tbuckley/cabot-search huggingface dataset:
P5-18-09: The Incidence of Febrile Neutropenia in the First Course of Adjuvant Chemotherapy with Docetaxel/Cyclophosphamide with or without Pegfilgrastim.
Authors: S Jones, D Paul, S Sedlacek, S Vukelja, ST Wilks, C Stokoe, CR Osborne, L Krekow, K McIntyre, FA Holmes, L Guerra, F Zhan, L Asmar, J O'Shaughnessy, JL Blum
Journal: Cancer Research (2011)

Abstract Background In our original doxorubicin-cyclophosphamide/docetaxel-cyclophosphamide (AC/TC) adjuvant study (JCO 27: 1177–1183, 2009), we reported an incidence of febrile neutropenia (FN) of 5% (8% in women ≥65 years) with the TC regimen without prophylactic WBC growth factors but with a recommendation for prophylactic antibiotics. There is a paucity of data on the incidence of FN with the TC regimen aside from this clinical trial. Because we have been conducting a randomized adjuvant study of TC compared to other regimens, we used this opportunity to analyze the incidence of FN during the first course of chemotherapy with TC in the first cohort of randomized patients (US Oncology Network study 06090). The prophylactic use of WBC growth factors was at the investigator's discretion. Patients and Methods The study included 1298 patients entered between May 2007 and May 2009. Of these, 649 were included in the TC arm. Median age was 54 years (range 27–71), 75.5% were Caucasian, 561 (86.4%) were in PS 0 at baseline, and about half were node negative. Eight patients did not receive study treatment for various reasons. Among the 641 patients who received TC; 213 (33.3%) received pegfilgrastim, 48 (7.5%) received filgrastim and were not included in this analysis, and 380 (59.2%) patients did not receive either during the first cycle. Thus, this analysis focused on 593 women who did or did not receive prophylactic pegfilgrastim in cycle 1. Results: All patients with a reported adverse event of FN or with a reported AE of fever with some degree of neutropenia (in order to capture all possible cases of FN) during the first cycle of TC were identified [Table 1]. FN and fever + neutropenia occurred in a total of 6 (2.8%) patients who received pegfilgrastim and 36 (9.5%) patients who did not. A comparison of age, race, performance status and stage of disease between these 2 groups revealed that they were similar. The 213 patients who received pegfilgrastim were slightly older (median 56 years, range 27–71) compared to those who did not (median 53 years, range 30–71). During all 6 cycles, 41 patients reported FN, and 30 (73%) of these patients experienced FN during cycle 1. Conclusion: Among 593 women who received TC as adjuvant chemotherapy, the incidence of FN during the first cycle was under 10% whether or not the patients received prophylactic pegfilgrastim. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-09.
Abstract 1631: Protection of colon carcinogenesis by estrogen receptor-beta may involve regulation of angiogenesis and invasion specific signaling molecules
Authors: Diana Saleiro, Genoveva Murillo, Michael Hawthorne, Rajendra Mehta
Journal: Cancer Research (2012)

Abstract Estrogen receptor-beta (ERα) has been suggested to exert anti-tumorigenic effects in the colon. However, its mechanism of action in colon cancer remains unclear. Previously, we demonstrated that azoxymethane (AOM) treated ERα knockout (≥ERKO) mice showed a significantly higher incidence of colonic precancerous lesions compared to AOM-treated WT mice. These results were associated with a decrease in apoptosis and loss of crypt organization in the colonic epithelium of αERKO mice. In the present study, we investigated whether ERα deficiency would also correlate with a higher incidence of colonic tumors. For this, αERKO and WT mice were injected subcutaneously with AOM (10mg/kg) once a week, for six weeks. Forty weeks after the beginning of the study, mice were sacrificed and colonic sections were collected for histopathology, RNA, and protein expression analysis. Evaluation of hematoxylin and eosin sections from each group showed that αERKO mice developed higher number of colonic adenomas (1.40 ± 0.40) than WT mice (0.33 ± 0.21) (p &amp;lt; 0.05). Furthermore, Mouse Cancer PathwayFinder Superarray revealed a greater than two-fold increase of angiogenesis and invasion specific signaling molecules in ERα-deficient tumors compared to WT ones. These findings highlight the importance of ERα against colon carcinogenesis progression. 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 1631. doi:1538-7445.AM2012-1631
Abstract P2-05-20: Validation and comparison of CS-IHC4 score with a nomogram based on Ki67 index, Adjuvant! Online, and St. Gallen risk stratification to predict recurrence in early Hormone Receptor (HR)-positive breast cancers
Authors: YH Park, S-A Im, EY Cho, JH Ahn, SY Woo, S Kim, B Keam, JE Lee, W Han, SJ Nam, IA Park, D-Y Noh, JH Yang, JS Ahn, Y-H Im
Journal: Cancer Research (2012)

Abstract Background: Recently, the information in the IHC score was reported to be similar to that in the 21-gene Genomic Health recurrence score (GHI-RS). The aim of this study is to develop a nomogram based on Ki67 index to predict recurrence and to validate the nomogram by comparison with CS-IHC4 as well as Adjuvant! Online and St. Galen risk stratification. In addition, we validated our nomogram with external cohort. Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of 1,070 postoperative HR-positive breast cancer patients between 2004 and 2007 at the Samsung Medical Center to determine recurrence-free survival (RFS). We constructed nomogram using Cox proportional hazard model and validated externally in a cohort of 1,028 at Seoul National University Hospital. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four IHC markers (IHC4 score) were created and assessed in our cohort by LR-χ2 test using the bootstrapping method. Results: Nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.70 (95% CI, 0.62–0.75) in the training set. The validation set showed a good discrimination with an AUC of 0.65 (95% CI, 0.58–0.72). In LR-χ2 test, the nomogram score was found to be more informative than the IHC4 with CS (LR-χ2 4.0539 [df1], 95% CI; 0.1038–8.004 for CS-IHC4 + nomogram score vs. CS-IHC4). Prognostic significance was more prominent in N1 diseases than in the others (LR-χ2 4.199, 95% CI; 1.496–6.902 for CS-IHC4 + nomogram score vs. CS-IHC4). However, Adjuvant! Online and St. Galen risk stratification did not show any definitive additional prognostic value. Conclusions: We developed and validated a nomogram based on Ki67 index in external patients' cohort. It was compared with CS-IHC4 in our patients' cohort in early HR-positive breast cancers. This study implicates the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-20.
Abstract 3009: Alternative pre-mRNA splicing in digestive tract malignancy
Authors: Koh Miura, Shinobu Ohnuma, Wataru Fujibuchi, Kazuyuki Ishida, Iwao Sasaki
Journal: Cancer Research (2012)

Abstract Alternative pre-mRNA splicing plays an important role in the generation of functional diversity of genome. The process of pre-mRNA splicing is regulated by cis- and trans-elements, and their deregulations result in aberrantly-spliced individual variants and aberrant expression profiles. Accumulating evidence has revealed that aberrant splicing contributes to a number of diseases including human neoplasms. Germ line mutations in cis-element of tumor suppressor genes such as MMR genes, APC gene, and CDH1 gene are involved in Lynch syndrome, familial adenomatous polyposis, and hereditary diffuse gastric cancer, respectively. In addition, somatic mutations in cis-elements also play a role in tumorigenesis. These genetic alterations including nonsense, missense, or silent mutations in cis-elements, led to aberrant transcripts by exon skipping, retention of the intron, or introduction of new splice site (Miura et al., Cancer Science 2011 Feb;102(2):309-16). We present our results and current knowledge of the regulatory mechanism underlying alternative pre-mRNA splicing and aberrant splicing, particularly focusing on digestive tract malignancies. 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 3009. doi:1538-7445.AM2012-3009
Abstract 543: A loss of function Cbl-c mutation in a murine breast cancer model.
Authors: Stephen C. Kales, Philip E. Ryan, Marion Nau, Jeffrey E. Green, Stanley Lipkowitz
Journal: Cancer Research (2013)

Abstract Receptor Tyrosine Kinase (RTK) signaling is essential for normal biological processes and inappropriate RTK activity can result in malignant transformation. Cbl proteins are a family of RING finger ubiquitin ligases that negatively regulate a variety of RTKs, including EGFR, MET, RET and components of the TCR pathway and disruption of this negative regulation can lead to tumor initiation and progression. Recent studies have identified a growing number of Cbl mutations associated with human myeloid neoplasias and epithelial tumors. Cbl-c is the most recently identified human Cbl protein and is expressed exclusively in epithelial cells. Recently, a novel Cbl-c cDNA has been isolated from a ductal carcinoma which developed in a C3(1)SV40Tag mouse, a murine model of breast cancer driven by Large T antigen. This mutant cDNA encodes a Cbl-c protein which lacks the catalytic domain of Cbl-c, thereby resembling known Cbl family mutations associated with myeoloid neoplasias. Genomic analysis of both parental and transgenic lines shows no evidence of germline mutation indicating that this mutation is likely somatic and may contribute to malignant transformation in this animal model. In overexpression studies, this mutant Cbl-c protein fails to mediate ubiquitination and degradation of activated EGFR and acts as a dominant negative protein, preventing ubiquitination of the EGFR by wild type Cbl proteins. The mutant Cbl-c protein also enhances transformation of NIH 3T3 cells by SV40 Large T antigen and through subsequent analysis of transforming capacity and signal pathway regulation, we are assessing interacting partners of Cbl-c and the potential role of this mutation in tumorigenesis. This mutant Cbl-c protein is the first functional evidence for the involvement of Cbl-c in transformation. Citation Format: Stephen C. Kales, Philip E. Ryan, Marion Nau, Jeffrey E. Green, Stanley Lipkowitz. A loss of function Cbl-c mutation in a murine breast cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 543. doi:10.1158/1538-7445.AM2013-543
Timing of endoscopy in high-risk patients with nonvariceal upper gastrointestinal bleeding
Authors: G. Corbett, E. Cameron
Journal: Endoscopy (2011)

We read with interest the study by Lim et al. [1], which suggests that earlier endoscopy is associated with better outcomes for high-risk patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). NVUGIB has a significant mortality. Whilst endoscopic therapy has been shown to significantly improve this, there is also good evidence that most of the mortality in patients presenting with NVUGIB is not directly related to bleeding [2] and little evidence to suggest that very early endoscopy affects outcomes although consensus suggests that it should be performed within 24 hours [3].
Entrance of Bacteria into the Female Urinary Bladder
Authors: Jose L. Bran, Matthew E. Levison, Donald Kaye
Journal: New England Journal of Medicine (1972)

Although bladder urine is normally sterile, it seems likely that small numbers of bacteria may enter the bladder commonly in women, especially in association with trauma to the urethra. Our investigation was undertaken to study bladder urine from women without urinary-tract infection and to determine the effect of mild urethral trauma (urethral milking) on isolation of bacteria from bladder urine. Forty suprapubic bladder aspirations were performed in 28 women; bacteria were isolated in low numbers from 10 (25 per cent) of the aspirates. Only one of 16 aspirates before urethral milking was positive, whereas nine of 24 aspirates after milking were positive, often with the same organism as in the external urethra. At urine culture 48 to 72 hours after the aspiration no patient had "significant" bacteriuria (105 or more bacteria per milliliter of urine) with the same organism as isolated from the aspirate. Thus, small numbers of bacteria may enter the urinary bladder in women, especially in association with urethral trauma, without causing urinary infection.
Undetectable Serum Thyroglobulin in a Patient With Metastatic Follicular Thyroid Cancer
Authors: ILSE J. R. MERTENS, JOHN M. H. DE KLERK, PIERRE M. J. ZELISSEN, JOS H. H. THIJSSEN, DAISY M. D. S. SIE-GO, SHIUW H. HAN, PETER P. VAN RIJK
Journal: Clinical Nuclear Medicine (1999)

The case of a 54-year-old woman with metastatic follicular thyroid cancer and undetectable serum thyroglobulin is presented. Many years after the patient had a subtotal thyroidectomy for a large goiter that had no clear evidence of malignancy, metastatic bone disease developed. When the bone metastases were detected and during the follow-up period, serum thyroglobulin values remained undetectable, but radioiodine uptake in the metastases was abundant. This case indicates that the combination of I-131 scintigraphy and serum thyroglobulin values is superior to the measurement of serum thyroglobulin alone in detecting well-differentiated, metastatic thyroid cancer.
Amelioration of Metabolic Acidosis with Fludrocortisone Therapy in Hyporeninemic Hypoaldosteronism
Authors: Anthony Sebastian, Morris Schambelan, Stanley Lindenfeild, R. Curtis Morris
Journal: New England Journal of Medicine (1977)

In four patients with renal hyperchloremic acidosis and hyperkalemia, hyporeninemic hypoaldosteronism and chronic renal insufficiency (glomerular filtration rates of 13, 31, 35 and 44 ml per minute per 1.73 m2), prolonged administration of fludrocortisone increased urinary potassium and net acid excretion, corrected hyperkalemia and substantially ameliorated acidosis. Except in the patient with the lowest glomerular filtration rate, the increased net acid excretion was due mostly to increased ammonium excretion. Urine pH decreased initially in each patient, but in the three patients with the highest filtration rates, it increased subsequently as ammonium excretion increased, indicating that renal ammonia production increased. Urinary ammonium excretion correlated inversely with serum potassium concentration and did not decrease on discontinuation of therapy if hyperkalemia was prevented from recurring. In patients with renal acidosis and hyporeninemic hypoaldosteronism, administration of mineralocorticoid hormone can augment both renal hydrogen-ion secretion and, by correction of hyperkalemia, renal ammonia production, and thereby ameliorate metabolic acidosis.
Abstract 3725: Bortezomib-induced neuropathic pain: Evaluation of anti nociceptive effect of a new analgesic compound
Authors: Annalisa Canta, Cristina Meregalli, Valentina Alda Carozzi, Norberto Oggioni, Alessia Chiorazzi, Giovanni Tredici, Marco Lanza, Ornella Letari, Gianfranco Caselli
Journal: Cancer Research (2010)

Abstract Bortezomib (Btz) is a highly effective and widely used antineoplastic drug for the treatment of many tumors, primarily multiple myeloma. Despite its effectiveness, the use of this proteasome inhibitor is limited by its toxicity. Among Btz side effects, peripheral neurotoxicity is a major and clinically relevant problem. In fact, since the earliest Phase I and Phase II studies, sensory peripheral neuropathy emerged as a dose-limiting side effect. Moreover, a significant proportion of Btz-treated patients developed severe neuropathic pain. The treatment of Btz-induced neuropathic pain is extremely difficult with the currently available drugs and still remains a major challenge for oncologists and neurologists. Aim of this study was to demonstrate if the new analgesic compound CR4056 could reverse the neuropathic pain induced by a chronic treatment with Btz in the rat. The anti-nociceptive and dose-dependent effect of CR4056 was assessed in a well-established experimental rat model in which Btz was administered to Wistar rats (0.20 mg/kg three times/week for 8 weeks) followed by treatment with CR4056 (6, 20 or 60 mg/kg daily p.o.) or buprenorphine administered 28,8 µg/kg/day p.o. for 2 weeks. Body weight change, hematological and histopathological parameters, nerve conduction velocity (NCV) and sensory behavioral tests were evaluated during the experiment. No remarkable effect of Btz administration or of any dose of CR4056 was observed in the hematological parameters and blood chemistry. After 8 weeks of treatment, Btz induced a severe reduction in NCV; this impairment was not reversed by CR4056 or by buprenorphine. The behavioral assessment showed a significant mechanical allodynia in rats treated with Btz for 8 weeks (delta vs. controls −6 g). Buprenorphine significantly reduced Btz-induced allodynia during the fist day by about 63%. However, this effect was lost during the following days of treatment (i.e 20% reduction on the 3rd day). The mid and high dose of CR4056 (20 and 60 mg/kg) showed a significant (i.e &amp;gt; 80 %) reduction of allodynia till the 3rd day of administration, afterwards a slight reduction in efficacy was recorded. On the contrary, the oral daily administration of 6 mg/kg CR4056 persistently counteracted Btz-induced allodynia, showing an even complete reversion after 2 weeks of treatment. The present study gives evidence for a relevant and persistent anti-allodynic effect of CR4056, suggesting a role for CR4056 in the management of neuropathic pain in patients treated with Btz. 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 3725.
Abstract 4732: Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb.
Authors: Koji Kurose, Shingo Eikawa, Yu Mizote, Yoshihiro Ohue, Midori Isobe, Akiko Uenaka, Mikio Oka, Eiichi Nakayama
Journal: Cancer Research (2013)

Abstract Objectives: Tregs down-regulate immune responses against various antigens including tumor cells. Impairment of Tregs cause autoimmune responses. CC chemokine receptor 4 (CCR4) is expressed selectively on Foxp3+CD4 T-cells, so that the treatment of PBMCs with KM2760, anti-human CCR4 mAb with a defucosylated Fc region, could deplete CCR4+Tregs by ADCC. In this study, we analyzed depletion of Tregs phenotypically and functionally after treatment of PBMCs with KM2760. Methods and main results: CCR4 expression was analyzed on CD4 T-cells purified from healthy donor PBMCs by FACS. CCR4 positivecells were 21% in CD4 T-cells, and 71% in Foxp3+cells. Depletion of CCR4 positive cells by treatment with KM2760 was examined. PBMCs were incubated with KM2760 (0, 0.01, 0.1, 1, 10 μg/ml) for 4 or 20 hours, and analyzed by FACS. Efficient depletion was observed with higher antibody concentration and longer incubation time. Then we examined inhibition of CFSE dilution of labeled CD4 or CD8 T cells stimulated with anti-CD3 mAb after culture with an equal number of CD4+25+127low Tregs and CD4-8- cells pretreated with or without KM2760. Proliferating responder cells were 68% in culture with CD4+25+127low Tregs pretreated with KM2760, whereas those cells with CD4+25+127low Tregs without pretreatment was 38% in CD4 T-cells, 77%and 40% in CD8 T-cells,respectively. Conclusions: Efficient Treg depletion was observed in vitro by treatment of PBMCs with KM2760. In vivo treatment with the same mAb may induce tumor immune responses by Treg depletion. Citation Format: Koji Kurose, Shingo Eikawa, Yu Mizote, Yoshihiro Ohue, Midori Isobe, Akiko Uenaka, Mikio Oka, Eiichi Nakayama. Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4732. doi:10.1158/1538-7445.AM2013-4732
Increased F-18 FDG Uptake in the Stomach
Authors: RODOLFO F. NUNEZ, HENRY W. D. YEUNG, HOMER MACAPINLAC
Journal: Clinical Nuclear Medicine (1999)

A 66-year-old man with prostate cancer and an increasing prostate-specific antigen level was referred to the authors' department to undergo a fluorine-18 fluorodeoxyglucose (F-18 FDG) whole-body PET scan to evaluate the extent of his disease. The coronal whole-body PET image showed intense F-18 FDG uptake below the heart in what appeared to be another heart below the diaphragm. When more anterior coronal and sagittal PET images were reviewed, it became clear that the uptake represented the fundus of the stomach. The patient had diffusely increased uptake throughout the stomach. He had a history of gastritis, which most likely was the cause for this unusual finding.
Endoscopic closure of a perforated peptic ulcer
Authors: F. Swahn, U. Arnelo, L. Enochsson, M. Löhr, T. Agustsson, K. Gustavsson, M. D’Souza, L. Lundell
Journal: Endoscopy (2011)

A 42-year old woman with Wilson’s disease was admitted with a history of acute-onset upper abdominal pain. Physical examination revealed signs of peritonitis in the upper abdomen, and an abdominal CT scan demonstrated a localized pneumoperitoneum ([Fig. 1]).
P692 HIGH NORMAL ALT AND BORDERLINE HBVDNA WERE PREDICTORS FOR FUTURE TREATMENT ELIGIBILITY IN CHRONIC HEPATITIS B (CHB) PATIENTS WHO INITIALLY DID NOT MEET CRITERIA
Authors: L. Uribe, N. Nguyen, L. Nguyen, L.H. Kim, H.N. Trinh, M.H. Nguyen
Journal: Journal of Hepatology (2014)
Balloon overtube-assisted placement of self-expanding metal stents
Authors: H. Neumann, C. Wilcox, K. Mönkemüller
Journal: Endoscopy (2013)

Occasionally, placement of a self-expanding metal stent (SEMS) into the distal stomach, colon, or small bowel may not be possible because of an angulated or torqued lumen [1]. This problem can be solved by either advancing the stent over stiffer wires or by through-the-scope placement. However, the large-diameter delivery system of esophageal SEMS impedes its application through the endoscopic channel. Here we present a novel balloon overtube-assisted technique for successful placement of SEMS in patients whose upper gastrointestinal tract has deranged, tortuous, and/or stenotic lumens.
Feasibility and Yield of Offering Genetic Counseling to All Patients with Gastric Cancer, in a Public Hospital of Argentina
Authors: Silvina Otero, Maria Colica, Gabriela Marraco, Karina Óleary, Erika Stegmayer, Maria Bianconi, Gabriela Lavelli, Luciana Gennari, Carolina Sanchez, Gustavo Jankilevich
Journal: Annals of Oncology (2013)
Grading a Physician's Value — The Misapplication of Performance Measurement
Authors: Robert A. Berenson, Deborah R. Kaye
Journal: New England Journal of Medicine (2013)

By 2017, the value-based payment modifier will be used to reward or penalize all Medicare physicians on the basis of the relative calculated value of the care they provide. But a physician's overall value cannot be assessed with current or foreseeable measures.