tbuckley/cabot-search huggingface dataset:
Effectiveness of S1 after palliative gastrectomy for advanced gastric carcinoma with peritoneal metastasis
Authors: S. Ohigashi, N. Hayashi
Journal: Journal of Clinical Oncology (2005)

4247 Background: Since S1 reveals high response ratio for advanced gastric carcinoma, it is expected to be a promising drug for gastric carcinoma. This study was to verify the effectiveness of S1 after palliative gastrectomy for advanced gastric carcinoma with peritoneal metastasis and to evaluate the utility of thymidylate synthase and dehydropyrimidine dehydrogenase (TS/DPD) activity as an effective drug prediction of S1. Methods: Thirty-seven patients of gastric carcinoma with peritoneal metastasis inclusive of malignant ascites only, who underwent palliative resection of primary lesion, were divided into 3 groups as follows: Group A (n=13) of S1 after surgery, Group B (n=9) of chemotherapy (5FU/MTX, 5FU/MMC and 5FU only) excluding S1 after surgery, Group C (n=15) of surgery alone. The differences in clinicopathological backgrounds (age, surgical procedure, hepatic metastasis, distant lymph nodes metastasis, umber of malignant ascites only and performance status) were not recognized in the 3 groups. Survival rate and adverse effects were analyzed in all 3 groups and TS/DPD activity of Group A was investigated by RT-PCR methods. Results: The mean survival time was 505 (145–1125 days) for Group A, 447 (128–738) for Group B and 255 (63–1058) for Group C respectively. Two patients of Group A have been living without recurrence for 623 and 1125 days after the surgery. Although the significant difference was observed between Group A and Group C in survival rate (p=0.005), there was no difference between Group B and Group C. Adverse effects over Grade 3 were observed in a case of Group A (hematological toxicity), in 3 cases of Group B (2 cases of hematological toxicity and 1 case of gastrointestinal toxicity). Grade 4 toxicity was observed in neither Group A nor B. There was no statistical correlation (Pearson’s test) between survival time and TS/DPD activity (TS; p=0.055, DPD; p=0.428). Conclusions: Post-operative adjuvant S1 for the advanced gastric carcinoma with peritoneal metastasis revealed not only survival improvement but good compliance because of less adverse reactions, though TS/DPD activity was not useful as an effective drug prediction of S1. No significant financial relationships to disclose.
구연 : 카멜리아홀 ; 중국에서 간이식 받은 환자 351명의 장기 성적: 서울대학교병원의 경험
Authors: 이남준, 서경석, 김주현, 김태훈, 신우영, 이해원, 조재영, 이건욱
Journal: Clinical and Molecular Hepatology (2008)
Abstract P316: Very Low Prevalence of Ideal Cardiovascular Health in Young Adults Studying at the Université de Sherbrooke
Authors: Marie-France Hivert, Myriam Doyon, Geneviève Forget, Guillaume Lacerte, Melissa Labonté, Christine Brown, Marie-France Langlois
Journal: Circulation (2012)

Introduction: In 2010, the American Heart Association (AHA) published a special report to define and set national goals for cardiovascular health promotion and disease reduction (2020 Strategic Impact Goals). Ideal cardiovascular health was defined based on seven metrics including both ideal health behaviors (nonsmoking, body mass index &amp;lt 25 kg/m2, physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol &amp;lt 200 mg/dL [5.2 mmol/L], untreated blood pressure &amp;lt 120/ &amp;lt 80 mm Hg, and fasting blood glucose 8h of overnight fasting, using standardized procedures. Resting blood pressure was measured in the sitting position (twice, using the average for analyses). Physical activity was assessed by a validated questionnaire. Dietary intake was assessed by 3-day food diary; the average per day or the estimations per week were used accordingly to the specific dietary component recommendation. Results: The cohort was composed of young adults (20.6 ± 2.9 years old), mainly of European origin (97.8%), and 74.6% were female. Overall, only one participant (0.4%) achieved ideal cardiovascular health (all seven ideal health metrics). Very few participants (2.2%) achieved ideal healthy diet score (4-5 components /5). Investigating individual dietary component, our results showed that 9.4% consumed ≥ 4.5 cups/day of fruits and vegetables, 25.7% had ≥ two servings/week of fish, 14.5% reported ≥ three servings/day of fiber-rich whole grains, 8.0% consumed &amp;lt 1500g/day of sodium, and 75.4% reported drinking &amp;lt 36oz / week of sugar-sweetened beverages. Concerning the other health metrics, 22.8% achieved the recommended level of physical activity, 93.8% were non-smokers, 75.7% had a BMI &amp;lt 25kg/m2, 42.4% had a blood pressure in the ideal range ( &amp;lt 120/ &amp;lt 80 mmHg), 99.6% had a normal fasting glucose ( &amp;lt 5.6 mmol/L), and 42.4% had a total cholesterol &amp;lt 5.2 mmol/L. Conclusions: The prevalence of ideal cardiovascular health is very low, even in a population of young adults interested in healthy lifestyle. The low prevalence is mainly dependent on the healthy dietary score where the biggest challenges seem to be consumption of fruits and vegetables, and limiting sodium intake. Public health actions are seriously needed to improve these health metrics.
Epirubicin (E), cisplatin (C) and capecitabine (X) in first-line chemotherapy for patients with advanced gastric cancer
Authors: E. K. Cho, W. K. Lee, S. A. Im, S. N. Lee, S. H. Park, S. M. Bang, D. B. Shin, J. H. Lee
Journal: Journal of Clinical Oncology (2004)

4074 Background: ECF has been regarded as a highly active regimen for the advanced gastric cancer. Capecitabine (X) is an oral fluoropyrimidine carbamate and may be less toxic and more active than infusional 5-FU. We evaluated the antitumor activity and toxicity of ECX combination for untreated patients (pts) with advanced gastric cancer. Methods: Eligibility included (a) histologically proven gastric adenocarcinoma, (b) locally unresectable, metastatic or relapsed disease after resection, (c) measurable disease, (d) no previous chemotherapy or radiation therapy, (e) PS ECOG 0–2, (f) aged 18 years or older, and (g) no contraindication to chemotherapy. Pts received E (50 mg/m2 IV on D1), C (60 mg/m2 IV on D1) and X (2,000 mg/m2/day PO on D1–14) every 3 weeks. Results: Between May 2001 and January 2003, 54 pts were enrolled in this study; median age was 56 years (range, 32 to 73) with 41 male and 13 female pts; 32 metastatic diseases, 20 relapsed diseases after surgery and 2 locally advanced diseases. A total of 250 cycles were administered with a median of 4 cycles per patient (range, 1–12). Fifty-three pts were assessable for toxicity and 50 for responses. The most common grade 3/4 hematological adverse event was neutropenia in 76 cycles (31%). Grade 3/4 leukopenia and febrile neutropenia occurred in 27 cycles (11%) and 11 cycles (4.8%), respectively. Non-hematological toxicity was generally mild and reversible. Grade 3/4 nausea, vomiting and stomatitis occurred in 8%, 9%, and 8% of the patients, respectively. Hand-foot skin reaction developed in 51% of patients, but grade 3 occurred only in 4%. One patient died of neutropenic sepsis. The overall best response rate by intent-to-treat analysis was 59% (95%CI, 46–72%) including 52% of PR and 7% of CR. Median follow-up was 16 months (range 8 to 28 months). Median response duration and time to progression was 5.8 months (95%CI, 4.7–6.9) and 6 months (95% CI, 3.8–8.2), respectively. Median survival for all patients was 9.6 months (95% CI, 8.7–10.5). Conclusions: ECX combination regimen showed high anti-tumor activity with a tolerable toxicity as a front line chemotherapy for pts with advanced gastric cancer. No significant financial relationships to disclose.
The absolute oral bioavailability (BA) of 150-mg and bioequivalence (BE) of six 25- and one 150-mg erlotinib (E) tablets, a small molecule inhibitor of the epidermal growth factor receptor (EGFR), in healthy volunteers
Authors: B. L. Lum, J. Lu, S. M. Eppler, M. Hamilton, J. Wolf, A. Rakhit, P. Frohna
Journal: Journal of Clinical Oncology (2005)

3163 Background: Single agent E (Tarceva, OSI Pharmaceuticals) produced a survival benefit in patients with locally advanced or metastatic NSCLC after failing at least one prior chemotherapy. The objectives of this study were to: 1) determine if a single dose of six 25-mg oral tablets are bioequivalent to a single 150-mg erlotinib oral tablet, and 2) determine the absolute oral BA of the 150-mg oral tablets in healthy volunteers. Methods: Adult subjects were assigned to 1 of 2 study arms (A or B): Arm A (n = 42) received a single E dose of six 25-mg tablets followed by one 150-mg tablet after a 14-day washout period. Arm B (n = 20) received E as a single 25-mg IV infusion given over 30 minutes followed by a single 150-mg tablet after a 14-day washout period. All oral doses were following an overnight fast. Non-compartmental analysis (NCA) was used to determine BA and BE. Once nonlinear clearance (CL) was observed in Arm B, a subsequent BA analysis was performed using a 2-compartment nonlinear model in NONMEM with the POSTHOC option. Results: The ratio of geometric means for AUCinf and Cmax following administration of six 25-mg tablets and one 150-mg tablet, were 1.00 (90% CI, 0.96–1.05) and 0.95 (90% CI, 0.88–1.04), respectively; indicating bioequivalence. With NCA, BA was >100% due to nonlinearity in CL. When analyzed using the 2-compartment nonlinear model, the predicted bioavailability (F) was 59% (95% C.I. 55%, 63%). A greater exposure to E was observed in female subjects (n=23) as compared to male subjects (n=19) in Arm A. Conclusions: E is well absorbed following oral administration, with a bioavailability of 59%, with six 25-mg tablets of E showing bioequivalency to a single 150-mg tablet. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Hoffmann-La Roche, OSI Genentech, OSI
Fibrillar Structures in the Cells of Blood-Forming Organs
Authors: Y. Tanaka, M.D.
Journal: JNCI Journal of the National Cancer Institute (1964)

Fibrillar formations similar to those recently described by de Petris et al. in phagocytic monocytes were observed consistently in reticulum cells and endothelial cells in a variety of normal and abnormal bone marrows. The fibrils were also noted in malignant cells, including those of 3 lymphomas, 1 undifferentiated leukemia, and in 2 cases tentatively identified as reticulosis. The occurrence of fibrillar formations may possibly provide a clue to the classification of malignancies of the hematopoietic system.
Abstract 128: Pim1 kinase Overexpression Enhances ckit+ Cardiac Stem Cells Cardioreparative Ability After Intramyocardial Delivery
Authors: Vasileios Karantalis, Viky Y Suncion, Frederic C McCall, Luiza L Bagno, Bo Wang, Samuel Golpanian, Sadia Mohsin, Jose E Rodriguez, David Valdes, Marcos Rosado, Wayne Balkan, Muzammil Mushtaq, Mark A Susman, Joshua M Hare
Journal: Circulation Research (2014)

Background: Pim-1 kinase plays an important role in cell division, survival and commitment towards myocardial lineage. We hypothesized that Pim-1 overexpression in ckit+ cardiac stem cell (CSCs) enhances cardioreparative effects. Methods: Immunosuppressed Yorkshire swine (n=31) received human ckit+ CSCs (n=9), Pim1 modified human ckit+ CSCs (n=9) or PBS (n=13) two weeks after myocardial infarction. Cardiac MRI and PV loops were obtained before and after cell administration. Results: At 8 weeks post transplantation, scar mass (Fig. 1A), viable tissue (Fig. 1B), ejection fraction (Fig. 1C) and stroke work (Fig. 1D) was significantly improved in Pim-1 modified ckit+ CSC compared to control ckit+, while both cell groups showed partial recovery compared to placebo (two way ANOVA, p&lt;0.05). Both cell types similarly reduced preload (end diastolic pressure; Fig. 1E) and afterload (Arterial elastance; Fig 1F) compared to placebo, while only administration of Pim-1 CPCs improved regional contractility at both the infarct (Fig. 1G) and border zones (Fig. 1H). Collectively, mechanoenergetic recoupling was superior in the Pim-1 group compared to ckit+ controls (Cardiac Efficiency; Fig. 1I). Conclusions: Cardioreparative potential of CSCs delivered by intramyocardial injection to infarcted porcine hearts is significantly enhanced by overexpress Pim1, supporting translational development of Pim-1 as a validated genetic modification of CSCs for incorporation into clinical trials.
Economic burden of resected squamous cell carcinoma of the head and neck (SCCHN) in a U.S.-managed care population.
Authors: B. Chastek, M. Amonkar, N. Samant
Journal: Journal of Clinical Oncology (2010)

5595 Background: In 2009, an estimated 48,010 new cases of head and neck cancer were diagnosed and 11,260 deaths reported in the United States, with a majority of those cases being squamous cell carcinomas. This study examined healthcare costs and utilization in a US managed care population of patients with resected SCCHN. Methods: This retrospective study used claims data from a large (13.9 million members in 2008) US health plan. Patients ≥18 years of age were included if they had at least two claims associated with a diagnosis of lip, tongue, oral cavity, pharynx, or larynx cancer ≥21 days apart between 01/01/2004 and 12/31/2007; underwent surgical resection; and were continuously enrolled in the health plan for 6 months before and at least 1 year following the first observed resection. Patients with nasopharyngeal or other primary cancers were excluded from the study. Patient demographics, healthcare utilization, and inflation-adjusted healthcare costs were identified following the first resection. Results: A total of 1,104 patients (mean age 56.6 years; 71.9% male) were included in the study. Patients were followed up for an average of 2.3 years, and 13 (1.2%) died in an inpatient or outpatient facility during follow-up. Six hundred thirty-nine patients (57.9%) had an inpatient stay and 496 (44.9%) had an emergency department (ER) visit during the postoperative period. On average, patients spent 0.45 days in the hospital and had 27.4 ambulatory visits per- year. Mean annualized postoperative total healthcare costs were $34,450 per patient. The majority of the costs were medical expenses ($32,401) and primarily included ER visits, physician visits, hospitalization costs, and other outpatient costs; the remaining $2,050 were pharmacy costs. Following their first resection, the 1,104 patients accrued more than $94 million in total healthcare costs. Conclusions: Treatment of resected SCCHN in the United States is associated with significant healthcare utilization and costs. This suggests the need for new therapies that could improve outcomes and reduce the economic burden. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline i3 Innovus GlaxoSmithKline
Morphologic Aspects of Rous Sarcoma Virus Elaboration&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Ursula Heine, Guy de Thé, Hideo Ishiguro, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1962)

In ultrastructural studies of 7 avian tumors induced by the Bryan strain of the Rous sarcoma agent, we observed virus elaboration and elimination from the cell by budding of the cytoplasmic membrane in about 5 percent of the cells of 5 growths. The process could be traced from the earliest stages of budding to separation of the particle from the pedicel of the cell membrane. Newly formed particles exhibited a central region of low density, and the electron-dense nucleoid, typical of the “mature” virus, developed after separation of the particle from the cell. Nonviral bodies, “mucoastrosomes,” of approximately the same size as virus particles were present in the intercellular material. The probable origin of the structures from cytoplasmic membrane is discussed.
Reduced breast cancer risk seen with Mediterranean diet and added olive oil
Authors: Jacqui Wise
Journal: BMJ (2015)

A Mediterranean diet that is supplemented with extra virgin olive oil may help prevent breast cancer, a randomised trial published in JAMA Internal Medicine indicates.1

The research was carried out as part of the PREDIMED study, which was designed to test the effects of a Mediterranean diet, one based on plant foods, fish, and extra virgin olive oil, on the primary prevention of cardiovascular disease.

The study, which was conducted at primary health centres in Spain, involved 4282 women aged 60 to 80 years who were at …
The prognostic importance of left ventricular geometry in uremic cardiomyopathy.
Authors: R N Foley, P S Parfrey, J D Harnett, G M Kent, D C Murray, P E Barré
Journal: Journal of the American Society of Nephrology (1995)

The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units. A total of 433 patients who (1) survived > 6 months from the start of ESRD therapy and (2) had a technically satisfactory baseline echocardiogram were studied. Measurements included a baseline clinical, laboratory and echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation was present in 36% of patients. In patients with normal cavity volume (< or = 90 mL/m2) and normal systolic function, high LV mass index (> 120 g/m2) and mass-to-volume ratios (> 2.2 g/mL) were independently associated with late mortality (> 2 yr after starting dialysis therapy). After adjusting for baseline age, diabetes, and ischemic heart disease, the relative risk for the former was 3.29 and for the latter was 2.24. Cavity volume was of no prognostic significance in this group. In patients with LV dilation and normal systolic function, high cavity volume (> 120 mL/m2) and low mass-to-volume ratio (< 1.8 mL/m2) were independently associated with late mortality, the relative risk in the former being 17.14 and the latter being 4.27. LV mass index was of no prognostic significance in this group. The baseline echocardiographic classification, based on LV mass and cavity volume, was the strongest predictor of late mortality, after adjusting for age, gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of second line chemotherapy (CHT) in platinum-sensitive advanced/metastatic small cell lung cancer (SCLC) patients: Results of an ongoing Italian multicenter survey
Authors: O. Martelli, M. Cinquini, A. Mancuso, K. Borgonovo, F. Petrelli, C. Sergi, D. Paleari, S. Fatigoni, A. Sdrobolini, S. Aglione
Journal: Journal of Clinical Oncology (2007)

18090 Background: Despite CHT and radiotherapy for SCLC, most patients (pts) die within 2 years. Response rates for second-line CHT are low, with a median survival of 5 months in platinum-refractory pts. Re-challenge with platinum salts or salvage regimens is a standard option for pts with platinum-sensitive disease with a median overall survival (OS) of 6.5–8 months (Chua et al., Cancer Treat Rev. 2004). The purpose of this study was to explore the benefits of different second line regimens in this platiunum sensitive population. Methods: Clinical records of 73 platinum sensitive SCLC pts (first line relapse free survival &gt; 6 months) were reviewed from 13 medical oncology departments in Italy from January 1993 to December 2006. Pt. characteristics: 59 males, 14 females, median age 64 years (range 27–93), median ECOG performance status (PS): 1, limited/extended disease: 33/40 pts. Pts received salvage chemotherapy which consisted of monotherapy in 37% and platinum-containing doublets in 55%. Doublets without platinum salts were administered in the remaining 8%. Results: Of 67 evaluable pt, second line CHT produced partial responses (PR) in 58 (79%) and stable disease (SD) in 9 pts (12%) by RECIST criteria. Overall tumor growth control (PR+SD) was 91%. Despite these encouraging results, the median TTP was 3 months and OS for all evaluable pts was 6.5 months. Survival at 1 year was 11%. Multivariate analysis revealed that the most important prognostic factor for response was age ( p&lt;0.04) and there was no statistically significant difference between platinum-based regimens and monotherapy. Multivariate analysis showed no impact on survival by prior response to first line treatment, female sex or smoking status. Conclusions: Within the limits of a retrospective study, despite the high rate of responses obtainable in this setting, TTP and OS do not appear significantly improved by salvage regimens. Second line CHT has marginal activity and should be considered only in younger pts with a good PS. On the basis of these results, re-treatment with platinum salts could be avoided in these pts. No significant financial relationships to disclose.
Abstract 161: ABCB10 Plays a Role in Heme Synthesis and Mitochondrial δ-Aminolevulinic Acid Export
Authors: Arineh Khechaduri, Marina Bayeva, Hossein Ardehali, Rongxue Wu
Journal: Circulation Research (2012)

Introduction: Heme is essential for cardiovascular health, as it is a component of myoglobin, cytochrome P450, electron transport chain complexes, and antioxidant enzymes. The eight steps of heme synthesis are well characterized; however, it is not known how the synthetic intermediates are transported between mitochondria and cytosol. We hypothesized that the mitochondrial ATP-binding cassette protein-B10 (ABCB10) plays a role in heme synthesis by mediating the export of δ-aminolevulinic acid (ALA) out of the mitochondria. Results: Lentiviral shRNA-based knockdown of ABCB10 in H9c2 cardiac myoblasts significantly reduced cytosolic and mitochondrial heme levels and the activities of heme-containing proteins (catalase, peroxidase and complex IV), while their mRNA levels remained unchanged. The observed heme deficiency was not due to a defect in heme synthesis, iron incorporation, or enhanced heme degradation, as ABCB10 shRNA had no effect on the expression of enzymes mediating these steps. We then tested whether ABCB10 regulates mitochondrial export of ALA. Addition of exogenous ALA completely reversed the reduction in heme levels and normalized the activities of heme containing enzymes in cells with ABCB10 knockdown. However, overexpression of ALA synthase 1 (ALAS1), an enzyme catalyzing the production of ALA in the mitochondria, resulted in increased heme levels at baseline, but failed to restore heme content in ABCB10 shRNA-treated cells. To examine the role of ABCB10 in cardiac disease, we measured ABCB10 expression in the hearts of mice subjected to myocardial infarction and in explanted human hearts with ischemic cardiomyopathy. ABCB10 protein was significantly elevated in mouse and human hearts, and adenoviral overexpression of ABCB10 in H9c2 cardiac myoblasts significantly attenuated the production of reactive oxygen species (ROS), suggesting the protective role for ABCB10 in heart disease. Conclusions: Our studies place ABCB10 between the mitochondrial synthesis of ALA by ALAS1 and the cytosolic conversion of ALA into heme, suggesting that ABCB10 plays a role ALA export out of the mitochondria. Furthermore, its overexpression exerts protective effects against oxidant induced cell death in cardiac cells.