tbuckley/cabot-search huggingface dataset:
Radioimmunoassay of Myelin Basic Protein in Spinal Fluid
Authors: Steven R. Cohen, Robert M. Herndon, Guy M. McKhann
Journal: New England Journal of Medicine (1976)

With a sensitive radioimmunoassay that can measure as little as 2 ng of basic protein in cerebrospinal fluid we studied 303 patients with a variety of neurologic diseases. Patients with active demyelinating diseases had high levels (17 to 100 ng per milliliter) of basic protein. Moreover, patients with multiple sclerosis in acute exacerbation had these high levels, those with slowly progressive multiple sclerosis had lower levels (6 to 16 ng per milliliter), and those in remission had less than 4 ng per milliliter, comparable to the control population. Thus, the assay appears to be a useful index of active demyelination. (N Engl J Med 295:1455–1457, 1976)
P4-08-04: Preoperative Thrombin Pathway Activation Identifies Node Positive Patients in Early Breast Cancer.
Authors: H Shaker, C Kirwan, G Landberg, NJ Bundred
Journal: Cancer Research (2011)

Abstract Activation of the thrombin pathway (TP) is seen in 50% of cancers and plays a significant role in promoting metastasis. Cancer-induced TP activation is exacerbated by surgery, and this activation may be greater in the presence of metastases. Our aim was to determine if pre-operative plasma d-dimer, a marker of TP activation, correlated with the presence of LN metastases in early breast cancer. We also examined whether surgery-induced TP activation is affected by tumour-associated factors. Methods Plasma d-dimer was measured using automated ELISA pre-operatively and at days 1 and 42 following surgery in 103 prospectively recruited patients undergoing surgery for early breast cancer(87 invasive,13 DCIS). D-dimer values were log-transformed and correlated with LN metastases, tumour size and grade and hormone receptor status using parametric statistical tests. Results Median age was 68 years (range 46–82). Mean tumour size was 14.6 mm (range 7.5-40). Seventy invasive cancer patients had wide local excision(WLE) and sentinel node biopsy(SNB) and 17 had mastectomy(MX) +/− axillary clearance(ANC). Twenty-two patients had positive lymph nodes at primary surgery (MX 8,WLE 14). Of these 3(14%) were ER-ve and 19(86%) were ER+ve. Mean pre-operative d-dimer was higher (p&amp;lt;0.01) in LN positive (704ng/ml, 95% confidence interval, CI, 455–1088) versus LN node negative invasive cancers (443ng/ml, CI 304–627) or DCIS (366ng/ml, CI 284–471). D-dimer was also higher in patients with lymphovascular invasion (612ng/ml, CI 423–886) than in those without (454ng/ml, CI 385–534) and this approached significance (p=0.084). Post-operative d-dimer was higher (p&amp;lt;0.05) after MX compared to WLE at all timepoints. Following WLE + SNB for invasive cancer, post-operative d-dimer rose and was higher at day 1 and day 42 in LN positive vs LN negative and in ER negative versus ER positive cancers (see table). Repeated measures ANOVA analysis showed that the change in d-dimer over time was significantly different between subjects according to LN status (p=0.037) or ER status (p=0.015). Only one patient in the ER negative group had LN metastases. There was no association between pre or postoperative d-dimer and tumour size, tumour grade or PR status. Conclusion Pre-operative TP activation and the thrombotic response to surgery (as measured by d-dimer) is greater in the presence of LN metastases regardless of tumour size. ER negative cancers (7/8 of which were LN negative) also resulted in a greater d-dimer rise, suggesting a difference in the thrombotic response to surgery between different cancer phenotypes. Ongoing work will determine if peri-operative TP activation can act as an independent predictor of node status and cancer recurrence. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-04.
Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
Authors: Haiming Luo, Christopher G. England, Sixiang Shi, Stephen A. Graves, Reinier Hernandez, Bai Liu, Charles P. Theuer, Hing C. Wong, Robert J. Nickles, Weibo Cai
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Pancreatic adenocarcinoma is a highly aggressive cancer, currently treated with limited success and dismal outcomes. New diagnostic and treatment strategies offer the potential to reduce cancer mortality. Developing highly specific noninvasive imaging probes for pancreatic cancer is essential to improving diagnostic accuracy and monitoring therapeutic intervention. Experimental Design: A bispecific heterodimer was synthesized by conjugating an anti-tissue factor (TF) Fab with an anti-CD105 Fab, via the bio-orthogonal “click” reaction between tetrazine (Tz) and trans-cyclooctene (TCO). The heterodimer was labeled with 64Cu for PET imaging of nude mice bearing BXPC-3 xenograft and orthotopic pancreatic tumors. Results: PET imaging of BXPC-3 (TF/CD105+/+) xenograft tumors with 64Cu-labeled heterodimer displayed significantly enhanced tumor uptake (28.8 ± 3.2 %ID/g; n = 4; SD) at 30 hours postinjection, as compared with each of their monospecific Fab tracers (12.5 ± 1.4 and 7.1 ± 2.6 %ID/g; n = 3; SD). In addition, the activity–concentration ratio allowed for effective tumor visualization (tumor/muscle ratio 75.2 ± 9.4 at 30 hours postinjection.; n = 4; SD). Furthermore, 64Cu-NOTA-heterodimer enabled sensitive detection of orthotopic pancreatic tumor lesions with an uptake of 17.1 ± 4.9 %ID/g at 30 hours postinjection and tumor/muscle ratio of 72.3 ± 46.7. Conclusions: This study demonstrates that dual targeting of TF and CD105 provided synergistic improvements in binding affinity and tumor localization of the heterodimer. Dual-targeted imaging agents of pancreatic and other cancers may assist in diagnosing pancreatic malignancies as well as reliable monitoring of therapeutic response. Clin Cancer Res; 22(15); 3821–30. ©2016 AACR.
TR-09 * THE EFFECT OF REGADENOSON-INDUCED TRANSIENT DISRUPTION OF THE BLOOD BRAIN BARRIER ON TEMOZOLOMIDE DELIVERY TO RAT BRAIN PARENCHYMA
Authors: S. Jackson, N. Anders, A. Mangraviti, H. Brem, B. Tyler, M. Rudek, S. Grossman
Journal: Neuro-Oncology (2015)

PURPOSE: The blood-brain barrier (BBB) poses a serious challenge to effective delivery of systemically administered agents to the central nervous system. Temozolomide is the only systemically delivered chemotherapeutic agent to significantly improve survival in patients with glioblastoma. Brain temozolomide concentrations are only 20% of that in blood. Regadenoson is an FDA approved adenosine receptor agonist that transiently disrupts rodent's BBB allowing dextran (70 kD) brain entry. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brains. METHODS: Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing female F344 rats. Sixty to 90 minutes later two-thirds of the animals received a single dose of intravenous regadenoson. The animals were sacrificed 120 or 360 minutes after temozolomide administration. Brain and plasma temozolomide concentrations were determined using HPLC/MS/MS. RESULTS: At 120 minutes, brain temozolomide concentrations were significantly higher when given with regadenoson vs. alone (8.1 ± 2.7 µg/g and 5.1 ± 3.5 µg/g, P < 0.05), with a similar trend in brain:plasma ratios (0.45 ± 0.08 and 0.29 ± 0.09, P < 0.05). 360 minutes after temozolomide administration brain and brain:plasma were increased without statistical significance. There was no difference in plasma temozolomide concentration with or without regadenoson. CONCLUSION: These results suggest co-administration of regadenoson with temozolomide results in 60% higher temozolomide levels in normal brain without changing plasma temozolomide concentrations. This novel approach to increasing intracranial concentrations of systemically administered agents can potentially improve the efficacy of therapeutic agents used in patients with brain tumors and other neurologic disorders.
Abstract B24: Thoc1 is required for mouse prostate tumorigenesis initiated by loss of Rb and p53
Authors: Meenalakshmi Chinnam, Yanqing Wang, Xiaoling Wang, Xiaojing Zhang, David L. Gold, Alexander Yu Nikitin, David W. Goodrich
Journal: Cancer Research (2009)

Abstract A large percentage of prostate cancers show either mutational inactivation or deregulation of the Rb tumor suppressor gene. Rb mediates its tumor suppressor function through its association with other cellular proteins. Most of the Rb-binding proteins interact with the A/B pocket domain and the C terminal region. Less than 10 proteins are known to interact with Rb N terminal domain, a domain that appears to be required for normal Rb function in vivo. The Thoc1 gene encodes a protein that binds the Rb N terminal domain. We hypothesize that some of pRb functions in vivo could be mediated in part by interaction with pThoc1. Thoc1 protein has been found to be an essential component of the TREX (transcription/export) complex which is important for mRNP biogenesis and physically couples transcription elongation with RNA processing and export. We have previously reported that E1A/Ras transformed MEFs (mouse embryonic fibroblasts) but not normal MEFs were dependent on Thoc1 for their survival. These observations suggest that tumor cells specifically may be dependent on Thoc1 for survival and Thoc1 may play a role in tumorigenesis. To test our hypothesis, we used a mouse model of prostate cancer where prostatespecific deletion of Rb and p53 genes leads to development of metastatic adenocarcinoma. We find that compound loss of Thoc1, Rb and p53 increased the life-span of mice compared to mice with loss of Rb and p53 alone. Histopathological analyses of prostate tissue showed that initiation of tumorigenesis is delayed in the absence of Thoc1. Tumors that do arise in these mice retain expression of Thoc1. These findings indicate that Thoc1 is required for prostate tumorigenesis. Conditional deletion of Thoc1 alone in mouse prostate does not appear to affect normal prostate development. To test whether Thoc1 is relevant to human prostate cancer, we examined expression of Thoc1 protein in matched normal and prostate tumor tissue cores on tissue microarray. Analysis of nearly 600 patient samples reveals that Thoc1 is significantly overexpressed in tumor tissue compared to normal prostate tissue and pThoc1 levels positively correlated with tumor grade and negatively correlated with biochemical recurrence as indicated by elevated PSA (prostate-specific antigen) levels. Taken together the above findings suggest that Thoc1 is synthetic lethal with the genetic and epigenetic alterations in prostate tumor cells, and hence it may be a potential target for prostate cancer therapy. Citation Information: Cancer Res 2009;69(23 Suppl):B24.
A Comparison of Management Patterns after Acute Myocardial Infarction in Canada and the United States
Authors: Jean L. Rouleau, Lemuel A. Moye, Marc A. Pfeffer, J. Malcolm O. Arnold, Victoria Bernstein, Thomas E. Cuddy, Gilles R. Dagenais, Edward M. Geltman, Steven Goldman, David Gordon, Peggy Hamm, Marc Klein, Gervasio A. Lamas, John McCans, Patricia McEwan, Francis J. Menapace, John O. Parker, Francois Sestier, Bruce Sussex, Eugene Braunwald
Journal: New England Journal of Medicine (1993)

There are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care.
120 SEVERE VITAMIN D DEFICIENCY IS ASSOCIATED WITH COMPLICATIONS OF PORTAL HYPERTENSION AND A WORSE PROGNOSIS IN ALCOHOLIC CIRRHOSIS
Authors: E. Trépo, R. Ouziel, P. Pradat, Y. Momozawa, E. Quertinmont, C. Gervy, T. Gustot, D. Degré, V. Vercruysse, P. Deltenre, L. Verset, B. Gulbis, D. Franchimont, J. Devière, A. Lemmers, C. Moreno
Journal: Journal of Hepatology (2013)
Urinary Leak After Intravenous Urography
Authors: KOTTEKKATTU BALAN, BOB BARBER
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom Received for publication September 6, 2000. Revision accepted December 1, 2000. Reprint requests: Dr. K. K. Balan, Department of Nuclear Medicine, Box 170, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom. E-mail: [email protected]
PROPHYLACTIC ELECTROSHOCK
Authors: G. H. STEVENSON, J. J. GEOGHEGAN
Journal: American Journal of Psychiatry (1951)

1. Recurring manic-depressive illnesses can frequently be prevented by the technique of prophylactic electroshock. 2. Persons whose manic-depressive illnesses are very prolonged or frequently recurrent, and who do not respond adequately to electroshock, may respond to prefrontal lobotomy. 3. Persons whose attacks are very infrequent may have such attacks aborted by the intensive application of electroshock at the first appearance of prodromal symptoms. 4. Failures of prophylactic electroshock are more likely to occur when the patient is faced with insoluble frustrating environmental factors. Hence the need for adequate social psychotherapy. 5. Because of the dislike many patients have for electroshock every effort should be put forth to make the prophylactic electroshock as free as possible from unpleasant features. 6. Good aftercare is essential. 7. Prophylactic electroshock is of limited value in recurring schizophrenic illnesses.
Regulation of T cell hyperactivity in SLE: the negative co-stimulatory molecule PD-1 regulates miR-21 expression in SLE T lymphocytes
Authors: E Stagakis, G Bertsias, P Verginis, M Nakou, Maria Hatziapostolou, P Sidiropoulos, G Goulielmos, D Iliopoulos, D T Boumpas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Polymorphisms to PD-1, a negative regulator of T cell function involved in peripheral tolerance, increase the susceptibility to SLE. The authors sought to define the mechanisms involved by exploring its effects on miR-21 expression known to promote T cell hyperactivity in lupus. <h3>Materials and methods</h3> PD-1 expression levels were quantified by real time PCR in purified CD4<sup>+</sup> T cells. Ambion miRVana Kit and primers were used for the detection of miR-21. T cells were stimulated with plate-bound anti-CD3/anti-CD28 mAb and PDL1.Ig was used for PD-1 crosslinking. Silencing of PD-1 was performed with a specific siRNA. <h3>Results</h3> Under basal conditions, freshly isolated T cells from active lupus patients had 2.3-fold higher miR-21 levels compared to healthy T cells. Combined anti-CD3/anti-CD28-stimulation induced higher miR-21 levels in SLE T cells than in controls (mean 4.0-fold vs 1.6-fold, respectively), suggesting aberrant regulation of miR-21 expression in SLE. PD-1 mRNA and miR21 levels correlated with disease activity. There was an inverse correlation between PD-1 mRNA and miR-21 levels in SLE patients (r2=−0.93) suggesting a co-regulation. This was documented by stimulating SLE T cells with anti-CD3/anti-CD28 in the presence or not of PDL1.Ig. PD-1 cross-linking reduced miR-21 levels by 45%. Moreover, silencing of PD-1, using a specific siRNA, was associated with 4.5-fold up-regulation of miR-21. Experiments are underway to elucidate the mechanisms of transcriptional regulation of miR-21 by mediators downstream to PD-1 and to correlate PD-1 genotypes with mir-21 expression. <h3>Conclusions</h3> PD-1 may exert its anti-proliferative effects through suppression of miR-21 and breakdown of this pathway in lupus can disturb the balance between immune activation and tolerance. Our data suggest that both genetic and epigenetic factors regulate T cell hyperactivity in SLE.
Miliary Tuberculosis Involving the Central Nervous System
Authors: K Murphy, J A Brunberg
Journal: New England Journal of Medicine (1996)

Figure 1. A 28-year-old woman with a 10-year history of systemic lupus erythematosus presented with fever, back pain, and bilateral paresthesias and weakness of the legs of 10 days' duration. She had been taking prednisone for the preceding nine months for the management of flares. On examination her neck was supple. She had decreased power and sensation in her legs, with diminished knee and ankle reflexes, an extensor right-plantar response, and an equivocal left-plantar response. T1-weighted magnetic resonance imaging after the administration of contrast medium revealed an enhancing lesion within the spinal cord at the T11 level (Panel . . .
Abstract 504: First in vitro radiobiological characterizations of cells from chordoma origin
Authors: Takamitsu Kato, Akihisa Tsuda, Akira Fujimori, Tadashi Kamada, Hirohiko Tsujii, Ryuichi Okayasu
Journal: Cancer Research (2010)

Abstract Although chordoma, a rare bone cancer, has been treated with surgery and/or radiation including heavy ions, few in vitro characterizations of chordoma cells are available. The main reason for this is the extremely long doubling time associated with the only recognized cell line, U-CH1. Here, we derived a cell line (designated as U-CH1-N) from U-CH1 and made the in vitro characterization possible, and results with U-CH1-N were compared with those with HeLa (cervical cancer) and U87-MG (glioblastoma) cells. The cell doubling times for HeLa, U87-MG and U-CH1-N were 18 h, 24 h and 3 days respectively. U-CH1-N had the most DNA content among the three, was near tetraploid, and showed an abnormal karyotype. U-CH1-N and U87-MG were more sensitive to x-irradiation than HeLa cells. Heavy ion irradiation more efficiently killed all three cell lines than x-rays did. Relative biological effectiveness (RBE) at 10% survival for U87-MG and HeLa cells was about 2.5 for 70keV/μm carbon ions and 3 for 200keV/μm iron ions, while for U-CH1-N it was 2.5 for carbon and 4 for iron ions. Four different chemical agents producing various DNA lesions were used for further characterization of these cells. Although camptothecin, mitomycin C or cisplatin did not reveal strong cytotoxity to U-CH1-N compared with other cells, bleomycin, which produces DNA strand breaks, showed marked cytotoxic effect on U-CH1-N. Our data provide the first chronological cell survival information using cells of chordoma origin and also help explain the successful chordoma treatment by heavy ions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 504.
Feasibility study on radiofrequency ablation followed by partial mastectomy for stage I breast cancer patients.
Authors: S Imoto, N Wada, N Sakemura, T Hasebe
Journal: Cancer Research (2009)

Abstract Abstract #4150 Backgrounds: Breast-conserving surgery (BCS) is a standard care for early breast cancer patients. However, local control is not sufficient for surgery alone and breast irradiation and hormonal treatment in hormone-sensitive tumor are recommended to reduce 10% or less of local failure rate. To evaluate the safety and reliability of thermal ablation therapy instead of BCS, we performed radiofrequency ablation (RFA) for clinical stage I breast cancer patients.&amp;#x2028; Patients and methods: The subject was T1N0 breast cancer patient with no extensive intraductal components. Under general anesthesia, sentinel node biopsy, and then RFA immediately followed by BCS was performed. Resected specimens were examined at 5 mm intervals by hematoxylin-eosin (HE) staining and several slices of tumor and non tumor lesions in each case were also evaluated by nicotinamide adenine dinucleotide (NADH) diaphorase staining.&amp;#x2028; Results: Thirty of the 34 eligible patients were enrolled (88%) about 2 years. Tumor diameters by ultrasound ranged from 9 mm to 24 mm. RFA-relating adverse events were observed in 2 cases of skin burn and 7 of muscle burn in major pectral muscle. There was one case of technical failure due to insufficient electrode replacement into the tumor. Twenty-eight cases (93%) revealed pathological degeneration changes of tumor specimens with HE staining. However, 2 cases had viable tumor cells of intraductal components beyond ablated breast tissues. In 24 of the 26 cases (92%) examined by NADH diphorase staining, tumor viability was diagnosed as negative. Finally, the complete ablation rate was 87% (26/30).&amp;#x2028; Conclusions: RFA proved to be reliable and feasible in clinical stage I breast cancer without extensive intraductal components. RFA will be an alternative to BCS as surgical treatment in such a case. Randomized clinical trials to compare RFA with BCS in breast cancer should be required. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4150.
Is closure of only the mucosal layer really sufficient?
Authors: Yin Zhang, Zhining Fan
Journal: Endoscopy (2013)

We read with great interest the article by Shi et al.: “Complete closure of large gastric defects after endoscopic full-thickness resection, using endoloop and metallic clip interrupted suture.” The authors presented their experience of closing large gastric defects following endoscopic full-thickness resection (EFTR) for gastric submucosal tumors, using conventional endoloops and metallic clips. In their study, endoloops were anchored with clips to normal mucosa near the proximal and distal resection margins, and tightened slightly to approximate the borders of the defect. This technique closed both sides of the defect but was limited to the mucosal layer and did not involve the full thickness.
SAT0170 Decreased expression of FCΓRIIB on B cells from primary sjögren’s syndrome patients
Authors: S. Zhou, X. Li, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Abnormalities in B cell are characteristic features of primary Sjögren’s syndrome (pSS). FcγRIIb (CD32b), an inhibitory receptor on B cells, is a key regulator of B cells and might be expected to be involved in the pathogenesis of autoimmune diseases. <h3>Objectives</h3> This work was carried out to evaluate the expression of FcγRIIb on B cells from pSS patients, and the influence of high-dose methylprednisolone (HD-MP) pulse therapy. <h3>Methods</h3> FcγRIIb expression on peripheral B cells from 19 pSS patients and 15 healthy controls was examined by flow cytometry (FACS). The levels of serum ant-SSA and SSB antibodies were determined using enzyme-linked immunosorbent assay (ELISA). Five patients who suffered from serious thrombocytopenia and underwent a three-day high-dose methylprednisolone pulse therapy were further assessed for FcγRIIb changes on their B cells <h3>Results</h3> The percentages of memory CD19<sup>+</sup>CD27<sup>+</sup> B cell subpopulation were significantly lower in pSS patients compared to normal controls (p&lt;0.01). The expression of FcγRIIb in active pSS memory CD19<sup>+</sup>CD27<sup>+</sup> B cells was significantly reduced than that in both inactive (p&lt;0.01) and normal controls (p&lt;0.001). pSS patients in serum ant-SSA/SSB antibodies positive group displayed a decreased expression of FcγRIIb on memory CD19<sup>+</sup>CD27<sup>+</sup> B cell compared to those patients with serum negative ant-SSA/SSB antibodies (both p&lt;0.01).The expression of FcγRIIb memory CD19<sup>+</sup>CD27<sup>+</sup> B cells was inversely correlated with anti-SSA antibody titers in active pSS. After a three-day high-dose methylprednisolone pulse therapy, the expression of FcγRIIb on B cells was almost normalized, especially on memory B cells, meanwhile with raised number of platelet. <h3>Conclusions</h3> There is a reduced expression of FcγRIIb on peripheral memory B cells from active pSS patients, which is inversely associated with ant-SSA/SSB antibodies levels. Decreased expression of FcγRIIb might play an important role in the pathogenesis of pSS. HD-MP could induce FcγRIIb expression on B cells from pSS. The upregulation of FcγRIIb is expected as a new therapeutic strategy in pSS. <h3>Disclosure of Interest</h3> None Declared