tbuckley/cabot-search huggingface dataset:
Validation of a multimarker blood assay for postoperative assessment of stage IV melanoma patients in a prospective international phase III trial
Authors: S. Hoshimoto, T. Shingai, H. Wang, R. M. Elashhoff, D. L. Morton, D. S. Hoon
Journal: Journal of Clinical Oncology (2009)

9045 Background: Currently there are no validated prognostic molecular biomarkers for assessment of outcome after complete resection of stage IV melanoma patients. To validate blood molecular biomarkers for prognostic value and monitoring of these patients, we evaluated the clinical utility of a multimarker quantitative reverse-transcription PCR (qRT-PCR) for detecting circulating tumor cells (CTC) of patients blood enrolled in a multicenter international (29 sites) phase III trial of postoperative adjuvant therapy. After complete metastasectomy, AJCC stage IV patients underwent immunotherapy with bacille Calmette-Guerin (BCG) plus placebo or BCG plus melanoma vaccine. Methods: Bleeds were taken before and during treatment in both randomized treatment arms. Pre- and during treatment bleeds from patients were assessed by an optimized qRT-PCR assay for MART1, MAGEA3, and PAX3 genes mRNA. Median clinical follow-up time was 21.8 and 24.2 mos. for disease-free survival (DFS) and overall survival (OS), respectively. Results: MART1, MAGEA3, and PAX3 were detected in 64 (26%), 56 (23%), 73 (29%) of 244 post-operative pretreatment patients, respectively. Multivariate Cox analysis showed that biomarker-negative patients had significantly higher DFS than biomarker- positive patients (risk ratio 1.56, 95% CI, 1.14 - 2.15; P=0.0062). In serial-bleeds (pretreatment, mos 1 and 3) analysis of 214 patients, biomarker-negative patients had significantly higher OS than patients with 1–2 positive- or 3 positive-biomarkers (risk ratio 2.37, 95% CI 1.14 - 4.94, P=0.021; and risk ratio 2.90, 95% CI 1.28 - 6.53, P=0.01, respectively). Multivariate analysis confirmed that 1–2 positive- and 3 positive-biomarkers were significant independent prognostic factors for poor OS (risk ratio 2.44, 95% CI 1.16 - 5.12, P=0.019; and risk ratio 3.08, 95% CI 1.36 to 6.98, P=0.007, respectively). Conclusions: This prospective multicenter blood biomarker validation study demonstrates that multimarker qRT-PCR analysis of CTC has significant clinical utility as a prognostic factor of disease outcome at pretreatment, and as a treatment monitoring prognostic factor in stage IV melanoma patients. No significant financial relationships to disclose.
Cancer Prevention and Control: From Research Through Applications&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P Greenwald, J W Cullen, J W McKenna
Journal: JNCI Journal of the National Cancer Institute (1987)

As the understanding of the magnitude and social impact of cancer has advanced, three major forces have shaped the current state of the art in cancer prevention and control: the maturation of organizational approaches to solving the cancer problem; the accumulation of scientific evidence that justified and illuminated the concept of cancer as a controllable disease; and, most recently, the development of a systematic cancer control research process that provides efficiency and clearer direction to the planning of a national cancer control program. The National Cancer Institute, recognizing the need for goal setting and scientific accountability in the conduct of cancer control research, has established quantified mortality reduction objectives for the year 2000 related to smoking cessation, diet changes, early detection, and state-of-the-art treatment. The cancer control research process and these objectives will guide the allocation of cancer control resources toward the application of effective health promotion strategies.
Preclinical pharmacodynamic studies of Aurora A inhibition by MLN8054
Authors: K. M. Galvin, J. Huck, O. Burenkova, K. Burke, D. Bowman, V. Shinde, B. Stringer, M. Zhang, M. Manfredi, K. Meetze
Journal: Journal of Clinical Oncology (2006)

13059 Background: The mitotic kinase Aurora A is implicated in the development of multiple tumor types. MLN8054 is an oral, potent and selective small-molecule inhibitor of Aurora A with broad efficacy in preclinical models of cancer. Inhibition of Aurora A by MLN8054 induces accumulation of mitotic cells, followed by apoptosis. This study explores relationships between Aurora A inhibition, mitotic index, and tumor growth inhibition for xenograft models with different sensitivity to MLN8054. The marker response in mouse skin was also studied. Methods: Mice bearing subcutaneous xenografts were dosed orally qd or bid with MLN8054 for 21 days. Pharmacodynamic markers were studied after 1–2 doses. Formalin-fixed xenograft tissues were stained with the mitotic markers pHisH3 and MPM2, or with an antibody to the T288 autophosphorylation site on Aurora A. Tumor growth inhibition (TGI) was calculated using the formula 100 - [ΔT/ΔC * 100], where ΔT is the volume change for treated tumors, and ΔC is the volume change for control tumors. Results: HCT116 human colon xenografts were sensitive to MLN8054 on a qd or bid schedule (84% and 96% TGI respectively for 30mg/kg dose). The T288 autophosphorylation site was used to directly demonstrate inhibition of Aurora A, which resulted in dose-dependent duration of the elevation in mitotic index. Efficacy was similar for qd vs bid dosing of 30mg/kg MLN8054, and accordingly we found that a single dose was sufficient to elevate the mitotic index for about 20–24h in this model. SW480 human colon xenografts have MLN8054 sensitivity similar to that of HCT116, but more modest effects on mitotic index were observed. The mitotic index profile of SW480 is similar to that of MDA-MB-231 xenografts, the most insensitive model studied. Elevated mitotic index was also observed in mouse skin. Conclusions: We found that mitotic index measurements coupled with the T288 autophosphorylation site as a direct marker of Aurora A activity are useful for monitoring inhibition of Aurora A by MLN8054 in tumor and/or skin biopsies. In a sensitive model, greater duration of mitotic index elevation results in greater efficacy. Our continuing work aims to better understand the differences in marker and efficacy responses between xenograft lines, incorporating the pT288 antibody as a direct marker of Aurora A inhibition. [Table: see text]
What Other Industries Can Learn From Health Care
Authors: W. Joost Wiersinga, Marcel Levi
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.
Authors: S Pavlovsky, C Corrado, M T Santarelli, J Saslavsky, F Cavagnaro, M Palau, M de Tezanos Pinto, A Huberman, J M Lein
Journal: Journal of Clinical Oncology (1988)

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.
Retrospective study of the patients with unresectable gastric cancer (UNGC) who underwent a gastrectomy after receiving S-1 or S-1 combination chemotherapy (S-1+α)
Authors: K. Kobayashi, A. Tsuji, Y. Hata, S. Morita, T. Horimi
Journal: Journal of Clinical Oncology (2009)

e15668 Background: At the 2007 ASCO annual meeting, JCOG 9912 and the SPIRITS trial showed that S-1 (S) and CDDP/S-1 (S+P) therapy to now be an accepted standard chemotherapy for advanced and recurrent gastric cancer (ARGC). Today in Japan, S- 1+αincluding S+DTX, S+CPT-11 and S+PTX are the mainstay treatments for ARGC. There are some case reports of pts with UNGC who were operated on due to the good anti-tumor effect of S-1+α, however, no consensus for performing a gastrectomy after chemotherapy has yet been reached. This study aims to identify the factors which make it appropriate to perform a gastrectomy after S- 1+α and to examine the validity of this chemotherapeutic regimen in combination with surgery. Methods: Twenty-five chemo-naïve pts with UNGC who received S-1+α (excluding neo-adjuvant) between May 2005 and Dec. 2007 were retrospectively reviewed, using the RESIST, Kaplan-Meier method, and Japanese Classification of Gastric Carcinoma (Eng. ed.). Results: The characteristics were: mean age 62; sex: M/F=18/7; cancer status; locally advanced (L):11, distant metastasis (D):9, lymph node swelling ≥group 3 (N):12, and peritoneal dissemination (P):11. Treatment regimens; S:13, S+DTX:3, and S+P:9. The median number of courses was 5. RR was 56% (PR:14, SD:9, PD:2). MST was 780 days. Twelve pts underwent a gastrectomy. The reasons for performing an operation were downstaging (DOWN):8, and palliative (PAL):4 (anemia:2/passage disturbance:2). The features were DOWN (M/F=5/3/65 yrs/PR:8/L:6, D:0, N:4, P:3) and PAL (M/F=4/0/57 yrs/SD:4/L:1, D:3, N:1 P:1). The median PFS and mean OS were 445 days and 312 days, respectively. No significant difference was observed between DOWN and PAL regarding the PFS and OS. All PAL cases were free from painful symptoms. Three pts received a curative A resection. In addition, 8 pts experienced histological changes, in particular, one pt achieved Grade 3 (No viable tumor cells were found.). Ten pts received adjuvant chemotherapy. Nine pts are alive at this writing. Conclusions: The findings of this study suggest that the above described chemotherapeutic regimen combined with a second-look gastrectomy might therefore be a new potentially effective strategy for the treatment of UNGC. No significant financial relationships to disclose.
Reversal of titanium-induced myelofibrosis
Authors: H. M. Chung
Journal: Journal of Clinical Oncology (2008)

18028 A.V. was a 32 yo woman who was found to have an elevated alkaline phosphatase and a large mass in her liver by ultrasound. Hepatology referral believed the liver lesion to be benign focal hyperplasia (could not biopsy due to location in dome of liver) and she was referred to hematology for a hemoglobin of 8.0 g/dL. White cell and platelet counts, iron studies, B12, folate, LDH, haptoglobin, and Parvo- B19 were normal. Erythropoietin level was markedly elevated and peripheral smear showed a normocellular normochromic anemia and no dysplastic or malignant cells. Bone marrow biopsy, difficult due to the extreme hardness of bone, showed hypercellular marrow at 95% with extensive marrow fibrosis by reticulin staining. Cytogenetic testing and flow cytometry were negative. Levels of vitamin D, hydroxyvitamin D, 24-hr urine for protein and creatinine, PTH, ANA, ESR, and bone radiographs were normal. Infectious diseases such as tuberculosis and histoplasmosis were also ruled out. Her only medication was ibuprofen. Past medical history included right ankle fracture and a titanium (Ti) ankle joint replacement. The original joint had been updated 4 months later due to ongoing pain. Due to discomfort of the second Ti ankle joint and discussion of lab results and hypothesis of Ti-induced myelofibrosis, it was removed 6 months after placement. There was rapid resolution in hemoglobin after Ti joint removal, counts returning back to normal within 2 months. Repeat bone marrow biopsy 6 months after joint removal showed markedly decreased myelofibrosis and cellularity of 50%. The lesion in the dome of the liver decreased in size significantly upon MRI exam. These results are suggestive of an inflammatory response resulting in myelofibrosis and possible secondary hematopoiesis and resolution of this condition with removal of the offending agent, a Ti ankle joint. Titanium has an incredible strength-to-weight ratio making its use in the health care ideal. Reports of effects of Ti mini-plates, used for facial osteosynthesis, on surrounding tissue include formation of local fibrosis, inflammatory cells, and granulation tissue, almost exclusively at the site of Ti metal or salt exposure. Patients with inhaled Ti dioxide particles and resultant pulmonary fibrosis have also been reported extensively. Effects on bone marrow have never been reported until now. No significant financial relationships to disclose.
Abstract 3976: Expression of formyl peptide receptor 1 (FPR1) in neuroblastoma: Implications in tumorigenesis
Authors: Igor Snapkov, Per Kogner, John-Inge Johnsen, Baldur Sveinbjørnsson
Journal: Cancer Research (2014)

Abstract The formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor with pattern recognition properties. It is mainly expressed by myeloid cells and is involved in a broad range of host defense mechanisms. However, a variety of host-derived agonists of FPR1 have been identified, including formyl peptides released from disrupted mitochondria of necrotic cells. In the present study, we demonstrate that FPR1 is expressed in neuroblastoma cell lines and primary tumors and high expression is correlated with poor overall survival. Addition of the FPR1 agonist N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to neuroblastoma cells in vitro causes enhanced proliferative activity, increase of intracellular calcium response and activation of STAT3 and MAPK/Erk signaling pathways. Currently, clonal neuroblastoma cell line with inducible activity of FPR1 gene is under testing in a mouse model to assess the significance of this receptor in vivo. Our findings so far suggest that FPR1 may play a significant role in neuroblastoma tumorigenesis and that therapeutic intervention of the FPR1 pathway may become an important clinical strategy in neuroblastoma therapy. Citation Format: Igor Snapkov, Per Kogner, John-Inge Johnsen, Baldur Sveinbjørnsson. Expression of formyl peptide receptor 1 (FPR1) in neuroblastoma: Implications in tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3976. doi:10.1158/1538-7445.AM2014-3976
Abstract P134: Higher Optimal Lifestyle Score is Associated with Greater Workplace Productivity
Authors: Jackie L Boucher, Jeffrey J VanWormer, Heather R Britt, James M Peacock, Kevin J Graham
Journal: Circulation (2012)

Introduction: Unhealthy lifestyles are associated with low workplace productivity, but lifestyle risks tend to cluster and the impact of this is not well studied. This analysis examined the cross-sectional association between an optimal lifestyle score (OLS) and overall workplace productivity in the Heart of New Ulm Project. Hypothesis: It was hypothesized that a higher OLS would be associated with higher workplace productivity relative to a lower OLS. Methods: Complete data was available from 2,987 adults age 18-85 years (with ≥0.40 FTE work agreement) without self-reported diabetes or heart disease, who underwent a cardiovascular risk factor screening in 2009. For each participant, an OLS of 0-4 total points was created by summing one point for each of the following factors: non-smoker, ≥150 min/wk of moderately equivalent physical activity, 1-14 alcoholic drinks/wk, and ≥5 serv/d of fruits and vegetables. Overall productivity loss combined absenteeism and presenteeism from the Work Productivity and Activity Impairment questionnaire, reflecting the percentage loss of all available work hours (per work agreement) due to health reasons. Results: After adjustment for age, sex, body mass index, and Perceived Stress Scale score, least squares adjusted mean±SE productivity loss was 9.9±1.9% for an OLS of 0, 5.7±0.6% for an OLS of 1, 4.9±0.4% for an OLS of 2, 4.9±0.4% for an OLS of 3, and 4.7±1.0% for an OLS of 4 (p for trend &lt;0.001). Post hoc comparisons revealed that OLS’s of 0 were significantly different (p =0.05) from all other OLS’s, while OLS’s of 1, 2, 3, or 4 were statistically indistinguishable (p=0.05) from one another. Conclusions: A beneficial threshold of having at least one optimal lifestyle factor was observed. When productivity loss is converted to lost dollars under the assumptions that all employees work full time with an annual salary of $50,000, an OLS of 0 (-$4,950/employee) has over two-fold higher annual estimated workplace productivity losses relative to an OLS of 4 (-$2,350/employee). Employees with no optimal lifestyle habits, however, represent a very small proportion (1.5% of this analysis; 46 of 2,987) of the total workforce. As such, greater absolute economic benefits may be realized by focusing interventions primarily on supporting the maintenance of existing optimal lifestyle habits.
Comparison of efficacy and safety of capecitabine (CAP) compared with intravenous continuous infusion (CIV) of 5-FU administration in advanced colorectal cancer (CRC)
Authors: S. Cole, D. Carey, M. W. Saif
Journal: Journal of Clinical Oncology (2005)

3591 Background: Standard therapy for CRC involves 5-FU-based regimens such as FOLFOX and FOLFIRI with CIV 5-FU. CAP offers a convenient oral replacement for CIV 5-FU. There are few randomized controlled trials comparing CAP with CIV 5-FU-based therapies for CRC. We compared the safety and efficacy of CAP-based regimens with well-established CIV 5-FU-based regimens. Methods: We collected data on 3224 pts treated on either CIV 5-FU (1815) or CAP (1409) for CRC. This included Phase II or III studies published or available from ASCO, ESMO, ECCO (1997 - 2004) alone, with (XRT, eloxatin, CPT-11), as 1st line and 2nd line. Safety was assessed by determining proportion of pts who experienced grade 3/4 adverse effects. Efficacy was assessed by determining RR and their 95% confidence intervals (CI). Chi-square tests and Fisher’s Exact tests were used to compare the two regimens. P<0.05 was considered statistically significant. All statistical tests were performed with SAS (9.0). Results: RR was not significantly higher in pts on CAP vs. CIV 5-FU (34% v 39%; overall RR odds ratio, 0.7917; 95% CI, 0.6784 to 0.9239; P = .999). Average MOS was similar in both regimens (CAP: 14.2 m vs. CIV 5-FU: 14.9 m). Grade 3/4 hematologic toxicity was more frequent in pts on CIV 5-FU vs. CAP (16.31% vs. 3.40%; P < 0.0001), whereas HFS was more frequent in CAP group (9.30% vs. 6.34%; P < 0.999). CAP is associated with a significantly lower incidence of grade 3/4 neutropenia (4.79% vs. 27.7%), leading to significantly less grade 3/4 neutropenic fever (1.16% vs. 7.72%). Thromboses was noticed in 8% of pts on CIV 5-FU and none reported on CAP. Conclusions: CAP offers a superior toxicity profile and at least equivalent RR, TTP, and MOS compared with CIV 5-FU when used alone or in combination with other agents or XRT in CRC. HFS is more frequent in CAP pts, but never life threatening and can be effectively managed. CAP can replace CIV in regimens to treat CRC. No significant financial relationships to disclose.
Integrative Analysis of Two Prospective Neoadjuvant Studies with Breast Cancer Patients and Microarray Analysis
Authors: H.S. Okuma, F. Koizumi, A. Hirakawa, M. Nakatochi, J. Hashimoto, M. Kodaira, M. Yunokawa, H. Yamamoto, K. Yonemori, C. Shimizu, Y. Fujiwara, K. Tamura
Journal: Annals of Oncology (2014)
The expression of the chosen proteins in ovaries of BRCA1 gene mutation carriers after prophylactic adnexectomy
Authors: J. Markowska, R. Madry, J. P. Grabowski
Journal: Journal of Clinical Oncology (2008)

22191 Among women with BRCA1 mutation the risk of developing breast cancer is 50 - 80%, ovarian cancer 40% and about 10% for Fallopian tube and peritoneal cancer. One of the possibilities to reduce the risk of developing cancer in BRCA1 positive patients is prophylactic adnexectomy. It decreases the risk of ovarian cancer to 5% and breast cancer to 30 - 40%. The aim of our study was to investigate the expression of the TP53, BRCA1, NM23 and KAI1 in the ovaries of the 14 operated women that might be involved in development of breast and ovarian cancer in BRCA1 positive patients. As a control we have studied 11 patients operated at our department which were BRCA1 negative. The determination of TP53, BRCA1, NM23 and KAI1 was performed using immunohistochemistry method. We have observed the differences in the expression of BRCA1, NM23 and KAI1 between study group and control group. The expression of these proteins in the study group were respectively: 78,6%, 71,4%, 92,8% and in control and in the control group: 45%, 36,4% and 63,6%. The expression level of the analysed proteins differs between right and left ovary in BRCA1 carriers. In cases of BRCA1, NM23 and KAI1 the expression was higher in right ovary in case of TP53 the expression was higher in left ovary. No significant financial relationships to disclose.