tbuckley/cabot-search huggingface dataset:
The role of human cyclin B1 protein in resistance to the cyclin-dependent kinase inhibitor, JNJ-7706621
Authors: Catherine A. Rugg, Jennifer A. Seamon, Stuart Emanuel, Steven A. Middleton
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4425 

Cyclin-dependent kinases (CDKs) are key components involved in cell cycle progression. CDK inhibitors that block cell division and arrest growth are potential targeted therapeutics for cancer. Previously, we have shown that JNJ-7706621, a novel 3,5-diamino-1,2,4-triazole, selectively inhibits in vitro kinase activity of CDKs, particularly CDK1, by an ATP-competitive mechanism. This compound blocks cell cycle progression in G2/M phase and is also cytotoxic in a wide range of tumor cell types. JNJ-7706621 is not affected by P-glycoprotein, a transmembrane efflux pump that decreases intracellular accumulation and is a mechanism for resistance to a variety of drugs. Resistance of tumor cells to therapeutic drugs is a major obstacle to successful cancer therapy, therefore understanding the mechanism of resistance is crucial. In the present study, a population of HeLa cells was selected for resistance to JNJ-7706621 and the molecular mechanism involved in the resistance was assessed. Selection resulted in a population of cells that cycle in a concentration of drug that induces cell cycle arrest in sensitive cells. The resistant cells showed an increase in CDK1 kinase activity. Analysis of proteins involved in the activation of CDK1 kinase revealed that the resistant cells also express high levels of cyclin B1, the regulatory component of CDK1. This protein, which normally peaks in the G2 phase of the cell cycle, was observed to be present at unusually high levels during G1 in synchronized resistant cells. Resistant cells that were removed from drug for 12 weeks reverted to susceptibility to JNJ-7706621 and showed normal cyclin B1 levels and near normal CDK1 kinase activity. These results show that cyclin B1 may play a role in the responsiveness of cells to JNJ-7706221 and could be used as an indicator of drug efficacy.
Radiation recall dermatitis after docetaxel administration: absolute indication to replace the drug?
Authors: F. Borgia, C. Guarneri, F. Guarneri, M. Vaccaro
Journal: British Journal of Dermatology (2005)

Conflicts of interest: None to declare Sir, Docetaxel is a semisynthetic chemotherapeutic agent, belonging to the taxane family, which is used with increasing frequency in advanced and refractory ovarian, breast, lung, and head and neck cancers. Recent trials show significant activity also in prostate cancer, pancreatic and gastric carcinomas, extramammary Paget's disease and disseminated Kaposi sarcoma.1 Cutaneous reactions to docetaxel occur in approximately 50% of patients, including maculopapular exanthems, acral erythrodysaesthesia, scleroderma‐like fibrosis and nail changes;2, 3 interestingly, despite the wide use of the drug, only a few cases of radiation recall dermatitis (RRD) have been reported. On this topic, we report the case of a 63‐year‐old woman, affected by oestrogen‐negative, infiltrating ductal carcinoma of the left breast with involvement of homolateral axillary lymph nodes (T3N2). She underwent neo‐adjuvant chemotherapy with 5‐fluorouracil (Fluorouracile DBL®, Teva Pharma B.V., Mijdrecht, the Netherlands), epirubicin (Farmorubicina®, Pharmacia Italia, Milan, Italy) and cyclophosphamide (Endoxan Asta®, Baxter, Trieste, Italy) (six courses), and successive segmental mastectomy and lymph node dissection, that showed multiple lymphatic metastases (six of 12 axillary nodes). Because of resistance to prior anthracycline chemotherapy, radiotherapy was started, with a total dose of 5000 cGy in 5 weeks. One week after radiotherapy, adjuvant treatment with intravenous docetaxel (Taxotere®, Rhone Poulenc Rorer, Collegeville, PA, U.S.A.) was initiated (100 mg m−2 h−1 every 3 weeks). Four days after the second course, the patient developed an acute, painful erythematous reaction, classified as grade 1 using a scale based on the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Criteria for skin,4 limited to the previously irradiated cutaneous area (Fig. 1). The diagnosis of RRD was made; treatment with oral methylprednisolone (16 mg day−1 for seven consecutive days) induced rapid (10 days), complete remission of the clinical features. On the basis of the mild cutaneous involvement, we decided, together with the oncologists, to continue docetaxel administration without modification of its dose. In order to reduce the probability of a recurrence of skin reactions, methylprednisolone (16 mg day−1 orally) was given for 5 days, starting the day before docetaxel infusion. No relapse of RRD was observed after seven courses of docetaxel.
Lesson of the week: Late onset interstitial nephritis associated with mesalazine treatment
Authors: J. Popoola, A. F Muller, L. Pollock, P. O'Donnell, P. Carmichael, P. Stevens
Journal: BMJ (1998)

Patients taking mesalazine should have renal function monitored regularly to avoid nephrotoxicity

Mesalazine is widely prescribed for the treatment of inflammatory bowel disease. It is a single molecule of 5-aminosalicylic acid (5-ASA), and is structurally similar to phenacetin and aspirin. Occasionally, treatment with mesalazine may lead to a severe indolent interstitial nephritis causing appreciable morbidity. Unless detected and treated early this may progress to end stage renal failure despite withdrawal of the drug.1 It is obvious from the increasing number of reports of nephritis and renal failure occurring after treatment with mesalazine that the premise that “there is no need for routine monitoring of renal function”2 needs to be reviewed; the need for a review has been suggested by a number of recent reports. 1 3–9 We report two cases of late onset interstitial nephritis induced by mesalazine (Asacol); the first presented after at least 5 years of continuous treatment with the drug and the second after 1 year.

### Case 1

A 38 year old laboratory technician began taking mesalazine for ulcerative colitis. After 2 years of continuous treatment he remained well with normal renal function (serum creatinine concentration 76 μmol/l; normal range 71-133 μmol/l) and negative results on urinalysis. He had an exacerbation of his colitis during the third and fourth years of treatment. On each occasion he responded to a combination of oral prednisolone treatment and an increase in the dose of mesalazine to 1.2 g twice a day. Each time, steroid treatment lasted for 3 months and began with 40 mg a day of prednisolone which was rapidly tapered down to a maintenance dose of 10 mg a day. Repeat serum creatinine concentration measured after 3 years of mesalazine treatment was 79 μmol/l. Thereafter the dose of mesalazine fluctuated between 800 …
Abstract 10918: High-Throughput Sequencing Analysis of microRNA Profile Dynamics in Patients with Advanced Heart Failure Undergoing Ventricular Assist Device Placement in Comparison to Normal Adult and Fetal Cardiac Expression
Authors: Kemal M Akat, Aleksandra Mihailovic, Zev Williams, Miguel Brown, Pavel Morozov, Hiroo Takayama, Konstantinos Drosatos, Thomas Tuschl, P. C Schulze
Journal: Circulation (2011)

Background To further elucidate the role of miRNAs in heart failure (HF), we performed a small RNA profiling using next-generation sequencing on cardiac samples from patients with advanced HF in co...
Phase III study of first-line XELOX plus bevacizumab (BEV) for 6 cycles followed by XELOX plus BEV or single-agent (s/a) BEV as maintenance therapy in patients (pts) with metastatic colorectal cancer (mCRC): The MACRO Trial (Spanish Cooperative Group for the Treatment of Digestive Tumors [TTD]).
Authors: J. Tabernero, E. Aranda, A. Gomez, B. Massuti, J. Sastre, A. Abad, M. Valladares, F. Rivera, M. Safont, E. Diaz-Rubio
Journal: Journal of Clinical Oncology (2010)

3501 Background: The optimal duration and content of first-line therapy inpts with mCRC once they have achieved the maximal response remains controversial. This multicenter, randomized, phase III study was aimed to evaluate the efficacy and tolerability of 6 cycles of BEV + XELOX (capecitabine + oxaliplatin) followed by maintenance XELOX-BEV or s/a BEV Methods: Previously untreated mCRC pts were randomized to receive BEV (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1) q3w x6 cycles continued by maintenance therapy with XELOX-BEV (Arm A) or s/a BEV (Arm B) until progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. The statistical design was based on a noninferiority hypothesis; a mPFS of 10 months in Arm A; unilateral α of 0.025 and β of 0.8; and a sample size of 470 pts for a hazard ratio (HR) of 1.2. Results: 480 pts (median age 64 years, range 30–82) were randomized: 239 Arm A, 241 Arm B; no significant differences in demographic characteristics. Median follow-up was 16 months (range: 0.7–35.7). There were not statistically significant differences in ORR, PFS, and OS between the 2 arms. Preliminary analysis of safety shows that tolerability was acceptable in the 2 arms, with grade 3/4 diarrhea in 11% and 13%, HFS in 12% and 6%, and neuropathy in 24% and 7% in Arms A and B, respectively. Conclusions: BEV as a maintenance therapy following induction XELOX-BEV was not inferior to continuation XELOX-BEV. This study suggests that maintenance therapy with s/a BEV is an appropriate option following induction XELOX-BEV in pts with mCRC. Further studies evaluating s/a BEV after standard chemotherapy in mCRC are warranted. Efficacy Arm A Arm B p value HR/OR (95% CI) mPFS, months 11.0 10.3 0.59 HR: 1.07 (0.84-1.36) mOS, months 25.3 20.7 0.63 HR: 1.07 (0.81-1.41) ORR, % 60 57 0.51 OR: 1.13 (0.79-1.63) M1 resection, % 10 8.3 0.51 OR: 1.23 (0.66- 2.32) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
Measuring quality with the Quality Oncology Practice Initiative (QOPI) at a university comprehensive cancer center
Authors: D. W. Blayney, G. Miela, D. Markstrom, D. Hanauer, K. McNiff, M. Neuss
Journal: Journal of Clinical Oncology (2007)

6535 Background: QOPI is a tool which measures adherence to both guidelines and to process for use in quality improvement. QOPI was designed and pilot tested predominately in physician office practices [Neuss et al, JCO 23:6233]. We tested QOPI at UMCCC, a large, hospital-based, academic cancer center, where medical documents are stored in a free-text electronic record, in a paper-based hospital record, and in clinic charts. In 2006, 136 physicians and 58 mid-level practitioners provided 66,699 clinic visits and oversaw 37,500 infusion visits. Methods: The tumor registry selected consecutive cases of breast (BrCa), lung, and colorectal cancer (CRC), and lymphoma (L), diagnosed between minus 6 and minus 30 months from day 0 of each QOPI round. Forty charts with each tumor type and 40 deceased patient records were identified for each round. A clinical pharmacist accessed the pharmacy database to obtain drug data, and the tumor registrar abstracted the three other chart formats, using an electronic text search tool [Hanauer et al Proc ASCO 2006 abs 6080] for the electronic record. De-identified data were submitted to a secure, ASCO-hosted server, for analysis. Results: In the Spring 2006 round, 163 charts yielding 1641 measures required 148 hours of abstractor effort, for an average of 54 minutes (mins) per chart and 5.4 mins per measure. In the Fall, 2006 round, 236 charts yielding 2334 measures required 256.5 hours of effort for 65 mins per chart and 6.6 mins per measure. For comparison, a survey of QOPI practices for the Fall round yielded 29 mins per chart. UMCCC treatment (Rx) and process measures are shown in the table . Conclusions: Abstracting for QOPI measures, using abstractors not involved in patient care, is labor intensive but feasible at a large cancer center. QOPI has allowed UMCCC to assess concordance with guidelines and other quality measures, provides comparison data to other practices, and identifies processes for improvement. The evolution of QOPI will include data transfer from electronic records. [Table: see text] [Table: see text]
Doctors subjected to “harsh treatment” over organ retention, says report
Authors: Roger Dobson
Journal: BMJ (2001)

Government and politicians have been criticised for over-reaction and a lack of awareness in the controversy surrounding organ retention in the wake of the inquiries at Bristol and Alder Hey hospitals.

The medical profession and some individual doctors have been treated harshly over the issue and have been left bewildered by what has happened, according to a report in Clinical Medicine , the journal of the Royal College of Physicians of London (2001;1:167-71). It warned, too, of a knock-on effect on hospital postmortem examinations, organ donation, genetic counselling, and future research involving human tissue.

The report, by Dr John Bennett, …
Impact of sepsis in respiratory mechanics of pulmonary arterial hypertension rat model. Preliminary results
Authors: Karla Mëtte Waldrich Tauil, César Augusto Melo-Silva, Carlos Eduardo Ventura Gaio dos Santos, Veronica Moreira Amado
Journal: European Respiratory Journal (2014)

Introduction : Sepsis is an important cause of mortality on patients with pulmonary arterial hypertension (PAH). The presence of inflammation is well established in sepsis and it is possible that the association of these two conditions could increase the impedance of respiratory system.

Objectives : To determine the effects of sepsis in respiratory mechanics in a monocrotaline PAH rat model.

Methods : We studied the respiratory mechanical propertiesof 24 rats divided in three groups: control (CTRL), monocrotaline induced PAH (PAH) and monocrotaline induced PAH with cecal ligation and puncture induced sepsis (PAHs). Results: Pressure dissipation against the viscoelastic components (ΔP2,rs) was increased in PAHs compared with CTRL(ΔP2,rs PAHs= 1.97±0.48; ΔP2,rs CTRL= 1.29±0.54, p= 0.34), but not with PAH(ΔP2,rs PAH= 1,54±0.18, p= 0.2). There is no difference in respiratory system elastance (E,rs) between the groups, but the lung elastance (E, L) of PAHs was elevated comparing to CTRL group(E,L PAHs=3.1±0.65; E,L CTRL=2.38±0.61, p=0.47). Respiratory system resistance (R,rs) was superior in CTRL comparing to PAHs and PAH (R,rs CTRL=0.18±0.7; R,rs PAHs=0.11±0.04, p= 0.01; R,rs PAH=0.12±0.02, p=0.05 ).

Conclusion : Sepsis does not increase elastic and resistive properties of respiratory system in a monocrotaline induced PAH.
Failure to observe pentolysis by the serum of rats bearing malignant tumors.
Authors: Joseph H. Roe, Joanne W. Cassidy, Ann C. Tatum, Eugene W. Rice
Journal: Cancer Research (1952)

Summary  1.Studies upon the Menkes pentolysis test for malignancy, with three methods for the determination of pentoses in serum, have been made.  2.No evidence was obtained of the presence of a pentose-destroying factor in the sera of rats bearing tumors induced by injection of 20-methylcholanthrene and in the sera of rats with malignant transplanted tumors of four different types.  3.The Roe and Rice procedure for the determination of pentose was found to have greater precision than the methods of Mejbaum and of Brachet.
Tumor-Promoting Activity of Certain Extracts of Tobacco
Authors: O. T. Chortyk, F. G. Bock
Journal: JNCI Journal of the National Cancer Institute (1976)

Tumor-promoting activities of extracts of fluecured and cigarette tobacco were evaluated. Initially, fluecured tobacco was extracted consecutively with hexane, chloroform, acetone, ethyl alcohol, methyl alcohol, and water; and the extracts were tested for tumor-promoting activity on mouse skin. The hexane and chloroform extracts were fractionated on silicic acid, and the fractions were devoid of tumorigenic activity. The acetone and alcohol extracts showed marginal activity. Subsequently, chloroform-extracted cigarette tobacco was extracted with water, and the aqueous extract was partitioned by solvent precipitation methods. Bioassay results showed tumor-promoting activity for the aqueous extract, with tumors in 38% of the animals. The aqueous extract appeared about five times as active as smoke condensate derived from an equal weight of tobacco.
Phase II study of weekly nanoparticle paclitaxel (ABI-007), carboplatin and trastuzumab as first-line therapy of HER2-positive metastatic breast cancer
Authors: A. D. Seidman, M. Danso, A. Bach, M. Smith, M. Liu, M. Dickler, M. Robson, M. E. Moynahan, D. Lake, C. A. Hudis
Journal: Journal of Clinical Oncology (2006)

10650 Background: The combination of carboplatin (C), paclitaxel (P) and trastuzumab (T) is active in HER2+ metastatic breast cancer (MBC) (Robert N et al. Proc ASCO 2003), and safer with weekly administration of all 3 agents (Perez E et al. Proc ASCO 2004). The superiority of nanoparticle paclitaxel (Abraxane, AB) over Cremophor-based paclitaxel (Gradishar W et al. JCO 2005), and the efficacy and safety of weekly AB in MBC (Blum J et al. Proc ASCO 2005) motivated us to conduct this study. Materials/Methods: To date 10 of 50 planned patients (pts) with measurable, HER2+ MBC have entered. After we established the safety of AB at 75 mg/m 2 on days 1, 8, and 15 every 28 days (n = 4 pts), all subsequent pts received AB at 100 mg/m 2 . C was dosed at AUC = 2 on the same schedule, and T was weekly at 2 mg/kg without interruption, after a 4 mg/kg load. Initially, no prophylactic anti-allergy medication was given. Treatment is until disease progression (PD) or prohibitive toxicity. Pts without PD at 6 months may opt to continue T alone. Median age: 42 yrs (29–66), ECOG PS 0/1 (70/30%); 6 pts had prior adjuvant chemotherapy; 1 with anthracycline (A) and 4 with A + taxane (&gt; 1 yr prior). Results: 68 cycles have been delivered to date (median: 8, range 1–9). Dose reductions of AB and C have been necessary in 4 pts (to 80 mg/m 2 and AUC of 1.5 weekly), with delays in 4 pts. 3 pts had hypersensitivity reactions (HSR) to C and continued protocol therapy without C (n = 2) or with C and the addition of anti-HSR premeds (n = 1). Grade ¾ toxicities include neutropenia (44/11%) with 1 episode of febrile neutropenia. Grade ¾ anemia or thrombocytopenia has not occurred. Grade ¾ non-hematologic toxicity has been rare: 1 instance of grade 3 neuropathy (2 pts with grade 2). 7 partial responses have been observed in the first 9 evaluable pts (78%, 95% CI 44–93%), in liver, lung, bone and soft tissue sites, including 4 pts with prior adjuvant taxane. The median time to PD is not reached at 9.9+ months (7.3–9.9+). Accrual continues as the trial expands to additional study sites. Conclusions: The weekly administration of AB, C, and T demonstrates promising preliminary efficacy as 1 st -line treatment for HER2+ MBC. With the exception of HSRs due to weekly C, a very favorable toxicity profile is observed. [Table: see text]
As New Orleans Looks to the Future, Questions Remain on Hurricane Katrina’s Long-term Mental Health Effects
Authors: Julie A. Jacob
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Guidelines for perioperative cardiovascular evaluation for noncardiac surgery
Authors: K A Eagle, B H Brundage, B R Chaitman, G A Ewy, L A Fleisher, N R Hertzer, J A Leppo, T Ryan, R C Schlant, W H Spencer, J A Spittell, R D Twiss, J L Ritchie, M D Cheitlin, T J Gardner, A Garson, R P Lewis, R J Gibbons, R A O'Rourke, T J Ryan
Journal: Journal of the American College of Cardiology (1996)
Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel
Authors: Willibald Hochholzer, Christian T. Ruff, Robert A. Mesa, John F. Mattimore, John F. Cyr, Lanyu Lei, Andrew L. Frelinger, Alan D. Michelson, David D. Berg, Dominick J. Angiolillo, Michelle L. O'Donoghue, Marc S. Sabatine, Jessica L. Mega
Journal: Journal of the American College of Cardiology (2014)
Newborn screening for cystic fibrosis improves lung function and growth at time of transfer to adult care
Authors: Nicole Dijk, Karen McKay, Federica Barzi, Dominic Fitzgerald
Journal: European Respiratory Journal (2011)

Introduction:  Newborn screening (NBS) for Cystic Fibrosis (CF) is associated with improved early nutritional outcomes and improved spirometry in children.   Aim:  To determine whether the early diagnosis and treatment of CF with NBS in NSW in 1981 led to better clinical status and survival at transfer to adult care.   Methods:  Retrospective observational study compromising 2 cohorts: diagnosed symptomatically in the 3 years before newborn screening was introduced (“non-screened”) and diagnosed in the first 3 years of NBS (“screened”). Patients were followed up until transfer to adult care, before age 19 years. ANOVA was used for clinical outcomes & survival was compared using a Cox proportional hazard model.   Results:  Compared with non-screened patients (n=55), screened patients (n=56) were less likely to have pseud. aeruginosa in sputum at diagnosis (p=0.001), older when they acquired pseudomonas (p=0.001) & had better lung function when transferred to adult care: higher FEV1%, (mean difference = 17.2%; P = 0.012), FVC% (16.7%; P = 0.013), FEF50% (20.6%; P = 0.021) and a non-significantly higher BMI (0.95 kg/m 2 ; P = 0.143). There was a non-significant 41% mortality risk reduction in screened patients as compared to non-screened patients (Hazard Ratio (95% CI): 0.59 (0.24-1.43); p =0.25) Each 1% increase in FEV1% was associated with a 3% decrease in risk of death (p=0.002) and each 1 unit BMI increase was associated with an 46% decrease in risk of death (p   Conclusion:  NBS for CF leads to better lung function and nutritional state at time of transfer to adult care in screened patients. Both outcome measurements are good predictors for long term-survival.
Emergency consultation clinics avert unnecessary admissions
Authors: H. Coleman, F. Finlay
Journal: BMJ (1996)

Alternatives to hospital careStudy's results may not apply elsewhere EDrroR,-I wish to urge caution in extrapolating the results ofJoanna Coast and colleagues' study, which implies that a tenth of patients admitted to general hospitals could be relocated to more appropriate care.'I am leading a "total fundholding" project in Winchester, in which the practice will purchase all care on behalf of our patients, and have been examining the practice's use of acute services.We obviously have an inter- est in using expensive acute services carefully, and to that end we have followed up all our acute