tbuckley/cabot-search huggingface dataset:
Phase I, PK, dose-finding, active controlled study of paclitaxel injection concentrate for nanodispersion (PICN) in subjects with metastatic breast cancer.
Authors: M. M. Jain, C. D. Deshmukh, N. N. Bhatt, S. A. Bondarde, R. V. Nagarkar, C. J. Desai, G. H. Divekar
Journal: Journal of Clinical Oncology (2011)

e11585 Background: Paclitaxel injection concentrate for nano-dispersion (PICN) is a novel cremophor-free formulation of paclitaxel developed by SPARC Ltd. which is stabilized with polymer and lipid by nano technology. Being alubumin free formulation, PICN does not have any risk of hypersensivity from processed human protein. The present clinical study was planned to determine MTD, and to evaluate safety, efficacy, and pharmacokinetics of PICN in subjects with refractory MBC (metastatic breast cancer). Methods: Thirty six (36) female subjects were treated in the study; 28 subjects received different dose levels of PICN (with 3+3 dose escalation scheme) for up to 6 cycles, 5 subjects received conventional paclitaxel for up to 6 cycles, and 3 subjects received Abraxane for 1 cycle. Serial blood samples were collected and used for pharmacokinetic analysis after administration of dose in Cycle 1 till 48-hrs post dose. Dose limiting toxicities were assessed after Cycle 1. At weekly follow-up visits, laboratory investigations were conducted to monitor safety. CT scan was conducted at screening and after every other cycle to evaluate tumor response per RECIST 1.0. PICN was administered by 30-min intravenous infusion on Day 1 of 21 day cycles to cohorts of subjects beginning at the 135 mg/m2 dose level. Subsequent subjects were enrolled in escalating cohorts and treated at the 175, 260, 325, and 295 mg/m2 dose levels. Results: The MTD of PICN was 295 mg/m2. Neutropenia was the primary dose limiting toxicity. No unexpected or new toxicities were reported with PICN. PK data showed PICN exposure (AUC and Cmax) increased in a dose proportionate manner from 135 to 175, 260, 295, and 325 mg/m2. At 260 mg/m2, AUC of PICN and Abraxane were similar; however Cmax of PICN was lower than Abraxane. With PICN, 10 (40%) subjects had partial response as their best response, and 5 (20%) subjects had stable disease. Conclusions: The recommended dose for phase II studies of PICN is 295 mg/m2. There was no hypersensitivity reaction in subjects treated with PICN despite lack of pre-medication. Objective tumor response was observed in 10 of 25 (40 %) PICN treated subjects evaluable for efficacy.
Confounders Regarding the Association of Insulin Resistance and Alzheimer Disease
Authors: Sevilay Muratli, Ozlem Soyluk, Fatih Tufan
Journal: JAMA Neurology (2015)

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 Neurology 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 Neurology journal
Association Between Obesity and Postmenopausal Breast Cancer Risk
Authors: NaNa Keum, Edward Giovannucci
Journal: JAMA Oncology (2015)

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 Oncology 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 Oncology journal
Response to treatment varies
Authors: I. P Palmer
Journal: BMJ (1995)

EDITOR,--Beverley Raphael and colleagues' editorial raises many questions about psychological debriefing and post-traumatic stress reactions.1 A military debriefing is an analysis of the events occurring on a mission and the lessons learnt. The primary aim of psychological debriefing is to provide the person with as much information as possible from all the sources available to enable the cognitive appraisal and emotional processing of a traumatic experience. This may be therapeutic or may not be. Traumatic incidents irrevocably change people as …
Computational discovery and experimental validation of novel drug targets in immuno-oncology
Authors: Ofer Levy, Arthur Machelnkin, Galit Rotman, Amir Toporik, Gady Cojocaro, Liat Dassa, Ilan Vaknin, Spencer Liang, John Hunter, Eyal Neria, Zurit Levin
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The past few years have witnessed a renaissance in the field of immuno-oncology largely due to the clinical success in targeting the immune checkpoints CTLA-4 and PD-1. Towards identification of novel immune checkpoint drug targets we developed a dedicated predictive discovery
A programmable and implantable pumping system for systemic chemotherapy: a performance analysis in 52 patients.
Authors: N J Vogelzang, M Ruane, M J Ratain, K Dhowlatshahi, G W Chodak
Journal: Journal of Clinical Oncology (1987)

We have prospectively evaluated the performance of the implanted battery-powered Medtronic (Minneapolis) SynchroMed infusion system. Between July 1984 and July 1986, fifty-three SynchroMed pumps were implanted in 52 patients for phase I and II trials of low-dose continuous-infusion doxorubicin (N = 35) or vinblastine (N = 17). The median duration of pump function was 145 days (mean, 180; range, 20 to 787 +) and the systems infused drugs for 61% (range, 32% to 100%) of their patient implant time. During 10,045 patient days (27.5 years) of implantation, there have been no failures of the pump mechanism and pump accuracy was excellent (2.2% error rate in 256 analyzed refills). The median cost of the hospitalization for implantation was +17,140 in 14 analyzed cases. Complications requiring a second surgical procedure occurred with 13 systems (24%). Two of the complications were related to localized cutaneous hypersensitivity to vinblastine, four were directly related to system complications, and seven were secondary to implant procedure problems. Seven patients (13%) requested removal of the device after tumor progression occurred. Based on this experience, the company has made improvements in certain aspects of system design and has implemented a comprehensive user training program to minimize procedure-related problems. The Medtronic SynchroMed is an accurate and sophisticated system that allows infusion of low-dose doxorubicin and of vinblastine for prolonged periods. Extravasation of these vesicant agents must be carefully prevented. The financial cost of this implanted system may limit its use to patients with an expected survival of 5 months or longer.
Research pointers: Improvement in cholesterol emboli syndrome after iloprost therapy
Authors: E. Elinav
Journal: BMJ (2002)

Improvement in cholesterol emboli syndrome after iloprost therapyCholesterol emboli syndrome is a disorder in which multiple cholesterol crystals dislodge from atherosclerotic plaques, either spontaneously or after vascular interventions, treatment with anticoagulation, or thrombolytic treatment.The syndrome typically presents with painful ischaemic skin lesions, livedo reticularis, and acute renal failure.Treatments such as aspirin, statins, discontinuation of anticoagulation, and surgical correction of the embolic source are of limited efficacy. 1 2We report four cases of cholesterol emboli in which treatment with iloprost, a prostacyclin analogue, 3 improved both ischaemia of the distal extremities and renal failure.
Changing patterns of asthma medication use related to US Food and Drug Administration long-acting β2-agonist regulation from 2005-2011
Authors: Melissa G. Butler, Esther H. Zhou, Fang Zhang, Yu-te Wu, Ann Chen Wu, Mark S. Levenson, Pingsheng Wu, Sally Seymour, Sengwee Toh, Aarthi Iyer, Solomon Iyasu, Meghan A. Baker
Journal: Journal of Allergy and Clinical Immunology (2015)
Enzalutamide: A new hormonal treatment for triple-negative breast cancer?
Authors: Francesco Caiazza, Alyson Murray, Stephen F. Madden, Naoise C Synnott, Norma O'Donovan, John Crown, Michael J. Duffy
Journal: Journal of Clinical Oncology (2015)

1071 Background: Like the estrogen receptor (ER), the androgen receptor (AR) is present in approximately 80% of invasive breast cancer. However, in contrast to the ER which is never expressed in triple-negative breast cancer (TNBC), the AR can be present in up to 30% of patients with this molecular subtype of breast cancer. The aim of this study was therefore to investigate the targeting of AR with the second generation anti-androgen enzalutamide as a possible new hormonal approach for the treatment of breast cancer. Methods: IC50values for enzalutamide were determined for 14 breast cancer cell lines (8 TN; 6 non-TN), using the colony formation assay. AR was measured using both Western blotting and ELISA. Cell motility was determined using Boyden chamber assays in 4 TN cell lines. Results: enzalutamide IC50values across 14 breast cancer cell lines varied from 4 µM to > 50 µM. Response to the anti-growth activity of enzalutamide was similar in TN and non-TN cell lines but depended on the presence of AR. In addition to blocking cell growth, enzalutamide also inhibited cell migration and invasion in 3 out of 4 TN cell lines, again in an AR-dependent manner. Similar to enzalutamide, the first generation anti-androgen flutamide also blocked cell growth, migration and invasion in TNBC cell lines. The addition of doxorubicin to enzalutamide enhanced growth inhibition in 4 of 5 breast cancer cell lines investigated, including 2 TN cell lines. In contrast to doxorubicin, no enhancement of growth inhibition was found with cisplatin, carboplatin or 5-FU. Conclusions: We conclude that targeting AR with enzalutamide may represent a new approach to breast cancer treatment, especially for patients with AR-positive TN disease. The current availability of anti-androgens for the treatment of metastatic prostate cancer should facilitate their clinical investigation in TNBC. Finally, since the AR is expressed in several different types of cancer, targeting with enzalutamide may have wide application in cancer treatment.
A phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of the combination of an oral antimicrotubular agent, DJ-927 (D), and capecitabine (C) in patients (Pts) with advanced cancers
Authors: M. Beeram, W. M. Saif, J. Sarantopoulos, G. Schwartz, A. Patnaik, A. W. Tolcher, F. Mehdi, K. Feit, C. H. Takimoto
Journal: Journal of Clinical Oncology (2006)

2016 Background: DJ-927, an oral microtubule stabilizer, has impressive cytotoxic activity in taxane-resistant tumors and an acceptable toxicity profile. C and Taxane combinations are active in solid tumors such as breast cancer. Non-overlapping mechanism of action and toxicity profiles and the convenience of an orally administered therapy have prompted a phase I evaluation of the combination. D was given orally once on day 1 and C for 14-days (D1–14), every three weeks. Methods: Eligible pts had evaluable cancer, minimal prior therapy and PS 0 - 2 ECOG. D was started at 18 mg/m 2 on day 1 along with 1,250 mg/m 2 of C orally B.I.D for 14 days, of a 21-day cycle. Incremental doses of both drugs were explored until the maximum tolerated dose (MTD) was reached. PK samples were collected during cycles 1 and 2, for assays of C and for D when given concurrently with C during cycle 1 and D given alone during cycle 2. Results: Twenty-seven pts [18 Male/ 9 Female; median age (range)- 58 yrs (33–70); PS 0 (n=8) ; PS 1 (n=19)] received 81 cycles [median (range)- 3 (1–8)] in 5 cohorts, with D and C 18/ 1250 mg/m 2 (n = 3), 27/ 1250 mg/m 2 (n = 7), 27/ 1900 mg/m 2 (n = 7), 35/ 1900 mg/m 2 (n = 3),and 27/ 2500 mg/m 2 (n = 7). Dose-limiting toxicity (DLT) was grade 4 neutropenia in 2 of 3 pts at 35/ 1900 mg/m 2 dose. Other common drug-related toxicities were leukopenia, nausea &amp; vomiting (12 pts each, 44.4%), neutropenia, diarrhea and hand-foot syndrome (11 pts each, 40.7%), and fatigue (7 pts, 25.9%). A pt with hepatocellular carcinoma had an unconfirmed partial response at cycle 2 and 10 pts experienced disease stabilization lasting ≥ 12 weeks. The median elimination half-life (t½) of D was 182 hrs for cycle 1 (with C) and 204 hrs for cycle 2 (without C). Median t max values for D with and without C occurred at 2 hours. Median clearance values (CL/F) for D in plasma were similar with and without C at 18.4 L/h/m 2 and 19.8 L/h/m 2 , respectively. Conclusions: The combination of D and C is feasible and safe at the MTD of 27 mg/m 2 and 2500 mg/m 2 , respectively. Co-administering C with D did not alter the PK of either drug. Preliminary evidence of antitumor activity suggests that further studies of this combination are warranted. [Table: see text]
Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy.
Authors: F G LeVeque, J B Parzuchowski, G C Farinacci, S W Redding, B Rodu, J T Johnson, G A Ferretti, P D Eisenberg, M B Zimmer
Journal: Journal of Clinical Oncology (1992)

PURPOSE This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area &lt; or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P &lt; .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.
The quest for the grail: multidimensional efforts for understanding and targeting severe asthma
Authors: Mina Gaga, Paul L.P. Brand, Neil C. Thomson
Journal: European Respiratory Journal (2015)

The exponential advance in biological and medical science, with the use of molecular and genetic testing as well as various "omics" approaches, has led to the elucidation of many disease pathways. It has also led to the identification of marked differences in the mechanisms, phenotypes and genotypes of diseases that were once thought to have similar characteristics and required similar therapies. An example of this approach is in cystic fibrosis, where patients with the specific G551D mutation respond extremely well to ivafactor (Kalydeco) [1]. Although this mutation is only found in about 5% of all cystic fibrosis patients, their response to treatment is so dramatic that it is truly life changing. However, the cost of this medication is extremely high and it is difficult to imagine that similar costs can be sustained in the long term for other, more common diseases. The number of available monoclonal antibodies and targeted drugs for severe or life-threatening disease, such as cancer and rheumatoid arthritis, is increasing rapidly and expected to continue to rise in the next decade [2, 3]. Moreover, we are now faced with the severe end of the spectrum of many diseases, in which the clinical characteristics and response to treatment differ considerably from mild disease. First results from the U-BIOPRED studies of adults and children with severe asthma <http://ow.ly/RKJZ7>
Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme
Authors: F Radaelli, S Paggi, C Hassan, C Senore, R Fasoli, A Anderloni, F Buffoli, M F Savarese, G Spinzi, D K Rex, A Repici
Journal: Gut (2015)

<h3>Objective</h3> Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR. <h3>Design</h3> In a multicentre, randomised, endoscopist-blinded study, 50–69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a '<i>split-dose</i>' (Split-Dose Group, SDG) or '<i>day-before</i>' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at <i>per-patient</i> analysis and the total number of lesions. <h3>Results</h3> 690 subjects were included in the study. At <i>per-patient analysis</i>, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At <i>per-polyp analysis</i>, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p &lt;0.001; 0.36 vs 0.22, p&lt;0.001). <h3>Conclusions</h3> In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended. <h3>Clinical trial registration number</h3> NCT02178033.
Molecular and immune heterogeneity in synchronous melanoma metastases
Authors: Alexandre Reuben, Christine Spencer, Jason Roszik, John Miller, Lawrence Kwong, Hong Jiang, Cara Haymaker, Pei-Ling Chen, Jacob Austin-Breneman, Whijae Roh, Latasha Little, Yu Cao, Haven Garber, Marie-Andrée Forget, Vancheswaran Gopalakrishnan, Rodabe Amaria, Michael Davies, Chantale Bernatchez, Edwin Roger, Parra Cuentas, Jaime Rodriguez, Michael Tetzlaff, Scott Woodman, Karen Dwyer, Padmanee Sharma, James Allison, Lynda Chin, Andrew Futreal, Zachary Cooper, Jennifer Wargo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Despite recent advances in the treatment of metastatic melanoma through targeted and immunotherapy, the majority of patients do not achieve a durable response. Research efforts to better understand responses are underway, and numerous molecular mechanisms of resistance to targeted
Smoking and Subarachnoid Haemorrhage
Authors: A Taha, K P Ball, R D Lllingworth
Journal: Journal of the Royal Society of Medicine (1983)

An enquiry was made into the smoking habits of 199 patients who had survived a subarachnoid haemorrhage (SAH). Information was obtained from 189, giving a 95% response rate. Those with a cerebral aneurysm had on average smoked considerably more cigarettes daily than those with arteriovenous malformations (AVM) or with normal angiographic findings (NAF) whose smoking habits were similar to those of the UK population. SAH due to cerebral aneurysm should be considered another smoking-related disease.
Continuation of Trastuzumab Beyond Progression for Her2-Positive Advanced Gastric Cancer as Second-Line Treatment
Authors: Yukiya Narita, Shigenori Kadowaki, Hiroya Taniguchi, Daisuke Takahari, Takashi Ura, Masashi Andoh, Yasumasa Niwa, Hiroki Hara, Kensei Yamaguchi, Kei Muro
Journal: Annals of Oncology (2014)
Involvement of IL-4 in human glomerulonephritis
Authors: A Furusu, M Miyazaki, T Koji, K Abe, Y Ozono, T Harada, P K Nakane, K Hara, S Kohno
Journal: Journal of the American Society of Nephrology (1997)

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in human kidney has not been fully determined. Nonradioactive in situ hybridization was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were strongly expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells, and cells of the Bowman's capsule. The relationship between the expression of these mRNA and the degree of glomerular injury was different in different types of glomerulonephritis. In IgA nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hypercellularity and extracellular matrix expansion. However, IL-4R expression was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these mRNA forms were observed in individual cells. In tubulointerstitium with severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and some of the infiltrating cells and fibroblasts. The interstitial expression of these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulo-interstitial changes. These results suggest that an autocrine and/or paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may be involved in tissue injury in glomerulonephritis.