tbuckley/cabot-search huggingface dataset:
A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA).
Authors: K. H. Lu, S. Skates, T. B. Bevers, W. Newland, R. G. Moore, L. Leeds, S. Harris, O. W. Adeyinka, H. A. Fritsche, R. C. Bast
Journal: Journal of Clinical Oncology (2010)

5003 Background: There are currently no effective screening tools for the early detection of ovarian cancer in women at average population risk. We evaluated a screening strategy that incorporates change of CA-125 over time and age of the participant to estimate risk of ovarian cancer, referring a small fraction (∼2%) of apparently healthy individuals annually to transvaginal sonography (TVS). Methods: A single arm, prospective, multicenter screening study enrolled postmenopausal women age 50 to 74 with no significant family history of breast or ovarian cancer. Participants underwent a CA-125 blood test annually. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to the next annual CA-125 (low risk), repeat CA-125 in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). Based on clinical findings and TVS, the gyn onc made the decision whether to proceed with surgery. Results: 3238 women participated over an eight year period. The average annual rate of referral to 3 monthly CA125 was 6.8%, and the average annual rate of TVS and gyn onc referral was 0.9%. Cumulatively 85 women (2.6%) received TVS and referral to a gyn onc. Eight women subsequently underwent surgery based on the TVS and referral, with 3 invasive ovarian cancers, 2 borderline ovarian tumors and 3 benign ovarian tumors, providing a positive predictive value of 37.5% (95% CI 8.5%,75.5%).The combined specificity of ROCA followed by TVS for referral to surgery is 99.7% (95% CI 99.5%, 99.9%). The 3 invasive ovarian cancers were high-grade epithelial tumors that were all early stage (two stage 1C and stage IIB). All 3 women with invasive ovarian cancer had at least 3 years with low risk, annual CA-125 values prior to a rising CA-125. Conclusions: In this prospective, single arm study, the ROCA followed by TVS demonstrated excellent specificity and PPV in a population of U.S. women at average risk for ovarian cancer. As expected, less than 1% of participants annually required a TVS. In addition, the invasive high-grade ovarian cancers that were detected were early stage. This study provides early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years of age. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fujiresio Diagnostics Inc Roche Diagnostics Royalties for CA 125
Immediate Administration of Intraarticular Triamcinolone Acetonide After Joint Injury Modulates Molecular Outcomes Associated With Early Synovitis
Authors: Jakob T. Sieker, Ugur M. Ayturk, Benedikt L. Proffen, Manuela H. Weissenberger, Ata M. Kiapour, Martha M. Murray
Journal: Arthritis & Rheumatology (2016)

To test whether intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection (ACLT) and to characterize the synovial response using a functional genomics approach in a preclinical model of posttraumatic osteoarthritis.Yorkshire pigs underwent unilateral ACLT without subsequent corticosteroid injection (the ACLT group; n = 6) or ACLT with immediate injection of 20 mg triamcinolone acetonide (the steroid group; n = 6). A control group of pigs (the intact group; n = 6) did not undergo surgery. Total synovial membrane cellularity and synovial fluid concentration of C1,2C neoepitope-bearing collagen fragments 14 days after injury were primary end points and were compared between the ACLT, steroid, and intact groups. Cells were differentiated by histologic phenotype and counted, while RNA sequencing was used to quantify transcriptome-wide gene expression and monocyte, macrophage, and lymphocyte markers.In the intact group, total cellularity was 13% (95% confidence interval [95% CI] 9-16) and the C1,2C concentration was 0.24 μg/ml (95% CI 0.08-0.39). In the ACLT group, significant increases were observed in total cellularity (to 21% [95% CI 16-27]) and C1,2C concentration (to 0.49 μg/ml [95% CI 0.39-0.59]). Compared to values in the ACLT group, total cellularity in the steroid group was nonsignificantly decreased to 17% (95% CI 15-18) (P = 0.26) and C1,2C concentration in the steroid group was significantly decreased to 0.29 μg/ml (95% CI 0.23-0.35) (P = 0.04). A total of 255 protein-coding transcripts were differentially expressed between the ACLT group and the intact group. These genes mainly enriched pathways related to cellular immune response, proteolysis, and angiogenesis. Mononuclear leukocytes were the dominant cell type in cell-dense areas. MARCO, SOCS3, CCR1, IL4R, and MMP2 expression was significantly associated with C1,2C levels.Early intraarticular immunosuppression mitigated injury-induced increases in collagen fragments, an outcome better predicted by specific marker expression than by histologic measures of synovitis.
Epoetin beta treatment of chemotherapy induced anemia in cancer patients: Results of a large prospective cohort study
Authors: I. Ray-Coquard, J. Tourani, T. Facon, C. Haïoun, B. Audhuy, S. Mathoulin-Pelissier, C. Ollivier, M. Barbaza, L. Bergougnoux, A. Jenabian
Journal: Journal of Clinical Oncology (2007)

19582 Background: The efficacy of epoetin beta (E) is well documented in clinical trials in anemic cancer patients (pts). This study was conducted to assess E use, efficacy, safety and effect on quality of life in cancer pts, in usual practice. Methods: This prospective, multicenter, longitudinal, observational French study assessed a 4-month follow-up of informed consent cancer pts (including both solid tumors (ST) and hematological malignancies (H)) treated with E for chemotherapy-related anemia. Data were collected between January 2005 and March 2006. Results: Among 3100 pts enrolled by 423 specialists, 2810 were analysed. Pts’ characteristics were: mean age 63±13 yrs, male 50%, performance status 0 (13%), 1 (46%), =2 (41%). 74% of pts suffered from a ST and 26% from a H. The most frequent cancer types were lung (22%), breast (15%), non-Hodgkin lymphoma (12%), colon (9%), multiple myeloma (7%), ovary (7%), prostate (3%), head and neck (3%) and chronic lymphocytic leukemia (3%). The mean time from diagnosis to inclusion was 2 yrs. 52% of pts received their first line of chemotherapy, 25% their second one. 55% and 10% of ST and H pts received platinum based regimen, respectively. At inclusion, hemoglobin levels were distributed as follows: &lt; 9 g/dl (ST 14%, H 32%), [9–11 [g/dl (ST 70%, H 56%), [11–13 [g/dl (ST 16%, H 11%). Regarding pre-treatment biological tests, endogenous erythropoietin rate was controlled for only 3% of pts (ST 1% and H 7%, median 37 IU/ml [0; 388]), ferritin was available for 15% of pts (ST 11% and H 28%), transferrin saturation for 12% of pts (ST 10% and H 17%) and reticulocytes for 11% of pts (ST 7% and H 24%). At initiation, pts received a median dose of 30000 U/week of E on a once weekly regimen schedule for 98% of pts. E was associated with iron supplementation in 49% and 13% of ST and H pts, and with blood transfusion in 5% and 15% of ST and H pts. Conclusion: These preliminary results describe baseline characteristics of cancer patients treated with epoetin beta. The study suggests very few biological controls before initiation of E in routine practice. Final analyses of hemoglobin evolution and quality of life will be presented. [Table: see text]
Phase I trials of PS-341 (bortezomib, B) in combination with topotecan (T) in advanced solid tumors: Evaluation of sequence-dependent toxicity.
Authors: R. Morgan, F. Valdes-Albini, T. W. Synold, P. H. Frankel, C. Ruel, M. I. Carroll, D. Lim, M. C. Cristea, M. Koczywas, L. A. Leong
Journal: Journal of Clinical Oncology (2010)

e13035 Background: Preclinical data has demonstrated that B when combined with camptothecins enhances apoptotic effects. In mice, the combination of B with irinotecan (I) has resulted in increased inhibition in colon cancer xenografts than I alone. This may be due to the inhibition of NF-KB activated by camptothecin. It is hypothesized that B will act synergistically with T and enhance the apoptotic effects of T. Conflicting data exists regarding schedule dependent synergistic cytotoxicity of the combination and this study examined both sequences of administration. Methods: A standard 3 + 3 schedule was used in both sequences (S). The dose of B was fixed with escalating doses of T. S1: B 1.3 mg/m2 on days 1, 4, 8, and 11. T 2 to 3.5 mg/m2 on days 1 and 8 was given 6 h before B. S2: B 1.3 mg/m2 on days 1, 4, 8, 11 followed by T 2 to 3 mg/m2 given 6 h after B. Cycle length was q28 days. Pharmacokinetic sampling for both sequences have been obtained. Results: 43 pts (S1: 27, S2: 16) received a median of 2 cycles (range 0-7) of therapy. Primary tumors included: GI (11), lung (7), ovary (7), breast (4), head/neck (5), other (9). The median age was 57 (range 21-83; 21 pts were male, 22 female; 34 were Caucasian, 5 African-American, and 4 Asian). The median ECOG PS was 1 (range 0-2). Previous treatments included surgery (42), radiation (17), and chemotherapy (23). For S1, the maximum tolerated dose (MTD) of B and T were 1.3 and 3 mg/m2 respectively. For S2, the MTD of B and T were 1.3 and 2.5 mg/m2respectively. Dose-limiting toxicities (2 pt in each sequence) were gr 3 thrombocytopenia in S1, and gr 4 thrombocytopenia in S2. Stable disease was seen in 6/27 pts in S1, and 2/16 in S2. Conclusions: The MTD, tolerability, and toxicity of both sequences were similar. Combination therapy with B and T was well tolerated and the SD observed in the heavily pretreated populations suggests that phase II studies of the combination are warranted (CA62505). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories
Histochemical Changes in Livers From Portacaval-Shunted Rats
Authors: Ritva P. Evarts, Mandy Raab, Elizabeth Marsden, Snorri S. Thorgeirsson
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Histochemical Changes in Livers From Portacaval-Shunted Rats Get access Ritva P. Evarts, Ritva P. Evarts Search for other works by this author on: Oxford Academic PubMed Google Scholar Mandy Raab, Mandy Raab Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth Marsden, Elizabeth Marsden Search for other works by this author on: Oxford Academic PubMed Google Scholar Snorri S. Thorgeirsson Snorri S. Thorgeirsson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 731–736, https://doi.org/10.1093/jnci/76.4.731 Published: 01 April 1986 Article history Received: 08 March 1985 Revision received: 30 September 1985 Accepted: 21 November 1985 Published: 01 April 1986
Unexpected increased biliary toxicity when systemic bevacizumab is added to hepatic arterial infusion.
Authors: D. G. Power, M. Capanu, D. Patel, A. Gewirtz, W. R. Jarnagin, Y. Fong, M. I. D'Angelica, R. P. DeMatteo, N. E. Kemeny
Journal: Journal of Clinical Oncology (2010)

3559 Background: Hepatic arterial infusion (HAI) with floxuridine + dexamethasone can be added safely and effectively to systemic (SYS) oxaliplatin + irinotecan in unresectable colorectal cancer liver metastases (CLM) and after CLM resection. HAI is also feasible in unresectable intrahepatic cholangiocarcinoma (primary liver, PL). Bevacizumab (Bev) is an active agent that was added to these HAI regimens to increase efficacy (disease-free survival) in CLM and PL. Methods: We combined Bev with HAI in 3 separate trials: (1) phase II trial of unresectable CLM with best SYS, (2) phase II trial in PL (no SYS), and (3) phase II randomized trial ± Bev after CLM resection with best SYS. The phase II trials of unresectable CLM and PL were compared to prior HAI trials (no Bev). The phase II trial after CLM resection compared two arms. Fisher's exact test was used to assess the association of clinicopathologic variables, e.g., Fong score, previous SYS, dose of HAI, KPS, blood tests, and toxicity data (grade 3-4 NCI CTCAEv3.0) with/without Bev. Bilirubin toxicity was reported as ≥ 2mg/dl. Multivariate analysis to further characterize risk of hepatic toxicity was not possible due to small numbers of events. Results: In all 3 trials patients exhibited similar characteristics. In univariate analyses, no clinicopathologic variable was significantly associated with increased risk of hepatic toxicity. Usual Bev toxicity (e.g., increased clotting and hypertension) was seen as expected. However, increased hepatic toxicity was also noted with the addition of Bev (Table). Conclusions: Although our analyses were limited by sample size, we found unexpected increased biliary toxicity with Bev+HAI±SYS resulting in increased biliary stenting. Impaired healing of HAI-induced biliary injury due to angiogenesis inhibition may be the mechanism of increased biliary toxicity. Efficacy data will be presented. Studies HAI ± SYS HAI ± SYS + BEV p value Colorectal adjuvant Stents 0 4 0.05 (n=73; 38 with Bev) Total bilirubin ≥ 2 0 5 0.02 SGOT 5 5 1.00 Colorectal unresectable Stents 0 3 0.06 (n=76; 30 with Bev) Total bilirubin ≥ 2 1 7 0.005 SGOT 6 0 0.08 Primary liver unresectable* Stents 0 2 0.15 (n=56; 22 with Bev) Total bilirubin ≥ 2 2 5 0.10 *No SYS SGOT 0 5 0.006 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Pfizer, sanofi-aventis
Validation of a genomic classifier for prediction of metastasis following postoperative salvage radiation therapy.
Authors: Robert Benjamin Den, Voleak Choeurng, Lauren Howard, Amanda de Hoedt, Marguerite Du Plessis, Kasra Yousefi, Lucia L.C. Lam, Christine Buerki, Edouard John Trabulsi, Adam Dicker, Elai Davicioni, Jeffrey Karnes, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2016)

4 Background: Management of patients with a postoperative rising prostate-specific antigen (PSA) level is complex. Additional local treatment such as salvage radiation therapy (SRT) may be sufficient for many patients but some may require concurrent systemic therapy in order to delay or prevent metastatic disease. As PSA recurrence on its own is a poor surrogate for metastatic disease we hypothesized that the Decipher genomic classifier (GC), a validated predictor of metastasis may be able to better distinguish those patients where additional therapy is beneficial from those where SRT on its own is likely sufficient. Methods: Genomic classifier (GC) scores were calculated from 170 prostate cancer patients, who received SRT at the Veteran Affairs Medical Center Durham, Thomas Jefferson University and Mayo Clinic, between 1990 and 2010. SRT was defined as administration of RT with Pre-RT PSA levels &gt; 0.2 ng/ml. GC and CAPRA-S scores were compared using survival c-index, competing-risks and Cox regression analysis for the prediction of metastasis. Results: Survival c-index for predicting metastasis 5 years post SRT was 0.85 (95% CI: 0.73-0.88) for GC and 0.63 (95% CI: 0.49-0.77) for CAPRA-S. The cumulative incidence of metastasis at 5 years post-SRT was 2.7%, 8.4%, and 33.1% for low, average, and high GC scores (p &lt; 0.001) and 16.9%, 2.3% and 17.2% for low, average and high CAPRA-S scores (p = 0.113). In univariable analysis only GC, extraprostatic extension, path GS and Pre-RT PSA were significant predictors of metastasis. In multivariable analyses with clinical risk factors or the CAPRA-S risk model, GC was the only independent predictor of metastasis with a HR of 1.63 (1.22-2.18, p &lt; 0.001) for a 10% unit increase in risk score. Conclusions: In patients treated with postoperative SRT for PSA recurrence, GC is a powerful predictor of metastasis. Patients with low Decipher have excellent prognosis with SRT and may avoid concurrent hormonal therapy. Patients with high Decipher risk are at highest risk for metastatic disease and SRT failure and may benefit from intensified systemic therapy.
Chloroquine in Treatment of Infectious Mononucleosis
Authors: I TALSTAD
Journal: JAMA (1963)

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
A phase I trial of imatinib, hydroxyurea and RAD001 for patients with recurrent malignant glioma
Authors: D. Reardon, J. A. Quinn, J. N. Rich, J. J. Vredenburgh, A. Desjardins, S. Sathornsumetee, S. Gururangan, M. J. Egorin, A. Salvado, H. S. Friedman
Journal: Journal of Clinical Oncology (2006)

1580 Background: This study attempts to extend the anti-glioma activity of imatinib mesylate (Gleevec, IM) plus hydroxyurea (H), by adding RAD001 (R), an orally bioavailable inhibitor of mTOR, a critical intracellular mediator of signal transduction and metabolism. Methods: We employ a “3+3” dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IM + H + R administered daily among adult recurrent malignant glioma patients s with ≤ 3 prior recurrences, KPS &gt; 60% and adequate organ function. Patients are stratified based on concurrent enzyme-inducing anticonvulsant use (EIAC), and both strata are independently escalated. Initial dose level for each stratum: IM - 400 mg/day; H - 500 mg bid; R - 2.5 mg/day. Each treatment cycle is 28 days. Response is evaluated every other cycle. Pharmacokinetic (PK) studies are performed on days 1 and 28 of cycle 1. Results: Twenty-two recurrent GBM patients have enrolled. The median age is 53 (range 37 to 75), 41% are male, and 45% are on EIAC. Two DLTs (grade 4 hypercholesterolemia and thrombocytopenia) occurred among 5 patients on dose level one (non-EIAC stratum). No other DLTs have occurred. The dose escalation schema has been amended to include alternate day R dosing. IM PK were consistent with those previously reported for patients on IM and HU. IM clearance on day 1 was 492 ± 247 ml/min in the EIAC stratum and 231 ± 100 ml/min in the non-EIAC stratum. On day 28, IM clearance was decreased in both strata (243 ± 93 ml/min in the EIAC stratum and 116 ± 47 ml/min in the non-EIAC stratum) PK results for HU and R are pending. Nine patients continue on study having received 2–8 cycles of therapy. Four partial responses have been observed and accrual is ongoing. Conclusions: Further accrual is warranted. An update of outcome, toxicity and pharmacokinetic analyses will be presented. [Table: see text]
Mitochondrial control-region sequences in two shorebird species, the turnstone and the dunlin, and their utility in population genetic studies.
Authors: P W Wenink, A J Baker, M G Tilanus
Journal: Molecular Biology and Evolution (1994)

We determined the mitochondrial control-region sequences of five turnstones (Arenaria interpres) and three dunlins (Calidris alpina). Comparisons revealed that the central part (part II) is conserved relative to much more variable parts at the beginning (part I) and the end (part III). This pattern of sequence conservation is also found in the control regions of other vertebrates. The average sequence divergence between turnstone and dunlin was 21.8% for part I, 7.5% for part II, and 29.5% for part III. Within-species sequence divergence over the entire control region was much lower, at 0.9% for turnstones and 2.0% for dunlins. In both shorebird species, part III contains a repetitive sequence composed only of A and C nucleotides, which has not been found in the control regions of other birds. A survey of the part I sequences of 25 turnstones and 25 dunlins sampled around the world revealed that these species have very different population genetic structures. Dunlins are not only much more differentiated in their sequences but also have a strongly subdivided population genetic structure. Pleistocene vicariant events combined with strong natal philopatry and high mutation rates of the sequences are likely responsible for this population genetic subdivision. Conversely, part I sequences of turnstones are weakly differentiated and are geographically unstructured. We argue that this is not the result of global gene flow but that, instead turnstones have recently expanded from a refugial population that was bottlenecked.
Transplacental chemical carcinogenesis in man. [Editorial]
Authors: Miller Rw
Journal: JNCI Journal of the National Cancer Institute (1971)

This editorial was prompted by the published association of maternal diethylstilbestrol (DES) ingestion during pregnancy and subsequent development of vaginal adenocarcinoma among female offspring and explores various factors involved in transplacental chemical carcinogenesis in humans.  Known prenatal determinants of carcinogenic transmission are 1) germ cells 2) transplantation and 3) ionizing radiation.  Other chemicals besides DES which may be implicated in transplacental carcinogenesis are cytotoxic anticancer agents such as therapy.  The hypothesis of DES-associated maternal-fetal exchange was developed as a result of physician recognition of a cluster of cases with commonality; it is hoped that further epidemiological studies more systemitized will lead to hypotheses regarding the epidemiology of other in utero carcinogenesis.