tbuckley/cabot-search huggingface dataset:
Evaluation of sensitivity to 5-FU on the basis of TS and DPD activity in micro tissue specimens
Authors: M. Kusama, H. Kaise, D. Ota, S. Nakayama, T. Miisaka, A. Tsuchida, T. Aoki, Y. Hakamada, M. Arima
Journal: Journal of Clinical Oncology (2004)

651 Background: Preoperative assessment of the anticancer drug sensitivity of tumors plays an important role in the selection of therapy. Evaluation of the 5-FU sensitivity of micro tissue specimens obtained by techniques such as core needle biopsy is often performed before preoperative chemotherapy. The addition of 5-Fluorouracil(F) or its derivatives to AC (EC), the current mainstay of therapy, may further enhance response rate. TS and DPD are used to evaluate the sensitivity and predict the response of tumors to fluoropyrimidine derivatives. Conventional techniques for measuring the activities of these enzymes require large tissue samples, often difficult to obtain before surgery. In contrast, assay of mRNA by PCR permits the use of micro tissue samples obtainable by biopsy. Methods: We measured TS and DPD enzyme activities and mRNA levels in 48 cases of tumor tissue and in the surrounding normal tissue. We also gave 5-FU postoperatively to 107 women with early-stage breast cancer, and divided tissue specimens obtained from these patients into a high-level group and a low-level group to examine the relation to recurrence. Results: TS activities were consistently higher in tumor tissue than in normal tissue, but the difference was not significant (p=0.37, p=0.1454). DPD activity was significantly higher in tumor tissue (p=0.0134), but the DPD mRNA level was higher in normal tissue (p<0.001). The TS activity of tumor tissue correlated with the TS mRNA level (r=0.518, p=0.0017). In contrast, there was no correlation between DPD activity and the DPD mRNA level (r=0.139, p=0.4423). The 5-year disease-free survival rate in patients with low TS activity (68.8%) was significantly better than that in patients with high TS activity (17.9%) (p=0.0018). The 5-year disease-free survival rate did not differ significantly between patients with low DPD activity (50.8%) and those with high DPD activity (66.5%). Conclusions: Our results indicate that TS activity can be used to prognostic factor to 5-FU, even when only micro tumor tissue specimens are available. DPD activity did not correlate with the response to 5-FU. No significant financial relationships to disclose.
Hepatitis G Virus RNA and Hepatitis G Virus-E2 Antibodies in Dutch Hemophilia Patients in Relation to Transfusion History
Authors: Eveline P. Mauser-Bunschoten, Marjolein Damen, Hans L. Zaaijer, Margret Sjerps, Goris Roosendaal, P. Nico Lelie, H. Theo M. Cuypers, H. Marijke van den Berg
Journal: Blood (1998)
Predictors of Nonsevere and Severe Hypoglycemia During Glucose-Lowering Treatment With Insulin Glargine or Standard Drugs in the ORIGIN Trial
Journal: Diabetes Care (2014)

OBJECTIVE Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting. RESEARCH DESIGN AND METHODS A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of ≤5.3 mmol/L (≤95 mg/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of ≤3 mmol/L [≤54 mg/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models. RESULTS During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care. CONCLUSIONS Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy.
A comparison of the survival and disease-specific survival of surgically resected, node-positive bronchioloalveolar carcinoma to that of non-small cell lung cancer: Implications for adjuvant therapy
Authors: M. M. DeCamp, J. C. Flickinger, A. Recht, M. C. Nikolov, J. M. Varlotto
Journal: Journal of Clinical Oncology (2008)

7536 Background: Node postive presentations of Bronchioloalveolar Carcinoma are quite rare. The purpose of our investigation is to assess whether disease-specific survival (DSS) and overall survival (OS) are different for patients with N1 and N2 bronchioloalveolar carcinoma (BAC) compared to non-BAC non-small cell lung cancer (NSCLC). Methods: The Surveillance, Epidemiology, and End Results (SEER) program data-base from 1992–2002 contained 684 patients with BAC and 9809 patients with non-BAC NSCLC with N1/N2 presentations who underwent a definitive surgical procedure. Overall survival (OS) and Disease-specific survival (DSS) rates were compared according to potential prognostic factors, including use of a matched-pair analysis. Results: The BAC patients with either pathologic N1 or N2 nodal stage were significantly more likely to be of female gender, non-black/non-white Race, and significantly less likely to have poorly differentiated or undifferentiated grade than patients with non-BAC cancers of comparable nodal stages. Median follow-up of patients was 29 months. There was a significant difference in DSS between patients with N2 BAC and non-BAC cancers, but not for patients with N1disease. There was a non-significant trend for higher OS for patients with N2 BAC compared to non-BAC cancers. Conclusions: Patients with node-positive BAC have distinctly different patient and tumor characteristics than patients with node-positive non-BAC NSCLC. Because DSS appears to be better for patients with N2 BAC, they may not benefit as much from adjuvant therapy as patients with non-BAC NSCLC. Multivariate analysis of OS and DSS for N1 and N2 patients in the matched pair data set Variable P(N1-OS) P(N1-DSS) P(N2-OS) P(N2-DSS) Age 8.7E-07 0.000908 0.345176 0.455014 Grade 0.227318 0.498733 0.541656 0.050089 Nodes,# Examined 0.772861 0.76045 0.816499 0.675187 Nodes, # Positive 5.24E-05 1.26E-05 0.04167 0.290783 BAC pathology 0.857825 0.850597 0.133668 0.017227 Diagnosis after 1998 0.002815 0.007124 0.492203 0.254192 Stage 0.292619 0.083372 0.163028 0.047375 Surgery Extent 0.812828 0.295294 0.114624 0.057384 Tumor Diameter 0.105579 0.670346 0.168403 0.226083 No significant financial relationships to disclose.
Continuous Intravenous Injection Of Mesna Can Reduce Acute Hemorrhagic Cystitis Occurrence Rate In Hematopoietic Stem Cell Transplantation: 359 Allo-HSCT Cases Report
Authors: Qianli Jiang, Qifa Liu, Jing Sun, Hongsheng Zhou, Zhiping Fan, Yu Zhang, Fen Huang, Dan Xu, Qi Wei, Guopan Yu, Jie Zhao, Xiaofang Li, Min Dai, Na Xu, Hao Huang, Kefeng Shen, Yang Lu, Lezhong Yuan, Yanyan Chai, Fanyi Meng
Journal: Blood (2013)
Effect of the response to first-line chemotherapy (chemo) in the chemotherapy-induced anemia control with the administration of Erithropoyetins (Epos) in metastatic non-small cell lung cancer (NSCLC) patients (pt)
Authors: J. Gasent Blesa, V. Giner Marco, V. Alberola Candel, O. Juan, V. Giner-Bosch, A. López, M. Provencio Pulla, E. Grande Pulido
Journal: Journal of Clinical Oncology (2009)

e20647 Background: The aim of this retrospective study, is to measure the influence of the tumor control with chemo on the results of the chemo-induced anemia treatment with epos in pts with nsclc, that were non-anemic before chemo, and in whom the only recorded cause of anemia was chemotherapy treatment. cycle. Methods: We analyzed 57 stage IV nsclc pt (21 Squamous, 26 Adenocarcioma, 4 Lare cell, 6 non specified), 41 male, 16 female, 30 with tumor progression (progression) and 27 with partial response (responders). Average age was 60.3 years (CI 95%: 57.2; 63.4). Pt were treated between April 2004 and May 2008. Any patient with disease stabilization was included. 52 pt were treated with platin-gemcitabine, and 5 with cisplatin-paclitaxel. 17 pt received Erithropoyetin-α and 40 darbepoetin. Pt who received radiotherapy as part of their treatment, were excluded of the analysis. Pt began treatment of epos when hemoglobin (hgb) was &lt;12gr/dl. Epos treatment was discontinued if the hgb level increased over 13gr/dl. No patient received epos with the first chemo cycle. Results: Pt with progression began the epos significantly before ( 100% before 4 th chemo, 50% in the 2nd cycle) than responders ( 100% before 5 th cycle, 7,4% at 2 nd cycle) (p&lt;0.001). Pt with progression, had a lower value of hgb at the beginning of the epos (median 9.82 in responders; 8.89 in progression; p=0.009). Recovery of the anemia was observed in 25.9% of the responders front to 3.3% of the pt with progression (p=0.014). No significant differences appeared in the requirements for red-cells transfusion (14.8% responders vs 30% progression; p=0.172). The mean hgb increase by each chemo cycle with epos was of 0.74gr/dl in responders and of 0.25gr/dl in pt with progression (p&lt;0.001 CI 95%: 0.232–0.748 for the odds ratio). The mean absolute hgb increase in responders was singnificanly greater than in pt with progression (1.49 gr/dl vs 0.7 gr/dl p=0.008CI 95% 0.21–1.368 for the difference of the means). Conclusions: From the obtained data, we can conclude that the tumor response can have a direct impact on the efficacy of chemo-induced anemia treatment with epos; and that anemia control may reflect beneath disease control. No significant financial relationships to disclose.
Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes
Authors: J Drach, A Gsur, G Hamilton, S Zhao, J Angerler, M Fiegl, N Zojer, M Raderer, I Haberl, M Andreeff, H Huber
Journal: Blood (1996)
Phase I study of sorafenib (S) with gemcitabine (G)-based radiotherapy (G-RT) in patients (pts) with locally advanced unresectable pancreatic adenocarcinoma (LAUPC).
Authors: S. Anderson, H. R. Cardenes, F. Akisik, E. L. Johnston, R. Clark, S. M. Perkins, C. S. Johnson, P. J. Loehrer, B. P. Schneider, E. G. Chiorean
Journal: Journal of Clinical Oncology (2010)

4139 Background: The E4201 study showed survival benefit with G-RT for LAUPC. RT is known to increase VEGF and activate RAF, thus we hypothesize that adding S, a multi-kinase inhibitor of RAF/VEGFR, to G-RT will improve outcomes. The purpose of this study was to evaluate the safety and efficacy of G-RT + S in LAUPC. Methods: Pts with biopsy-proven LAUPC, with no luminal duodenal invasion, were treated with G 1,000 mg/m2 iv weekly (QW) × 3 every 4 wks/cycle for 1 cycle (cy), followed by G 600 mg/m2 QW with concurrent intensity modulated RT (IMRT) 50 Gy to the gross tumor volume in 25 fractions. Up to 4 cy of G were administered after G-RT. S was dosed orally daily 400 mg BID until progression, except during RT, when it was dose escalated in a "3+3" design from 200 mg QD, 400 mg QD and 400 mg BID, with expansion at MTD. DLTs were assessed during the first 2 cycles. Pharmacodynamic studies (PD) included dynamic contrast enhanced (DCE)-MRI and angiogenic genes polymorphisms. Results: 27 pts were enrolled (18 pts at MTD with S 400 mg BID), median age 59 yrs (40-81), 16 male, ECOG PS 0/1 (16/11). No DLTs occurred. The most common grade 3/4 toxicities were fatigue (6), thrombocytopenia (8), neutropenia (5), and anemia, nausea, vomiting (4 each). Treatment was discontinued for toxicity in 11 pts, including: hemorrhagic gastropathy (2), ulcers (4), and perforated colon diverticuli, hand-foot skin reaction, fatigue, anemia and rectal bleeding (1 each); physician's decision (4) and disease progression (2); 4 pts are ongoing. One toxic death (Pseudomonas infection) occurred during study. Median cycles were 4 (2-13). Among 24 evaluable pts (3 pts came off study in cy 1 due to skin rash [1] and catatonic reaction [1] from S, and 1 had bone metastases), 6 (22%) had PR and 17 SD (71%). No patient progressed locally. Three pts underwent R0 resections with no perioperative complications. With a median follow-up of 27 mos, the median progression-free and overall survival were 11 (95% CI 7-15) and 16 mos (95% CI 10-24), respectively. PD data will be presented. Conclusions: The addition of S to G-RT has increased gastrointestinal toxicity but demonstrated encouraging activity warranting further study in LAUPC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Bayer/Onyx Bayer/Onyx
Potentiation of Anticancer Agents by New Synthetic Isoprenoids. I. Inhibition of the Growth of Cultured Mammalian Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K Ikezaki, T Yamaguchi, C Miyazaki, H Ueda, T Kishiye, Y Tahara, H Koyama, T Takahashi, H Fukawa, S Komiyama
Journal: JNCI Journal of the National Cancer Institute (1984)

In this study, 9 new synthetic isoprenoids with 9-10 isoprene chains were tested. One-fifth of the D10 value (concentration of drug that reduced colony-formation ability to 10% that of control) for each isoprenoid was calculated from dose-response curves of Chinese hamster V79 cells or human HeLa cells in culture. That dose was combined with various anticancer agent [1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-n itrosurea HCl, bleomycin A2 (BLM), cisplatin, doxorubicin (Dx), 5-fluorouracil, mitomycin, and 6-mercaptopurine] to test whether isoprenoids can potentiate the cytotoxic effect of anticancer agents against cultured mammalian cells. Among the 9 isoprenoids tested, decaprenoic acid, dacaprenylamine.HCl, and N-(p-methylbenzyl)decaprenylamine.HCl significantly potentiated BLM and Dx. Some isoprenoids increased intracellular levels of anticancer agents. Both enhanced uptake and reduced efflux of Dx were observed.
Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low β2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase
Authors: J. Rodriguez, W.C. Pugh, J.E. Romaguera, R. Luthra, F.B. Hagemeister, P. McLaughlin, M.A. Rodriguez, F. Swan, F. Cabanillas
Journal: Annals of Oncology (1994)
Defining the expression pattern and role of paralemmin in breast cancer
Authors: Casey Turk, Joe Gozgit, Christopher Otis, Sharon Marconi, Manfred Kilimann, Kathleen Arcaro
Journal: Cancer Research (2007)

2162   Paralemmin is a phosphoprotein first identified in brain tissue where it is thought to play a role in the control of cell shape, plasma membrane dynamics, and cell motility. Paralemmin is lipid-anchored to the cytoplasmic face of membranes through prenylation and di-palmitoylation of a COOH-terminal cluster of three cysteine residues. Phosphorylation and mRNA splicing of paralemmin is tissue-specific and developmentally regulated. The differential splicing, lipidation, and phosphorylation of paralemmin contribute to electrophoretic heterogeneity resulting in an array of multiple bands on Western blots. Paralemmin is expected to interact and co-localize with specific partner molecules, such as certain integral membrane proteins and/or cytoskeletal proteins, possibly aiding as an adaptor or chaperone in their trafficking. Here we report for the first time that paralemmin is differentially expressed in breast cancer versus non-tumorigenic breast cell lines and that paralemmin is overexpressed in breast cancers. We propose that paralemmin plays a role controlling the membrane dynamics of cancer cells. A cDNA microarray comparison between the estrogen receptor (ER)-positive, MCF-7 breast cancer cell line and the tamoxifen-selected, TMX2-28 breast cancer cell line indicated that paralemmin was overexpressed in the ER-negative TMX2-28 cells. Using real time-RT PCR we confirmed that paralemmin mRNA is 8-fold higher in TMX2-28 cells as compared to MCF-7 cells. Furthermore, paralemmin mRNA is almost undetectable in the non-tumorigenic, breast cell lines, 184, 184A1, 184AA2 and MCF10A. A Western blot analysis of paralemmin in the breast cancer and non-tumorigenic breast cell lines revealed two major protein bands between 60 and 70 kDa for both MCF-7 and TMX2-28 (albeit darker bands for TMX2-28), and a lower and a higher molecular weight band for the non-tumorigenic breast cell lines suggesting differential splicing, lipidation, or phosphorylation between the cancer and non-tumorigenic breast cell lines. To examine the relevance of paralemmin expression in breast disease we isolated RNA from 30 frozen breast tumors and determined the levels of paralemmin mRNA using real time RT-PCR. Paralemmin was highly expressed in 9 of the 30 tumors. Next we examined paralemmin protein on tissue microarrays. Paralemmin was overexpressed in 15 out of the 33 tumors; in all cases paralemmin was significantly localized to the plasma membrane. Studies are underway to determine whether paralemmin is expressed in a specific subset of breast cancers and to investigate its role in the membrane dynamics of cancer cells.
An Universal and Easy‐to‐Use Model for the Pressure of Arbitrary‐Shape 3D Multifunctional Integumentary Cardiac Membranes
Authors: Yewang Su, Zhuangjian Liu, Lizhi Xu
Journal: Advanced Healthcare Materials (2016)

Recently developed concepts for 3D, organ-mounted electronics for cardiac applications require a universal and easy-to-use mechanical model to calculate the average pressure associated with operation of the device, which is crucial for evaluation of design efficacy and optimization. This work proposes a simple, accurate, easy-to-use, and universal model to quantify the average pressure for arbitrary-shape organs.
Phase II trial of erlotinib (OSI-774), an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), in patients (pts) with metastatic breast cancer (MBC)
Authors: M. Dickler, H. Rugo, J. Caravelli, E. Brogi, D. Sachs, K. Panageas, S. Flores, M. Moasser, L. Norton, C. Hudis
Journal: Journal of Clinical Oncology (2004)

2001 Background: Aberrant VEGFR expression in breast tumor cells and EGFR expression in endothelial cells may contribute to tumor growth and progression (Baker, 2002; Kranz, 1999). Preclinical evidence suggests that EGFR blockade may inhibit angiogenesis (Hirata, 2002), and combined blockade of the VEGFR and EGFR pathways may increase anti-tumor activity in xenograft models (Jung, 2002). We performed this two stage phase II study to explore the activity of erlotinib and bevacizumab in MBC, as a phase I/II trial in lung ca showed no pharmacokinetic interaction (Mininberg, ASCO 2003). Methods: Erlotinib (150 mg orally/day) and bevacizumab (15mg/kg IV q3 weeks) is given to pts with measurable MBC following 1–2 prior chemotherapy regimens (CRx). The primary endpoint is response rate; secondary endpoints include safety and time to tumor progression. Markers of the EGFR and VEGFR pathways will be evaluated in archival tumor tissue and in pre/post treatment tumor biopsies in several pts. Levels of circulating endothelial cells, epithelial cells, VEGF and βFGF will be measured in serial plasma samples. Results: Thirteen pts have been enrolled to date: median age 55 (range 35–71); ECOG 1 (0–2); 75% had 2 prior CRx for MBC. Pts received a total of 38 cycles of study therapy, with median of 2 cycles/pt (range 1–9). Response is evaluable in 9 pts (75%), with 3 pts too early for response assessment. One pt had a confirmed PR (11%), 2 had SD at 9 wks (22%), 5 had POD (56%), and 1 (11%) came off study after 1 cycle due to an allergic drug eruption. Two pts (15%) experienced grade (gr) 4 toxicities: pulmonary embolus 1 (8%) and neutropenia 1 (8%). Toxicity potentially related to OSI-774 and/or bevacizumab include: rash (gr 2: 46%), diarrhea (gr 2: 23%), hypertension (gr 3: 15%), nausea/vomiting (gr 3: 8%). Conclusions: Activity in the first stage of this phase II trial justifies expanded study of erlotinib and bevacizumab in MBC. Updated results with additional pts will be presented. Supported by CTEP, NCI and in part by Genentech Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Inc. Genentech
Quality-of-life (QoL) outcome of standard chemotherapy for advanced non-small cell lung cancer (NSCLC): A comparison between cisplatin- and non-cisplatin-based regimens
Authors: T. Tanvetyanon, H. Soares, B. Djulbegovic, P. Jacobsen, G. Bepler
Journal: Journal of Clinical Oncology (2007)

18067 Background: Among standard chemotherapy regimens for NSCLC, cisplatin-based regimen is known to be associated with significant nausea and vomiting. QoL during treatment with cisplatin-based chemotherapy, when compared with others is unclear. Methods: We performed a MEDLINE search for all phase III randomized controlled trials of NSCLC that reported QoL outcomes and used standard chemotherapy regimens containing cisplatin in one arm and non-cisplatin in the other. Two reviewers independently extracted data and assess quality. QoL reporting criteria were priori hypothesis stated, rationale for instrument reported, psychometric properties reported, cultural validity verified, adequacy of domains covered, instrument administration reported, baseline compliance reported, timing of assessment documented, missing data documented, clinical significance addressed, and presentation of results (Efficace et al, JCO 2003). Results: Out of 893 potential titles, 9 studies were identified. Two did not meet the minimum QoL reporting criteria and were excluded. Of the 7 included studies (N=3439), only one measured QoL as a primary endpoint; only two satisfied all 11 quality criteria for QoL reporting. Due to the heterogeneity of the reporting formats, we were unable to pool data on QoL. Two of seven studies indicated that a cisplatin-containing regimen was associated with a significantly worse QoL when compared with a non-cisplatin regimen (Table). Among these selected studies, treatment-related death was higher with cisplatin-based regimens [reported from 8 studies, N=3290, RR=0.66;95%CI (0.46–0.95), p=0.03]. Grade 3 and 4 neutropenia and neutropenic fever were also more common in the cisplatin-based arms. Conclusion: We found a suboptimal quality of QoL reporting and a lack of standardization of QoL analysis method in these trials. This limits a comparison between studies and the usefulness of QoL endpoint for clinical decision-making. [Table: see text] No significant financial relationships to disclose.
WITHDRAWN: Therapeutic approach of familial amyloidotic polyneuropathy by targeted delivery of siRNA complex with PEG-appended lactosylated dendrimer/cyclodextrin conjugate
Authors: Yuya Hayashi, Taishi Higashi, Keiichi Motoyama, Hirofumi Jono, Yukio Ando, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

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