tbuckley/cabot-search huggingface dataset:
Use of genetic profiling to discover molecular signatures of the pattern of metastatic spread in human colorectal cancer
Authors: S. L. Anzick, J. Winter, S. Wong, S. Davis, M. McCall, P. S. Meltzer, M. A. Choti
Journal: Journal of Clinical Oncology (2005)

3678 Background: Metastatic disease is the hallmark of human malignancy that continues to challenge even the most recent advances in cancer treatment. In colorectal cancer, the major site of metastatic spread is the liver, but other sites include lung, and peritoneum, among others. In addition to elucidating mechanisms of tumor spread, predicting the pattern of metastatic spread could allow a more focused surveillance and adjuvant therapy. The aim of this study was to study the pattern of metastatic spread in colorectal cancer using gene expression micorarrays. Methods: Using microarrays consisting of ∼35,000 spotted oligonucleotides, we profiled 40 primary colorectal cancer samples from patients with resected primary tumors who developed metastatic disease. Patients were grouped into three patterns of isolated or dominant metastatic spread: liver, lung, and peritoneum/mesentery. Class comparison analysis and hierarchical clustering was performed on the array data. Results: An evident distinction could be made on profiled primary tumors based on their metastatic pattern. A list of candidate genes were identified which were associated with this clinical parameter. Conclusions: Confirmation of this result in a larger sample set may allow development of a predictive model for metastasis which could be utilized clinically to improve postoperative surveillance and therapy. No significant financial relationships to disclose.
A mathematical model for doxorubicin cardiotoxicity: Added evidence for the concept of sequential stress
Authors: M. S. Ewer, M. T. Vooletich, R. S. Benjamin
Journal: Journal of Clinical Oncology (2004)

2086 Background: Anthracycline cardiotoxicity (AC) is widely recognized and limits the use of this group of drugs. The agents are usually considered safe at low cumulative doses (CD) but show increasing AC as CD increase. Observations based on cardiac biopsy have shown cell damage at CD below where abnormalities in non-invasive cardiac parameters become detectable by the usual tests of systolic cardiac function. This failure to detect, in part, may result from the considerable compensatory reserves of the heart, a factor that must be considered in any model of cardiotoxicity. Methods: We have explored a mathematical model based on the assumption that each dose of anthracycline starting with the first administration causes AC. Subsequent damage is additive and depends on the extent of the toxic exposure (agent and cycle dosage) as well as on the status of the heart at the onset of each subsequent administration. Total AC depends on sequential cardiac stress. Results: Plotting the result of a sequential stress model produces a curve similar in shape to the historical curves based on clinical observations that correlate CD with the incidence of AC. For doxorubicin (dox) historical data is approximated by the equation y = x2 / 13, where y equals the percentage of patients who will demonstrate congestive heart failure, and x the number of cycles. The factor 13 is the correction factor when 50 mg/m2 cycles of dox are administered every three weeks without cardioprotection. This model encompasses both sequential stress and cardiac reserves. Conclusions: The mathematical relationship suggests that AC takes place from the onset of treatment, and therefore cardioprotection should be initiated with the first dose. Of note is the fact that toxicity related to non-anthracyclines given following anthracyclines, such as is the case with trastuzumab, exert their effect in part as a result of sub-clinical yet real early AC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia
Gynecologic oncology patients’ satisfaction with care and quality of care
Authors: A. M. Reidy, H. E. Frasure, E. M. Eldermire, N. L. Fusco, J. R. Hutchins, V. E. von Gruenigen
Journal: Journal of Clinical Oncology (2005)

8226 Background: Research on quality of care during palliative care in oncology patients has been limited. The objective was to assess patients’ satisfaction with care and ratings of quality of care during palliative chemotherapy. Methods: A prospective cohort study of patients with gynecologic malignancies receiving chemotherapy were enrolled after a diagnosis of recurrent cancer. Patients completed the QUEST Survey regarding quality of care and satisfaction with care upon enrollment in an outpatient setting and again a week later. Patients also completed the Mini-Mental Status Exam, the Hospital Depression/Anxiety Scale, Symptom Severity Scale and a demographic survey. Percent agreement and kappa were calculated for the QUEST. T-tests and correlation analysis were used. Results: Twenty-five patients were enrolled (2 patients refused). Twenty-two completed both QUEST surveys. Mean (SD) quality of care score was 42.04 (2.55) for physicians and 43.26 (2.40) for nurses (maximum score was 45; p=0.076 for difference in score between providers). Mean (SD) satisfaction of care score was 28.83 (2.08) for physicians and 29.65 (1.30) for nurses (maximum score was 30; p=0.039 for difference between providers). Test/Retest for both quality of care and satisfaction with care showed high percent agreement (75–100%, with the exception of the question regarding the provider arriving late). Kappa values ranged from 0.06 to 1.0 and were low in this setting as patients routinely rated both providers high on all questions. Mental scores were high (range 27–30, maximum 30). Symptom severity correlated with the number of prior chemo regimens (r=0.44; p=0.03) and time since diagnosis (r=0.53, p=0.008). Depression and anxiety scores were correlated only with each other (r=0.51; p=0.01). Conclusions: The QUEST Survey is reliable when used as a written instrument in an outpatient setting with gynecologic oncology patients. As patients’ cancer progresses despite chemotherapy, they should be frequently assessed and offered interventions for cancer symptoms. In this pilot dataset, women receiving palliative chemotherapy were not at increased risk for depression and anxiety or mental status changes. No significant financial relationships to disclose.
Impact of growth hormone on sleep disordered breathing in infants with Prader-Willi syndrome
Authors: Tom Carlisle, Emma Carruthers, Felicity Gray, Mark Rosenthal, Nicola Bridges, Hui-Leng Tan
Journal: European Respiratory Journal (2014)

Introduction   Growth hormone (GH) is a recommended treatment for Prader-Willi Syndrome (PWS), however, it has been implicated in cases of sudden death, with the first few weeks after starting GH therapy the most vulnerable time for developing significant sleep disordered breathing (SDB). UK guidelines recommend sleep studies to detect the severity of SDB pre and post GH initiation. This study investigates the effects of GH on respiratory sleep parameters in PWS infants.   Methods   14 patients were identified from hospital records aged    Results   There were no significant differences in any of the RP values pre and post GH initiation (Table 1).   Discussion   The SDB events were predominantly central rather than obstructive events. In contrast to some previous studies, no infant in our cohort developed obstructive sleep apnoea necessitating cessation of GH. This may be because they are a younger cohort and longer follow up is required. GH therapy appears safe in PWS infants.  Table 1. Demographics and RP parameters pre and post growth hormone initiation.  Data are presented as median (interquartile range). Abbreviations: GH, growth hormone; AHI, apnoea-hypopnoea index; AI, apnoea index; ODI, oxygen desaturation index.
Correlation between expression of MCM6, a new proliferative marker, and treatment outcome in patients with Hodgkin's disease
Authors: K. Khodadad, S. Karimi, Z. Esfahani Monfared
Journal: Journal of Clinical Oncology (2009)

e19547 Background: MCM6 is a proliferative marker, which in contrary to Ki67, is involved in all cell cycle phases, including early G1. We evaluated MCM6 expression in Hodgkin's disease (HD) patients in order to find any correlation between MCM6 expression and treatment outcome. Methods: Formalin-fixed paraffin-embedded lymph node specimens of 55 patients with HD treated with ABVD regimen (± radiotherapy) were assessed for MCM6 expression by IHC. The percentage of nuclear positivity in RS and mononuclear Hodgkin cells was evaluated in each case. Clinical data, response to treatment and relapse rates were obtained from patients’ medical records. These data were analyzed by SPSS software. Results: Mean MCM6 expression was 80.7% (ranging 35%-99%) with no significant difference between histology subtypes. In univariate analysis, MCM6 expression was not statistically significant for B-symptoms (P=0.27), sex (P=0.91), stage (P=0.18) and response to treatment (P=0.53), but was significant for age (P=0.008) (≤23 vs &gt;23 yrs old). The MCM6 mean expression between relapsed and non-relapsed groups was marginally significant (21% vs 29.4%, P=0.057). In multivariate analysis, we evaluated MCM6 expression, B-symptoms, stage, response rate and age for relapse. None of risk factors were statistically significant predictor for relapse, including MCM6 expression (P=0.238), however, were significant regarding to response (P&lt;0.001) and stage (P=0.048). We divided patients in 4 quartiles based on their MCM6 expression (Q1&lt;74.25%, N=13, Q2=74.26–85.5%, N=14, Q3=85.6–91.75%, N=13, Q4&gt;91.75%, N=12). Relapse and PFS were not significantly different between these quartiles (P=0.27 and P=0.83, respectively). Conclusions: Our study on a limited number of patients revealed MCM6 is not a strong predictor for treatment outcome in patients with HD. Our findings can be possibly explained by early G1 arrest of tumor cells and the role of cytokine production in pathogenesis of HD. We believe determining the accurate predictive role of proliferative markers needs to be focused on the markers which are exclusively involved in S phase. No significant financial relationships to disclose.
The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands
Authors: Fumitaka Kobayashi, Kenichi Matsuzaka, Takashi Inoue
Journal: International Journal of Oral Science (2015)

This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration. Collagen gel containing basic fibroblast growth factor could assist the regeneration of submandibular glands after damage during surgery. The slow healing of these large salivary glands, which lie beneath the floor of the mouth, causes difficulties with speaking, swallowing and digestion, and an increased susceptibility to oral infection. These problems can significantly impair a patient's quality of life. Fumitaka Kobayashi at Tokyo Dental College and co-workers explored the healing potential of basic fibroblast growth factor in collagen gel using rats that had been wounded to model surgical damage. They also monitored the proliferation and development of the specific types of cell involved in repairing the wounded tissue. Treating the wounds using collagen containing growth factor accelerated and improved healing to a greater extent than using collagen gel alone.
Abstract #4774: Discovery of a potent and selective small molecule inhibitor of PKD functionality
Authors: Q. Wang, Elizabeth Sharlow, Karthik Giridhar, Courtney LaValle, Jun Chen, Stephanie Leimgruber, Rebecca Barrett, Karla Bravo-Altamirano, Peter Wipf, John Lazo
Journal: Cancer Research (2009)

Protein kinase D is a novel family of serine/threonine kinases targeted by the second messenger diacylglycerol. It has been implicated in many important cellular processes and pathological conditions. However, further analysis of PKD in these processes is severely hampered by the lack of a PKD-specific inhibitor that can be readily applied to cells and in animal models. We now report the discovery of the first potent and selective cell-active small molecule inhibitor for PKD - benzoxoloazepinolone CID755673. This inhibitor was identified from the National Institutes of Health small molecule repository library of 196,173 compounds using a human PKD1 (PKCmu)-based fluorescence polarization high throughput screening assay. CID755673 suppressed half of the PKD1 enzyme activity at 182 nM and exhibited selective PKD1 inhibition when compared to AKT, PLK1, CAK, CAMKIIalpha and three different PKC isoforms. Moreover, it was not competitive with ATP for enzyme inhibition. In cell-based assays, CID755673 blocked phorbol ester-induced endogenous PKD1 activation in LNCaP cells in a concentration-dependent manner. Functionally, CID755673 inhibited the known biological actions of PKD1 including phorbol ester-induced class IIa histone deacetylase 5 nuclear exclusion, vesicular stomatitis virus glycoprotein transport from the Golgi to the plasma membrane, and the Ilimaquinone-induced Golgi fragmentation. Moreover, CID755673 inhibited prostate cancer cell proliferation, cell migration and invasion. In summary, our findings indicate that CID755673 is a potent and selective PKD1 inhibitor with valuable pharmacological and cell biological potential.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4774.
Radioimmunotherapy for consolidation and relapse therapy for aggressive B-cell non-Hodgkin lymphoma: Retrospective analysis of the International RIT-Network.
Authors: K. Hohloch, C. Windemuth-Kiesselbach, M. Lorsbach, P. L. Zinzani, L. Trümper
Journal: Journal of Clinical Oncology (2010)

8105 Background: Radioimmunotherapy (RIT) for lymphoma has shown high response rates and durable remissions especially in indolent lymphomas. In aggressive lymphoma, data are sparse, studies with RIT are ongoing. Data of pts with DLBCL in the international RIT-Network (RIT-NT) were analyzed with regard to indication, line of therapy and outcome. Methods: The RIT-NT, started in December 2006, is a web-based registry that collects observational data from RIT-treated patients with malignant lymphoma from across the world. As of January 1, 2010, data of 1,111 pts have been entered into the database. In the following analysis data from patients with DLBCL (n=198) are evaluated. Results: 198 pts with DLBCL are registered. Histologic subtypes: 180 diffuse large B-cell, primary mediastinal, 6 large cell anaplastic, 2 intravascular. Median age 61 years (range 17-88), 27% of pts > 70 years old. Stage at diagnosis: stage I 16 pts, II 52 pts, III 57 pts, IV 70 pts. 171 pts had 1-3 previous chemotherapies (Ctx), 19 pts 4-6 Ctx, 1 pts had seven Ctx. 12 pts with previous RIT, 23 pts with stem cell transplantation prior to RIT. 6 pts had bone marrow infiltration prior to RIT, 3 pts >25%. 82 pts had RIT as first line (70 pts consolidation, 1 primary therapy, 11 other), and 81 pts received RIT in relapse (2d to 8 th. line therapy) (31 pts consolidation, 25 recurrence, 19 therapy refractory, 6 other). Haematotoxicity was grade IV for neutrophils, platelets, and grade III for haemoglobin after RIT. Median time to recovery of blood count was 81 days (range 0-620 days). Overall response rate was 52%; CR 42%; PR 10%; SD 1% and PD 25%. CR rate for first line pts was 68%, for relapse 36%. In first-line therapy median overall survival (OS) was 278 days (range 43-1,076 days) and 224 days (range 22-1,139) for pts treated for relapse. Conclusions: Most pts with DLBCL receive RIT as consolidation after first-line therapy with excellent CR rates and OS. In relapse RIT is a safe and feasible treatment leading to satisfactory response rates with a low toxicity. Especially in elderly pts not fit for very aggressive chemotherapy and/or stem cell transplantation, RIT should be explored in prospective clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration The Binding Site Bayer
Developing an economic model to estimate the cost-effectiveness of first-line treatments for chronic myelogenous leukemia.
Authors: M. Taylor, T. Patton, C. Davis
Journal: Journal of Clinical Oncology (2010)

e17008 Background: Chronic myelogenous leukaemia (CML) is a progressive disease that is associated with significant health and economic burden. This study aims to develop an economic model to assess the costs and outcomes associated with various treatments when used as a first-line therapy and to identify the key issues to be addressed in the modeling of CML. The model differs from previous CML models in that it estimates the cost-effectiveness of different treatment sequences rather than simply the cost-effectiveness of each individual intervention. Methods: An economic model was developed using Markov methods to estimate the lifetime non-drug costs and health outcomes associated with treatments for CML in the chronic phase of the disease. A key feature of the model is that it models treatment sequences rather that individual treatments. Overall outcomes in the model are driven by treatment response. Patients progressed through the stages of the disease at different rates, based on their initial best response to treatment, drawn from pivotal trial data and published studies. Costs for the model were derived from national claims/insurance databases. Resource use was dependent upon the patient's current health and response level. Health benefits are measured using quality-adjusted life years (QALYs). The key output for the model will be cost per QALY. Results: The development of this model has raised a number of interesting features that highlight the importance of using the correct data and model design. For instance, when assessing treatment sequences, the model requires information not only on when patients discontinue each line of therapy, but why they discontinued, since the choice of next therapy may depend on whether the patient discontinued due to safety issues or due to lack of efficacy. Conclusions: This study has demonstrated the key features that are required in the modeling of CML and has highlighted the most appropriate sources of information to populate such analyses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb, Expert Opinion Journals
A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer.
Authors: S B Howell, S Kirmani, W E Lucas, S Zimm, R Goel, S Kim, M C Horton, L McVey, J Morris, R J Weiss
Journal: Journal of Clinical Oncology (1990)

We conducted a phase II trial of intraperitoneal (IP) cisplatin (DDP) and etoposide (VP-16) in stage III and IV newly diagnosed ovarian carcinoma patients with residual disease of any size. Twenty-three patients were entered, 19 had stage III and four stage IV disease. DDP 200 mg/m2 and VP-16 350 mg/m2 were given in 2 L saline IP via a Port-A-Cath (Pharmacia-Deltec, St Paul, MN). Sodium thiosulfate 4 g/m2 was given intravenously (IV) just before the start of IP instillation, and continued as a constant IV infusion of 2 g/m2/hr IV for a total of 6 hours. Treatment was given once every 4 weeks; six cycles of therapy were planned. Thirteen patients (56%) were in complete clinical remission at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125, and peritoneal cytology). Seven of these 13 underwent a second-look laparotomy: three (13%) were in pathologic complete remission and four (17%) had microscopic disease only. Projected survival is 68% at 27 months, with 10 patients being alive and continuously free of disease. There was a very rapid fall in mean CA-125 to within normal limits at the end of the second course of treatment. The major toxicity was myelosuppression with median nadir WBC, granulocyte, and platelet counts of 2,600, 896, and 205,000/microL, respectively. There was no cumulative renal damage, anemia, hypomagnesemia, or chemical peritonitis. Neurotoxicity was similar to that observed with IV dosing. We conclude that therapy with the IP DDP/VP-16/IV thiosulfate regimen, in which all cytotoxic drugs are given only by the IP route, produces less anemia and renal damage than standard IV DDP-containing regimens, and that survival with this regimen appears to be at least as good as that produced by IV programs.