tbuckley/cabot-search huggingface dataset:
Relationships between clinical and biochemical predictors of chemotherapy-related amenorrhea in premenopausal adjuvant breast cancer patients
Authors: I. Su, J. Alton, L. Sherman, C. Stankiewicz, S. Ratcliffe, A. DeMichele
Journal: Journal of Clinical Oncology (2007)

11011 Background: Premature ovarian failure (POF) is a major side effect of breast cancer adjuvant therapy. Predicting post- chemotherapy POF and reproductive status impacts decisions about fertility, contraception, menopausal issues and breast cancer treatment. We examined clinical and biochemical predictors of chemotherapy related amenorrhea (CRA) in premenopausal adjuvant breast cancer patients. Methods: We conducted a cohort study of 121 breast cancer patients with stages I-III disease, premenopausal at diagnosis, enrolled 1 to 4 years from chemotherapy. All patients received 4 cycles of doxorubicin and cyclophosphomide with or without 4 cycles of paclitaxel or docetaxel, at q2 (dose-dense) or q3 week intervals. The primary endpoint was CRA (amenorrhea &gt; 12 months from chemotherapy start). Pretreatment menstrual status and clinical factors were collected prospectively; subjects were recontacted for additional information and venipuncture. Regression models were used to examine risk factors for CRA and log FSH. Results: Mean age was 43.2 years (range 26.7–57.8). Mean follow up from chemotherapy start to enrollment was 2.1 years (range 1.0–4.1). 68 subjects developed CRA, while 53 continued menstruating. In a model including age, tamoxifen use, dose density, chemotherapy regimen, ovarian suppression during chemotherapy, smoking, body mass index and race, only age (OR 1.57[CI 1.29–1.89], p&lt;0.001), tamoxifen use (OR 7.25 [CI 5.89–34.87], p=0.01), and dose density (OR 3.38 [CI 1.16–16.50], p=0.03) had independent associations with CRA. Serum FSH at enrollment (n=112) was higher in CRA than in non-CRA (11.8 vs 45.8, p&lt; 0.001). However, 39% (25/65) of CRA subjects had FSH &lt; 40 mIU/mL, the biochemical threshold for menopause (mean 26.4, range 10.1–39.9). FSH was not associated with chemotherapy regimen (p=0.51) or schedule (p=0.21). Conclusions: Age, tamoxifen use, dose density and subsequent FSH were independently associated with CRA. Clinically, amenorrhea for more than 12 months did not always represent biochemical menopause. Better methods are needed to characterize ovarian function in patients after adjuvant chemotherapy. No significant financial relationships to disclose.
Serum Tryptase Levels in Acute Leukemia at Diagnosis: Correlation with CBF AML.
Authors: Roberto Cairoli, Carla B. Ripamonti, Simonetta Granata, Daniele Folli, Paola Brasca, Giovanni Grillo, Gianbattista Bertani, Liliana Intropido, Paola Marenco, Annamaria Nosari, Laura Pezzetti, Enrica Morra
Journal: Blood (2005)
Identification of a 6 gene molecular predictor of lapatinib related benefit: From breast cancer cell lines to a phase III trial
Authors: J. W. Gray, D. Das, N. Wang, W. Kuo, M. F. Press, A. Di Leo, C. Ellis, M. Arbushites, L. Williams, M. Koehler
Journal: Journal of Clinical Oncology (2008)

1043 Background: Identification of molecular predictors of response is an important aspect of efforts to individualize cancer treatment. Responses to lapatinib (L), an oral, dual inhibitor of HER2 and EGFR approved in combination with capecitabine for HER2+ metastatic breast cancer (MBC), were evaluated in a panel of BC cell lines. Computational approaches were then used to identify a 6-gene predictor of quantitative response to L. Methods: The clinical utility of the 6-gene predictor was tested retrospectively using a Panomics assay in tumor tissue samples from HER2-negative or HER2-untested MBC patients (pts) enrolled in a phase III trial of paclitaxel (P) or P+L. Panomics results were compared with HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) status and discordant cases were analyzed. Dichotomous response patterns of HER2+ pts and a computational model that predicts L sensitivity or resistance is described. Results: Tissue samples from 302 pts were tested using the branch capture Panomics assay, FISH and IHC. In the Panomics assay, pts with HER2 levels greater than 50% of GAPDH levels were considered HER2-positive. Pearson's correlation coefficient indicated a linear correlation of 0.75 (p<0.001) between FISH ratio and Panomics assay. Panomics and progression-free survival (PFS) data were available for 159 pts on L+P. Median PFS in panomics HER2+ group was 32.9 weeks vs. 22.4 weeks in the HER2-negative group. The 6-gene model was used to predict responders and non-responders to L in the HER2+ group. PFS comparison of 24 hypothesized sensitive tumors vs. 25 hypothesized resistant tumors treated with L+P indicated that the predictor developed in vitro has the potential to predict clinical response to L (HR=0.58, 95% CI=0.30, 1.11). FISH and Panomics assay discordance analysis is ongoing and will be reported. Validation of this approach will be evaluated in additional pt cohorts. Conclusions: This study establishes proof of principle strategies for identification of predictive markers, and can be further developed to guide their broad clinical introduction to appropriately target pts treated with L. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Roche GlaxoSmithKline Genentech, GlaxoSmithKline, Roche Genentech, GlaxoSmithKline
Symptom profile and clinical characteristics of metastases in metastatic renal cell carcinoma
Authors: R. Sawhney, F. Kabbinavar, A. Pantuck, T. Klatte, N. Zomorodian, A. Belldegrun
Journal: Journal of Clinical Oncology (2007)

19638 Background: In the US, 39,000 new cases of renal cell carcinoma (RCC) will be diagnosed and 13,000 people will die of RCC, in 2006(1). While incidence has increased 126% since 1950 (2,3), little information is available regarding prevalence of symptoms &amp; signs or metastases in patients presenting with metastatic RCC. Significance of such information is high as patients will be living longer, in this emerging era of targeted therapies for RCC. Method: Data were taken from prospective database of 1818 patients evaluated at UCLA with histologically confirmed RCC. From this 631 patients were identified with metastatic disease &amp; surveyed at diagnosis. Data was obtained on matching variables, that included age, gender, ethnicity, smoking status, comorbidities, performance status, symptoms, site of metastasis &amp; therapy. Results: 449 (71%) men, 182 (29%) women, were evaluated. Weight loss, hematuria, fatigue, flank pain, cough and musculoskeletal pains were the five most prevalent symptoms and signs. Of these patients, 557 (88%) were symptomatic with atleast one or more symptom on presentation and their presence lead to a diagnosis in 565 (90%) patients. In only 55 (8%) patients was metastatic RCC diagnosed incidentally. Most common metastatic site were the lungs 461 (73%), bones 200 (32%), followed by adrenals, non regional lymph nodes and soft tissue.Conclusion: In a large survey of metastatic RCC patients, weight loss, hematuria, fatigue, flank pain, cough and musculoskeletal pains were the five most prevalent symptoms and signs. Presence of atleast one or more of the above mentioned signs and symptoms led to a diagnosis in 90% of patients. Involvement of lungs and bones was most common at presentation. We believe that a better understanding of symptom and signs in patients with metastatic RCC, will lead to the development of better symptom assessment strategies, as well as early and thus cost-effective interventions. Especially in an era of increased disease control with targeted therapies. No significant financial relationships to disclose. [Table: see text]
Authors’ reply: A norovirus intervariant GII.4 recombinant in Victoria, Australia, June 2016: the next epidemic variant? Reflections and a note of caution
Authors: Leesa Bruggink, Michael Catton, John Marshall
Journal: Eurosurveillance (2016)

Preview this article: Authors’ reply: A norovirus intervariant GII.4 recombinant in Victoria, Australia, June 2016: the next epidemic variant? Reflections and a note of caution, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/21/41/eurosurv-21-30373-4-1.gif
A phase I study of MK-0646, a humanized monoclonal antibody against the insulin-like growth factor receptor type 1 (IGF1R) in advanced solid tumor patients in a q2 wk schedule
Authors: M. Hidalgo, M. Tirado Gomez, N. Lewis, J. L. Vuky, G. Taylor, J. L. Hayburn, K. Hsu, M. Kosh, V. J. Picozzi
Journal: Journal of Clinical Oncology (2008)

3520 Background: IGF1R is a receptor tyrosine kinase which is overexpressed in many primary tumor cells, including breast, colon, lung and prostate cancers. Activation of this signaling pathway induces mitosis, is required to establish and maintain a transformed phenotype, and protects cells against apoptosis. MK-0646 is a humanized IgG1 monoclonal antibody that binds to IGF-1R and is being developed for the treatment of cancer. Methods: In Parts 1 and 2, patients were treated with loading doses of MK-0646 from 2.5 - 20.0 mg/kg (mpk) followed by maintenance doses from 2.5 - 15.0 mpk IVq2W. In Part 3, patients will be treated at a 15 mpk loading dose and 10 mpk maintenance dose. The objectives of the study are to determine safety and tolerability, formation of human anti-MK-0646 antibodies, pharmacokinetics (PK), and tumor response. Results: 29 patients (M/F 22/7), with a median age of 62 yrs (range 23–84) were treated. The median number of days on treatment was 64 (range 14 to >351). Two patients have remained on study greater than 1 yr. One dose limiting toxicity (Gr 4 thrombocytopenia) was observed at the 15.0 mpk loading 5.0 mpk maintenance cohort. Adverse events include fatigue (9), vomiting, nausea, constipation (8 each), and diarrhea, weight loss, abdominal pain (7 each). PK analyses suggest that mean MK-0646 serum concentration following the loading dose decline at least biexponentially after peak; the terminal half-life averaged approx. 100 hours (range 54–296). The clearance (CL) for the loading dose was relatively unchanged at doses of 10 mpk and higher. Conclusions: MK-0646 appears to be well tolerated at loading doses up to 20 mpk and maintenance doses up to 15 mpk. Constant CL for loading doses higher than 10 mpk suggests saturation of IGF1R receptors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck
Colorectal Cancer Screening
Authors: Paul F. Pinsky, Maryam Doroudi
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Early disease progression in a phase I study of bortezomib (B), cetuximab (C), and intensity-modulated radiation therapy (IMRT) for squamous cell carcinoma of the head and neck (SCCHN).
Authors: C. Van Waes, A. G. Duffy, N. L. Simone, M. K. Gibson, Y. Arai, S. F. Rudy, T. Cooley-Zgela, M. Nyati, J. J. Wright, A. Argiris
Journal: Journal of Clinical Oncology (2010)

2575 Background: Preclinical studies combining proteasome inhibitor B and epidermal growth factor receptor (EGFR) inhibitor C, or B and RT, provided evidence for anti-tumor and radiosensitizing activity. These observations provided a rationale for a first-in-human phase I study combining B with standard concurrent C and IMRT in patients with advanced SCCHN. Methods: Cohorts of patients with chemo +RT naive stage IV or recurrent SCCHN were treated with escalating doses of B, (0.7, 1.0 and 1.3 mg/m2), given IV twice weekly on days 1, 4, 8 + 11 every 3 weeks. B + C 400 mg/m2 was started 1 week before, followed by B + weekly C 250 mg/m2 concurrent with IMRT 2Gy/5 days per week to 70 Gy. Results: 6 patients with stage IV and 1 with recurrent neck SCCHN were accrued; 6 had oropharyngeal and 1 had a laryngeal primary. 3 patients each received B 0.7 or 1.0 mg/m2, without dose-limiting toxicities, and 1 patient treated with B 1.3 mg/m2 was taken off study in week 5 due to recurring Gr 2 infusion reaction to C and progressive disease (PD). Expected Gr 3 toxicities included radiation mucositis (4), dermatitis (4), and rash (1). The study was terminated after 5/6 of the previously untreated patients had PD within one year, 2 in the lung and 3 locoregionally, despite 5 having better prognosis oropharyngeal SCCHNs (3 testing HPV+ before and 2 testing p16+ at the site of PD). The patient with a laryngeal primary had a CR and remains disease-free >10 months, and 1 patient each with PD were salvaged by surgery, or cisplatin and RT. In SCCHN cells, B was found to inhibit C and RT-induced degradation of EGFR, and enhance ERK1/2 pathway signaling and cell survival. Conclusions: The combination of B, C, and IMRT was well tolerated but resulted in a median progression free survival of <12 mos, which compared unfavorably to 17 mos reported for C+RT. Translational studies reveal B unexpectedly prevents C+RT induced EGFR degradation, enhancing tumor prosurvival signaling and radioprotection. Supported by NIHIntramural Project ZIADC-000016 and Millennium Pharmaceuticals. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium
A new timepiece: an epigenetic mitotic clock
Authors: Brock C. Christensen, Karl T. Kelsey
Journal: Genome biology (2016)

A new mitotic clock and mathematical approach that incorporates DNA methylation biology common among human cell types provides a new tool for cancer epigenetics research. Please see related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1064-3
In Vivo Tumor Dynamic Studies in Stable CLL Show an Association between CLL Turnover Rates and IgVH Mutational Status and Provide Evidence That the Bone Marrow Is Not a Major Site of Neoplastic Cell Generation.
Authors: Arnon P. Kater, Rogier van Gent, Annelieke Jaspers, Jose A.M. Borghans, Sigrid Otto, An F.C. Ruiter, Shulamit Wittebol, Eric Eldering, Marinus H.J. Van Oers, Marie-Jose Kersten, Frank Miedema
Journal: Blood (2007)
Glucose Metabolism Reprogrammed by Overexpression of IKKϵ Promotes Pancreatic Tumor Growth
Authors: Haseeb Zubair, Shafquat Azim, Sanjeev Kumar Srivastava, Aamir Ahmad, Arun Bhardwaj, Mohammad Aslam Khan, Girijesh Kumar Patel, Sumit Arora, James Elliot Carter, Seema Singh, Ajay Pratap Singh
Journal: Cancer Research (2016)

Aberrant expression of the kinase IKKε in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKε in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKε in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate. IKKε silencing also attenuated c-Myc in a manner associated with diminished signaling through an AKT/GSK3β/c-MYC phosphorylation cascade that promoted MYC nuclear accumulation. In an orthotopic mouse model, IKKε-silenced PDAC exhibited a relative reduction in glucose uptake, tumorigenicity, and metastasis. Overall, our findings offer a preclinical mechanistic rationale to target IKKε to improve the therapeutic management of PDAC in patients. Cancer Res; 76(24); 7254-64. ©2016 AACR.
In patients with type 2 diabetes and CVD, empagliflozin reduced incident or worsening nephropathy at 3.1 y
Authors: Tejas Patel
Journal: Annals of Internal Medicine (2016)

ACP Journal Club18 October 2016In patients with type 2 diabetes and CVD, empagliflozin reduced incident or worsening nephropathy at 3.1 yTejas Patel, MD, MPH, MBATejas Patel, MD, MPH, MBAIcahn School of Medicine at Mount Sinai St. Luke's and Mount Sinai West Hospital, New York, New York, USA (T.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2016-165-8-039 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWanner C, Inzucchi SE, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-34. https://pubmed.ncbi.nlm.nih.gov/27299675Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: Nephrology: References1 US Food and Drug Administration. FDA drug safety communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. May 2015. www.fda.gov/Drugs/DrugSafety/ucm446845.htm (accessed 31 Jul 2016). Google Scholar2 Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580-91. [PMID: 18256393] Google Scholar3 Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379:165-80. [PMID: 21840587] Google Scholar Author, Article, and Disclosure InformationAffiliations: Icahn School of Medicine at Mount Sinai St. Luke's and Mount Sinai West Hospital, New York, New York, USA (T.P.)This article was published at Annals.org on 4 October 2016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 October 2016Volume 165, Issue 8Page: JC39KeywordsAlbuminsCardiovascular diseasesCreatinineDrugsEstimated glomerular filtration rateHazard ratioPatientsRenal diseasesRenal failureType 2 diabetes ePublished: 18 October 2016 Issue Published: 18 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Plant-Derived Agent Silvestrol Has B-Cell Selective Activity In Vitro in Chronic Lymphocytic Leukemia Patient Cells and In Vivo in the Tcl-1 Mouse Model of CLL.
Authors: David M. Lucas, Ryan B. Edwards, Michael D. De Lay, Derek A. West, Gerard Lozanski, Amy J. Johnson, Angela A. Salim, Thomas S. Lin, John C. Byrd, A. Douglas Kinghorn, Michael R. Grever
Journal: Blood (2007)
PKC412, a FLT3 Inhibitor, Effectively Induces Apoptosis of Leukemia Cells with 11q23 Translocation Particularly Having D835 Mutation.
Authors: Kazuya Takahashi, Kumiko Goi, Yoshiyuki Furuichi, Takeshi Inukai, Kanji Sugita, Shinpei Nakazawa
Journal: Blood (2004)
Abstract A19: Inhibition of MK2 reduces chronic inflammation and regresses tumors in a mouse model of colorectal cancer
Authors: Anita L. Ray, Eliseo F. Castillo, Robert A. Nofchissey, Ellen J. Beswick
Journal: Cancer Research (2016)

Abstract Chronic inflammation is a known risk factor for colorectal cancer (CRC). Cancers in patients with increased inflammatory cytokines in tumor tissue are associated with increased drug resistance, metastasis, and mortality. We have identified mitogen-activated protein kinase-activated protein kinase 2 (MK2) as a regulator of pro-inflammatory cytokines and promoter of proliferation in CRC progression. MK2 signaling induces IL-1, IL-6, and TNF-alpha production, which have been associated with CRC development and progression. We investigated this pathway in an inflammation-related model of CRC. This model relies on an initial dose of the carcinogen azoxymethane, followed by administration of dextran sodium sulfate to model chronic inflammation. C57BL/6 mice were found to develop colon tumors by day 54 in this model. Thus, we treated mice with MK2 inhibitors starting at this time point, 3 times a week for 3 weeks. At day 80, neoplasm number and size were measured, as well as pro-inflammatory cytokines and immune cell profiles in the colon using flow cytometry and multiplex bead-based arrays. MK2 inhibition drastically reduced colon pro-inflammatory cytokines, influx of immune cells, and tumor burden compared to vehicle control treated mice. Upon testing two separate MK2 inhibitors, 6/7 and 5/7 mice were completely free of tumors after treatment. We conclude that this pathway is an important contributor to CRC and could be a promising therapeutic target. Citation Format: Anita L. Ray, Eliseo F. Castillo, Robert A. Nofchissey, Ellen J. Beswick. Inhibition of MK2 reduces chronic inflammation and regresses tumors in a mouse model of colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A19.