective responses like PTL. AR- 42 inhibits NF-κB but, unlike PTL, does not activate HMOX-1. AR-42- mediated apoptosis is associated with activation of caspase 8, PARP cleavage. Further studies found that AR-42 induced inhibition of HSP90 in conjunction with degradation of FLT3 protein. Altogether, these findings indicate that AR-42 may be a promising LSC-targeted therapeutic agent. 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 2145. doi:10.1158/1538-7445.AM2011-2145
THU0444 Review of ultrasound findings in patients with shoulder pain. Sonografic study in 735 patients:
Authors: S. Muraja, B. Markulinčić
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Shoulder pain is a common symptom and it may be related to many different diseases. It is often difficult to identify the site of anatomic alterations with clinical examination and convention radiography.In contrast, sonography of soft tissues successfully evaluates changes of both articular and periarticular structures. <h3>Objectives</h3> The aim of the this study was to present ultrasound findings in patients with shoulder pain. <h3>Methods</h3> In our study 735 patients with shoulder pain were included (368 female and 367 male) with average age of 54,9 year (range 20-85). Moreover the shoulders of 450 healthy control subjects were examined. They were 220 female and 230 male and their mean age was 52.3 years (range 20-70). All of the patients underwent an ultrasound examination of shoulder by means of Shimatzu 2200 using a linear probe at the frequency of 8,5-10 MHz. Investigations included the long head of biceps tendon, rotator cuff tendons (peritendinous effusion, thickening, thinning, tears, calcifications); the subacromial and the subscapularis bursae (effusion); the acromioclavicular and glenohumeral joint (osteoarthritis, effusion). The chi square test was used for statistical analysis of the results above the level of p&lt;0.001. <h3>Results</h3> Results are reported on table 1. In 45 patients (6.1%) sonography did not show any changes of articular and periarticular soft tissues. Calcifications were found in 563 cases (76,5%) <h3>Conclusions</h3> The diagnostic ultrasound was proved to be very useful in detection of changes of the soft tissues in patients with shoulder pain. The sensitiveness of the technique is confirmed by the finding of alterations in 93.9% of cases. Sonography is a noninvasive and low cost imaging method and it is valuable either for monitoring the therapeutic response or for the possibility of ultrasound guided interventions. <h3>References</h3> Chhem R, Cardinal E. Guidelines and Gamuts in Musculosceletal Ultrasound,New York,Wiley-Liss, 1999, pp.1-71 de Jesus JO, Parker L, Frangos JA, Nazarian LN. Accuracy of MRI, MR Arthrography and Ultrasound in the Diagnosis of Rotator Cuff Tears: A Meta- Analysis AJR 2009 June;192:1701-1707. <h3>Disclosure of Interest</h3> None Declared
AB0109 The soluble form of CD18 is associated with clinical findings, CRP and MRI activity in spondyloarthritis
Authors: T.W. Kragstrup, M. Hvid, R. Østgård, B. Schiøttz-Christensen, A.G. Jurik, T. Vorup-Jensen, B. Deleuran
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lack of measures of disease activity and prognosis is a key challenge in spondyloarthritis (SpA). Several soluble biomarkers have been proposed, but very few have been found to relate to MRI activity and add to the diagnostic value of CRP.(1) Leukocytes are key players in SpA disease activity.(2) The soluble form of CD18 (sCD18) has been found to be shed from leukocytes in inflammation and to be present in the blood.(3) <h3>Objectives</h3> This study examines the association of sCD18 in the blood and SpA disease activity. <h3>Methods</h3> Plasma from a study population with 84 SpA patients at baseline and 33 patients at three-year follow-up and a control group of age and gender matched normal healthy volunteers (NHV) were studied. The samples were analyzed for sCD18 by a time resolved immunoflourometric assay (TRIFMA) using the KIM185 antibody as capture antibody and the KIM127 antibody as detection antibody as previously described.(3) <h3>Results</h3> The level of sCD18 was decreased in plasma from SpA patients compared to plasma from NHV (p&lt;0.0005). The level of sCD18 showed inverse correlations to the clinical parameters clinician defined disease activity on a 100-mm visual analog scale (VAS) (p&lt;0.05) and Bath Ankylosing Spondylitis Metrology Index (BASMI) (p&lt;0.005) and the paraclinical measures CRP (p&lt;0.005) and sacroiliac joint (SIJ) MRI activity score (p&lt;0.05). Interestingly, CRP did not show any significant relation to clinical findings or MRI activity in this study. Patients with BASMI improvement at three-year follow-up also had increases in sCD18 concentration compared to patients without BASMI improvements (p&lt;0.05). <h3>Conclusions</h3> sCD18 is associated with clinical findings, CRP and SIJ MRI activity in SpA. sCD18 could be a novel disease activity marker in SpA directly measuring leukocyte activity. <h3>References</h3> Maksymowych WP. Biomarkers in spondyloarthritis. Current rheumatology reports. 2010;12(5):318-24. Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011;377(9783):2127-37. Gjelstrup LC, Boesen T, Kragstrup TW, Jorgensen A, Klein NJ, Thiel S, et al. Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure. J Immunol. 2010;185(7):4154-68. <h3>Disclosure of Interest</h3> None Declared
AB1060 Bisphosphonate intravenous allows a rapid contrast of pain in complex regional pain syndrome (CRPS)
Authors: F. Bartoli, G. Fiori, F. Peruzzi, F. Galluccio, S. Cappelli, V. Denaro, G. Guidi, S. Pfanner, M. Ceruso, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The treatment of CRPS remains controversial, but multidisciplinary and interdisciplinary approaches seem to be inevitable to prevent long-standing or permanent disability (1). Bisphosphonates, apart from their antiresorptive activity, could also have other properties through a specific analgesic or anti-inflammatory effect.Bisphosphonate therapy has been shown to be effective in single cases of CRPS (2). <h3>Objectives</h3> to evaluate the efficacyof intravenous compared with intramuscular bisphosphonates in reducing pain in patients with CRPS. <h3>Methods</h3> 14 patients (one male and 13 females; mean age 64.3±8 years) diagnosed with CRPS of carpal and metacarpals bones (confirmed by clinical and MRI) from two weeks, were treated with non-steroidal anti-inflammatory drugs (NSAID), supplemental calcium and Vitamin D, physical therapy and clodronate. Seven patients were treated with iv (Group A) and seven with im clodronate (Group B) for 2 weeks. Then all patients were subjected to im clodronate 100 mg/weekly for 3 months. Pain scales (VAS 0-100) and joint examination were performed before, after one week and after 3 months of clodronate therapy. <h3>Results</h3> pain was 92.7±12 mm in group A and 91±7.5 mm in group B, before starting clodronate (t0). Clodronate reduces pain significantly (p=0.0001) in both groups after one week of therapy, but reduction of pain was significantly higher (p=0.0001) in patients treated with iv clodronate (VAS 21.8±7 mm in group A <i>vs</i> 48.2±9.1 mm in group B). After 3months, nostatistical significant difference (p=0.7) in painwas found. Rapid reduction of pain in group A is associated also to a rapid reductionof hyperhidrosis, edema and joint stiffness after one week of therapy.No adverse effects were reported during therapy. <h3>Conclusions</h3> Iv clodronate achieves a rapid reduction of pain compared to im formulation, in patients with CRPS. Early intervention and reduction of pain is also associated with a rapid clinical improvement that might help in the prevention of long-standing disability. <h3>References</h3> Tran de QH, Duong S, Bertini P, Finlayson RJ. Treatment of complex regional pain syndrome: a review of the evidence. Simm PJ, Briody J, McQuade M, Munns CF. The successful use of pamidronate in an 11-year-old girl with complex regional pain syndrome: response to treatment demonstrated by serial peripheral quantitative computerised tomographic scans. Bone 2010 Apr;46(4):885-8. Epub 2009 Dec 5. <h3>Disclosure of Interest</h3> None Declared
PATIENT BELIEFS REGARDING BENEFITS OF PERCUTANEOUS CORONARY INTERVENTION IN CHRONIC STABLE ANGINA: HAVE THEY CHANGED?
Authors: Auras R. Atreya, Mohammad Amin Kashef, Reva Kleppel, Paul Visintainer, Janice Fitzgerald, Carla Lauture, Marc Schweiger, Aaron Kugelmass, Michael Rothberg, Sarah L. Goff
Journal: Journal of the American College of Cardiology (2015)