tbuckley/cabot-search huggingface dataset:
Split, low-dose docetaxel (D) and low-dose capecitabine (C) is an active regimen in metastatic breast cancer with minimal toxicity
Authors: O. E. Silva, G. Lopes, D. Morgensztern, C. Lobo, S. Abdullah, P. Doliny, J. Slingerland, S. Gluck, E. Santos, C. Welsh, J. Hurley
Journal: Journal of Clinical Oncology (2006)

10618 Background: Successful therapeutic regimens in metastatic breast cancer must balance efficacy and tolerability. D and C is an active and commonly used doublet in this setting. D upregulates thymidine phosphorylase and thus potentiates the anti-tumor effects of C. A schedule with split, low-dose D in combination with low dose C could improve the therapeutic index of this regimen without compromising its clinical activity. Methods: Patients with previously untreated her2-neu negative metastatic breast cancer were included. A Simon 2-stage Phase II clinical trial was designed to assess the response rate (primary end-point), and toxicity of docetaxel 25 mg/m 2 on days 1 and 8 in combination with capecitabine 750 mg/m 2 bid on days 1–14 of a 21-day cycle. RECIST criteria were used for response assessment, which was performed every 2 cycles. Results: Thirty-one women have been enrolled. Median age was 55. Twenty patients had hormone receptor positive disease. Sites of metastasis were as follows: bone, 24 patients; liver, 14; lungs or pleura 14. A total of 189 cycles have been delivered (median: 4 cycles, range 1–33). Grade 3 and 4 toxicities were as follows: peripheral neuropathy, 2 patients; edema, 1 patient; skin, 1 patient. Two women had fever without neutropenia. Another patient had a gastric perforation but recovered without sequela. Twenty-two patients are available for response evaluation. One patient with a single bone metastasis had a complete response after chemotherapy followed by radiation. Partial responses were seen in 10 patients, for an overall response rate of 50% (95% CI, 30 to 70). Four women had stable disease and 7 had progressed at the time of first assessment. With a median follow-up of 15 months (range 1–26), the median time to treatment failure (all patients) was 7 months (range 1–26+). Median survival has not yet been reached. Out of 8 patients older than 65, seven were evaluable and 4 had a partial response. Conclusions: Split, low-dose Docetaxel and low-dose Capecitabine is an effective combination in the first-line treatment of patients with metastatic breast cancer. Toxicity with this schedule was minimal, making it an attractive regimen for further study. [Table: see text]
Structure and function of the von Willebrand factor A1 domain: analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation
Authors: Mariagrazia De Luca, David A. Facey, Emmanuel J. Favaloro, Mark S. Hertzberg, James C. Whisstock, Tracy McNally, Robert K. Andrews, Michael C. Berndt
Journal: Blood (2000)
Absence of HeLa Cell Contamination in 169 Cell Lines Derived From Human Tumors2
Authors: Jørgen Fogh, William C. Wright, James D. Loveless
Journal: JNCI Journal of the National Cancer Institute (1977)

Numerous cell lines derived from human tumors are not HeLa contaminants, Of 192 lines established in this or other laboratories, 169 lines were found to be G6PD type B, Twenty-three lines were type A as HeLa; three of these were of Negroid origin, There is reasonable doubt that the remaining 20 lines will all be shown to be confounded with HeLa.
Sorafenib for recurrent hepatocellular carcinoma after liver transplantation.
Authors: B. Ryoo, D. Yoon, M. Ryu, S. Lee, S. Hwang, D. Suh, J. Lee, T. Kim, H. Chang, Y. Kang
Journal: Journal of Clinical Oncology (2010)

e14669 Background: Sorafenib is the only drug that has shown a survival benefit in patients with hepatocellular carcinoma (HCC) in randomized phase III trials. The efficacy and safety of sorafenib in the treatment of recurrent HCC after liver transplantation, however, has not been determined. Methods: We retrospectively analyzed 13 patients who were treated with sorafenib for recurrent HCC after liver transplantation. Results: All 13 patients underwent living-donor liver transplantation for HCC with underlying liver cirrhosis caused by hepatitis B virus (HBV) infection. The median model for end-stage liver disease (MELD) score at transplantation was 7.6 (range, 4.2-25.2). The median time from liver transplantation to detection of recurrent HCC was 12.3 months (range, 0.5-33.4 months). The median serum alpha-fetoprotein (AFP) concentration before sorafenib administration was 193 ng/mL (range, 1-20,500 ng/mL). Eleven of 13 patients had a starting dose of 400mg twice daily and two had a starting dose of 200 mg twice daily at the discretion of the attending physician. The median duration of sorafenib treatment was 2.4 months (range, 0.3-9.9 months). Single or multiple immunosuppressants were coadministered in these patients during sorafenib treatment. Six of 10 evaluable patients showed stable disease, which was the best response and the median duration of stabilization was 3.9 months (95% confidence interval [CI], 1.6–6.2 months). At a median follow-up duration of 3.7 months (range, 0.3-10.9 months) in living patients, the median progression-free survival and the median overall survival from commencement of sorafenib were 2.9 months (95% CI, 1.2-4.6 months) and 5.4 months (95% CI, 3.7-7.0 months), respectively. Grade 3 neutropenia was observed in one patient, which was the only high grade hematologic toxicity observed. Grade 3 hand-foot skin reactions were observed in three patients. Adverse events could be managed with dose adjustment. Conclusions: These findings suggest that the efficacy of sorafenib for recurrent HCC after liver transplantation may not be inferior to that observed in phase 3 trials conducted in non- transplant patients and the drug may be safely administered with careful monitoring in these patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer
Pharmacological treatment with tetrahydrobiopterin in pulmonary hypertension
Authors: Bahaa Francis, Martin Wilkins, Lan Zhao
Journal: European Respiratory Journal (2011)

Introduction:  Tetrahydrobiopterin (BH4), by “recoupling” endothelial nitric oxide synthase (eNOS), increases NO bioavailability and decreases superoxide production. It is critical in maintaining pulmonary vascular homeostasis and may offer a treatment for pulmonary hypertension (PH).   Methods:  BH4 administration was studied in both monocrotaline and hypoxia models of PH.   Results:  In vivo BH4 administration (1mg bolus) caused minimal change in pulmonary artery pressure (PAP) in control rats (from 22.9 to 20 mmHg), but a significant acute reduction in the monocrotaline model (from 36 to 18 mmHg). In a Langendorff heart preparation, BH4 increased right ventricular systolic pressure (RVSP) in the hypertrophied right ventricle (RVH) compared to control (ΔRVSP=5.7±1.3 mmHg vs 0.7±1 mmHg respectively, p  In hypoxia, BH4 (100 mg/kg) reduced RVSP over 7 days (radiotelemetry, from 63±4 to 44.5±4 mmHg). At two weeks, BH4 (100 mg/kg) partially reversed RVH compared to placebo and BH4 (10 mg/d) (0.50±0.02, 0.58±0.03 and 0.57±0.1 respectively, p  BH4 (100 mg/kg) increased eNOS enzymatic activity in lung homogenates (but not protein levels). BH4 moderately increased cGMP (p>0.05) and significantly reduced superoxide.   Conclusions:  BH4 is a potential therapy which addresses the vasoconstrictive, hyperproliferative and hypertrophic nature of PH and warrants further investigation.
Phase 1 study of CWP232291 in relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
Authors: Jorge E. Cortes, Stefan Faderl, John Pagel, Chul Won Jung, Sung-Soo Yoon, Youngil Koh, Animesh Dev Pardanani, Robert S Hauptschein, Kyoung-June Lee, Je-Hwan Lee
Journal: Journal of Clinical Oncology (2015)

7044 Background: CWP232291, a novel peptidomimetic small molecule identified via a phenotypic drug discovery screen, shows selective inhibitory activity at submicromolar levels on a Wnt gene reporter and decreases expression of the β-catenin target genes, cyclin D1 and survivin. It has broad anti-cancer efficacy in vitro, with significant preclinical tumor regression outperforming standard cytotoxic AML drugs. Methods: Subjects with relapsed AML or MDS were infused CWP232291 iv over 5 -30 minutes for 7 days in 21-day cycles until disease progression in a first in human, 3+3 dose-escalation, Phase 1 design. Results: Results to January 27, 2015 over a dose range of 4 – 257 mg/m2 in 56 patients (53 AML; 3 MDS) are reported. Common ( ≥ 10% patients) drug-related adverse events (AEs) included nausea (43%), infusion-related reaction (36%), vomiting (29%), diarrhea (16%), and anorexia (11%). Toxicity was mostly ≤ grade 2 (91%), grade 3/4 events comprised 9%, observed similarly across all dose cohorts. Related serious AEs comprised fever, nausea, and anaphylactic reaction, at 19, 54 and 198 mg/m2, respectively. Dose-limiting toxicity included nausea, rash and anaphylactic reaction (54, 153 and 198 mg/m2, respectively). Toxicity was managed effectively with standard-of-care medications and, in the event of recurrence, could be mitigated with prophylaxis in subsequent cycles. Within 30 minutes CWP232291 was completely converted to its active metabolite, CWP232204. CWP232204 maximum plasma concentration (Cmax) and area under the time-concentration curve (AUC) values were dose proportional. At the highest dose with data (153 mg/m2; n = 6), the mean terminal elimination half-life (t½) was 6.3 hrs, mean Cmax was 9922 ng/mL, and AUC was 6797 ng•hr/mL. A complete remission was seen in one AML patient after 2 cycles at 153/118 mg/m2, with normalization of neutrophil and platelet counts; maximum reduction from baseline in β-catenin and survivin expression were > 90% and 77%. No other objective responses were seen but higher doses showed significant reductions in these biomarkers. Conclusions: CWP232291 single agent efficacy was observed in AML. MTD has not been defined; accrual is ongoing. Clinical trial information: NCT01398462.
Selective Effects of Two Chloromethyl Ketones on Amino Acid and Phosphate Uptake in Rat Liver and Tumors&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M A Lea, M R Koch
Journal: JNCI Journal of the National Cancer Institute (1979)

Injection of L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) at a level of 10 mg/100 g body weight inhibited the incorporation of 3H-labeled amino acids into protein in Morris hepatomas 7777and 9618A2. The degree of inhibition was similar in cytoplasmic proteins and in histone and nonhistone nuclear protein fractions. There was no inhibitory effect on 3H-labeled amino acid incorporation in the livers of the tumor-bearing rats. The inhibitory effect of N-tosyl-L-lysine chloromethyl ketone (TLCK) on incorporation of 3H-labeled amino acids was observed in both the slowly growing hepatoma 7787 and the rapidly growing hepatoma 7777. In hepatoma 7777, TLCK (2.5 mg/100 g body wt) exerted a greater inhibitory effect on incorporation when administered 60 minutes before [3H]leucine injection than when injected simultaneously. Studies on tissue uptake of amino acids, thymidine, and phosphate indicated that inhibitory effects of TPCK and TLCK on active transport may be a major factor in the action of these drugs on macromolecular synthesis. The inhibitory effects of TPCK and TLCK seen in transplanted hepatomas and a colon tumor were not generally seen in normal tissues of the tumor-bearing rats.
Treating IgA Nephropathy
Authors: JOHN J. DILLON
Journal: Journal of the American Society of Nephrology (2001)

IgA nephropathy may be the most common type of glomerulonephritis, worldwide. Once thought benign, it causes end-stage renal disease in 15 to 20% of individuals within 10 yr of onset ([1][1]) and in 30 to 35% of individuals within 20 yr of onset. Proteinuria, an elevated serum creatinine
Use and Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer: A Population-Based Study
Authors: Christopher M. Booth, Sulaiman Nanji, Xuejiao Wei, Yingwei Peng, James J. Biagi, Timothy P. Hanna, Monika K. Krzyzanowska, William J. Mackillop
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: International guidelines recommend adjuvant chemotherapy (ACT) for patients with stage III colon cancer. Whether efficacy observed in clinical trials translates to effectiveness in routine practice is less well understood. Here we describe use and outcomes of ACT in routine practice. Methods: All cases of colon cancer treated with surgery in Ontario 2002–2008 were identified using the population-based Ontario Cancer Registry. Linked electronic records of treatment identified surgery and ACT use. Pathology reports were obtained for a random 25% sample of all cases; patients with stage III disease were included in the study population. Modified Poisson regression was used to evaluate factors associated with ACT. Cox proportional hazards model and propensity score analysis were used to explore the association between ACT and cancer-specific survival (CSS) and overall survival (OS). Results: The study population included 2,801 patients with stage III colon cancer; 66% (n=1,861) received ACT. ACT use rates varied substantially across age groups; 90% among patients aged 20 to 49 years versus 68% among those aged 70 to 79 years (P<.001). ACT use was inversely associated with comorbidity (P<.001) and socioeconomic status (P=.049). In adjusted analyses advanced age is associated with inferior CSS and OS. Use of ACT was associated with decreased risk of death from cancer (hazard ratio [HR], 0.63; 95% CI, 0.54–0.73) and decreased risk of death from any cause (HR, 0.63; 95% CI, 0.55–0.71). This result was consistent in the propensity score analysis. Conclusions: One-third of patients with stage III colon cancer in the general population do not receive ACT. Use of ACT in routine practice is associated with a substantial improvement in CSS and OS.
Symptom Diagnosis, Regional and General.
Journal: JAMA (1927)

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
The effect of single-nucleotide polymorphism in IL-13 on airway hyperresponsiveness in asthmatics
Authors: Yu Utsumi, Takayuki Miyamoto, Kenshi Sekimura, Nobuhito Sasaki, Naomi Suzuki, Yutaka Nakamura, Hitoshi Kobayashi, Kohei Yamaucho
Journal: European Respiratory Journal (2012)

Background : Single-nucleotide polymorphism (SNP: rs20541) of IL-13 has been recognized as a risk factor of asthma. We recently demonstrated that FEV1 in asthmatics with the Q110 variant IL-13 declined faster (Allergol Int 2011). However, the effects of the variant IL-13 on airway hyperresponsiveness (AHR) have never been elucidated.

Objectives : To evaluate the effects of SNP (rs20541) in IL-13 on AHR in asthmatics, we analyzed the relationship between SNP and AHR.

Methods : We recruited 182 asthmatics to the current study who visited the asthma out-patient clinic in Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped using rs20541 by 7500 Fast Real-Time PCR System, (Applied Biosystems USA). Therapeutic steps (GINA 2011), eosinophil counts in peripheral blood and serum IgE concentration in those asthmatics were also studied. AHR to methacholine was measured by Astograph; Jupitor 21 (Chest, Japan). AHR was expressed as Dmin (U) (average ± SE). Statistical analysis was performed by one way ANOVA. This study was approved by the ethics committee of Iwate Medical University.

Results : Genotyping of rs20541 showed that 26 A/A, 77 A/G and 79 G/G. D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G and 2.85±0.39 in G/G. D min in the 3 genotypes was proved to be significantly different by Kruskal-Wallis One Way Analysis of Variance (p=0.007). There was no significant difference in therapeutic steps, eosinophil counts or serum IgE concentration among the 3 genotypes of asthmatics. Conclusion : SNP (rs20541) in IL-13 was associated with AHR, suggesting that IL-13 was involved in the progress of AHR through its biological activity on airway smooth muscles.
Morphological subclassification of follicular lymphoma: variability of diagnoses among hematopathologists, a collaborative study between the Repository Center and Pathology Panel for Lymphoma Clinical Studies.
Authors: G E Metter, B N Nathwani, J S Burke, C D Winberg, R B Mann, M Barcos, C R Kjeldsberg, C C Whitcomb, D O Dixon, T P Miller
Journal: Journal of Clinical Oncology (1985)

A collaborative study between the Repository Center for Lymphoma Clinical Studies and the members of the lymphoma pathology subcommittee of the major cooperative oncology groups was undertaken in an effort to ascertain the reproducibility and the interobserver agreement for the cytologic diagnosis of follicular lymphomas. A group of 105 patients with follicular lymphomas were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes, and Collins, and Working Formulation systems. In these systems, follicular lymphomas are subclassified by estimation of the different cell populations without the actual counting of cells. With this method, great variability in diagnosis was noted. For example: (1) The consensus diagnosis was that of poorly differentiated lymphocytic lymphoma (PDL) in 39 cases, but among the individual pathologists the number of cases thus diagnosed ranged from 24 to 65; (2) In 40 cases, the consensus diagnosis was follicular lymphoma, mixed-cell type; however, all seven pathologists independently agreed on this subtype in only one case; (3) A major disagreement was noted in 39 cases (37%), in which both diagnostic extremes (small cleaved and large noncleaved) were expressed. In the second method, only precise counts of different cells were made, according to a modification of the method recommended by Berard. With this counting method, diagnoses were independently derived based on the counts provided by the seven pathologists for large cleaved, small noncleaved, and large noncleaved cells. The variability in the results was wide also with this second method. For example, the average number of large cells found by each pathologist was ascertained, and the ranges were determined. The average range was 28 cells, which was considered high. The same determinations were performed only for large noncleaved cells, and the range was found to be 15 cells, which was also considered high. When the diagnoses derived from counts of only large noncleaved cells were compared with the traditional, more subjective diagnoses, fairly close agreement was obtained. In summary, the great variability in diagnoses of follicular lymphomas among pathologists may be attributed to the difficulties inherent in accurate determination of cell size and of the precise percentages of different cells. Until solutions to these problems are developed, one can subclassify follicular lymphomas according to the Berard method or the estimation method.
An EBV genome carrying pre-B cell leukemia in a homosexual man with characteristic karyotype and impaired EBV-specific immunity.
Authors: I Ernberg, M Björkholm, L Zech, B Sandstedt, R Szigeti, J Andersson, W Henle, G Klein
Journal: Journal of Clinical Oncology (1986)

A Burkitt-like lymphoma/leukemia confined to bone marrow was detected in a human T cell leukemia virus (HTLV)-III/LAV- and Epstein-Barr virus (EBV)-seropositive homosexual man. The tumor cells were EBNA-positive and contained at least 22 EBV genomes per cell. They were totally immunoglobin negative, but showed other markers for B cells detected with monoclonal antibodies. The patient had an impaired cellular immunity to EBV antigens and EBV-infected cells at diagnosis, but these reactions normalized during treatment. Cell clones derived from the bone marrow tumor in vitro also carried EBV and had six different marker chromosomes, including the typical 14q+ chromosome and a t(8 - ;8), which resulted in trisomy for the largest part of 8q. Partial trisomy for 12q was also observed. The patient completed six courses of combination chemotherapy and remains in excellent health after 34 months of follow-up.
Interferon Inhibition of Autogenously Induced Virions (C Particles) in Synchronized L-929 Cell Cultures&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: M V O'Shaughnessy, K B Easterbrook, S H Lee, L J Katz, K R Rozee
Journal: JNCI Journal of the National Cancer Institute (1974)

The growth rate of monodispersed monolayer cultures of L-929 cells was reversibly reduced by the incorporation of mouse interferon into the growth medium. In synchronously growing cells, interferon delayed DNA synthesis and subsequent mitosis. The production of C-type virions was replicatively linked to the cell cycle and was significantly affected in this cell system.
The relationship between obesity and distal airways
Authors: Gregory Marin, Nicolas Molinari, Isabelle Vachier, Philippe Godard, Pascal Chanez, Anne-Sophie Gamez, Arnaud Bourdin
Journal: European Respiratory Journal (2011)

Introduction:  Obesity is a risk factor for asthma-like symptoms. Small airway involvement has been linked to difficulties in controlling asthma. Forced Vital Capacity (FVC) fall at PC20 has been suggested as a potent marker of distal airway abnormalities. Whether obesity is associated with increased distal airway involvement remains unknown.   Hypothesis:  We hypothesized that FVC fall at PC20 during a methacholine challenge was increased in overweight and obese patients with asthma-like symptoms.   Methods:  298 consecutive adult women with asthma-like symptoms underwent a methacholine bronchial provocation test according to ATS-guidelines. PC20 methacholine and FVC fall at PC20 were computed for all subjects. Bronchial Hyper-Responsiveness (BHR) was considered when PC20 was ≤1600μg. PC15 and FVC fall at PC15 were recorded in patients who did not achieve a 20% fall of Forced Expiratory Volume in 1 second (FEV1s).   Results:  A logistic regression with age, smoking and Body Mass Index showed that only obesity (BMI ≥ 30) increased the risk of BHR with an odds-ratio of 4.2 (95 CI: 1.670–12.295) (p=0.0041). BMI had no impact on the relationship between FEV1s and FVC (p=0.2490). On the other hand, BMI influenced the percentage fall in FVC at the PC15 only in patients with PC20>1600μg (normal 9±13%; overweight 10±16% and obese 15±32%, p=0.0073).   Conclusion:  Obesity is a risk factor for BHR in women patients with asthma symptoms. FVC fall at PC20 is not affected by the BMI. Nonetheless, in obese women with asthma symptoms but negative methacholine challenge, we observed a potential involvement of distal airways measured by the FVC.