tbuckley/cabot-search huggingface dataset:
A role of chemotherapy for malignant peripheral nerve sheath tumors (MPNSTs): A retrospective analysis of 40 cases in a single institution.
Authors: Y. Funakoshi, A. Kawai, A. Hosono, A. Yoshida, H. Chuuman, A. Makimoto, Y. Beppu
Journal: Journal of Clinical Oncology (2010)

e20512 Background: Although surgery is the mainstay of the therapy for MPNSTs, chemotherapy has a role in the management of selected patients. The optimal chemotherapeutic regimen was not confirmed yet because of the rarity of the disease. To assess the efficacy of various chemotherapeutic regimens for MPNSTs, we analyzed the consecutive case series experienced in the National Cancer Center Hospital (NCCH) in Japan. Methods: Medical charts of 40 patients (Pts) who were histologically diagnosed with MPNSTs in NCCH between 1997 and 2009 were reviewed. The efficacy of chemotherapy was evaluated based on the best response per RECIST criteria. In localized Pts, surgical respectability was also evaluated. Results: Among 40 Pts aged 44 (range 4-78) years including 11 NF-1, twenty (12 newly diagnosed and 8 relapsed including 10 metastatic Pts) received chemotherapy. The median age of Pts who received chemotherapy was 32 (range 14-54) years. Among 10 Pts with localized disease, 8 received neoadjuvant chemotherapy and 5 could undergo complete resection of the tumor after obtaining response (2 PR, 2 SD, and 4 PD) while 2 received only adjuvant chemotherapy. In evaluation of the best response, 10 ifosfamide/etoposide (median 4.5 courses, range 2-7) resulted in 3 PR, 4 SD, and 3 PD, 7 ifosfamide alternating with doxorubicin, cyclophosphamide ± vincristine (median 4 courses, range 2-8) 1 PR, 3 SD, 2 PD, and 1 NE, 3 ifosfamide/doxorubicin (median 2.5 courses, range 2-3) 1 PR and 2 PD, 2 cisplatin/doxorubicin (median 5 courses, range 4-6) 2 PD, and 1 ifosfamide alternating with cisplatin/doxorubicin 1 PR. Other than above, the regimens which produced long-term stabilization of the disease in the metastatic Pts included 1 combination of cisplatin/docetaxel, and 1 anti-angiogenesis tyrosin kinase inhibitor. Conclusions: Chemotherapy could be used in neoadjuvant setting to improve surgical resectability as well as maintenance setting to stabilize disease for MPNSTs. Our data suggests that the ifosfamide containing regimen, especially comprising ifosfamide and etoposide, appears most active regimen for MPNSTs. Well-designed clinical trials to evaluate promising regimen are warranted. No significant financial relationships to disclose.
A8.13 Natural autoantibodies against citrate synthase and DNA topoisomerase I in patients with rheumatoid arthritis and spondyloarthritis receiving anti-TNF-α therapy
Authors: D Simon, A Pusztai, J Najbauer, P Németh, Z Szekanecz, T Berki
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Natural autoantibodies bind to evolutionarily conserved antigens in organs and tissues of the body and may have regulatory functions in the immune system and play a role in the clearance of apoptotic cells. It has been known that some patients treated with anti-TNF-α agents develop autoantibodies, including antinuclear and anti-double-stranded DNA antibodies. However, in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with TNF-α blockers there have been no studies regarding the presence of natural autoantibodies against citrate synthase (CS), a mitochondrial inner membrane enzyme, and DNA topoisomerase I (topo I), an enzyme that relaxes the superhelical stress in DNA. Therefore, our aim was: (1) to investigate whether patients with RA and SpA receiving anti-TNF-α treatment produce natural autoantibodies to CS and topo I; and (2) to test whether such therapy affects the levels of these autoantibodies. <h3>Materials and methods</h3> The study included a total of 36 patients (20 with RA, 16 with SpA) who received certolizumab or etanercept therapy. The levels of anti-CS and anti-topo I (immunodominant fragment) autoantibodies (IgM and IgG) were measured in the blood serum using enzyme-linked immunosorbent assay developed in our laboratory. The measurements were done at the starting point (0), 6, or 12 months of therapy. <h3>Results</h3> In the combined patient group (RA + SpA) we detected significantly increased levels of anti-CS IgM and IgG antibodies after 6 and 12 months of anti-TNF-α therapy. The anti-topo I IgM and IgG were significantly elevated only after 12 months of therapy, when compared to baseline antibody levels before the start of treatment. <h3>Conclusions</h3> The significance of the presence of anti-CS and anti-topo I natural autoantibodies is still a subject of research. We hypothesise that the increase in the levels of these natural autoantibodies might be a marker for the functional role of the natural immune system in patients treated with anti-TNF-α blockers. Because TNF-α is a pleiotropic cytokine, blocking its function can elicit various side-effects, including haematological, immunological, and others. Natural autoantibodies may function in the clearance of apoptotic cells and they may help restore the immunological milieu by reducing inflammation and protecting against some infections, functions in which the natural immune system has been implicated.
730 CONVENTIONAL SEROMARKERS FOR PREDICTION OF HEPATITIS B VIRUS-ASSOCIATED HEPATOCELLULAR CARCINOMA: AN EASY-TO-USE RISK SCORE
Authors: Y.-J. Lin, M.-H. Lee, H.-I. Yang, C.-L. Jen, S.-L. You, L.-Y. Wang, S.-N. Lu, C.-J. Chen
Journal: Journal of Hepatology (2012)
Reply to H. J. N. Andreyev
Authors: A. Postgate, B. Saunders
Journal: Endoscopy (2007)

We thank Dr. Andreyev for his interest in our technical review but would strongly disagree with the nihilistic tone of some of his comments regarding argon plasma coagulation (APC). Patients with bleeding from radiation proctitis may have a greatly reduced quality of life and to offer nothing except short-term drug therapy is, in our opinion, inappropriately defeatist. We share Dr. Andreyev’s frustration with the lack of carefully conducted randomized studies in this area and this was why our article was an expert opinion of APC technique rather than a comprehensive review of the management of radiation proctitis.
Poststreptococcal Glomerulonephritis without Proteinuria
Authors: L. B. Berman, P. Vogelsang
Journal: New England Journal of Medicine (1963)

THE question of whether poststreptococcal acute glomerulonephritis may occur without clinically detectable proteinuria is an elusive one. If one insists on bacteriologic or serologic evidence of a hemolytic streptococcal infection and histologic evidence of acute, diffuse glomerular involvement, no acceptable case has been recorded so far as we are aware. This is so, in spite of several affirmative answers to the question posed above. In 1872 Fenini1 presented a group of postscarlatinal nephritides with either absent or intermittent proteinuria, but without histologic description. One year later, Henoch2 described his often cited 2 autopsied patients with postscarlatinal nephritides, 1 of whom, . . .
Single-balloon endoscopy to remove a migrated esophageal stent in the small bowel
Authors: Na Li, Xiao-jun Zhao, Hai-hong Wang, Xin Wang, Jian-qiu Sheng
Journal: Endoscopy (2014)

A 49-year-old woman was admitted to the hospital emergency department having had abdominal pain for 16 hours. She had previously undergone placement of a fully covered anti-reflux metal stent to treat esophageal achalasia (achalasia of cardia). On physical examination, the abdomen was soft with normal bowel sounds. However, there was tenderness on deep palpation of the left lower abdomen. All laboratory test results were within reference ranges. An abdominal radiograph demonstrated an impacted metal foreign body in the left lower portion of the abdomen without signs of pneumoperitoneum ([Fig. 1]). Single-balloon endoscopy was performed (Olympus SIF-Q260; Olympus, Inc., Tokyo, Japan). At approximately 150 cm from the pylorus, the stent was found ([Fig. 2]). It was grasped with a snare and extracted ([Fig. 3], [Fig. 4]). An abdominal radiograph that was performed after the end of the procedure did not reveal pneumoperitoneum. The patient was discharged the following day.
Lymphoblastic Leukemia with Lymphomatous Features Associated with Abnormalities of the Short Arm of Chromosome 9
Authors: Robert R. Chilcote, Elizabeth Brown, Janet D. Rowley
Journal: New England Journal of Medicine (1985)

Patients with acute lymphoblastic leukemia (ALL) who present with bulky disease of the lymph nodes, spleen, or mediastinum — so-called "lymphomatous ALL" — appear to represent a distinct subgroup among patients with ALL of T-cell lineage who have different clinical findings, but the biologic basis for these differences is not known. While studying 65 patients with lymphoblastic leukemia whose karyotype was determined at diagnosis, we compared the findings in 8 patients with lymphomatous ALL and 57 patients whose presentations were more typical of ALL. Six patients with lymphomatous ALL had karyotypic abnormalities leading to loss of bands p21–p22 on the short arm of chromosome 9. The mechanisms varied and included deletions, unbalanced translocations, or loss of the entire chromosome. Only 1 of the 57 patients without lymphomatous ALL had an abnormality of chromosome 9 at diagnosis (P<0.001). These findings indicate that loss of chromosomal material in the region of 9p21–p22 is closely associated with lymphomatous ALL; by analogy with retinoblastoma, in which gene deletions are associated with an enzyme deficiency, this disease may be related to the loss of the enzyme methylthioadenosine phosphorylase, previously reported in some of these patients. (N Engl J Med 1985; 313: 286–91.)
Abstract 2022: Wnt ligands are overexpressed in murine mammary tumors in BK5.ATF3 transgenic mice
Authors: Leqin Yan, K. Leslie Powell, Michael C. MacLeod
Journal: Cancer Research (2011)

Abstract The Wnt/β-catenin signaling pathway is up-regulated in mammary tumors that arise with 70% incidence in parous female BK5.ATF3 transgenic mice. Nuclear accumulation of β-catenin is seen in both basal and supra-basal tumor cells in this model, whereas nuclear expression of the transcription factor ATF3 is only seen in the basal cell layer of the tumors. If ATF3 acted as a positive regulator of one or more Wnt ligands in the basal cells, one might expect paracrine upregulation of the Wnt/β-catenin pathway in neighboring supra-basal cells. To test this, we measured mRNA expression levels for 9 Wnt genes in BK5.ATF3 induced mammary tumors and normal mammary glands. The genes for five known positive acting Wnt ligands, Wnt3, Wnt3a, Wnt5a, Wnt7b, and Wnt10b, were significantly upregulated in tumors as compared to transgenic mammary glands. One of these, Wnt3, was significantly down-regulated in non-transgenic glands. In a mouse mammary tumor cell line, EMT6, in which the endogenous Atf3 gene is overexpressed, the only Wnt gene for which expression could be detected by qPCR was Wnt7b. ChIP assays demonstrated binding of both Atf3 and Jun proteins to two putative AP-1 sites upstream of the Wnt7b transcription start site in these cells. ATF3 and JUN are known in other systems to form heterodimers that exhibit positive transactivation through AP-1 sites, and we have identified a physical interaction between ATF3 and JUN in BK5.ATF3-induced tumors. 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 2022. doi:10.1158/1538-7445.AM2011-2022
Acute esophageal necrosis: possible association with terlipressin
Authors: Konstantinos Efthymakis, Chiara Massacesi, Angelo Milano, Francesco Laterza, Emanuele Tafuri, Francesco Cipollone, Matteo Neri
Journal: Endoscopy (2014)

A 75-year-old man was admitted to our department with abdominal pain, hematemesis, and melena. His significant medical history included erosive gastritis, alcohol-related chronic liver disease, and chronic pancreatitis. He was not receiving any medication. His blood pressure was low (80/50 mmHg); results of laboratory testing showed macrocytic anemia and liver dysfunction (hemoglobin 11.8 g/dL, mean cell volume [MCV] 106.4 fL, international normalized ratio [INR] 1.53). After a second episode of hematemesis, his hemoglobin dropped to 8.9 g/dL and he was treated by infusion of a colloidal solution, two units of packed red blood cells, a proton pump inhibitor, and terlipressin (2 mg every 4 hours).
The management of severe open lower limb fractures at a major trauma centre
Authors: Damien Gill, Michelle Baker, Scott Adams
Journal: International Journal of Surgery (2013)

To audit adherence to the British Orthopaedic Association and British Association of Plastic, Reconstructive and Aesthetic Surgeons 2009 review of the acute management of severe open lower limb fractures (BOAST4).  Audit: Retrospective study of adherence to BOAST4 standards of 37 cases treated at Derriford Hospital between March 2010 and 2011.  Intervention: a multidisciplinary approach towards the management of such injuries. Assigning department-specific roles across all specialities involved and establishing an early patient transfer pathway from non-specialist centres in the region.  Re-audit: Prospective data collection of adherence to BOAST4 of 18 cases between October 2011 and April 2012.  Eleven of 15 standards were comparable. Statistical analysis was performed using Fisher9s exact test (p≤0.05). Six standards showed statistically significant improvement: antibiotic therapy; regular assessment of neurovascular status; urgent surgery for contaminated wounds; initial wound care; appropriate splinting and early patient transfers. One standard was adhered to in all cases. 3 standards showed improvement, although not statistically significant and 1 standard remained consistently low in adherence.  Although doctors are familiar with BOAST4, many are not aware of the specific details. A coordinated and informed multidisciplinary team has enabled the successful application of an evidenced-based approach to the management these injuries.
Abstract 189: Kaempferol induces apoptosis in ovarian cancer cells through intrinsic pathway
Authors: Haitao Luo, Gary Rankin, Laura DePriest, Yi C. Chen
Journal: Cancer Research (2011)

Abstract The purpose of this study is to investigate whether and how kaempferol, a dietary flavonoid, induces apoptosis in human ovarian cancer cells. Ovarian cancer cell lines, OVCAR-3, A2780/CP70, and A2780/wt, were treated with kaempferol for 24 hours and analyzed for cell proliferation and cytotoxicity by genomic DNA staining and LDH assay, respectively. Apoptosis of cells were detected with Caspase-Glo 3/7 Assay. Intrinsic apoptotic pathway was further confirmed by pre-treating cancer cells with caspase-9 inhibitor, and tested for caspase 3/7 levels after kaempferol treatment. Protein levels of pro-apoptosis genes including p53, Bad, and Bax, and anti-apoptosis gene, Bcl-XL, were analyzed by western blots. Our data demonstrate that kaempferol inhibits cell proliferation but causes no necrosis in all 3 ovarian cancer cell lines. For apoptosis, caspase 3/7 levels were escalated by kaempferol treatment concentration-dependently and significantly. This effect can be diminished by pre-treatment with caspase-9 inhibitor, indicating an intrinsic apoptosis pathway involved in kaempferol-induced apoptosis in ovarian cancer cells. Western blot analysis revealed that protein levels of anti-apoptosis gene, Bcl-xL were decreased in ovarian cancer cells, while pro-apoptotic genes, p53, Bad, and Bax, were up-regulated by kaempferol treatment. In conclusion, kaempferol induces apoptosis in ovarian cancer cells through regulating expression of both pro-apoptotic and anti-apoptotic genes within the intrinsic apoptosis pathway. As a natural flavonoid wildly distributed in fruits and vegetables, kaempferol is a good candidate for chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are warranted. 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 189. doi:10.1158/1538-7445.AM2011-189
Abstract 2252: ALDH7A1 expression is associated with recurrence in patients with resected non-small cell lung carcinoma
Authors: Nicholas J. Giacalone, Rosana Eisenberg, Heidi Chen, Sandra Olsen, Pierre Massion, David P. Carbone, Thao P. Dang, Bo Lu
Journal: Cancer Research (2011)

Abstract The aldehyde dehydrogenase (ALDH) enzymes are important for detoxification of endogenous and exogenous aldehydes. Expression of ALDH family members has recently been described as a potential marker for tumor-initiating cancer stem cells in a variety of human malignancies, including lung cancer. We were interested to determine whether expression of ALDH7A1, a member of the ALDH family, has prognostic significance in resected non-small cell lung carcinoma (NSCLC). Tumor specimens were obtained for 107 patients with completely resected stage I through stage III NSCLC from paraffin-embedded tissue microarrays and stained with an antibody specific for ALDH7A1. Staining patterns were graded by a pathologist based on the intensity of staining and the percentage of cells stained. A staining score index was calculated by multiplying intensity score by the percentage area with positive staining. An index of ≥100 was considered positive, while an index &amp;lt;100 was deemed negative, as determined by visually determining a clear positive stain supported by histograms of the range of scores. Staining index was subsequently correlated with clinical data. Positive ALDH7A1 staining was identified in 46 patients, and negative staining was noted in 48 patients, with 13 tumor sections missing. Multivariate analysis demonstrated that NSCLC patients with positive ALDH7A1 expression had decreased overall survival relative to ALDH7A1-negative tumors, although this did not reach significance (hazard ratio 1.42, 95% confidence interval 0.84 to 2.389; p=0.192). However, patients with ALDH7A1-expressing NSCLC tumors had a significantly higher incidence of lung cancer recurrence compared to patients with ALDH7A1-negative tumors (hazard ratio 6.24, 95% confidence interval 2.06 to 18.86; p=0.001). These data indicate that ALDH7A1 staining is present in a substantial number of NSCLC tumors and may be a biomarker predictive for increased incidence of cancer recurrence in patients with surgically resected NSCLC. 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 2252. doi:10.1158/1538-7445.AM2011-2252
Comparative breast tumor imaging to identify the expression of type I IGF receptor (IGF1R) by anti-IGF1R antibody-conjugated small molecule fluorophore or quantum dots <i>in vivo</i>.
Authors: H Zhang, X Zeng, D Yee
Journal: Cancer Research (2009)

Abstract Abstract #6001 The type I insulin-like growth factor (IGF) receptor (IGF1R) is a transmembrane receptor tyrosine kinase involved in breast cancer proliferation, survival, and metastasis. Several antibodies against IGF1R, including some in clinical trials, downregulate the level of IGF1R both in cell line studies and in in vivo animal experiments. Thus, this downregulation is a biodynamic marker of antibody delivery to the tumor. To date, identification of IGF1R expression and its downregulation in vivo in a non-invasive way is still challenging. In this study, we sort to use two different fluorescent technologies, small molecule fluorophores, or quantum dots (QDs), to detect receptor expression and its downregulation by antibodies in vivo. Alexa 680 is a small molecule fluorophore that can be excited with a peak emission at 705 nm. QDs are nanocrystals that emit fluorescence upon excitation, and QDs with a peak emission at 705 nm was used in this study. Both Alexa 680 and QDs were conjugated with AVE-1642, a humanized anti-IGF1R antibody developed by sanofi-aventis. After conjugation, they both were able to detect the expression of IGF1R and its downregulation in in vitro cell line studies. We used mouse xenograft tumor models to examine their efficacies in vivo. AVE-1642 conjugated Alexa 680 or QDs (705 nm) was intravenously delivered to mice bearing mammary xenograft tumors that express IGF1R. After 24 hours of circulation, Alexa 680 fluorescence was shown to solely localize to the xenograft tumor, with little non-specific targeting to other tissue or organs in mice. In addition, Alexa 680 fluorescence was diminished in tumors that had downregulated IGF1R by antibody pretreatment. In contrast, conjugated QDs fluorescence was mainly localized to liver, spleen, bone marrow and lymph nodes, with very small amount of QDs in the xenograft tumors. The QDs fluorescence in xenograft tumors remained unchanged even when IGF1R was downregulated by antibody pretreatment. Furthermore, we identified that QDs were mainly localized to the hepatic sinusoids, and subsequently engulfed by Kupffer cells. Taken together, our data suggest that small molecule fluorophores, such as Alexa 680, are useful agents to detect the expression and downregulation of IGF1R in vivo. Our data provide valuable insight not only into the clinical development of anti-IGF1R antibodies, but also to other targeted therapy as well. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6001.
P1145 PEG-INTERFERON PLUS RIBAVIRIN WITH OR WITHOUT BOCEPREVIR OR TELAPREVIR FOR HCV GENOTYPE 1: A META-ANALYSIS ON ROLE OF RESPONSE PREDICTORS
Authors: N. Coppola, M. Pisaturo, C. Sagnelli, E. Sagnelli, I.F. Angelillo
Journal: Journal of Hepatology (2014)
Website of the week: Open archives
Authors: D Carnall
Journal: BMJ (1999)

Just as open source software (for which the programming code is freely available to allow modification and redistribution of the software) seems likely to supplant the proprietary offerings of Microsoft and others in the long term (www.opensource.org/), so open academic archives seem likely to replace the baffling and expensive proliferation of minority specialist journals. At the Open Archives initiative (vole.lanl.gov/ups/) a group of academics with experience of managing electronic archives call for the creation of “a fundamental and free layer of scholarly communication above which free and commercial services could flourish” (vole.lanl.gov/ups/ups-invitation-ori.htm). The site is an interesting example of a web based development paradigm: every important development is archived on the site, and the email discussions of the participants have been archived at vole.lanl.gov/pipermail/ups/. You can read, for example, the underlying discussion on why the name was changed from the original Universal Preprint Service initiative and a deconstruction of the argument, made by some commercial publishers, that some servers are “public” and some “private” (vole.lanl.gov/pipermail/ups/1999-November/000081.html).

The grand-daddy of all open print archives is the physics preprint archive at xxx.lanl.gov/. Naturally its index page is a 12 kb model of swiftly downloading propriety, though the underlying information structures are highly sophisticated. One of the new skills of the academic is to combine aptitude for LaTeX typesetting with some nifty optimisation of graphic files for the web. Neither skill is trivial to acquire, nor is it insurmountably difficult. The physicists, at least, have judged the price of their acquisition worth paying for the immediacy of publication on the web. To get a feel for the conventions that have made free and immediate communication possible in any academic subject, peruse the links from xxx.lanl.gov/help/.