tbuckley/cabot-search huggingface dataset:
Role of <i>SULT1A1</i> copy number in tamoxifen treated breast cancer: Findings from the North Central Cancer Treatment Group (NCCTG) adjuvant trial 89–30–52
Authors: M. P. Goetz, A. M. Moyer, R. M. Weinshilboum, V. A. Suman, S. J. Hebbring, M. M. Ames, J. C. Berg, C. Reynolds, E. A. Perez, J. N. Ingle
Journal: Journal of Clinical Oncology (2008)

22041 Background: Tamoxifen is biotransformed to the potent antiestrogen, endoxifen, by the cytochrome P450 (CYP) 2D6 enzyme, followed by conjugation by SULT1A1. While we (Goetz JCO 2005) and others (Schroth JCO 2007) have published that patients (pts) with impaired CYP2D6 metabolism have significantly shorter disease-free survival (DFS), the role of SULT1A1 genetic variation on treatment outcome is unclear (Nowell JNCI 2002). We previously discovered that SULT1A1 liver and enzyme activity was highly correlated with SULT1A1 copy number (p<0.0001), which explained the majority of the variation in SULT1A1 in vitro activity after considering all known sources of SULT1A1 genetic variability (Hebbring Hum Mol Genet 2007). Therefore, we examined whether SULT1A1 copy number differences influenced DFS in pts receiving tamoxifen as adjuvant therapy for breast cancer. Methods: We determined SULT1A1 copy number from paraffin-embedded tissues using a quantitative multiplex PCR assay in pts randomized to tamoxifen alone for 5 years in NCCTG 89–30–52. Additionally, we evaluated the effect of SULT1A1 copy number in the subset of patients in which CYP2D6 genotype (*4) and drug history were known. The relationship between genotype and disease outcome was determined using the log-rank test. Results: SULT1A1 copy number genotype was obtained in 170/223 pts with available tissue. The frequency of SULT1A1 copy number alleles was similar to those for Caucasian-Americans in our original report and was as follows: 1 (5%), 2 (67%), 3 (19%), and 4 or more alleles (9%). We observed no difference in DFS among pts stratified by SULT1A1 copy number alleles (log rank p=0.74). In the subset of pts classified as intermediate or extensive CYP2D6 metabolizers (defined as pts with 1 or no CYP2D6 *4 alleles who were not co-administered a potent CYP2D6 inhibitor) (n=158), we observed a non-significant trend towards improved DFS in women with 1 SULT1A1 allele (SULT1A1 gene deletion) compared to patients with ≥ 2 alleles (HR 0.76; p=0.22). Conclusion: SULT1A1 copy number did not influence DFS in this tamoxifen-treated cohort. Further study in larger cohorts is needed to determine if SULT1A1 gene deletion is a predictor of tamoxifen benefit. No significant financial relationships to disclose.
Functional annotation of colorectal cancer susceptibility loci identifies<i>MLH1</i>rs1800734 associated with MSI patients
Authors: Gaoxiang Ma, Yuqiu Ge, Dongying Gu, Mulong Du, Haiyan Chu, Jinfei Chen, Zhengdong Zhang, Meilin Wang
Journal: Gut (2016)

Recently, we read the article by Ma et al with great interest. They conducted a comprehensive meta-analysis that nominated 62 variants in 50 candidate genes with high level of cumulative evidence for genetic susceptibility to colorectal cancer (CRC).1 Interestingly, the authors found that 10 variants in 7 genes were graded strong and moderate association with CRC risk. However, functional annotations of these variants remain largely unknown. To investigate their functional relevance, we annotated the variants and their high related single nucleotide polymorphisms (SNPs) (linkage disequilibrium, r2>0.9) using publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus datasets.

After exclusion of the variants with minor allele frequency <0.05, a total of four SNPs (rs1801155, rs1569686, rs1800734 and rs2736100) were included in further analysis (table 1). We then evaluated the effect of risk alleles on gene epigenetic and expression alterations in CRC tumour tissues from TCGA. Three SNPs (rs1569686, rs1800734 and rs2736100) were identified as methylation quantitative trait loci (meQTL) in the 500 kb upstream and …
How conversations about adjuvant hormonal therapy differ from ‘typical‘ oncology discussions: Results of an observational linguistic study
Authors: B. Davidson, V. Vogel, L. Wickerham
Journal: Journal of Clinical Oncology (2006)

6141 Background: Adjuvant hormonal therapy in breast cancer presents a conversational challenge for oncologists. Oral medications are a relatively new therapeutic paradigm, and many aspects of typical oncology communication, e.g., risk-benefit presentation, goal of therapy, and the role of patient in selecting/continuing therapy, require a different approach in this setting. An observational linguistic study was undertaken to capture how oncologists and patients discuss adjuvant therapy, and to develop recommendations to improve communication. Methods: Letters of invitation were mailed to 800+ community-based oncologists; of these, 14 met the screening criteria and agreed to participate in this study. 28 postmenopausal, early breast cancer patients on or initiating hormonal therapy were recorded during their regularly scheduled visits. Results: Adjuvant hormonal therapy discussions differ from infusional chemotherapy-focused oncology discussions in several ways: Selection of therapy is based on more than efficacy (e.g., cost, side effects); Chance of recurrence is discussed directly, without significant hedging; Disease name (“cancer”) is discussed openly–the word “cancer” is notably absent from other types of oncology discussions; Visits are routine–patients’ lives are no longer “on hold” (unlike other treatment discussions, where chemotherapy is assumed to be at the center of the patient’s life); Time between visits often moves from every three months to every six months after being on hormonal therapy for a year (unlike other therapies, where patients are seen frequently). Conclusions: Analysis of conversations shows that these patients are seen as, in some way, “cured” (goal of therapy is to prevent recurrence) and that patients are “given their lives back.” The conversational frame displays a lack of urgency and emotion, similar to that of discussions of dyslipidemia management and not like other chemotherapy discussions where the emotional content is very high. New models of therapy require new conversational approaches, e.g., where issues like adherence should be addressed directly, and longer-term therapeutic goals take on primary importance. [Table: see text]
Abstract 13762: SDF 1 Alpha and Carotid plaque Characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study
Authors: Razvan T Dadu, Rhiannon Dodge, Salim S Virani, Vijay Nambi, Ron C Hoogeveen, Josef Coresh, Thomas H Mosley, James S Pankow, Eric Boerwinkle, Christie M Ballantyne
Journal: Circulation (2013)

Objective: Stromal cell-derived factor 1 alpha [SDF1α, C-X-C motif chemokine 12, (CXCL12)] is a chemokine expressed in atherosclerotic plaques and genetic variants have been associated with both in...
Regular Drug Use and Cancer2
Authors: P. G. Smith, Hershel Jick
Journal: JNCI Journal of the National Cancer Institute (1977)

An extensive survey study of 25,000 patients admitted to 24 Boston-area hospitals during the first 10 months of 1972 provided data which were used to estimate the proportion of cancer that is likely to be due to recent regular intake of drugs normally used to treat illness. Cancer was diagnosed for the first time In some 800 patients. The regular drug use before admissions among these patients was compared to that of 3,443 non-cancer patients admitted for conditions thought to be unrelated to any regular drug use. Controlling for age and sex, the risk ratio point estimate for any regular drug use among cancer patients was 0.88 when compared to that of reference patients. The 90% upper confidence bound was 1.02. These data indicate with 90% confidence that less than 1% of the cancers identified in this study were likely to have been caused by any recent regular use of drugs.
Autism Screening or Smoke Screen and Mirrors?
Authors: Craig M. Powell
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Dose escalating study of 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) and cetuximab in first-line therapy of patients with metastatic colorectal cancer
Authors: T. Trarbach, K. Schuette, J. Stoehlmacher, E. Goekkurt, H. Guenther, U. Ubbelohde, C. Stroszczynski, G. Ehninger, G. Folprecht
Journal: Journal of Clinical Oncology (2009)

e15025 Background: Highly active chemotherapy schedules are necessary in several clinical situations, i.e. for conversional chemotherapy in order to resect liver metastases. Adding oxaliplatin or cetuximab to 5-FU / FA / irinotecan was shown to increase the efficacy of chemotherapy in patients with metastatic colorectal cancer (Falcone et al, JCO 2007, Van Cutsem et al, ASCO 2008). Methods: We performed a phase I study in patients (pts) with metastatic colorectal cancer, WHO PS 0–1 who had not been pretreated for metastatic disease. They received cetuximab (500 mg/m 2 , 2h), oxaliplatin (85 mg/m 2 , 2h), folinic acid (400 mg/m 2 , 2h), irinotecan (95, 125, or 165 mg/m 2 , 1h), 5-FU (3200 mg/m 2 , 46 h), each on day 1 in biweekly cycles. Dose was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if &lt;2 DLTs in six pts. Non-evaluable pts were replaced. Pts were not selected for EGFR IHC or KRAS status. Results: Twenty-one pts were enrolled into the study between Jan 2007 and June 2008, six evaluable pts per each cohort. Two pts who had adverse events deemed unrelated to study during the first cycle (morphine overdosing, mechanical ileus) were replaced, one patient (port dysfunction during first dose) was excluded from analysis. Patient characteristics were as follows: median age 59 (33–72) years, 16 pts WHO PS 0, 15 pts male, 10 pts rectal cancer primary, 3 pts previous adjuvant chemotherapy. In the first two cohorts, 95 and 125 mg/m 2 irinotecan, one DLT occurred per dose level (neutropenia gr. 4 and diarrhea gr. 3). In the 165 mg/m 2 cohort, 2 DLTs were observed (neutropenia grade 4). Most common grade ≥ 3 toxicities were neutropenia (40%), diarrhea (25%), skin toxicities (15%), thrombopenia (10%) and infections (15%). One patient had a confirmed complete response, 14 pts had confirmed partial response (ORR 75%, 95% CI: 51–91%), 5 pts stable disease. Median progression free survival has not yet been reached. Conclusions: With the combination of FOLFOXIRI/cetuximab, the recommended dose of irinotecan is 125 mg/m 2 for further investigation in clinical trials in patients with good performance status. The observed response rate of 75% is very promising. [Table: see text]
Cost-effectiveness analysis of oxaliplatin/5-FU/LV in adjuvant treatment of stage III colon cancer in the U.S
Authors: S. Aballea, J. Chancellor, M. Raikou, M. Drummond, M. Weinstein, S. Jourdan, P. Carita, J. Bridgewater
Journal: Journal of Clinical Oncology (2005)

3532 Background: The MOSAIC trial demonstrated that oxaliplatin/5-FU/LV (FOLFOX4) as adjuvant treatment of stage II/III colon cancer significantly improves disease-free survival (DFS) at 3 years, compared to 5-FU/LV (78.7% vs 73.3%, p<0.001).[1] FOLFOX4 has become the new standard in stage III. This analysis evaluates the long-term cost-effectiveness of using FOLFOX4 in this setting, from a US Medicare perspective. Methods: We estimated the cost per life-year (LY) gained over a lifetime. Using stage III patient data from the MOSAIC trial (median follow-up 44.2 months), we estimated DFS and overall survival (OS) up to 4 years from randomization. We extrapolated DFS from 4 to 5 years by fitting a Weibull model, and thereafter using a life table for the US general population. We assumed no relapse occurred beyond 5 years. We predicted OS beyond 4 years using the extrapolated DFS estimates and observed survival after relapse. Costs were calculated from trial data up to relapse, accounting for censoring; while for periods after relapse or 4 years they were estimated using literature. Uncertainty was explored using a bootstrap approach. Results: The extrapolated life-expectancy of stage III patients on FOLFOX4 was 19.99 years vs. 18.33 years for patients on 5-FU/LV. The lifetime extrapolated incremental disease-free survival between FOLFOX4 and 5-FU/LV was 2.31 years (95% CI: 0.72, 3.89). The expected cost of treatment following relapse was estimated at $54,000. Total lifetime disease-related costs were $55,525 with oxaliplatin vs. $38,093 with 5-FU/LV. The resulting incremental cost-effectiveness ratio for FOLFOX4 compared to 5-FU/LV was $17,900 per LY gained, after discounting costs and outcomes at 3% per annum. Conclusions: Adjuvant chemotherapy with FOLFOX4 has shown a significant DFS benefit over 5-FU/LV in the MOSAIC trial. We extrapolated the within-trial data to estimate a 1.66 (0.10, 3.22) year benefit in overall life expectancy in patients with stage III disease. If this benefit is confirmed, we estimate that FOLFOX4 would cost $17,900 per LY gained, which compares favorably with other accepted interventions in oncology. [1]André T NEJM 2004; 350:2343–51 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Preoperative serum microRNA-203 as a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.
Authors: Yuji Toiyama, Keun Hur, Yoshinaga Okugawa, C. Richard Boland, Ajay Goel
Journal: Journal of Clinical Oncology (2015)

564 Background: Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. Epithelial-mesenchymal transition (EMT) is a key process that converts polarized immotile epithelial cells into motile, invasive mesenchymal cells, enabling cancer cells to gain stem cell characteristics and an aggressive malignant phenotype such as metastasis. Mir-203 has been shown to directly suppress EMT activators such as ZEB2 and SNAI1/2. However, in spite of the key functional role of miR-203 in cancer metastasis, no previous studies have investigated the clinical significance of miR-203 in patients with CRC. Methods: To examine whether CRCs secret miR-203 in vitro and vivo,we first determined extracellular miR-203 levels in CRC cell culture media. Then, we quantified miR-203 levels in serum from mice with or without metastasis. Next, we investigated miR-203 expression in 58 pairs of primary CRC (pCRC) and corresponding matching liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from CRC patients. Results: HT-29 cells released miR-203 into culture media, which was dependent on cell number and duration of culture. In addition, high serum miR-203 levels were observed in mice with liver metastasis compared to control animals (p=0.0181). Mir-203 expression was significantly upregulated in LM compared to matching pCRC tissues (p=0.0002). Serum miR-203 was significantly upregulated in a tumor stage-dependent manner (p=0.0070), and high miR-203 expression was associated with poor survival in CRC patients (p&lt;0.0001). In contrast to serum, no significant association between miR-203 expression in CRC tissues and clinicopathological findings was recognized. High serum miR-203 expression was an independent risk factor for poor prognosis (HR=2.1) as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2), and distant organs (OR=4.4), respectively. Conclusions: High levels of serum miR-203, which may be derived from several metastatic sites, are associated with poor survival and metastasis, suggesting it is a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.
Effect of light irradiation by light emitting diode on colon cancer cells and cancer stem cells.
Authors: Masaaki Nishi, Mitsuo Shimada, Kozo Yoshikawa, Jun Higashijima, Toshihiro Nakao, Chie Takasu, Shohei Eto, Hiroki Teraoku
Journal: Journal of Clinical Oncology (2015)

271 Background: Recent studies demonstrate the efficacy of irradiation from light emitting diodes (LED) for wound healing and anti-inflammation and anti-cancertherapies. However, little is known about the effects of LED in colon cancer cells. Furthermore, most solid cancers are believed to be initiated from and maintained by cancer stem cells (CSCs). The purpose of this study was to evaluate the biological response of human colon cancer cells and CSCs to LED irradiation. Methods: &lt;Experiment 1, Effect of LED on normal cancer cells&gt; Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. Cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. &lt;Experiment 2, Effect of LED on CSCs&gt; HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Cancer sphere were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-LED. Stemness gene and cell surface markers of CSCs expressions (Oct4, CD44, Nanog, EPCAM) were analyzed by RT-PCR. Results: &lt;Experiment 1&gt; Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase3, capase8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. &lt;Experiment 2&gt; Cell viability of cancer sphere were significantly decreased by LED irradiation(p&lt;0.05). And, stemness gene and cell surface markers of CSCs expressions (Oct4, CD44, Nanog, EPCAM) were significantly decreased by LED irradiation (p&lt;0.05) Conclusions: LED irradiation at 465 nm inhibited the proliferation of both normal colon cancer cell lines and CSCs.
B-cell non-Hodgkin lymphomas in childhood: 20 years experience in a single institution.
Authors: A. Pourtsidis, M. Servitzoglou, M. Baka, D. Bouhoutsou, M. Varvoutsi, D. Doganis, C. Strantzia-Michail, H. Kosmidis
Journal: Journal of Clinical Oncology (2011)

9569 Background: Our objective was to analyze the clinical and demographic characteristics of children with B-cell lymphoma treated in a single centre in Athens-Greece over the last two decades. Methods: Data were collected by a retrospective review of the charts of all 85 patients (pts) treated to our unit, from 1989 until end of 2009, according to FAB LMB 89, 96 protocols and 2003 modifications. We studied the therapeutic outcome in correlation with their diagnostic group, age at diagnosis, site of disease, response to initial prophase chemo (CT) and status of disease at reevaluation point. Results: 15 pts were excluded due to insufficient data. For the remaining 70 pts the median age was 7.5 years, with a male predominance 3.8:1. According to LMB staging criteria, 6 pts (8.6 %) were classified as Group A, 52 (74.3%) as Group B and 12 (17 %) as Group C all with bone marrow involvement and in 5 combined with CNS involvement. Most of our pts (43/70 – 61.4%) had abdominal tumours, 11 in ENT region, 3 in bones, 4 with cervical disease and 9 had more than one involved sites. 10 of the 58 children of A and B Group (16.3%) were upgraded to Group C due to poor response to initial CT treatment with CycloOncovinPrednizone (COP) or remaining viable tumor at the point of remission assessment after 4 cycles of CT. Regarding outcome 10 pts died (15%), 7 due to progression, 3 due to toxicity, 2 in induction and 1 post autograft. Relapse occurred in 9 children (13%), all with abdominal disease, one of them with concurrent thoracic involvement. Most relapsed patients (7/9) were initially treated as Group B (7/52, 14%), 1 as C and 1 as Group A. The outcome of relapsed children was dismal as 6/9 (67%) died, four initially classified as Group B. Conclusions: In our results, the survival rate is generally excellent (85 %) more than one year off treatment which generally means cure in Burkitt like lymphomas. Children from Group B with unsatisfactory initial response to COP seem to have the worse prognosis.
B‐cell depletion in autoimmune hepatitis: Is it safe for the bowel?
Authors: Mostafa M. Sira, Ahmad M. Sira
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: We read with great interest the article by Béland et al.1 in a recent issue of hepatology. They investigated the possible role of B cells in the pathogenesis of autoimmune hepatitis (AIH) and the beneficial effect of B‐cell depletion on disease remission. They demonstrated that anti‐CD20 resulted in a drastic reduction of liver inflammation accompanied by a significant reduction of alanine aminotransferase levels. However, we are concerned about the results in this article. It is known that rituximab (anti‐CD20 monoclonal antibody) therapy in AIH is used in patients who had failed initial therapy with the first‐line immunosuppressives (prednisolone and/or azathioprine).2 At this stage, AIH patients have an immunological status that is different from that in naïve patients. In spite of the elegant work by Béland et al., the real immunological status in which rituximab is indicated differs from their study model,1 and thus it may not explain precisely the immunological changes underlying the AIH remission caused by B‐cell depletion. Moreover, it has been previously reported that B‐cell depletion with anti‐CD20 ameliorates autoimmune cholangitis, but exacerbates colitis in an animal model. The exacerbation of colitis was suggested to be the result of depletion of regulatory B cells, though it was not handled in the study.3 Béland et al.1 studied both regulatory T and B cells. In Fig. 3C, they described that type 1 regulatory T cells (Tr1) were not affected by anti‐CD20. Nonetheless, the figure provides a noticeable decrease of Tr1 in the liver with anti‐CD20 treatment, and it is somehow difficult to be described as "not affected." The absence of statistical significance may be the result of the small number (n = 8). The role of Tr1 in suppressing autoimmune disease has been appreciated even more than the role of FoxP3+ regulatory T cells.4 The association between inflammatory bowel disease and AIH has been described in a considerable proportion of patients.5 For that, the current study results cannot be generalized to treatment of AIH without considering the possibility of associating inflammatory bowel disease in such patients in whom the condition may be worsened.