tbuckley/cabot-search huggingface dataset:
Activity of ixabepilone and PARP inhibitors in triple-negative breast cancer (TNBC) based on gene expression.
Authors: C. E. Horak, G. Alexe, J. Baselga, L. T. Vahdat, V. Valero, G. Xing, P. Mukhopadhyay, D. M. Opatt, J. Sparano
Journal: Journal of Clinical Oncology (2010)

601 Background: TNBC comprises 15%-20% of all breast cancers (BCs) and is associated with a poor prognosis. In the ixabepilone (Ixa) study CA163-080 (-080) (n = 161), 26% of the patients (pts) had TNBC and overall clinical response rate (ORR) in this subset was 64%. PARP inhibitors (PARPi) also exert activity in TNBC and BRCA1/2-associated BCs (which share molecular and biological similarities to TNBCs) through synthetic lethality, whereby inhibition of PARP is only lethal in the context of defects in DNA repair mechanisms. We hypothesized that tumors resistant to Ixa might overexpress genes associated with PARPi synthetic lethality and the 2 drugs might be active in different subsets of TNBC. Methods: Gene expression profiles are available for breast tumors from 134 pts with stage II-III BC treated on -080. Of these 134 pts, 19 (14%) had a pathologic complete response (pCR) or near total pCR at surgery (collectively called sensitive [Ixa-S]); 9 of 35 pts (26%) with TNBC were Ixa-S. The genes that exhibit synthetic lethality with PARPi treatment in vitro were evaluated in Ixa-S compared with resistant (Ixa-R). In addition, an Ixa-S signature composed of the top 30 negatively and positively-correlated genes with Ixa-S, was applied to gene expression dataset, which included 18 known familial BRCA1-mutated specimens (van't Veer et al, NEJM 2002). Results: Expression of some genes that exhibit synthetic lethality with PARPi (eg, BRCA1/2, RAD51, CHK1/2, FANCA/C, LIG1, PCNA) were significantly down-regulated in Ixa-R pts. However, not all genes associated with PARPi-induced synthetic lethality exhibited significantly different expression in Ixa-S vs Ixa-R pts (eg, ATR, ATM, RPA1, DDB1, XAB2). In the TNBC population, fewer PARPi synthetic lethality genes exhibited significantly lower expression in Ixa-R pts, including BRCA1/2, CHK1/2 and RAD51, although the sample size was small. The Ixa-S signature did not correlate with the expression patterns observed in most of the BRCA1-mutated tumors in the van't Veer dataset. Conclusions: These data suggest that Ixa and PARPi may be active in different subsets of TNBC, but is limited by sample size and needs prospective validation in future BC studies with both PARPi and Ixa. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Value of intensity modulated radiotherapy for local control and salivary flow compared with conventional radiotherapy for stage II nasopharyngeal carcinoma
Authors: D. L. Kwong, A. McMillan, E. Pow, J. Sham
Journal: Journal of Clinical Oncology (2007)

6036 Background: Xerostomia is ubiquitous after conventional radiotherapy (CRT) for nasopharyngeal carcinoma (NPC). Intensity modulated radiotherapy (IMRT) has been advocated to spare the parotids for early disease. However, in T2 disease where there is a need to cover parapharyngeal involvement, it is uncertain if IMRT can still preserve salivary function without compromising local control. Methods: Patients with T2N0/1M0 NPC to be treated with RT alone were eligible. Patients were randomized to receive CRT or IMRT. The end points were salivary flow and local control. The aim was to recruit 25 patients for salivary flow study in each arm. All patients underwent stimulated parotid (SPS) and whole salivary (SWS) flow assessment before RT and at 2, 6 and 12 months after RT. Results: From 2000 to 2005, 42 and 40 patients were randomized to IMRT and CRT respectively. 19 (47.5%) and 27 (64.3%) of patients treated with CRT and IMRT had N1 disease respectively (p=0.18). The median dose for CRT patients was 68 Gy and 75% patients received additional parapharyngeal boost dose of 10 Gy. The median dose to NP for patient treated with IMRT was 70 Gy with no additional boost. Disease control and survival rates were shown in the Table. 25 patients in each arm underwent prospective salivary flow assessment. There was gradual recovery of SWS and SPS among patients treated with IMRT while patient on CRT showed no improvement over time. The mean SWS and SPS flow at 12 months were 26% and 114% of baseline among patients treated with IMRT, compared with 5% and 0% among patients treated with CRT. There was significant difference in SWS and SPS between patients treated with IMRT and CRT at 2, 6 and 12 months post-RT. The average mean dose to parotid gland was 41Gy. Conclusions: IMRT can reserve salivary flow despite a relatively high mean dose to the parotid glands. The significant improvement in local control with IMRT was unexpected but can be due to better coverage of disease with 3-dimensional planning. No significant financial relationships to disclose.
Hysterical psychosis and hypnotizability
Authors: D Spiegel, R Fink
Journal: American Journal of Psychiatry (1979)

The very existence of hysterical psychosis as a diagnostic entity has been questioned as part of the general difficulty in defining both hysteria and psychosis. However, several recent investigations have documented a syndrome that usually involves brief and intense periods of psychotic behavior, generally with graphic decompensation, severe environmental stress, and rapid recompensation, in individuals with other hysterical features. The authors assert that such a syndrome does exist as a clinical entity and that the differential diagnosis can be facilitated by using a standardized measure of hypnotic trance capacity. They hypothesize that patients with hysterical psychosis are highly hypnotizable, while those who are schizophrenic and psychotic have low hypnotizability. The authors review the literature and present two case examples.
Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities
Authors: Carol E. DeSantis, Rebecca L. Siegel, Ann Goding Sauer, Kimberly D. Miller, Stacey A. Fedewa, Kassandra I. Alcaraz, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2016)

In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016;66:290-308. © 2016 American Cancer Society.
One hundred thirteen men with hormone-refractory prostate cancer died today.
Authors: N J Vogelzang
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.6.1753 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8656242 One hundred thirteen men with hormone-refractory prostate cancer died today. N J VogelzangxN J VogelzangSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.6.1753 First Page PDF © 1996 by American Society of Clinical Oncology
A Phase II Study of the Combination of FCR-Lite and Lenalidomide Followed By Lenalidomide Maintenance in Front-Line CLL: The FCR2 Regimen
Authors: Anthony R. Mato, Kenneth A. Foon, Tatyana Feldman, Stephen J. Schuster, Jakub Svoboda, Kar Fai Chow, Marisa Valentinetti, Mary Morin, Kelly Azzollini, Gabriella Magarelli, Pritish K. Bhattacharyya, Joshua Zenreich, Christina Howlett, Lauren-Nicole Pascual, Kara Yanotti, Sabrina Kdiry, David Porter, Andre Goy
Journal: Blood (2014)
Transformation and Neoplastic Development &lt;italic&gt;In Vitro&lt;/italic&gt; of Hamster Embryonic Cells by 4-Nitroquinoline-1-Oxide and Its Derivatives&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Toshio Kuroki, Haruo Sato
Journal: JNCI Journal of the National Cancer Institute (1968)

Transformation and neoplastic development of cells after exposure to chemical carcinogens in vitro were investigated. 4-Nitroquinoline-1-oxide and its carcinogenic derivatives successfully induced transformation and neoplastic development of hamster embryonic cells in tissue culture. Transformation occurred about 20–80 days after the first treatment with carcinogens, the earliest occurring at 15 days. The transformed cells were characterized by: proliferation in vitro, the cells forming a piled-up, dense layer; stable and unlimited growth in tissue culture; the ability to produce a progressively growing, transplantable fibrosarcoma when inoculated into hamsters. The shortest time at which progressively growing tumor was seen was 49 days after the first treatment, but histologic evidence of neoplastic development was observed as early as 23 days after treatment. In some cultures, neoplastic development was much later than the transformation of cells. The cultures of untreated cells contrasted strikingly with those of the treated cells, i.e., the control cultures had a limited lifespan and failed to produce tumor, except for one culture in which spontaneous transformation and neoplastic development occurred around 300 days in vitro.
Polymorphisms of genes involved in gemcitabine metabolism correlate with prognosis in patients receiving neoadjuvant therapy for pancreatic cancer
Authors: M. M. Javle, T. Okazaki, D. B. Evans, R. A. Wolff, J. L. Abbruzzese, D. Li
Journal: Journal of Clinical Oncology (2008)

4501 Background: Genetic variations in gemcitabine transport and metabolism may affect the clinical response, toxicity, and prognosis of pancreatic cancer patients treated with gemcitabine. Methods: We evaluated 17 single nucleotide polymorphisms (SNPs) of 8 genes (CDA, dCK, RRM1, DCTD, hCNT1, hCNT2, hCNT3, and hENT1) involved in gemcitabine metabolism in a homogeneous population of 126 patients with resectable pancreatic cancer treated with neoadjuvant gemcitabine- based chemotherapy plus radiation therapy. Whole blood was collected from patients at the time of enrollment, and DNA was extracted from peripheral lymphocytes using a DNA isolation kit (Qiagen Valencia, CA). Polymorphisms were detected using the TaqMan genotyping assays provided by Applied Biosystems (Foster City, CA). Survival was determined from pathologic diagnosis to death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype. Results: Six of the 17 SNPs had a borderline-significant effect on OS (p <0.1, log-rank test). A significant combined genotype effect on OS was observed for the metabolic or target gene SNPs CDA 111CC, CDA -76AA, RRM1 42GG, and DCTD -47CT (p <0.001) and for the transporter gene SNPs hCNT1 -16AA/AG, hCNT2 -17CC, and hENT1 913CC (p = 0.006). The CDA C111T and dCK C-1205T genotypes were also significantly associated with toxicity (p = 0.05 and 0.03, respectively). The CDA 111CC and dCK -1205TT alleles that were associated with poorer survival actually conferred less toxicity. Conclusion. These observations suggest that polymorphic variants of gemcitabine metabolic genes play an important role in affecting the efficacy of gemcitabine treatment for patients with pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Genentech, Merck, sanofi-aventis
Prior Taxane Use in the Lume-Lung 1 Phase III Trial and the Effect on Outcome Following 2Nd-Line Treatment with Nintedanib (Bibf 1120) and Docetaxel in Patients with Advanced Nsclc
Authors: M. Krzakowski, A. Mellemgaard, S. Orlov, J. von Pawel, M. Gottfried, I. Bondarenko, M. Liao, J. Barrueco, B. Gaschler-Markefski, R. Kaiser, S. Novello, J. Douillard, M. Reck
Journal: Annals of Oncology (2014)
In Vitro Infection of Lymphocytes With Marek's Disease Virus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: B W Calnek, K A Schat, W R Shek, C L Chen
Journal: JNCI Journal of the National Cancer Institute (1982)

Suspension cultures of splenic lymphocytes, incubated at 41 degrees C, became infected with Marek's disease virus (MDV) following exposure to a) other infected lymphocytes, b) infected chicken kidney monolayer cultures, or c) cell-free MDV. Both viral antigen expression and virus isolation could be demonstrated after more than 40 passages made by the addition of fresh spleen cells at 2- to 3-day intervals. Susceptibility of spleen cells from bursectomized chickens was markedly lower than that of cells from intact birds. Furthermore, when spleen cell suspensions were depleted of cells having characteristics of bursa-derived cells, e.g., those with surface IgM, Fc receptors, or ability to adhere to nylon wool, the susceptibility of the cell suspension was diminished. Enrichment of the suspension with cells having those features enhanced overall susceptibility. The target cells for virus infection in vitro also were shown to be nonphagocytic, to be of low or medium density, and to bear Ia-like antigen. In vitro susceptibility to infection of spleen cells did not correlate with the genetic susceptibility of the donor to Marek's disease.
Epithelial galectin-3 during human nephrogenesis and childhood cystic diseases.
Authors: P J Winyard, Q Bao, R C Hughes, A S Woolf
Journal: Journal of the American Society of Nephrology (1997)

Galectin-3 is a beta-galactoside-binding protein with putative roles in development, oncogenesis, and inflammation. Its expression in human nephrogenesis has not been previously reported. This study examines galectin-3 expression in early human embryos by Western blot and immunohistochemistry. This 33-kD protein was detected in the apical domain of distal tubules of the mesonephros and also in the mesonephric duct. In the metanephros, the adult kidney precursor, galectin-3 was detected in the apical domains of ureteric bud branches, and there was intense expression in fetal medullary and papillary collecting ducts in both the cytoplasm and plasma membranes. Low levels of galectin-3 were detected in the cytoplasm of a subset of cells in adult collecting ducts; these were alpha-intercalated cells because they expressed basal band 3 protein. In human multicystic dysplastic kidneys, all diseased epithelia had an embryonic apical expression pattern of galectin-3 and, in addition, all cystic epithelia in autosomal recessive polycystic kidneys expressed this molecule. It is concluded that galectin-3 is expressed by cells of the mesonephric duct/ureteric bud lineage, and it is speculated that the different subcellular locations may be implicated in both the regulation of normal growth and differentiation of this lineage, as well as in the pathogenesis of cystic epithelia.
Phase I study of a novel capecitabine schedule based on Norton-Simon mathematical modeling
Authors: M. Theodoulou, T. A. Traina, U. Dugan, D. Lake, M. Fornier, K. Feigin, S. Patil, C. Edwards, L. Norton, C. A. Hudis
Journal: Journal of Clinical Oncology (2007)

1045 Background: We have previously described a mathematical method to optimize chemotherapy dose and schedule (Norton et al, AACR 2005). Capecitabine (C) has activity in breast cancer when conventionally dosed for 14 days (d) q3 weeks (14/7). However, the predicted optimal dosing schedule for C using our model is 7d followed by a 7d rest (biweekly, 7/7). We tested this hypothesis in a Phase I/II study described below. Methods: Eligible patients (pts) have measurable, metastatic breast cancer (MBC), ECOG performance status (PS) =2 and normal organ function. There is no limit to number of prior chemotherapy (CRx) regimens. Pts with prior fluoropyrimidine for MBC are excluded. HER2+ pts must not be candidates for trastuzumab. C is given in divided daily doses for 7d followed by a 7d rest. A standard “3+3” dose escalation scheme employs flat dosing which begins at 1,500mg BID and increases by 500mg/dose level. Primary endpoint is the maximum tolerated dose (MTD), defined as the highest dose for which the incidence of dose-limiting toxicity (DLT) is &lt;33%. Results: 19 pts are now accrued; 17 pts have been treated, 2 withdrew prior to receiving C. Medians: age 47 y (range 34–62 y) and ECOG PS 0 (range 0–2). Sites of MBC: bone 8, viscera 16, soft tissue 11. ER/PR+ 11. HER2+ or unknown 2. Prior adjuvant tx: CRx 17, hormone tx 10. Six pts had adjuvant fluoropyrimidine-based tx. Three pts had 1 prior CRx for MBC; 12 pts received first-line hormone tx for MBC. Fifteen pts had prior anthracycline and taxane. Treatment-related toxicities after a median of 4 cycles (range 1–10) are shown in the table . The MTD has not been reached. Pts continue accrual to the 2500mg/2500mg dose level. Conclusions: Capecitabine 7/7 is well tolerated and allows for safe delivery of higher daily doses than routinely used in practice, as predicted by the mathematical model. Capecitabine 7/7 will be tested in a Phase II program at MSKCC in combination with targeted agents. [Table: see text] No significant financial relationships to disclose.
Abstract 12638: The Activation of STAT3 via CamKII is Critical for the Induction of Cardiac Differentiation by Wnt11 in Bone Marrow Mesenchymal Stem Cells
Authors: Lei Chen, Yu-Ting Xuan, Harold Elias, Amy Cantilena, Ewa Zuba-Surma, Arash Davani, Guangming Cheng, Ou-Li Wang, Robert J Vincent, Yanjuan Yang, Buddhadeb Dawn
Journal: Circulation (2012)

Wnt11, a member of the evolutionarily conserved Wnt family of glycoproteins, plays important roles in cellular migration, proliferation, and differentiation during embryogenesis. Although Wnt11 ind...
Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy
Authors: Stacie M. Jones, A. Wesley Burks, Corinne Keet, Brian P. Vickery, Amy M. Scurlock, Robert A. Wood, Andrew H. Liu, Scott H. Sicherer, Alice K. Henning, Robert W. Lindblad, Peter Dawson, Cecilia Berin, David M. Fleischer, Donald Y.M. Leung, Marshall Plaut, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2016)
Final efficacy and safety results of an Italian, multicenter clinical trial in 312 breast cancer patients with newly diagnosed bone metastases treated with zoledronic acid
Authors: G. G. Cartenì
Journal: Journal of Clinical Oncology (2004)

830 Background: Zometa (zoledronic acid, Zol), a new, highly potent, heterocyclic nitrogen-containing bisphosphonate has demonstrated to significantly reduce the risk of developing skeletal related events (SREs) in a wide variety of solid tumors and multiple myeloma. Methods: In 2001 we started a multicenter, open-label, prospective clinical trial in order to describe the course over 12 months in SREs in breast cancer patients with newly diagnosed bone metastases treated with Zol 4 mg every 3 or 4 weeks via 15-min infusion, in addition to antineoplastic therapy. The main secondary objectives included: bone pain and analgesic use evaluation, quality of life and tolerability of Zol 4 mg. In the 60 participating centers, 312 patients were enrolled. Results: 29.9 % of patients reported at least one SRE. Regarding the proportion of patients with each SRE the following distribution was observed: radiation therapy to bone (22.5%), pathological non vertebral fracture (4.8 %), pathological vertebral fracture (3.5 %), spinal cord compression (2.3 %), hypercalcemia ( 1 %) and surgery to bone (0.6 %).The mean skeletal morbidity rate was 0.9 (sd: 3.8) and the median time to first SRE was not reached. 53.1 %, 23.8 % and 23.1 % of patients reported respectively a decrease, no change and an increase in BPI composite score at the end of the study. 19.3 %, 63.9 % and 16.7 % of patients reported respectively a decrease, no change and an increase in the use of analgesics at the end of the study. Pyrexia (21.5 %), bone pain (10.3%), hypocalcemia (9 %), vomiting (3.2 %), nausea (2.9 %) and asthenia (2.6 %) were the most common adverse events considered related to study drug. No renal safety concerns were observed. Conclusions: This data confirms Zol as an effective and safe therapeutic option for breast cancer patients with newly diagnosed bone metastases. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
The (un)importance of quality of life outcomes in palliative chemotherapy: A review of RCT’s in advanced colorectal cancer
Authors: S. Kort, P. Willemse, J. Habraken, H. Haes, D. Richel, D. Willems
Journal: Journal of Clinical Oncology (2005)

8200 Background: The objective of this study is to clarify what is and what should be the main goal of palliative chemotherapy (PCT). Oncologists disagree whether PCT is intended to improve Quality of Life (QoL), to prolong duration of survival/tumour response, or both. If the goal of PCT would be clear, this would have important clinical consequences for the indication and evaluation of cancer care. By studying trend-setting RCT’s of PCT, we tried to contribute to the discussion. Methods: To define what authors consider to be the primary goal of PCT, 28 RCT’s of PCT in advanced colorectal cancer that used a QoL assessment were selected for a review. From every single article that presented a trial, the results on the different endpoints were compared to the conclusion, given by the authors in the abstract, regarding the use of the experimental arm. Results: We found that most trials in their study design and results focused on both life prolonging and QoL-outcomes. However, authors clearly gave more positive conclusions on basis of life prolonging results, even if the results of the experimental arm were equal to the control arm, than they did on basis of QoL results. Conclusions: Our review showed that the conclusions about the value of experimental arms were mainly focussed on life prolonging outcomes. QoL-outcomes were not of overriding importance, so will rarely be used as the main treatment goal via RCT’s in clinical decision making. Our review shows that in the context of chemotherapy palliative refers to non-curative treatments with life-prolonging intention, however in palliative care it refers to QoL-improvement. To prevent misunderstandings it probably would be better to use the term PCT only in the few cases when the goal of the chemotherapy is QoL-improvement. Otherwise we suggest that the term life prolonging chemotherapy would be clearer. No significant financial relationships to disclose.