tbuckley/cabot-search huggingface dataset:
Survival variation of the ER/PR/HER2 subtypes by race in a single institution.
Authors: C. Parise, V. Caggiano
Journal: Journal of Clinical Oncology (2011)

183 Background: We have investigated breast cancer in California noting variation in survival among race/ethnicity, age, and the ER/PR/HER2 subtypes. The purpose of this study is to determine if similar variation exists in a single institution in California. Methods: We indentified 994 cases of first primary invasive breast cancer between January 2004 and December 2007. Descriptive statistics were used to assess the distributions of race/ethnicity, ER/PR/HER2 subtype, age, and treatment status. Kaplan-Meier survival estimates were computed and the Log-Rank Test used to compare 5-year survival. Results: The most common subtype was ER+/PR+/HER2- (49.6%). There were 221 cases of the HER2-positive subtype; 25% of these were the HER2 over-expressed subtype (ER-/PR-/HER2+). There were 113 cases of ER-/PR-/HER2- (14.0%) and only 3 cases of the ER-positive/PR-positive subtype. The distributions of race and subtype were similar to statewide data for this region. Of the 994 cases, 81% were White, 5.9% Black, 6.5% Asian, 6.2% Hispanic, and 0.3% were American-Indian. For all subtypes and stages combined, 5-year survival was worse for African-Americans (70%) when compared with White patients (83%) Χ 2 = 15.29, p &lt; 0.001. There were no statistically significant differences in mean age of diagnosis among the eight subtypes. Of the 113 cases of ER-/PR-/HER2-, 80 were White, 15 Black, 8 Asian, and 8 Hispanic. Only one Black patient with ER-/PR-/HER2- was younger than age 45. African-American patients with ER+/PR+/HER2+ and ER+/PR-/HER2- were more often diagnosed in stages 3 and 4. The ER-/PR-/HER2- subtype had worse 5-year survival (64%) than both the ER+/PR+/HER2+ (88%) and the ER+/PR+/HER2- (85%) subtypes (p &lt; 0.001). There was no difference in survival by race for the ER-/PR-/HER2- subtype. For ER-positive patients, African-Americans had worse 5-year survival than whites (66% versus 86%) Χ 2 = 16.18, p &lt; 0.001 despite comparable hormonal and chemotherapy regimens. Conclusions: The ER+/PR+/HER2+ subtype does not always mean poor survival. The triple-negative subtype has the worst survival for both Black and White patients. African-American patients with any ER-positive subtype fare poorly. Referral bias and small sample sizes are study limitations.
Pathogenesis of Mammary Carcinomas Induced in Rats by 7, 12-Dimethylbenz[a]anthracene2
Authors: Jose Russo, Joseph Saby, William M. Isenberg, Irma H. Russo
Journal: JNCI Journal of the National Cancer Institute (1977)

The pathogenesis of mammary carcinomas was studied in Spragu-Dawley virgin female rats after gastric Instillation of 7,12-dimethylbenz[a]anthracene (DMBA) at 55 days of age. Nine rats were killed weekly, from the time of DMBA inoculation until the 15th week after treatment. All the glands of each animal were studied in both cleared wholemounts and paraffin sections. The earliest observed lesion was hyperplasia of the end-bud epithelium, which appeared as a multifocal phenomenon as early as 14 days post Inoculation. Intraductal proliferation of end buds evolved to intraductal carcinomas, which formed either cribriform or papillary patterns. Every carcinoma observed was ductal in origin. Differentiation of the alveolar portion of the gland led to adenomas, hyperplastic alveolar nodules, and cysts. The presence of the terminal end buds at the time of DMBA administration was considered to play an important role in the genesis of carcinomas.
Nicotinic receptors in the ventral tegmental area promote uncertainty-seeking
Authors: Jérémie Naudé, Stefania Tolu, Malou Dongelmans, Nicolas Torquet, Sébastien Valverde, Guillaume Rodriguez, Stéphanie Pons, Uwe Maskos, Alexandre Mourot, Fabio Marti, Philippe Faure
Journal: Nature Neuroscience (2016)
Systematic analysis of both steady state and actively translated mRNA transcripts regulated by thymidylate synthase and 5-FU treatment in human colon cancer
Authors: Y. Xi, G. Nakajima, E. Chu, J. Ju
Journal: Journal of Clinical Oncology (2005)

2034 Background: Thymidylate synthase (TS), is a critical target for cancer chemotherapy and is one of the most extensively studied predictive biomarkers for fluoropyrimidine-based chemotherapy. In addition to its critical role in enzyme catalysis, TS functions as an RNA binding protein by regulating its own protein synthesis via a negative autoregulatory mechanism. As an RNA binding protein, TS also regulates the expression of other cellular mRNAs, such as p53 and c-Myc at the translational level. Methods: In this study, genes affected by TS/5-FU treatment at both transcriptional and post-transcriptional levels were investigated using human Codelink array with a TS-depleted human colon cancer C18 cell that had been stably transfected with the human TS cDNA. Both steady-state mRNAs and actively translated mRNAs were isolated from control C18 (TS-), C18 (TS+) cells and C18 (TS+) cells treated with 10 μM 5-FU for 4 hr and 24 hr. Gene expression analysis was performed using GeneSpring 7.0 software. Results: A total of 590 genes were found to be significantly affected (p<0.01, 2-fold cut-off) by TS and 5-FU treatment based on steady state mRNA transcripts. However, there are over 1857 genes were potentially effected by TS and 5-FU treatment based on actively translated mRNA transcripts. This indicates that additional post-transcriptional regulated genes can be captured with profiling actively translated mRNA population. This unique approach provides a comprehensive overview of gene regulation by TS and 5-FU treatment. Many potential novel post-transcriptional regulated genes affected by TS overexpression and 5-FU treatment were identified, including TS, protein phosphatase A2, IGF-II, RNA binding protein 9, and Mad2. The known translational regulated genes such as phosphatase 2A and TS provide the validation of this novel approach. Conclusions: This was the first time that a comprehensive gene expression profile regulated by TS was analyzed at the multiple steps of regulation. Such work may provide a guideline to select marker genes that can be potentially used for predicting therapeutic outcomes for fluoropyrimidine-based chemotherapy. No significant financial relationships to disclose.
Allogeneic stem cell transplantation (allo-SCT) in adult acute lymphoblastic leukemia (ALL)
Authors: S. J. Wu, M. Yao, J. L. Tang, Y. C. Chen, A. L. Cheng, H. F. Tien
Journal: Journal of Clinical Oncology (2007)

17513 Background: Although viewed as a potentially curable disease, the outcome of adult ALL is extremely poor. The role of allo-SCT, a possible curative modality, is of debate. Although the solid evidence is lacking, allo-SCT is viewed as a standard treatment in some institutions and some trials. The objective of the study is to clarify the effect of allo-SCT in the treatment of adult ALL patietns. Methods: From Jan. 1999 to Jun. 2006, we included 103 adult ALL patients whose age were between 15 and 55, the upper limit of age for allo-SCT in this institution. Their data, including clinical characteristics, cytogenetic results, treatment response and outcomes, were collected. To avoid the “immortal-time bias” in assessing the effect of transplant, the results from a time-independent and time-dependent Cox proportional hazards model were compared. We also conducted a population-based study to compare the outcomes of these patients with those diagnosed between Jan. 1986 and Dec.1993 in our institution. Results: There were 46 females and 57 males. The median age was 25.8, with 63 patients (61.2%) younger than 30. The median survival was 21.9 months and the 3-year overall survival was 34.2%. 48 patients(46.6%) received allo-SCT. The transplant conferred to marginally better survival in univariate analysis (p=0.049), but by time-dependent regression method, there was, after adjusting for other risk factors, no survival benefit for patients receiving transplant (HR 1.452, 95% CI 0.766∼2,751, p=0.253). The outcomes of these 103 patients were compared with another group of 69 patients diagnosed in the early period, among whom 13 patients(18.8%) received transplant. Although with higher proportion of patients undergoing allo- SCT, there was no advance in overall survival (p=0.157). Conclusions: In adult ALL, the outcome is still poor. Although there are new treatment protocols and modalities in chemotherapy and transplantation, these advances do not reflect to survival improvement. Transplantation provides limited survival benefit in population-based viewpoint. The candidates of allo-SCT should thus be carefully selected and allo-SCT should not be viewed as a standard in the treatment of adult ALL patients. No significant financial relationships to disclose.
Early results of a phase I clinical trial of capecitabine in combination with CPT-11 for metastatic breast cancer (MBC) pre-treated with anthracycline and taxane
Authors: M. Kashiwaba, T. Inaba, Y. Hayakawa, I. Takiyama, G. Wakabayashi
Journal: Journal of Clinical Oncology (2006)

10750 Background: Capecitabine (C) is administrated with other drugs to improve response rate of single agent and to extend time to progression for MBC expecting up-regulation of thymidine phosphorylase activity. Conversely, administration of CPT-11 (TOP) against MBC is less common while superiority of combination therapy C and TOP is established in metastatic setting of colorectal cancer. Therefore a phase I clinical trial was conducted to determine the recommended dose (RD) of TOP administrated with fixed dose of C (1,657 mg/m 2 /day) against MBC pre-treated with antracycline and taxane. Methods: Five dose level of CPT-11 (80, 90, 100,110 and 120 mg/m 2 ) on Day 1 and 15 and C (1,657 mg/m 2 /day) on Day 1–21 were given every 28 days. A standard “3+3” design is used and dose limiting toxicity is defined in cycle 1. Results: To date, five patients were enrolled from October 2005 to January 2006 and 8 cycles were administrated without grade 3–4 toxicities as followed: 3 pts in Level I (TOP: 80 mg/m 2 ), 2 pts in Level II (TOP: 90mg/m 2 ). 5 pts have archived a response: PR in 1, SD in 2. Conclusions: Combination therapy C and TOP against MBC pre-treated antracycline and taxane is well-tolerated. Enrollment will continue until the RD is identified for further phase II clinical trial. No significant financial relationships to disclose.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, ameliorated capecitabine (X) hand &amp; foot syndrome (HFS) &amp; enhanced survival in metastatic colorectal cancer (MCRC)
Authors: E. H. Lin, G. Ayer, C. Crane, G. Shi, J. Morris, M. Delcos, S. Daniels, M. Rodriguez, N. Janjan, S. Curley
Journal: Journal of Clinical Oncology (2004)

3584 Background: Cyclooxygenase-2 (COX-2) is a putative therapeutic target for MCRC and may also be the culprit of X-induced HFS. Treatment (tx) of MCRC with X + CEL, a specific COX-2 inhibitor, (XCEL) may improve both HFS and survival. Methods: From 2000–2003, 57 unresectable MCRC pts received twice-daily X at 1000 mg/m2/d for 2 wks every 3 wks or Mon-Fri with radiation (RT) plus twice-daily CEL for pain at 200 mg (3 pts at 400 mg). Pts showing radiographic and/or CEA response continued XCEL. RT (35–50.4 Gy) sites were: liver (13 pts), lung (1 pt), pelvis (6 pts), peritoneum (6 pts), and para-aortic nodes (5 pts). Results: Of 57 pts (male: female ratio, 3:1; median age, 65 years [range, 29–80 years]; ECOG performance status of 0–1 [87%], extensive visceral metastases [50%]), 29 pts had failed Irinotecan [IRI] + 5FU/LV (IFL) and 5 pts failed oxaliplatin [LHOP] + IRI (IROX) or LHOP + 5FU/LV (FOLFOX). Of the 33 pts on XCEL ≥ 6 mo, 12 pts took tx for 12–32 mo with 8 pts still on tx. Rate of grade 1 and grade 2 HFS was 30% (17 pts) and 12% (7 pts). Most of the grades 2 HFS were late events (> 6 mo). Grade 3 events were rare: HFS (1 pt), diarrhea (4 pts) and deep venous thrombosis (1 pt). Grade 2 events were: rash (1 pt), agitation (2 pts), fatigue (2 pts), and thrombocytopenia (2 pts). Favorable complete (CR) or partial responses (PR), stable disease > 4 mo, median progression-free (PFS) and overall survival (OS) were noted (Table). 9 pts had post-tx metastectomy and 17 pts (30%) had all three agents (IRI, oxaliplatin, 5-FU). Conclusions: MCRC is a very heterogeneous disease and its survival could be maximized through an individualized, multi-modality tx paradigm. Limited by its retrospective design, XCEL +/- RT may prove to be an active, low-toxic, oral regimen in a planned prospective phase III randomized trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Genentech; Pharmacia; Roche; Pfizer; Novartis
Early response to clozapine in schizophrenia
Authors: R G Stern, R S Kahn, M Davidson, R M Nora, K L Davis
Journal: American Journal of Psychiatry (1994)

Forty schizophrenic patients were treated with clozapine for 5 weeks. Patients were then classified as treatment responders or nonresponders according to a priori established criteria. After only 1 week of treatment, the responders showed a significant decrease on the Brief Psychiatric Rating Scale (BPRS) total score and the psychosis and tension subscale scores. Higher BPRS scores at baseline and larger improvements in BPRS scores after the first week predicted a more favorable outcome in this trial and yielded good classification accuracy.
Emetogenicity of multiday chemotherapy regimens: Drug and patient factors affecting control of CINV
Authors: J. D. Howell, H. Brown
Journal: Journal of Clinical Oncology (2009)

e20683 Background: Multi-day chemo regimens have particular advantages in increasing tolerability and maintaining dose intensity of combination cytotoxic therapy. However repeated daily insults of therapy can make control of CINV challenging. Increased knowledge of factors affecting poor control of multi-day chemo, under current CINV prevention conditions, would be beneficial. Methods: A dataset of 621 patients treated in a blinded, randomised non-inferiority study (Grunberg SM, Gabrial NY, Clark G, MASCC 2007, Abstract # 18) of a granisetron transdermal patch (TDS, Sancuso) and oral granisetron, was analysed. As TDS was shown to be non-inferior to oral granisetron, data from both arms were used. All patients had received 3–5 days of moderately or highly emetogenic chemotherapy. Total Control of CINV over Day 1 and Days 1–3 was used as the efficacy endpoint. Stepwise logistic regression analysis was used to assess the predictive performance of patient and chemotherapy factors. Wald chi-squared statistics and Akaike criteria were used to measure significance of predictive factors and model fit, respectively. Results: The simple sum of emetogenicity scores of each cytotoxic (Grunberg SM,(2005) Evaluation of new antiemetic agents_an update. Support Care Cancer (2005) 13: 80–84) provided best overall prediction of emetogenicity of the multiday regimen. Cisplatin was more emetogenic and doxorubicin less so compared to established scoring (Grunberg SM,(2005) Evaluation of new antiemetic agents_an update. Support Care Cancer (2005) 13: 80–84). Age and gender were significant in predicting control: females &lt;60 and males &lt;40years being at risk. A genitourinary site of cancer was also an independent risk factor. Smoking, alcohol use, previous chemotherapy and performance score had no significant effect on risk of CINV. Conclusions: Established emetogenicity scores, derived from historical data on untreated patients, are relevant to multi-day chemo but could be revised to improve prediction of CINV. Cisplatin has a stronger impact on poor control in multi-day than single-agent scoring predicts. Age and gender factors remain important; but with different age breaks for male and female. These and tumour site factors should be taken into account when designing clinical trials or analysing data relating to antiemetics and CINV. [Table: see text]
The phylogeny of the Hyphochytriomycota as deduced from ribosomal RNA sequences of Hyphochytrium catenoides.
Authors: G Van der Auwera, R De Baere, Y Van de Peer, P De Rijk, I Van den Broeck, R De Wachter
Journal: Molecular Biology and Evolution (1995)

Based on biochemical and ultrastructural data, hyphochytriomycetes are believed to share an ancestor with oomycetes and heterokont algae. In order to study the phylogeny of the hyphochytriomycetes, we determined both the small- and large-subunit ribosomal RNA sequence of Hyphochytrium catenoides. Phylogenetic trees were constructed using the neighbor-joining and maximum-parsimony method and include representatives of Chlorobionta, Fungi, Metazoa, Alveolata, and all known Heterokonta. Our main conclusion is that the hyphochytriomycetes form a monophyletic group with the oomycetes and heterokont algae and that they are probably the closest relatives of the oomycetes. However, the order of divergence between the various heterokont algal phyla and the oomycete-hyphochytriomycete cluster remains uncertain.
Establishment and Characteristics of a Hamster Lung Adenocarcinoma In Vivo and In Vitro 2
Authors: Margaret Terzaghi, John B. Little
Journal: JNCI Journal of the National Cancer Institute (1975)

Several cell lines designated HLAC were derived from primary lung carcinomas induced in Syrian hamsters by polonium-210 or benzo[a]pyrene. Primary tumor nodules were initially transplanted into cheek pouches, and the tumors that grew were passed into tissue culture and into the cheek pouches of other hamsters for continued in vivo passage. By serial passage and cloning, cell lines were isolated with plating efficiencies of 20–50% in vitro and 10–25% when cultured directly from solid tumors. These cells formed adenocarcinomas in vivo. The radiosensitivities in vitro of HLAC-4 and HLAC-14 varied; observed D0 (the inverse of the slope of the exponential portion of the survival curve) values were 80 and 155 rads, respectively; ñ (the dose at which the exponential portion of the survival curve extrapolates to 100% survival) values were approximately 1.8. Survival curves obtained following in situ irradiation of 4- to 5-mm3 HLAC-4 tumors showed a D0 of 80 rads and an ñ of 7. Morphology and growth characteristics of two HLAC cell lines in vivo and in vitro were describe.
Serologic Analysis of the Antigenic Specificities of Simian Virus 40-Transformed Cells and Their Relationship to Tumor-Associated Transplantation Antigen2
Authors: Chou-Chik Ting, John R. Ortaldo, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1974)

In tests with the isotopic antiglobulin technique, the antisera produced by immunization of (BALB/c × C57BL)F1 mice with syngeneic simian virus 40 (SV40) tumor (SVT2) reacted against at least 2 different specificities. Some sera only reacted with the tumor-associated cell-surface antigen (TASA) of SV40-transformed cells. Other sera also reacted with a common antigen found in non-SV40 tumor cells but not in normal spleen cells. Only TASA was found to be correlated with the tumor-associated transplantation antigen. Although all sera reacted with various SV40-transformed cells, they had different patterns of reactivity. These results indicate that the SV40 TASA may be composed either of different molecules or of single molecules with several antigenic determinants.
Exercise-induced bronchoconstriction in schoolchildren
Authors: Joanna Jerzynska, Lukasz Cichalewski, Wlodzimierz Stelmach, Katarzyna Smejda, Iwona Stelmach
Journal: European Respiratory Journal (2014)

Background: Association between exercise-induced bronchoconstriction (EIB) and physical activity has not been investigated in a natural environment in a general pediatric population. The aim of the study was to determine the prevalence of EIB among schoolchildren during physical education (PE).  Methods: 557 children from 7 schools were enrolled. All children attended 45 minutes PE lesson with similar exercise intensity. Pulmonary function tests were performed before and immediately after PE lesson. The diagnosis of EIB was defined as a FEV1 decrease from baseline of ≥ 10% with exercise. Cough and dyspnea after exercise were recorded.  This study was supported by the National Science Centre (NCN) grant number UMO-2012/07/B/NZ5/02684  The study was approved by the Medical Ethical Committee of the Medical University of Lodz.  Results: 557 participants were included into the analysis. After PE lesson, 16,1% children suffered from cough, 5,8% reported dyspnea and 10,4% had more than 10% fall in FEV1 from baseline. Among children with cough, 21,5% had asthma and 17,6% experienced EIB. Among asthmatics (6,6%), 48,6% suffered from cough and 18,2% had more than 10% fall in FEV1 from baseline after PE lesson. EIB was not affected by age, gender, BMI, asthma diagnosi. Only cough (OR: 2.21, 95%CI: 1.16-4.23; p=0.0161) was independently associated with EIB.  Conclusion: We showed a high prevalence of exercise-induced cough and/or 10% fall in FEV1 during activity lesson in a natural environment in a large urban population of schoolchildren. Our results call for another studies addressing the impact of environment on exercise-induced symptoms.
Changing paradigms in the management of breast cancer.
Authors: R J Lee
Journal: Journal of Clinical Oncology (1997)

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.1997.15.6.2476 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9196166 Changing paradigms in the management of breast cancer. R J LeexR J LeeSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.6.2476 PDF "Changing paradigms in the management of breast cancer.." Journal of Clinical Oncology, 15(6), pp. 2476–2477© 1997 by American Society of Clinical Oncology