tbuckley/cabot-search huggingface dataset:
A multicenter, open-label, phase I/II study in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with L-BLP25: 2-year survival and safety results
Authors: N. R. Murray, C. Butts, C. Smith, P. M. Ellis, K. Jasas, A. Maksymiuk, G. Goss, G. Ely, D. Soulieres
Journal: Journal of Clinical Oncology (2008)

3047 Background: L-BLP25 (Stimuvax; BLP25 liposomal vaccine) is an innovative cancer vaccine that incorporates the immunoadjuvant monophosphoryl lipid A and a synthetic MUC1 lipopeptide in a liposomal delivery system. Previous studies have shown that L- BLP25 has the potential to extend the survival of patients (pts) with stage IIIB locoregional NSCLC (Butts C et al., J Clin Oncol 2005;23:6674- 81). The primary objective of this study was to assess the safety of the current formulation of L-BLP25 in pts with unresectable stage IIIA or IIIB NSCLC with survival as a secondary objective. Methods: Pts with stable disease (SD) or an objective response to upfront chemoradiation received L-BLP25 + best supportive care. All pts were vaccinated according to a previously described schedule (Butts C et al., J Clin Oncol 2005;23:6674–81). Maintenance vaccinations were administered q6w until disease progression. Primary and secondary endpoints were safety and survival, respectively. Results: At September 17, 2007, 22 pts were evaluable for survival and toxicity. Of these, 1 had a complete response, 17 had a partial response and 4 had SD following chemoradiation. The 2-year survival rate was 64% (95% CI: 44–84) with a median follow-up of 2.2 years. Adverse events (AEs) occurred in all pts (16 considered L-BLP25-related). Most common (>10%) L-BLP25- related AEs besides injection site reactions were fatigue and nausea (all grade 1 or 2 except 1 case of grade 3 pneumonia). Eleven pts (50%) had an injection site reaction. Two pts discontinued L-BLP25 due to toxicity. As of September 2007, 9 pts remained on study treatment. Conclusions: The 2-year survival rate of 64% with maintenance L-BLP25 seen in this trial is similar to the 2-year survival rate recently observed in a phase IIb study of L-BLP25 in NSCLC (L-BLP25: 57%, control: 33%) (Butts C et al., J Thoracic Oncol 2007;2[Suppl. 4]:S332–33). It also compares favorably with previously reported survival for chemoradiation in stage III NSCLC. In addition, L-BLP25 was well tolerated with a similar safety profile to previous studies. A global phase III study is ongoing to further evaluate L-BLP25 in this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Biomira, Merck Merck
The Schizophrenia Polygenic Risk Score
Authors: Kenneth S. Kendler
Journal: JAMA Psychiatry (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma
Authors: Sarah Schrödter, Martin Braun, Isabella Syring, Niklas Klümper, Mario Deng, Doris Schmidt, Sven Perner, Stefan C Müller, Jörg Ellinger
Journal: Molecular Cancer (2016)

Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. In order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3. Differential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death. Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.
Abstract 18239: Evaluation of Right Ventricular Function in Patients Undergoing Mitraclip Implantation
Authors: Vitantonio Di Bello, Cristina Giannini, Marco De Carlo, Fabio Guarracino, Andrea Pieroni, Francesca Donati, Erica Minuti, Anna S Petronio
Journal: Circulation (2012)

Background: Patients with severe mitral regurgitation (MR) at high surgical risk can undergo percutaneous mitral valve repair by Mitraclip device implantation, yielding good results in terms of quality of life, MR reduction and improvement of left ventricular (LV) function. Our aim was to assess the changes in right ventricular (RV) function after Mitraclip implantation. Methods: Forty consecutive patients affected by severe symptomatic MR underwent clinical evaluation and echocardiographic assessment before Mitraclip implantation and during follow-up at 1, 3 and 6 months. Results: The mean age of patients was 75.8±7.5 years, 57.5% (n=23) were male with a mean logistic EuroSCORE of 32.2%±26.3 and a mean LV ejection fraction (EF%) of 38±11. All patients were symptomatic with 36 (90.0%) in NYHA classIII-IV. Thirty-one patients (77.5%) had functional MR, while 7 (22.5%) had a degenerative MR. Acute device success of implantation was achieved in all patients. One clip was placed in 29 patients (72.5%) while 2 clips were deployed in 11 patients (27.5%). Overall mortality was: 0% in-hospital, 2.9% at 1 month, and 14.7% at 1 year follow-up. We didn’t find significant changes in all others RV parameters. Furthermore no differences in RV function changes were present between degenerative and functional MR groups. A significant mild correlation was found between the improvement of NYHA class and the improvement of RV TDI S’ wave at six month follow-up (r=-0.38, p =0.04). Conclusion: MitraClip implantation has induced a significant reduction of left ventricular volume overload. The concomitant reduction of left ventricular filling pressure, reflected nearly immediately on clinical profile and on hemodynamics of the right sections. In fact, since the first month of follow up, we observed both a significant reduction of estimated pulmonary artery systolic pressure and a significant increase of longitudinal RV systolic function as shown by the increase of TAPSE and RV S’TDI.
Gemcitabine, etoposide and dexamethasone in the treatment of heavily pretreated patients with non Hodgkin's lymphoma
Authors: G. Spectre, N. Goldchmidt, A. Gural, O. Paltiel, D. Ben-Yehuda
Journal: Journal of Clinical Oncology (2004)

6691 Background: Approximately 30%–60% of patients with aggressive non Hodgkin lymphoma (NHL) will require a second line treatment. Gemcitabine, a new non cross resistant drug has been evaluated as a single drug in >90 patients with this disease. We evaluated the response rate to the combination of gemcitabine, etoposide and dexamethasone in patients with relapsed or refractory NHL. Methods: 20 patients with refractory or resistant aggressive NHL were treated with gemcitabine 1000 mg/m2 on days 1 and 8, etoposide 100mg/m2 on day 1 and dexamethasone 8mg/m2 on days 1,2,8,9, on a 21 days cycle. Results: These were mostly heavily pretreated patients, who were not candidates for stem cell transplantation. All were symptomatic and required treatment for palliation. The median age was 64 years. The patients received between 1–6 courses of treatment .The only grade 3–4 toxicity documented was myelosupression. Neutropenia was well controlled with GCSF and there were no major bleeding events. There were 4 hospitalizations for febrile neutropenia in 65 total courses administered. 2 patients died of infections (1 was neutropenic). 7 patients stopped treatment before their disease could be objectively evaluated. Among the 13 patients who could undergo restaging,1 patient achieved complete remission, 6 partial remission, and 6 progressed. Initial subjective and/or objective improvement was documented in 11 patients; however 9 progressed during or immediately after stopping the protocol. Reasons for stopping the protocol were no response or disease progression (13 patients), end of protocol (2), death from infections (2), bone marrow transplantation (1) and evidence of myelodysplastic syndrome( 2). None of the 20 patients had long term remission, however 11 patients experienced symptomatic improvement lasting between 2–5 months. Conclusions: Despite a relatively low response rate, this regimen has a low toxicity profile and some heavily pretreated patients with NHL experienced a few months of of subjective palliation with maintenance ambulatory lifestyle. Further studies are required to assess the response rate earlier in the course of the disease. No significant financial relationships to disclose.
Control of δ-Aminolevulinic Acid Synthetase and Tyrosine Aminotransferase in Tumors and Livers of Tumor-Bearing Rats2
Authors: Herbert L. Bonkowsky, Donald P. Tschudy, Annie Collins, Joyce M. Doherty
Journal: JNCI Journal of the National Cancer Institute (1973)

Administration of allylisopropylacetamide (AIA) increased the levels of δ-aminolevulinic acid synthetase (ALAS) and tyrosine aminotransferase (TAT) in rat liver. Induction of these enzymes was measured in the tumors and livers of rats bearing Morris hepatomas 5123, 7288C-TC, 7777, 7800, 7794A; Walker carcinosarcoma 256; Fibrosarcoma 4956; and Snell hepatoma 648. a) ALA synthetase was low and not inducible in any tumors studied; b) in livers of tumor-bearing rats, basal levels and peak-induced levels of ALA synthetase were decreased below those seen in normals; c) TAT levels were variable in the tumors, and the enzyme was clearly induced in 4 of the 8; and d) in host livers, basal TAT levels and induced levels were as high as or higher than in controls. Failure to observe induction of ALAS in the tumors did not result from the presence of an inhibitor. Hepatic ALA synthetase induction is known to be blocked by heme and certain carbohydrates (“glucose effect” ). Evidence was obtained indicating that the damped induction of host hepatic ALA synthetase was not caused by heme or lactate released from tumors.
Gemcitabine plus irinotecan (GI) in recurrent cervical cancer: A pilot study
Authors: A. Porras, F. Quistían, D. Gallardo, R. Herrera-Aguilera
Journal: Journal of Clinical Oncology (2004)

5118 Background: Cervical cancer is the most common tunor among mexican female population. The majority of cases are seen in advanced stages. 40% of all the patients will have recurrent disease and the 5 years survival of these patients is of 20 to 30%. Gemcitabine and Irinotecan are active as single agents The aim of this trial was to prove the combination with gemcitabine plus irinotecan in patients with recurrent cervical cancer,. Patients and Methods: 10 patients were treated with the combination of Gemcitabine plus Irinotecan until disease progresión or limited toxicity. (25–79); All patients had histologically proven disease,; and all patients had clinically measurable disease by CT scan. Treatment: Gemcitabine 1000 mg/m2, Irinotecan 100 mg/m2 days both day1 and 8, repeated q 21 days as blood count permited. Results: We included 10 pt feb 03 to oct 03, median age was 50.5 years and all 10 had epidermoid tumors and recurrent disease, pelvic in 7, metastatic in 1 and both in 2, initial treatment was radiotherapy in 8 and, in 2 patients concurrent with gemcitabine as radiosensitizer; GI was administered as first line therapy in 8 and as a second line in 2, Toxicity G3,4: we administered 37 courses and we had Anemia in 9/37 (24%), Leucopenia in 1/37 (2.7%); thrombocytopenia 2/37 (5.4%), Non hematological toxicity: alopecia G3,4 in 2 pt, one patient with diarrea G4 who died. OR 3/10 (33%) CR was 2/10 (22%), PR 1/10 (11%) and PD 6/10 (66%). the duration response in three pt has been 6, 6 and 4 mo, Median follow up was 5mo (range 3–9), MOS was 4.85 months. Actually we have one patients alive without evidence disease and two alive with tumoral activity. Conclusión: Gemcitabine plus Irinotecan is an active and well tolareted scheme (R0 33%) in a very difficult group of patients with recurrent cervical cancer, we got responses in the three pt with metastasic disease one of them CR, except for the gastrointestinal toxicity in one patient. No significant financial relationships to disclose.
Stage III non small lung cancer (NSCLC): Docetaxel (D), gemcitabine (G), and cisplatin (C) as induction chemotherapy, an Italian phase I study
Authors: S. De Santis, V. Donato, M. R. Migliorino, B. Tedesco, S. Condo, F. De Marinis
Journal: Journal of Clinical Oncology (2007)

18201 Background: Based on the several clinical trials, combined modality therapy became the standard of care for patients with stage III NSCLC “unresectable” with good performance status (Kathy S. Albain, Educational Book ASCO 2006, 453–461; Thomas E. Stinchcombe, Oncologist 2006, 11, 809–823). The most effective induction chemotherapy has yet to be determined. The objective of this prospective phase I study was to define the maximum tolerated dose (MTD), and to evaluate the activity and safety of one of the third generation triplets as a full dose neoadjuvant regimen in patients (pts) with unresectable Stage III NSCLC. Methods: In this study, chemotherapy-naïve pts with stage IIIA-N2 bulky and IIIB (except malignant pleural effusion) NSCLC were eligible. Inclusion into the trial and treatment decisions were done by multidisciplinary panel involving surgeons, medical oncologists and radiotherapists. All drugs were given intravenously on days 1 and 8, and repeated every 3 weeks up to 2 cycles followed by concurrent chemoradiation. D (30–35 mg/m 2 ) was given first, followed by C (35 mg/m 2 ) and G (1000 mg/m 2 ). Results: From Jan ‘06 to Jul ‘06 twelve eligible pts were enrolled, 10/2 m/f gender; median age 63 (50–72), 1 patient with ECOG PS 0, 11 pts with PS 1; 5 pts with stage IIIA-N2 bulky, 7 pts with stage IIIB NSCLC; nine pts were smokers. All pts were evaluable for toxicity. Toxicity grade 3–4 by CTC criteria was: grade 3 neutropenia in 2/3 patients and grade 3 thrombocytopenia in 1/3 patients on the second dose level of chemotherapy (i.e. docetaxel 35 mg/m 2 ), and was considered dose-limiting. Of 9 pts treated at the MTD (i.e. docetaxel 30 mg/m 2 ), only 1 patient developed grade 4 neutropenia and 1 patient grade 3 thrombocytopenia; 3 patients (30%) had grade 2 neutropenia and grade 2 stomatitis. Of 12 evaluable pts for response, after induction chemotherapy eighty-three percent of patients (9/12 pts) had an objective response and 16,6% (2/9 pts) stable disease. Phase II is continuing for larger patient accrual. Conclusions: The recommended doses for further phase II studies are D (30 mg/m 2 ) followed by C (35 mg/m 2 ) and G (1000 mg/m 2 ) every 3 weeks. This regimen is well tolerated and effective, and appears to be an excellent choice for stage III NSCLC. No significant financial relationships to disclose.
Fluid transport in a cultured cell model of kidney epithelial cyst enlargement.
Authors: G A Tanner, M R Maxwell, J A McAteer
Journal: Journal of the American Society of Nephrology (1992)

Madin-Darby canine kidney (MDCK) cells, when seeded into collagen gel, from polarized, spherical, epithelial cysts, which grow by a process involving fluid secretion and cell proliferation. These cysts are a useful model for understanding the dynamics of cyst enlargement in renal cystic disease. The hypothesis that MDCK cyst fluid secretion depends upon chloride secretion was tested, and a cell model for this process is presented here. Lumen and epithelial cell volumes were measured by video microscopy in acute experiments. Fluid absorption (-0.073 +/- 0.007 microliters.h-1.cm-2; N = 8) was observed when cysts were superfused with unsupplemented Dublecco's modified Eagle's medium at 36 to 37 degrees C. Fluid secretion (0.221 +/- 0.0016 microliters.h-1.cm-2; N = 25) was seen when 1 mM dibutyryl cAMP plus 0.1 mM 3-isobutyl-1-methylxanthine were added to the superfusate. cAMP-induced fluid secretion was significantly inhibited by basolateral 1 mM ouabain, 0.1 mM furosemide, or 1 mM amiloride. It was not significantly affected by 1 mM chlorothiazide, 0.01 mM bumetanide, or 0.1 mM acetazolamide in the presence of normal bicarbonate/CO2. In the nominal absence of bicarbonate/CO2 fluid secretion was 18% of control. Vasopressin-induced fluid secretion was significantly inhibited by pretreatment of cysts with 0.1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Cyst cell shrinkage in isosmotic chloride-free Ringer's solution (chloride replaced by gluconate) was inhibited by 0.1 mM basolateral DIDS. The results suggest that chloride-bicarbonate exchange in the basolateral membrane of MDCK cyst epithelial cells plays a critical role in cyst fluid secretion.
Abstract 16320: A Network Meta-Analysis and Diversity-Adjusted Trial Sequential Analysis of Angiotensin Converting Enzyme Inhibitors in Patients With Heart Failure: Evidence of Class Effect
Authors: Saurav Chatterjee, Ahana Roy, Antonio Abbate, Fabrizio D'Ascenzo, Debabrata Mukherjee, Giuseppe Biondi-Zoccai
Journal: Circulation (2013)

Background: Angiotensin converting enzyme inhibitors (ACEIs) represent a mainstay in the management of heart failure. However, it remains unclear if any particular ACEI is superior to the others or...
Better approach needed to detect and treat military personnel with adverse effects from mefloquine
Authors: Jane C Quinn
Journal: BMJ (2016)

The use of mefloquine in militarny personnel has long been controversial.1 Recent evidence presented to the current defence select committee inquiry called mefloquine the “least safe of the available antimalarial regimens currently used,”2 yet anecdotal evidence suggests that mefloquine has been routinely issued without an individual risk assessment for several decades. The Ministry of Defence (MOD) admitted that defined protocols for prescribing mefloquine had been available since 1997, …
Renal outcomes with aliskiren in patients with type 2 diabetes: a prespecified secondary analysis of the ALTITUDE randomised controlled trial
Authors: Hiddo J L Heerspink, Frederik Persson, Barry M Brenner, Nish Chaturvedi, Patrick Brunel, John J McMurray, Akshay S Desai, Scott D Solomon, Marc A Pfeffer, Hans-Henrik Parving, Dick de Zeeuw
Journal: The Lancet Diabetes & Endocrinology (2016)
Immunohistochemical analysis of pathway HER2 4B5 performance in breast carcinoma expressing HER4.
Authors: Julie I Jay, Patrick S Brunhoeber, Margie H Smith, Ryan R Williams, Michael Sugarman, Heather L Free, David E Tast
Journal: Journal of Clinical Oncology (2012)

16 Background: The ability of pharmacodiagnostic antibodies to specifically detect their target antigen is essential to their performance. Non-clinical protein based models for specificity of two human epidermal growth factor 2 (HER2) pharmacodiagnostic antibodies, Oracle CB11 and PATHWAY HER2 4B5 (4B5) (Ventana Medical Systems Inc., Tucson, AZ, USA), have been reported to demonstrate affinity to both HER2 and HER4. To date there has been no evidence showing that affinity of 4B5 for HER4 impacts the IHC clinical HER2 assay. We therefore sought to investigate whether there exists any risk of the 4B5 antibody detecting HER4-positive but HER2-negative cases as falsely positive due to a hypothetical cross reactivity to HER4. Methods: A HER4 IHC assay was developed by screening ten HER4 antibodies for specificity by staining FFPE blocks of recombinant HEK-293 cells expressing HER1, HER2, HER3 and HER4. Specific HER4 antibodies were then evaluated in breast carcinoma to identify a clone that provided distinct membrane staining in tumour cells. This pattern was used as a reference in order to detect any potential interference of HER4 detection in determining the HER2 score. The HER4 antibody E200 (Epitomics) was selected and used to evaluate a cohort of breast carcinoma cases. The HER2 expression in these cases was then assessed using anti-HER2 clone PATHWAY HER2 4B5 and a HER2 reference antibody, clone SP3 (Spring Bioscience). Results: 117 out of 241 (48%) breast tissue cases evaluated were HER4 positive for membrane staining by IHC using E200. The scoring criteria for determining the HER4 score was based on the system used to score HER2, however a positive score indicated any membrane staining and therefore a 1+, 2+ or 3+ score was considered HER4-positive. 4B5 exhibited similar staining patterns as SP3 in co-expressing HER4 and HER2 tissues indicating that 4B5 was detecting only the HER2 antigen. Eighteen cases were HER4-positive by E200 and level 0 by 4B5 including a HER4 level 3+ case. Conclusions: PATHWAY HER2 4B5, a clinically relevant pharmacodiagnostic antibody for detecting HER2 expression in breast carcinoma, does not demonstrate cross reactivity to HER4 in IHC of FFPE clinical tissues.