tbuckley/cabot-search huggingface dataset:
Complement Synthesis by Guinea Pig Peritoneal Macrophages: Failure To Detect Chemical Carcinogens&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: K S Kunke, R C Strunk
Journal: JNCI Journal of the National Cancer Institute (1981)

In vitro production of the second and fourth components of complement (C2 and C4, respectively) by peritoneal macrophages from noninbred Hartley guinea pigs was tested after the animals had been inoculated with known carcinogens. The system demonstrated the capacity of N-nitrosodimethylamine to decrease C2 and C4 production. However, a similar decrease in C2 and C4 production was seen with only CCl4, 1 of the 10 chemical carcinogens studied. This system had little usefulness as a short-term screening procedure for the detection of carcinogenicity. The effect of the carcinogens on several other functions of peritoneal macrophages was also determined. The number of peritoneal exudate cells (PEC) was significantly lower in carcinogen-inoculated animals than in solvent-inoculated controls for three carcinogens: BeSO4, P < 0.005; CHCl3, P < 0.025; and CCl4, P < 0.01. However, the capacity of the PEC to adhere to plastic was decreased by only CHCl3 (P < 0.05), and adherent cells from all guinea pigs produced normal amounts of total secreted protein.
Development of neuropathy in patients (pts) with multiple myeloma (MM) treated with thalidomide (thal)—Patterns of occurrence and the role of electrophysiologic monitoring
Authors: L. R. Mileshkin, R. Stark, B. Day, J. F. Seymour, J. B. Zeldis, H. M. Prince
Journal: Journal of Clinical Oncology (2006)

7618 Background: Given new treatment options for pts with MM, physicians are faced with the dilemma of how best to sequence these drugs in order to optimize efficacy and toxicity. Peripheral neuropathy frequently limits the duration of treatment (Rx) with thal. In this study we assessed the utility of serial nerve electrophysiological studies (NES) to detect the onset of neuropathy, and assessed the time course of occurrence and possible clinical and Rx-related predictive factors. Methods: 75 pts with relapsed/refractory MM were enrolled in a multi-centre trial of thal. In addition to clinical assessment, pts underwent sensory and motor NES at baseline and every 3 months in order to identify neuropathy. We examined the value of baseline and serial NES for development of neuropathy, with time to development of neuropathy according to clinical or NES criteria compared using Kaplan-Meier analysis. Differences between pt and Rx-related variables were compared using a Mann-Whitney U-test or a Fisher’s exact test. Results: Thirty nine percent had some NES abnormalities at baseline. Pts were treated with thal at a median dose intensity of 373 mg/day and followed for a median of 18 months (range 6–26). Thirty-one of the 75 pts (41%) developed neuropathy during thal Rx, with 11 (15%) ceasing thal due to neuropathy. The actuarial incidence of any neuropathy increased from 38% at 6 months to 73% at 12 months with 81% of responding pts developing this complication. The use of NES did not reliably predict the imminent development of clinical neuropathy requiring cessation of thal. Nor were pt age, gender or type of prior therapy (ie vincristine) predictive. Development of neuropathy was related to duration of thal exposure with a median time of 268 days thal in those who developed neuropathy compared to 89 days in those who did not (p = 0.0001). Cumulative dose or dose intensity received were not predictive. Conclusions: The majority of pts will develop peripheral neuropathy given sufficient length of thal Rx and to minimize the risk of neurotoxicity, therapy should be limited to less than six months. NES monitoring provides no clear benefit over careful clinical evaluation for the development of clinically significant neuropathy. [Table: see text]
Use of multidrug-resistance gene (MDR1) expression levels to predict outcome to adjuvant cisplatin/gemcitabine based chemotherapy in patients with with locally advanced urothelial cancer
Authors: T. Gauler, A. C. Hoffman, P. Wild, C. Leicht, S. Bertz, K. D. Danenberg, R. Stöhr, M. Stöckle, W. E. Eberhardt, J. Lehmann, A. Hartmann
Journal: Journal of Clinical Oncology (2009)

e22081 Background: The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp), whose function is the energy dependent export of substances from the inside of cells, and from membranes, to the outside. MDR1 mRNA levels have been shown to influence metabolism of cancer drugs. We tested whether MDR1 gene expression is associated with outcome in patients with locally advanced bladder cancer. Methods: 43 formalin fixed paraffin embedded (FFPE) tumor samples from patients with locally advanced and/or lymph node-positive bladder cancer undergoing treatment with cisplatin/gemcitabine were analyzed.FFPE tissues were dissected using laser-captured microdissection and analyzed for MDR1 expression using a quantitative real- time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: MDR1 was significantly correlated to overall survival. We included tumor stage (pT), lymph node status (pN) and the blood vessel invasion along with the measured gene expression in a stepwise multivariate Cox proportional hazards regression model. The overall model fit had a significance level of p=0.04 (&lt;0.05). The relative risk for shorter survival in patients with High MDR1 expression was 1.9. Conclusions: These results suggest that MDR1 gene expression levels predict response and overall survival in patients with locally advanced urothelial cancer. MDR1 gene expression levels may allow the selection of patients who benefit likely from adjuvant cisplatin/gemcitabine based chemotherapy. Further studies are warranted to study this association. [Table: see text]
Suppression of HOX A cluster genes inhibits proliferation and induces cell death in human mixed-lineage leukemias
Authors: J. Faber, A. Krivtsov, M. Stubbs, R. Wright, M. van den Heuvel-Eibrink, A. Kung, C. Zwaan, S. Armstrong
Journal: Journal of Clinical Oncology (2007)

14020 Background: Leukemias harboring translocations of the mixed lineage leukemia locus (MLL) are generally associated with poor clinical prognosis. Using gene expression profiling we and others have previously shown that Homeobox (HOX) A cluster genes are highly expressed in leukemias with MLL rearrangements. Methods: Here we studied the role of aberrant HOXA9 expression in human MLL- rearranged and non-rearranged leukemias utilizing an shRNA mediated knockdown approach. Results: Three different shRNA constructs targeting human HOXA9 were synthesized and stably introduced into t(9;11) MOLM14 cells utilizing a lentiviral vector system. 75–80% HOXA9 RNA knockdown was confirmed by quantitative PCR and Western Blot analysis. In a panel of 17 AML/ALL cell lines (7 MLL rearranged, 10 non rearranged), HOXA9 directed shRNA inhibited cell proliferation starting as early as 48h after transduction, and induced apoptosis beginning at 72h. Interestingly, impaired cell proliferation and induction of apoptosis was significantly higher in the MLL rearranged cell lines (mean viability: 51.88%) than in the non-rearranged cells (mean viability: 90.98%; p=0.007) and also significantly correlated with the baseline HOXA9 mRNA expression before knockdown (R= 0.8, p=0.00017). We then further analyzed the effect of HOXA9 knockdown in MLL rearranged and non-rearranged primary human AML cells. Similar to our findings in cell lines, a marked induction of cell death was observed, which was significantly higher in leukemias with an MLL translocation (p=0.005) and also significantly correlated with the baseline HOXA9 mRNA expression (R= 0.8, p=0.001). Next, the in vivo effect of HOXA9 knockdown was assessed by transplanting luciferase-expressing SEMK2 (t4;11) cells into SCID-beige mice followed by in vivo bioluminescent imaging. Leukemia burden was significantly reduced in HOXA9 shRNA treated mice (n=10) with a peak difference at day 15 (p=0.000059) shortly before mice of the control group (n=10) succumbed from overt leukemia. At this point all mice of the HOXA9 shRNA treated group were still healthy with no signs of leukemia. Conclusions: Taken together our data implicates that depletion of HOXA9 might be a novel approach for targeted therapy in human MLL rearranged leukemias. No significant financial relationships to disclose.
Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34
Authors: K Kita, K Nakase, H Miwa, M Masuya, K Nishii, N Morita, N Takakura, A Otsuji, S Shirakawa, T Ueda
Journal: Blood (1992)
Abstract 242: A Standardized Template for Measuring and Reporting Dispatch Prearrival CPR
Authors: Jeffrey Tully, Christian Dameff, Ryan Anne Murphy, Aaron Dunham, Micah Panczyk, Uwe Stolz, John Tobin, Brian Kotsur, Madalyn Karamooz, Daniel Spaite, Bentley Bobrow
Journal: Circulation (2012)

Introduction: Dispatch-Assisted CPR (DACPR) is a method for improving bystander response and survival from out-of-hospital cardiac arrest (OHCA). No standardized methodology exists for measuring and reporting this intervention. We developed a template for collecting, analyzing, and reporting DACPR. Methods: Five trained evaluators reviewed 161 suspected OHCA audio recordings from an urban 911 dispatch center. Key metrics in the evaluation of pre-arrival CPR instructions were recorded on a structured data form: dispatch recognition of OHCA, time interval to initiation of CPR instructions, and interval to first chest compression. Using the tool, evaluators identified common themes in the delivery of DACPR. Results: See Figure for template and results. Conclusion: Utilizing key components of the AHA DACPR Scientific Advisory Statement, we developed a method for collecting, analyzing, and reporting key metrics for DACPR that could act as a template to help improve the DACPR process and increase rates of Dispatch-Assisted bystander CPR (DA-BCPR). DACPR data collected in this manner may help identify targets for improvement in the prehospital response to OHCA. In addition, the template may support collaborative, inter-system investigations by providing a standardized, Utstein-type approach to data reporting.
Abstract B19: Functional translation of total RNA packaged in microparticles shed from multidrug resistant cancer cells
Authors: Jamie Fung Lu, Deep Pokharel, Frederick Luk, Mary Bebawy
Journal: Clinical Cancer Research (2015)

Abstract Microparticles (MPs) are submicron (0.1 -1 µM) membrane vesicles released from various cell types including malignant cells. Long considered to be inert cellular debris, MPs have recently been identified to play a crucial role in cellular cross-talk. MPs represent a heterogeneous mixture of surface antigens, proteins, lipids and cytoplasmic components resembling its parental cell. Our previous studies have identified the packaging and transfer of the transcripts, regulatory nucleic acids and proteins which are associated with the acquirement of multidrug resistance (MDR) between cancer cells. In this study we verify the functionality of packaged transcripts via in vitro translation of extracted total RNA from MPs isolated from cancer cells. We confirm the translation of exogenous RNA in a rabbit reticulocyte translation system via Western Blot analysis, 2-D SDS and mass spectrometry. These findings have significance in understanding the impact of MPs on cancer cell biology and reiterate their potential as a target in clinical oncology. Citation Format: Jamie Fung Lu, Deep Pokharel, Frederick Luk, Mary Bebawy. Functional translation of total RNA packaged in microparticles shed from multidrug resistant cancer cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B19.
Percutaneous vertebroplasty and/or kyphoplasty is an effective and safe treatment for painful vertebral compression fractures in multiple myeloma (MM)
Authors: S. K. Thomas, M. L. Wang, K. Yao, H. Villareal, M. Fukshansky, D. Suki, E. Mendel, D. M. Weber, R. Alexanian, A. Burton
Journal: Journal of Clinical Oncology (2006)

7610 Background: Painful vertebral compression fractures are a major source of morbidity in MM. Vertebroplasty involves percutaneous injection of polymethylmethacrylate (PMMA) into a vertebral body, while kyphoplasty involves inflation of a balloon for painful kyphotic deformity prior to stabilization with PMMA. Methods: We assessed safety and efficacy of 100 vertebroplasties and/or kyphoplasties in 81 consecutive myeloma patients between 12/2000 and 2/2005. Results: Median age was 63 (range 32–84), with 29% having prior radiotherapy to the vertebra treated. Contraindications included epidural compression of neural elements and failure to localize a symptomatic level. Kyphoplasty was preferred if kyphosis of &gt; 20 degrees contributed to pain, or if the posterior vertebral cortex was disrupted so that controlled delivery of bone cement was difficult. Vertebroplasty was performed when vertebral collapse was either slight or so severe that insertion of balloon device was not possible, or if patient could not tolerate the general anesthesia required for kyphoplasty. The median preoperative visual analog pain score (0–10) was 8(range 2–10); the median postoperative pain score was 3 (range 0–10) (p &lt; 0.01). There were no significant complications . Conclusions: Percutaneous vertebroplasty and kyphoplasty provided rapid and marked pain relief. These procedures are safe and feasible and represent the treatment of choice in selected MM patients with severe refractory pain due to pathologic compression fractures. No significant financial relationships to disclose.
Impact OF PIK3CA Mutations and P95HER2 Expression on the Outcome of HER2-Positive Metastatic Breast Cancer Patients Treated With a Trastuzumab-Based Therapy
Authors: I. Stasi, A. Fontana, G. Allegrini, C. Mazzanti, S. Lucchesi, E. Bona, I. Ferrarini, B. Salvadori, A. Falcone, K. Zavaglia
Journal: Annals of Oncology (2012)
Tumor-Associated Antigen Levels (Carcinoembryonic Antigen, Human Chorionic Gonadotropin, and Alpha-Fetoprotein) Antedating the Diagnosis of Cancer in the Framingham Study 1
Authors: Roger R. Williams, K. Robert McIntire, Thomas A. Waldmann, Manning Feinleib, V. L. W. Go, William B. Kannel, Thomas R. Dawber, William P. Castelli, Patricia M. McNamara
Journal: JNCI Journal of the National Cancer Institute (1977)

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.
Efforts in Epilepsy Prevention in the Last 40 Years
Authors: Matti Sillanpää, Mika Gissler, Dieter Schmidt
Journal: JAMA Neurology (2016)

<h3>Importance</h3> Prevention of new-onset epilepsy is an important public health issue and presents a pressing unmet need. It is unclear whether progress has been made in preventing new-onset epilepsy. <h3>Objective</h3> To determine whether progress has been made in the prevention of epilepsy in Finland during the last 40 years. <h3>Design, Setting, and Participants</h3> Using a long-term national register study of 5.04 million Finnish individuals, we looked at first-time inpatient admissions in Finland for a diagnosis of epilepsy from 1973 to 2013. Patients with epilepsy were defined by the occurrence of 2 or more unprovoked seizures. This study was conducted on July 29, 2015. <h3>Main Outcomes and Measures</h3> In Finland, patients with epilepsy are routinely hospitalized at time of diagnosis, thus providing evidence for the incidence of epilepsy. <h3>Results</h3> Of the mean 5.04 million Finnish individuals followed up for the development of epilepsy from 1973 to 2013, 100 792 people were identified as having epilepsy. Of these, 46 995 (47%) had focal epilepsy. The mean age for those included in the study was 45 years for men (interquartile range, 24-65 years) and 46 years for women (interquartile range, 23-71 years). We found no change in the incidence of epilepsy in the age range of those younger than 65 years (60 per 100 000 in 1973 and 64 per 100 000 in 2013). However, there was a significant increase in epilepsy among those older than 65 years (from 57 per 100 000 to 217 per 100 000). <h3>Conclusions and Relevance</h3> We found no evidence that progress has been made in preventing new-onset epilepsy in those younger than 65 years in the last 40 years; in fact, there was a nearly 5-fold rise of new-onset epilepsy among the elderly population.
Epothilone B (Epo-B) analogue BMS-247550 (NSC #710428) administered every 21 days in patients (pts) with hormone refractory prostate cancer (HRPC). A Southwest Oncology Group Study (S0111)
Authors: M. Hussain, J. Faulkner, U. Vaishampayan, P. Lara, D. Petrylak, D. Colevas, W. Sakr, E. D. Crawford
Journal: Journal of Clinical Oncology (2004)

4510 Background: The epothilones are a new class of non-taxane tubulin polymerizing agents with activity both in taxane-sensitive and resistant tumor models. This Phase II trial with a 2-stage design evaluated the efficacy and toxicity of Epo-B in pts with metastatic HRPC. Methods: Eligible pts had chemotherapy-naive metastatic HRPC, a Zubrod performance status 0–2, and adequate organ function. All patients received Epo-B (40 mg /m2) over 3 hours every 3 weeks. Disease was assessed after every 2 cycles. The primary end point was rate of PSA response (greater or equal to 50% decrease below baseline with stable or better objective disease). Results: Two-stage accrual was completed in November, 2003. Of the 48 registered pts 41 were eligible with a median age of 74 years. To date complete data is available for the 28 pts registered to the first stage (22 analyzable, 5 ineligible, 1 did not receive protocol specified treatment). Grade (G) 3 and 4 toxicities occurred in 11 and 1(neutropenia) pts, respectively. The most frequent G3 toxicities were fatigue (3 pts) and sensory neuropathy (3 pts). There were 9 PSA responses (41%, 8 confirmed and 1 unconfirmed, 95% CI 21–64%). Ten of the 22 pts had measurable disease and 3/10 had an objective response (30%, 1 unconfirmed complete and 2 unconfirmed partial responses). The estimated median progression free survival was 8 months (95% CI 6–11 months) and the estimated 1-year survival was 75%. The median survival was not reached at this time. Final results on all patients will be presented. Conclusions: Early results from this multicenter trial indicate that BMS-247550 has activity in patients with metastatic HRPC. Supported by CTEP. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Tamoxifen versus tamoxifen plus octreotide LAR as adjuvant therapy for early-stage breast cancer in postmenopausal women: Update of NCIC CTG MA14 trial.
Authors: M. N. Pollak, J. W. Chapman, K. I. Pritchard, J. E. Krook, H. S. Dhaliwal, T. A. Vandenberg, T. J. Whelan, S. E. O'Reilly, C. F. Wilson, L. E. Shepherd
Journal: Journal of Clinical Oncology (2010)

542 Background: Early preclinical data involving insulin/IGF physiology suggested a potential role for the use of a somatostain analogue in the adjuvant treatment of breast cancer. In 1996, the NCIC CTG initiated a trial of tamoxifen (T) alone versus the combination of tamoxifen with LAR octreotide (oct) in postmenopausal women with early-stage breast cancer. The final analysis for event-free survival (EFS) was reported at ASCO in 2008; this is an update. Methods: This phase III trial randomized early- stage postmenopausal women to T 20 mg daily for 5 years with or without oct (90 mg depot injections monthly) initially prescribed for 5 years and then reduced to 2 years due to concerns over cholelithiasis. Patients were stratified by nodal status, adjuvant chemotherapy and ER. EFS, the primary endpoint, defined as time from randomization to recurrence, second malignancy, or death due to any cause, along with relapse free survival ( RFS) and overall survival (OS) were assessed with an adjusted log- rank statistic and step-wise forward adjusted Cox analyses. Results: 667 women were accrued (333 to T and 334 to T + oct). MA.14 now has a median follow-up of 9.8 years, and 252 EFS events (130 on T and 122 on T +oct). The EFS hazard ratio (HR) is 0.93 (95% CI 0.73, 1.20; p-value = 0.57). We saw significantly longer EFS for women under 60 (p = 0.003), who had less than T2 tumours (p = 0.03), with N0 disease (p = 0.01), median or lower BMI (p < 0.0001), and lower c-peptide levels (p < 0.0001). Relapse-free survival (RFS, 78 events on T and 70 on T + oct) likewise had a non-significant (p = 0.40) HR of 0.87 (0.63, 1.21) as did OS (86 deaths on T and 84 on T + oct) with a HR of 0.94 (0.69, 1.27; p = 0.69). The number of breast cancer specific deaths in this older population was 54 on T, 57 on T + oct. Conclusions: Attempted manipulation of the insulin/IGF pathway with somatostatin analogue did not result in the intended declines in IGF-I or insulin levels in this trial. Insulin secretion estimated by c-peptide level is confirmed as an important negative prognostic factor. Targeting the insulin/IGF axis with metformin and/or antireceptor antibodies and/or specific tyrosine kinase inhibitors in ongoing trials will be of interest. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer
Original article: Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site
Authors: N. Pavlidis, P. Kosmidis, D. Skarlos, E. Briassoutis, M. Beer, D. Theoharis, D. Bafaloukos, A. Maraveyas, G. Fountzilas
Journal: Annals of Oncology (1992)