tbuckley/cabot-search huggingface dataset:
Preoperative endoscopic ultrasound can predict the risk of recurrence after operation for gastric carcinoma.
Authors: J W Smith, M F Brennan, J F Botet, H Gerdes, C J Lightdale
Journal: Journal of Clinical Oncology (1993)

PURPOSE Endoscopic ultrasonography (EUS) has been shown to determine accurately the depth of invasion of the stomach wall in gastric carcinoma. We undertook this study to determine if T (tumor) stage as determined by EUS correlated with recurrence after resection and could be used to identify patients preoperatively at high risk for recurrence. MATERIALS AND METHODS We reviewed the surgical pathology and obtained follow-up data from the first 50 patients who underwent preoperative EUS for staging of gastric carcinoma. Rotating sector-scan ultrasound endoscopes were used with switchable frequencies of 7.5 MHz and 12 MHz. RESULTS Of 50 patients, 43 underwent resection with curative intent and were available for follow-up. The concordance of EUS T stage with pathologic T stage in these patients was 86%. At a median follow-up duration of 25 months, only two of 13 patients with preoperative EUS stage T1 or T2 disease were found to have recurrence, while 23 of 30 patients with EUS stage T3 or T4 disease had recurrence (P = .0002) and 22 died. CONCLUSION We conclude that patients with a preoperative EUS stage T1 or T2 are at low risk for postoperative recurrence, while patients with EUS stage T3 or T4 are at high risk for early postoperative recurrence. The latter patients are reasonable candidates for controlled trials of alternative preoperative management programs, such as chemotherapy, in an effort to improve their poor prognosis.
Comparison of 3 commercially available immunohistochemical tests for EGFR expression in colorectal cancers. Is immunohistochemitry (IHC) reliable?
Authors: J. C. Sabourin, A. Cayre, L. Arnould, F. Bibeau, M.-P. Bralet, P. Rochaix, H. Cure, F. M. Penault-Llorca
Journal: Journal of Clinical Oncology (2005)

9705 Background: IHC appears to be the required test for the selection of patients for a monoclonal antibody based targeted treatment with C225 (Erbitux). To validate the usefulness of IHC, confirmation of assays and scoring systems are mandatory. In an attempt to standardize the immunohistochemical detection of EGFR, we have retrospectively evaluated three commercially available EGFR kits or antibodies and analyzed the discrepancies between the tests in terms of percentage of positive cells, intensity, cut off value and fixatives. Methods: we extracted 230 paraffin embedded samples from a metastatic colorectal cancer trial. For all cases, EGFR expression have been assessed with the FDA approved Dako EGFR pharmaDx kit, the Zymed EGFR kit and the Ventana CONFIRM™ EGFR 3C6 antibody. Different cut off were tested, intensity was scored 0, 1+,2+, 3+ following the suppliers’ recommendations. Results: Performances of the tests i)percentage of positive cells: Ventana > Dako (p<10-7), Zymed > Dako (p = 0,000002), Ventana > Zymed (p=0,75, ns); ii) The intensity of staining was correlated to the percentage of positive cells for Ventana (p < 10-6) and Zymed (p < 10-5). iii) No interaction with staining was identified for any of the fixative, or with the nature of samples. Each technique has pros: full automation for Dako and Ventana tests, easier interpretation with Ventana’s test (counterstaining), lower costs for Zymed kit. Conclusion: our data showed a higher number of positive cases detected by Ventana and Zymed, whatever the cut off value for positivity was. No scoring system showed, to date, its accuracy, and more studies have to be conducted with an evaluation of response to C-225. Whether and how the EGFR status has to be tested for the selection of patients for C225 is still a non-answered question. The proper selection might be through a co-evaluation of other markers involved in EGFR regulation. No significant financial relationships to disclose.
Adult mouse cortical cell taxonomy revealed by single cell transcriptomics
Authors: Bosiljka Tasic, Vilas Menon, Thuc Nghi Nguyen, Tae Kyung Kim, Tim Jarsky, Zizhen Yao, Boaz Levi, Lucas T Gray, Staci A Sorensen, Tim Dolbeare, Darren Bertagnolli, Jeff Goldy, Nadiya Shapovalova, Sheana Parry, Changkyu Lee, Kimberly Smith, Amy Bernard, Linda Madisen, Susan M Sunkin, Michael Hawrylycz, Christof Koch, Hongkui Zeng
Journal: Nature Neuroscience (2016)
Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients.
Authors: G M Clark, M C Mathieu, M A Owens, L G Dressler, L Eudey, D C Tormey, C K Osborne, K W Gilchrist, E G Mansour, M D Abeloff
Journal: Journal of Clinical Oncology (1992)

Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF).All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years.Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012).S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node-negative breast cancer patients with small, ER-positive tumors.
Capecitabine plus Vinorelbine: An active drug combination with evidence of synergy and sequence dependence
Authors: Cheryl Brewer, Barbara Sommers, Steven Evans, Cheryl Kollin, Yong-Zhuang Su, Robert Nagourney
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2811 

Introduction: Capecitabine, (Cap) is a pro-drug of 5 Fluorouracil (5FU) that, via sequential metabolism, delivers intracellular 5FU under the action of thymidine phosphorylase (TP). TP is over-expressed in human tumors and up-regulated by exposure to cytotoxic drugs. Docetaxel & Cap has been studied in breast cancer revealing activity but with toxicity. Vinorelbine (Vin) has a favorable toxicity profile, making it attractive for combination with Cap. We applied a human tumor 1o culture platform (EVA/PCD®) to examine the activity of Vin/Cap in human tumors, including breast, NSCLC & Ovary.    Methods: 861 specimens were examined by EVA/PCD®. Using modified Z-score, the activity profile favored breast, followed by NSCLC and Ovary. Synergy analyses by median effect, revealed antagonism in 21%, synergy in 25% and favorable interactions in and additional 47%. Further analyses that compared the metabolic intermediate DFUR (TP substrate) with 5FU revealed superior activity for DFUR over 5FU and evidence of sequence dependence, only for DFUR, favoring Vin or Taxane followed by Cap. Based upon these findings a series of patients have received the Vin/Cap regimen with several durable remissions observed in heavily pre-treated ovarian and uterine cancers.Conclusions: 1) Vin/Cap has activity in several human tumor types. 2) The superior activity for DFUR over 5FU and evidence of sequence dependence for Vin/Taxane sequenced to Cap is consistent with a role for TP up-regulation in these drug combinations. 3) The observed clinical activity in select, drug refractory patients, may offer a well tolerated option in some patients with advanced/recurrent malignancies including gynecologic primaries. 4) Further clinical study of this combination with consideration of pretreatment candidate selection appears warranted.
NSAIDs, osteoarthritis, and colorectal cancer risk: Can administrative data provide a window into the effectiveness of a cancer prevention?
Authors: E. B. Lamont, L. E. Dias
Journal: Journal of Clinical Oncology (2006)

1022 Background: Randomized trials show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of pre-cancerous polyps and may reduce the risk of invasive colorectal cancer (CRC), but studies of effectiveness have not been reported. Given the ubiquity of NSAIDS, existing population-level data sources may be leveraged to provide a window into the effectiveness of NSAIDs in CRC prevention. Methods: With data from the National Center for Health Statistics’ National Ambulatory Medical Care Survey, we established the suitability of the diagnosis of osteoarthritis (OA) as an instrument or marker of NSAID therapy among the elderly. With data from the National Cancer Institute’s SEER-Medicare program, we then identified elderly Medicare beneficiaries diagnosed with CRC in 1995 and compared them to elderly Medicare beneficiaries without histories of CRC according to antecedent OA diagnoses in Medicare claims files. Using logistic regression, we estimated the odds of CRC diagnosis among elderly Medicare beneficiaries with histories of OA compared to those without. As a control analysis, we also estimated the odds of a breast cancer diagnosis among those elderly female Medicare beneficiaries with histories of OA compared to those without. Results: Within the SEER-Medicare data files, we identified 4,599 elderly patients with a SEER diagnosis of invasive CRC and 100,270 patients without a SEER diagnosis of invasive CRC. Individuals with a diagnosis of OA in Medicare claims in the prior three years had an 18% lower risk of being diagnosed with CRC than individuals whose claims did not reflect antecedent OA (OR 0.82, 95% CI: 0.77–0.88). No association between antecedent OA and subsequent breast cancer (OR 0.99, 95% CI: 0.92–1.05) was found. Conclusions: In this case-control study that treats certain ICD-9 codes within Medicare claims as instruments of NSAID use, we find that elderly Medicare beneficiaries with ICD-9 codes for OA have an18% lower odds of being diagnosed with invasive CRC. Further, the magnitude of the CRC odds reduction is similar to what would be expected from the excess NSAID use alone. No significant financial relationships to disclose.
Genome-wide expression profiling and tissue array analysis for prediction of recurrences in stage II-III colorectal cancer (CRC)
Authors: V. Boige, M. Svrcek, S. Michiels, M. Pocard, V. Laville, F. Drusch, J. Sabourin, P. Dessen, M. Ducreux, V. Lazar
Journal: Journal of Clinical Oncology (2006)

3572 Background: Despite substantial progress in molecular pathogenesis of colon cancer (CC), no reliable biomarkers of outcome have yet been identified in patients with resected stage II-III CC. Methods: We analyzed genome-wide mRNA expression profiles in 20 stage II or III left side CC from 10 patient who developed metastasis (M+) and 10 disease free patients followed up for at least 4 years (M-) using high-density oligonucleotide microarrays (Agilent technology). RNA from tumor tissue (T) was hybridized against normal tissue (NT) from the same patient and each experiment was replicated 4 times (with 2 dye-swaps). The goal was to select genes both differentially expressed between T and NT and between M+ and M-. A tissu-array was constructed using 212 stage II and III resected CRC (164 CC, 64 rectal cancers) and their matched NT. For survival analysis, immunohistochemistry (IHC) data was dichotomized at the median value. Results: Analysis of microarray data yielded 27 genes that had a 2-fold difference between the expression in T and NT in at least 5 out of 20 patients and for which the average expression was significantly different between M+ and M- (p&lt;0.01, t-test). Among the 6 most differentially expressed genes between M+ and M- in T, 4 of them were found to be involved in interferon γ pathway and could be evaluated by IHC: CXCL9, CXCL13, PPARγ, THSD. In order to assess macrophage and natural killer (NK) cell infiltration, CD68 and CD57 were also analyzed. Intensity was measured by semi-quantitative scores for the first 4 genes and by the number of infiltrating cells for the others. CXCL9, PPARGγ, CXCL13, CD57 and CD68 were significantly underexpressed in T as compared to NT (p&lt;0.0001, paired t-test). The logrank test stratified by cancer site indicated that high IHC expression of CD57 possessed a significantly better recurrence-free survival (RFS) than those low expression (p=0.004). Multivariate Cox analysis identified tumor site (p=0.001), node stage (p&lt;0.001) and CD57 (p=0.002) as independent predictors of RFS. Conclusions: NK cell infiltration within colorectal cancers is associated with prolonged recurrence-free survival in stage II and III CRC. No significant financial relationships to disclose.
Elevated osteopontin (OPN) plasma levels are highly prognostic in advanced non-small cell lung cancer (NSCLC): Analysis of SWOG S0003
Authors: P. C. Mack, M. W. Redman, K. Chansky, S. K. Williamson, N. Farneth, P. N. Lara, Q. Le, P. H. Gumerlock, J. J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2006)

7198 Background: OPN is a secreted glycoprotein with a diverse array of functions, including induction of uPA &amp; increased cell migration. OPN has been shown to be elevated in a number of tumor types, &amp; its downregulation reduces tumorigenicity &amp; metastasis in tumor models. High levels have also been associated with tumor hypoxia/angiogenesis, as are vascular endothelial growth factor (VEGF) &amp; plasminogen activator inhibitor (PAI-1). We hypothesized that secreted levels of these biomarkers would correlate with clinical outcome after treatment. Methods: Plasma concentrations of OPN, VEGF &amp; PAI-1 were measured by ELISA in 160 NSCLC patients enrolled on the Southwest Oncology Group (SWOG) trial S0003 (paclitaxel/carboplatin ± the hypoxic cytotoxin tirapazamine). Post-treatment plasma samples were available in 56 patients. Results: Baseline OPN plasma levels correlated significantly with patient overall survival (OS). High interpatient variability was observed, with levels ranging from undetectable to 2560 ng/ml, (median: 606.5 ng/ml). When dichotomized, median OS was 11 months for patients below median OPN levels &amp; 7 months for those above (p = 0.004). Survival decreases with increasing OPN concentration. Furthermore, OPN levels correlated with response rate (RR) (median responders: 497; median non-responders: 698 ng/ml. Wilcoxon rank-sum p = 0.03). No association between baseline levels of either VEGF or PAI-1 with RR or OS was observed. However, plasma levels of both PAI-1 &amp; VEGF were significantly inter-related &amp; trended together (p &lt; 0.0001), &amp; both decreased significantly after treatment (p = 0.0004 &amp; 0.04, respectively). Median decrease: OPN: 17%, PAI: 44%, VEGF: 42%. No significant differences were observed between study arms, suggesting that OPN is prognostic in NSCLC, but not predictive for response to tirapazamine. Conclusions: 1) There is a great need for development of tumor biomarkers which can be serially assessed pre- &amp; post-therapy. 2) High OPN plasma levels were significantly associated with reduced RR &amp; OS for patients on this trial. OPN is a strong candidate for inclusion in a panel of prognostic (&amp; perhaps predictive) markers for NSCLC. Supported by the Hope Foundation &amp; R01-CA107228. No significant financial relationships to disclose.
Phase II study of erlotinib combined with cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: D. Herchenhorn, F. L. Dias, R. M. Pineda, A. J. Fonseca, M. Bezerra, C. G. Ferreira, R. E. Knust, K. Fontão, R. G. Martins
Journal: Journal of Clinical Oncology (2007)

6033 Background: Preclinical data indicates synergy of erlotinib with both cisplatin and radiotherapy (RT). We previously reported the phase I results with the dose of erlotinib defined as 150 mg/day. Methods: Patients (pts) with stages III and IV SCCHN were included. Treatment consisted of RT (70.2 Gy in 8 weeks), and cisplatin (C) (100mg/m 2 , q 21 days for 3 doses), both starting on Day 8. Erlotinib (E) was started on Day 1 and continued until the end of RT. Patients with N2/N3 disease were evaluated for elective neck dissection post RT. Results: Thirty one pts have been accrued to the study. Median age was 55 years (35–73), 13 pts had larynx carcinoma (stage III 9pts, IVA 3pts, IVB 1pts), 13pts oropharynx (stage III 2pts, IVA 8pts, IVB 3pts) and 5pts hypopharynx (stage III 1pt, IVA 4pts). Twenty five pts completed treatment and are evaluable for response and toxicity. Grade III or IV toxicity included: in-field dermatitis (14pts), nausea (13pts), mucositis (9pts), emesis (8pts), cutaneous infection (3pts), acneiform rash (7pts), fatigue (7pts), dysphagia (6pts), respiratory infection (4pts), neutropenia (1pt), diarrhea (1pt) and 1pt died due to sepsis. The dose of C was reduced in 4pts and withheld in 3pts; RT was delayed in 6 pts (median of 8 days). Twenty one pts (84%) required enteral feeding. Response was accessed by endoscopy with biopsy and CT/MRI scans. Twenty one pts (84%) had complete pathological response, 2 had residual disease and were submitted to salvage surgery, and 1 had disease progression. The median follow-up is 10.8 months. Five pts (23%) had a local relapse. Nineteen pts are disease-free (16 with organ preserved), 2 alive with disease, and 3 pts died due to disease progression. Conclusions: The combination of RT+C+E showed a high complete pathological response and acceptable toxicity, despite the high incidence of grade III/IV in-field dermatitis. These results encourage the design of a phase III trial. Final results will be presented at the meeting. No significant financial relationships to disclose.
Abstract 14682: The Pi 3-kinase Isoform p110alpha is Essential for Neointima Formation Following Percutaneos Coronary Intervention (pci) by Mediating Vascular Smooth Muscle Cell Proliferation, Migration and Survival
Authors: Joana Jesus, Marius Vantler, Olli Leppanen, Eva Berghausen, Evren Caglayan, Hendrik ten Freyhaus, Jean Zhao, Florian Blaschke, Stephan Rosenkranz
Journal: Circulation (2012)

Proliferation, migration and survival of vascular smooth muscle cells (VSMC) play a pivotal role in the development of neointima formation following percutaneos coronary intervention (PCI) and are ...
Outcome of cancer patients admitted through the emergency department (ED) of a comprehensive cancer center: A call for ED-based palliative care.
Authors: Ahmed F. Elsayem, Julio Silvestre, Kelly W. Merriman, Patrick S. Chaftari, Carmen E. Gonzalez, Sai-ching J. Yeung
Journal: Journal of Clinical Oncology (2014)

194 Background: The National Cancer Policy Forum advocated for improving quality of end life care, and reducing cost for cancer patients. Identifying those at high risk for Intensive Care Unit (ICU) admission, and hospital death may allow earlier palliative care and avoid futile interventions. The purpose of this study is to examine risk factors for ICU admission, and hospital death among cancer patients admitted through the emergency department (ED). Methods: We queried MD Anderson Cancer Center databases for all patients who visited our ED in 2010. ICU admission and hospital deaths of these patients were reviewed, and individual patients’ data were analyzed. Results: In 2010, 16,038 ED visits were made by 9,246 unique cancer patients. Of these patients, 5,362 (58%) were admitted to the hospital at least once (range 1-13 admits). Of all patients admitted through the ED, 697 (13%) were admitted at least once to ICU. Of all patients admitted, 11% died during hospitalization; of those, 29% died in ICU. Among patients who died in ICU, 73/233 (31.3%) had hematologic malignancies and 96/354 (27.1%) had solid tumors (P&lt;0.001). Patients admitted to ICU had median lengths of hospital stay (MLOS) of 13 days for hematologic and 8 days for solid tumors (P&lt;0.001; using means); patients without ICU admission had MLOS of 6 and 5 days, respectively (P&lt;0.001). In a multivariate logistic regression model for predicting in-hospital mortality, we found that ED presenting symptoms of respiratory distress or altered mental status; primary tumor of lung cancer, leukemia, unknown primary, or lymphoma; and nonwhite ethnicities were independent predictors of death. Insignificant factors included age, gender, residence, fever and pain. Conclusions: Cancer patients admitted through the ED experience high ICU admission rate, and hospital mortality. Lung and certain other cancers; race; and symptoms of respiratory distress and altered mental status were associated with increased risk of in-hospital death. Patients with these risk factors may benefit from efforts to improve palliative care and prevent futile interventions.
A comparative study of predictive criteria in the predisposition of homicidal adolescents
Authors: I B Sendi, P G Blomgren
Journal: American Journal of Psychiatry (1975)

The authors evaluated the criteria that are cited in the literature as predictive of homicidal predisposition. They applied three categories of criteria--clinical, developmental, and environmental factors--to a study group of 10 adolescents who had committed homicide, 10 who had threatened or attempted homicide, and 10 hospitalized controls. Their findings did not support the presence of a well-crystallized predisposition for homicidal behavior in this population, but they did show that the adolescents who committed homicide were psychotic-regressive and those who threatened or attempted homicide were organic-impulsive. The study strongly suggests the importance of environmental factors in reinforcing homicidal behavior.