tbuckley/cabot-search huggingface dataset:
Identification of lung cancer risk biomarker candidates comprising transcript abundance levels of antioxidant, DNA repair, and transcription factor genes
Authors: James Willey, Thomas Blomquist, Erin Crawford, sadik Khuder, D'Anna Mullins, Youngsook Yoon, Jeffrey Hammersley, mohammed Al-Baghdadi, anas Balaa
Journal: Cancer Research (2008)

1894   Lung cancer is the leading cancer killer of both men and women in the United States and approximately 90% of cases can be attributed to cigarette smoking. The high death rate is in part because the disease typically is in advanced stage at time of diagnosis. High resolution coaxial tomography (HRCT) offers promise to markedly increase survival through diagnosis at early stage. However, the potential cost of screening is very high because there are greater than 40 million active or ex-smokers. Because only 10-15% of heavy smokers develop lung cancer, a biomarker that accurately predicts individuals at greatest risk could substantially reduce cost of screening. Previously, we published data supporting the hypothesis that individuals with sub-optimal regulation of transcript abundance (TA) for certain antioxidant and DNA repair genes in their normal bronchial epithelial cells were more likely to develop bronchogenic carcinoma. Here we assessed the TA levels of these antioxidant and DNA repair genes, along with TA levels of transcription factors that regulate them, in the normal bronchial epithelial cells of 25 lung cancer and 24 non-lung cancer individuals using standardized, quantitative RT-PCR. A computational model was developed to identify the “best” threshold level(s) of TA separating cancer from non-cancer individuals. Depending on whether the TA level for a gene was above or below the threshold, a subject was assigned a value of 1 or 0 for that gene. The values for each of 15 genes were totaled for each subject. The 15 genes in HGNC format are CEBPG, E2F1, E2F6, XRCC1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1 and CAT. For the composite 15 gene biomarker, cross-validation by logistic procedure estimated a total value cut-off of greater than or equal to 7 out of 15 genes as a biomarker for lung cancer individuals, which yielded an estimated accuracy of 84%, sensitivity of 88% and specificity of 79%. Recently, a 16 gene composite biomarker comprising the original 15 gene set plus ERCC1 demonstrated by cross-validation with logistic procedure an estimated total value cut-off of greater than or equal to 8 out of 15 genes as a biomarker for lung cancer individuals, which yielded an estimated accuracy of 82%, sensitivity of 88% and specificity of 75%. We hypothesize that at least some of the non-lung cancer individuals with positive result are at increased risk and that this will become manifest with additional time. Currently, cross-validation of additional composite biomarkers is underway to find the best set of genes which most reliably separates cancer from non-cancer. These results have justified a larger prospective study to determine whether these composite biomarkers will be useful in predicting risk for lung cancer in current and former smokers.
Effects of a single 5 mg infusion of zoledronic acid and oral risedronate (5 mg/day) on bone remodeling over one year in patients with glucocorticoid-induced osteoporosis
Authors: K. G. Saag, Jean-Pierre Devogelaer, D. M. Reid, P. Sambrook, S. Goemaere, S. Ish-Shalom, Julien Collette, P. Papanastasiou, A. Ferreira, E. F. Eriksen, T. Fashola, O. Schoenborn-Kellenberger, D. Chappard, Jean-Yves Reginster
Journal: Annals of the Rheumatic Diseases (2008)
“He’s taken longer to die than a horse”
Authors: Fay Murray-Brown
Journal: BMJ (2015)

A 70 year old dairy farmer was admitted acutely with bronchopneumonia two months after a diagnosis of glioblastoma, for which he received palliative radiotherapy.

Unfortunately, despite maximal antibiotic treatment, he deteriorated and his condition was considered irreversible. The medical team told his family that as he was unlikely to survive, all active treatments should be stopped. Over the next three days he was mostly awake and, although confused, was communicating with his family. On day 5 he became unconscious and was transferred to the local hospice.

Once there, his wife described his symptoms and signs in animal terms. She helped manage their farm and kept horses. …
Evaluation of the contribution of individual gene groups to a 17-gene prognostic prostate cancer signature.
Authors: Dejan Knezevic, Ruixiao Lu, Emily Burke, Megan Rothney, Nan Zhang, Phillip G. Febbo, H. Jeffrey Lawrence
Journal: Journal of Clinical Oncology (2015)

101 Background: A 17-gene biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) has been validated as a predictor of adverse pathology and biochemical recurrence (BCR) in clinically very low to intermediate-risk prostate cancer patients. The assay measures expression of 12 cancer and 5 reference genes that are combined to calculate a Genomic Prostate Score (GPS; scaled 0-100), providing a biologic measure of tumor aggressiveness. The cancer genes represent four biological pathways: androgen signaling, stromal response, cellular organization and proliferation. We examined the effects of variation in quantitative expression of individual gene groups on GPS results and prediction of clinical risk. Methods: The first 3,500 tumor specimens processed in the Genomic Health Inc.’s reference laboratory were included. Expression of individual genes was measured and expression of the four gene groups and GPS calculated. For each gene group, GPS of patients with the lowest 5% expression levels were contrasted with GPS of patients with highest 5% expression levels. Results: Percentages of NCCN very low, low and intermediate patients were 28%, 37%, 30%; median age was 65. Mean and median GPS were 24.6 (SD 12.0) and 23 (range 0-90). Individual gene groups exhibited wide expression ranges (e.g. proliferation-16-fold difference (FD) vs. cellular organization &gt; 8000 FD). Large differences in expression of each gene group were reflected in GPS values and, based on a prior clinical validation study, translate into large differences in BCR risk (Table). Conclusions: Each of the four gene groups show large variations in expression, meaningfully affect the GPS, and contribute to the prediction of PCa aggressiveness. [Table: see text]
Preceding Chronic Course and Watch and Wait Practice For Moderate Aplastic Anemia (MAA) Are Associated With Low Response Rate and Poor Long-Term Outcome After Immunosuppressive Therapy (IST)
Authors: Alexander Kulagin, Igor Lisukov, Maria Ivanova, Irina Golubovskaya, Irina Kruchkova, Sergey Bondarenko, Vladimir Vavilov, Natalia Stancheva, Elena Babenko, Natalia Pronkina, Vladimir Kozlov, Boris Afanasyev
Journal: Blood (2013)
Sepsis-induced immune dysfunction: can immune therapies reduce mortality?
Authors: Matthew J. Delano, Peter A. Ward
Journal: Journal of Clinical Investigation (2016)

Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.
Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling
Authors: Fernando G Osorio, Clara Soria-Valles, Olaya Santiago-Fernández, Teresa Bernal, María Mittelbrunn, Enrique Colado, Francisco Rodríguez, Elena Bonzon-Kulichenko, Jesús Vázquez, Montserrat Porta-de-la-Riva, Julián Cerón, Antonio Fueyo, Juan Li, Anthony R Green, José M P Freije, Carlos López-Otín
Journal: Nature Medicine (2015)
Phase II study of sorafenib with gemcitabine and erlotinib (GES) in first-line advanced pancreatic cancer.
Authors: D. J. Cohen, L. P. Leichman, E. Love, T. Ryan, C. G. Leichman, E. Newman, B. Levinson, H. S. Hochster
Journal: Journal of Clinical Oncology (2011)

266 Background: Addition of erlotinib (E) to gemcitabine (G) results in improved OS for patients (pts) with advanced pancreatic cancer. Many pancreatic tumors have constitutively activated ras/raf pathways and overexpress VEGF. Sorafenib (S), a multitargeted tyrosine kinase inhibitor, including VEGR 1-3, PDGFR-α and β and the RAF/MEK/ERK pathway, when combined with G and E may synergize, resulting in a more complete blockade of the signal transduction cascade in pancreatic cancer growth and progression, and improved outcome. Methods: Pts with previously untreated, histologically confirmed, unresectable pancreatic adenocarcinoma, PS 0-1, and adequate organ function were eligible and received G 1,000 mg/m 2 over 30 min qw x 3 every 4w. E 150 mg PO daily and S 400 mg PO bid were given continuously. CT scans were performed every 2 cycles (8w). Primary endpoint included PFS at 4 mos and secondary endpoints included safety and tolerability of the novel combination, RR, and OS. Results: 45 pts enrolled, 44 evaluable for toxicity(1 not treated), and 30 evaluable for response. Median age was 64 (45-84), 32 males (71%), 43 (96%) had metastatic disease, PS was 0 in 26 (58%). Median number of cycles was 2 (0-10). Grade (gr) 3 toxicity included: thrombocytopenia 5; diarrhea 4; vomiting 4; HFS, hyperbilirubinemia, hyperglycemia and SOB each 3 pts; 1 bowel perforation and 1 epistaxis. Gr 4 toxicity included 1 each: bowel perforation, GI bleed, transaminitis, hyperglycemia and sepsis with hypotension. 2 patients only required dose reduction of S for HFS. There were 2 PR (7%), 13 SD (43%), overall RR of 7% and DCR of 50%. Median TTP 111 days (95% CI = 53-175) and median OS 195 days (144-290). PFS at 16 weeks was 49%, just reaching statistical significance. Conclusions: The combination of G and E plus S in the treatment of advanced pancreatic cancer is a well tolerated regimen without significant increased toxicity as compared to G alone, except for very manageable cutaneous reactions. While the primary endpoint met our pre-determined criteria (compared with NCIC PA.3), this study does not suggest a major benefit for addition of S to G-E when compared to published data. Supported in part by grants from Bayer Healthcare Pharmaceuticals/Onyx and OSI. No significant financial relationships to disclose.
901 VITAMIN D STATUS AND LIVER HISTOLOGY IN CHRONIC HEPATITIS C GENOTYPE 1 INFECTION: ANALYSIS OF THE AUSTRALASIAN CHARIOT STUDY COHORT
Authors: M.T. Kitson, G.J. Dore, P. Button, G. McCaughan, D. Crawford, W. Sievert, M. Weltman, W. Cheng, S.K. Roberts
Journal: Journal of Hepatology (2012)
Functional antigen presenting cells generated from human dendritic cells (DC) derived induced pluripotent stem cell lines
Authors: Arvind Chhabra
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Human induced pluripotent stem cells (iPS) represent a unique source to create donor specific cells of choice. We here report the generation of induced pluripotent stem cell (iPS) lines from human dendritic cells (DC), through a non-integrating RNA virus, sendai virus, expressing
Hopelessness and attempted suicide: a reconsideration
Authors: A D Pokorny, H B Kaplan, S Tsai
Journal: American Journal of Psychiatry (1975)

The authors administered measures of depression, hopelessness, and strength of suicidal intent to a sample of 112 suicide attempters. The results for the 55 subjects diagnosed as depressive and admitted within 72 hours after their attempt were compared with results obtained by Minkoff and associates using comparable measures. Contrary to the findings of the earlier study, there was a lower correlation between hopelessness and intent than between depression and intent. The authors suggest that demographic differences between the two samples may provide explanations for this descrepancy, in the that they reflect the presence or absence of external societal supports that may influence the suicidogenic potential of hopelessness.
Activation of Epstein-Barr Virus in Hybrid Cells
Authors: Kwong Y. Tsang, William D. Hann
Journal: JNCI Journal of the National Cancer Institute (1977)

Human-primate hybrid cell lines were established by fusion of African green monkey kidney cells (VERO) with lymphoblastoid cells from patients with infectious mononucleosis (IM)(IMK101) and from Burkitt's lymphoma culture (HR1K). Both Epstein-Barr virus (EBV)-specific antigens and EBV particle-containing cells increased in the hybrid lines (IMK1-1/VERO,HR1K/VERO). Treatment of the hybrids with 5-bromodeoxyuridine induced more antigen-positive and more virus-containing cells. EBV could be activated from IM lymphoblastoid cells by fusion of the lymphoblastoid cells with the VERO cells. The increase of viral antigens and virus particles may have been due to the cellular interaction between VERO cells and the lymphoblastoid cells or to a possible derepressor supplied by the VERO component of the hybrid. Virus derived from the HR1K cell line was replicated in the human-primate hybrid, but further investigation may be necessary to determine if it was identical to the EBV derived from the human cell line.
Antitumor activity of combination 5,10-methylenetetrahydrofolate, 5-fluorouracil, and anti-vascular endothelial growth factor against human colorectal HT-29 tumors in nude mice
Authors: M. J. Cantwell, C. P. Spears, J. M. Robbins
Journal: Journal of Clinical Oncology (2004)

3768 Background: Folinic acid (leucovorin) has been used as the standard combination therapy as a modulator of 5-fluorouracil (5-FU) for cancer treatment. However, leucovorin is inactive directly and must undergo several metabolic transformations to its active metabolite 5,10-methylenetetrahydrofolate (CoFactor) to be effective. In contrast, CoFactor supplies 5,10-methylenetetrahydrofolate directly and has demonstrated enhancement of the antitumor effects of 5-FU in Phase I/II human clinical trials for colorectal and breast cancer. To determine if the antitumor activity of CoFactor/5-FU could be enhanced further, we examined its use in combination with a recombinant antibody specific for vascular endothelial growth factor (αVEGF), an inhibitor of angiogenesis, against human colorectal HT-29 tumors in nude mice. Methods: 6–8 week old nude mice (nu/nu) were inoculated subcutaneously with 2 x 106 HT-29 cells. When tumors reached 0.1 to 0.3 cm3 in volume, mice were treated with various combinations of 5-FU, CoFactor, leucovorin, and αVEGF administered by intraperitoneal injection. All drugs were dosed daily (0.6 mg/mouse/drug) for five consecutive days with the exception of αVEGF, dosed once (100 μg/mouse) on day 1. In addition, CoFactor or leucovorin were injected 20 minutes prior to 5-FU injection. Tumor volumes were calculated every 2 to 3 days. Results: One month following treatment, we observed smaller mean tumor volumes in mice treated with combination CoFactor/αVEGF/5-FU (0.48 cm3 ± 0.1, n=8, mean ± SEM) than mice treated with either 5-FU alone (0.75 cm3 ± 0.1), CoFactor/FU (0.52 cm3 ± 0.08), or leucovorin/5-FU (0.71 cm3 ± 0.09). Furthermore, there was greater survival of mice treated with CoFactor/5-FU either with or without αVEGF (57% and 88%, respectively) compared to mice treated with only 5-FU (25%). Conclusions: This study suggests combination CoFactor/αVEGF/5-FU treatment might have utility as a colorectal tumor therapy with greater antitumor activity than standard 5-FU therapies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ADVENTRX Pharmaceuticals
Pathologic complete response (pCR) in patient subgroups: An analysis of ABCSG-24, a phase III, randomized study of anthracycline- and taxane-based neoadjuvant therapy with or without capecitabine in early breast cancer (EBC).
Authors: G. G. Steger, R. Greil, R. Jakesz, A. Lang, B. Mlineritsch, M. Rudas, C. Marth, H. Stoeger, C. F. Singer, M. Gnant
Journal: Journal of Clinical Oncology (2010)

530 Background: pCR is a predictor of better outcomes, including improved survival. The integration of capecitabine (C) into a standard neoadjuvant regimen of epirubicin and docetaxel (ED) has been shown to significantly improve pCR rate in patients with EBC. This preplanned subgroup analysis was undertaken to determine whether the pCR benefit with C was achieved irrespective of baseline risk factors. Methods: Patients with biopsy proven operable breast cancer ± nodal involvement without distant disease who were scheduled to receive neoadjuvant therapy were randomized to 6x ED every 21 days (d1: E 75 mg/m2 iv and D 75 mg/m2 iv, d2: pegfilgrastim 6 mg2) with or without C (1,000 mg/m2 bid d1–14). The accrual target was 536 patients (510 eligible pts, power = 83%, p < 0.05) to detect a difference in pCR of 16% (ED±T) vs. 27% (EDC±T). Patients were stratified according to tumor stage (T1-4), clinical nodal stage (neg vs. pos), menopausal status (pre vs post), histology (ductal + mixed vs. lobular), hormone receptor status (HR; neg vs. pos), HER2 status (neg vs. pos), and grade (G; G1 + 2 vs. G3). Results: 512 pts are eligible for toxicity and efficacy assessment in the ED (n = 257) and EDC (n = 255) groups. Overall, the addition of C to ED was associated with higher but manageable toxicity and a significantly increased pCR rate (24.3% vs. 16.0%; p = 0.02). Odds ratios (OR; logistic regression analysis) for reaching a pCR demonstrated that the addition of C to ED was associated with a significantly greater chance of achieving a pCR in patients with smaller tumors (OR 0.61, 95% CI 0.44-0.84; p < 0.003), ductal histology (OR 0.39, CI 0.16-0.93; p = 0.03), HR negative disease (OR 0.21, CI 0.14–0.34; p < 0.0001), and G3 differentiation (OR 3.67, CI 2.3–5.9; p < 0.0001). Patients were equally likely to achieve a pCR with the addition of C to ED regardless of clinical nodal status, menopausal status, and HER2 status. Conclusions: The integration of capecitabine into standard ED neoadjuvant therapy achieves a significant pCR benefit even in patients with poor prognosis, such as those with hormone receptor negative or high grade disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Roche, sanofi-aventis Amgen, Roche, sanofi-aventis Amgen, AstraZeneca, GlaxoSmithKline, Janssen-Cilag, Novartis, Roche, sanofi-aventis
Allogeneic Stem Cell Transplantation for High-Risk Acute Myeloid Leukemia: No Increase in Relapse with Alemtuzumab-Depleted Grafts.
Authors: Kirsty J. Thomson, Karl S. Peggs, Emma C. Morris, Asim Khwaja, David C. Linch, Anthony H. Goldstone, Stephen Mackinnon
Journal: Blood (2005)
Gemcitabine, oxaliplatin (GEMOX) and cetuximab for treatment of hepatocellular carcinoma (HCC): Results of the phase II study ERGO
Authors: S. Louafi, M. Hebbar, O. Rosmorduc, C. Tesmoingt, A. Asnacios, O. Romano, L. Fartoux, P. Artru, T. Poynard, J. Taieb
Journal: Journal of Clinical Oncology (2007)

4594 Background: A promising efficacy of the GEMOX combination was previously reported in HCC. Moreover, the EGFR signalling pathway is involved in hepatic carcinogenesis and tumor progression. This phase II study of GEMOX plus cetuximab was therefore undertaken in patients with unresectable HCC. Methods: 44 patients were included in the study between November 2005 and October 2006. All patients received cetuximab (initial dose 400 mg/m 2 BSA then 250 mg/m 2 weekly) combined with GEMOX (gemcitabine 1000 mg/m 2 , Day 1 and oxaliplatin 100 mg/m 2 , Day 2), repeated every 14 days until disease progression or limiting toxicity. Inclusion criteria were: histologically proven HCC or morphologically typical hepatic tumor with alpha-feto protein (AFP) level &gt;250 ng/mL, ECOG performance status (PS) 0–2, age =18, measurable lesion, platelets &gt;100.10 9 G/L, PNN &gt;1.5.10 9 G/L, creatinine &lt;120 μmol/L, non decompensated Child A or B cirrhosis, documented tumor progression (RECIST), informed consent. Results: 43 patients, including 22 with baseline AFP &gt;400, were evaluable for safety and 35 for efficacy. Patients’ characteristics, toxicity and efficacy are summarized in the table below; 26% of patients received prior intra-arterial chemotherapy. Only one grade 4 toxicity was reported (thrombocytopenia). Grade 3 toxicities were: thrombocytopenia (21%) neutropenia (19%), acneiform rash (19%), asthenia (7%). Grade 2 and 3 neurotoxicity (specific scale) occurred in 16% and 5% of patients, respectively. No toxic death or other severe toxicity was reported. Conclusion: GEMOX plus cetuximab was well tolerated and induced a satisfactory control of disease in progressive HCC. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Multi-center prospective analysis of risk-reducing salpingo-oophorectomy to prevent <i>BRCA</i>-associated breast and ovarian cancer
Authors: N. D. Kauff, S. M. Domchek, T. M. Friebel, J. B. Lee, R. Roth, M. E. Robson, R. R. Barakat, L. Norton, K. Offit, T. R. Rebbeck
Journal: Journal of Clinical Oncology (2006)

1003 Background: Our groups previously reported on the efficacy of risk-reducing salpingo-oophorectomy (RRSO) for the prevention of BRCA-associated breast and ovarian cancer. (Kauff ND, et al. NEJM 2002; Rebbeck TR, et al. NEJM 2002) Limitations of those reports included relatively short prospective follow-up and lack of power to analyze the protection of RRSO when participants were stratified by BRCA1 vs. BRCA2. To address these limitations, we have pooled our updated datasets to provide robust estimates of the efficacy of RRSO. Methods: 886 women ≥ 30 years of age, with a deleterious mutation in BRCA1 or BRCA2 and ovaries in-situ at time of genetic test results, were enrolled on prospective follow-up studies at one of eleven centers from 11/1/1994 - 12/1/2004. Women chose to participate in either ovarian surveillance or undergo RRSO. Follow-up information was collected by questionnaire and medical record review. Follow-up time was counted from time of RRSO or from time of genetic test results for women who did not undergo RRSO. After excluding cancers diagnosed within the first 6 months of follow-up, the effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: 559 (63%) participants underwent RRSO a median of 5 months after genetic test results. 12 occult ovarian or fallopian tube cancers were diagnosed at time of RRSO. During a mean 40 months follow-up, RRSO was associated with a 52% reduction in breast cancer risk and a 91% reduction in ovarian cancer risk (see Table ). When the cohort was stratified by mutation status, RRSO was associated with a reduced risk of BRCA1-associated ovarian cancer and BRCA2-associated breast cancer. Conclusions: The results confirm that RRSO is highly protective against BRCA-associated breast and ovarian cancer. These results also generate the hypothesis that the protection conferred by RRSO against specific cancers may differ between carriers of BRCA1 and BRCA2 mutations. [Table: see text] No significant financial relationships to disclose.