tbuckley/cabot-search huggingface dataset:
Is positron emission tomography (PET) with FDG an early predictor of the RECIST morphological response to chemotherapy in metastatic colorectal cancer patients (mCRC)?
Authors: A. Hendlisz, P. Emonts, A. Covas, L. Ameye, M. Paesmans, R. Castany Prado Maria del Rosario, G. Machiels, M. Van den Eynde, B. Vanderlinden, P. Flamen
Journal: Journal of Clinical Oncology (2009)

2533 Background: Reliable early assessment of response would help identify active treatments and avoid unnecessary side effects. Our hypothesis was that FDG-PET metabolic changes 2 weeks after the first dose of chemotherapy predict standard morphological response. Methods: 45 mCRC patients undergoing 1st or 2nd-line chemotherapy are planned to be included in a prospective trial comparing early metabolic changes, as measured by serial FDG-PET, with the standard RECIST- based response assessment using multi-slice CT. A signed informed consent was obtained in all cases. For the lesion-by-lesion analysis, according to the EORTC recommendations, a metabolic response was defined as a ≥ 15% decrease of the standardized FDG uptake (SUVmax) on day 14. A patient was classified as having overall metabolic responsive disease if the majority or all lesions observed on the baseline PET showed a metabolic response, without any progressive lesion ( ≥25% increase). Results: At interim analysis, 28 patients (median age 65.9 yrs) were available for comparative metabolic and morphological analysis of 88 lesions. Mean number of lesions per patient was 3 (range 1–8). Patients received FOLFOX (18), FOLFIRI (9), and capecitabine (1) as first- (19) or second-line (9) treatments. Metabolic assessment showed 49 (56%) responding and 39 (44%) nonresponding lesions. The morphological response rate in metabolically non-responding lesions (5/39; 13%) was lower than in responding lesions (22/49; 45%) (p = 0.001; Fisher's exact test). A mixed metabolic response, combining responding and non-responding lesions within the same patient, was seen in 21/28 (75%) pts. A RECIST response was observed in 6/14 (43%) PET responding and in 0/14 (0%) PET nonresponding patients (p = 0.02; Fisher's Exact test). Updated results of this ongoing trial will be presented. Conclusions: Serial FDG PET seems able to identify non-responding mCRC disease after one course of chemotherapy. No significant financial relationships to disclose.
Review fails to advise on cannabis use because of poor research
Authors: Bob Roehr
Journal: BMJ (2017)

The chair of a group brought together to develop public policy and medical guidelines on the use of cannabis has said that her task had been thwarted by the poor quality of the evidence.

Marie McCormick, a professor of pediatrics and chair of the department of maternal and child health at the Harvard School of Public Health, chaired the US National Academies of Sciences, Engineering, and Medicine committee that examined the topic and issued a report on 12 January.1 She concluded: “The lack of any aggregated knowledge of cannabis related health effects has led to uncertainty about what, if any, are the harms or benefits of its use.” …
Augmented Reality Goes Bedside
Authors: Jeff Lyon
Journal: JAMA (2017)

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
Combination of a Spicamycin Analogue KRN5500 and Chemotherapeutic Agents Synergistically Enhances Their Cytotoxicity in Human Myeloma Cells.
Authors: Hirokazu Miki, Shuji Ozaki, Osamu Tanaka, Shiro Fujii, Shingen Nakamura, Ai Mihara, Kumiko Kagawa, Jin Asano, Kyoko Takeuchi, Kenichiro Yata, Toshihiro Hashimoto, Masahiro Abe, Toshio Matsumoto
Journal: Blood (2007)
An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer
Authors: Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
Journal: Journal of Thoracic Oncology (2017)
Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity
Authors: Shams-un-nisa Naveed, Debbie Clements, David J. Jackson, Christopher Philp, Charlotte K. Billington, Irshad Soomro, Catherine Reynolds, Timothy W. Harrison, Sebastian L. Johnston, Dominick E. Shaw, Simon R. Johnson
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma.Objectives: To investigate whether MMP-1 could be activated by mast cells and increase asthma severity.Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed.Measurements and Main Results: Airway smooth muscle cells generated pro–MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P < 0.05), which was dependent on MMP-1 activation. In asthma, airway pro–MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms.Conclusions: MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness.
Supression of FLT3-Expressing Leukemia by a Monoclonal Antibody-Auristatin Conjugate.
Authors: Yiwen Li, Hongli Li, Mei-Nai Wang, Rajiv Bassi, Dale Ludwig, Larry Witte, Zhenping Zhu, Peter Bohlen, Damon Meyer, Angelyn Larkin, Peter Senter, Daniel Hicklin
Journal: Blood (2004)
Exploring polyvinylpyrrolidone in the engineering of large porous PLGA microparticles via single emulsion method with tunable sustained release in the lung: In vitro and in vivo characterization
Authors: Rui Ni, Uwe Muenster, Jing Zhao, Lan Zhang, Eva-Maria Becker-Pelster, Martin Rosenbruch, Shirui Mao
Journal: Journal of Controlled Release (2017)
Sickle Cell Inflammatory Environment Is Associated with Products of the Eicosanoid Synthesis Pathways
Authors: Magda Oliveira Seixas Carvalho, Joao Henrique Oliveira Reis, Larissa Carneiro Rocha, Bruno Cerqueira, Theo de Araujo Santos, Nívea Farias Luz, Valma Maria Lopes do Nascimento, Mauricio Batista Carvalho, Valeria de Matos Borges, Marilda Souza Goncalves
Journal: Blood (2015)
Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis
Authors: Chuan-Jin Wu, Xu Feng, Michael Lu, Sohshi Morimura, Mark C. Udey
Journal: Journal of Clinical Investigation (2017)

Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated.
Benzoic acid metabolism reflects hepatic mitochondrial function in rats with long-term extrahepatic cholestasis
Authors: L Krähenbühl, J Reichen, C Talos, S Krähenbühl
Journal: Hepatology (1997)

ABSTRACT Benzoic acid metabolism, which is primarily a function of liver mitochondria, depending on the concentration of adenosine triphosphate (ATP), coenzyme A (CoA), and glycine in the mitochondrial matrix, was investigated in both rats with long–term cholestasis caused by bile duct ligation (BDL) and sham–operated control rats. In isolated liver mitochondria, hippurate production from benzoate in the presence of saturating glycine concentrations was reduced in BDL rats by 36% with l–glutamate as a source for ATP, by 21% in the presence of succinate, and by 31% in the presence of ATP plus oligomycine. This reduction in benzoate metabolism is in the same range as the previously observed reduction in the activity of the electron transport chain in liver mitochondria from BDL rats. The mitochondrial CoA pool, which can be rate–limiting for benzoic acid metabolism, was not different between BDL and control rats. The activity of benzoyl–CoA synthase, the enzyme catalyzing the rate–limiting step in benzoate metabolism, was reduced by 25%, and the activity of benzoyl–CoA:glycine N –transferase was reduced by 66% in BDL rats. The activity of benzoyl–CoA synthase was significantly inhibited by lithocholate, suggesting that hepatic accumulation of hydrophobic bile acids could contribute to the observed reduction of benzoate metabolism in BDL rats. Benzoate metabolism was also studied in vivo by monitoring the urinary hippurate excretion after intraperitoneal administration of benzoate (100 μmol/100 g of body weight). The time course of hippurate excretion was not different between BDL and control rats. Hippurate excretion over 24 hours after benzoate administration averaged 89.7 ± 4.0% of the administered dose in BDL and 74.4 ± 6.9% (mean ± SEM, difference not significant) in control rats. This finding could be explained by an increase in mitochondrial protein in BDL rats, averaging 2.34 ± 0.29 g per liver in BDL and 1.35 ± 0.07 g per liver in control rats (mean ± SEM, p &lt; .05). Thus, the studies show that benzoate metabolism reflects mitochondrial function in BDL rats both in vivo and in vitro , and that mitochondrial proliferation compensates for the observed decrease in benzoic acid metabolism in isolated mitochondria in vitro .
18F-NaF PET-CT in Symptomatic Fabella Syndrome
Authors: Sharjeel Usmani, Fahad Marafi, Najeeb Ahmed, Fareeda Al Kandari
Journal: Clinical Nuclear Medicine (2017)

Fabella is a sesamoid bone, located within the tendon of the lateral head of the gastrocnemius muscle. It may be associated with posterolateral knee pain because of repetitive friction over the posterolateral femoral condyle. We report a case of a 64-year-old woman presenting with right posterolateral knee pain. 18F-NaF PET-CT demonstrated increased uptake posterior to the right knee joint localizing to a fabella. Standard examination and radiographic imaging excluded other causes for posterolateral knee pain, and the increased activity was considered to be secondary to fabella syndrome. NaF PET-CT can provide useful information in the evaluation of posterolateral knee pain.
British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017
Authors: D. Berker, J.M. McGregor, M.F. Mohd Mustapa, L.S. Exton, B.R. Hughes, P.M. McHenry, K. Gibbon, D.A. Buckley, I. Nasr, C.E. Duarte Williamson, V.J. Swale, T.A. Leslie, E.C. Mallon, S. Wakelin, S. Ungureanu, R.Y.P. Hunasehally, M. Cork, G.A. Johnston, J. Natkunarajah, F.S. Worsnop, N. Chiang, J. Donnelly, C. Saunders, A.G. Brian
Journal: British Journal of Dermatology (2017)
Identification of BCL6 As a Therapeutic Target in RAS-Driven Acute Lymphoblastic Leukemia
Authors: Qiang Li, Christian Hurtz, Seyedmehdi Shojaee, Zhengshan Chen, Huimin Geng, Gang Xiao, Mignon L. Loh, B. Hilda Ye, Ari Melnick, Markus Muschen
Journal: Blood (2015)
Evaluation of a Large Renal Mass Using 99mTc-MIBI SPECT/CT in a Patient With Chronic Kidney Disease
Authors: Steven P. Rowe, Michael A. Gorin, Mehrbod S. Javadi, Mohamad E. Allaf
Journal: Clinical Nuclear Medicine (2017)

The differentiation of benign and indolent renal masses from aggressive tumor histologies cannot be reliably performed by CT or MRI. Additionally, renal mass biopsy risks complications and has a nondiagnostic rate of 10% to 20%. Tc-MIBI SPECT/CT has been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chormophobe tumors from other more aggressive renal tumor types. We present the case of an 84-year-old man with chronic kidney disease and an 11.2-cm renal mass. Results of his Tc-MIBI SPECT/CT allowed avoidance of a radical nephrectomy.
ULBP and MICA/B as Novel Indicators for Both Diagnosis of Immune-Mediated Marrow Injury and Favorable Response to Immunosuppressive Therapy in Bone Marrow Failure Syndromes.
Authors: Nobuyoshi Hanaoka, Tatsuya Kawaguchi, Kentaro Horikawa, Shoichi Nagakura, Yasuchika Tsuzuki, Yuji Yonemura, Hideki Nakakuma
Journal: Blood (2006)
uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis
Authors: Yan Liu, Yun Feng Pan, You-qiu Xue, Lin-kai Fang, Xing-hua Guo, Xin Guo, Meng Liu, Bi-yao Mo, Meng-ru Yang, Fang Liu, Yun-ting Wu, Nancy Olsen, Song Guo Zheng
Journal: Cellular and Molecular Immunology (2017)
The risk of contralateral non sentinel metastasis in patients with primary vulvar cancer and unilaterally positive sentinel node.
Authors: Linn Lena Woelber, Christine Eulenburg, Donata Grimm, Fabian Trillsch, Inga Bohlmann, Jihad Dowaji, Eike Burandt, Fritz Jaenicke, Sven Mahner, Katharina Prieske
Journal: Journal of Clinical Oncology (2015)

e16600 Background: In patients with primary vulvar cancer and bilateral sentinel node (SLN) biopsy bilateral complete inguino-femoral lymphadenectomy (LAE) is recommended even in cases with only unilaterally positive SLN by most guidelines. The risk of contralateral non-SLN metastasis is unclear. Methods: All patients with primary vulvar cancer receiving a SLN dissection with radioactive tracer +/- blue dye at the University Medical Center Hamburg-Eppendorf between 2001 and 2013 were retrospectively evaluated. There were three cohorts: patients with positive uni/bilateral SLN and bilateral LAE, patients with negative uni/bilateral SLN without further LAE and patients with LAE despite negative SLNs when the technique was established at our center. Median follow-up was 26 months. Results: 143 patients (median age 57 years, range 20-87) were included; 122 with bilateral and 17 with unilateral SLN dissection (in 4 cases this information was not available). A median number of 2 SLN (range 1-7) per groin were dissected. Of 55 (55/143, 38.5%) patients that received a subsequent LAE, 40 (40/143; 28.0%) had presented with a positive SLN (31 unilateral, 8 bilateral, 1 missing). 31 patients underwent bilateral SLN biopsy and had a unilateral positive SLN and contralateral negative SLN (31/122, 25.4%). Of these, none presented with a contralateral non-SLN metastasis (0/31, 0%). 69.2% (99/143) of patients had node-negative disease. PFS at 24 months was: 91.4% in node-negative patients with SLN biopsy only, 83.6% in node-negative with LAE and 77.5% in node-positive patients. One of the node-negative patients with SLN biopsy only developed groin recurrence (1/82, 1.2%) after 17 months. No groin recurrences were observed in node-negative patients with LAE (0/17, 0%). Conclusions: In case of bilateral SLN biopsy for clinically node-negative disease and only unilaterally positive SLN the risk for contralateral non-SLN metastases seems to be low. These data support the omission of contralateral LAE in selected patients to reduce morbidity.
Prescription data for open toe sandals syndrome
Authors: Richard Croker, Ben Goldacre
Journal: BMJ (2017)

Borman and Johnson describe seasonal variation in GP requests for analysis on dermatophyte samples in southwest England, peaking in July, and then argue that this may reflect the presence of open toe sandals syndrome in the UK.1 We found that NHS primary care prescribing data show a similar seasonal variation in prescription of the most common treatments for tinea unguium (oral terbinafine2 and amorolfine nail laquer3), with more in summer months.

The data also indicate guideline breaches. They show a …
Therapeutic doses of tamoxifen only partially inhibit the non-genomic effects of estrogen: Evidence for additive anti-proliferative effect of tamoxifen with MEK inhibitor
Authors: S. Djahansouzi, T. Heimerzheim, M. Reinhardt, B. Hanstein, P. Dall, H. G. Bender, D. Niederacher
Journal: Journal of Clinical Oncology (2005)

3195 Background: Recent data suggests that non-genomic effects of Estradiol (E2) in estrogen-sensitive carcinoma cell lines result in the activation of the MAP-Kinase (MAPK) pathway (p44/42). MAPK activation is a potent proliferative stimulus and E2 activation of this cascade seems to occur rapidly at the plasma membrane level and distinct from the classical mechanism of E2-E2 receptor interaction at the DNA level. We investigated the interaction of the SERM Tamoxifen (Tam) and a MAPK inhibitor (MEK inhibitor PD98059) on the non-genomic effects of E2. Methods: Human breast cancer cells (MCF-7) were maintained in DMEM with 10% FCS. For proliferation experiments, cells were counted and cultured into 96-well plates using seeding densities of 5000 cells /cm3. After incubation, the culture media were replaced with media containing vehicle E2 (10-9 & 10-8 M) or EGF (100ng/ml). Defined number of wells contained Tam (10–8 M) and/or PD98059 (23μM) in addition to the vehicle. Proliferation was analyzed after 48 & 96 hrs using MTS assay. Metabolic active cells reduce MTS to formazane with subsequent detection in an ELISA-Reader. Western blots were performed on protein extracts obtained from cells untreated or treated (E2, EGF, Tam or PD98059). Defined number of wells contained Tam and/or PD98059 in addition to treatment. Cell extracts containing 20μg of total protein per sample were analyzed with SDS/PAGE, transferred to nitrocellulose filters and probed with Abs specific for p44/p42 MAPKs. Results: Data reconfirms the proliferative effects of E2 and EGF when compared with controls. Tam at therapeutic doses weakly reduces the proliferative effects of E2 and partial reduction of MAPK activity. PD98059 highly and significantly reduces proliferation rates and MAPK activity. The effects of Tam and MAPK inhibition seem to be additive. Conclusion: Experimental data suggests a higher anti-proliferative efficacy in the combination of Tam at therapeutic doses and MAPK inhibitors. The weak inhibition of MAPK activity with Tam may clinically translate in favor of complete inhibition of E2 production or combination with MAPK inhibitors. No significant financial relationships to disclose.
In Vivo Effects of Lenalidomide on T Cell Proliferation and Immune Checkpoint Molecules in Patients with Advanced Stage CLL: Results from a Phase II Study
Authors: Maria Winqvist, Fariba Mozaffari, Marzia Palma, Sandra Eketorp Sylvan, Hakan Mellstedt, Anders Osterborg, Jeanette Lundin
Journal: Blood (2015)
TEL/AML1 Expression in a Non-B Cell Line Induces a Set of Differentially Expressed Genes, but Points to Cell Type Specific Effects of the Fusion Protein in Leukemic Blasts of TEL/AML1 Positive Patients.
Authors: Kerstin Hasse, Renate Kirschner-Schwabe, Claudio Lottaz, Jutta Proba, Ute Ungetuem, Rainer Spang, Guenter Henze, Karl Seeger
Journal: Blood (2006)
The definition of stroke
Authors: Alexander P Coupland, Ankur Thapar, Mahim I Qureshi, Harri Jenkins, Alun H Davies
Journal: Journal of the Royal Society of Medicine (2017)

Hippocrates could never have imagined the progress made in stroke care since this statement, yet the world is still unable to agree on a universal definition. This review charts the evolution of the definition of stroke and highlights current problems.
Activation of T- and NK- Cells through CD19xCD3 and CD19xCD16A Bispecific TandAb Antibodies in Patients with B-Cell Non-Hodgkin's Lymphoma.
Authors: Lisa Poertner, Markus Uhrberg, Kathrin Schoenberg, Daniela Bruennert, Uwe Reusch, Melvin Little, Rainer Haas, Frank Neumann
Journal: Blood (2009)