tbuckley/cabot-search huggingface dataset:
A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991)
Authors: T. Hogberg, P. Rosenberg, G. Kristensen, C. F. de Oliveira, R. de Pont Christensen, B. Sorbe, C. Lundgren, T. Salmi, H. Andersson, N. S. Reed
Journal: Journal of Clinical Oncology (2007)

5503 Background: Adjuvant therapy for early stage high-risk endometrial cancer remains controversial. Methods: Patients with surgical stage I, II, IIIA (positive peritoneal fluid cytology only), or IIIC (positive pelvic lymph nodes only) were eligible if they, according to departmental guidelines, had a sufficiently high risk for micrometastatic disease to qualify for adjuvant therapy. Most patients had two or more of the risk factors: grade 3, deep myometrial invasion, or DNA non-diploidy, while some patients had only one of these. Patients with serous, clear cell, or anaplastic carcinomas were eligible regardless of risk factors. Patients with para-aortic metastases were not eligible. Lymph node exploration at staging surgery was optional. Pelvic RT ± vaginal brachytherapy was given to a dose =44 Gy. CT was given before or after RT. Before August 2004 CT consisted of four courses of cisplatin =50 mg/m 2 + doxorubicin 50 mg/m 2 or epirubicin 75 mg/m 2 (AP). Thereafter several CT regimens were allowed, of which AP, paclitaxel 175 mg/m 2 + epirubicin 60 mg/m 2 + carboplatin AUC 5, and paclitaxel 175 mg/m 2 + carboplatin AUC 5–6 were used. Progression-free survival (PFS) was the primary end-point. The study was terminated before the aimed goal of 400 patients because of slow recruitment. We decided to make an early analysis since new studies on endometrial cancer are presently discussed. Results: 372 patients were entered between May 1996 and Oct 2006. Of 367 evaluable patients 190 were randomized to RT and 177 to RT+CT. Risk factors were well balanced between the randomization arms. The median follow-up time was 3.5 years. The hazard ratio for PFS was 0.58 in favor of RT+CT (95 % confidence interval (CI) 0.34 - 0.99; p=0.046). This translates to an estimated 7 % absolute difference in 5-year PFS from 75 % (95 % CI 67 % - 82 %) to 82 % (95 % CI 73 % - 88 %). Conclusion: RT+CT was better than RT alone. Next question is if RT+CT is better than CT alone. No significant financial relationships to disclose.
Peg-ifn-alfa 2b With Ribavirin for the Treatment of Mild-moderate Recurrent Hepatitis C After Liver Transplantation (lt) : Impact On Fibrosis Progression. a Multicenter Randomized Controlled Study
Authors: Luca S. Belli, Peter Starkel, Riccardo Volpes, Ivo Graziadei, A. K. Burroughs, Patrizia Burra, Stefano Fagiuoli, Alberto B. Alberti, Maria Guido, Luisa Pasula, Wolfgang Vogel, Bruno Gridelli, Umberto Cillo, Luciano De Carlis, Giovambattista Pinzello
Journal: Hepatology (2009)
Identification of the BRCA1 187delAG mutant allele in New Mexican Hispanic families with hereditary breast and ovarian cancer (HBOC)
Authors: P. R. Duncan
Journal: Journal of Clinical Oncology (2005)

9588 Background: The 187delAG mutant allele has been identified in patients with HBOC and Jewish ancestry in Spain (Diez et al BJCancer 1999;79:1302–03), Chile (Proc ASCO,22:Abst#3535,2003) and Brazil (Mew et al Clin Genet 2002;62:151–56). Recently 6 non-Jewish Hispanic HBOC families in the San Luis Valley of southern Colorado have been reported with the 185delAG mutation (Mullineaux et al Cancer 2003;98:597–602). Spaniards beginning in 1598 colonized New Mexico and the population included conversos and crypto-Jews who were escaping religious persecution by the Inquisition. Descendents of this colonial society continue living within New Mexico and surrounding states. Methods: New Mexico residents referred to the author’s familial cancer clinic with a risk of HBOC were counseled. If the risk for a BRCA mutation was determined to be >10%, the analysis was carried out at Myriad Genetic Laboratories. Results: A deleterious mutation was found in 17 New Mexican families. Seven (41%) of the 17 families identified themselves as Hispanic. Five (71%) of the 7 Hispanic families carried the 187delAG mutation and a member in all 5 families identified descent from a colonial family. Three families have California or Colorado relatives with breast and ovarian cancer. Only one family knows of Sephardic Jewish ancestry in 16th century Portugal and Spain. Conclusions: Our data as well as others support the thesis that some individuals descended from populations founded by the Hispanic colonial expansion of the 16th-18th century carry a 187delAG mutant allele founder mutation. Single site mutational analysis for 187delAG should be considered as the first step, when BRCA testing is recommended to evaluate Hispanic families with risk of HBOC. No significant financial relationships to disclose.
Prevalence and ancestral origin of <i>BRCA</i> mutations in the Hispanic population: Insights for ancestry-informed genetic cancer risk assessment.
Authors: J. N. Weitzel, J. N. C. DeHart, R. M. Ogaz, A. E. Martir-Negron, J. Herzog, C. Ricker, J. Congleton, C. Cina, P. R. Duncan, G. W. Unzeitig, J. S. Saldivar, M. Beattie, N. R. Feldman, S. Sand, D. Port, E. M. John, C. Haiman, R. Varma, S. L. Neuhausen, G. P. Larson
Journal: Journal of Clinical Oncology (2011)

1514 Background: Little is known about prevalence or ancestral origins of BRCA1and BRCA2 (BRCA) mutations among high-risk Hispanics, the fastest growing relatively underserved population in the U.S. Methods: Individuals of self-reported Hispanic origin with a personal or family history of breast and/or ovarian cancer were enrolled in an IRB-approved registry and underwent genetic counseling and BRCA testing within a consortium of 14 high risk clinics across the U.S. Multigenerational pedigrees and data on grandparental geographic origins were obtained. Screening for recurrent BRCA mutations was done in three population-based cohorts. Haplotypes were constructed for recurrent mutations, and mutational age was estimated for a large BRCA1 rearrangement mutation (ex9-12del). Genotyping of 59 ancestry informative SNPs was performed and STRUCTURE analysis was used to determine ancestry admixture in BRCA carriers, with Los Angeles Mexican-American HapMap reference samples and an AmerIndian reference population seeded in the analyses. Results: Deleterious BRCA mutations were detected in 189/746 (25%) Hispanics (124 in BRCA1, 65 in BRCA2); 34 (5%) had one or more unclassified variants, and 523 (70%) had negative results. Mean age at diagnosis was 41 years for the 656 women with breast cancer. The most frequent mutations (n>5) were BRCA1 185delAG (n =18; occurring on the Jewish haplotype), ex9-12del (n=13), R71G (n=9), R1443X (n=6), and BRCA2 3492insT (n=10); accounting for 30% of all mutations. Large rearrangements (n=21) constituted 11% of all mutations. From mutational age analyses, BRCA1 ex9-12del was estimated to have arisen 74 generations (~1,480 years [920-2260]) ago; all carriers reported Mexican descent and admixture analyses suggested greater Amerindian ancestry than either the Mexican American reference panel or the Mexican 185delAG carriers who had more European ancestry. Conclusions: With a large sample of BRCA mutations among U.S. Hispanics from Mexico and Central America, our results suggest that ancestry-informed genetic screening for recurrent mutations (many of Spanish origin, as well as the Mexican BRCA1 ex9-12del founder mutation) could be cost effective.
Edward Hare Donald McLarty Philip Edmund Clinton Manson-Bahr Michael O'Sullivan Robert William Trainer Mason Desmond Richard Levinge Newton Ian Rea Smith Kenneth Arthur Tomlinson June Rosalind Wilkie (nee Hill)
Authors: Edward Hare
Journal: BMJ (1997)

# Edward Hare {#article-title-2}

The son of a clergyman, Edward Hare first read biochemistry at Cambridge before deciding to switch to medicine. Found to be unfit for military service in the war because of partial deafness, he soon entered psychiatry at Cardiff City Mental Hospital and later at Bristol. Here he wrote an MD thesis on the ecology of mental hospitals, with its effects on patients. He then turned to studying why the rates of schizophrenia are higher in the centre of cities than elsewhere. His findings supported the “drift” hypothesis-that those who are developing serious mental illness become detached from their families and move into areas of anomie. This work impressed (Sir) Aubrey Lewis, who subsequently invited him to apply for a vacant consultant post at the Bethlem-Maudsley Hospitals. Here he remained a committed clinician (though his time included a spell as chairman of the medical committee) and a detached and critical commentator of the passing fashions within and outside the joint hospitals.

In 1983 Hare electrified the research community with his elegant Maudsley lecture asking in its title whether insanity was on the increase. In the 19th century in Britain and the United States there had been a progressive increase in demand: both the numbers of asylums and of their inmates had increased. The “nosocomialists” believed that this was a result of demographic and social changes; the “alarmists” argued for an increase in incidence. In this debate Hare allied himself with the alarmists, concluding that “this increase was principally the type of insanity which in the 1890s Kraepelin called dementia praecox and which we now call schizophrenia.” This thesis challenged the complacent but ill documented established view that the incidence is constant across variations in time and place. Hare concluded that the historical evidence was compatible with a somatic cause and himself …
Decreasing tumor size explains some improvement in survival from localized breast cancer
Authors: E. B. Elkin, D. Schrag, C. Hudis, C. B. Begg
Journal: Journal of Clinical Oncology (2004)

6046 Background: Population-based comparisons of breast cancer survival across different time periods are frequently used in health services investigations and in studies of trends in prognosis. These comparisons can be affected by stage migration, even within conventional stage categories, since the distribution of tumor size can change substantially within these categories. We examined changes in tumor size and breast cancer survival over time. Methods: We used Surveillance, Epidemiology, and End Results (SEER) data to obtain tumor size and 5-year relative survival for women with localized invasive breast cancer diagnosed between 1975–99. By definition, these cancers were node-negative and confined to the breast. Tumor size was categorized as <5mm, 5–9mm, 1–1.9cm, 2–2.9cm, 3–3.9cm, 4–4.9cm, and 5+cm. We calculated age-adjusted, tumor size-adjusted relative survival for cohorts diagnosed in 5-year time intervals. We also calculated relative survival standardized to the tumor size distribution of the 1975–79 cohort. For each of the later cohorts, we calculated change in observed and standardized relative survival compared with the 1975–79 cohort, and we estimated the percent of improvement in relative survival attributable to decreasing tumor size. Results: Among localized invasive breast cancers, the proportion of tumors 2cm or larger declined from 59% in 1975–79 to 30% in 1995–99. More than half of the increase in relative survival from 1975–79 to 1995–99 was eliminated after standardization of the contemporary cohort to the tumor size distribution of the 1975–79 cohort. (See table) Conclusions: Gains in survival from localized breast cancer realized over the last three decades may be explained in part by a shift in the tumor size distribution. When making temporal comparisons, it is important to adjust for changes in tumor size in order to fully accommodate the effects of stage migration. No significant financial relationships to disclose.
Inhibition of mTORC2/Akt signaling to enhance the therapeutic potential of CD8 T cells
Authors: Lianjun Zhang, Benjamin Tschumi, Susanne Oberle, Markus Ruegg, Michael Hall, Dietmar Zehn, Jean-Pierre Mach, Alena Donda, Pedro Romero
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts CD8 T cells mediate protective immune responses against infections and cancer. Upon infection, antigen-specific naïve CD8 T cells are activated and differentiate into short-lived effector (SLEC) and memory precursor cells (MPEC). The T cell intrinsic signaling pathways underlying
Long-Term Effects of Retinal Gene Therapy in Childhood Blindness
Authors: Alan F. Wright
Journal: New England Journal of Medicine (2015)

Current ocular imaging techniques provide extraordinarily high-resolution visualization of the retinal layers, amounting to what has been called in vivo microscopy. Combine this with a battery of sophisticated retinal-function tests, and the retina becomes unusually accessible in the evaluation of trials of retinal gene therapy for the treatment of conditions such as Leber's congenital amaurosis.Leber's congenital amaurosis is a group of inherited retinal dystrophies associated with blindness early in life and can be caused by mutations in at least 19 different genes. Loss-of-function mutations in one of these genes, RPE65, account for 5 to 10% of recessive Leber's . . .
Sentinel lymph node dissection provides similar local-regional control compared to axillary dissection in patients with node negative breast cancer
Authors: N. Khakpour, A. Lucci, M. Yi, F. Meric-Bernstam, H. M. Kuerer, G. V. Babiera, M. I. Ross, T. Buchholz, A. Garg, K. K. Hunt
Journal: Journal of Clinical Oncology (2005)

588 Background: Recent studies have documented low axillary recurrence rates in breast cancer patients undergoing axillary sentinel lymph node dissection (SLND). The purpose of this study was to compare axillary control rates in patients staged with SLND versus complete axillary lymph node dissection (ALND). Methods: 1597 patients with T1-T4 N0 M0 breast cancer, node negative by H&E, were identified from prospective databases of two institutions from 1994 to 2003. All patients had mastectomy or breast conservation combined with either SLND followed by ALND as part of a training protocol or SLND alone. Factors evaluated included tumor size, nuclear grade, ER, PR, HER-2/neu, lymphovascular invasion (LVI), and the number of nodes removed. Results: Of 1597 node negative patients, 1334 underwent SLND alone and 263 had SLND with ALND. There were no significant differences in T stage, LVI, ER, PR, HER-2/neu, nuclear grade, or surgical procedure between the two groups. Significantly more patients in the ALND group received systemic chemotherapy (p<0.05), but there was no difference in use of endocrine therapy. A median of 2.0 SLN and 0 non-SLN were removed in the SLND group versus 2.0 SLN and 15 non-SLN in the ALND group. At a median follow-up of 28 months (range 3–119 mos), 40 patients (2.5%) had local-regional or distant disease. There were no differences in disease-free and overall survival between the SLND and ALND groups at a median follow-up time of 26 mos and 53 mos, respectively. Specifically, four patients (0.25%) developed axillary recurrence, 2 in the SLND group (0.15%) and 2 in the ALND group (0.76%). Axillary recurrences in the SLND group were noted at 27 and 32 mos versus 55 and 61 mos in the ALND group. Conclusions: SLND alone appears to provide similar axillary control compared to ALND in node negative breast cancer patients. Long-term follow-up is needed to determine if the low axillary failure rates seen with SLND alone are durable. No significant financial relationships to disclose.
P0875 : Predictors of sustained viral response to 4–6 week duration therapy with ledipasvir + sofosbuvir + GS-9451 +/− GS-9669 in early and advanced fibrosis (NIH/UMD synergy trial)
Authors: S. Kattakuzhy, S. Sidharthan, E. Wilson, A. Price, R. Silk, C. Gross, E. Akoth, E. Meissner, G. Teferi, V. Jenkins, P. Pang, H. Mo, A. Osinusi, H. Masur, S. Kottilil, A. Kohli
Journal: Journal of Hepatology (2015)
EXTERNAL VALIDATION OF THE BIOMARKER-BASED ABC-STROKE RISK SCORE FOR ATRIAL FIBRILLATION
Authors: Jonas Oldgren, Ziad Hijazi, Johan Lindback, John Alexander, Stuart Connolly, John Eikelboom, Michael Ezekowitz, Christopher Granger, Elaine Hylek, Renato Lopes, Agneta Siegbahn, Salim Yusuf, Lars Wallentin
Journal: Journal of the American College of Cardiology (2016)
Association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and statins and the risk of cutaneous melanoma (CM): A case-control study
Authors: C. Curiel, M. L. Gomez, M. B. Atkins, T. Nijsten, R. S. Stern
Journal: Journal of Clinical Oncology (2007)

8500 Background: CM accounts for more than 77% of skin cancer deaths. Chemoprevention strategies have been hampered by the lack of supporting epidemiological data. Methods: A case control study examined the association between statins and NSAIDs use and CM in people over 40 years of age. A total of 400 histologically confirmed CM cases were recruited within 3 months from diagnosis between 3/04 and 12/06. Controls included 600 individuals without history of CM matched for age, gender and neighborhood in a ratio of 1:1.5. All completed a standardized telephone questionnaire that captured demographic characteristics, CM risk factors, and drug exposure history (length and frequency of use). Odds ratios were calculated with testing for statistical significance based on Chi square analysis. Results: To date, all 400 CM cases and 547 controls have been recruited. Interview results out of 387 cases (192 F/195 M) and 505 controls (254 F/251 M) were included for data analysis. Mean age was 58.4 and 58.5 years. The most significant CM risk factors included: red hair phenotype OR: 2.29, history of non-CM skin cancer OR: 2.28, family history of CM OR: 1.76, light complexion OR: 2.7, and history of more than 4 sunburns in childhood OR: 4.06. 100 cases vs. 190 of the controls had been exposed to statins OR 0.58 (CI:0.43–0.78); no greater protective effect was detected with increased duration of statin use (p=0.87 for heterogeneity of ORs for =5 vs. &lt;5 yrs). 238 cases vs. 397 controls reported the use of NSAIDs, OR 0.44 (CI 0.32–0.59). 43 cases reported the use of aspirin-ASA for = 5 years vs. 92 controls OR: 0.37 (CI: 0.20–0.68). Similar results were observed with exposure to other NSAIDs with 38 cases reporting the use for = 5 years vs.109 controls, OR: 0.35 (CI: 0.24- 0.50). Conclusions: This study suggests that extended use of NSAIDs decreases the risk of CM development. Although any statin use demonstrated a decreased risk, the lack of an association between duration of use and protective effect raises questions about a true causal relation. Further analysis with respect to the CM subtype and specific exposure (by dose, and frequency of use) to these groups of drugs may lead to the design of CM chemopreventive clinical trials. Final analysis will be presented at ASCO. No significant financial relationships to disclose.
Personalized therapy for metastatic colorectal cancer: A closer possibility?
Authors: M. Pierobon, V. Calvert, M. Lipsky, K. Sheehan, R. Speer, E. Mammano, C. Belluco, D. Nitti, L. Liotta, E. Petricoin
Journal: Journal of Clinical Oncology (2007)

4131 Background: Colorectal cancer (CRC) is the second leading cause of cancer related death in the Western world, and survival rate is closely associated with the development of metastases. Personalized targeted therapies promise to have a dramatic impact on the treatment of cancer over the next decade. The molecular fingerprint of a patient’s tumor is the basis for specific targeted therapy. Most often, we are not measuring what we are treating. If we choose therapy based on the primary tumor, but we are treating the metastasis, we are likely giving the wrong therapy if the two microenvironments are not equivalent. In this study we employed reverse phase protein microarrays (RPPA) to compare the protein kinases signal pathway derangements in the primary CRC and in its synchronous liver metastasis. Methods: Pure cell populations of 34 cases of patient-matched CRC and hepatic metastases (collected at the same surgical time) were isolated through laser capture microdissection and then lysed. The lysed cells were evaluated using RPPA technology that allowed us to analyze the activation status of 80 different kinases. Data analysis was performed using commercially available software. Results: Of the 80 kinases only 20 endpoints were significantly (p&lt; 0.05) altered between the two populations. These endpoints were contained within just a few signaling pathways, including the PI3K-AKT prosurvival pathway and the c-kit/PDGFr/c-abl growth factor pathway. We noted a significant increase in phosphorylation of AKT along with a decrease in phosphorylation of PTEN in the liver metastasis compared to the matched primary tumors. This is in keeping with what is known about AKT since phosphorylation of PTEN serves to destabilize the protein, which serves as a natural upstream suppressor of AKT kinase. Conclusions: Specific cell signaling pathways, such as the PI3K-AKT and the c-kit/PDGFr/c-abl growth factor signaling pathway, are significantly altered and activated in hepatic metastasis compared to the primary colorectal site. Since the data reveals elevation in kinase activity increases on a pathway-wide level, a rational hypothesis can be developed whereby combinations of drugs such as an AKT- mTOR inhibitor and/or Gleevec may be an effective and novel therapeutic strategy for the treatment of metastatic CRC. No significant financial relationships to disclose.
You can run but you can't hide: tracking T cells in metastatic melanoma patients treated with tumor-infiltrating lymphocytes
Authors: Cara Haymaker, Marie-Andrée Forget, Caitlin Creasy, Krit Ritthipichai, Patrick Hwu, Chantale Bernatchez
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive T cell therapy using tumor-infiltrating lymphocytes (TIL) for patients with metastatic melanoma has been shown to have a 45-50% response rate as demonstrated by multiple institutions worldwide. However, understanding how long infused T cells persist in patients remains