tbuckley/cabot-search huggingface dataset:
Risk of Death From Intercurrent Disease Is Not Excessively Increased by Modern Postoperative Radiotherapy for High-Risk Resected Non–Small-Cell Lung Carcinoma
Authors: Mitchell Machtay, Jason H. Lee, Joseph B. Shrager, Larry R. Kaiser, Eli Glatstein
Journal: Journal of Clinical Oncology (2001)

Some studies report a high risk of death from intercurrent disease (DID) after postoperative radiotherapy (XRT) for non-small-cell lung cancer (NSCLC). This study determines the risk of DID after modern-technique postoperative XRT.A total of 202 patients were treated with surgery and postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III disease. Many patients (41%) had positive/close/uncertain resection margins. The median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was calculated actuarially and included patients who died of unknown/uncertain causes. Median follow-up was 24 months for all patients and 62 months for survivors.A total of 25 patients (12.5%) died from intercurrent disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4-year actuarial rate of DID was 13.5%. This is minimally increased compared with the expected rate for a matched population (approximately 10% at 4 years). On multivariate analysis, age and radiotherapy dose were borderline significant factors associated with a higher risk of DID (P =.06). The crude risk of DID for patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%) versus 17% for XRT dose > or = 54 Gy. The 4-year actuarial overall survival was 34%; local control was 84%; and freedom from distant metastases was 37%.Modern postoperative XRT for NSCLC does not excessively increase the risk of intercurrent deaths. Further study of postoperative XRT, particularly when using more sophisticated treatment planning and reasonable total doses, for carefully selected high-risk resected NSCLC is warranted.
Bioequivalence of 20-mg once-daily tamoxifen relative to 10-mg twice-daily tamoxifen regimens for breast cancer.
Authors: A U Buzdar, G N Hortobagyi, D Frye, D Ho, D J Booser, V Valero, F A Holmes, B K Birmingham, K Bui, C Yeh
Journal: Journal of Clinical Oncology (1994)

PURPOSE We studied the bioequivalence of a new once-daily regimen of tamoxifen citrate relative to the standard twice-daily regimen of tamoxifen citrate, an established antiestrogenic treatment for breast cancer. PATIENTS AND METHODS Of 30 women with breast cancer, 27 completed this open, two-period, crossover randomized trial. During one 3-month period, patients took one standard 10-mg tamoxifen tablet twice daily; during the preceding or following 3-month period, patients took one of the new 20-mg tablets once daily. Pharmacokinetic profiles and safety parameters were assessed at the end of each 3-month treatment period. RESULTS Overall, measured concentrations of tamoxifen and its principal active metabolite, N-desmethyltamoxifen, remained relatively constant over the 24-hour sampling periods at the end of each treatment sequence. For both compounds, the percentage differences of the geometric means for all pharmacokinetic parameters indicated bioequivalence of the once-daily regimen of tamoxifen relative to the standard twice-daily regimen. Both treatment sequences were well tolerated; reported adverse events occurred at similar frequencies with the two treatment regimens. CONCLUSION The 20-mg tamoxifen tablet taken once daily was bioequivalent to the 10-mg tamoxifen tablet taken twice daily, with no difference in relative risk. The once-daily treatment is a simpler regimen and may facilitate compliance, which may enhance therapeutic outcomes during long-term treatment of breast cancer.
Search for Evidence of Feline Leukemia Virus Infection in Humans With Leukemias, Lymphomas, or Soft Tissue Sarcomas&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: P P Sordillo, R P Markovich, W D Hardy
Journal: JNCI Journal of the National Cancer Institute (1982)

Two-hundred and thirty-nine patients, including 66 with soft tissue sarcomas and 173 with hematologic cancers, were investigated for evidence of infection with feline leukemia virus (FeLV). Included in this group were 2 patients with acute lymphocytic leukemia who had lived in the same household with leukemic cats. None of the patients demonstrated measurable levels of neutralizing antibody to FeLV or had detectable FeLV antigens in peripheral blood normal leukocytes or leukemic cells. In a smaller number of patients, there was no evidence of antibody to FOCMA or of FOCMA on tumor cells in the bone marrow.
A<i>TPL2 (MAP3K8)</i>disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion
Authors: Matija Hedl, Clara Abraham
Journal: Gut (2015)

<h3>Objective</h3> IBD is characterised by dysregulated intestinal immune homeostasis and cytokine secretion. In the intestine, properly regulating pattern recognition receptor (PRR)-mediated signalling and cytokines is crucial given the ongoing host–microbial interactions. TPL2 (MAP3K8, COT) contributes to PRR-initiated pathways, yet the mechanisms for TPL2 signalling contributions in primary human myeloid cells are incompletely understood and its role in intestinal myeloid cells is poorly defined. Furthermore, functional consequences for the IBD-risk locus rs1042058 in <i>TPL2</i> are unknown. <h3>Methods</h3> We analysed protein, cytokine and RNA expression, and signalling in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR and flow cytometry. <h3>Results</h3> PRR-induced cytokine secretion was increased in MDMs from rs1042058 <i>TPL2</i> GG risk individuals. TPL2 activation by the Crohn9s disease-associated PRR nucleotide-oligomerisation domain (NOD)2 required PKC, and IKKβ, IKKα and IKKγ signalling. TPL2, in turn, significantly enhanced NOD2-induced ERK,&nbsp;JNK and NFκB signalling. We found that another major mechanism for the TPL2 contribution to NOD2 signalling was through ERK-dependent and JNK-dependent caspase-1 and caspase-8 activation, which in turn, led to early autocrine interleukin (IL)-1β and IL-18 secretion and amplification of long-term cytokines. Importantly, <i>Salmonella typhimurium</i>-induced cytokines from human intestinal myeloid-derived cells required TPL2 as well as autocrine IL-1β and IL-18. Finally, rs1042058 GG risk carrier MDMs from healthy individuals and patients with Crohn9s disease had increased TPL2 expression and NOD2-initiated TPL2 phosphorylation, ERK, JNK and NFκB activation, and early autocrine IL-1β and IL-18 secretion. <h3>Conclusions</h3> Taken together, the rs1042058 GG IBD-risk polymorphism in <i>TPL2</i> results in a gain-of-function by increasing TPL2 expression and signalling, thereby amplifying PRR-initiated outcomes.
Phase II study of <i>nab</i>-paclitaxel plus carboplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer
Authors: B. B. Benigno, J. F. Hines
Journal: Journal of Clinical Oncology (2006)

15033 Background: This open-label, non-randomized study was designed to determine the efficacy and safety of nab-paclitaxel (a 130-nm albumin-bound particle form of paclitaxel) plus carboplatin in patients with metastatic ovarian or primary peritoneal carcinoma following platinum-based chemotherapy. Methods: Eligible patients had to have either measurable disease (based on RECIST criteria) or pretreatment CA-125 levels ≥2 times the upper limit of normal in the absence of measurable disease. Patients also had to have good performance status, adequate hepatic/renal function, peripheral neuropathy ≤ grade 1, and life expectancy ≥6 months. Patients may have received prior chemotherapy for ovarian cancer, including taxane-containing regimens, provided the treatment was completed at least 6 months before enrollment. nab-Paclitaxel 100 mg/m 2 was administered IV over 30 minutes on days 1, 8, and 15 every 28 days. Carboplatin AUC6 was administered IV over 1−2 hours on day 1 every 28 days. Treatment continued for 6 cycles (or longer in the absence of unacceptable toxicity). Planned sample size was 43 patients (39 evaluable). Efficacy was determined by changes in tumor size for patients with measurable disease or changes in CA-125 levels for those with non-measurable disease. Results: To date, 10 patients have been enrolled, 2 of whom completed 2 treatment cycles; both patients had a 50% reduction in their disease (partial response). One patient had grade 4 neutropenia; grade 3 hematologic events were neutropenia (2 patients), thrombocytopenia (3), and anemia (1). Severe headache and severe nausea were reported for 2 patients each; all 4 events required medication. Conclusions: Preliminary results suggest that nab-paclitaxel 100 mg/m 2 plus carboplatin AUC6 will have antitumor activity in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer and that treatment appears to be well tolerated. Updated response and toxicity data from this study will be presented. No significant financial relationships to disclose.
Recent advances in search of oral heparin therapeutics
Authors: Rishi Paliwal, Shivani R. Paliwal, Govind P. Agrawal, Suresh P. Vyas
Journal: Medicinal Research Reviews (2011)

Abstract Unfractionated heparin (UFH) and low‐molecular‐weight heparin (LMWH) are first choices of clinicians among available anticoagulants. Currently, these agents are administered either parenterally or subcutaneously, which reduces patient compliance and acceptability. Oral heparin may serve as an alternative to both parenteral heparin as well as presently available oral anticoagulants such as warfarin. This review focuses mainly upon recent perspectives in the development of heparin as an oral anticoagulant. The possibility of its success with special emphasis to nanotechnological approaches has been elaborated. Important strategies such as the use of penetration enhancers, the development of lipid conjugates of heparin, and the incorporation of heparin in polymeric matrix systems have been discussed. Additionally, introductory information on biological activities, physiochemical aspects, and pharmacokinetic and pharmacodynamic parameters of heparin is summarized. A brief comparison of UFH and LMWH is also included for reader's benefit. Informative discussion on clinical trials with the successes and limitations of oral heparin formulations is also presented. Overall, the present review provides complete insight to the research that has been carried out for the development of heparin as oral anticoagulant. © 2011 Wiley Periodicals, Inc. Med Res Rev
Pathology of Skin Tumors Found on English Sole and Starry Flounder From Puget Sound, Washington<xref ref-type="fn" rid="FN2">2</xref>
Authors: Glynn E. McArn, R. G. Chuinard, Bruce S. Miller, Robert E. Brooks, S. R. Wellings
Journal: JNCI Journal of the National Cancer Institute (1968)

Flounders of the teleost family Pleuronectidae were collected in Port Gardner, Port Susan, and Bellingham Bay, Washington, on five occasions during 1965–66. A significant incidence of skin tumors was observed in four species: the English sole (Parophrys vetulus), the starry flounder (Platichthys stellatus), the butter sole (Isopsetta isolepis), and the sand sole (Psettichthys melanostictus). It was established that the gross and microscopic morphology of the disease in the English sole and starry flounder was identical to a disease previously described in the flathead sole, Hippoglossoides elassodon. Evidence was obtained suggesting that the three morphological patterns (angioepithelial nodule, epidermal papilloma, and angioepithelial polyp) are histogenetically related, with the angioepithelial nodule representing the earliest stage of the disease. The incidence of tumors was highest on the pigmented (eyed) side in both the starry flounder and English sole.
Subtle assessment of quality of life in PH patients on inhaled iloprost treatment
Authors: Vera Reuber, Henning Tiede, Frank Reichenberger, Robert Voswinckel, Friedrich Grimminger, Werner Seeger, Ardeschir Ghofrani
Journal: European Respiratory Journal (2012)

Background - Pulmonary hypertension (PH) is a disease characterized by vasoconstriction, remodeling of the small pulmonary vessels, and a lack of endogenous prostacyclin. Prostacyclin and its analogues are potent vasodilators and widely used in PH treatment. Information on the quality of life of PH patients is limited.  Methods - 74 patients who suffer from different forms of PH and receive inhaled Iloprost, either as first line or as add-on therapy, are followed. Patients received questionnaires concerning multiple aspects of their quality of life. NYHA functional class (NYHA), 6-minute-walk-distance (6MWD), results of the right-heart catheterization, and biomarker levels were recorded at the moment of baseline and follow-up (Nov. 2007 - Feb. 2009).  Results - 76% of patients described an improved state of health compared with the situation before start of inhalation. Furthermore significant correlations between quality of life and other important measures of PH could be shown. Improvements of NYHA-class, 6MWD, laboratory values (uric acid, BNP) and also of hemodynamic measurements (i.e. mPAP, PVR, CO, CI) during inhalative therapy with iloprost were detected. 6MWD improved significantly from 314.2±128.8 m to 354.4±131.0 m (p  Conclusion - Quality of life is an important measure for PH patients. Improvement in quality of life correlated very well with other important measures of PH.
Patients recall of an educational programme
Authors: Karen Leech, Maryam Ahmed, Carole Lynch, Barbara Rickard, Gill Owen, Wayne Kempson, Martin Allen
Journal: European Respiratory Journal (2014)

Introduction 

Education of patients with COPD is an integral part of many care pathway, but we are uncertain if delivery in hospital at the time of an acute exacerbation is effective. We delivered a standardised program that included verbal and written information and evaluated patients recall post discharge.

Method 

An anonymous questionnaire asked about the education given was posted out to patients. The time frame of the questionnaire varied from 8–52 weeks post discharge.

Results 

A total of 155 patient questionnaires were sent out of which 57 (37%) were returned.

45 (79%) patients remembered being given verbal information.

36 (64%) understood all the information they were given and 16 (28%) understood some of the information. All literate patients were issued with written information however, 34 of 56 patients stated they received the information.

90% of patients received a management plan.

34 (59%) patients stated they received a plan, 5 (9%) couldn't remember and 18 (32%) reported to have not received a plan.

28 patients smoked prior to admission. 2 declined advice, 7 had no recall of having had advice while 19 ( 68%) recalled having smoking cessation advice prior to discharge: 14 reported to still smoke. Recognising the audit period of 8 weeks, half of the patients who smoked prior to admission had managed to stop.

Conclusion 

Information given to patients during an exacerbation is not always recalled in the weeks and months that follow. The education we give as care providers needs to be reinforced. However, smoking advice given during an exacerbation did appear to have an impact, with half the smokers reporting they stopped. The reason why the recall from smoking cessation differs to that of inhaler technique or self-management is unclear.
Suppression of Natural Killer Cell Activity by Friend Murine Leukemia Virus
Authors: Dewey J. Moody, Steven Specter, Mauro Bendinelli, Herman Friedman
Journal: JNCI Journal of the National Cancer Institute (1984)

BALB/c mice infected with Friend murine leukemia virus (F-MuLV) evinced a decreased natural killer (NK) cell activity to susceptible target cells. This suppression increased as the interval between infection and assay was lengthened. The decrease in NK activity due to F-MuLV infection was partially reversible when spleen cells were pretreated with interferon before the cytolytic assay. The ability of F-MuLV-infected splenocytes to bind to target cells was unaltered, indicating that the defect was in the lytic phase of NK cytolysis. When mixed with uninfected spleen cells, F-MuLV-infected splenocytes suppressed their NK cell activity. This suppression was associated with a nylon wool-adherent cell population in the F-MuLV-infected spleens.
Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Giuseppe Frasci, Vito Lorusso, Nicola Panza, Pasquale Comella, Gianpaolo Nicolella, Andrea Bianco, Giuseppe De Cataldis, Annunziato Iannelli, Domenico Bilancia, Mario Belli, Bruno Massidda, Francovito Piantedosi, Giuseppe Comella, Mario De Lena
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate whether the addition of gemcitabine (G) to vinorelbine (V) improves survival and quality of life (QoL) among elderly patients with advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC aged ≥ 70 years with advanced disease were randomly allocated to receive V 30 mg/m 2 on days 1 and 8 every 3 weeks or G 1,200 mg/m 2 + V 30 mg/m 2 on days 1 and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned based on the first 60 patients per arm. RESULTS: In May 1999, the survival data were analyzed of 120 eligible patients (V group = 60; G + V group = 60) who had been randomized from June 1997 to February 1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had died (G + V group = 41; V group = 52). In the G + V group, median survival time was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks and 13% in the V group. According to multivariate Cox analysis, the risk of death in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0.29 to 0.79; P &lt; .01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The overall response rates were 22% and 15% in the G + V and V groups, respectively. CONCLUSION: In elderly patients with NSCLC, G + V treatment is associated with significantly better survival than is V alone.
First-Line Chemotherapy With Epirubicin, Paclitaxel, and Carboplatin for Advanced Ovarian Cancer: A Phase I/II Study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group
Authors: A. du Bois, H. J. Lück, T. Bauknecht, W. Meier, B. Richter, W. Kuhn, J. Quaas, J. Pfisterer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the “third drug” into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m 2 ) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m 2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m 2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m 2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.
Impact of cigarette smoke on function and expression of immunoproteasomes
Authors: Ilona Keller, Angela Dann, Oliver Vosyka, Shinji Takenaka, Petra Nathan, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2014)

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease (COPD). While there is profound evidence for involvement of MHC II-mediated immune responses in COPD pathogenesis, MHC I-mediated immunity, however, has not been investigated in detail. MHC I antigen presentation requires the breakdown of cellular proteins by the proteasome.  Here, we analyzed the effects of CS on the composition and activity of the proteasome. In particular, we focused on a specialized form of proteasome, namely the immunoproteasome (IP), whose proteolytic activities contribute to improved generation of antigenic peptides.  The catalytic IP subunits LMP2 and LMP7 are present at low levels in parenchymal cells of the lung such as alveolar and bronchial epithelial cells and fibroblasts, but can be rapidly induced by treatment with IFNγ. Repeated treatment of epithelial A549 or fibroblast HFL-1 cells with CS extract not only reduced basal IP expression but also attenuated IFNγ mediated induction of IP. In contrast, immune cells, such as splenocytes and spleen-derived dendritic cells, responded to CS treatment by further increasing IP expression. Importantly, MHC I-mediated antigen presentation was severely impaired in CS-treated cells as evidenced by two independent antigen presentation assays.  In vivo , immune cells of the lung revealed altered IP expression in response to smoke. Low parenchymal but high immune cell-mediated expression of the IP-subunit LMP2 was also observed in COPD tissues as determined by immunohistochemical analysis.  Our data suggest that altered MHC I antigen presentation in response to CS might contribute to the pathogenesis of COPD.
Tolerance Induction and Sensitization by Preincubation of Bone Marrow With Allogeneic Erythrocytes
Authors: Delta E. Uphoff
Journal: JNCI Journal of the National Cancer Institute (1971)

In vitro preincubation of donor bone marrow with allogeneic erythrocytes greatly influenced the success of bone marrow transplantation into lethally irradiated recipients. The effect was the abolition of the graft-versus-host reaction, diminution of the severity of the reacti on, or an increased reactivity, depending on the antigenic relationships among the marrow donors, the erythrocytes, and the various recipients. Unresponsiveness or tolerance resulted when the recipient was as immunogenic or less immunogenic than the erythrocytes used in the incubation as “priming” antigen for the bone marrow. However, when the recipient was more immunogenic than the erythrocyte donor strain, a graft-versus-host reaction of varying degrees of severity occurred. From these observations, the concept that antigenicity (or immunogenicity) can be ranked was developed. A direct relationship was established between tolerance and sensitization by demonstration of a graded responsiveness from the unresponsive state, through varying degrees of responsiveness, to an accelerated response (sensitization).