tbuckley/cabot-search huggingface dataset:
T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
Authors: Hannah Dzimitrowicz, Michael Berger, Craig Vargo, Annette Hood, Osama Abdelghany, Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, Christos Hatzis, Lajos Pusztai, Rashmi Murthy
Journal: Journal of Clinical Oncology (2016)

Purpose Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.
P-Glycoprotein Content and Mediation of Vincristine Efflux: Correlation with the Level of Differentiation in Luminal Epithelium of Mouse Small Intestine
Authors: M B Meyers, K W Scotto, F M Sirotnak
Journal: Cancer Communications (1991)

Luminal epithelium from mouse small intestine was fractionated into four distinct components ranging from the most differentiated (absorptive epithelial cells, fraction I) to the least differentiated (proliferative crypt cells, fraction IV). Immunoblot analysis of these fractions with monoclonal antibodies to P-glycoprotein, C219, and HYB-241, indicated that the amount of P-glycoprotein increased in cells as they progressed in level of differentiation from crypt to the villar surface of the lumen of the small intestine. P-glycoprotein in these normal intestinal cells functioned as a transporter of vincristine, one of a group of cancer chemotherapeutic agents to which cells can develop multidrug resistance. Transport ability was shown by efflux studies with vincristine as substrate. Efflux increased with differentiation and correlated with the increase in the amount of P-glycoprotein. Fraction I cells effluxed vincristine about seven times more rapidly than fraction IV cells. Efflux of vincristine was almost entirely inhibited from fraction I cells after treatment with antibody HYB-241, which recognizes an external epitope of P-glycoprotein. This finding would appear to demonstrate that P-glycoprotein was directly responsible for at least the majority of efflux of vincristine in these cells. The observed Mr of P-glycoprotein in fraction I cells was 140,000 when cells were solubilized with sodium dodecyl sulfate at room temperature before electrophoresis and immunoblot analysis. When solubilized fraction I protein was heated with 2-mercaptoethanol before electrophoresis, P-glycoprotein was seen by immunochemical procedures as an Mr 50,000-55,000 protein. No Mr 170,000 or 180,000 forms of P-glycoprotein (forms that are found in multidrug-resistant cell lines and are stable to heat or sulhydryl agents) were detected in any fraction of these epithelial cells under the conditions used. Functional P-glycoprotein was, therefore, associated with differentiation of luminal epithelium in small intestine, and the P-glycoprotein produced by these cells may be a type not previously described.
Foot and Ankle Hepatocellular Carcinoma Metastasis
Authors: Kalind Parashar, Neeta Pandit-Taskar
Journal: Clinical Nuclear Medicine (2015)

Bone is the third most common site of metastasis from hepatocellular carcinoma (HCC), the first two being the lung and lymph nodes, respectively. Metastatic HCC has been reported in the vertebrae, ribs, pelvis, and femur, which are more common sites of bone metastases. We present a case of HCC with metastasis to the distal tibia, fibula, and small bones of the feet as the only sites of bone metastasis, along with a brief literature review.
AT-04TOWARDS AN EPIGENETIC THERAPY FOR RHABDOID TUMORS -IN VITRO RESULTS FOR THE EPIGENETIC MODULATORS RESMINOSTAT AND 4SC-202
Authors: Hella Kohlhof, Tanja Wulff, Daniel Vitt, Michael Fruehwald
Journal: Neuro-Oncology (2016)

Among others histone deactyleases 1 and 2 (HDAC1, 2) are overexpressed across all molecular subgroups of AT/RT.Resminostat is an orally available inhibitor of HDAC classes I and IIb; whereas 4SC-202 is a combined inhibitor of HDAC1/2/3 and the lysine specific demethylase LSD1.Additionally, 4SC-202 inhibits the SMO-independent HH signaling which is often aberrantly activated in AT/RT.Both inhibitors have proven tolerability and efficacy in phase I or II trials in adults.Their toxicity profile appears to be favorable while maintaining targeting efficacy.Proliferation and viability of cell lines G401 (RTK), A204 (MRT) and CHLA-02 (AT/ RT) were evaluated by crystal violet staining and MTT, spheroid and colony formation assays.Expression of genes associated with the phenotype of rhabdoid tumors such as SMARCB1, CDKN1C, MYC, CyclinD1 and HHIP was examined by qRT-PCR.As comparative HDACi Vorinostat, Panobinostat, Entinostat, Mocetinostat and Ricolinostat were tested.Resminostat and 4SC-202 exhibited a dose dependent inhibition of proliferation and viability of RT cells.Inhibition of the capacity for clonogenic growth was demonstrated.Gene expression data are currently evaluated.Rhabdoid tumors as paradigmatic epigenetic malignancies appear to be the optimal foci for drugs targeting the epigenetic scaffolding of tumor cells.The epigenetic modulators Resminostat and 4SC-202 warrant further testing in clinical trials in children with rhabdoid tumors.Likely combinatorial therapy will be needed to prove a significant effect on outcome for affected high-risk patients.Overall survival
Preoperative Evaluation of Renal Cell Carcinoma by Using 18F-FDG PET/CT
Authors: Miwako Takahashi, Haruki Kume, Keitaro Koyama, Tohru Nakagawa, Tetsuya Fujimura, Teppei Morikawa, Masashi Fukayama, Yukio Homma, Kuni Ohtomo, Toshimitsu Momose
Journal: Clinical Nuclear Medicine (2015)

This study aimed to characterize the FDG uptake of renal cell carcinoma (RCC) by the pathological subtype and nuclear grade.We retrospectively identified patients who underwent F-FDG PET and subsequent partial or radical nephrectomy for renal tumors. The relationships of the SUV of renal tumor with subtypes, nuclear grade, and clinicopathological variables were investigated.Ninety-two tumors were analyzed, including 52 low-grade (G1 and G2) and 18 high-grade (G3 and G4) clear cell RCC; 7 chromophobe, 5 papillary, and 1 unclassified RCC; and 9 benign tumors (7 angiomyolipoma and 2 oncocytoma). The SUVs of high-grade clear cell RCC (mean ± SD, 6.8 ± 5.1) and papillary RCC (6.6 ± 3.7) were significantly higher than that of the controls (2.2 ± 0.3). The SUV of high-grade clear cell RCC was higher than that of low-grade tumors (median, 4.0 vs. 2.2; P < 0.001). The optimal SUV cutoff value of 3.0 helped to differentiate high-grade from low-grade clear cell RCC, with 89% sensitivity and 87% specificity. On multiple regression analysis, a high grade was the most significant predictor of SUV for clear cell RCC.FDG uptake higher than that observed in normal kidney tissues suggests a high-grade clear cell RCC or papillary RCC subtype. FDG-PET using SUV may have a role in prediction of pathological grade of renal tumor.
Braf Mutation Analysis in Cell Free Tumoral Dna (Cfdna) of Melanoma Patients: Preliminary Results from the Spanish Melanoma Group Prospective Study Gem1304
Authors: M. Gonzalez-Cao, V. Soriano, D. Rodriguez, T. Puertolas, E. Muñoz, A. Soria, C. Mayo de Las Casas, M.A. Molina, E. Perez, M. Magem, A. Garcia, J.L. Manzano, J. Cortes, R. Rosell
Journal: Annals of Oncology (2014)
Human H5N1 infections: so many cases – why so little knowledge?
Authors: A Nicoll
Journal: Eurosurveillance (2006)

This month edition contains an account of clusters of H5N1 infection in humans in Azerbaijan [1]. The account is doubly rare: It describes the first occasion where the source is seemingly wild birds. Reading what happened is reassuring as the people infected had probably killed and defeathered infected swans. I.e. this was not casual exposure to wild birds but rather qualitatively similar to when humans are intimately exposed to sick domestic poultry, which remains the most potent risk factor (one recent analytic study came up with an odds ratio of 29 [2]).
Capsule Endoscopy in a Patient with Zenker’s Diverticulum
Authors: L. Aabakken, J. Blomhoff, T. Jermstad, A. Lynge
Journal: Endoscopy (2003)

Capsule endoscopy was recently introduced for endoluminal visualization of the small bowel [1]. The clinical utility of the procedure is undisputed [2] [3] [4], and for most patients, swallowing the capsule (11 × 33 mm in size) does not pose any problems.
EPN-16THE SIOP II EPENDYMOMA MULTI-DISCIPLINARY ADVISORY GROUP (EMAG): THE UK APPROACH
Authors: Lisa C.D. Storer, Timothy Ritzmann, Rebecca J. Chapman, Mitzi Hanson, Tim Jaspan, Robert Dineen, Shivaram Avula, Stavros Stivaros, Donald MacArthur, Conor Mallucci, Aabir Chakraborty, Kristian Aquilina, Ian Kamaly-Asl, John Goodden, Nicky Thorp, Gillian Whitfield, Simon Paine, Astrid Marie Sehested, John-Paul Kilday, Martin English, Richard G. Grundy
Journal: Neuro-Oncology (2016)
Value
Authors: Nancy L Greengold
Journal: JAMA (2002)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Leprosy
Authors: C H Tung, J I Sattler
Journal: New England Journal of Medicine (2001)

Figure 1 Two years after emigrating from Pakistan to the United States, a 28-year-old man began to have a progressive erythematous eruption, which appeared on his right medial thigh and gradually spread to his trunk and arms (Panel A), legs, and face. The lesions were not pruritic or hypoesthetic. He had paresthesias of both feet. On examination, he had decreased sensation in the third and fourth toes of his left foot. He was taking no medications. A skin biopsy demonstrated granulomatous inflammation with numerous histiocytes in the dermis in a neurovascular distribution. Fite's stain (oil-immersion lens, ×100) showed numerous mycobacteria in histiocytes as well as focal infection of cutaneous nerves (Panel B). Leprosy (Hansen's disease) of the borderline lepromatous type was diagnosed, and treatment with dapsone, rifampin, and clofazimine was initiated. Eight months later, the patient's neuropathic symptoms had resolved and his rash had faded substantially. Figure 1 Two years after emigrating from Pakistan to the United States, a 28-year-old man began to have a progressive erythematous eruption, which appeared on his right medial thigh and gradually spread to his trunk and arms (Panel A), legs, and face. The lesions were not pruritic or hypoesthetic. He had paresthesias of both feet. On examination, he had decreased sensation in the third and fourth toes of his left foot. He was taking no medications. A skin biopsy demonstrated granulomatous inflammation with numerous histiocytes in the dermis in a neurovascular distribution. Fite's stain (oil-immersion lens, ×100) showed numerous mycobacteria in histiocytes as well as focal infection of cutaneous nerves (Panel B). Leprosy (Hansen's disease) of the borderline lepromatous type was diagnosed, and treatment with dapsone, rifampin, and clofazimine was initiated. Eight months later, the patient's neuropathic symptoms had resolved and his rash had faded substantially. Candice H. Tung, M.D.Jon I. Sattler, M.D.Northwestern University Medical School, Chicago, IL 60611
The Prothrombin Gene 3′-Untranslated Region Mutation Is Frequently Associated With Factor V Leiden in Thrombophilic Patients and Shows Ethnic-Specific Variation in Allele Frequency
Authors: Tom E. Howard, Mira Marusa, Jody Boisza, Andrew Young, Judy Sequeira, Cindy Channell, Cindy Guy, Elizabeth Benson, Alexander Duncan
Journal: Blood (1998)
Old Age and Steatohepatitis: A Dangerous Liaison?
Authors: Mark J. Czaja
Journal: Hepatology (2012)

I thank Dr. Vinciguerra for his kind comments about the significance of our study. It is important to note that the old age group studied was fed a high-fat diet from the ages of 18 to 22 months and that this group was analyzed at 22 months.1 At the time of analysis the mice in the aged group therefore corresponded to a human age of 69 years.2 This is an appropriate experimental group for an examination of the effects of aging as the current human life expectancy in the United States is 78.7 years.3 While I cannot rule out a different effect in even older mice, there is no reason to think that this would occur. I disagree with the statement that there is no association between nonalcoholic fatty liver disease (NAFLD) and aging, as evidence exists for an increased prevalence of this disease in aged individuals, particularly for steatohepatitis, as discussed in our article.1 Our work was not designed to examine the effects of aging on the development of hepatocellular carcinoma (HCC), as the high-fat diet mouse model employed in our studies does not develop HCC. HCC is certainly prevalent in the elderly and the relationship of the incidence of this cancer to age is difficult to assess, as it varies with the patient population and underlying etiology of the HCC. In low-risk populations the highest incidence of HCC has been noted to be in individuals aged 75 or older.4 With more cases of HCC arising in patients with chronic hepatitis C virus (HCV) infection, the association of HCC with aging will likely increase. As the HCV-infected patient population has now aged, HCV-associated HCC from this etiology has been found to be 15-fold greater in those over 65 as compared to young individuals.5 As the burgeoning population with long-standing nonalcoholic steatohepatitis (NASH) ages, it is possible that a greater incidence of HCC will be detected in aged individuals with this disease as well. Certainly there are potential mechanisms for the preferential development of HCC in the elderly with NASH, such as the decrease in the tumor-suppressive pathway of autophagy that occurs from both steatosis and aging.6 The risk of complications of NAFLD such as HCC in the aged therefore remains an open question. Mark J. Czaja M.D. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
Book: Physician's Guide to Terrorist Attack
Authors: Paul Grant
Journal: BMJ (2004)

Paranoia is a wonderful stimulus for the imagination, and after reading this new guide you'll be surprised at the mind boggling ingenuity of 21st century terrorists. The very American interpretation of modern warfare suggests that there will be a move away from traditional theatres of war to more urban and civilian targets. This means that at any moment we can expect our local shopping centre to explode, the very water we drink to be contaminated while we receive anthrax through the post, and “rogue states” to drop dirty nuclear bombs on city centres. Mass transport systems are also highlighted, as attacks on these have the potential for widespread disruption and high numbers of casualties. The Supreme Truth sect's gassing of the Tokyo underground and the recent bombings of commuter trains in Madrid have, unfortunately, become textbook examples.​examples.




Figure 1



Ed Michael Roy

Humana Press, $89.55, pp 420 ISBN 1 59259 663 0

Rating: ★★★




This well written guide provides in-depth, practical advice for dealing with a whole range of potential terrorist scenarios and, interestingly, for dealing with the psychological aftermath. Using numerous examples, it gives comprehensive and up to date information on the proper diagnostic and treatment methods for dealing with terrorist attacks.

When Russian special forces stormed a Moscow theatre being held siege by Chechens last year they used a noxious opiate gas that caused rebels and hostages alike to collapse, vomit, and asphyxiate. The government hindered its own health services by refusing to identify the agent used, compromising many lives. In Japan, medical services were slow to respond after the sarin gas attacks, and this cost lives. In contrast, after the attacks on the World Trade Center and the Pentagon in 2001 the emergency services went into overdrive, efficiently putting major incident plans into action. Triaging of survivors—although initially difficult and chaotic—was streamlined, helping to reduce the mortality of such a large attack. This guide outlines the typical initial response to an attack and describes well the disorientating nature of the disorder that results, as well as the problems for hospitals needing to receive mass casualties or even responding to anxious patients fearful of exposure to a biological agent.

Medical experts with a military background (think Dustin Hoffman in Outbreak) review possible infectious diseases and chemical agents that could be used in terrorist attacks. The book also deals with important issues of an “efficiently lethal” nature: casualties from blasts, nuclear and radiological weapons, guns, and mines. The possibilities for carnage are limitless, but this book provides an action plan for doctors at the front line of a terrorist attack response team and everyone working in an emergency department. It's scary reading but a good defence.
The Effect of Arterial Occlusion on Epidermal Carcinogenesis in the Rabbit
Authors: A C RITCHIE
Journal: JNCI Journal of the National Cancer Institute (1952)

Journal Article The Effect of Arterial Occlusion on Epidermal Carcinogenesis in the Rabbit Get access A. C. Ritchie A. C. Ritchie Oxford University Research Centre of the British Empire Cancer Campaign, Sir William Dunn School of Pathology, Oxford, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 4, February 1952, Pages 847–850, https://doi.org/10.1093/jnci/12.4.847 Published: 01 February 1952 Article history Received: 11 October 1951 Published: 01 February 1952
MB-88QUANTITATIVE PROTEOMIC PROFILING IN MEDULLOBLASTOMA RECAPITULATES SUBGROUPING BASED ON TRANSCRIPTIONAL PROFILES
Authors: Petra Dvorakova, Michal Kyr, Marta Nekulova, Marta Jezova, Zdenek Pavelka, Ondrej Slaby, Jaroslav Sterba, Borivoj Vojtesek, Lenka Hernychova, Karel Zitterbart
Journal: Neuro-Oncology (2016)

There is an important need to identify clinically reliable
protein markers, which can be used for medulloblastoma
subgroups assignment. Using our established proteomics-based
target discovery program, we propose to identify and validate
protein-based markers that are main pro-oncogenic signaling
components in different molecular and clinical subgroups in
medulloblastoma.
Last Words
Authors: Robert E Johnstone
Journal: JAMA (2006)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 Consideration of Flow Diversion in Modern Cerebrovascular Neurosurgery
Authors: Babu G. Welch, H. Hunt Batjer
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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