tbuckley/cabot-search huggingface dataset:
No Increase in Second Tumors after Cytotoxic Chemotherapy for Gestational Trophoblastic Tumors
Authors: Gordon J. S. Rustin, Frances Rustin, Joan Dent, Margaret Booth, Sandra Salt, Kenneth D. Bagshawe
Journal: New England Journal of Medicine (1983)

We investigated the incidence of second tumors after cytotoxic chemotherapy in 457 long-term survivors treated for choriocarcinoma or an invasive mole between 1958 and 1978. Treatment was given according to regular intermittent schedules and over a mean period of four months, with no maintenance. Methotrexate was given to all but two patients, and 261 (57 per cent) also received other cytotoxic drugs, most commonly dactinomycin, vincristine, cyclophosphamide, mercaptopurine, and 6-azauridine. After a mean period of 7.8 years since the beginning of treatment and a total of 3522 patient-years of risk, second neoplasms had developed in only two women (acute leukemia in one and carcinoma of the breast in the other). This figure is less than the number of cases of cancer that would have been expected (3.5) in this group and suggests that the use of methotrexate as chemotherapy for choriocarcinoma is not carcinogenic in the medium term.
Abstract 327: Properties associated with cancer progression in primary clonal epithelial and mesenchymal-like murine mammary tumor cells
Authors: Katie A. Palen, Bryon D. Johnson, Jill A. Gershan
Journal: Cancer Research (2012)

Abstract The majority of cancer patients die from tumor relapse. Consequently, characteristics of tumor cells that may contribute to aggressive cancer progression are under intense investigation. Tumors are composed of heterogeneous populations of cells that express a continuum of epithelial and mesenchymal markers. There is mounting evidence that mesenchymal tumor cells acquire invasive features and are refractory to conventional treatment, but in order to decipher the contribution of both epithelial and mesenchymal-like tumor cells to disease relapse we must understand the cellular and molecular properties of each cell type. Using a combination of different culture conditions and cell sorting strategies, we cloned epithelial and mesenchymal-like tumor cells that were derived from FVB Tg MMTV/Neu spontaneous mammary tumors. The availability of these clonal primary cell lines provides an unique opportunity to compare tumor cell properties that may contribute to aggressive disease such as proliferation, resistance to apoptosis, tumorigenicity, invasiveness, expression of growth factor and cytokine receptors, inflammatory cytokine secretion, immunogenicity, and expression or down-regulation of immune-modulatory molecules. Some of our preliminary data has revealed that (1) Epithelial cells are more proliferative in vitro, and cell proliferation was reduced upon exposure to the tyrosine kinase inhibitor, TKI-258. TKI-258 did not significantly decrease the proliferation of mesenchymal-like tumor cells, (2) A population of epithelial-enriched cells was more tumorigenic as compared to mesenchymal-like-enriched cells when administered to an immune competent syngeneic host, (3) Epithelial cells express greater Neu transgene, IL-6 and TNF-α transcripts than mesenchymal-like cells, and (4) When low passage clonal epithelial and mesenchymal-like cells were used as a whole cell tumor vaccine in FVB wild-type mice there was an increase in CD8 T cell activation as compared to that elicited by administration of a non-clonal high passage tumor cell line. We are continuing to explore molecular and functional differences between the clonal epithelial, clonal mesenchymal and the non-clonal tumor cell line cells. Characterization of epithelial and mesenchymal-like tumor cells represents an initial step in deciphering how tumor cells contribute to aggressive cancer progression and will offer insight into how epithelial and mesenchymal-like tumor cells respond to therapeutic interventions. The ultimate goal will be to tailor anticancer therapy toward eradicating the unique type of tumor cells that populate patient tumors. 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 327. doi:1538-7445.AM2012-327
THU0404 A Comparative Study of FRAX Vs DEXA in Predicting Osteoporotic Fracture Risk
Authors: S. F. Bari, U. Srinivasan, N. Amos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoporosis is a disease characterised by low bone mass and structural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Case finding strategies form the basis of current clinical practice in identifying those patients who are at risk of osteoporotic fracture and would most benefit from preventative treatment. WHO guidelines using BMD (via DEXA scan) to stratify risk categories underpin clinical decision making and National Institute of Clinical Excellence (NICE) Technology Appraisals (TAs) define treatment options using this process. FRAX is a risk assessment tool which can be used without BMD assessment in a variety of clinical settings to define absolute fracture risk over a 10 year period. This, together with NOGG, is used to define whether patients should receive treatment, have further investigation with DEXA scan or receive lifestyle advice only. The recent NICE Clinical Guidelines (CG 146) promotes the initial use of FRAX (or QFracture) in the majority of patients at risk of osteoporotic fracture rather than referring them for DEXA scanning. This study compares the two methodologies of FRAX and DEXA in 355 patients who recently attended the osteoporosis service at Princess of Wales Hospital, Bridgend. <h3>Objectives</h3> To find out if FRAX is a reliable alternative to DEXA in assessing fracture risk <h3>Methods</h3> We included 355 patients with confirmed osteoporosis (T score ≤ -2.5 at total hip or total spine) on DEXA scan. We used their details from the CELLMA database to calculate FRAX and then compared with DEXA. <h3>Results</h3> 355 patients were included in the study (313 female and 42 male). - DEXA scan was recommended in 57% of the patients. - In 14% treatment was recommended. - In 29% of all patients, lifestyle advice alone would have been suggested. - 81% of the male patients would have only been given lifestyle advice. - 10% of the patients with established or severe osteoporosis (i.e. those with prevalent low trauma fractures in addition to osteoporotic T scores on DEXA scan) would not have been recommended for treatment using FRAX alone. <h3>Conclusions</h3> 29% of total patients with confirmed Osteoporosis on DEXA scan would have only been given lifestyle advice. 81% of males would have been missed by using FRAX tool alone. Of most concern is the 10% of patients with severe osteoporosis (recognized to have the highest risk of further fracture). The recent Clinical Guidelines from NICE recognize that an underestimate of fracture risk may occur if FRAX assessment alone is used to identify osteoporotic risk. This has been borne out by the above study. <h3>References</h3> NICE Clinical Guidelines (CG146) <h3>Disclosure of Interest</h3> None Declared
Anaphylactic shock-induced ischemic proctocolitis following bee stings: first case report
Authors: S. Park, H. Chun, B. Keum, Y. Seo, Y. Kim, Y. Jeen, H. Lee, S. Um, C. Kim, H. Ryu
Journal: Endoscopy (2010)

A 41-year-old male patient was referred for hematochezia following resuscitation from a hypotensive shock. The history revealed that while working outdoors, the patient had been attacked by a swarm of bees and received multiple stings, rendering him unconscious. Following initial recovery at the local hospital, he developed hematochezia and was referred to us. On examination at admission, the patient was alert and not pale, and his vital signs were stable. He denied any previous allergic history related to drugs or other substances, and he was not taking any medication. There was no notable family history. Pain and tenderness were elicited in the periumbilical region but without rebound tenderness. Digital rectal examination revealed bloody and mucoid discharge. The initial laboratory results showed leukocytosis and mild elevation of serum aminotransferases without anemia. Abdominopelvic computed tomography (CT) disclosed edematous wall thickening in the rectosigmoid and cecal regions. Electrocardiography did not show any sign of cardiac arrhythmia. On sigmoidoscopy, the rectal mucosa was hemorrhagic and greatly swollen with narrowing of the lumen, whitish exudates, and intermittent, deep ulcerations ([Fig. 1 a]). This presentation persisted as the scope was advanced and then relatively normal mucosa was seen at 25 cm from the anal verge with a sharply distinct margin ([Fig. 1 b]). Total colonoscopy carried out the next day revealed cecal pathology with similar findings ([Fig. 1 c]). Following administration of empirical antibiotics, bowel rest, and copious intravenous hydration, the abdominal pain subsided and the hematochezia ceased. The patient resumed his normal diet 11 days after admission. Pathologic examination verified the diagnosis of ischemic colitis. Follow-up total colonoscopy before discharge revealed much improvement ([Fig. 1 d – f]), and a later endoscopic review examination revealed minimal changes in the colonic mucosa with no evidence of stricture or other deformities.
503 HCV NEUTRALIZING ANTIBODY RESPONSE DURING SPONTANEOUS AND TREATMENT-INDUCED VIRAL CLEARANCE OF ACUTE HCV INFECTION IN HIV-INFECTED MSM
Authors: X.V. Thomas, R. Molenkamp, S.M. Koekkoek, J.T.M. van der Meer, M. Prins, S. Merat, T. Beaumont, J. Schinkel
Journal: Journal of Hepatology (2013)
Abstract 1297: IL-1a promotes neovascularization in prostate cancer via activated macrophages by BMP-6
Authors: Geun Taek Lee, Seok Joo Kwon, Jae-ho Lee, Yeon Suk Jung, Isaac Yi Kim
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most commonly diagnosed non-cutaneous cancer in men in the US. Active surveillance, radiation, and surgery are the recommended treatments for localized prostate cancer. However, approximately 35% of patients eventually develop biochemical recurrence within 5 years after the initial treatment. In the present study, we have investigated the significance of prostate cancer derived BMP-6 in the context of macrophages. BMP-6 activated macrophages and dramatically increased the production of interleukin-1α (IL-1α) in vitro. Mechanistically, optimal ligand/receptor/Smad combination for IL-1α induction was BMPRII (BMP type II receptor), ALK3 (BMP type I receptor), and Smad 1(R-Smad)/4(Co-Smad). We used a serial promoter deletion assay and found that −1,856 −1,655 bp region of IL-1α promoter contained the BMP-6 responsive element. Surprisingly, this region did not have the consensus Smad binding element. Additional analysis of this 200 bp region demonstrated multiple NF-κB binding sites. When NF-κB was inhibited, IL-1α induction was completely blocked. Moreover, BMP-6 increased NF-κB reporter vector activity and phosphorylated p50 and p65, suggesting NF-κB's role in induction of IL-1α [[Unsupported Character - &amp;#61472;]]by BMP-6. Immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) showed that Smad1 binds to the 200 bp region and interacts with NF-κB directly. Finally, VEGF expression increased in TRAMP-C2 prostate cancer cells co-cultured with macrophages. Based on these results, we propose that tumor-derived BMP-6 induces IL-1α expression in macrophages and that this induction requires Smad and NF-κB pathways; IL-1α, in turn, induces angiogenesis in prostate cancer. 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 1297.
P2-15-10: Do Patients with Incurable Advanced Breast Tumor and Distant Metastasis Derive Any Benefit from Primary Tumor Resection?
Authors: M Takahashi, S Shibasaki, H Jotoku, K-I Watanabe
Journal: Cancer Research (2011)

Abstract Background Metastatic breast cancer (MBC) is considered incurable. Surgical removal of primary tumors has not been established as a standard treatment for MBC because it is generally accepted that local therapy provides no survival advantage once metastases have occurred. Additionally, tumor excision may further stimulate metastasis.4 Therefore, primary tumor resection in patients with MBC is usually only applied as a palliative treatment for symptomatic wound complications such as bleeding, ulcer formation, unpleasant smell, and purulent discharge. In recent years, however, some retrospective studies have reported advantages of debulking surgery in terms of improving patient outcome. We retrospectively analyzed the surgical benefits and prognostic factors for patients with MBC who were treated at our center. Methods: We retrospectively reviewed individual medical records from the Hokkaido Cancer Center. In this study, incurable advanced breast cancer is defined as the presence of a tumor, larger than 5 cm, and shows either (invasion to chest wall or skin or is an inflammatory carcinoma) and at least one metastatic site, including distant lymph nodes, bone, or visceral organs (lung, pleura, mediastinum, liver, and brain) at diagnosis. Between January 2000 and June 2010, 92 women were diagnosed with incurable advanced breast cancer at our institute. The effect of surgical treatment on survival was evaluated. Patient demographics and tumor characteristics were also investigated. Results: Thirty-six patients had surgery for resection of primary tumors. There were no substantive differences between individuals, or between tumor characteristics, for patients who underwent surgery versus patients who did not. The median survival time for surgically treated patients was 25.0 months versus 24.8 months for patients who did not undergo surgical resection (P=0.352). Only three patients relapsed within three months of surgery. For the remaining majority of patients, primary tumor resection gave some relief from the often severe symptoms that come from harboring a large tumor for an extended time. In univariate and subsequent multivariate analyses of predictive indicators, a diagnosis of triple-negative breast cancer and/or metastasis to more than three sites was significantly associated with a severe prognosis. Conclusion: Primary tumor resection failed to prolong overall survival times in patients with incurable advanced breast cancer that was greater than 5 cm. However, surgery did improve the quality of life in patients who were expected to have a relatively long prognosis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-10.
Ability of Normal Human Keratinocytes That Grow in Culture in Serum-Free Medium To Be Derived From Suprabasal Cells
Authors: M. S. Wilke, M. Edens, R. E. Scott
Journal: JNCI Journal of the National Cancer Institute (1988)

The current studies were performed to determine from which regions of the skin keratinocytes that grow in vitro are derived. Normal human foreskin specimens were first separated by differential trypsinization into two suprabasal fractions and one basal fraction. Utilizing complete MCDB 153 basal nutrient culture medium containing epidermal growth factor and insulin, we then evaluated the clonogenic potential of cells in these three fractions. Suprabasal cell fractions demonstrated a colony-forming efficiency as great as or greater than that of the basal cell fraction, and 10%-15% of the keratinocytes that grew in primary and secondary cultures expressed involucrin, a suprabasal keratinocyte differentiation marker. Of such involucrin-containing keratinocytes, 80% also possessed the potential to undergo DNA synthesis, as determined by autoradiography following a 48-hour incubation with [3H]thymidine. These observations support the conclusion that the human keratinocytes that grow in vitro in serum-free medium can be derived from suprabasal cells and, therefore, that a state of nonterminal keratinocyte differentiation exists.
Abstract 4533: Interaction between androgen receptor and its corepressor SLIRP is regulated by Ack1 tyrosine kinase
Authors: Zhentao Zhang, Dinuka De Silva, Yuanbo Liu, H. Shelton Earp, Young E. Whang
Journal: Cancer Research (2011)

Abstract Reactivation of androgen receptor (AR) is critical to castration resistant progression of prostate cancer. We previously demonstrated that Ack1 (activated cdc42-associated kinase) promotes growth of prostate xenograft tumors in castrated animals by activation of AR through phosphorylation of the Tyr-267 site. However, the molecular mechanisms underlying activation of AR by Ack1 need to be fully elucidated. Using the proteomics-based approach of Differential In-Gel Electrophoresis, we searched for proteins whose interaction with AR was regulated by Ack1 by characterizing proteins coimmunoprecipitating with AR in transfected 293T cells in the absence or in the presence of activated Ack1 kinase. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. We confirmed that the interaction between AR and SLIRP is abrogated by Ack1 expression and dihydrotestosterone (DHT) in 293T cells and in LNCaP prostate cancer cells. Additionally, treatment with heregulin, a ligand activating HER-2/HER-3 and Ack1 downstream, also led to dissociation of AR and SLIRP in LNCaP cells. Tyrosine kinase activity of Ack1 was shown to be required for its ability to dissociate AR and SLIRP through the use of a kinase-dead mutant in 293T cells and the use of an Ack1 inhibitor dasatinib in LNCaP cells treated with heregulin. However, disruption of interaction between AR and SLIRP by Ack1 cannot be attributed to any known AR tyrosine phosphorylation sites since Ack1 expression led to disruption of binding between SLIRP and AR Y267F, Y363F, and Y534F mutants. Since SLIRP does not contain tyrosine residues, the substrate of Ack1 involved in AR-SLIRP dissociation is not known yet. We showed that SLIRP functions as a physiologically relevant corepressor of AR in prostate cancer cells. Chromatin immunoprecipitation analysis demonstrated that SLIRP was bound to the androgen regulated enhancers of AR target genes in the absence of androgen and that androgen or heregulin treatment led to loss of SLIRP binding at the androgen regulated enhancers. AR-dependent reporter activity was inhibited by overexpression of SLIRP and was increased by SLIRP knockdown. SLIRP knockdown also increased the expression of endogenous AR target mRNA levels of PSA and hK2. In summary, our data suggest that Ack1 kinase inhibits the interaction between AR and the SLIRP corepressor and causes dissociation of SLIRP from the AR target gene enhancers and thereby enhance AR transcriptional activity. 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 4533. doi:10.1158/1538-7445.AM2011-4533
SINGLE NUCLEOTIDE POLYMORPHISMS AT THE NIEMANN-PICKC1-LIKE1 GENE LOCUS SIGNIFICANTLY PREDICT CARDIOVASCULAR EVENTS IN CORONARY PATIENTS WITH TYPE 2 DIABETES
Authors: Axel Muendlein, Andreas Leiherer, Christoph Saely, Elena Kinz, Philipp Rein, Alexander Vonbank, Peter Fraunberger, Heinz Drexel
Journal: Journal of the American College of Cardiology (2016)
FRI0309 A Phase I Pharmacokinetics TRIAL Comparing PF-05280586 (A Potential Biosimilar) and Rituximab in Subjects with Active Rheumatoid Arthritis with Active Disease in TNF Failures (Reflections B328-01)
Authors: D. Yin, J.-C. Becker, L.A. Melia, R. Li, B. Gumbiner, D. Thomas, G. Spencer-Green, X. Meng
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> PF-05280586, a proposed biosimilar to rituximab, has the same primary amino acid sequence as rituximab with similar physicochemical and in vitro functional properties. <h3>Objectives</h3> This study was designed to demonstrate pharmacokinetic (PK) similarity of PF-05280586 to rituximab sourced from the US (rituximab-US) and EU (rituximab-EU), and between rituximab-US and rituximab-EU. Safety was also evaluated. <h3>Methods</h3> In this double-blind trial (NCT01526057), 220 subjects with active rheumatoid arthritis on a background of methotrexate who had an inadequate response to one or more TNF antagonist therapies were randomized 1:1:1 to one course of IV PF-05280586, rituximab-US or rituximab-EU 1000 mg on Days 1 and 15 (with stable background regimen of methotrexate). The primary analysis was the PK similarity testing using full PK profiling. PK similarity for a given test-to-reference comparison was considered demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to infinity (AUC<sub>0–∞</sub>) and maximum concentration (C<sub>max</sub>) were within 80.00–125.00%. <h3>Results</h3> Baseline demographics for 198 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar disposition profiles and PK parameters. The 90% CI for the ratios of C<sub>max</sub>, AUC from time 0 to 2 weeks (AUC<sub>0–2wk</sub>) and to the last measurable time point (AUC<sub>T</sub>), and AUC<sub>0–∞</sub> were within 80.00–125.00% for the comparisons of PF-05280586 to rituximab-US and rituximab-EU, and rituximab-EU to rituximab-US. A similar number of subjects discontinued for safety reason. 8 subjects reported serious adverse events of which 2 were considered treatment-related (rituximab-US: grade 2 atrial flutter [resolved]; rituximab-EU: grade 2 thrombocytopenic purpura [resolved although the subject was permanently discontinued from the study]). <h3>Conclusions</h3> This study demonstrates PK similarity of PF-05280586 to both rituximab-US and rituximab-EU and rituximab-EU to rituximab-US. All 3 treatments were generally well tolerated, with a low incidence of treatment-related AEs and discontinuations due to AEs. <h3>Disclosure of Interest</h3> D. Yin Employee of: Pfizer Inc., J.-C. Becker Employee of: Pfizer Inc., L. Melia Employee of: Pfizer Inc., R. Li Employee of: Pfizer Inc., B. Gumbiner Employee of: Pfizer Inc., D. Thomas Employee of: Pfizer Inc., G. Spencer-Green Employee of: Pfizer Inc., X. Meng Employee of: Pfizer Inc. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5444
Non-DNA-binding Ikaros isoform gene expressed in adult B-precursor acute lymphoblastic leukemia
Authors: K Nishii, N Katayama, H Miwa, M Shikami, E Usui, M Masuya, H Araki, F Lorenzo, T Ogawa, T Kyo, K Nasu, H Shiku, K Kita
Journal: Leukemia (2002)
Eggshell Calcifications of the Bladder
Authors: Pankaj Nepal, Devendra Kumar
Journal: New England Journal of Medicine (2016)

A 43-year-old man presented with dysuria and intermittent hematuria. Similar episodes had occurred several times in the preceding 6 months, with episodes of rectal bleeding. CT revealed hydroureteronephrosis of the right ureter and kidney, with mural calcifications.