tbuckley/cabot-search huggingface dataset:
Concordance of study objectives with efficacy findings in metastatic breast cancer (MBC) treatment trials
Authors: D. Frame, S. D. Ross
Journal: Journal of Clinical Oncology (2007)

6600 Background: Despite ongoing development of new agents, overall survival in MBC remains discouraging. We reviewed large randomized controlled trials (RCTs) published since 2000 to compare stated objectives with efficacy endpoints. Methods: Systematic review of RCTs of systemic antineoplastic treatment in advanced / metastatic breast cancer, published 2000–2006 in English. Studies enrolling fewer than 100 patients or performed only at sites outside North America and Europe were excluded. Study success was characterized with regard to the primary endpoint as described in prospective power calculations. Results: 68 RCTs, enrolling 24,956 patients, met inclusion criteria. The 68 RCTs comprised 83 efficacy comparisons due to multiple arms and/or more than one primary endpoint. Frequency of success was similar by geographic location and presence of industry sponsorship, but higher for noninferiority comparisons ( Table 1 ). 5 of 13 non-inferiority studies reported unplanned superiority findings for the experimental arm, while 11 of 39 studies failing to meet planned superiority endpoints made statements regarding equivalence or superiority to control treatments. For 10 of 20 successful superiority studies, reported results did not match/exceed planned between-group differences, though the comparisons reached statistical significance: 4 such studies substantially exceeded planned enrollment (2 of which recalculated sample size after reviewing interim data), while reasons for attaining superiority in 6 cases were unclear. Of the remaining 10 superiority comparisons, 4 reached significance due to underperforming control arms (enabling PFS/TTP differences of &lt;2 months to establish superiority), 2 exceeded point estimates, and 4 exceeded estimated between- group ratios. Conclusions: Slippage from prospective study goals, even in large randomized trials, may contribute to a disconnect between the profusion of research activity and disappointing efficacy gains in MBC. No significant financial relationships to disclose. [Table: see text]
Challenging the Association Between Screen Time and Cognitive Development—Reply
Authors: Dillon Browne, Nicole Racine, Sheri Madigan
Journal: JAMA Pediatrics (2019)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
OP0032 Invasion of synoviocytes is inhibited by gene transfer of tnf-bp or il10 in an<i>in vitro</i>invasion model
Authors: EJ Pieterman, PH Goossens, WH vd Laan, AL Huidekoper, MJ Rabelink, RC Hoeben, FC Breedveld, TW Huizinga
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In RA fibroblast like synoviocytes (FLS) degrade and invade into adjacent cartilage. An <i>in vivo</i> model is the SCID-mouse/Human cartilage/synoviocyt model (S. Gay). Previous studies indicate that the invasive behaviour of fibroblast like synoviocytes can be tested <i>in vitro</i> in a matrigel transwell system. Matrigel, mainly composed of laminin and collagen IV, serves as a model for cartilage. <h3>Objectives</h3> The aim of this study was to compare the invasive behaviour of FLS from RA and osteoarthritis (OA) patients and to investigate the effect of adenoviral (Ad) transfer of genes encoding IL-10 and TNF-binding protein (p55) (TNF-BP) on the invasive behaviour of FLS from RA patients. <h3>Methods</h3> FLS from 43 RA and 28 OA patients obtained from synovial tissue harvested at joint replacement surgery, were seeded at confluency in serum free medium on top of a matrigel coated transwell filter with 8 μm pores. Medium with 10% Fetal Calf Serum and 10% Human Serum was used in the lower compartment. Three days post incubation cells were fixated, stained and the invaded synoviocytes on the lower side of the filter were counted. To test the effect of IL10 and TNF-BP, RA synoviocytes were infected overnight with 5, 10, 50 and 100 plaque forming units (pfu)/cel of Ad. IL10, Ad. TNF-BP or Ad. luciferase (negative control) and then tested in the invasion model. <h3>Results</h3> Significantly more RA synoviocytes invaded through the matrigel (median = 4035 cells) as compared to OA synoviocytes (median = 1900 cells; p &lt; 0.001). IL10 and TNF-BP gene transfer both resulted in a dose dependent inhibition of invasion with a maximal inhibition of 93.7% (± 10.7) and 86.6% (± 14.5) respectively, while luciferase gene transfer showed a maximal inhibition of 17.6% (± 1.7). <h3>Conclusion</h3> In conclusion, the invasive behaviour of FLS can be studied in the matrigel transwell system. This assay discriminates between the invasive behaviour of RA and OA FLS. The invasive behaviour of RA synoviocytes can be strongly inhibited by IL10 indicating that IL10 is able to downregulate the proteins involved in invasive growth. The inhibitive effect of TNF-BP indicates that continuous production of TNF is involved in invasive behaviour of synoviocytes.
Risk of malignancy associated with chronic lymphocytic leukemia: A population based Canadian study
Authors: M. W. Pitz, V. Banerji, A. A. Demers, Z. Nugent, J. Strutinsky-Mason, C. Morales, D. Hewitt, H. Zhang, S. Gibson, J. B. Johnston, M. D. Seftel
Journal: Journal of Clinical Oncology (2006)

20020 Background: Patients with Chronic Lymphocytic Leukemia (CLL) may have an increased risk of other malignancies. Available literature reports on malignancies that develop after the diagnosis of CLL, but does not discuss malignancies that precede the diagnosis of CLL. Methods: All patients diagnosed with CLL between 01/1998 and 12/2003 were extracted from the provincial cancer registry and a centralized flow cytometry database. All other malignancies were obtained from the cancer registry. Dates of diagnoses were compared. A malignancy within 30 days before or after the diagnosis of CLL was considered synchronous with that diagnosis. Results were compared with the age-adjusted incidence of cancer in the province, excluding CLL. Results: Of the 713 cases of CLL, 333 invasive cancers and 38 in situ neoplasia were identified before, synchronous to, or after the diagnosis of CLL. Synchronous malignancies occurred in 4% of cases. The Standardized Incidence Ratio (SIR) for other malignancy subsequent to CLL was 1.40 (95% confidence interval [CI] 1.09–1.80) derived from 65 tumors for males, and 1.29 (95% CI 0.90–1.80) from 35 tumors for females. Mean time to diagnosis of subsequent cancer was 2.0 years (standard deviation[SD] 1.5). The SIR for other malignancy in the 5 years preceding the diagnosis of CLL was 1.36 (95% CI 0.93–1.94) from 31 tumors for males and 0.77 (95% CI 0.54–1.08) from 35 tumors for females. Mean time from diagnosis of preceding malignancy to CLL was 9.4 years (SD 8.7). Conclusions: In this population based study, patients with CLL are at increased risk of other invasive and in situ cancers. This risk is apparent after but not before the diagnosis of CLL, particularly in males. The mechanism of this increased risk may be acquired with the presence of CLL through an underlying but undetermined mechanism, as opposed to an inherent or more longstanding predisposition to malignancy. No significant financial relationships to disclose.
Snake fang–inspired stamping patch for transdermal delivery of liquid formulations
Authors: Won-Gyu Bae, Hangil Ko, Jin-Young So, Hoon Yi, Chan-Ho Lee, Dong-Hun Lee, Yujin Ahn, Sang-Hyeon Lee, Kyunghun Lee, Joonha Jun, Hyoung-Ho Kim, Noo Li Jeon, Woonggyu Jung, Chang-Seon Song, Taesung Kim, Yeu-Chun Kim, Hoon Eui Jeong
Journal: Science Translational Medicine (2019)

A microneedle patch that uses snake fang–inspired multiple open grooves can rapidly deliver liquid-phase drugs and vaccines under capillary action.
Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study
Authors: F. Joly, T. Petit, P. Pautier, E. Guardiola, F. Mayer, A. Chevalier-Place, R. Delva, E. Sevin, M. Henry-Amar, H. Bourgeois
Journal: Journal of Clinical Oncology (2007)

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m 2 ) and topotecan (2.5 mg/m 2 ) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI &lt; 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI &lt; 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI &lt; 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.
PTH-048 The use of a novel non-diathermic endoscopic mucosal resection device in the management of scarred colonic polyps
Authors: K Kandiah, S Subramaniam, P Bhandari
Journal: Gut (2017)

Introduction  The current management of large colonic polyps is endoscopic resection via endoscopic mucosal resection (EMR). This widely practiced technique is evidently safe but carries a risk of polyp recurrence with rates varying between 10%–15% in polyps larger than 20 mm in size. Post-EMR recurrences are often scarred and there is a loss of the submucosal planes. This makes endoscopic management of these polyps very challenging with a high risk of complications. EndoRotor is a novel non-diathermic EMR device designed to reduce diathermy related complications (eg. perforation and delayed bleeding). We present a video demonstrating the use of a novel non-diathermic EMR device in the management of a scarred polyp.  Method  The novel non-diathermic device contains a fixed outer cannula and a rotating inner cannula. There is an opening at the end of both cannulas. There is an opening of both cannulas where tissue is sucked into and dissected by the rotating inner cannula. The dissected tissue is then transported into a tissue trap as the polyp is being treated. The device does not employ the use of diathermy thereby reducing the risk of perforation and delayed bleeding.  Results  A 55-year-old female who had a multi-piece EMR for a 50 mm laterally spreading tumour in the recto-sigmoid junction was found to have a 10 mm residual tissue in the resection base during her 3 month post-EMR check. The histology of the resected tissue was reported to show tubulovillous adenoma with low grade dysplasia. Endoscopic assessment demonstrated a scarred polyp with predominantly Type III surface pattern. The polyp was overlying 1 fold and encompassed less than 20% of the lumen circumference. Lifting solution consisting of gelofusine, indigo carmine and dilute adrenaline was injected around the polyp. However, due to scarring, there no lift was obtained. EndoRotor was then used to successfully resect the polyp without the need for diathermy. Pooled fluid in the lumen was removed using the same device.  Conclusion  Scarred polyps can be very challenging to manage endoscopically as the submucosal plane is often lost due to fibrosis. This heightens the risk of perforation and delayed bleeding when traditional endoscopic resection techniques are applied. EndoRotor is a novel device that is able to resect scarred polyps without the use of diathermy.  Disclosure of Interest  K. Kandiah: None Declared, S Subramaniam: None Declared, P Bhandari Conflict with: Receives educational grants from Fujifilm, Olympus and Pentax
Bridging sunitinib exposure to time-to-tumor progression in hepatocellular carcinoma patients with mathematical modeling of an angiogenic biomarker.
Authors: Sihem Ait-Oudhia, Donald E. Mager, Garin Tomaszewski, Adrienne E. Groman, Patricia D. Zagst, Gerald J. Fetterly, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2012)

e14690 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with 250,000 new annual cases in the US. Sunitinib (SU), an oral tyrosine kinase inhibitor, inhibits tumor cell proliferation, selectively binds to the angiogenesis biomarker (VEGFR2), and is metabolized to an equipotent metabolite (SU12662). The objective of this study is to utilize mathematical modeling to bridge drug exposure and VEGFR2 dynamics to tumor growth inhibition (TGI) and time-to-tumor progression (TTP). Methods: Plasma concentrations of SU, SU12662, and VEGFR2, and tumor growth and TTP measurements were obtained from a phase-II study in 16 patients with unresectable HCC. SU was administered at 37.5 mg daily 7-days prior to chemoembolization, then on days 15-35. A MAP Bayesian approach was utilized to model SU and SU12662 pharmacokinetics (PK), both captured with a two-compartment model including linear clearances. Inhibition of VEGFR2 production was mediated by predicted active unbound concentrations (AC ub ) of SU and SU12662. VEGFR2 concentrations were the driver for TGI. The TTP probability was modeled with exponential hazard function dependent on a time varying covariate -the difference in VEGFR2 concentration from its baseline (ΔVEGFR2). Results: Drug and metabolite clearances (CL d , CL m ) were estimated at 30.3 (19, %RSE) and 19.7L/h (14). Their volumes of distribution (V d , V m ) were 1,780 (39) and 1840L (25). SU exposure was within target range for VEGFR2 inhibition. VEGFR2 half-life in plasma was calculated at 4h. The slope (α) for AC ub effect on VEGFR2 production was 0.77(µg/mL) -1 (14). The ΔVEGFR2 effect on TGI was assumed maximal, whereas its potency (ΔIC 50 ) was estimated at 1.83x10 -2 µg/mL (41). The between-subjects variabilities were 37.4, 51, 44.7, 64.8, 21, and 36% for CL d , CL m , V d , V m , α, and ΔIC 50 . The median observed tumor size baseline was 91 mm 3 . The simulated mean TTP was 7 months. Conclusions: The time-course of SU, SU12662, and VEGFR2 were captured well with final PK/pharmacodynamic models. VEGFR2 profiles successfully linked drug exposure to TGI and TTP. This model may serve as a general platform for the dynamics of anti-angiogenic drugs.
An open-label phase II study evaluating the safety and efficacy of PTK787 in patients with progressive metastatic neuroendocrine cancer
Authors: L. B. Anthony, M. Cronin, T. O’Dorisio, S. O’Dorisio
Journal: Journal of Clinical Oncology (2006)

14124 Background: PTK787, an aminophthalazine, is an orally active angiogenesis inhibitor blocking all known vascular endothelial growth factor receptors (VEGFR)- and platelet-derived growth factor receptor (PDGFR)-tyrosine kinases . The majority of metastatic neuroendocrine malignancies express VEGF and PDGF receptors. Since both growth factors have been implicated in tumor-induced angiogenesis, PTK787 offers a novel approach for inhibiting tumor growth. Methods: In a phase II trial, we investigated the safety and antitumor activity of PTK787 in patients who had biopsy-proven metastatic neuroendocrine cancer, such as carcinoid, and had shown evidence of progression on somatosatin analog therapy. Eligible patients had measurable lesions other than bone, a Karnofsky performance status &gt;60 and normal hematologic, renal and hepatic functions. Patients on octreotide therapy were required to be on a stable dose not exceeding 30 mg monthly of the LAR formulation. Initial dosing of PTK787 was 1,250 mg daily. Results: Six patients (4 males) were enrolled between 5/20/05 to 8/09/05. Median age was 61 years (range, 48 to 65). There was 1 withdrawal of consent. The remaining 5 patients continue on treatment as of January 2006. One patient required a 10 day discontinuation for rising SGOT/SGPT and alkaline phosphatase. Resumption of PTK787 at 1,000 mg daily was well tolerated in this patient. Radiographically and scintigraphically, all 5 patients have demonstrated stable disease by CT and OctreoScan, respectively. Recruitment to this trial continues. Conclusions: PTK787 is generally well tolerated in patients with metastatic neuroendocrine cancer and may be effective in controlling somatostatin analog resistant disease though partial radiographic responses have not been observed. No significant financial relationships to disclose.
Massive ST-Segment Elevation and QTc Prolongation in the Emergency Department
Authors: Akihiro Takasaki, Shiro Nakamori, Kaoru Dohi
Journal: Circulation (2019)

ECG CHALLENGEA previously healthy 62-year-old man presented to the emergency department with presyncope that occurred 3 days ago.He reported feeling recent emotional stress from work and progressive fatigue after the event.He had been drinking excessively since then.He denied any chest pain or palpitations.There was no family history of arrhythmias, sudden cardiac death, or any psychiatric disorders.His blood pressure was 141/99 mm Hg.Laboratory evaluation revealed a troponin level of 441.9 pg/mL (normal range, ≤34.2 pg/mL), a brain natriuretic peptide level of 348.0 pg/mL (normal range, ≤18.4 pg/mL), a serum potassium level of 3.5 mmol/L, and a serum magnesium level of 1.5 mg/dL.An ECG (Figure 1) showed a prominent ST-segment elevation.What is the most likely cause of the patient's ECG abnormalities, and how should it be managed?Please turn the page to read the diagnosis.
Low-Count Monoclonal B-Cell Lymphocytosis Persists after 7 Years of Follow-up and Confers a Higher Risk of Death
Authors: Alberto Orfao, Ignacio Criado, Arancha Rodríguez-Caballero, M. Laura Gutiérrez, Carlos Eduardo Pedreira, Miguel Alcoceba, Wendy Grey Nieto, Cristina Teodosio, Paloma Barcena, Alfonso Romero, Paulino Fernández-Navarro, Marcos González, Julia Almeida
Journal: Blood (2017)
Patients with carcinoma of unknown primary and “colon cancer profile”: Clinicopathologic features and survival data.
Authors: Gauri R. Varadhachary, Siddharth Karanth, John D. Hainsworth, Huamin Wang, Heather R. Carlson, Renato Lenzi, James L. Abbruzzese, Martin N. Raber, Frank A. Greco
Journal: Journal of Clinical Oncology (2012)

4130 Background: We have previously proposed a “colon cancer profile” (CCP-CUP) favorable subset. CCP-CUP is ~ 8% of all CUP with features resembling lower gastroinestional cancers. Distinguishing this entity from other CUP pts is of significance given the progress in the treatment of metastatic colorectal cancer (CRC). Additionally, emerging data suggests a high level of agreement between histology+IHC and tissue of origin profiling for CCP-CUP. Methods: The retrospective cohort includes 74 pts from MD Anderson (50) and Sarah Cannon (24) Cancer Centers from 2004 -2010. Pts with CDX2+ tumors and pathology suggesting a "GI profile" were chosen. All pts met the definition of CUP and most had a negative colonoscopy. Results: 2 cohorts were created - Cohort 1 (34 pts), labeled “consistent with lower GI profile” [CDX2+, CK20+, CK7-] and Cohort 2 (40 pts), labeled “probable lower GI profile” [CDX2+, irrespective of CK7/CK20 status]. Most pts had a good PS; 58% women, median age 59 yrs; 20 (27%) pts had ascites on presentation and the predominant sites of metastases included liver (30%), carcinomatosis (50%), and nodes (51%). 53 pts received first line CRC regimens (FOLFOX or FOLFIRI based), 15 pts received gemcitabine or taxane based and 3 ‘other’ regimens. OS was 37 mo (C.I 22- 52). 6 of these were "outliers" (Stage 4 NED or indolent pathology). Excluding these, cohorts 1 and 2 had 32 and 36 pts - their OS were 37 and 21 mo respectively. There was no difference in OS of pts with or without ascites on presentation. Kras data was available for 17; 12 were Kras mutant. On multivariate analysis, the factors found to negatively influence survival were age, PS (of 2) and 3 or more sites of disease. Conclusions: Survival of IHC defined CCP-CUP pts (which may include colorectal, appendiceal and small bowel profile) exceeds historical control and illustrates a new "favorable" subset. IHC is not without its limitations – nonetheless, pts with CDX2 + tumors and CUP should undergo evaluation for GI cancers and likely best served with an armamentarium of drugs used for CRC. Since carcinomatosis and liver mets are predominant sites, all patients with abdominal CUP should undergo optimal IHC (CDX-2, CK7, and CK20) testing to rule out a CCP-CUP.
Abstract 20248: Assisted Reproductive Technologies Induce Left Ventricular Hypertrophy and Systolic Dysfunction in Mice
Authors: Theo A Meister, Rodrigo Soria, Guillaume Ajalbert, Aurélien Frobert, Marie-Noelle Giraud, Stephane Cook, Afzal M Dogar, Stefano F Rimoldi, Urs Scherrer, Emrush Rexhaj
Journal: Circulation (2017)

Introduction: More than 5 million persons generated by assisted reproductive technologies (ART) are living worldwide and currently these techniques account for up to 5% of births in developed count...