tbuckley/cabot-search huggingface dataset:
Interstitial high dose rate (HDR) brachtherapy + IMRT vs. HDR monotherapy for early stage prostate cancer
Authors: T. Neumann, R. Mark, P. J. Anderson, M. Nair
Journal: Journal of Clinical Oncology (2006)

14606 Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using High Dose Rate (HDR) + External Beam Radiation Therapy (EBRT) or IMRT has been reported with favorable results. The role of supplemental EBRT or IMRT in brachytherapy is undefined. We compare our results of HDR + IMRT vs. HDR monotherapy. Methods: Between 1997 and 2006, 276 patients with T1 and T2 localized prostate underwent TRUS interstitial implant. After discussion of treatment options, 109 patients elected HDR Implant + IMRT and 167 patients underwent HDR alone. No patient received Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.8 (0.60 to 39.8). In patients who received IMRT + HDR, 4500 cGy in 25 fractions was given via IMRT and 1650 cGy in 3 fractions via HDR. Our protocol for HDR alone, has called for two HDR Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2 nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Results: There was no significant difference between the treatment groups with respect to T-Stage, Gleason Score, and PSA. With a median follow-up of 66 months (range: 6 months to 120 months), the overall PSA disease free survival (DFS) was 89.5% (247/276). In patients undergoing IMRT + HDR, PSA DFS was 89.0% (97/109) vs. 89.8% (150/167) for patients undergoing HDR alone (p = 0.6). The 5 year actuarial survival was 86% for the group receiving IMRT + HDR vs. 89% with HDR (log rank = 0.5). Urinary stress incontinence has occurred in 2.5% (7/276). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.3% (9/276) Grade 2. RTOG late rectal toxicities were: 0.4% (1/276) Grade 4, 0% Grade 3, 3.6% (10/276) Grade 2, and 4.7% (13/276) Grade 1. RTOG late rectal toxicity was higher in patients undergoing HDR + IMRT with 14.7% (16/109) of patients experiencing Grade 2 and 1 symptoms, vs. 3.0% (5/167) receiving HDR alone (p ≤ 0.01). Conclusions: We have observed no difference in PSA DFS in patients undergoing HDR vs. HDR + IMRT. Complications were similar, though RTOG Grade 1 and 2 late toxicity was higher in patients receiving HDR + IMRT. By omitting IMRT, rectal complications may be reduced. No significant financial relationships to disclose.
Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial.
Authors: D H Johnson, F A Greco, J Strupp, K R Hande, J D Hainsworth
Journal: Journal of Clinical Oncology (1990)

Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC.
Synergistic Effect of FLT-3 Ligand on the Granulocyte Colony-Stimulating Factor–Induced Mobilization of Hematopoietic Stem Cells and Progenitor Cells Into Blood in Mice
Authors: Yoshikazu Sudo, Chihiro Shimazaki, Eishi Ashihara, Takehisa Kikuta, Hideyo Hirai, Toshiya Sumikuma, Noboru Yamagata, Hideo Goto, Tohru Inaba, Naohisa Fujita, Masao Nakagawa
Journal: Blood (1997)
Abstract 9480: Contrasting Effects of Imidapril and Losartan on Matrix Metalloproteinase in Human Abdominal Aortic Aneurysm
Authors: Toru Miyoshi, Tomoko Yonezawa, Kazufumi Nakamura, Masashi Yoshida, Hiroshi Morita, Masashi Yoshida, Masayuki Doi, Atsushi Aoki, Kengo Kusano, Yoshifumi Ninomiya, Hiroshi Ito
Journal: Circulation (2012)

Background: Abdominal aortic aneurysm (AAA) is characterized is characterized by the destruction of tissue architecture due to chronic inflammation. Emerging clinical evidence showed the effectiveness of angiotensin-converting enzyme inhibitor (ACEI) on the prognosis of AAA more than angiotensin II receptor blockers (ARB). We investigated the effects of an ACEI, imidapril and an ARB, losartan, on the activity of matrix metalloproteinase (MMP)-2 and -9 in human and murine AAA tissues. Methods: Five specimens were obtained as a whole abdominal aortic tissue (from proximal margin to distal margin). A whole sample was categorized into three zone; zones of margin, middle, and maximum diameter. Whole tissues were cut into around one inch of pieces, and then characterized for the histological parameters. The activities of MMPs were detected on AAA tissues by in situ gelatin zymography. Results: The MMP activities were increased in middle zone compared with other zones. The in sizu gelatin zymograhy showed that MMP activities on human AAA tissue in middle zone were significantly reduced by adding imidapril compared with losartan into reaction reagents. In addition, in vitro experiments showed that activities of human MMP-9 in a tube were significantly inhibited by imidapril, but not losartan in dose dependent manner. Next, we investigated the effects of imidapril (10mg/kg/day), losartan (10mg/kg/day), and hydralazine (10mg/kg/day) on CaCl 2 -induced AAA in mice. Six week after CaCl 2 -treatment, imidapril significantly prevented the enlargement of aorta compared to treatments with losartan and hydralazine (28%, 60% and 84%, respectively, p&lt;0.01), while blood pressures were similarly lowered among three groups. The elevated expressions of MCP-1 and TNF-alpha and the recruitment of macrophages to AAA lesion were significantly reduced in imidapril-treated mice compared to losartan and hydralazine-treated mice. The in situ gelatin zymographies in mice also showed that lower MMP activities in AAA in imidapril treated mice compared with losartan and hydralazine treated mice. Conclusion: The direct inhibitory effect of imidapril on gelatinolytic activities may contribute to the protection of AAA.
Abstract 18563: Pulmonary Artery Pressure Response Pattern in Heart Failure with Preserved Ejection Fraction
Authors: Bishnu P Dhakal, Ryan M Murphy, Neal A Chatterjee, Marc J Semigran, Gregory D Lewis
Journal: Circulation (2012)

Background: Inefficient ventilation during exercise, defined by steep relationship between ventilation and carbon dioxide output (VE/VCO 2 ) purports a poor prognosis in heart failure (HF) patients regardless of ejection fraction (EF). However the extent to which VE/VCO 2 slope reflects hemodynamic impairment during exercise in HFpEF is unknown. We therefore investigated hemodynamic response patterns in relation to exercise gas exchange parameters in HFpEF compared to normal controls. Methods/Results: We studied consecutive patients referred for cardiopulmonary exercise testing with hemodynamic monitoring who had RER &gt;1.05 and either resting supine pulmonary capillary wedge pressure (PCWP) &gt;15 or exercise PCWP &gt;20 mmHg and LVEF &gt;0.50 (HFpEF, N=54, Age 62±11, Male 54%) and normal controls (N=16, Age 47±16, Male 37%). We measured simultaneous cardiac filling pressures, VO 2 and arterial and mixed venous blood gases (to determine Fick cardiac outputs [CO]) during every minute throughout incremental upright cycle ergometry CPET. HFpEF patients had higher VE/VCO2 slope than controls (36±7 vs. 31±7) and steeper, linear increments in PAP and PCWP relative to CO (3.6 and 2.7 mmHg/L min -1 compared to 1.6, and 1.1 mmHg/L min -1 respectively, all p&lt;0.05, Figure ).Upon stratification of the HFpEF patients by median VE/VCO2 (36) we found that higher VE/VCO2 was associated with steeper PAP slope (4.3 vs. 3.1 mmHg/L, p=0.02) and PCWP slope (3.6 vs. 2.5 mmHg/L, p=0.04) despite no difference between the two HFpEF sub-groups in resting upright PAP or PCWP. Conclusion s: We observed a linear increment in PAP and PCWP in HFpEF and controls during incremental cycle ergometry exercise. Ventilatory inefficiency is an easily measured, non-invasive variable that reflects impaired pressure-flow response patterns to exercise in patients with HFpEF.
A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway
Authors: Kathy K. Wang, Laura K. Stone, Tami D. Lieberman, Michal Shavit, Timor Baasov, Roy Kishony
Journal: Molecular Biology and Evolution (2015)

Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid's components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance.
Predictive values of (18)f-FDG PET standardized uptake value for adjuvant chemotherapy in patients with nasopharyngeal carcinoma.
Authors: Ching Chan Lin, Te-Chun Hsieh, Tzu-Ting Chen, Ching-Yun Hsieh, Chen-Yuan Lin, Hsin-Hui Huang, Li-Yuan Bai, Po-Han Lin, Chang-Fang Chiu, Su-Peng Yeh, Yu-Min Liao, Woei-Chung Lo
Journal: Journal of Clinical Oncology (2013)

6052 Background: Concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy is the mainstay of treatment for locally advanced nasopharyngeal carcinoma (NPC). However the benefit of adjuvant chemotherapy has been controversial and search for adequate predictive factors is warranted. We conduct this study to evaluate the predictive values of mean standardized uptake value (SUV) measured in [(18)F]-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for adjuvant chemotherapy in patients with locally advanced NPC. Methods: From January 2004 and July 2010, Data collection were performed in 108 NPC patients who underwent (18)F-FDG-PET before CCRT and adjuvant chemotherapy. The SUV was recorded for the primary tumor. All patients received intensity modulated radiotherapy. Concurrent chemotherapy was composed of cisplatin 100mg/m 2 triweekly. Adjuvant chemotherapy was consisted of 3 cycles of cisplatin 75 milligrams/m 2 and fluorouracil 1000 milligrams/m 2 for 4 days. Results: The median follow-up was 41months. The optimal cutoff value was 8.35 for SUV. 63.8% of patients had lower SUV (n=69), and 36.2% had higher SUV (n=39). Patients with a lower SUV had a significantly better 3-year overall survival (OS), disease-specific survival (DDS), and distant relapse-free survival (DRFS), but showed no difference in local relapse-free survival. Multivariate analysis showed only stage, SUV and adjuvant chemotherapy were significant in terms of overall survival. In patients with higher SUV, those receiving adjuvant chemotherapy had significantly higher 3-year OS, DDS, and DRFS compared with those without adjuvant chemotherapy. However, in those with lower SUV, there was no difference of OS, DDS and DRFS between patients with and without adjuvant chemotherapy. Conclusions: SUV of (18)F-FDG-PET for primary tumor could identify NPC patients who benefit from adjuvant chemotherapy. [Table: see text]
Succinate dehydrogenase inhibition with malonate during reperfusion reduces infarct size by preventing mitochondrial permeability transition
Authors: Laura Valls-Lacalle, Ignasi Barba, Elisabet Miró-Casas, Juan José Alburquerque-Béjar, Marisol Ruiz-Meana, Marina Fuertes-Agudo, Antonio Rodríguez-Sinovas, David García-Dorado
Journal: Cardiovascular Research (2015)

AimsPrevious studies demonstrated that pre-treatment with malonate, a reversible inhibitor of succinate dehydrogenase, given before ischaemia, reduces infarct size. However, it is unknown whether administration of malonate may reduce reperfusion injury.
The conversion ratio (CR) for opioid rotation (OR) from strong opioids to transdermal fentanyl (TDF) in cancer patients.
Authors: Akhila Sunkepally Reddy, Ali Haider, Supakarn Tayjasanant, Jimin Wu, Diane D Liu, Sriram Yennu, Maxine De la Cruz, Marieberta Vidal, Suresh K. Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

9612 Background: Cancer patients frequently undergo OR for uncontrolled pain or opioid induced neurotoxicity (OIN). TDF is one of the most common opioids prescribed to cancer patients. However, the accurate CR for OR from other opioids to TDF is unknown and various currently used methods result in a wide variation of CRs. Our aim was to determine the CR of morphine equivalent daily dose (MEDD) to TDF when correcting for MEDD of breakthrough opioids (net MEDD) in cancer outpatients. Methods: We reviewed records of 22,532 consecutive patient visits at our Supportive Care Center in 2010-13 for OR from other opioids to TDF. Data regarding Edmonton Symptom Assessment Scale (ESAS) and MEDD were collected in patients who returned for follow up within 5 weeks. Linear regression analysis was used to estimate the CR between TDF dose and net MEDD (MEDD prior to OR minus MEDD of breakthrough opioid used along with TDF after OR). Successful OR was defined as 2-point or 30% reduction in pain score and continuation of the new opioid at follow up. Results: 129 patients underwent OR from other opioids to TDF. The mean age was 56 years, 59% male, and 88% had advanced cancer. The median time between OR and follow up was 14 days. Uncontrolled pain (80%) was the most frequent reason for OR and 59% had a successful OR with significant improvement in ESAS pain, constipation, and symptom distress scores. In 101 patients with OR and no worsening of pain at follow up, the median CR (range) from net MEDD to TDF mg/day was .01 (-0.02-0.04) and correlation of TDF dose to net MEDD was .77 (P < .0001). The CR was not significantly impacted by variables such as mucositis, serum albumin, and body mass index (BMI). The CR of .01 suggests that MEDD of 100mg is equivalent to 1mg TDF/day or 40mcg/hour TDF patch (1000mcg/24hours). Conclusions: The median CR from MEDD to TDF mg/day is .01 and the CR from MEDD to TDF mcg/hour patch is 0.4. Further validation studies are needed. Comparison of Fentanyl (mg/day)/ Net MEDD Ratio Variables Level N Median CR Min-Max p-value All 101 .01 -0.02-0.04 Mucositis No 49 .01 0 -0.03 .67 Yes 52 .01 -0.02-0.04 . BMI ≤ 20 13 .01 0-0.02 .43 20-30 62 .01 -0.02-0.04 . > 30 26 .01 0-0.03 . Albumin g/dl < 3 4 .01 0-0.02 .41 3-3.5 17 .01 0-0.02 . > 3.5 78 .01 -0.02-0.04
Impact of a cancer management program.
Authors: J. Russell Hoverman, Ira Klein, Deb Harrison, Jad Hayes, Jody S. Garey, Greg C. Nelson, Maria Sipala, Scott Houldin, John Ciaglo, Cynthia Taniguchi, Melissa Jameson, Mitra Abdullahpour, Jessica McQueen, Diana K. Verrilli, Roy Beveridge
Journal: Journal of Clinical Oncology (2012)

227 Background: US Oncology, Inc., Texas Oncology (TxO) and Aetna are engaged in a pilot program, Innovent Oncology (IOP) to evaluate clinical and financial impacts of Pathways (PW), a nursing call intervention for chemotherapy patients (pt support services-PSS), and an advance care planning (ACP) initiative. We report quality initiatives, PW compliance and ACP, from the program at 18 months, and IP and ER admits at 12 months. Methods: Eligible Aetna pts with PW diagnoses, treated by TxO were enrolled. PW compliance was tracked. PSS calls occurred at regular intervals during chemotherapy. Symptoms, quality of life, and depression were screened each call with referrals to TxO as needed for management. ACP was initiated in month 2 of IOP. To support IOP, a leadership team comprising physicians, pharmacists and nurses was established. IP,ER data on predefined subgroups were compared to diagnosis-adjusted rates from the baseline prior year. Results: The program enrolled 184 patients from June 1, 2010 – Decembe 30, 2011 with 278 regimens ordered. Pathway adherence improved from 67% to 75%. 81% enrolled in PSS; of these, 83% were introduced to ACP, with 11% (n=16) completing a full ACP discussion. PSS made 906 calls to pts and assessed pain at 80% of contacts. IP, ER utilization rates after 12 months of IOP are reported (see Table). Conclusions: This is a preliminary evaluation with small numbers. Results suggest cancer patients can be identified pre-treatment; a proactive nurse call system is feasible and well received; a symptom assessment tool can be systematically implemented, communication on ACP initiated; and a pathways program enhanced. A reduction of ER visits by 39.8%, IP admits by 16.5 %, and inpatient days/member by 35.9% are very promising trends. A bootstrap shows 97% of scenarios with IP utilization reduction, and 96% with ER utilization reduction. [Table: see text]
Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial
Authors: Melanie J. Davies, Stephen C. Bain, Stephen L. Atkin, Peter Rossing, David Scott, Minara S. Shamkhalova, Heidrun Bosch-Traberg, Annika Syrén, Guillermo E. Umpierrez
Journal: Diabetes Care (2015)

OBJECTIVE Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment. RESEARCH DESIGN AND METHODS In this 26-week, double-blind trial, 279 patients with HbA1c 7–10%, BMI 20–45 kg/m2, and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2; MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139). RESULTS The estimated treatment difference in HbA1c from baseline to week 26 was −0.66% (−7.25 mmol/mol) (95% CI −0.90 to −0.43 [−9.82 to −4.69]), P &amp;lt; 0.0001). Fasting plasma glucose decreased more with liraglutide (−1.22 mmol/L [−22.0 mg/dL]) than with placebo (−0.57 mmol/L [−10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (−2.41 kg) than with placebo (−1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: −1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P &amp;lt; 0.0001). CONCLUSIONS Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment.
Relationship between sex hormone binding globulin and estrogen receptors in breast cancer.
Authors: S R Plymate, F H Stutz, B L Fariss
Journal: Journal of Clinical Oncology (1984)

It has been suggested that the level of sex hormone binding globulin (SHBG) is a better predictor of response of breast cancer to hormone treatment than the measurement of estrogen receptor (ER). However, no correlation of SHBG with ER status has been shown. To define the relationship between SHBG and the ER, the following study was undertaken. Fifty women with breast cancer and known ER status had SHBG measured by dextran-coated charcoal saturation analysis. The mean SHBG in all ER-positive patients was 20.7 +/- 2.4 (ng DHT bound/mL) and in all ER-negative patients was 11.5 +/- 2.0 (p less than 0.01). The mean premenopausal level of SHBG was 22.2 +/- 3.8 ng/mL and postmenopausal level was 20.0 +/- 5.7 ng/mL. There was no significant difference between these groups. ER-positive patients on tamoxifen had a SHBG of 29.8 +/- 9 ng/mL and ER-negative subjects on tamoxifen had a mean SHBG level of 8.3 +/- 3.4 ng/mL, p less than 0.01. ER-positive patients have a higher SHBG level than ER-negative patients; furthermore, this difference between ER-positive and ER-negative subjects was further demarcated by changes in SHBG after the subjects had been placed on tamoxifen.
AKT1 Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer through Phosphorylation-Dependent Twist1 Degradation
Authors: Chia-Wei Li, Weiya Xia, Seung-Oe Lim, Jennifer L. Hsu, Longfei Huo, Yun Wu, Long-Yuan Li, Chien-Chen Lai, Shih-Shin Chang, Yi-Hsin Hsu, Hui-Lung Sun, Jongchan Kim, Hirohito Yamaguchi, Dung-Fang Lee, Hongmei Wang, Yan Wang, Chao-Kai Chou, Jung-Mao Hsu, Yun-Ju Lai, Adam M. LaBaff, Qingqing Ding, How-Wen Ko, Fuu-Jen Tsai, Chang-Hai Tsai, Gabriel N. Hortobagyi, Mien-Chie Hung
Journal: Cancer Research (2016)

Abstract Epithelial-to-mesenchymal transition (EMT) is an essential physiologic process that promotes cancer cell migration, invasion, and metastasis. Several lines of evidence from both cellular and genetic studies suggest that AKT1/PKBα, but not AKT2 or AKT3, serves as a negative regulator of EMT and breast cancer metastasis. However, the underlying mechanism by which AKT1 suppresses EMT remains poorly defined. Here, we demonstrate that phosphorylation of Twist1 by AKT1 is required for β-TrCP–mediated Twist1 ubiquitination and degradation. The clinically used AKT inhibitor MK-2206, which possesses higher specificity toward AKT1, stabilized Twist1 and enhanced EMT in breast cancer cells. However, we discovered that resveratrol, a naturally occurring compound, induced β-TrCP–mediated Twist1 degradation to attenuate MK-2206–induced EMT in breast cancer cells. Taken together, our findings demonstrate that resveratrol counteracts the unexpected metastatic potential induced by anti-AKT therapy and therefore suggest that the addition of resveratrol to an anti-AKT therapeutic regimen may provide extra support for limiting EMT. Cancer Res; 76(6); 1451–62. ©2016 AACR.