tbuckley/cabot-search huggingface dataset:
Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone.
Authors: P Mauch, T Goffman, D S Rosenthal, G P Canellos, S E Come, S Hellman
Journal: Journal of Clinical Oncology (1985)

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.
Efficacy of oral moxifloxacin monotherapy for Japanese HCAP patients with low potentially drug-resistant pathogens
Authors: Yu Kasamatsu, Kiyokazu Yoshinoya, Masatoshi Kadoya, Yoshihiro Kasamatsu
Journal: European Respiratory Journal (2012)

Background:  Moxifloxacin (MFLX) is one of the recommended drugs for the patients with low potentially drug-resistant pathogens according to Japanese healthcare-associated pneumonia (HCAP) guideline. The difference between MFLX monotherapy and combination therapy of MFLX and β-lactam for Japanese HCAP patients was unclear.  Method:  A retrospective cohort study was conducted at Matsushita Memorial Hospital in Japan. Eligible patients were diagnosed as mild or moderate grade HCAP with chest radiography findings and their history and treated with oral MFLX. The evaluation of efficacy was judged from improvement of clinical symptom, laboratory data and chest radiography findings within 7days.  Result:  Of 151 Japanese HCAP patients from December 2008 to October 2011 were eligible. Their mean age was 74.6 years (SD 11.4), and 101 patients (66.9%) were treated with MFLX monotherapy. Efficacy rate was 81.2% and 80% (p=n.s.). The rate of gastroenterological trouble in the combination therapy group was significantly higher than that of the trouble in the monotherapy group (p=0.05).  Conclusion:  Combination antibiotic therapy did not improve the outcome in HCAP patients with low potentially drug-resistant pathogens. If HCAP patients with low potentially drug-resistant pathogens can ingest, they should be treated with oral MFLX monotherapy.
A phase II study of denileukin diftitox (ONTAK) in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia
Authors: M. Lilly, P. Kuriakose, F. Turturro, J. Berdeja, R. Kerr, A. Surendranathan, J. Black, A. Frankel
Journal: Journal of Clinical Oncology (2005)

6649 Background: Some chronic lymphocytic leukemia (CLL) cells express CD25, a component of the IL-2 receptor. Denileukin diftitox (ONTAK, Ligand Pharmaceuticals) is a fusion protein of the enzymatically active domain of diphtheria toxin with interleukin-2 (IL-2),targeting malignancies expressing the medium and high affinity IL-2 receptors. We performed a phase II study to evaluate the efficacy and toxicity of ONTAK in patients with fludarabine-refractory CLL. Methods: Denileukin diftitox dose was 18μg/kg IV daily for 5 days every 3 weeks, for a maximum of 8 cycles. Patients were evaluated for response by clinical criteria. Results: Sixteen patients have been enrolled, with 11 patients being evaluable for response (completed 3 cycles), and 13 evaluable for toxicity (completed at least one full 5-day cycle). Fifty-six percent (9/16) were Rai stage III-IV, with a median of 3 prior therapies (range 1–6). Seven of 15 evaluated patients had more than 20% CD25(+) cells. The overall response was 27%, with 1 CR (9%, duration of response 9+ months) and 2 PR (18%, duration of response 5+, and 7+ months). One patient had a 71% decrease in absolute lymphocyte count while his lymphadenopathy increased on treatment. Four patients (45%) had progressive disease after cycles 3, 4, 4, and 7, respectively. Three of 16 patients treatment, and an additional 3/16 were removed from study by the investigators for toxicity. The grade 3/4 toxicities encountered were: neutropenia 4/13, thrombocytopenia 4/13, vascular leak syndrome 3/13, left ventricular cardiac dysfunction 1/13, hypotension 2/13, tachyarrhythmia 3/13, elevated PT 1/13, fatigue 1/13, rash 1/13, SIADH 1/13, constipation 1/13, vomiting 2/13, petechiae 1/13, transient elevation of GGT 1/13, transient elevation of AST/ALT 7/13, hyperglycemia 4/13, electrolyte imbalance 8/13, infection and/or febrile neutropenia 4/13, insomnia 1/13, visual disturbance 1/13, dyspnea 2/13, hypoxia 2/13. Conclusions: Denileukin diftitox has moderate activity in CLL, with toxicities that can be managed with adequate premedication and close monitoring. Two of three responses in peripheral blood lymphocytosis were seen in subjects with CD25(+) CLL cells. No significant financial relationships to disclose.
Metastatic Capacity of Cloned T10 Sarcoma Cells That Differ in H-2 Expression: Inverse Relationship to Their Immunogenic Potency&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Katzav, S Segal, M Feldman
Journal: JNCI Journal of the National Cancer Institute (1985)

Clones of the T10 sarcoma, originated in a (H-2b × H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.
Abstract 11: Transgenic Overexpression of Snf1-Related Kinase in the Heart Improves Cardiac Metabolic Efficiency and Response to Myocardial Ischemia
Authors: Amy Rines, Michael Burke, Rongxue Wu, E Dale Abel, Hossein Ardehali
Journal: Circulation Research (2012)

Introduction: Snf1-related Kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated kinase. The function and substrates of SNRK are unknown. We have found that SNRK is upregulated in hearts from patients with ischemic cardiomyopathy, and our previous gene array data suggested that SNRK alters metabolic gene expression. Here, we assessed the hypothesis that SNRK regulates cardiac metabolism. Results: SNRK transgenic mice with specific overexpression of SNRK in the heart displayed decreased glycolysis (1267.66 vs. 1925.60 nmol/min/g dhw, p=0.004, n=6), glucose oxidation (441.73 vs. 602.68 nmol/min/g dhw, p=0.068, n=6), and palmitate oxidation (262.39 vs. 385.07 nmol/min/g dhw, p=0.005, n=6) compared to wild type littermate controls in perfused working hearts. However, cardiac power output and function were maintained, demonstrating that SNRK transgenic mice have increased metabolic efficiency. Mitochondria isolated from SNRK transgenic mice had increased state 3 respiration and oxidative capacity, along with an increased respiratory control ratio (state 3/state 4 respiration), indicating reduced mitochondrial uncoupling. To identify the mechanism for the effects of SNRK on metabolic flux, we performed a yeast two hybrid screen with SNRK bait. Tribbles homolog 3 (Trb3), an inhibitor of Akt, was identified as a SNRK-interacting protein, which was verified by co-immunoprecipitation and mammalian two hybrid assay. Trb3 protein levels were increased in the SNRK transgenic mice, and phosphorylation of Akt and its substrate GSK3 was reduced. SNRK transgenic mice also had decreased mRNA levels of glucose transporter 1 and 4, hexokinase II, and phosphofructokinase. Additionally, mRNA levels of the fatty acid metabolism regulators peroxisome proliferator-activated receptor (PPAR) α and PPARγ were reduced, as well as their targets uncoupling protein 2 and 3. Finally, SNRK transgenic mice had decreased infarct size compared to wild type littermates (14.35% vs. 20.63% total left ventricle area, p=0.023, n=6) following myocardial infarction for seven days. Conclusions: Our results demonstrate that SNRK increases cardiac metabolic and mitochondrial efficiency and resistance to myocardial infarct cell death.
Chronic Granulocytic Leukemia (CGL) During the Course of Chronic Lymphocytic Leukemia (CLL): Correlation of Blood, Marrow, and Spleen Morphology and Cytogenetics
Authors: Jacqueline Whang-Peng, Harvey R. Gralnick, Ralph E. Johnson, Elaine C. Lee, Arnold Lear
Journal: Blood (1974)
Promising targets in renal cell cancer: Met and ron-beta
Authors: J. J. Lambea, I. Alvarez, R. Lastra, M. Ortega, E. Aguirre, M. Ruiz-Echarri, E. Millastre, J. I. Mayordomo, P. Escudero, W. Storkus, A. Tres
Journal: Journal of Clinical Oncology (2006)

20119 Background: The activation of Tyrosin Kinase Receptors (RTKs) produces several effects about cellular response. These are membrane receptors that bind differentiation signals, grow factors and cellular mediators. The interaction with their ligand causes the phosphorilation and internalization in the endosome. By a metabolic way, these receptors are degradated into the proteasome to small peptides that are expressed over the cellular surface joined to MHC class I mollecules, getting a better immunogenic recognition of the tumor cells. It is known that the bigger expression of the tyrosin kinase receptors in tumors is associated with an aggressive phenotype. For example overexpression of ephA2 or EGFR. Our study is based in the demostration of the overexpression of other receptors in renal cell cancer, a tumour with a disappointing response with treatment in advanced stages. On this way we can use them as targets for monoclonal antibodies and for citotoxic lymphocites CD8 stimulated that will join to peptides presented in MHC class I after the proteasomic degradation. Methods: We use Western-Blot for identifying the overexpressed RTKs in relation to normal tissue and as a reference the expression of beta-actin, that is present in every cells. The cells are from 5 murine renal cell cancer lines, (thanks to Hillman Cancer Center Institute, University of Pittsburgh. Pennsylvania. USA). The control is a murine cell line that is very similar to normal renal tissue (HK). We calculate the ratio of expression compared with the expression of normal tissue with an statistical analysis. Results: HER-2, VEGFR-2, Met, Ron-beta are overexpresed in renal cell cancer in a murine model, as EGFR (epidermic growing factor receptor). Conclusions: Met may be excellent therapeutic and inmunologic target and in selected cases of renal cell cancer. It’s known that EGFR and VEGFR are also good targets. Future research about these targets will get new options of combined immunotherapy (vaccines and monoclonal antibodies). No significant financial relationships to disclose.
Adjuvant chemotherapy for head and neck cancer.
Authors: C Jacobs
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.7.823 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2738620 Adjuvant chemotherapy for head and neck cancer. C JacobsxC JacobsSearch for articles by this author Show More Stanford University School of Medicine, CA. https://doi.org/10.1200/JCO.1989.7.7.823 First Page PDF © 1989 by American Society of Clinical Oncology
A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial
Authors: S. Yoshino, T. Nishimura, S. Hazama, M. Oka, H. Ozasa, R. Shimizu, T. Furuya, S. Fukuda, T. Satoh, T. Hara
Journal: Journal of Clinical Oncology (2007)

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m 2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.
Phase I study of RX-0201 in patients with advanced or metastatic solid tumors
Authors: S. M. Malik, J. Hwang, J. Marshall, P. Ramzi, J. A. Posey, C. Ahn, Y. Lee
Journal: Journal of Clinical Oncology (2006)

13102 Background: RX-0201 is a 20-mer oligonucleotide that is complementary to Akt-1 mRNA. Strong evidence exists that Akt plays a very important role in cancer progression by stimulating cell proliferation and inhibiting apoptosis. Over-expression of constitutively activated Akt in many cell types promotes cellular transformation. In addition to reducing Akt mRNA levels and inhibiting the expression of Akt protein, in vitro pharmacology studies have demonstrated that RX-0201 suppressed cell proliferation in carcinomas of the brain, breast, cervix, colon, head &amp; neck, kidney, liver, lung, ovary, pancreas, prostate, stomach and melanoma. In vivo studies have also shown that RX-0201 significantly inhibits the growth of tumor in human prostate and brain cancer of nude mice models. This study is designed to determine the maximum tolerated RX-0201 dose in patients with advanced malignancies. Methods: Patients with solid tumors for whom no standard therapies exist, Karnofsky PS&gt;70, adequate hepatic and renal function and normal coagulation parameters were eligible. Eligible patients were scheduled to receive 2 treatment cycles with RX-0201 via continuous infusion for 14 days with 7 days off q 21 days. Dose escalation was based on observed treatment-related toxicities. One patient was enrolled at each dose level (6 mg/m2/day - 315mg/m2/day). Tumor measurements were performed at screening and at the completion of treatment cycle 2. Tumor biopsies were obtained at screening and at the completion of treatment cycle 2 to look for inhibition of AKT in tumor cells. Plasma samples for pharmacokinetic analyses were collected. Results: To date 9 patients have been enrolled, 4 with GI malignancies, 1 with small cell lung cancer, 2 with breast cancer and 1 with locally advanced Basal Cell carcinoma. 6/9 patients were able to complete the 2 cycles.1/9 patients were taken off study because of withdrawal of consent due to grade 1 vomiting. 8 patients were taken off for disease progression. Drug related toxicities were Grade 1 and included fatigue, dizziness, cough vomiting and myalgia. Conclusions: While enrolment is still ongoing, the RX-0201 has been well tolerated upto 315mg/m2 in this previously heavily treated patient population. Once MTD is reached phase II trials will be planned. PK and PD data will be presented. [Table: see text]
Intravesical therapy for superficial bladder cancer: is it a wash?
Authors: K L Kilbridge, P Kantoff
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8270966 Intravesical therapy for superficial bladder cancer: is it a wash? K L KilbridgexK L KilbridgeSearch for articles by this author , P KantoffxP KantoffSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.1.1 First Page PDF © 1994 by American Society of Clinical Oncology
The weight of radiological severity in patients with non-CF bronchiectasis
Authors: Sara Lonni, Nicola Sverzellati, Anna Maria Zanaboni, James D. Chalmers, Giulia Bonaiti, Giulia Suigo, Sara Annoni, Paola Faverio, Alberto Pesci, Stefano Aliberti
Journal: European Respiratory Journal (2014)

In the recently published Bronchiectasis Severity Index (BSI), radiological severity of non-CF bronchiectasis (NCFBE) has been assessed by a modified Reiff score (RS). A better accuracy of the BSI could be obtained if the more comprehensive Bhalla score (BS) will be used. To test this hypothesis, an observational, prospective study was performed on NCFBE patients at the bronchiectasis clinic of the San Gerardo University Hospital, Monza, Italy, during the year 2011. Both modified Reiff and Bhalla scores were calculated from chest HRCT scans by two external radiologists and compared among the BSI. The occurrence of at least one hospitalization for exacerbation during 2011 was the study outcome. Rounded averaged beta-coefficients of the BS identified by a Cox regression analysis were used to award points for the BSI score. The performance of the BSI including either the RS or the BS for hospital admission was assessed using the area under the receiver operator characteristic curve (ROC). A total of 146 consecutive NCFBE patients (48% males; median age: 68 years) were enrolled. Median values of the RS and BS in the study population were 6 and 19, respectively. 0 points were given for a RS
Abstract 12610: Effect of Smoking Reduction on Endothelial Glucocalyx and Arterial Wave Reflection During Medically-aided Smoking Cessation Program
Authors: Ignatios Ikonomidis, Kalliroi Kourea, Georgios Pavlidis, Elias Tsougos, Margarita Marinou, Ioannis Papadakis, Hellen Triantafyllidi, Maria Anastasiou-Nana, John Lekakis
Journal: Circulation (2013)

The integrity of endothelial glucocalyx plays a vital role in vascular permeability and inlammation.Smoking cessation is related with improved vascular function.Pharmacotherapy is a standard component of evidence based smoking cessation treatment.This study investigated the effects medically-aided smoking cessation on glucocalyx thickness and arterial elasticity.

Methods: We examined 119 smokers (58% males,age:51±10y )without cardiovascular disease treated with transdermal nicotine patches(60%) and/or varenicline (40%) before, at 4 and 12 weeks after treatment during validated smoking cessation program.We measured a )exhaled carbon monoxide(CO, ppm), self-reported number of cigarretes/day b)carotid-femoral pulse wave velocity(PWVc m/sec) and augmentation index(AI %)c)perfused boundary region (PBR)of the sublingual arterial microvessels (ranged from 5-25 microns) using Sideview Darkfield imaging.The PBR in microvessels is the cell-poor layer which results from the phase separation between the flowing red blood cells (RBC)and plasma.The PBR includes the most luminal part of glycocalyx that does allow cell penetration.Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glucocalyx.Twenty non-smokers served as controls

Results: At baseline smokers had higher PBR,PWVc and AI than non-smokers (2.05±0.17vs.1.77±0.14,10±2 vs.8.5±2,33±18vs.15±10,p≤0.05).At 12 weeks of follow-up there was a reduction of CO,number of smoked cigarettes (32±18 vs.10±13 and 31±8 vs.6±9,) and a parallel reduction of PBR (2.05±0.17 vs.1.93±0.24),and AI (33±18vs.15±1 )(p≤0.05).These differences in vascular markers were not evident after 4 weeks of f/u. At 12 weeks a decreasing CO was related with improved PBR,PWV and AI (r=0.88,r=0.53,r=0.47,p≤0.05) while an improved PBR was related with reduced AI (r=0.47,p≤0.05)

Conclusion: Endothelial glucocalyx thickness is reduced in smokers compared to non-smokers.Medically-aided smoking reduction contributes to restoration of glucocalyx thickness and reduction of abnormal arterial wave reflections. Improvement of Endothelial glucocalyx is linked with improved arterial elasticity during smoking cessation.
Extending IVF cycles beyond usual three or four shows benefit
Authors: Jacqui Wise
Journal: BMJ (2015)

Extending the number of in vitro fertilisation (IVF) cycles beyond the usual three or four could be beneficial, a UK study published in JAMA has found.

The prospective study included 156 947 women who received 257 398 IVF ovarian stimulation cycles from 2003 to 2010 and were followed up until 2012.1 The median age of the women at the start of treatment was 35, and they had been infertile for an average of four years.

Overall, the live birth rate from …