tbuckley/cabot-search huggingface dataset:
Prognostic factors in patients with recurrent gastric cancer after curative gastrectomy
Authors: S. Su Jin, J. Baek, H. Kim, J. Park, G. Kim, D. Kim, M. Kim, H. Kim, Y. Min
Journal: Journal of Clinical Oncology (2008)

15612 Background: The effect of the location and the timing of disease recurrence after curative gastrectomy for gastric cancer on patient survival has not been elucidated. We hypothesized that the location and timing of recurrence would have a significant influence on survival. Methods: Among 478 patients who had underwent curative resection for gastric cancer in the Ulsan university hospital between Dec. 2002 and Dec. 2005, 62 patients who recurred were included into this study. The patients were divided according to the patterns of recurrence into 2 groups: a peritoneal recurrence group (n=16) and other recurrence group (n=46). And the patients were divided according to the timing of recurrence into 2 groups: an early recurrence group that was before 1 year after surgery (n=27) and a late recurrence group after 1 year (n=35). All survival rates were estimated using Kaplan-Meier method and the differences were analyzed by log rank test. Results: Median age was 58 years (range 24, 83 years) and the proportion of male was 73%. Median interval from surgery to recurrence was 13 months (range 1, 38 months) and median survival from diagnosis of recurrence was 6 months (range 0, 37 months). Survival duration after diagnosis of recurrence was influenced by age (<65 versus ≥65 years; p=0.009) at surgery and peritoneal recurrence (p=0.002), not nodal status at surgery and degree of differentiation of tumor. Median survival of peritoneal recurrence group was 3 months (range 0, 11 months) compare with 9.4 months (range 1, 37 months) of other recurrence group. Median survival of early recurrence group was shorter than late recurrence group (4 months versus 9 months; p=0.055). Multivariate analysis showed that old age (p=0.003) and peritoneal metastasis (p=0.001) independently correlated with survival after diagnosis of recurrence. The histology of tumor of all 16 patients (100%) with peritoneal recurrence was undifferentiated, whereas in other recurrence group, only 78% were undifferentiated (p=0.05). Conclusions: This study showed that old age and peritoneal recurrence negatively influenced on survival from recurrence for patients who had underwent curative gastrectomy for gastric cancer. And some relationship between undifferentiated histology and peritoneal recurrence was observed. No significant financial relationships to disclose.
Use of plasma angiome to predict PFS in patients with metastatic colorectal cancer (mCRC) treated with capecitabine, oxaliplatin, and bevacizumab (XELOX-A).
Authors: A. Nixon, M. Starr, H. Pang, A. Bulusu, W. Honeycutt, A. Amara, J. C. Bendell, H. Hurwitz
Journal: Journal of Clinical Oncology (2010)

e21009 Background: Biomarkers that predict benefit and define mechanisms of resistance to VEGF inhibitors are urgently needed. Methods: Plasma samples from patients (pts) treated on a phase II trial of XELOX-A in mCRC were analyzed via a multiplex ELISA platform (SearchLight; Aushon Biosystems, Inc.) for 44 factors related to tumor growth, angiogenesis, and inflammation. This platform was extensively optimized for use in cancer patients and nearly all factors had coefficients of variation between 10-20%. Patterns of expression were analyzed at baseline and on-treatment (day 28). Baseline and percent change from baseline (PCFB) values were correlated with progression free survival (PFS) using univariate Cox proportional hazard regression models and multivariate Cox models with leave-one-out cross validation. Results: 38 pts were evaluable at both baseline and on-treatment. Spearman's rank correlation coefficients were calculated for all pairs of analytes at both baseline and PCFB. Unsupervised hierarchical clustering of analytes was also performed to produce dendrogram plots. Data indicate that several analyte clusters reflect known biological categories. Predictors of PFS found to be significant using univariate models included: baseline analytes – von Willebrand Factor (p=0.001), angiopoietin-2 (p=0.034), VEGF-C (p=0.075); and PCFB analytes – TGFb2 (p=0.011), osteopontin (p=0.013), TGFb1 (p=0.0149), and IGF-1 (p=0.05). Leave-one-out cross validation analysis was performed to identify potential baseline and PCFB signatures for PFS. Kaplan-Meier plots and log-rank tests were also used to assess how well the set of analytes predicted the outcome of interest. Conclusions: Multiplex angiome analysis defines biologically and clinically informative patterns of expression. The current analysis has identified a profile that may predict for clinical benefit for mCRC patients treated with the VEGF inhibitor, bevacizumab. Confirmatory studies from separate datasets are now in progress. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Roche Genentech, Roche Genentech, Roche
Effects of X-Ray Irradiation on the Development of Ovarian Tumors in Intrasplenic Grafts in Castrated Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Min Hsin Li, Ph. D., W. U. Gardner, Ph. D., Henry S. Kaplan, M. D.
Journal: JNCI Journal of the National Cancer Institute (1947)

Effects of X-Ray Irradiation on the Development of Ovarian Tumors in Intrasplenic Grafts in Castrated Mice Get access Min Hsin Li, Ph. D., Min Hsin Li, Ph. D. Departments of Anatomy and Radiology, Yale University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar W. U. Gardner, Ph. D., W. U. Gardner, Ph. D. Departments of Anatomy and Radiology, Yale University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry S. Kaplan, M. D. Henry S. Kaplan, M. D. Departments of Anatomy and Radiology, Yale University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 8, Issue 3, December 1947, Pages 91–98, https://doi.org/10.1093/jnci/8.3.91 Published: 01 December 1947 Article history Received: 01 October 1947 Published: 01 December 1947
New IRB guidelines: Will cancer patient safety improve?
Authors: C. Angelotta, D. Dorr, D. West, R. Burdon, J. Lagman, D. Workman, J. Hurdle, S. Belknap, C. L. Bennett
Journal: Journal of Clinical Oncology (2007)

6520 Background: Beginning in the 1990s, drug companies increasingly sent reports of all serious adverse events (AEs) to any Institutional Review Board (IRB) overseeing a trial using the agent involved, whether or not the same study was underway at that IRB site and regardless of the likelihood of a causal link between the event and agent. This led to a flood of AE reports and a small signal-to-noise ratio. Recent federal draft guidance emphasizes that regulations require investigators to notify IRBs only when there are “unanticipated problems involving risks to subjects or others. Consequently, many IRBs relaxed their reporting requirements, focusing only on unanticipated events. The objective of this study is to estimate how adoption of the new guidance affects IRB workload and patient safety. Methods: We reviewed AEs reported since 2004 to the IRB at Oregon Health &amp; Science University for eight oncology drugs: bevacizumab, gefitinib, imatinib mesylate, oxaliplatin, bortezomib, sorafenib, sunitinib, and cetuximab. We defined unanticipated AE as any AE not included in the patient consent forms. Results: Forty-seven studies were reviewed with 885 unique AEs reported for the eight drugs. Of these, 494 were unanticipated, meaning the event was not described in the consent form. Thus, the IRB workload would decrease by 44% under the new guidance. Twenty-six AEs led to actual consent form changes, suggesting these signal events represented serious, related, but previously unknown toxicities of the study drug. This led to a signal-to-noise ratio improvement from 3% to 5.3%. For imatinib mesylate, the signal-to-noise ratio improved from 4.1% (14 signals out of 339 reports) to 7.8% (14 signals out of 179 reports), the largest improvement of the drugs studied. Conclusions: These results suggest that adoption of the new guidance may improve signal detection capabilities of local IRBs while decreasing workload. More empirical evidence is needed to ensure patient safety. Enhanced pharmacovigilance practices at the IRB level should lead to improved detection of serious AEs during clinical trials - before the drug is approved and widely available to veterans. In addition, improving the signal-to-noise ratio should allow IRBs to improve the welfare of cancer research subjects. [Table: see text]
Abstract 5421: HER3 inhibition has little efficacy on hepatocellular carcinoma cell lines
Authors: Yong-Shi Li, Yu-Yun Shao, Han-Yu Wang, Ann-Lii Cheng, Chih-Hung Hsu
Journal: Cancer Research (2015)

Abstract Background: HER3 is a member of the ErbB family of receptor tyrosine kinases that are involved in the pathogenesis of many malignancies, including hepatocellular carcinoma (HCC) (Hsieh et al: Hepatology 2011). When bound with neuregulins (NRGs) or in the presence of HER2 amplification, HER3 dimerizes with HER2 and activates the signaling transduction cascade. We planned this study to evaluate the efficacy of HER3 inhibition by an anti-HER3 monoclonal antibody, LJM716 (Novartis®), in HCC. Methods: Human HCC cell lines Huh7, HepG2, PLC5, Hep3B, and SK-Hep1 were used in the experiments. We used the quantitative RT-PCR to evaluate the mRNA expression levels of HER2, HER3 and NRGs in HCC cell lines. We used the MTT assay to evaluate the growth inhibitory efficacy of LJM716 alone or in combination with sorafenib, and used the Western blotting to study the expression phospho-HER3 downregulated by LJM716 in these cells. Results: None of the HCC cell lines have HER2 amplification. Huh7 and HepG2 had higher HER2 expression, SK-Hep1 had lower HER3 expression, SK-Hep1 and Hep3B had higher NRG1 and NRG2 expression, and PLC5 had higher NRG2 but not NRG1 expression compared with other HCC cells. In HCC cells cultured with ordinary serum-containing medium, we found LJM716 up to 20 μg/ml showed little suppressive effect in the proliferation of HCC cells; in HCC cells cultured in the presence of NRG1, LJM716 could induce a 20 to 30% growth-suppressive effect at best. LJM716 inhibited NRG1-induced phosphorylation of HER3 in HCC cells dose-dependently. The treatment of sorafenib slightly increased RNA expression levels of NRG1 and HER2 in PLC5, Huh-7, and HepG2 cells. We combined LJM716 and sorafenib to evaluate their combination effect in HCC cells, but found that LJM716 failed to show any synergistic effect to sorafenib. Conclusions: Despite inhibitory effect on HER3 phosphorylation, LJM716 showed minimal therapeutic efficacy on HCC cell lines, either alone or in combination with sorafenib. Citation Format: Yong-Shi Li, Yu-Yun Shao, Han-Yu Wang, Ann-Lii Cheng, Chih-Hung Hsu. HER3 inhibition has little efficacy on hepatocellular carcinoma cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5421. doi:10.1158/1538-7445.AM2015-5421
An advanced computerized decision support technology to support breast multidisciplinary meetings.
Authors: V. Patkar, D. Acosta, T. Davidson, A. Jones, J. Fox, M. R. Keshtgar
Journal: Journal of Clinical Oncology (2010)

658 Background: Cancer multidisciplinary meetings (MDM) or tumour boards have become standard of care in management of breast cancer. As the number of cases continue to increase, better tools are required to support these heavily loaded meetings which play a pivotal role in patient management. We investigate the role of an advanced computerized decision support (CDS) technology in further enhancing the outputs of breast MDM. Methods: We have built a novel decision-support system called MATE to assist evidence-based decision making in breast MDM. MATE implements recommendations from 17 high quality breast screening, diagnosis and management guidelines. MATE provides prognostication and risk assessment and also flags up patients eligible for trials. In our pilot study, the data of 1,000 consecutive breast cases presented at the Royal Free Hospital breast MDM along with their documented MDM recommendations were entered into MATE. MDM recommendations and MATE suggestions were analyzed and compared. Results: The MATE system was able to suggest the treatment recommendations in concordance with evidence based guidelines in 97% of the cases. MATE also identified 62%more patients suitable for ongoing clinical trials. Deviations that occur specially in unaided MDMs can be minimized using electronic data capture and decision support system. MATE also significantly improved the transparency and the documentation of MDM decisions. Conclusions: This study has shown the feasibility of implementing MATE in the cancer multi-disciplinary meeting and its potential to improve certain aspects of the MDM by helping overburdened clinicians. The evidence adaptive decision support component of MATE can improve guideline-compliance and transparency in decision-making and also identify more patients to be considered for recruitment into clinical trials. Other important benefits include educational use, improved documentation for clinical and ethico-legal purposes. To collect level I evidence, MATE is currently being evaluated in a randomized controlled trial at our institution. No significant financial relationships to disclose.
Impact of azacytidine induction chemotherapies on post-transplant outcomes in patients with myelodysplastic syndromes
Authors: C. R. Cogle, I. Imanirad, J. Scornik, J. R. Wingard
Journal: Journal of Clinical Oncology (2009)

7032 Background: With the advent of azacytidines for treatment of MDS, disease remissions are achievable; however the disease nearly always relapses. In contrast, allogeneic hematopoietic cell transplantation (HCT) can be curative. Whereas cytotoxic induction chemotherapy in patients with MDS provides no clear benefit after HCT, the effects of azacytidine therapy prior to HCT are unknown. Methods: To address this question, we analyzed post-transplant outcomes in 43 MDS patients, 9 who received an azacytidine before transplant and 34 who did not. Although patients in both groups were equivalent in time to transplant, performance status, and transfusion dependence, patients who received an azacytidine were older (61 vs 48, p &lt; 0.01), more immunosuppressed at HCT (absolute lymphocyte count 815 vs 1339, p = 0.04), and less likely to receive myeloablative conditioning (38% vs 78%, p = 0.03). Azacytidine patients were marginally more likely to have higher disease burden at HCT (WPSS 4 vs 3, p = 0.08) and more likely to have received a graft from an unrelated donor (66% vs 33%, p = 0.07). These patient characteristics reflect the current practice of using an azacytidine as a bridge to transplant for older patients who have no readily available, matched related donors. Results: With a median follow-up of 7 months, the group that received azacytidine pre-transplant demonstrated higher donor chimerism at days 30, 60 and 100 (p &lt; 0.01). Rates of acute and chronic GVHD, and median overall survival (OS) did not differ significantly between groups. There was a trend toward higher relapse in the azacytidine group (44% vs 18%, p = 0.09). Conclusions: Our data indicate that induction with azacytidines results in higher short-term donor chimerism post-transplant. This effect is likely due to increased immunosuppression in an older population after azacytidine therapy. The increased rate of relapse in the azacytidine group likely reflects the progressive nature of chemotherapy-insensitive disease at HCT. Although only randomized controlled trials can establish a definite conclusion regarding use of azacytidines prior to HCT and duration of induction therapy before proceeding to HCT, the data presented support administration of azacytidines to MDS patients prior to HCT. [Table: see text]
사례보고 : 중증 간질환을 동반한 적혈구조혈성 포르피린증 환자에서의 cholestyramine 치료: 사례보고
Authors: 유동준, 이한주, 유은실, 진영주, Ju Hyun Shim, 김강모, 임영석, 정영화, 이영상, 서동진
Journal: Clinical and Molecular Hepatology (2010)

EPP는 ferrochelatase의 결핍이나 활성 감소로 프로토포르피린이 적혈구, 간, 혈장 등에 축적되는 유전질환이다 축적된 프로토포르피린은 EPP의 주된 임상적 특징인 광과민 증상과 간질환을 일으키게 된다. EPP로 인한 간질환에 대해 다양한 치료법이 개발되고 있으나, 효과적인 치료 방법은 아직 없다. 그 중 cholestyramine resion의 유용성에 대한 보고는 드물며, 다른 치료와 같이 대부분 사용되었다. 저자들은 cholestyramine resion의 단독치료로 성공적인 결과를 나타낸 사례를 보고하는 바이다. 향후 EPP로 인한 간질환의 증상 및 예후 개선을 위해서, 이번 사례를 포함한 더 많은 연구가 필요하다.
Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age
Authors: Reto Auer, Eric Vittinghoff, Kristine Yaffe, Arnaud Künzi, Stefan G. Kertesz, Deborah A. Levine, Emiliano Albanese, Rachel A. Whitmer, David R. Jacobs, Stephen Sidney, M. Maria Glymour, Mark J. Pletcher
Journal: JAMA Internal Medicine (2016)

Marijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function.
Effects of sex hormones on bronchial reactivity during the menstrual cycle
Authors: Francesca Polverino, Maria Matteis, Giuseppe Spaziano, Fiorentina Roviezzo, Carlo Santoriello, Maria Laucho Contreras, Nikol Sullo, Maria Rosatia Bucci, Francesco Rossi, Caroline Ann Owen, Mario Polverino, Bruno D'Agostino
Journal: European Respiratory Journal (2014)

Background: Perimenstrual asthma(PMA) is defined as the exacerbation of the respiratory symptoms in asthmatic premenopausal females during the premenstrual phase and/or the first days of menstruation. We studied the effect of the menstrual cycle on bronchial reactivity(BR) in a group of women with PMA.  Methods: 36 pre-menopausal women underwent testing for resting pulmonary function, measurement of the diffusing lung capacity for carbon monoxide(DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured circulating levels of prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone, progesterone and 17β-estradiol in plasma, and levels of cyclic adenosine monophosphate(cAMP) which is a mediator of bronchial smooth muscle contraction, and testosterone in induced sputum.  Results: About 70% of the women with asthma had increased BR in the follicular phase of the menstrual cycle, and there was a significant correlation between BR and serum testosterone levels. Moreover, we observed a marked increase in sputum testosterone levels and cAMP concentration during the luteal phase of the menstrual cycle in the PMA patients. We excluded a direct effect of testosterone on inhibiting PDE activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity.  Conclusions: BR is increased in the follicular phase of the menstrual cycle of premenopausal women, and was also associated with lower testosterone and cAMP levels in sputum samples which may contribute to bronchoconstriction. Targeting testosterone and/or cAMP in patients with PMA could improve the management of the asthma symptoms during the menstrual cycle.
Prognostic factors associated with treatment response to octreotide in advanced hepatocellular cancer (HCC)
Authors: G. Treiber, T. Wex, C. Roecken, P. Malfertheiner
Journal: Journal of Clinical Oncology (2004)

4185 Background: Results from clinical trials using octreotide for treatment of advanced HCC are conflicting. Current objective was to evaluate prognostic factors before and during treatment with Sandostatin LAR 30 mg (monthly). Methods: Prospective cohort of 75 patients. They were treated for a minimum of six months or until one final endpoint (progression or death) was reached. Optimal cut-offs were derived from ROC analysis. Results: (logrank tests): Progression within or later than 90 days of treatment was the best clinical decision making for longterm survival outcome (p<0.0001), median PFS was 468 days. A CLIP score > 2 decreased median survival from 230 to 113 days (p<0.01), okuda stage 3 was similiar. 79% of patients had an increased uptake by octreoscan (>1.5 fold than non-tumorous liver). An uptake <2 fold was associated with longer survival (median: 391 vs. 158 days, p=0.05), in patients evaluable during follow up, octreoscan uptake was unchanged in most cases. A prestudy serum VEGF-A value of >660 pg/ml shortened survival from 205 to 95 days (p <0.01). A decrease in VEGF-A by month 3 or 6 of treatment below a ratio of 0.7 was predictive best: by 2.5 years 45% of patients vs. 8% of patients survived (p=0.01). Other serum markers evaluated with significant differences in survival were soluble interleukin 2 receptor and osteopontin. Their corresponding cut-offs of 1310 pg/ml and 1060 U/l discriminated between 220–230 and 114 days of survival (p<0.01 each). In contrast to previous reports, serum IGF-1 was marginally associated with survival outcome in this study. Conclusions: Overall median time to progression (122 days) and median survival (153 days) in our study was short. However, for the first time, we are able to identify a subgroup of patients with no measurable HCC tumor progression and long-term survival due to treatment with octreotide. The most intriguing finding was the association between VEGF-A decline and treatment response, thus suggesting the inhibition of angiogenesis as the main factor of action for octreotide. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma, Nueremberg, Germany
The violation of psychiatric standards of care in prisons
Authors: E Kaufman
Journal: American Journal of Psychiatry (1980)

The author evaluated psychiatric care in three U.S. prison systems. Major problems included limitations imposed by prison architecture, inadequate staff, medication prescription and distribution by unlicensed, untrained personnel, and a punitive rather than therapeutic attitude. Following the standards of care recommended by American Correctional Association would correct most of these problems. Psychiatrists should guard against prescribing unnecessary medications, particularly minor tranquilizers and sedatives, and should be concerned with prison conditions conductive to mental illness, particularly overcrowding, abuses of solitary confinement, and inadequate programs for inmates who are mentally disturbed but not overtly psychotic. The author recommends minimum staffing standards and suggests considering the transfer of mentally ill inmates to appropriate psychiatric hospitals outside the prison system.