tbuckley/cabot-search huggingface dataset:
Early detection of mammary tumors in vivo using a highly specific tumor antibody.
Authors: Didier Dréau, Laura Jeffords Moore, Lopamudra Das Roy, Shu-ta Wu, Rahul Puri, Pinku Mukherjee
Journal: Journal of Clinical Oncology (2015)

14 Background: Earlier detection of abnormal cells using target-specific techniques holds great promise. One of those targets Mucin-1 (MUC1) is expressed as a hypo-glycosylated form (i.e., tMUC1) in 95% of breast tumors and plays a crucial role in cancer progression. We have developed Tab004, a monoclonal antibody highly specific to a protein sequence accessible in tMUC1. Here we present data assessing the specificity and sensitivity of Tab004 in vitro and in genetically engineered mice in vivo overtime. Methods: We have developed human MUC1 Tg mice that were bred to mice that carry the oncogene, polyoma middle T antigen driven by the MMTV promoter. These mice designated MMT develop mammary gland tumors spontaneously and expresses the human form of tMUC1. PyVMT and C57Bl/6 served as controls. Mice develop mammary gland hyperplasia between 8-10 weeks of age that progresses to ductal carcinoma in situ by 12-14 weeks and adenocarcinoma by 18-24 weeks. Approximately 40% of the mice develop metastasis to the lung and other organs. The tumor progression appropriately mimics the human disease. MMT mice (n = 20) were injected twice monthly retro-orbitally with 12.5ug (100uL) of Tab004-conjugated to indocyanine green (ICG) and imaged thereafter from 8 to 22 weeks of age. Fluorescence was assessed 4 and 24 hrs post injection using the IVIS system. At euthanasia, tissue was collected for further analyses. Further, human breast tumor and normal mammary epithelial tissues were evaluated by immunohistochemical staining. Results: Tab004 specifically recognizes tMUC1 and not normal MUC1. In MMT mice, ICG-conjugated Tab004 allowed early detection of tumors in vivo sparing recognition of normal mammary epithelia in the C57BL/6 mice or in the PyV MT tumors. Detection with ICG-conjugated Tab004 allowed monitoring of tumor progression overtime. Importantly, ICG-conjugated Tab004 permitted significantly earlier detection than physical examination. Conclusions: The data highlight the specificity and the sensitivity of Tab004 in detecting tMUC1 in vitro, in situ and in relevant murine models in vivo. Thus, Tab004 will have significant clinical relevance for development as a targeted imaging agent and in the future for targeted drug delivery.
Reexamining the Threshold for Reexcision of Histologically Transected Dysplastic Nevi
Authors: Nathaniel H. Fleming, Barbara M. Egbert, Jinah Kim, Susan M. Swetter
Journal: JAMA Dermatology (2016)

Controversy persists regarding the appropriate management of incompletely excised, biopsy-proven, mild and moderate dysplastic nevi (DN).To determine long-term risk of associated melanoma in biopsied mild or moderate DN with positive histologic margins that were clinically observed vs reexcised with negative margins.Retrospective cohort study of mixed referral and community patients from an academic pigmented lesion clinic and dermatology clinics of the affiliated Veteran Affairs medical center with biopsy-confirmed DN with positive histologic margins diagnosed from May 15, 1991, to July 8, 2015, and followed up through May 30, 2016. A consecutive sample of 1473 histologically confirmed DN was identified using surgical pathology databases at the study sites; 590 cases in 498 patients met eligibility criteria.The primary outcome was the proportion of biopsied DN that progressed to histologically confirmed invasive or in situ melanoma. Secondary outcomes included local nevus recurrence and development of primary melanoma at other anatomic sites.The 498 patients had a mean (range) age of 57.6 (14-93) years and 90% were male. Among 590 positive-margin DN, 191 were reexcised and 399 clinically observed without further surgery; 170 reexcised and 304 observed DN had available follow-up data, with mean (SD) follow-up of 5.5 (4.6) years. Cases in the observation group were more likely to demonstrate nevus recurrence than those that were reexcised (3.3% vs 0%; P = .02). Six of 304 (2.0%) observed DN subsequently developed melanoma at the same site, compared with 1 of 170 (0.06%) that were reexcised (P = .43). Five of 6 observed patients who developed melanoma initially underwent partial biopsy with grossly positive margins; 1 melanoma in situ evolved from an excisionally biopsied moderately dysplastic nevus 5 years later. Only 1 case of thin invasive melanoma (≤1 mm) was observed, and no deaths from melanoma arising from biopsy-proven DN occurred through the latest dermatology follow-up. New primary melanoma developed at other sites in 9.9% of excised and 9.4% of resected DN.In cases of mild and moderate DN with microscopically positive margins and no concerning clinical residual lesion, observation, rather than reexcision, was a reasonable management option. Partial biopsies of pigmented lesions suspicious for melanoma may lead to delayed melanoma diagnosis and should be discouraged.
BTS recommendations to respiratory physicians for organising the care of patients with lung cancer
Journal: Thorax (1998)

These guidelines have been replaced by 2010 Guideline On Radical Management Of Patients With Lung Cancer and NICE Lung Cancer Guideline CG121 2011 Superseded By 2010 Guideline On Radical Management Of Patients With Lung Cancer And NICE Lung Cancer Guideline CG121 2011: BTS recommendations to respiratory physicians for organising the care of patients with lung cancer. Thorax 1998 Jun;53(Suppl 1): 1-8.
Folate-conjugated gene-carrying microbubbles with focused ultrasound for concurrent blood-brain barrier opening and local gene delivery
Authors: Ching-Hsiang Fan, En-Ling Chang, Chien-Yu Ting, Yu-Chun Lin, En-Chi Liao, Chiung-Yin Huang, Yuan-Chih Chang, Hong-Lin Chan, Kuo-Chen Wei, Chih-Kuang Yeh
Journal: Biomaterials (2016)
Temozolomide chemotherapy versus radiotherapy in molecularly characterized (1p loss) low-grade glioma: A randomized phase III intergroup study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033).
Authors: Brigitta G Baumert, Warren P. Mason, Gail Ryan, Jacoline E Bromberg, Martin J. Van Den Bent, Khê Hoang-Xuan, Alba Ariela Brandes, Guy Kantor, Martin JB Taphoorn, Mohamed Ben Hassel, Jeremy Rees, Wolfgang Wick, Andreas Von Deimling, Christian Hartmann, Johan M Kros, Monika E. Hegi, Nicolas Dif, Denis A. Lacombe, Thierry Gorlia, Roger Stupp
Journal: Journal of Clinical Oncology (2013)

2007 Background: Outcome of low-grade glioma (LGG) is highly variable. We investigated whether primary chemotherapy in comparison to standard radiotherapy (RT) prolongs progression-free (PFS) and overall survival (OS), and whether prognostic molecular factors could be defined. Methods: Progressive, symptomatic or high-risk patients with a LGG requiring treatment other than surgery were randomized (after stratification for 1p-status) to either conformal RT (50.4 Gy/28 fractions) or dose-dense temozolomide [TMZ] (75 mg/m² daily x 21 days, q28 days, max. 12 cycles). Primary endpoint was PFS, secondary analyses included OS and impact of 1p status. Results: 477 patients were randomized (2005-2012, median FU 45.5 months). Analysis was performed after 246 progression events. Hematological toxicity ≥ grade 3 was observed in 9.4% of TMZ patients. PFS was not significantly different, median OS not reached. 1p deletion was a positive prognostic factor irrespective of treatment (p-value stratified by treatment (PFS: 0.0003;HR=0.59 95% CI(0.45-0.78)/OS: 0.002;HR=0.49 95% CI (0.32-0.77)). Conclusions: First-line treatment with TMZ compared to RT did not improve PFS in high-risk LGG patients. Although interaction test was not significant, there was a trend for inferior PFS in patients treated by TMZ with 1p intact, while OS may be better when 1p-deleted patients receive TMZ upfront. Survival analysis requires further maturation of the data. Clinical trial information: EudraCT number 2004-002714-11. [Table: see text]
Assessment Of Endothelial Damage and Cardiac Injury In a Mouse Model Mimicking Thrombotic Thrombocytopenic Purpura
Authors: Maelle Le Besnerais, Julie Favre, Cecile V. Denis, Bernard Lenormand, Paul Mulder, Lionel Nicol, Agnes Veyradier, Alexandra Schiviz, David G Motto, Herve Levesque, Paul Coppo, Vincent Richard, Ygal Benhamou
Journal: Blood (2013)
Accuracy of a modeling algorithm to optimize perfusion MRI detection of glioma recurrence.
Authors: L. S. Hu, L. C. Baxter, D. S. Pinnaduwage, T. Jensen, A. C. Dueck, J. M. Eschbacher, J. E. Heiserman, J. P. Karis, J. Debbins, K. M. Schmainda
Journal: Journal of Clinical Oncology (2010)

2081 Background: This study establishes Perfusion MRI (pMRI) correlation with tissue microvasculature and accuracy to predict histopathologic diagnosis of tumor recurrence or post-treatment radiation effect (PTRE), in recurrent high-grade glioma (HGG). Methods: We recruited previously treated (including chemo-radiation therapy) HGG patients undergoing surgical re-resection of new enhancing lesions on surveillance MRI. Preoperatively, we acquired pMRI and contrast-enhanced stereotactic T1-weighted (T1W) MRI data sets. Intraoperatively, we recorded stereotactic locations of multiple biopsies based on T1W data sets that guided surgery. We coregistered pMRI and T1W data sets to calculate localized relative cerebral blood volume (rCBV) (IB Neuro, Imaging Biometrics, LLC) for each specimen location. For each specimen, we performed 1) H&E staining to diagnose tumor or PTRE; and 2) CD-34 staining to highlight tissue vessels and calculate total microvessel area (MVA), normalized to total slide specimen area (μ m2) (Axiovision Automeasure 3.4, Carl Zeiss). We calculated Pearson correlations for rCBV and MVA and created a Receive Operator Characteristic (ROC) curve to determine rCBV accuracy to distinguish tumor from PTRE. A neuroradiologist performed all coregistration and pMRI calculations, and a neuropathologist reviewed all tissue specimens, without knowledge of corresponding data. Results: From 10 subjects, we collected 31 tissue specimens, each diagnosed as tumor (n = 18) or PTRE (n = 13). The rCBV values showed high correlation with total vessel area (MVA) (r = 0.61, p = 0.0003) and predicted histopathologic diagnosis with high accuracy (AUC = 0.92). Conclusions: These preliminary results show the promise of perfusion MRI to non-invasively estimate tissue microvessel density and distinguish tumor recurrence from treatment effects. The current study is ongoing to confirm results in a larger patient population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Imaging Biometrics, LLC Imaging Biometrics, LLC Imaging Biometrics, LLC Arizona Biomedical Research Commission, Barrow Neurological Foundation
Thioguanine Compared with Mercaptopurine in Childhood Lymphoblastic Leukaemia: Results of the United Kingdom Medical Research Council Randomised Trial ALL97.
Authors: Lynne Lennard, S. M. Richards, C. D. Mitchell, C. Cartwright, T. O. Eden, S. E. Kinsey, J. S. Lilleyman, Ajay J. Vora
Journal: Blood (2005)
Viral reactivation and clinical hepatitis in patients with hepatitis C who receive rituximab as part of chemotherapy for treatment of lymphoma: A case series.
Authors: S. F. Boyle, E. G. Reid
Journal: Journal of Clinical Oncology (2010)

e18559 Background: Rituximab has been implicated in the reactivation of quiescent viruses, although its impact on Hepatitis C (HCV) remains poorly understood. We report outcomes from a case series of 9 HCV+ patients who received rituximab-based chemotherapy. Methods: We obtained IRB approval to perform a retrospective chart review on HCV+ patients who received rituximab-based chemotherapy for lymphoma from 2001-08. Clinical hepatitis (CH) was defined as either an AST or ALT 2x ULN. Viral reactivation (VR) was defined at a viral load (VL) increase of 10x the pretreatment value. Results: Eight of 9 patients developed a CH within 12 months of exposure to r- chemo, average months to CH was 3.86. Five of 7 patients developed CH before VR, 2 of 7 patients develop CH after VR. Of the 5 patients whose CH occured before their VR, only 1 has a VL that increases at time of CH. Two of 5 patients do not have viral loads reported around the time of CH. Two of 5 do not have increasing VL at time of CH. Four of 6 VR occurred within 12 months, on average 7.25 months post exposure. Six of 8 patients with >2 VL had a VR. Of those 6, 4 had a VR within 12 months of being exposed to r-chemo. Average AST at VR was 89.6, average ALT at VR was 72.5 Two of the 3 HIV+ patients developed VR within 12 months of receiving r-chemo. The average time to VR was similar in the HIV+ (7.5 months) vs. in the HIV- (7 months) patients. One patient's chemo regimen was changed due to HCV reactivation. None of the patients received dose reduction in other chemo agents for hepatitic insufficiency and none developed hepatitic failure. Conclusions: In this study we noted a trend toward increasing LFTs and VLs in HCV+ patients who received rituximab-based chemotherapy. Patients were more likely to have a CH after exposure to rituximab, but were not more likely to have a CH following VR. This pattern makes it difficult to say whether CH was a marker of liver toxicity due to VR vs. ongoing chemo or other co-morbidities. Despite impaired cellular immunity, the 3 HIV+ patients had the same rate of VR as the HIV- patients. Our study illustrates the possible relationship between rituximab exposure and increasing VL, but no clear relationship could be determined between VR and CH. No significant financial relationships to disclose.
Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis
Authors: Salvatore Vaccarella, Silvia Franceschi, Freddie Bray, Christopher P. Wild, Martyn Plummer, Luigino Dal Maso
Journal: New England Journal of Medicine (2016)

Dramatic increases have been seen over recent decades in the reported incidence of thyroid cancer, but owing to new modes of screening, hundreds of thousands of cases may be overdiagnoses — diagnosis of tumors that would not, if left alone, result in symptoms or death.
Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure
Authors: Federica Barbagallo, Bing Xu, Gopireddy R. Reddy, Toni West, Qingtong Wang, Qin Fu, Minghui Li, Qian Shi, Kenneth S. Ginsburg, William Ferrier, Andrea M. Isidori, Fabio Naro, Hemal H. Patel, Julie Bossuyt, Donald Bers, Yang K. Xiang
Journal: Circulation Research (2016)

In heart failure, myofilament proteins display abnormal phosphorylation, which contributes to contractile dysfunction. The mechanisms underlying the dysregulation of protein phosphorylation on myofilaments is not clear.This study aims to understand the mechanisms underlying altered phosphorylation of myofilament proteins in heart failure.We generate a novel genetically encoded protein kinase A (PKA) biosensor anchored onto the myofilaments in rabbit cardiac myocytes to examine PKA activity at the myofilaments in responses to adrenergic stimulation. We show that PKA activity is shifted from the sarcolemma to the myofilaments in hypertrophic failing rabbit myocytes. In particular, the increased PKA activity on the myofilaments is because of an enhanced β2 adrenergic receptor signal selectively directed to the myofilaments together with a reduced phosphodiesterase activity associated with the myofibrils. Mechanistically, the enhanced PKA activity on the myofilaments is associated with downregulation of caveolin-3 in the hypertrophic failing rabbit myocytes. Reintroduction of caveolin-3 in the failing myocytes is able to normalize the distribution of β2 adrenergic receptor signal by preventing PKA signal access to the myofilaments and to restore contractile response to adrenergic stimulation.In hypertrophic rabbit myocytes, selectively enhanced β2 adrenergic receptor signaling toward the myofilaments contributes to elevated PKA activity and PKA phosphorylation of myofilament proteins. Reintroduction of caveolin-3 is able to confine β2 adrenergic receptor signaling and restore myocyte contractility in response to β adrenergic stimulation.
Gender disparities in chemotherapy use and survival in patients with metastatic bladder cancer (BCa).
Authors: Tracy Lynn Rose, Allison Mary Deal, Hojin Yang, Matthew Edward Nielsen, Angela Smith, Matthew I. Milowsky
Journal: Journal of Clinical Oncology (2015)

e15508 Background: Women with metastatic BCa have inferior survival compared to men. However, women with metastatic BCa treated on clinical trials do not have a survival disadvantage. It is not known if less frequent administration of systemic chemotherapy in women with metastatic BCa has a role in the inferior survival compared with men. Methods: We identified patients with metastatic BCa from 2003-2010 using the National Cancer Data Base (NCDB), a national outcomes database that includes 70% of all newly diagnosed cancer cases in the United States. Gender differences in demographics, systemic chemotherapy administration,and overall survival (OS) were compared using t-tests, chi square, multivariable logistic regression, and Cox proportional hazards regression treating chemotherapy receipt as time-varying. Results: 9802 patients were identified. 34% were female, 87% were white (median age 70). Compared with men, women were older, more likely to be Black, and less likely to be insured on univariate analysis (p < 0.01 for all). Charlson Deyo comorbidity score did not differ between men and women. Women were less likely to receive systemic chemotherapy than men (45% vs 53%, p < 0.01). Women had a lower median OS compared to men (5.6 vs 7.0 months, p < 0.001). After adjusting for age, race, insurance status, comorbidity score and presence of distant metastases, women remained less likely to receive systemic chemotherapy (OR 0.76, p < 0.001). OS remained lower for women on multivariable analysis (HR 1.14, p < 0.001), even after adjusting for administration of systemic chemotherapy (HR 1.13, p < 0.01). Conclusions: Women are less likely than men to receive systemic chemotherapy for metastatic BCa and this difference may partially account for poorer OS in women. OS remains lower in women, however, independent of chemotherapy use. This may be related to unmeasured comorbidities, functional status, or tumor biology.
Record demand on NHS is pushing services above safe thresholds, report warns
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Record levels of demand on the NHS in England are straining the service as growing numbers of people attend emergency departments, wait for elective procedures, and have their hospital discharge delayed, a new report warns.

The latest quarterly monitoring report from the health think tank the King’s Fund,1 published on 8 September, says that “relentless” demand for services is driving up waiting times and intensifying financial pressures on the NHS. The report considers the views of NHS trust finance directors and clinical commissioning group …
Health Outcomes in Long-term Survivors of Childhood Cancer—Reply
Authors: Leontien C. M. Kremer, Mathilde C. Cardous-Ubbink, Maud M. Geenen, Flora E. van Leeuwen, Huib N. Caron
Journal: JAMA (2007)

In Reply: Drs Kakaki and Theleritis describe the effect of psychological trauma in children exposed to chronic illness, especially life-threatening illness. They state that for these children certain preventive measures should be implemented.
Management of Intractable Nausea and Vomiting in Patients at the End of Life
Authors: Amy J. Markowitz, Michael W. Rabow
Journal: JAMA (2008)

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
P1174 : Microbiota-dependent marker trimethylamine-N-oxide (TMAO) is associated with the severity of primary sclerosing cholangitis
Authors: M. Kummen, M. Vesterhus, M. Trøseid, B. Moum, A. Svardal, K.M. Boberg, P. Aukrust, T.H. Karlsen, R.K. Berge, J.R. Hov
Journal: Journal of Hepatology (2015)
Dose-dense nab-paclitaxel (nanoparticle albumin-bound paclitaxel) in adjuvant chemotherapy for breast cancer: A feasibility study
Authors: H. J. Burstein, E. L. Mayer, J. Peppercorn, L. M. Parker, K. Hannagan, B. Moy, J. Younger, L. Schapira, G. Wulf, R. Gelman, E. P. Winer
Journal: Journal of Clinical Oncology (2007)

594 Background: We sought to evaluate the feasibility of substituting nab-paclitaxel (ABI-007) for paclitaxel as part of “dose-dense” adjuvant sequential doxorubicin / cyclophosphamide (AC) followed by taxane chemotherapy. Patients and Methods: Eligible patients had stage I-III breast cancer receiving adjuvant/neoadjuvant chemotherapy, ANC &gt; 1500, and LVEF &gt; 50%. Patients received AC (60 mg/m 2 and 600 mg/m 2 ) every 2 weeks × 4 cycles with G-CSF support, followed by nab- paclitaxel 260 mg/m 2 every 2 weeks × 4 cycles. The endpoint was incidence of treatment delay during nab-paclitaxel therapy. Results: 66 women (median age 48 years) were enrolled. Among the first 11 given nab-paclitaxel without G-CSF support, one developed febrile neutropenia, and 4 had nab-paclitaxel treatment delays related to neutropenia (ANC &lt; 1,000). The protocol was amended to require G-CSF support (filgrastim or pegfilgrastim) during nab-paclitaxel. Among the next 55 patients, 3 had febrile neutropenia, none during nab- paclitaxel. In cycles 6–8, nab-paclitaxel was delayed only 6 times (1 neutropenia, 3 hepatic toxicity, 2 patient scheduling); 96% of these cycles were delivered on time. By comparison, 82% of such cycles were delivered on time in a prior institutional study using paclitaxel. In the full cohort, 8 patients had nab-paclitaxel dose reduction, 4 for neuropathy, while other neuropathy was moderate (grade 2, n = 6; grade 3, n=1; grade 4, n=0). Conclusions: Administration of nab-paclitaxel every 2 weeks is feasible but requires G-CSF support. Data comparing nab-paclitaxel dose-delivery, toxicities and quality of life to paclitaxel as seen in prior studies will be presented. No significant financial relationships to disclose.