tbuckley/cabot-search huggingface dataset:
Phase I Trial of the Anti–Lewis Y Drug Immunoconjugate BR96-Doxorubicin in Patients With Lewis Y–Expressing Epithelial Tumors
Authors: Mansoor N. Saleh, Steve Sugarman, James Murray, Joy B. Ostroff, Diane Healey, Dennie Jones, Carol R. Daniel, Donna LeBherz, Hannah Brewer, Nicole Onetto, Albert F. LoBuglio
Journal: Journal of Clinical Oncology (2000)

We conducted a phase I clinical trial of BR96-Doxorubicin (BR96-Dox), a chimeric anti-Lewis Y (Le(Y)) monoclonal antibody conjugated to doxorubicin, in patients whose tumors expressed the Le(Y) antigen. The study aimed to determine the toxicity, maximum-tolerated dose, pharmacokinetics, and immunogenicity of BR96-Dox.This was a phase I dose escalation study. BR96-Dox was initially administered alone as a 2-hour infusion every 3 weeks. The occurrence of gastrointestinal (GI) toxicity necessitated the administration of BR96-Dox as a continuous infusion over 24 hours and use of antiemetics and antigastritis premedication. Patients experiencing severe GI toxicity underwent GI endoscopy. All patients underwent restaging after two cycles.A total of 66 patients predominantly with metastatic colon and breast cancer were enrolled onto the study. The most common side effects were GI toxicity, fever, and elevation of pancreatic lipase. At higher doses, BR96-Dox was associated with nausea, vomiting, and endoscopically documented exudative gastritis of the upper GI tract, which was dose-limiting at a maximum dose of 875 mg/m(2) (doxorubicin equivalent, 25 mg/m(2)) administered every 3 weeks. Toxicity was reversible and generally of short duration. Premedication with the antiemetic Kytril (granisetron hydrochloride; SmithKline Beecham, Philadelphia, PA), the antacid omeprazole, and dexamethasone was most effective in ameliorating GI toxicity. A dose of 700 mg/m(2) BR96-Dox (doxorubicin equivalent, 19 mg/m(2)) every 3 weeks was determined to be the optimal phase II dose when administered with antiemetic and antigastritis prophylaxis. BR96-Dox deposition on tumor tissue was documented immunohistochemically and by confocal microscopy. At the 550-mg/m(2) dose, the half-life (mean +/- SD) of BR96 and doxorubicin was 300 +/- 95 hours and 43 +/- 4 hours, respectively. BR96-Dox elicited a weak immune response in 37% of patients. Objective clinical responses were seen in two patients.BR96-Dox provides a unique strategy to deliver doxorubicin to Le(Y)-expressing tumor and was well tolerated at doses of 700 mg/m(2) every 3 weeks. BR96-Dox was not associated with the typical side-effect profile of native doxorubicin and can potentially deliver high doses of doxorubicin to antigen-expressing tumors. A phase II study in doxorubicin-sensitive tumors is warranted.
Distinctive Cells Similar to Fetal Hepatocytes Associated With Liver Carcinogenesis by Diethylnitrosamine. Electron Microscopic Study 2 3
Authors: Carlo Bruni
Journal: JNCI Journal of the National Cancer Institute (1973)

This electron microscopic study was primarily of 2 aspects of rat liver carcinogenesis induced by chronic diethylnitrosamine (DENA) administration. An abnormality induced initially by DENA in the hepatocytes was an increase in the volume of the smooth endoplasmic reticulum (SER) in the form of tubules and vesicles. Between 49 and 70 days from initial administration, small foci of hepatocytes were found that differed distinctly from others because of the absence or greatly reduced volume of the SER. This system was also lacking in the tumors, observed between 91 and 122 days, but was present in increased quantity in the non-neoplastic areas both adjacent and nonadjacent to the tumors. Because of the lack of SER and other characteristics, neoplastic hepatocytes appeared similar to fetal hepatocytes. The discussion focused on: a) the observation that under these experimental conditions the lack or the greatly reduced volume of the tubular and vesicular SER was distinctive of the neoplastic hepatocytes; b) the functional significance of the increase of SER in response to DENA during the induction phase and of the absence of this system in the tumor cells; c) the rarity of SER-free cells in liver conditions other than undifferentiated tumors and fetal liver; d) the distinctive time relationship for growth between the small number of SER-free cells during the 49- to 70-day stage and the size of the tumors in the 91- to 122-day stage. Two conclusions were: 1) The few cells free of SER between 49 and 70 days might represent the initial stage in tumor formatlon, 2) the fine structure of these tumor cells expressed permanently arrested differentiation.
Uncontrolled hypertension and hyperreninemia after hemorrhage in a patient with end-stage renal disease and acquired renal cysts.
Authors: S Bongu, P F Faubert, J G Porush, F Gulmi
Journal: Journal of the American Society of Nephrology (1994)

Acquired cystic kidney disease occurs in over 74% of patients with ESRD on hemodialysis for more than 4 yr. A variety of complications have been associated with these cysts including bleeding, lithiasis, infection, obstruction, and malignant transformation. An ESRD patient who developed accelerating hypertension secondary to an acute perinephric hematoma due to a bleeding-acquired renal cyst is described. The hypertension, which was refractory to aggressive drug therapy, was controlled only after the involved kidney was removed, after the demonstration of an elevated ipsilateral renal vein renin level. This is the first case reported in which worsening hypertension, apparently due to the "Page Kidney," developed as a complication of perinephric bleeding in an ESRD patient with acquired cystic kidney disease.
AER score: An efficient predictor for sleep apnea syndrome
Authors: Mihai Udrescu, Alexandru Topirceanu, Ana Muresan, Stefan Mihaicuta
Journal: European Respiratory Journal (2014)

Objectives.  To quantitatively predict the risk of obstructive sleep apnea (OSA) without measuring the patient9s AHI, based solely on the anthrophometric risk factors in a relevant population, validated with our previous network-based methodology (Mihaicuta et. al, ERJ Sept. 2013, pp.407s).   Methods.  A reference database of 1367 patients and a newer 231 validation database from Timisoara “Victor Babes” Hospital (2005-2012; Fall 2013), with over 100 measured criteria, were used to define a methodology inspired by Network Medicine. The  AER  Score considers 4 relevant metrics: BMI, blood pressure, neck circumference and the Epworth score. The  AER  scale from 1 to 7 is divided in four risk-severity intervals: low, moderate, high and very high risk of OSA.   Results.  The  AER  predictor emerges from the statistical analysis of both patient databases and helps easily assess the risk of OSA of a new patient. Using it to prioritize patient treatment/evaluation we manage to achieve an overall risk-class correlation of 68.8% between the predicted OSA severity and actual severity determined by measuring the AHI. The rate of cumulative AHI is diagnosed based on patient scheduling  .   Conclusion.  The score serves as a predictive classifier of severity, with a high degree of accuracy, if a patient is prone to developing OSA. This model is used to categorize OSA severity and triage patients for diagnostic evaluation without the need for expensive and time-consuming investigations.
Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.
Authors: E Eisenberg, C S Berkey, D B Carr, F Mosteller, T C Chalmers
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.
Antiplatelet therapy and atherosclerotic events
Authors: C. Sudlow
Journal: BMJ (2002)

Compiling list of non-diseases is medical arroganceEditor-The arrogance of the concept of compiling a list of non-diseases is breathtaking. 1ad this list been compiled 50 years ago, which illnesses would have been listed?Multiple sclerosis, Crohn's disease, hypothyroidism?The medical community's inability to learn from past mistakes-namely, to acknowledge that most patients are honestly relating their symptoms and sincerely wish to recover-will doom generations of innocent people to the kind of humiliation and insult this ballot encapsulates.Unable to perceive their own ignorance, these commentators will enjoy a brief moment in the spotlight sneering at the proponents of non-diseases, utterly failing to advance medical science.And you wonder why the benighted sufferers of their non-diseases resort to alternative practitioners.
Antigenicity of Murine Skin Tumors Induced by Ultraviolet Light2
Authors: Margaret L. Kripke
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Antigenicity of Murine Skin Tumors Induced by Ultraviolet Light Get access Margaret L. Kripke Margaret L. Kripke 3University of Utah College of Medicine, Department of Pathology, Salt Lake City, Utah 84132. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1333–1336, https://doi.org/10.1093/jnci/53.5.1333 Published: 01 November 1974 Article history Received: 07 May 1974 Accepted: 10 July 1974 Published: 01 November 1974
Kinetic of chronic myeloid leukaemia (CML) prevalence in Northern France since the introduction of imatinib
Authors: S. Corm, J. Micol, A. Leroyer, A. Daudignon, C. Preudhomme, S. Poulain, B. Bregman, A. Oukessou, J. Lai, T. Facon
Journal: Journal of Clinical Oncology (2008)

7088 Background: We conducted a retrospective study in the Nord Pas de Calais (NPC) area of France (4 millions inhabitants) in order to assess the CML prevalence since the introduction of imatinib in 2000. Methods: We recorded from 1985 to 2006 all new CML cases living in the NPC confirmed either by cytogenetic or molecular tests. Age-standardized incidence rates were calculated on the basis of the standard world population (1990–2005 period). The raw prevalence rates were calculated year by year for the last ten years, considering the known pts diagnosed before 1985 and still alive and the possible geographic mobility of the pts. Results: 906 newly diagnosed pts were identified, corresponding to a mean age-standardized incidence rate of 0.84/100 000 person-year. Survival data were obtained for 865 (95.5%) of them. 145 pts (16%) underwent allogeneic SCT, 387 pts (42.7%) were treated with interferon (median 13.2 months, 0–157), and 416 pts (46%) were treated with imatinib (median 37.3 months, 0.1–90). In the cohort of early chronic phase CML patients treated by imatinib the rates of major and complete cytogenetic responses are respectively 75.3% (186/247) and 70.8% (175/247) and the overall 5 years survival is 82.3%. The annual CML prevalence rates (/100 000 inh.) from 1998 until 2007 are respectively (frequency of patients on imatinib (%) and mean daily dose (mg)) : 5.76 (NA-NA), 5.78 (NA-NA), 6.17 (NA-NA), 6.48 (20–448), 6.77 (15.1–449), 7.31 (50.3–410), 7.97 (62.3–403), 8.83 (67.7–421), 9.75 (65.5–416) and 10.42 (67.3–420). The mean annual increase of the prevalence is 4.1% during 1998–2002 and 9.3% during 2003–2007. Conclusions: The progression of CML prevalence in the NPC greatly accelerated after 2002, which was concomitant to a large imatinib use and may have a substantial medico-economic impact. The complete results of this unique epidemiological study will be presented at the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Leukemia Virus-Induced Alteration of Lymphocyte Ig Surface Receptors and the “Capping” Response of Mouse Spleen and Lymph Node Cells 2
Authors: John R. Kateley, John Holderbach, Herman Friedman
Journal: JNCI Journal of the National Cancer Institute (1974)

The presence of B lymphocytes in mouse spleens and lymph nodes and the ability of such cells to redistribute their surface immunoglobulin (Ig) receptors into “caps” after infection with Friend leukemia virus (FLY) were investigated. As FLY infection proceeded, the B-Iymphocyte population decreased in the spleen and increased in the lymph nodes. However, the ability of B lymphocytes to cap in either lymphoid tissue was markedly inhibited. Both the dose of FLY and the virus preparation used for infection influenced the number of Ig-Iymphocytes in the spleen and lymph nodes and the capping response of these cells. Furthermore, the inability of spleen cells to cap occurred when FLY-infected mice were immunosuppressed.
Mapping the Pathways of Resistance to Targeted Therapies
Authors: Kris C. Wood
Journal: Cancer Research (2015)

Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. Recently developed methods enable the direct and scalable identification of the signaling pathways capable of driving resistance in specific contexts. Using these methods, novel pathways of resistance to clinically approved drugs have been identified and validated. By combining systematic resistance pathway mapping methods with studies revealing biomarkers of specific resistance pathways and pharmacologic approaches to block these pathways, it may be possible to rationally construct drug combinations that yield more penetrant and lasting responses in patients.
Treatment of small-cell lung cancer on protocol: potential bias of results.
Authors: E Quoix, H Finkelstein, N Wolkove, H Kreisman
Journal: Journal of Clinical Oncology (1986)

During a 27-month period, 215 new cases of lung cancer were diagnosed at five McGill University hospitals. Only 44 patients (20%) so diagnosed were treated on available chemotherapy protocols. Six categories were used to define reasons for nonparticipation. The most important were medical reasons (MRs), 46%; non-medical reasons (NMRs), 20%; and physician preference (PP), 16%. The three remaining categories, representing 18% of exclusions, were death before diagnosis (DBD), surgical treatment (S), and a miscellaneous group (M). Median survival of patients on and off protocol was 10 and 7 months, respectively. Patients with limited disease treated off protocol for NMR and those treated with surgery did better than patients on protocol. Patients with extensive disease not enrolled because of MR did worse, and those excluded because of PP did better than patients treated on protocol. The implication of these findings for other cancer studies is that analysis of chemotherapy trials often represents treatment results in a small proportion of all patients with a given neoplasm. As such, caution must be exercised when extrapolating results to the group as a whole. We suggest that complete demographic data, including proportion of patients participating and reasons for exclusion, be included in all chemotherapeutic trial reports.
Recruitment for psychological therapy in chronic obstructive pulmonary disease (COPD) What factors influence participation
Authors: Karen Heslop, Chris Stenton, Michelle Jambon, Julia Newton, Debbie Carrick-Sen, Chris Baker, Graham Burns, Anthony De Soyza
Journal: European Respiratory Journal (2013)

Aims and Objectives 

This prospective study compared patients with COPD who participated in a randomised controlled trial (RCT) of cognitive behavioural therapy (CBT) delivered by respiratory nurses with those who were eligible but declined.

Methods 

Patients with COPD attending out-patient respiratory clinics were screened for symptoms of anxiety using the Hospital Anxiety & Depression Score (HADS). Patients with HADS score ≥8 for anxiety were invited to participate in a RCT of CBT.

Participants in the RCT were compared with those who were eligible but had declined participation in the study. Data including gender, age, COPD severity (as per NICE Criteria, 2010), anxiety and depression scores were analysed using Chi-Square tests and linear regression.

Results 

In total data from 336 patients were analysed. 174 patients were recruited to the study compared to 162 patients were eligible but declined. There were no gender differences between those who participated and those who declined (Chi-Square = 2.015, DF = 1, p>0.1). Those recruited were on average 3 years younger (p 0.1). They were not more anxious (t = -0.57 p>0.5) but they were more depressed (t= -2.05 p<0.05).

Conclusion 

There are recognised difficulties in recruiting patients with COPD for non-pharmacological treatments such as pulmonary rehabilitation. We have shown that younger patients and those who more depressed are more likely to agree to a study involving psychological treatment. Further analysis of why patients decline potentially beneficial treatments and novel strategies to engage them are needed.
Modulation of high-dose infusional fluorouracil by low-dose methotrexate in patients with advanced or metastatic colorectal cancer: final results of a randomized European Organization for Research and Treatment of Cancer Study.
Authors: G Blijham, T Wagener, J Wils, J de Greve, M Buset, H Bleiberg, A Lacave, M Dalmark, J Selleslag, L Collette, T Sahmoud
Journal: Journal of Clinical Oncology (1996)

PURPOSE Methotrexate (MTX) has been described to modulate the activity of fluorouracil (5-FU) in patients with metastatic colorectal cancer. The European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Cooperative Group (GITCCG) conducted a phase III trial to investigate the efficacy and tolarability of the addition of low-dose MTX (40 mg/m2) to high-dose infusional 5-FU (60 mg/kg over 48 hours) given weekly for 4 weeks and thereafter every 2 (for 4 weeks) and 3 weeks. PATIENTS AND METHODS Three hundred ten patients were randomized between 1987 and 1992. Eligible patients had measurable advanced or metastatic colorectal cancer and had not been pretreated with antifolates or fluorodinated pyrimidines. All 297 eligible patients were evaluated for survival; toxicity was assessed in 292 patients who received at least one course of treatment. Patients with bidimensionally measurable disease (n = 230) were also evaluated for response according to standard criteria. RESULTS The addition of low-dose MTX to high-dose infusional 5-FU led to a doubling of the response rate from 10% to 21% (P = .025). The median survival time also increased from 9.3 to 12.5 months, but this difference was not statistically significant (P = .12). High-dose infusional 5-FU with or without low-dose MTX was well tolerated, with grade 3 to 4 toxicity in greater than 10% of patients only occurring for stomatitis with the combination treatment. Performance status was the sole prognostic factor for survival in a multivariate analysis. CONCLUSION Low-dose MTX effectively modulated high-dose infusional 5-FU in a large, randomized trial in which less than 5% of patients received leucovorin.
Late-breaking abstract: Improving cell mediated immunity to non-typeable haemophilus influenzae in children with chronic suppurative lung disease
Authors: John Upham, Susan Pizzutto, Stephanie Yerkovich, Wayne Thomas, Belinda Hales, Anne Chang
Journal: European Respiratory Journal (2014)

Finding an effective vaccine to protect against non-typeable Haemophilus influenzae (NTHi) is an important goal in bronchiectasis & chronic suppurative lung disease (CSLD). NTHi infection is common in both conditions and impaired cell-mediated immunity against NTHi has been documented. Aim: Determine if a H. influenzae protein D containing conjugate vaccine improves cytokine responses to NTHi in children with CSLD. Methods: 108 children with CSLD and 32 healthy children (median age 2 yrs) were included. Those who received the 10-valent pneumococcal H. influenzae protein D conjugate vaccine (PHiD-CV) were compared with those who received multi-valent pneumococcal vaccine without protein D. Blood mononuclear cells were cultured with live NTHi. Results: Cells from CSLD children who had received 3 doses of PHiD-CV produced significantly more interferon gamma (IFN median 939; IQ range 247-2142 pg/ml) than cells from children who had received the alternative vaccines (median 338; IQ range 108-938 pg/ml; p=0.007). Importantly, the amount of IFN produced by cells from CSLD children receiving 3 doses of PHiD-CV approached that seen with healthy children. Having received 3 doses of PHiD-CV was also associated with small but significant increases in IL-13 and IL-5 (p