tbuckley/cabot-search huggingface dataset:
Immunoregulatory properties of TRX585, a novel monoclonal antibody specific for immunoglobulin-like transcript 5.
Authors: I. Apostolou, J. Guild, L. Vaickus, M. Rosenzweig
Journal: Journal of Clinical Oncology (2010)

e13107 Background: Several mechanisms account for the ability of the immune system to mount protective immunity while maintaining self-tolerance. At the single-cell level, the integration of signals delivered by activating and inhibitory receptors determines whether immunity will be initiated or suppressed. Immunoglobulin-like transcripts (ILTs) are polymorphic receptors found on the surface of human and nonhuman primate leukocytes and have the potential for either activating or inhibitory function. ILT5, an inhibitory member of the ILT family with unknown function, is predominantly expressed on antigen-presenting cells (APCs), such as dendritic cells and monocytes. Here, we report on the potent immunoregulatory properties of TRX585, a novel monoclonal antibody (Mab) that targets ILT5. Methods: The immunoregulatory potential of TRX585 was investigated in vitro using mixed leukocyte cultures. T-cell proliferation and activation were monitored using 3H-thymidine incorporation or flow cytometry. Cytotoxicity and Fas ligand release by T cells were quantified by flow cytometry and ELISA, respectively. Results: Upon exposure to APCs with cell-bound TRX585, human T cells proliferated in a T-cell receptor (TCR)-independent manner, upregulated the innate immune receptor, NKG2D, and sustained elevated levels of NKG2D under conditions that normally trigger its internalization. In addition, T cells showed increased responsiveness to subsequent TCR stimulation, secreted high levels of Fas ligand, and acquired cytotoxic potential. Both CD4 and CD8 T cells that were isolated from TRX585-containing cultures efficiently killed a variety of human tumor cell lines. This was shown to be major histocompatibility class I antigen- and Fas ligand-dependent. Conclusions: Our studies uncovered a novel pathway, involving the ILT5 receptor, by which human T cells can be potently activated, become cytotoxic, and acquire an innate immune receptor known to have an important role in preventing the dissemination of tumor cells and viruses. Because TRX585 activates this pathway, it may be useful in the treatment of viral infections and/or malignancies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tolerx, Inc. Tolerx, Inc.
Indian diabetes lifestyle interventions work at many ages and weights
Authors: Cheryl Travasso
Journal: BMJ (2016)

Lifestyle interventions to prevent diabetes may be effective in Indians with impaired glucose tolerance, irrespective of their age or weight, a study has found.1

Using data from 709 Indian patients that were pooled from two previous primary diabetes prevention programmes, the analysis showed that these interventions were as effective in obese participants as in non-obese participants. Likewise, similar effectiveness was seen in participants younger than 45 years old as in those who were over 45.

The International Diabetes Federation2 has estimated that in 2013 there were 65.1 million people …
PSA flare-up in patients with hormone-refractory prostate cancer (HRPCA) receiving docetaxel-based chemotherapy: Incidence and differentiation from progressive disease
Authors: D. Sahi, C. H. Ohlmann, I. Cordia, U. Engelmann, A. Heidenreich
Journal: Journal of Clinical Oncology (2006)

14523 Background: Docetaxel-based chemotherapy displays the standard therapy for patients with hormone-refractory prostate cancer. A subset of patients will experience an initial PSA increase after initiation of therapy followed by a subsequent PSA decrease. The aim of our study was to investigate the incidence of this phenomenon and to identify factors that differentiate the flare-up from progressive disease. Methods: We retrospectively analyzed the patient records of 46 patients who received docetaxel as monotherapy or in combination with either mitoxantron or estramustine for hormone-refractory prostate cancer. PSA flare-up was defined as an initial PSA increase of more than 25% after initiation of therapy over baseline followed by a PSA decrease of at least 75% compared to the maximum increase over baseline. Progressive disease was defined as a PSA increase of at least 25% over baseline in patients with no PSA response which had to be confirmed four weeks later. Results: Of 46 patients who received docetaxel-based chemotherapy 16 (34.8%) showed a PSA decrease of at least 50%, 6 (13.0%) between 30–50%, 17 (37.0%) had stable disease and 7 (15.2%) patients experienced progressive disease. An initial PSA increase followed by a subsequent PSA decrease was seen in 6 (13.0%) of the patients. Median PSA increase compared to baseline was 81.0% (25–239). The median following PSA decrease was 110.5% (77–160) compared to the initial increase. Median PSA doubling times of patients with PSA flare up or progressive disease were 113.3 and 100.7 days (p = 0.7941), respectively. Conclusions: PSA flare-up seems to be a common phenomenon in patients being treated with docetaxel-based chemotherapy for hormone-refractory prostate cancer. In order not to prevent those patients from a subsequent PSA decrease by early cessation of therapy it would be useful to discriminate them from patients with progressive disease. According to the results of our study PSADT does not differ between patients with flare-up or progressive disease and can therefore not be used to distinguish between the two. No significant financial relationships to disclose.
Rapid Expansion of Naive CD4+ Cord Blood Lymphocytes Restores Adaptive Immunity within 2 Months After Unrelated Cord Blood Transplantation
Authors: Robert Chiesa, Prashant Hiwarkar, Kanchan Rao, Waseem Qasim, Kimberly Gilmour, Nicholas Goulden, Persis J Amrolia, Paul Veys
Journal: Blood (2010)
Expression of Heterophil Forssman Antigen as Glycoprotein on Transformed Rat Cell Lines: Shedding of the Antigen From the Cells<xref ref-type="fn" rid="FN2">2</xref>
Authors: T Mori, E Mori, T Sudo, K Kano
Journal: JNCI Journal of the National Cancer Institute (1984)

Monoclonal Forssman (F) antibodies of the IgM class were obtained by hybridization of spleen cells from an immunized F344 rat with murine myeloma cells. By means of the indirect immunofluorescence test with monoclonal F-antibodies, F-antigen was demonstrated on rat cell lines derived from a normal cell line that was transformed by transfection with whole adenovirus type 12 DNA or a fragment (E1a + E1b) of adenovirus type 12 DNA. These transformed cells were shown to shed the F-antigen into the culture supernatant, depending on their degree of malignancy. The F-antigen was demonstrated in a glycoprotein, but not in a glycolipid fraction of the supernatants. The glycoprotein purified by affinity chromatography was subjected to gel electrophoresis and subsequent Western blotting. The F-active molecules were identified as three distinct bands of approximately 130,000, 60,000, and 27,000.
PTH-031 Pillcam sb2 and sb3 small bowel capsule endoscopy – comparisons and implications for practice: Abstract PTH-031 Table 1
Authors: S Dunn, L Neilson, C Davison, F Butt, S Panter
Journal: Gut (2015)

<h3>Introduction</h3> South Tyneside Hospital has been a referral centre for capsule endoscopy since 2005, performing over 1000 studies. We have previously shown that the diagnostic yield (DY) of the PillCam SB3 capsule (Given Imaging, Israel) is significantly higher than that of the PillCam SB2.<sup>1</sup>Here we present additional data on “learning curve” and offer suggestions for practice. <h3>Method</h3> Previous work compared the DY of the last 100 SB2 capsules with the first 100 SB3s. To assess for a “learning curve” effect we reviewed our first 100 SB2 capsules (Oct 2007–Aug 2008). Indications, completion rates, small bowel recording times and pathology were recorded. Pathology was classed as significant if it related directly to indication. <h3>Results</h3> 46 of the first 100 SB2 capsules were abnormal, of which 31 had significant pathology; almost identical to the last 100 SB2s (45 abnormal, 30 significant). Most tests (255/300, 85%) were for unexplained anaemia or Crohn’s disease assessment. More capsules are now done for acute GI bleeding; 4 of the first 100 SB2 capsules, 12 of the last 100 SB2s and 15 of the first 100 SB3s. There were 23 incomplete SB2 capsules (11.5%) of which 18 (9%) were in small bowel at the end of recording and 5 were held up by pathology (2.5%). Only 5 SB3 studies (5%) were incomplete, with 4 (4%) not entering the colon and 1 (1%) held up by pathology. On average SB3 capsules had a longer recording time of 9 h and 24 min compared to 8 h and 2 min for the SB2s. <h3>Conclusion</h3> 219 capsules were reported before the SB2 was introduced. Between the first hundred and last hundred SB2 capsules there were 1003 SB2 studies. This suggests that the increased DY is not due to a “learning curve”, supporting our finding of increased DY with the SB3. Any “learning curve” is likely to be from the first 200 studies. Most studies are for iron deficiency anaemia and Crohn’s disease assessment but there is a trend towards using capsules as a diagnostic tool in overt GI bleeds. Fewer SB3 studies were incomplete compared to SB2s. Our unit is now more proactive in monitoring gastric transit and colonic entry using the real time viewer and this change in practice may have helped with this. Longer recording times due to increased battery life may also play a part. We recommend monitoring capsules in real time and leaving the recorder on for longer if gastric transit is delayed or colonic entry is not clear. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Dunn, S. <i>et al</i>. PTU-053 Is It Worth Repeating Previous Unremarkable Sb2 Capsules With The New Sb3? Gut 63 Suppl 1(2014):A61–A62
Neoplasia and the erythron.
Authors: D C Doll, R B Weiss
Journal: Journal of Clinical Oncology (1985)

Neoplasms may affect the erythroid system in a variety of ways. By far the most common abnormality associated with neoplastic disorders is anemia. It is important to recognize that there are multiple causes of anemia associated with neoplasms, because therapy of the anemia varies according to the causative mechanism. Less commonly, the paraneoplastic syndrome of erythrocytosis may occur in some patients with neoplasia. More subtle abnormalities of the erythrocytes associated with malignant disease include modification of the RBC membrane, changes in erythrocyte enzymes, and abnormalities in hemoglobin production. Clinical awareness of the multiple effects of neoplasms on the erythron will lead to better patient management and may also improve our understanding of erythropoiesis.
Clinical Characteristics and Treatment Outcomes in Patients Diagnosed with Primary Mediastinal Large B-Cell Lymphoma at Princess Margaret Cancer Centre from 1994-2012
Authors: Anna M. Dyszkiewicz-Korpanty, Manjula Maganti, David C. Hodgson, John G. Kuruvilla, Vishal Kukreti, Rodger E. Tiedemann, Alexander Sun, Richard Tsang, Mary Gospodarowicz, Melania Pintilie, Anna Porwit, Michael Crump
Journal: Blood (2014)
Oral contraceptives and malignant melanoma. (Letter to the editor)
Authors: Ellerbroek Wc
Journal: JAMA (1968)

A case report of a 25-year-old nulliparous woman complaining of indigestion nervousness and weight loss is presented.  Internal genitalia were found to be moderately underdeveloped.  She was treated with 4 injections of nandrolone phenpropionate (Durabolin) and weight improved.  Administration of Combid (prochlorperazine and isopropamide) twice daily and small doses of Atarax (hydroxyzine hydrochloride) whenever necessary were given.  Later she was treated with ethynodiol diacetate with mestranol (Ovulen 21) and protriptyline hydrochloride (Vivactil) 5 mg daily.  About 3 months later a change in a pigmented mole on her forearm was noted.  Excision biopsy revealed malignant melanoma.  Wide excision was done.  A casual relationship of the melanoma to the steroid therapy is suggested.
Age Incidence and Site Distribution of Mammary Dysplasias in Young Beagle Bitches23
Authors: M. R. Warner
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Age Incidence and Site Distribution of Mammary Dysplasias in Young Beagle Bitches Get access M. R. Warner M. R. Warner Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 1, July 1976, Pages 57–61, https://doi.org/10.1093/jnci/57.1.57 Published: 01 July 1976 Article history Received: 07 August 1975 Accepted: 11 November 1975 Published: 01 July 1976
Do we classify by feeling mixed COPD-asthma phenotype patients with GesEPOC?
Authors: Silvia Alvarez, Xavier Flor, Laia Lamarca, Inma Grau, Anna de Pedro, Victoria Feijoo
Journal: European Respiratory Journal (2014)

INTRODUCTION

The new Spanish COPD guideline, GesEPOC, classifies patients into differents phenotypes. The mixed COPD-asthma phenotype (MCAP) is the originality. It needs very strong criteria for its classification.

OBJECTIVES

1. To asses how many MCAP patients meet criteria

2. Which is the most frequent criteria

MATERIAL AND METHODS

From 401 COPD patients from 6 differents Primary Care (PC) centres in Barcelona we find 36 MCAP patients. We analysed how many meet criteria (2 major criteria or 1 major and 2 minor criteria).Major criteria were:1.To have a bronchodilator test(BT) of 400mL and more than 15% 2. Asthma antecedent. 3. Sputum eosinophilia. Minor criteria were:1.To have atopia 2. To have 2 BT of 220mL and more than 12%. 3.High blood level of IgE. Descriptive and bivariant analysis was made with Chi-square and t-Student tests.

RESULTS

36 patients out of 401 enrolled the study. Mean age 64,3 year old (SD 8,5). 83,3% were men. 27,8%were current smokers. 19,4% had BT more than 400mL and more than 15%. None of them had sputum eosinophilia. 86,1% had anterior antecedents of asthma. 13,9% were tested for IgE. 19,4% had atopia. 38,9% had 2 or more positive BT. Only 19,4% met criteria (13,8% 2 major criteria and 5,5% with1major+2minor criteria) which may correspond to 7 patients. 91% of the patients are mild/moderate disease. If we classify theses patients with GOLD guideline there are 38,9% A, 13,9% B, 16,7% C and 30,6% D.

CONCLUSION

There are very few MCAP in general. For this phenotype classification it is required very strict criteria and some of them are not usual in primary care (as sputum eosinophilia). The most frequent criteria is to have antecedent of asthma.
Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors
Authors: I. E. Krop, M. Kosh, I. Fearen, J. Savoie, A. Dallob, C. Matthews, J. Stone, E. Winer, S. J. Freedman, P. Lorusso
Journal: Journal of Clinical Oncology (2006)

10574 Introduction: Activation of Notch signaling occurs in ∼40% of human BCs and high Notch expression is associated with poor outcome. Inhibition of Notch inhibits BC cell proliferation in vitro. Notch signaling requires gamma secretase (GS), which cleaves Notch, releasing the Notch intracellular domain (NICD) to activate transcription of target genes. MK-0752 is a potent GS inhibitor. Methods: In Part 1 of the study, pts with advanced solid tumors were enrolled using an accelerated dose escalation with 1 pt/dose level until the occurrence of ≥Grade 2 toxicity, then 3–6 pts/dose level. MK-0752 was administered by once-daily oral dosing in 28-day cycles. Once a maximum tolerated dose (MTD) was established, an additional 22 pts with advanced BC were to be enrolled in Part 2. Six-point PK plasma profiles were collected over 24 hours on Days 1 and 28 and assayed by LC/MS/MS. PD measurement of plasma Abeta 40 peptide (another gamma secretase substrate) was performed pre/post dose on Days 1 and 28. Tumor biopsies on Days 1 and 28 were obtained from a subset of pts to assess changes in Notch activity by immunohistochemical analysis of NICD. Results: In Part 1, two pts were enrolled at 450mg daily, and five pts at 600mg daily. Dose-limiting toxicities (DLTs) were Grade 3 diarrhea, constipation, nausea, and abdominal cramping at 600 mg. In Part 2, an additional 14 pts with BC were enrolled at 450mg daily. In this cohort, Grade 2/3 fatigue requiring dose reduction occurred in 6 pts. Grade 3 diarrhea (1pt), nausea (1 pt) and elevated liver transaminases (2 pt) were also observed. Mean PK parameters (at 450mg, 600 mg) on Day 1 were AUC 0–24hr = 1036, 1065μM·hr, C max = 72, 61μM, C 24hr = 25, 32μM, and t max = 3, 7 hr. PD measurements of GS inhibition showed a 12–78% (mean 46%) decrease in plasma Abeta 40 at 4 hours on Day 1 compared to predose. Conclusion: Continuous dosing of MK-0752 at 450mg daily in pts with BC was associated with significant toxicity, predominantly fatigue, and cannot be considered a MTD. An intermittent dosing schedule is being explored. MK-0752 at all doses inhibited GS, as demonstrated by decreases in plasma Abeta 40 . Analysis of efficacy and intratumoral Notch inhibition will be reported at the meeting. [Table: see text]
Tumorigenicity of Tetramethylhydrazine Hydrochloride in Swiss Mice2
Authors: Bela Toth, Donald Nagel, James Erickson, Robert Kupper
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Tumorigenicity of Tetramethylhydrazine Hydrochloride in Swiss Mice Get access Bela Toth, Bela Toth Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald Nagel, Donald Nagel Search for other works by this author on: Oxford Academic PubMed Google Scholar James Erickson, James Erickson Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Kupper Robert Kupper Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 5, November 1976, Pages 1179–1183, https://doi.org/10.1093/jnci/57.5.1179 Published: 01 November 1976 Article history Received: 02 February 1976 Accepted: 02 April 1976 Published: 01 November 1976
Ductal carcinoma in situ (DCIS): USC/Van Nuys Prognostic Index (VNPI) and the impact of micropapillary histotype
Authors: S. Fracchioli, R. Bellino, R. Arisio, K. Mingrone, A. Durando, G. Giardina, D. Katsaros, M. Massobrio, M. Porpiglia, R. Vicelli
Journal: Journal of Clinical Oncology (2004)

662 Background: As our knowledge of DCIS has evolved during the past decade, treatment decision making has become much more complex and controversial. We examined the use of VNPI and the effectiveness of micropapillary histotype as a predictor of local recurrence (LR). Methods: We retrospectively collected 408 patients treated from 1988 to 2002 for DCIS or microinvasive DCIS (mi-DCIS), with conservative surgery or mastectomy according to the VNPI. We added to the classic VNPI the micropapillary histotype: with this novel algorithm, score 1 was given to micropapillary DCIS (M-DCIS) G1 and to other histotypes G1–2, while score 3 was given to M-DCIS G2–3, and to other histotypes G3 and/or to mi-DCIS. Finally, we compared sensitivity and specificity of the two prognostic indexes. Results: DCIS was diagnosed in 337 patients and mi-DCIS in 71 women. 267 patients underwent conservative surgery, while 141 underwent mastectomy (96 after a conservative surgery). Adjuvant radiotherapy was given in 58% of conservative-treated patients, and Tamoxifene was prescribed in 25% of cases. Median follow-up was 55 months. Micropapillary histotype was observed in 90 cases. According to the VNPI, LR was significantly related to tumor grade (LR was 0.9% vs 5.3% in grade 1 vs grade 2–3) and size (1.9% vs 6.4% in lesions <15mm vs >15mm), and to the involvement of tumor margins (2.7% vs 7.6% with clear margin >10mm vs <1mm). LR was found in 11.5% of G2–3 M-DCIS vs 4% of other histotypes G3 (p<0.006): it was observed in 3.3% of DCIS vs 8.5% of mi-DCIS (p=0.056). Patients with VNPI score 3–6 showed LR in 1.2% (4/246) vs 8% (13/162) of women with VNPI score 7–9 (p=0.003): with the novel score, only 126 women had score 7–9, with LR in 9.5%, vs 1.75% in the 282 women with score 3–6 (p=0.002). Specificity and sensitivity were 77% and 72% (vs 72% and 76% of VNPI), respectively. Conclusions: Our data showed that micropapillary histotype is of prognostic value of LR in DCIS patients. It could be therefore included in the VNPI in order to identify a low risk group of patients, avoiding overtreatment. Further studies are warranted to confirm our preliminary results. No significant financial relationships to disclose.
Data were misrepresented
Authors: Wendy S Biggs
Journal: BMJ (2008)

Rates of lung microsomal dimethylaniline (DMA) demethylation and N-oxidation as well as cytochrome P-450 concentrations from 20- and 28-day pregnant rabbits were observed to be as much as 2 times the values measured in lung microsomes from adult female nonpregnant rabbits. These increases were not seen in lung microsomes from 10-day pregnant rabbits, and only small increases were observed in lung microsomes from 15-day pregnant rabbits. In contrast, no differences were seen in hepatic microsomal DMA demethylase or N-oxidase activities at any stage of pregnancy. An attempt was made to correlate high plasma concentrations of steroids during pregnancy with the elevated enzyme activities observed in lung microsomes. Adult nonpregnant rabbits were treated with a variety of steroids, the concentrations of which have been shown to increase in plasma during late pregnancy. No effect on lung or liver microsomal DMA metabolism was observed when rabbits were treated with testosterone propionate. However, after animal pretreatment with the glucocorticoids, dexamethasone and hydrocortisone, there was a 40-60% increase in DMA demethylase and N-oxidase activities in liver and lung microsomes from adult male and nonpregnant female rabbits. Following pretreatment of adult female nonpregnant rabbits with the mineralocorticoid, deoxycorticosterone, an increase of 50% in rate of microsomal DMA metabolism in lung but not in liver was observed.