bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-Line Vinorelbine-Mitoxantrone Combination in Metastatic Breast Cancer Patients Relapsing after an Adjuvant Anthracycline Regimen: Results of a Phase II Study
Authors: Llombart-Cussac Antonio , Pivot Xavier , Rhor-Alvarado Alba , Le Cesne Axel , Le Chevalier Thierry , Tursz Thomas , Spielmann Marc 
Published: April 2003

<b>Purpose:</b> Previous studies demonstrated that doxorubicin and vinorelbine combinations in first-line chemotherapy are highly active in metastatic breast cancer. Mitoxantrone is an anthracenedione with low cardiotoxicity, and seems to be effective when combined with vinorelbine after prior exposure to anthracyclines. <b>Patients and Methods:</b> Seventy-two patients with metastatic breast cancer were included in a phase II study. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbine was administered at 25 mg/m<sup>2</sup> in a 20-min intravenous (i.v.) infusion, days 1 and 8. Mitoxantrone was given at 10 mg/m<sup>2</sup> (66 patients) or 12 mg/m<sup>2</sup> (6 patients) in a slow i.v. infusion on day 1. Courses were repeated every 3 weeks. <b>Results:</b> Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37–63%), including four complete and 28 partial responses, with a median duration of response of 7 months (range 2.3–27). Median overall survival was 19 months (range 2–48). Grade 3–4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% of patients for febrile neutropenia. Seven patients (10%) experienced grade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failure. Other side effects were rare and mild. <b>Conclusions:</b> The vinorelbine and mitoxantrone combination is an active regimen with low toxic complications when cumulative doses of mitoxantrone are limited to 70 mg/m<sup>2</sup>. The results in this phase II study make it worthwhile including this regimen in a phase III study for patients who have previously received an anthracycline-containing regimen.
Allelic Loss and Microsatellite Instability in Prostate Cancers in Japan
Authors: Watanabe Masatoshi , Shiraishi Taizo , Muneyuki Tsuyoshi , Nagai Moritaka , Fukutome Kazuo , Murata Mariko , Kawamura Jyuichi , Yatani Ryuichi 
Published: April 2003

A series of 25 primary prostate cancers in Japanese were screened for loss of heterozygosity and microsatellite instability using twelve microsatellite markers containing <i>APC, DCC, TP53, BRCA1</i>, and <i>BRCA2</i>. Frequent loss of heterozygosity was observed for <i>D8S201</i> (48%), <i>LPL</i> (48%), and <i>DCC</i> (26%). In contrast, the incidence did not exceed 15% at <i>BRCA1</i> and <i>BRCA2</i> loci. Microsatellite instability was observed in 28% of stage B, C, and D cancers. These data suggest that microsatellite instability and loss of unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate; however, <i>BRCA1</i> and <i>BRCA2</i> may not be largely involved in the development of prostate cancer in the Japanese population.
A Randomized Controlled Comparative Study of Oral Medroxyprogesterone Acetate 1,200 and 600 mg in Patients with Advanced or Recurrent Breast Cancer
Authors: Koyama Hiroki , Tominaga Takeshi , Asaishi Kazuaki , Abe Rikiya , Iino Yuichi , Enomoto Kohji , Miura Shigeto , Nomura Yasuo , Nakazato Hiroaki , Abe Osahiko 
Published: April 2003

A randomized controlled comparative study of oral medroxyprogesterone acetate (MPA) 1,200 mg (arm I) and 600 mg (arm II) was conducted in 80 patients with advanced or recurrent breast cancer. There were no significant differences between arm I and arm II in terms of response rate, duration of response and survival, or in terms of incidence and severity of adverse reactions. The lowest serum MPA concentration in responders tended to be higher than that in nonresponders. In the cohort of this study, the lowest concentration in partial response was 17.4 ng/ml, suggesting that this level may be the required minimum serum concentration.
Phase II Study of Irinotecan and Cisplatin as First-Line Chemotherapy in Advanced or Recurrent Cervical Cancer
Authors: Sugiyama Toru , Yakushiji Michiaki , Noda Kiichiro , Ikeda Masanori , Kudoh Ryouichi , Yajima Akira , Tomoda Yutaka , Terashima Yoshiteru , Takeuchi Shoshichi , Hiura Masamichi , Saji Fumitaka , Takahashi Takeshi , Umesaki Naohiko , Sato Shinji , Hatae Masanori , Ohashi Yasuo 
Published: April 2003

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m<sup>2</sup>) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m<sup>2</sup> i.v.) on day 1 over 90 min. The patients’ median age was 57 years (range 35–75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41–74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16–62 days). The median survival was 27.7+ months (range, 6.4–52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.
A Phase II Study of Gemcitabine and 5-Fluorouracil in Metastatic Pancreatic Cancer: An Eastern Cooperative Oncology Group Study (E3296)
Authors: Berlin Jordan D. , Adak Sudeshna , Vaughn David J. , Flinker David , Blaszkowsky Lawrence , Harris Jules E. , Al Bowen Benson III A.B. 
Published: April 2003

Gemcitabine has recently been compared favorably to 5-fluorouracil (5-FU) as the standard chemotherapy for advanced pancreas cancer. Based on phase I data that combining gemcitabine with 5-FU is safe and has evidence for clinical activity, a phase II trial was conducted by the Eastern Cooperative Oncology Group (ECOG). Patients with metastatic disease, good performance status and organ function were eligible and enrolled after providing informed consent. Patients were given gemcitabine (1,000 mg/m<sup>2</sup>) followed by 5-FU (600 mg/m<sup>2</sup>) weekly for 3 weeks of every 4. Of 37 patients enrolled over a 3-month period, 36 were eligible. Partial responses were seen in 5 patients (14%). Median survival was 4.4 months with a 1-year survival rate of 8.6%. A randomized trial of the combination of 5-FU and gemcitabine versus gemcitabine alone is currently accruing patients in ECOG.
An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer
Authors: Nishimura Reiki , Nagao Kazuharu , Miyayama Haruhiko , Matsuda Masakazu , Baba Kenichirou , Matsuoka Yukio , Yamashita Hiroya , Fukuda Makoto , Mizumoto Takao , Hamamoto Rieko 
Published: April 2003

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.
Oxaliplatin-Induced Fever and Release of IL-6
Authors: Ulrich-Pur Herbert , Fiebiger W.C.C. , Schüll B. , Kornek Gabriela V. , Scheithauer Werner , Raderer Markus 
Published: April 2003

<i>Background:</i> Oxaliplatin is a novel cytotoxic agent with documented activity in colorectal cancer. Side effects are generally moderate, and include peripheral neuropathy along with mild bone marrow suppression and gastrointestinal side effects. To our knowledge, induction of febrile episodes by this agents has not been described in the literature. <i>Case Report:</i> We present the case of a 74-year-old male patient admitted to our institution for palliative treatment of metastatic colorectal carcinoma. Due to progression during treatment with 5-fluorouracil and leucovorin, chemotherapy consisting of oxaliplatin 85 mg/m<sup>2</sup> on days 1 + 15 plus mitomycin C 8 mg/m<sup>2</sup> on day 1 repeated every 28 days was initiated. The first cycle of this combination was tolerated without side effects, but the patient experienced fever up to 39°C starting 2 h after oxaliplatin administration on day 15 of the second cycle, which persisted for 3 days. Fever again recurred at the same interval following administration of oxaliplatin on day 1 of the next cycle. Blood samples taken at regular intervals disclosed an increase in IL-6 serum levels parallel to the body temperature curve, with the peak corresponding to the highest temperature, while C-reactive protein values remained unchanged. In spite of intensive premedication with steroids, antipyretics and clarithromycin, fever promptly recurred during the third cycle of treatment. <i>Conclusion: </i>Our data suggest a clear- cut correlation between fever, the release of IL-6 and oxaliplatin administration. Whether IL-6 release is directly triggered by the application of oxaliplatin or is a bystander phenomenon, however, remains unclear at the moment.
CEA mRNA Identification in Peripheral Blood Is Feasible for Colorectal, But Not for Gastric or Pancreatic Cancer Staging
Authors: Piva Maria Grazia , Navaglia Filippo , Basso Daniela , Fogar Paola , Roveroni Giovanni , Gallo Nicoletta , Zambon Carlo-Federico , Pedrazzoli Sergio , Plebani Mario 
Published: April 2003

<i>Objective:</i> It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. <i>Methods:</i> We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. <i>Results:</i> The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (χ<sup>2</sup> = 14.6, p < 0.01), lymph node (χ<sup>2</sup> = 18.95, p < 0.001) and distant metastasis (χ<sup>2</sup> = 11.3, p < 0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. <i>Conclusions:</i> The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.
Autonomic Nervous System Responses to Personal Stressful Events in Patients with Acute Myocardial Infarction
Authors: Tsouna-Hadjis Evie D. , Mitsibounas Dimitris N. , Kallergis George E. , Sideris Dimitris A. 
Published: April 2003

<b>Background:</b> Life events specific for each individual may influence the onset of acute myocardial infarction (AMI), and we wondered whether recall of such events elicits autonomic nervous system responses in patients. <b>Methods:</b> Thirty-one subjects with AMI, which occurred about 1 month previously (study group), and 22 healthy subjects were interviewed. Whenever the presence of a stressful event was found within the last 2 months before AMI onset, a key phrase of the event was isolated. Each subject was faced with 20 written key sentences (including his/her own sentence if detected) at random order, for 40 s each. At the same time the heart rate (HR) and the galvanic skin response (GSR) were continuously recorded. Pearson r correlations, χ<sup>2</sup> and t tests were employed for comparisons between study and control group as well as within each group. <b>Results:</b> A recent exacerbating event was detected in 30/31 AMI patients and in 0/22 healthy subjects. For the 30 AMI patients the values of HR following the sentence of the suspected event, specific for each patient, were statistically significantly higher than the mean values of HR following the remaining 19 ‘neutral’ statements. The same significant difference appeared with regard to GSR values. The mean values of the AMI patients for the 19 neutral statements did not differ significantly from those of the healthy subjects for the 20 neutral statements, either for HR or GSR. <b>Conclusions:</b> Findings suggest that recall of personal stressful events elicited autonomic nervous system responses in AMI patients and, therefore, events with personal significance are related to coronary disease onset.
Lower Absorption of Cholesteryl Oleate in Rats Supplemented with <i>Areca catechu L.</i> Extract
Authors: Jeon Seon-Min , Kim Hee-Sook , Lee Taehoon G. , Ryu Sung-Ho , Suh Pann-Ghill , Byun Sung-June , Park Yong Bok , Choi Myung-Sook 
Published: April 2003

<i>Areca catechu L.</i> extracts I and II, prepared using two different solvent systems, exhibited strong inhibitory activities against pancreatic cholesterol esterase (pCEase) in vitro. To determine their cholesterol-lowering effects, these two extracts were investigated by analyzing plasma lipid levels, intestinal enzyme activities, and the absorption of cholesteryl oleate. For 6 days, male rats were fed a diet containing cholesteryl oleate (0.5 g/100 g of body weight) either with or without the Areca nut extract supplements. The supplementation of the two Areca nut extracts significantly lowered the concentrations of plasma cholesterol by 13.4 and 11.7% and plasma triglycerides by 35.0 and 36.9%, respectively, compared with the pre-experimental values. However, when the cholesteryl oleate diet was fed without any Areca nut extract in high-cholesterol control, the plasma cholesterol and triglyceride concentrations significantly increased by 13.6 and 15.9%, respectively, compared with the pre-experimental values. After 6 days of treatment, the intestinal pCEase activities were significantly lower in the groups supplemented with the Areca nut extracts (37.8 and 26.5%) than in the group with no extract supplement (83.2%). The supplements also significantly elevated the excretion of [1,2(n)-<sup>3</sup>H]cholesteryl oleate administered orally, when determined by the large intestinal contents, 930.5 Bq/day (Areca I) and 1,766.3 Bq/day (Areca II) vs. 98.1 Bq/day (high-cholesteryl oleate (CO) control). The inhibition of pCEase activity with the supplementation of the Areca nut extracts could account for the decrease in [1,2(n)-<sup>3</sup>H]cholesteryl oleate absorption that resulted in decreased radioactivity in blood.
Remarkable Removal of Beta-2-Microglobulin by On-Line Hemodiafiltration
Authors: Lornoy Willy , Becaus Ignace , Billiouw Jean-Marie , Sierens Luc , van Malderen Paul 
Published: April 2003

Eight chronic, anuric hemodialysis patients were randomly treated with a high-flux polysulphone dialyzer (F80), using 6 different modes: conventional bicarbonate hemodialysis (HD), hemodiafiltration (HDF) with a replacement solution at 40, 60, 80 or 100 ml/min in postdilution and 80 ml/min in predilution. The differences in β<sub>2</sub>-microglobulin (β2M) reduction ratio and clearance were evaluated statistically by analysis of variance (ANOVA). Both studies revealed no significant difference between HD and HDF40 in postdilution, but an increasing significant difference from HDF60 to HDF100 in postdilution and with HDF80 in predilution. The mean reduction ratio ranged from 49.7 (HD) to 72.7% (HDF 100 ml/min), showing an overall statistically significant difference (p = 0.0000). For the clearance, the range was between 63.8 (HD) and 116.8 ml/min (HDF 100 ml/min) (p = 0.0000). β2M in the effluent dialysate with HDF100 ml/min reached up to a mean of 258 mg/session. Concerning small molecules (BUN, creatinine and P), there was a statistically significant different clearance for creatinine and especially for P with HDF 100 ml/min. <b>Conclusion:</b> HDF with an on-line replacement solution at 100 ml/min and a high-flux and biocompatible polysulphone membrane represents a new tool for enhanced removal of β2M. Besides a significant increase in creatinine and especially in phosphorus clearance is noted.
Prevalence of Microalbuminuria and Relationship to the Risk of Cardiovascular Disease in the Japanese Population
Authors: Tomura Shigeo , Kawada Kenichi , Saito Keiko , Lin Yu-Lin , Endou Kazue , Hirano Chiaki , Yanagi Hisako , Tsuchiya Shigeru , Shiba Kiyoko 
Published: April 2003

The prevalence of microalbuminuria and its relationship to cardiovascular disease risk factors were examined in subjects participating in an annual physical and laboratory examination program. The urinary albumin concentration and the urinary albumin/creatinine ratio were determined in morning urine specimens. A turbidimetric immunoassay was used for the measurement of urinary albumin. Of the 731 subjects, 41 (5.6%) who were weakly positive or positive on a routine dipstick test for protein were excluded from the final analysis of data. Microalbuminuria was present in 14.5% of the men, in 12.4% of the women, and in 13.2% of the entire subject population when defined as a urinary albumin concentration of 30–299 μg/ml. The prevalence of microalbuminuria was significantly higher in subjects with a high normal blood pressure (15.0%) or hypertension (26.2%) as compared with normotensive subjects (6.5%). Subjects with impaired glucose tolerance (24.3%) or hyperglycemic subjects (50.0%) had a significantly higher prevalence of microalbuminuria than normoglycemic subjects (11.3%). The prevalence of microalbuminuria was significantly higher in subjects with left ventricular hypertrophy (47.1%) as compared with those with normal electrocardiograms (11.3%). A good correlation was observed between urinary albumin concentration and albumin/creatinine ratio, and both showed a significant positive correlation with age, systolic and diastolic blood pressures, and fasting plasma glucose, total serum protein, albumin, and triglyceride levels, but not with angiotensin-converting enzyme activity. Multiple regression analysis demonstrated that both the urinary albumin concentration and the albumin/creatinine ratio show a significant positive correlation with systolic blood pressure and fasting plasma glucose. The prevalence of microalbuminuria was about 13% in this Japanese cohort, and the systolic blood pressure and the fasting plasma glucose level were demonstrated as independent risk indicators for both urinary microalbumin level and urinary microalbumin/creatinine ratio.
Nephrotic Syndrome with Mesangial Proliferative Glomerulonephritis Induced by Multiple Wasp Stings
Authors: Tauk Bill , Hachem Hassan , Bastani Bahar 
Published: April 2003

We report the case of a young male who developed severe nephrotic syndrome within 2–3 weeks after being stung by 3 wasps. A percutaneous kidney biopsy specimen revealed mesangioproliferative glomerulonephritis with occasional subepithelial deposits suggestive of early membranous nephropathy. The patient was treated with oral prednisone 60 mg/day with no significant clinical response after 4 weeks, at which point he was started on oral cyclophosphamide, 100 mg/day, while the prednisone dose was tapered to 20 mg every other day over a 2-week period. Six months after initiation of cyclophosphamide, he still has severe nephrotic syndrome. We also briefly review the literature on Hymenoptera sting associated nephrotic syndrome.
Elevation of Reactive Oxygen Species following Ischemia-Reperfusion in Mouse Cochlea Observed in vivo
Authors: Ohlemiller Kevin K. , Dugan Laura L. 
Published: April 2003

An in vivo method for assessment of changes in hydroxyl radical levels in cochlear perilymphatic spaces is described and applied to cochlear ischemia-reperfusion in the mouse. Cochlear blood flow was reversibly reduced by compression of the anterior inferior cerebellar arterial network. Changes in the production of hydroxyl radicals, used as an index of tissue production of reactive oxygen species (ROS), were determined by measuring the conversion of salicylate to 2,3-dihydroxybenzoic acid. Low levels of salicylate (0.1 m<i>M</i>) in artificial perilymph were applied by perfusion of the cochlea using a round window entry and apical exit. Perfusate was collected and analyzed by high-performance liquid chromatography. Forty minutes of partial ischemia led to a > 10-fold average increase over baseline in the concentration of hydroxyl radical, which increase persisted for at least 40–80 min following reperfusion. Our observations support previous results obtained using less direct methods, indicating that cochear ischemia-reperfusion and related damage is associated with elevated ROS levels. Development of an in vivo method for assessing changes in cochlear ROS in mice will facilitate the study of the relation between deafness genes, vulnerability to insults and dynamics of cellular processes that produce and regulate ROS.