tbuckley/cabot-search huggingface dataset:
Overexpression of melanoma-associated antigen D4 as an independent prognostic factor in squamous cell carcinoma of the esophagus.
Authors: Mitsuro Kanda, Hisaharu Oya, Soki Hibino, Hideki Takami, Dai Shimizu, Masahiko Koike, Shuji Nomoto, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2014)

71 Background: To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. Methods: MAGE-D4 mRNA expression was analyzed in nine EC cell lines using quantitative reverse transcription-polymerase chain reaction (RT-PCR). In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. Results: The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative RT-PCR. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P &lt; 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n=17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥ 65 years), lymphatic involvement and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039), and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4mRNA profiling. Conclusions: Our results suggest that MAGE-D4 overexpression influences tumor progression and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.
SPECIAL DEPARTMENTS
Authors: Luke Akard, Omer N. Koç
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.16.3063 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10944143 Luke AkardxLuke AkardSearch for articles by this author Omer N. KoçxOmer N. KoçSearch for articles by this author Show More Indiana Blood and Marrow Transplantation IndianapolisINCase Western Reserve University ClevelandOH https://doi.org/10.1200/JCO.2000.18.16.3063 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse16082000In Reply:We appreciate Dr Akard’s comments regarding three important observations made in our article1 and his prior work.2,3 These include (1) clear demonstration of a higher number of CD34+ cells mobilized using chemotherapy plus cytokines compared with cytokines alone in the same patient, (2) the effect of the first mobilization regimen on the subsequent one, and (3) the increased cost of chemotherapy and cytokines owing to treatment-related complications and chemotherapy administration. We would like to stress the importance of a randomized cross-over study design, which permits statistically significant comparisons with relatively small numbers of patients between various mobilization regimens by eliminating interpatient variability. This approach should be used to test new, less toxic, and potentially more effective stem-cell mobilization strategies.6. Koç ON, Gerson SL, Cooper BW, et al: Randomized cross-over trial of progenitor-cell mobilization: High-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF. J Clin Oncol 18::1824,2000–1830, Link, Google Scholar6. Akard LP, Wiemann M, Thompson J, et al: Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide and G-CSF. J Hematother 5::271,1996–277, Crossref, Medline, Google Scholar6. Akard LP, Thompson JM, Dugan MJ, et al: Matched-pair analysis of hematopoietic progenitor cell mobilization using G-CSF vs. cyclophosphamide, etoposide, and G-CSF: Enhanced CD 34+ cell collections are not necessarily cost-effective. Biol Blood Marrow Transplant 5::379,1999–385, Crossref, Medline, Google Scholar
Malignant mesothelioma following treatment for Hodgkin's disease.
Authors: L B Weissmann, J M Corson, A I Neugut, K H Antman
Journal: Journal of Clinical Oncology (1996)

PURPOSE Asbestos exposure is the major known risk factor for mesothelioma, but several case reports have suggested a link between radiation therapy and subsequent development of malignant mesothelioma. This report explores a possible association between radiation therapy for Hodgkin's disease and mesothelioma. PATIENTS AND METHODS Four cases of malignant mesothelioma were observed following Hodgkin's disease at the Mesothelioma Clinic of the Dana-Farber Cancer Institute. A fifth such patient was found after a review of the literature. RESULTS In all five cases, the mesothelioma arose in the field of prior radiotherapy. No history of asbestos exposure was elicited by careful questioning or by review of chest radiographs. Examination of lung tissue in one patient showed 250 ferruginous bodies per gram of lung tissue, consistent with no significant prior exposure. The mean interval between radiation treatment for Hodgkin's disease and development of mesothelioma was 15 years, which emphasizes the need for continued follow-up and evaluation of these patients and supports a causal relationship. CONCLUSION Mesothelioma may need to be added to the list of second malignancies that arise following radiation therapy for Hodgkin's disease. Further support is given to a causal link between radiation exposure and mesothelioma.
Simple blood test for diagnosis of gastrointestinal and pancreas cancer using surface-enhanced Raman scattering.
Authors: Hiroaki Ito, Katsuyuki Hasegawa, Yuuki Hasegawa, Satoshi Kimura, Manabu Onimaru, Tohru Ohmori, Haruo Ikeda, Mitsuo Saito, Yohei Kitamura, Chiaki Sato, Kuniyo Gomi, Satoshi Sakaue, Masayuki Isozaki, Masaaki Matsukawa, Haruhiro Inoue
Journal: Journal of Clinical Oncology (2015)

32 Background: Surface-Enhanced Raman Scattering (SERS) has been widely applicated in industrial microanalysis, and researched to apply for various fields, for example biological research. We tried to detect the SERS spectra from blood samples obtained from patients with cancers or benign diseases by using a low intensity laser beam, and compared the SERS spectra pattern among the samples from the patient group. Methods: Blood samples were obtained from patients with gastric cancer (n=30), colorectal cancer (n=20), pancreas cancer (n=5) and benign diseases (n=20). All blood samples were centrifuged at 1600g for 7 minutes, and serum samples were extracted. The serum samples were placed on the phosphor bronze chip with silver nanoscale hexagonal columns (NHCs), and SERS spectra was detected by using low intensity helium-neon red laser beam with 633 nm as wavelength. Results: SERS spectra were detected in all samples within 4 minutes from irradiation. Limiting dilution of detecting SERS was 1/1000 of serum. SERS spectra patterns were different between cancer and benign disease patients, and maximum peak level of the SERS in the samples from cancer patients were significantly higher than those from benign disease patients. There was a difference on the wavelength of Raman shifting at the peak intensity and the pattern of the SERS spectra between the samples from the patients with cancers and benign diseases. And furthermore, there was a difference on the SERS spectra pattern among the samples from the patients with gastric, colon and pancreas cancer. Additionally, it was suggested that the elements combined with the silver NHCs were histone-and-DNA complex. Conclusions: Our data suggest that our simple blood test using SERS is useful for diagnosis of gastrointestinal and pancreas cancer. We have been trying molecular analysis of the element combined with the silver NHCs by next-generation sequencer. Clinical trial information: UMIN000009818.
Stage III and stage IV non-small cell carcinoma patients triple chemotherapy combination (carboplatin, paclitaxel, and gemcitabine) in good performance status
Authors: R. T. Webb, L. M. Gill
Journal: Journal of Clinical Oncology (2007)

18205 Background: Triple drug chemotherapy combinations for nonsmall cell lung cancer (NSCLC) have most recently begun to show promising results in regards to response rate and time to progression (TTP) of disease. This abstract presents data from 99 patients with advanced unresectable disease who were not felt to be candidates for concurrent radiation and chemotherapy for 1999 to 2005 treated with a split dose regimen of paclitaxel 65mg/m 2 (d1, 8,15 q29 days), carboplatin AUC 2 (d1, 8,15 q29days), and gemcitabine 650 mb/m 2 (d1, 8 or15 q29 days). All patients have completed a minimum of 3 courses of therapy. Methods: 57 males with mean age 72 years, and 42 females, mean age of 69 yrs with performance status of &lt; 1. Stage III A&amp;B-33 patients and Stage IV-56 patients. The regimen was well tolerated with 4% grade 3 to 4 neutropenia, 30% 2-to3 thrombocytopenia. There were no septic deaths, grade 3 to 4 nonhematologic toxicity included alopecia, universally, fatigue at 24% and emesis at 8%. Results: CR-14.4%, PR-31%, minimal/stable-26% with 27.6% progressive/resistant disease with a median survival time of 20.5 months. 37 patients did receive radiation therapy to the primary lesion. Conclusions: This 3-drug regimen administered in split dosing has proven to be highly active and well tolerated in good performance status patients seen in a community practice setting. This cohort of patients was representative and typical for the 85% of patients seen in community oncology practices. No significant financial relationships to disclose.
Prolonged survival in patients with ultra high-risk pediatric sarcomas following reduced intensity allogeneic peripheral blood stem cell transplantation
Authors: C. Mackall, K. Baird, C. Love, A. Wayne, T. Fry
Journal: Journal of Clinical Oncology (2008)

21000 Background: Standard therapies yield poor outcomes for patients with Ewing’s sarcoma (ES), rhabdomyosarcoma (RMS) and desmoplastic small round cell tumor (DSRCT) refractory to front line chemotherapy, with early recurrence, with bone/bone marrow metastases (ES, RMS) or any metastases (DSRCT) or following multiple recurrences. Historically, treatment related mortality was high in pediatric sarcoma patients treated with myeloablative allogeneic SCT. We sought to determine whether reduced intensity allogeneic PBSCT could improve outcome for this ultra-high risk population. Methods: Patients received up to 3 cycles of pre-transplant chemotherapy (infusional etoposide, vincristine, adriamycin, cyclophosphamide, prednisone, fludarabine), a fludarabine/cyclophosphamide/melphalan preparative regimen, and G-CSF mobilized PBSC from HLA-matched related donors. GVHD prophylaxis was cyclosporine alone or FK506/rapamycin. Results: 26 patients enrolled and 19 underwent PBSCT. The PBSCT was well tolerated with full donor engraftment by d28 in all patients, median 10d to ANC >500 and no 100d treatment related mortality. Acute grade 1–2 GVHD occurred in 58%, grade 3 in 10%, and was steroid responsive in all patients; chronic GVHD occurred in 75%. Median survival for all patients enrolled is 35 mos (range 8–111) from diagnosis and 16 mos (range 2–37) from study enrollment. Sarcomas recurring post-PBSCT demonstrated a slower growth pace compared to pre-transplant and tumor shrinkage attributable to a graft-versus-tumor effect was seen in one patient. In addition, chemosensitivity was enhanced post-transplant in response to the same chemotherapy agents administered pre-transplant, and this was accompanied by enhanced mucosal, but not hematopoietic toxicity. Conclusions: Reduced intensity HLA-matched related PBSCT was well tolerated and resulted in favorable median survival in this cohort of ultra high-risk pediatric sarcomas. Thus, this is an optimal platform for exploration of post-transplant therapies to prevent sarcoma recurrence. Further investigation into the novel observations of slower post-transplant growth rates and enhanced chemosensitivity following allogeneic PBSCT is warranted. No significant financial relationships to disclose.
Abstract 15753: Evidence that microRNA-21 plays a role in Atrial Natriuretic Peptide- and Nitric Oxide-dependent Human Vascular Smooth Muscle Cellcontraction/relaxation
Authors: Kumar U Kotlo, Bahar Hesabi, Robert S Danziger
Journal: Circulation (2011)

Micro-RNAs (miRs) are endogenous small RNA molecules that suppress gene expression by binding to complementary sequences in the 3’ untranslated regions (UTRs) of their target genes. MiRs have been ...
Tissue engineered humanized bone supports human hematopoiesis in vivo
Authors: Boris M. Holzapfel, Dietmar W. Hutmacher, Bianca Nowlan, Valerie Barbier, Laure Thibaudeau, Christina Theodoropoulos, John D. Hooper, Daniela Loessner, Judith A. Clements, Pamela J. Russell, Allison R. Pettit, Ingrid G. Winkler, Jean-Pierre Levesque
Journal: Biomaterials (2015)
Use of ERCC1 and EGFR expression to predict irinotecan efficacy in patients with metastatic colorectal adenocarcinoma.
Authors: H. J. Miller, S. Jhatakia, P. P. Grimminger, K. D. Danenberg, D. Sigal
Journal: Journal of Clinical Oncology (2010)

e14058 Background: Irinotecan (CPT-11) is a potent therapy in advanced colorectal cancer (CRC). EGFR plays an important role in cell proliferation promoting entry of cells into the S-phase. Cells with high EGFR expression are thought to be more sensitive to topoisomerase-I inhibitors which are predominantly active in the S-phase. ERCC1 reflects increased DNA repair in tumor cells with amplified replication. These unstable cells are highly sensitive to topoisomerase-I inhibitors. Furthermore, EGFR increases expression of ERCC1. Previous studies have identified that gene expression of EGFR and ERCC1 are predictive of clinical outcomes in advanced CRC patients treated first-line with a CPT-11 based regimen. Methods: EGFR and ERCC1 gene expression were measured from metastatic tumors (primary tumor tissue was used if metastatic was not available) via RT-PCR extraction of formalin-fixed, paraffin-embedded samples. A total of 36 patients treated with an irinotecan–based regimen for advanced colorectal cancer at any line of therapy were evaluated. Thirteen tissue blocks had limited tissue and analysis was not performed. Twenty-three patients had full follow-up data and are included in this interim analysis. The EGFR and ERCC-1 gene expression were correlated with clinical response. Primary endpoint was time to treatment failure (TTF). Results: High EGFR and ERCC1 gene expression were predictive of improved clinical outcomes based on TTF in patients treated at any line of therapy with an irinotecan-based regimen. These findings were statistically significant (Table). Conclusions: Our study supports the correlation of high EGFR and ERCC1 mRNA expression and improved efficacy of CPT-11 based regimens in patients with advanced CRC. This study is the first to demonstrate that EGFR and ERCC1 expression predicts for improved clinical outcomes in patients treated beyond front-line therapy. Gene expression (n = number of patients) TTF (weeks) p value Hazard ratio EGFR high (n=13) 32 0.0037 0.1929 EGFR low (n=10) 7 ERCC1 high (n=9) 32 0.0470 0.4013 ERCC1 low (n=14) 16 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Response Genetics Response Genetics
Patient preference in breast cancer radiotherapy.
Authors: M. Alvarado, J. S. Connolly, M. Oboite, C. Park, L. Esserman
Journal: Journal of Clinical Oncology (2010)

e11005 Background: The international TARGIT trial is testing definitive intraoperative radiotherapy (IORT) for equivalence to external beam radiotherapy (EBRT) as a means for local control of invasive breast cancer. This study tests the hypothesis that patients may still be interested in pursuing IORT, even if IORT is found to be inferior to EBRT in terms of local recurrence risk. Methods: Patients were presented with a slideshow comparing EBRT with IORT, including a slide on the possible link between local recurrence and survival, and one citing IORT's “unknown long-term side effects.” Patients were then asked whether they would choose EBRT or IORT given hypothetical recurrence risks. The initial Tradeoff Slide posits either that both forms of radiotherapy lead to a 10% 10-year risk of local recurrence, or that EBRT leads to a 10% risk versus an IORT risk of 20%. These two conditions are used to assess whether the initial risk tradeoff affects patients' switch points. Subsequent tradeoff slides incrementally increase or decrease the hypothetical IORT recurrence rate until the subject's preference changes. Results: Data from 58 patients were used to determine the additional risk of 10-year recurrence patients would accept in order to have IORT instead of EBRT. The median was 2% additional risk. The mean was 3.7%, with two outliers accepting 34 and 39% added risk. Only 4 subjects selected added risk for IORT < 0%, 15 chose IORT with equivalent risk, and the remaining 39 stated they would accept some added risk to undergo IORT. None of the factors studied affected the median switch point or the percentage of patients selecting higher than 10% risk for IORT. These included age, time since diagnosis, working status (FT or PT), type of therapy (chemo and/or hormone), ER, PR and HER2 status, tumor grade, and, if applicable, time since treatment, impact on work, treatment actually received and how well radiation was tolerated. Conclusions: Offering nonequivalent therapeutic options is common practice in breast cancer treatment. This study shows that some patients would choose to consider radiation treatment that is both experimental and less efficacious at local disease control, if it meets certain extratherapeutic goals. Thus, it may be appropriate to offer additional choices in radiation. No significant financial relationships to disclose.
ELECTROLYTES AND SMOOTH MUSCLE CONTRACTION
Authors: DAVID F. BOHR
Journal: Pharmacological Reviews (1964)

Attention to details concerning the individual components of the contractile process of smooth muscle creates the impression that there is a striking difference not only between this muscle and striated muscle, but also among smooth muscles from various sources. Examples of its dissimilarity are found in the great and variable permeability of the membrane to Na; the individuality of endoplasmic reticulum, relaxing factor, and response to Ca; and its relatively weak but very extensible contractile protein. Although the individualities may be only quantitative, they are responsible for large differences in the mechanical event which is the end-product of the overall contractile process. Emphasis in the past has been placed on the uniqueness, variabifity, and lability of the smooth muscle contractile system. However, when one looks within the basic mechanisms of the smooth muscle contractile process, its excitation, coupling, chemo-mechanical transducing, and energy metabolism, one sees processes that are generally similar to those of striated muscle.

Ca modulates membrane excitability, is essential for excitation-contraction coupling, and may have another more direct function in the relationship between the chemical energy source (ATP) and the contractile machine (actomyosin). Mg depresses membrane excitability or excitation-contraction coupling but, in some cases, has a positive influence on contraction. It does not seem to be essential for contraction and its usual effect reflects depressed excitation or coupling. The action of K is strikingly ambivalent; an increase in concentration of K in the environment of the cell results in depolarization, increased excitability, and increased contraction; whereas intracellular K is essential for the normal reversible contractile process. In its absence a rigid contracture develops and in excess it plasticizes the contractile machine so that tension development is impaired. Na is not essential for the contraction-relaxation cycle, but in the intact system it has an important controlling influence on membrane excitability and on excitation- contraction coupling. The action of Na is largely dependent on interrelationships between the concentrations of Na and Ca. The influence of anions on smooth muscle contraction is determined primarily by the ease with which they permeate the cell membrane. In accordance with this facility they influence membrane potential and may have a more direct effect on the rate of movement of Ca through the membrane.

The generalization most profitable to live with in dealing with the influence of electrolytes on the contractile process of smooth muscle is that each may affect several of the components of the overall contractile process. The net effect of a shift in electrolyte concentration on the size of the contraction will depend on the relative magnitude and direction of the influence of this change on each process. In a general way the basic components of the overall contractile process of smooth muscle resemble those of skeletal muscle.
Predictors of the benefits women consider necessary to make adjuvant chemotherapy (ACT) worthwhile for early breast cancer (EBC)
Authors: V. Duric, M. R. Stockler, P. Butow, L. Sharpe, J. Beith, A. Sullivan, F. Boyle, H. Dhillon, A. S. Coates, R. J. Simes
Journal: Journal of Clinical Oncology (2004)

787 Background: ACT for EBC improves survival but is inconvenient and has side effects. Past studies of preferences show that many women who have had ACT for EBC consider small benefits sufficient to make it worthwhile (Lancet Oncol 2001; 2: 691). We sought predictors of these preferences. Methods: 118 consecutive consenting women who completed ACT 3 to 34 months previously (mean 18) were presented 4 hypothetical scenarios based on known survival times (5 and 15 yrs) and rates (65% and 85% at 5 yrs) with and without ACT. All women provided data on demographics, disease, treatment and side effects of ACT. A representative subset of 83 women also completed validated scales assessing anxiety, depression, optimism, perceived cause and impact of breast cancer. Associations were assessed with linear regression after normal score transformation of preferences. Results: Median age was 55 (range 24 to 69), 68% had a current partner, 45% had tertiary education, 68% were employed, 79% had children, 54% had dependants, and 10% lived alone. Most had AC (54%) or AC+CMF (27%). Improvements of 1% in 5 year survival rates or 3 months extra life expectancy were considered sufficient to make ACT worthwhile by most women (62% to 65%). Factors associated with these preferences (and not) are summarised in the Table. Conclusions: Preferences were highly variable, but many women considered small benefits sufficient to make ACT worthwhile. Circumstances and experiences were stronger predictors of preferences than psychological factors. These issues should be considered when discussing ACT with women. No significant financial relationships to disclose.